Eye-tracking performance and engagement of attention. Eye-tracking dysfunction has previously been demonstrated in psychotic patients. To investigate possible influences on this finding of factors related to attention, subjects were required to read numbers while tracking an oscillating pendulum or a pendulum-like target displayed on an oscilloscope tube. Subjects for the pendulum task were 16 nonpatients and 21 patients; 10 nonpatients and 14 patients performed the other task. Introduction of the number-reading maneuver greatly improved tracking performance in both tasks in patients and nonpatients. The results indicate that poor eye-tracking can be improved by facilitating attentional effort; it is suggested that the number-reading maneuver improved tracking by providing extra feedback cues. The poorer the base line performance, the greater the improvement. However, differences between patients and nonpatients were not abolished with number reading.


Homospatial thinking in creativity.

Homospatial thinking in creativity. "Homospatial thinking" consists of actively conceiving two or more discrete entities occupying the same space, a conception leading to the articulation of new identities. Homospatial thinking has a salient role in the creative process in the following wide variety of fields: literature, the visual arts, music, science, and mathematics. This cognitive factor, along with "Janusian thinking," clarifies the nature of creative thinking as a highly adaptive and primarily nonregressive form of functioning.


The content and structure of adolescent self-images. Longitudinal studies. Using a specially designed Q-sort technique, multiple self-images held by 60 normal and psychiatrically hospitalized adolescents were studied initially and then every six months for 12 to 18 months. Each subject's self-images were analyzed for their overall coherence (integration) and for the evaluation of specific self-descriptive statements. The results showed that, as predicted clinically, the patients and normal subjects differed significantly on both integration and content evaluation dimensions. The patients had consistently lower integration scores on each trial, in contrast to the normal subjects' steadily increasing values. The patients evaluated their self-descriptive statements as steadily diminishing in importance while the normal subjects' evaluations remained at the same level over the trials. The patients' dual trends are discussed in terms of their reflecting the pattern of edentity diffusion described clinically by Erikson.


Empathy. We know what we mean, but what do we measure? In recent years, quantitative researches on the empathic process in psychotherapy have resulted in definite recommendations for the technique of psychotherapy and the training of psychotherapists. What is not always observed, however, is that the methods employed for studying empathy have been based on brief segments of patient-therapist interaction in which judgments of empathy do not depend on hearing the patient's communications, and are in several ways discordant with what is meant by empathy according to clinical theory. Evidence suggests that it is the rater's impression of the "goodness of psychotherapy" rather than empathy that is being captured by these methods.


The wish to be held. A transcultural study. In a previous study, it was noted that "a strong desire to be held or cuddled correlated with a general leaning toward openness in emotional expression." As is well known, some cultures foster openness, while others do not. This project was designed to assess the influence of cultural attitudes on the wish to be held. To do so, questionnaires were given to five groups of Asian women living in Kuala Lumpur, Malaysia. The most striking differences found were between two groups of Chinese women, one Chinese-educated, and the other, English-educated. The Chinese-educated group inhibited the expression of sensual needs. An English education overturned the traditional mode of response; women in this group scored highest in their wish to be held and lowest in their inclination to keep their body-contact desires secret. This study demonstrates that cultural as well as psychological forces exert a profound influence on the wish to be held.


Wish to be held and wish to hold in men and women. The present study focuses on the wish to be held and the wish to hold in men and women and is based on data collected from both a questionnaire and interviews. It was assumed that cultural sex-role stereotypes would influence the results. More specifically, it was postulated that men would find it easier to acknowledge and discuss their wish to hold rather than their wish to be held, but our data did not support this postulation. The chief differences between men and women were the trend for women to favor being held over holding and the much more sizeable group of women than men who were extremely high scorers on the body contact scale. Men, at least those who are psychiatric patients, can acknowledge their longings to be held, but the intensity of this feeling either does not reach the height attained by some women or, if it does, it is not reported.


The spouse's role in home hemodialysis.

The spouse's role in home hemodialysis. The role of the spouse as a factor in the success or failure of home dialysis becomes increasingly important as expectations rise that hemodialysis patients be home-trained. Home hemodialysis offers advantages to the patient but may add stress to the spouse. We present cases illustrating the types of responses spouses have to home hemodialysis. Present conditions are such that the spouse's ability to participate in home hemodialysis may be less affected by aspects of the patient-partner's chronic renal disease than the potential change in the marital relationship that can derive from home hemodialysis. Success in home dialysis is at risk when the spouse is naturally dependent on the patient-partner. These spouses will often require special supportive measures.


Some dynamics of male chauvinism.

Some dynamics of male chauvinism. Male chauvinism was studied in the psychoanalytic therapy of 11 men. It refers to the maintenance of fixed beliefs and attitudes of male superiority, associated with overt or covert depreciation of women. Challenging chauvinist attitudes often results in anxiety or other symptoms. It is frequently not investigated in psychotherapy because it is ego-syntonic, parallels cultural attitudes, and because therapists often share similar bias or neurotic conflict. Chauvinism was found to represent an attempt to ward off anxiety and shame arising from one or more of four prime sources: unresolved infantile strivings and regressive wishes, hostile envy of women, oedipal anxiety, and power and dependency conflicts related to masculine self-esteem. Mothers were more important than fathers in the development of chauvinism, and resolution was sometimes associated with decompensation in wives.


Sex-role related countertransference in psychotherapy. Data from one psychological and one psychiatric agency were collected to determine if psychotherapists' treatment decisions about opposite-sex persons might be influenced by sex-role prescriptions for dealing with sexual impulses. Accordingly, male therapists were hypothesized to prolong and female therapists to avoid treatment situations likely to arouse their sexual curiosities. The results at both facilities provide some support for these notions and, if generalizable, establish sex-role primed countertransference as a factor in patient selection and termination.


Length of hospitalization on a short-term therapeutic community. A multivariate study by sex across time. Patient length of hospitalization was examined in a private short-term therapeutic community unit using a longitudinal, multimethod, -ultivariate approach, with data analyzed separately by patient sex. Patient data were entered into stepwise linear regression analyses for weeks 1, 2, and 4 of an average seven-week hospitalization for male and female patients separately. Results for men were not specifically replicated among the women. Longer-staying men were diagnosed more frequently as "personality disorders," tended to be somewhat aloof, perceived the ward as encouraging denial, facade, order, and organization. Among women, verbal behavior, interpersonal relations, discontentedness with family, and other variables were related to length of hospitalization. Shorter-staying male and female patients tended to exhibit characteristics at the "feminine" end of a hypothetical masculinity-femininity continuum. Conforming, accepting behavior seemed reinforced for all patients.


The psychiatric examination in the walk-in clinic. Hypothesis generation and hypothesis testing. Rapid assessment for decision making is a major goal of the initial psychiatric interview in walk-in clinics, emergency psychiatric services, and the ambulatory services of community mental health centers. To accomplish this task, the clinician must learn to elicit specific data to confirm or refute clinical hypotheses rather than gather a complete history. This report, in formulating a hypothesis generating and testing approach for the initial psychiatric examination, proposes 16 hypotheses that organize the clinical data necessary for most decisions. This approach is intended to help the clinician make efficient use of limited time, guard him from coming to premature closure in the collection of data, and provide a stimulus for the exploration of relevant but neglected clinical questions.


Nerve conduction velocity determinations in juvenile diabetes: continuing study of 190 patients. Few prospective studies on the concomitant finding of neuropathy in juvenile diabetics exist. An ongoing study of motor and sensory nerve conduction determinations in 190 diabetic children, with sequential studies in 108 of them over an eight-year period, is the subject of this report. The incidence of neuropathy in our sample population under five years of age is neglible. In the children over five years of age, 8% had abnormal nerve conduction velocity (NCV) of the peroneal nerve, 4.5% had abnormal median motor and sensory NCV on initial study. In the sequential studies of the children over five years of age, the percentage of abnormal NCV rose from 14% to 48% as the duration of diabetes increased from one year to more than five years. It is the older juvenile diabetics with the longest duration of diabetes who would appear to have the highest incidence of neuropathy.


Cervical radiculitis: treatment and results in 82 patients. Depending on the severity of the clinical problem, three categories of treatment--home, outpatient and hospital--were utilized in 82 patients whose conditions met the strict criteria for cervical radiculitis. Details of the clinical picture, laboratory findings, electromyographic examinations, category and results of treatment are detailed. The follow-up results in 59 patients contacted one to two years after the initial treatment are also included. Eighty percent of the patients had good to excellent results when treated with conservative therapy during the initial episode whereas 71% continued to have good to excellent results after one to two years. Seventeen percent of those patients who were followed required a laminectomy.


Motor sensory dysfunction of upper limb due to conversion syndrome. Seven patients had functional paralysis that occurred in the dominant limb together with joint contracture and sensory disturbances associated with emotional problems. In five of these patients, the syndrome was preceded by trauma to the affected upper limb and in one patient by a myocardial infarction. The treatment consisted of persuasion, suggestion, general rhythmic exercises and emotional support given by the physiatrist (not a psychiatrist). In five of the subjects treated, the symptoms disappeared and the patients soon returned to work. In two patients the treatment did not succeed since no satisfactory rapport could be established between the patient and the physician.


Energy expenditure with advanced lower limb orthoses and with conventional braces. The purpose of this study was to measure the relative energy expenditure through quantification of oxygen consumed in subjects wearing various advanced designs of lower limb orthoses and conventional braces. The designs developed at the Institute of Rehabilitation Medicine were compared with conventional braces and were found to result in a reduction of oxygen consumed from 9% to 16% depending on the type of orthosis. Portable Douglas bags were employed and the gas analyzed per unit distance-time with relation to volume of oxygen and carbon dioxide under steady state conditions. Savings in consumed oxygen are rather consistent with the advanced orthotic designs, even though the subjects varied with respect to age, weight, sex and disability. No data were taken without a device as the subjects under this circumstance frequently required an auxiliary aid, which would introduce another variable.


Errors in EMG reporting.

Errors in EMG reporting. In a review of 112 electromyographic reports from 112 different electromyographers, errors were classified as anatomic, terminologic, technical and interpretative. Ninety-seven of the reports had substantive errors. The EMG report should be complete, precise, accurate and logical and include a summary of the anatomic and neurophysiologic data with a translation into a probable clinical diagnosis.


Prognosis in Bell's palsy.

Prognosis in Bell's palsy. This is a concluding report of a study in which only patients with Bell's palsy initially seen within ten days of onset are included. The purposes are to observe the natural course of the disorder and to illustrate electromyographic EMG) criteria by which early forecast of recovery is possible. Appraisals of facila muscle strength, nerve stimulation responses and electromyographic needle electrode examinations correlated with the time required for recovery and the relative degree of recovery of patients with Bell's palsy. Three categories of recovery are evident. Of 90 patients, 79% recovered completely within two months (class I), 7% recovered adequately within two to six months (class II) and 14% required longer than six months (class III). Using clinical and electromyographic methods it should be possible to forecast recovery within three days after onset in order to preselect patients in need of any proposed curative treatment program designed to salvage the facial nerve. For prognosis in patients without clinically detectable facial muscle function, the data suggest that they be evaluated on a daily basis from onset until day 4 (past 72 hours). Finding that residual motor unit potentials are sustained in four to five muscles during that period strongly indicates a favorable outcome. Finding activity in two to three muscles could be less favorable and finding zero to one muscle with activity is clearly unfavorable. During this period of time there is a tendency for progressive loss of EMG activity in the facial muscles, both in patients with favorable and with less favorable outcomes.


Mime in language therapy and clinician training. A speech pathologist developed a program with language goals which included spontaneous communication, focus, attention span, auditory memory, receptive and expressive vocabulary, and concepts such as body image, spatial relationships, and same and different polarities. The services of a professional mime were used to translate these goals into mimetic activities and to perform the activities in group sessions with the children. In addition, the mime taught the speech clinicians some simple mimetic activities. The subjects were five children with mental retardation, language delay, lack of spontaneity, short attention span and very poor visual and auditory memory. The results suggested increase in spontaneity and attention span in all the children and a facility to remember the illusions depicted for them by the mime. The experience with the mime training for clinicians was also positive.


Connective tissue activation: VIII. The effects of temperature studied in vitro. The effects of increasing environmental temperature were studied in two normal and two rheumatoid human synovial cell cultures. Control cultures showed an increased rate of hyaluronate synthesis and glucolysis as temperature was increased from 30 C to 39 C. Cultures which were activated (stimulated by a connective tissue activating peptide, CTAP) showed an especially striking increase in hyaluronic acid synthesis, glucose uptake and lactate formation at 36 C and 38 C. The data suggest that small changes in joint temperature may be associated with profound alterations in synovial metabolic activity.


Biofeedback treatment of foot drop after stroke compared with standard rehabilitation technique (part 2): effects on nerve conduction velocity and spasticity. Peroneal nerve conduction velocity (NCV) was determined in 20 hemiplegic patients with chronic foot drop. At the initial visit, relative slowing of NCV of the affected leg was observed. The patients were randomly separated into two groups, and treated for five weeks by different therapies--group 1 by conventional physical exercise and group 2 by physical exercise plus biofeedback training. Of these patients, six with severe spasticity were selected from each group to investigate the change of spasticity by patellar tendon reflex. Although with biofeedback remarkable improvement of function was observed (and reported in an earlier paper), there was no significant change of NCV and spasticity.


Communicating hydrocephalus. Cisternographic and neuropathologic studies. Chronic communicating hydrocephalus was produced in adult dogs by injection of silastic into the subarachnoid space. Electron microscopy was used to verify the sequence of pathologic changes in the ventricular wall. The pathologic findings were correlated with cisternographic images and measurements of cerebrospinal fluid (CSF) pressure. Early in hydrocephalus, the CSF pressure was increased and cisternograms showed ventricular entry and clearing; the ependyma was stretched and fluid accumulated in subependymal regions. In animals with chronic hydrocephalus, the CSF pressure was normal and cisternograms disclosed radioactivity persisting in the ventricles. At this time the ependyma was severely damaged, the subependymal white matter showed enlargement of the extracellular space, and degenerative changes were present in axons and myelin sheaths.


Radionuclide cisternography after head injury. Thirty-seven patients with severe head injury underwent radionuclide cisternography to detect early and late effects of trauma on cerebrospinal fluid (CSF) circulation. Thirty-one patients had subdural hematomas or hygromas and six had cerebral contusions without extracerebral masses. Cisternographic results were abnormal in 23 patients with subdural masses and normal in five who had only cerebral contusions. Of eight patients undergoing serial studies, one had persistent partial obstruction, five had partial resolution of abnormalities, and the two with progressive obstruction had their conditions improved by shunting. Angiography suggested transtentorial herniation in 11 patients with cisternal block, six of whom had clinical signs of herniation on the same side.


Immunoglobulin abnormalities and measles antibody response in chronic myelopathy. Patients with chronic myelopathy of unknown origin were separated into two groups on the basis of presence or absence of oligoclonal immunoglobulin G (lgG) in cerebrospinal fluid (CSF). Thirty-nine of 48 patients (81%) with oligoclonal lgG in CSF had measles virus antibodies in the CSF and 31 (65%) showed reduced serum/CSF measles virus antibody ratios, in comparison with the corresponding ratios of adenovirus, group-specific, penton hemagglutination-enhancement and poliovirus neutralization-enhancement antibodies. Of 25 patients with myelopathy, but without oligoclonal lgG in their CSF, three had detectable titers of measles CSF antibodies and one of these had a greatly reduced serum/CSF ratio. The conditions of patients with chronic myelopathy of unknown origin and oligoclonal lgG in CSF may be diagnosed as probable multiple sclerosis (MS), in contrast to patients with this disease who lack oligoclonal lgG IN CSF. However, the clinical features of the disease in these two groups do not differ substantially.


Peripheral nerve morphometry in myotonic dystrophy. Biopsy specimens of muscle and cutaneous branches of the common peroneal nerve from four patients with myotonic dystrophy (MD) were evaluated by morphometric techniques and compared to age-matched control nerves. Myelinated fiber densities were normal in the superficial and deep peroneal nerves of patients with MD. Internode length and frequency of abnormal fibers was not significantly different in MD and control nerves, nor were the number of myelin lamellae, number of neurofilaments per unit area, or number of microtubules per unit area to axis cylinder area. There was no evidence of morphologic abnormality of peripheral nerve in MD.


Schwann cell multiplication after crush injury of unmyelinated fibers. The intensity and duration of Schwann cell multiplication in unmyelinated fibers after crush injury of cervical sympathetic trunks (CSTs) in adult mice was studied using radioautography and electron microscopy. At the level of crush, labeling indexes rose to 22.5% on the second day after injury, but distal to this level, labeling reached a peak of only 2.5%. By the ninth day labeling declined to 1% or less at both sites. Electron microscopy confirmed that the increase in nuclei at the crush was mainly an increase in Schwann cells. Thus, the intensity of Schwann cell multiplication differed between crush and distal sites along the same unmyelinated nerve. The Schwann cell proliferation in the distal CSTs was less intense than that reported in previous studies on myelinated nerves.


Hypoxic-ischemic leukoencephalopathy in man. Three cases of hypoxic-ischemic leukoencephalopathy were studied. In two patients, the neurologic disorder followed drug overdosage; in the third, the apparent precipitating event was a postoperative myocardial infarction complicated by circulatory insufficiency. All patients were deeply unresponsive, with varying reflex patterns. In all three cases, the brain showed extensive symmetrical necrotic lesions of the central white matter, with minimal damage to gray matter structures. The lesions in case 3 showed, in addition, vascular necrosis and ring hemorrhages. Common to all cases was a prolonged period of hypoxemia, hypotension, and elevated venous pressure. Acidosis occurred in two. These observations and analysis of previous reports of similar cases suggest that leukoencephalopathy tends to occur when the hypoxemia is prolonged and is associated with periods of hypotension and metabolic imbalance.


Craniofacial dysostosis with syringomyelia and associated anomalies. A 16-year old boy had craniofacial dysostosis, hydrocephalus, and syringomyelia. Other anomalies included platybasia, a Klippel-Feil anomaly, webbed toes, and a cutaneous hemangioma. Evaluation included cerebral angiography, ventriculography, and myelography.


Progressive bulbar paresis in childhood. We present a case of progressive bulbar paresis in a 2-year-old child, with appropriate autopsy findings. A review of previously reported cases and a comparison with more extensive literature in Werdnig-Hoffmann disease suggest that Fazio-Londe disease is not unique, but belongs in the spectrum of progressive lower motor neuron disease.


Steroid therapy in acute cerebral infarction. Fifty-three patients with acute cerebral infarction were treated in a double-blind study with either dexamethasone or placebo within 24 hours of the onset of stroke. Forty-one of these survived for longer than 28 days, and the patients treated with the steroid fared slightly worse than those treated with placebo at the end of this time. Two of the five patients who died in the placebo group died of cerebral edema, compared with three out of seven patients who died in the steroid group. Infectious complications, gastrointestinal hemorrhage, and occasional serious exacerbations of diabetes occurred more commonly in the steroid group.


An unusually large human eye with abnormal scleral collagen. Severe progressive ocular enlargement of late onset accompanying chronic uveitis and secondary glaucoma occurred in an 18-year-old man. Electron microscopy of the thin sclera from the unusually large eye (40x40x37 mm) disclosed collagen fibrils with mean widths that exceeded that of controls, but that were within the range of the fibril size typically present in the outer sclera. Thinner fibrils that normally occur particularly within the inner sclera were conspicuously absent. Morphologic observations on corneal and cutaneous collagen from the patient were unremarkable. No abnormality was detected on chemical analysis of cutaneous collagen. The abnormal morphologic pattern of the scleral collagen is interpreted as a probable arrest in scleral collagen synthesis.


Subconjunctival dislocation of the lens. A traumatic phacocele in a previously injured eye is reported. Although subconjunctival dislocation of the lens is relatively rare, it should be considered in the differential diagnosis of an acquired, large conjunctival mass.


Upper eyelid retraction after blowout fractures. Two patients developed upper eyelid retraction secondary to a blowout fracture of the orbital floor. Posttraumatic overaction of Muller muscle is a possible cause of the eyelid retraction.


Cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis. A case of presumed cerebrotendinous xanthomatosis is described. The association of cataracts with central nervous system signs and tendon xanthoma is noted. Deposition of cholestanol appears to be the primary lesion in this disease.


6-Hydroxydopamine in treatment of open-angle glaucoma. In patients with open-angle glaucoma, subconjunctival injection of 6-hydroxydopamine produced chemical sympathectomy and sensitization to topically applied epinephrine. Prior to entry into this study, all patients had intraocular pressures (IOPs) greater than 30 mm Hg and had not responded to maximal medical therapy. The 6-hydroxydopamine was prepared in an ascorbic acid-buffered solution and was well tolerated by the patients. After subconjunctival administration of 6-hydroxydopamine, the mean decrease in IOPs was 50% in the treated eyes and 5% in the contraleteral eyes. Topical administration of 1% epinephrine to eyes injected with 6-hydroxydopamine resulted in a mean fall of IOP of 40% that persisted for as long as three months. Repeated subconjunctival injections of 6-hydroxydopamine renewed the pressure-lowering effects and sensitization to topically applied epinephrine.


Isolated foveal hypoplasia.

Isolated foveal hypoplasia. Although defective development of the fovea has long been known to occur in patients with aniridia and albinism, only rarely has isolated foveal hypoplasia unassociated with these conditions been reported. We have identified such foveal hypoplasia in nine patients with varying degrees of congenital nystagmus and poor visual acuity, but no evidence of albinism or aniridia, isolated foveal hypoplasia may be more common as a cause of congenital sensory nystagmus than has been appreciated in the past.


Acute hemorrhagic conjunctivitis in Tunisia. Report of viral isolations. Acute hemorrhagic conjunctivitis (AHC), a new disease entity first reported in 1969, has since become pandemic throughout the world. In Tunisia during an epidemic in 1972 to 1973 we studied 25 cases of AHC, which were characterized by explosive onset of lid edema, chemosis, conjunctival hemorrhages, follicular hypertrophy, and epithelial keratitis. Clinical signs peaked in 48 hours and cleared without sequelae in five to seven days. Paired acute- and convalescent-phase sera from six of the patients showed a rising titer of neutralizing antibody to the prototype strain of AHC virus (J6 70/71), which was isolated in Japan. Two viral isolates from Tunisian patients were also antigenically related to the Japanese strain, indicating that a single etiologic agent (a new member of the picornavirus group) is probably responsible for the current pandemic of AHC.


Expulsive choroidal effusion. A complication of intraocular surgery. Massive serous choroidal effusion may occur as an expulsive complication of intraocular surgery. The pathophysiology of expulsive hemorrhage involves rupture of the short posterior ciliary arteries, while that of effusion involves massive exudation through the walls of the choroidal vessels. Many of the predisposing factors may be shared including atherosclerosis, hypertension, and sudden surgical decompression. The treatment of both entities is the same--swift closure of the wound, drainage of suprachoriodal blood or effusion through a posterior sclerotomy site, and injection of a physiologic solution into the anterior chamber to tamponade the leaking vessels and restore normal intraocular anatomic relationships. The visual prognosis following expulsive choroidal effusion is much more favorable than that of expulsive hemorrhage.


Ocular injuries in hockey.

Ocular injuries in hockey. Ocular injuries suffered by 38 hockey players during a three-year period were studied. The severity of the injuries required hospitalization for 16 of the patients. Twelve players require follow-up care for possible late complications from the following conditions: angle recession (seven cases), subluxated lens (three cases), traumatic cataract (three cases), detachment of the retina (two cases), and enucleation (one case). The use of a full-face protective mask affixed to an adequate helmet is recommended for all hockey players.


Alkali retinopathy.

Alkali retinopathy. Two patients were seen with intense alkali burns of the eye and prominent chorioretinal damage. The course of one case illustrates the development of such lesions. The second case suggests that retinal damage can be the limiting factor in the visual prognosis following such burns.


Dendritic pigmented cells within human laryngeal mucosa. Melanocytes were seen within the basal layer of the laryngeal squamous epithelium in a biopsy specimen of the vocal cord. No dendritic pigmented cells were visualized in several sections of the entire mucosa of 15 autopsy specimens of the larynx, but clear, Langerhans-like cells were seen, suggesting that melanocytes in this location may possibly become effete. This may account for the infrequent occurrence of primary malignant melanotic lesions of the larynx.


Rhabdomyoma of the larynx. Report of a case. Review of the English literature shows six reported cases of "rhabdomyoma of the larynx." As far as we have been able to determine, only three cases of these have been undisputed rhabdomyoma. The case reported herein represents the first rhabdomyoma of the larynx that was removed under microsurgical conditions, and adds a fourth case to the literature.


Laryngeal rhabdomyosarcoma.

Laryngeal rhabdomyosarcoma. Laryngeal rhabdomyosarcomas are very rare, extremely malignant tumors. Approximately half of the reported cases have occurred in children. Diagnosis may be difficult, and adequate biopsy material is crucial in the identification of these lesions. Unil recently, rhabdomyosarcomas carried a dismal prognosis; however, combined treatment with surgery, irradiation, and triple chemotherapy appears to have improved the outlook. This should probably be the treatment for laryngeal rhabdomyosarcomas, and was successfully used in the case reported herein.


Inner ear pathologic features following mumps infection. Report of a case in an adult. Temporal bone studies in an adult with a moderately severe, bilateral sensorineural hearing loss revealed bilateral cochlear changes 13 years after mumps infection. The organ of Corti was completely absent in the greater part of the superior horizontal basal limbs, with occasional hair cell loss throughout the rest of the cochlea. The outer sulcus cell area was degenerated. The stria vascularis was normal, as was the tectorial membrane, except for small hyaline droplets. The number of nerve fibers was extremely decreased in the spiral bony lamina of the basal turns. Basophilic material, possibily representing degeneration of otoliths, was present in the saccule and utricle, bilaterally, with small amounts in all of the ampullae. This was considered to be either a possible result of cytotoxic cancerocidal therapy, or an incidental nonspecific change.


Bilateral carcinoma of the ears. Report of a case. We report a rare case of bilateral carcinoma of the ears in a 41-year-old man. The second tumor developed from the left mastoidectomized middle ear cavity eight years after the complete healing of the first tumor, which probably originated in the glands of the right external auditory canal.


Cricopharyngeal myotomy for dysphagia in oculopharyngeal muscular dystrophy. Report of a case. A case of dysphagia secondary to oculopharyngeal muscular dystrophy is described. On the basis of the patient's clinical condition, radiographic and manometric findings, a cricopharyngeal myotomy was performed, resulting in relief from dysphagia.


Apical pneumatocele.

Apical pneumatocele. Cervical herniation of the lung is a rare condition that results from congenital agenesis of Sibson Fascia. Occasionally, this may result from acquired causes like trauma. We report a rare case of a patient who was recently encountered in our Otorhinolaryngological Clinic and who posed an interesting problem of differential diagnosis. The management of such patients requires frequent checkups to safeguard against spontaneous pneumothorax. An otolaryngologist should not be caught unaware as the rhythmic "ballooning" of the supraclavicular area is quite characteristic with forced expiration.


Central vestibular compensation. Effect of the bilateral labyrinthectomy on neural activity in the medial vestibular nucleus. An attempt was made to reconstruct the central events that occurred in the various stages of vestibular compensation after a bilateral labyrinthectomy in the cat. Bilateral labyrinthectomized cats showed no nystagmus, but had unsteady head movements and wide gaits. Neural activity in both sides of the medial vestibular nuclei (MVN) was depressed during the critical stage of compensation; however, the neural activity was full and normal during the acute and compensated stage. The experimental results suggest that removing crossed inhibitory influence and reducing the cerebellar inhibitory influence by bilateral labyrinthectomy enhances the process of recovering neural activity in the vestibular nuclei during central compensation, and that the contralateral vestibular end organ is not a source of the driving force responsible for regeneration of electrical activity in the deafferented MVN after a unilateral labyrinthectomy.


Laryngeal aortic baroreceptor pathways and cardiac arrhythmia. This study was undertaken to confirm the effect of the ramus communicans baroreceptor pathway on cardiac rate during an upper-respiratory tract disturbance. The effects of destruction of this pathway were tested. It was found that cardiac rate could still be altered by stimulation of the main trunk of the superior laryngeal nerve, although the ramus communicans fibers were absent. Electrical stimulation of only the main trunk of the superior laryngeal nerve, but not any of its branches, is capable of causing cardiac changes. Cardiac changes also occur readily with mechanical stimulation of the area immediately superior to the vocal folds, despite bilateral destruction of the recurrent and superior laryngeal nerves. These findings question the proposed role of the laryngeal baroreceptor pathway as a major factor in the cause of cardiac changes related to intubation.


Persistent sensory disturbances and diplopia following fractures of the zygoma. In a follow-up study of 124 patients with fractures of the zygoma, 100 of whom had undergone surgery, sensory disturbances of the intraorbital nerve, mostly to a very moderate degree, were found in 46% of those operated on. Slight imperfections of the fracture reduction had no influence on the results, and no substantial difference in outcome was found between the different surgical methods employed. The diplopia that persisted in five patients was due to reduced motility of the globe, without  any displacement or sign of loss of orbital contents.


Nasopharyngeal pushback in treatment of velopharyngeal insufficiency. We describe a new technique for extensive retropositioning of the soft palate for the treatment of velopharyngeal insufficiency. This technique is identified as a nasopharyngeal pushback, and has been used repeatedly in conjunction with both a Cronin nasal flap and a superiorly based pharyngeal flap when maximum retropositioning was needed. This procedure has been used for over ten years, each time obtaining an additional pushback distance equal to or greater than the distance achieved by freeling the soft palate from the posterior border of the hard palate.


Actinomycosis of the face and neck.

Actinomycosis of the face and neck. Cervical actinomycosis is a rare condition. During the last six years, five patients were hospitalized in our department, suffering from swelling in the region of the face and neck that was identified bacteriologically as Actinomyces israelii. Soft tumors of the head and neck that do not respond to common antibiotic therapy should arouse the suspicion of actinomycosis.


Fume-induced fluorescence in diagnosis of nasal neuroblastoma. Nasal neuroblastoma, esthesioneuroblastoma, is frequently difficult to distinguish from the more common poorly differentiated epidermoid carcinoma of the nasal cavity and nasopharynx. We present a simple alternate method to electron microscopy, formaldehyde-fume-induced fluorescence, to demonstrate biogenic amine granules in neoplastic cells. This method is more specific and more sensitive, since it reveals the presence of biogenic amines, not merely membrane-bound granules, and it deals with larger quantities of tissue, thus avoiding some of the sampling errors inherent in electron microscopy. We also describe the histochemical relationship of this tumor to other neural crest neoplasms.


Abnormal microorganisms and cell-mediated immunity in patients with intraoral cancer. A substantial number of patients with intraoral malignant neoplasms have abnormal bacterial flora of skin, nasopharynx, and oropharynx, without a demonstrable relationship between tumor size, location, or degree of ulceration. Seventeen consecutive patients were studied to determine what relationship, if any, exists between the presence of abnormal microorganisms and the patients' immunological competence. Ten of 17 patients grew potentially pathogenic organisms, and all reacted to specific skin tests used to infer immunological competence. Thus, there appeared to be no relationship between cellular immunity and the presence of abnormal bacteria in patients with intraoral malignant neoplasms.


Flight-induced changes in human amino acid excretion. A biomedical appraisal of flight stress was made by means of a battery of urinary determinations on crewmen who participated in a 96-h airborne alert. The crewmen were divided into three teams, each consisting of 16 members and each manning an EC-135J aircraft. These teams took turns so as to assure that one team was airborne at all times during the alert; flights lasted either 8.5 or 12 h. Preflight baseline data were collected from only one of the three teams. Based on baseline and flight data obtained for that team, urea excretion correlated well with amino acid output which, in turn, correlated remarkably well with alpha-amino nitrogen output. These data collectively revealed the following flight effects: a) marked anticipatory stress immediately before the start of the airborne alert, b) marked flight stress late in each flight flown during the first 48 h, and c) adaptation to flight stress during the final 48 h.


Use of 85Sr as an indicator of bone mineral replacement in dogs after disuse demineralization. The left front legs of two beagle dogs were immobilized for 2 months; the right front legs of each were used as weight-bearing controls. Bone mineral replacement after immobilization was studied by giving intravenous injections of 85Sr. (Stroutium-85). After allowing the radioisotope to disappear from the soft tissues, measurements were made on only that remaining in the bone. The 85Sr uptake in the bone of the leg which had been immobilized was up to 400% higher than that in the control leg. This increased 85Sr uptake probably resulted from only a few percent loss in bone mineral during immobilization and suggests that losses of less than 1% can be detected and located. The sensitivity, simplicity and minimal radiation dose associated with this technique indicates potential application for use in human bedrest and space-flight studies.


Acclimation processes by daily exercise stints at temperate conditions followed by short heat exposures. In order to improve the conventional procedures for heat acclimation by making the process shorter and more efficient, four daily regimens of 30 min of exercise under temperate ambient conditions (22 degrees C) followed by a 30-min walk (5.6 km/hr under hot dry ambient conditions (50 degrees/25 degrees C, Tdb/Twb) were administered to three groups of subjects. The respective exercise part for each group was as follows: 1) 30 min of descent on a laddermill (negative work); 2) 30 min of ascent on a laddermill (positive work), and 3) 15 min of descent followed by 15 min of ascent on the laddermill. The four daily regimens of exercise and heat exposure were followed by four consecutive daily walks of up to 120 min in dry heat. A fourth control group was not subjected to the special acclimation regimen, but underwent the eight daily conventional acclimation procedures. Acclimation was judged by the increase in tolerance time (T) for the walk in the heat and decrease in heart rate (HR) rectal temperature (Tre) and mean skin temperature (Tsk). Partial acclimation was observed after the 4 d of the regimen for the three experimental groups and the 4 d of the conventional procedure on the fourth control group. The final state of acclimation was apparent on the eighth day for all four groups. When the partial acclimation after the 4-d regimen was compared to the final state of acclimation, the following improvements were observed: 90% increase in T; 72% decrease in HR; 56% decrease in Tre, and 45% fall in Tsk. These improvements were similar to those observed after the 4 d of the conventional treatment on the control group as well as to those reported by others.


Effects of hyperbaria upon morphine antidiuresis and analgesia in rats. The effects of helium-oxygen (He-O2) environments were observed upon the pharmacological actions of morphine in male albino rats given 100 mg/kg of body weight. Measurements of 8-h urine volumes revealed that animals maintained in ambient air and He-O2 at 1 ATA exhibited a marked antidiuresis. Animals exposed to He-O2 at 11 ATA showed a normal urine flow when compared with ambient air controls. Uninjected rats maintained in He-O2 at 11 ATA showed a marked diuresis. The study also included experiments to determine whether the excretion of free morphine is altered in He-O2 environments, and whether the analgesic effect of the drug is changed due to He-O2 environments. Exposure to He-O2 at 21 ATA was included in these studies. Significant decreases were noted in the excretion of free morphine during a 24-h period in those animals exposed to 11 and 21 ATA, although no difference was observed in the groups maintained at 1 ATA. Pressure was also shown to decrease the pain threshold in both uninjected and injected animals maintained at 11 and 21 ATA. The results indicate that the metabolism of morphine may be stimulated due to the effects of pressure.


Occupational differences between conventional and saturation divers. Diving experiences of 53 Divers First Class attending the U.S. Navy Saturation Diver Training Program were compared to 155 Divers First Class performing routine operational dives. The two groups were matched for years of diving experience, total number of dives, and total number of SCUBA dives. The Diving Experience Questionnaire (DEQ), which consisted of 43 items dealing with specific diving conditions and activites, was used to document the diving backgrounds of the two groups. Five of the 43 items were found to significantly and uniquely differentiate between the two groups. Those attending the Saturation Diving Program a) made more dives between 46-61 m (151-200 ft), b) had more experience with semiclosed-circuit SCUBA, c) attended more deep-diving training courses, d) made fewer dives in water warmer than 70 degrees F, and e) had fewer specialized qualifications outside deep diving. The multiple regression analysis which differentiated between the two groups resulted in an R of 0.48. These five items indicate that volunteering for saturation diving is consistent or congruent with past deep-diving experience, while remaining in conventional diving is congruent with previous shallow-water experience. These results indicate that the DEQ may be a highly useful method of differentiating between experienced divers.


Comparison of an impedance device to a displacement plethysmograph for study of finger blood flow. Empirical values of finger blood flow, determined with a commercial electrical impedance device, were compared with blood flow measurements made with a pulsatile air displacement plethysmograph. The measurements were made on the medial phalanges of the first, second, and third fingers of the left and right hands. Blood flow indices were calculated from extrapolated slopes of the recorded impedance and mechanical changes occurring during systole. Two series of observations were made on seven healthy male subjects. The first series consisted of 33 simultaneous measurements with the impedance rheograph and the air displacement plethysmograph on the same finger segment. In the second series of experiments, 16 measurements were made on comparable segments with the rheograph on one side of the body and the air displacement plethysmograph on the other side. The positions of the mechanical and electrical transducers were then exchanged and the procedure repeated. The right and left results were then averaged for each of the two flow measurement systems. Blood flow indices, determined with the impedance rheograph, were consistently 30% lower than those obtained with the air displacement system. The overall mean (+/- S.E.) for the impedance to air displacement blood flow ratio for the first series of measurements was 0.69 +/- 0.03 (range = 0.46 to 1.02). The mean (+/- S.E.) impedance to air displacement ratio for the second series of experiments was 0.68 +/- 0.06 (range = 0.30 to 1.14).


Disorienting effects of aircraft catapult launchings. II. Visual and postural contributions. Gx accelerations approximating those encountered in aircraft catapult launchings were generated on the human centrifuge Dynamic Flight Simulator at the Naval Air Development Center. Each of four catapult-experienced Naval aviators continuously oriented himself to the gravitational vertical both before and after exposure to the accelerations under two conditions: a) while he sat in total darkness, and b) while he viewed a small target projected at eye level in his mid-sagittal plane. The accelerations produce changes of pitch orientation that were affected by the presence or absence of the target, and the changes of orientation persisted well after the accelerations were terminated. Visual and postural illusions and their contributions to the disorientation are discussed, and the disorientation is related to certain water-collision accidents that have been reported to occur following aircraft catapult launchings at night.


Aircrew medical standards and their application in the Royal Australian Air Force. Aircrew selection and health maintenance are key factors in the Aviation Medicine Program of the Royal Australian Air Force. The physical standards employed by the RAAF in selecting aircrew are reviewed. The aircrew selection process for the 5 years 1969 to 1973 are presented with emphasis given to medical causes for rejection. A careful analysis of reasons for failure to complete aircrew training was conducted. The results of this analysis are presented with special emphasis being given to medical wastage. The process of medical evaluation of trained aircrew is discussed along with the 1969-1973 experience with aircrew duty restrictions and waivers granted for medical conditions. The RAAF experience with medical wastage of trained aircrew is similar to the experience of other nations, both as to wastage rates and body systems involved.


Attitudes and accidents aboard an aircraft carrier. A 22-item questionnaire, developed to measure various behavioral attitudes reportedly associated with accidents, was given to 879 enlisted air wing support personnel and 156 aviators on an aircraft carrier at the start of deployment. A factor analysis of these 22 items indicated six underlying concepts for which scales were created. Personnel injuries for the air wing and aircraft accidents for the aviators were recorded for the duration of the cruise, and correlations of these criteria with the 22 items and six scales were computed. Three items significantly predicted accidents in both populations and all three appeared in the same factor. The Adventurous scale developed from this factor was significantly (p less than or equal to 0.01) correlated with accidents in both groups. This scale appears to measure attitudes toward risk taking, which was the only concept found useful for the prediction of future accidents in this study.


Use of pilot heart rate measurement in flight evaluation. Experimental test pilots involved in the flight evaluation of handling qualities and systems were monitored for heart rate during an investigation to assess the possible use of this measure to augment their subjective opinions. Reference is made to examples from several different flight trials using a variety of aircraft types. It is concluded that pilot heart rate measurement is a worthwhile technique and can play a useful part in flight evaluation provided that certain limitations are recognised.


Human response to buffeting in an all-terrain vehicle. Suitably prepared subjects were exposed to the vibration imposed by driving a personal-type all-terrain vehicle over a heavily plowed track. Acceleration was measured in the Z-axis at the seat of the vehicle, and in the X, Y, and Z axes at the hip and head of the subjects. Acceleration peaks, rates of onset, durations, and frequency ranges were determined and a spectral analysis conducted. Results showed that, for this vehicle under the test circumstances, the subjects respond with a low-frequency (less than 4 Hz) oscillation at approximately 0.5 Gz above nominal, on which are imposed numerous peaks of 1 to 5 G, or higher with rates of onset within the range measured, of 20 to 100 G/s. Although the measurement system did not conform to ISO (International Standards Organization) requirements, the results suggest that continued exposure would exceed the ISO 1-min limit for "health and safety."


[Hematocrit in venous and capillary blood in children in shock]. Hematocrit was measured every 8 hours in the bloods of 20 shocked infants and in 10 healthy cases. Samples of blood were taken at the same time from the external jugular vein and following puncture on the heel. Whereas the difference of both measurements was 5.3% as an average in healthy cases, in patients it was of 25.7%. At the end of eight hours of treatment, there was still a difference of 28.8% in patients who finally died, but it dropped tp 8.8% in those who survived.


[Glomerulonephritis following an infected ventriculoatrial shunt. Report of 2 cases]. Two patients with shunt nephritis are reported. One of the patients had a positive blood culture to Staphylococcus albus; the kidney biopsy showed an immune complex disease. In the second patient, Klebsiella sp., was cultured in the blood, and this is the first report with such bacteria as the cause of nephritis. The finding of fibrin in the glomeruli by light, immunofluorescence and electron microsocopy studies, suggests a pathogenesis different from intravascular coagulation. In both patients, nephritis became inactive when the shunt was removed.


[Speed of intestinal passage and water content of feces in premature and full-term infants following exposure to phototherapy]. Fifty-one newborn infants were divided into five groups and were studied according to gestational age, hyperbilirubinemia and phototherapy. In each group, the speed of intestinal passage and content of water in feces was evaluated in terms of the variables mentioned. It was shown that neither hyperbilirubinemia nor phototherapy affect the content of water in feces, nor the speed of intestinal passage in pre-term infants. The same results were true for hyperbilirubinemia in full term infants in whom it was not possible to demonstrate the effect of phototherapy. Full term infants showed a greater content of water in feces and a higher speed of intestinal passage as compared with pre-term infants. This was possibly the result of different body weight due to a different gestational age.


[Renal response  to intravenous administration of sodium bicarbonate in newborn infants of different gestational ages]. The study comprised a series of 16 neonates made up of 5 patients of 33 weeks of gestation, 5 infants of 35 weeks and 6 more of 40 weeks of gestation. Blood pH, PaCO2 and HCO3- were measured together with bicarbonate, ammonium, titrable acidity and hydrogen ions in urine before and after intravenous infusion of sodium bicarbonate. Before infusion of bicarbonate, titrable acidity, ammonium and net acidity in urine were higher in accordance with a greater gestational age. As the administration of bicarbonate elapsed, titrable acidity, ammonium and net acidity dropped with increase in concentration of bicarbonate. A hypothesis is set forth that the differences found in the factors evaluated in urine before administration of bicarbonate depend on the physiologic characteristics set in the newborn by gestational age.


[Effect of minimal doses of phenobarbital on bilirubinemia in the newborn infant]. To evaluate the effect of lower than usual doses of phenobarbital on prevention of hyperbilirubinemia in the neonate, a study was carried out in neonates with subnormal weight and of similar characteristics regarding gestational age, intrauterine growth, absence of pathology, type and amount of milk formula ingested and values for indirect serum bilirubin previous to the initiation of the administration of phenobarbital on their second day of life; they were separate at random into three groups according to the dose of phenobarbital given (1 mg, 3 mg and 5 mg per kilo and per day, respectively) and were numerically distributed in similar manner. In all groups, serum indirect bilirubin rate was confirmed to be practically the same; the differences did not show statistical significance from the 2nd to the 6th day of life, when the study was done. As preventive of neonatal hyperbilirubinemia, the drug is efficient at doses as low as 1 mg/kg/day. It is believed that similar responses with different low doses of phenobarbital is due to the fact that the drug enzymatic induction phenomenon is brought forward, even at minimal doses, such as has been demonstrated through experiences in animals where the effect is produced even with doses of micrograms per kilogram of weight.


[Malignant reticuloendoteliosis. Prognostic analysis]. A description is made of the correlation between symptomatology and survivorship in 50 cases of malignant reticuloendotheliosis grouped as follows: 1. Cases with a single bone lesion, with several bony lesions, with lesions in bones and in soft tissues and with lesions only in soft tissues. 2. Each symptom is given the value of 1 and with the resulting addition, a rate is established. In the first part, it was found that survivorship was better in those groups that only showed bony lesion and within them, in those with a single lesion. The worst survivorship was for those cases with lesion only in soft tissues. In the second part, it was shown that survivorship was definitely less for cases with higher rating. Based on the previously described, this classification and rating is proposed to establish an earlier and more exact prognosis than usual.


[Retinoblastoma. Relation between choroid infiltration and orbital metastasis]. A late diagnosis of retinoblastoma is an unquestionable fact that allows its growth and leads to a deterioration in the outlook. It also gives way to the invasion of the choroidea by the retinal tumor. This event has been related by some authors to orbital recurrences or distant metastases. The evolution of intraocular retinoblastomas, with and without invasion to choroidea, is compared in this work. No significant differences were found in the thirty-three cases studied.


[Congenital toxoplasmosis].

[Congenital toxoplasmosis]. Judged by the cases studied at the Hospital de Pediatría, congenital toxoplasmosis may be transmitted to several descendants and the infection capacity of the mother persists for a long time. The possibility of toxoplasma infection should be investigated in cases of hydrocephalus, convulsions, microcephalia, ocular lesions or pictures of neonatal hepatitis. To explain invasion to the central nervous system by Toxoplasma gondii, a pathogenic hypothesis is offered.


[Psychological aspects of family planning]. In spite of the great impact on the public opinion produced by the diffusion of the threats on humanity derived from the so-called "demographic explosion", many factors prevail upon the acceptance or rejection of family planning. For instance, developed countries and privileged classes have been accused of promoting campaigns tending to limit the development of the destitute sections of the population, fearing to be overwhelmed by their disproportionate growth. At another level, certain male groups consider the advent of modern contraceptive procedures as a menace to the preponderance  of man over woman if she is allowed sexual intercourse free from unwanted pregnancies. Still other groups, with or without religious influences, contend against any interference with nature, in spite of the fact that "demographic explosion" is precisely the result of modern medicine which has actually interfered to a great extent on it. The emotional nature of these attitudes, frequently obscures many other psychological factors strange to any demographic consideration, but show a striking influence on family planning, especially on the use of different contraceptive procedures. In the present paper, two main groups are considered: a) psychological factors leading to parents wishing or not to have descendants. b) psychological factors and attitudes associated with contraception. Finally, considerations are made on the rejection of the unwanted child and on abortion. Both of these problems have deep psychosocial implications where family planning may play a preventive role of tremendous transcendency.


[Multiple congenital arthrogryposis as a cause of learning and communicating problems]. Since 1963, the authors have studied 83 cases of multiple arthrogryposis. Incidence at Hospital de Pediatria was 0.006%. It was shown that clinicians usually pay attention only to osteoarticular problems and very little attention to neurological problems. A new classification of arthrogryposis is proposed, including learning and communication problems with the aim of providing means for the study of the disease under a multidisciplinary approach.


[Intestinal infarction in the newborn].

[Intestinal infarction in the newborn]. Intestinal infarction was studied in 20 children with acute gastroenteritis. Eighteen cases (90%) died and 2 (10%) recovered. The disease was most frequently seen in infants under one month of age (85%) and in malnourished cases with subnormal weight at birth. It was suspected only in four patients and in the rest, it was a surgical or post mortem finding. No clinical or radiological findings were detected to orient diagnosis. The following signs are considered jointly to support a diagnostic suspicion; prolonged paralytic ileus, abdominal vascular distress, peritoneal irritation, shock and history of diarrhea. Considerations are made on its pathology, clinical picture and treatment, stressing the fact that an early surgical treatment may increase survival possibilities.


[Correlation between osmolarity and specific gravity of urine. Changes caused by the presence of abnormal solutes]. There is a high correlation index (0.97) in the measurement of urine osmolality and specific gravity in healthy children and adults and in children with renal disease without heavy proteinuria or glucosuria. This is a useful tool, because osmometers are not used in many laboratories, but specific gravity is of general use, so that urine concentration in mOsm/kg. can be derived from the specific gravity. The same parameters in urines with heavy proteinuria or glucosuria were also measured and the correlation index and the modifications per gram of abnormal solute that should be applied in order to obtain the correct urine concentration figures, were established.


[Absence of bacteremia after dental extractions]. A study was made on 100 subjects of both sexes between the ages of 3 and 15 years to detect the presence of bacteria in the circulation after performing dental extractions.  Two groups were formed of 42 and 57 subjects respectively. One of these groups was subjected to preoperative antisepsis of the region to be operated on, the rest of the conditions were similar for both groups. All the patients were submitted to a preoperative gingival smear and 5 c.c. of blood taken for cultures. Two postoperative blood cultures, one immediately after the operations and another 24 hrs. later were also done in all patients. All the extracted teeth presented severe infections at the root level and some showed complicated infection such as osteomyelitis. All blood cultures performed 24, 48, 72 hrs. and 21 days after the operation, were negative; therefore, there is no justification based on the study, to assume the existance of focal infection related to the presence of bacteremia.


[A new therapeutic approach to eczema in pediatrics]. Considering the disease as a psychophysiologic reaction of the skin, a psychologic therapeutic approach was used in 15 children with epidemiologic problems of atopic eczema.


[Congenital posterolateral diaphragmatic hernia]. Eighty-four cases of posterolateral diaphragmatic hernia in children are reviewed. The most frequent signs were respiratory insufficiency, cyanosis and costal indrawing. The diagnosis was clinically established in over one half of the cases. In most of the patients, the studies showed respiratory acidosis. Also, radiological studies showed, in most of the cases, elevation of the hemidiaphragm with basal opacity of the hemithorax. For surgical treatment, the choice route was the abdominal. Overall mortality reached 37%.


[Clinical characteristics of various neuroviroses in relation to their etiology]. No clinical, cytochemical nor electroencephalographic standards of behavior, specific for each etiology were found in a series of 67 cases of viral infection of the nervous system; however, the severeness was greater in cases of infectious mononucleosis with encephalic involvement and in cases caused by Coxsackie B5 possibly because these appeared in younger patients. The group with greater percentage of definitive motor and intellectual sequelae was found in cases with infectious mononucleosis and ECHO. Cases due to herpes simplex were not more severe during the acute stage, but followed a course with an important percentage of definitive sequelae. Meningoencephalitides from parotiditis were milder, and only in one case did they show permanent motor sequelae.


The interaction of alpha-thalassaemia and haemoglobin G Philadelphia. An American Negro woman was found to have HbH disease in association with HbG Philadelphia (alpha68-asn leads to lys). Starch gel electrophoresis failed to reveal the presence of any HbA or HbA2 and studies of globin chain synthesis indicated absence of alphaA production. The alphaG/beta synthesis ratio was 0.63. The woman's son and her two half-sibs had alpha-thalassaemia trait with no HbH and alpha/beta synthesis ratios of 0.84, 0.84 and 0.76. The data indicate that there is no functioning alphaA gene linked to the alphaG gene. The absence of alphaA synthesis by the propositus also indicates that the alpha-thalssaemia gene trans to the alphaG gene completely suppresses alpha chain production, the first evidence for such a gene in Negroes.


[Febrile syndrome of unknown etiology].

[Febrile syndrome of unknown etiology]. The results of the analysis of 114 patients with fever over 38 degrees C with minimal duration of one week, are reported. There were no data from the physical examination to produce a nosological diagnosis. The greater number of age groups were for infants (43%) and school children (35%). There was a predominance in males (62.3%). There were histories of potential usefulness for the diagnosis in 39 patients, but only in 7 cases was it possible to establish a relationship with the illness. In 70 patients (61.4%) it was not possible to determine exactly the cause of fever. In the remaining cases, a distribution into three etiological groups was made: infectious or parasitic, collagenous disease and malignant neoplasia. Considerations are made on these groups and on the usefulness, for the diagnosis, of the type of fever graph. The course is analyzed and conclusions are established.


[Congenital tuberculosis. Description of a case]. Presentation is made of a case in a premature newborn, the offspring of a mother with bilateral pulmonary tuberculosis, of placental lesions suggestive of tuberculosis and acute miliary congenital tuberculosis with lesions in liver, spleen, lymph nodes and lungs due to a possible blood stream dissemination starting from the placental infection.


Erythropoiesis and carbon monoxide production in Hodgkin's disease. Endogenous production of carbon monoxide (VCO), red cell survival and iron kinetics were studied in 15 subjects with Hodgkin's disease. The subjects were divided into two groups, namely: eight patients with anaemia (group A, haemoglobin (Hb) concentration less than 11.5 g/dl) and seven patients without anaemia (group B, Hb concentration greater than 11.5 g/dl). Red cell survival was not significantly different in the two groups being 91 +/- 40 days (mean +/- 1 SD) in group A and 111 +/- 54 days in group B. Relative VCO (mumol/mmol total body haem (TBH/d) was, however, significantly higher (0.01 greater than P greater than 0.001) in group A (20.7 +/- 4.7) compared to group B (12.0 +/- 3.8). When absolute VCO (mumol/d) was compared to the daily turnover of circulating red cell haemoglobin haem (Vhaem-c), the VCO/Vhaem-c quotient was 2.1 +/- 0.9 in group A and 1.2 +/- 0.3 in group B. Erythron turnover of iron (ET, mumol Fe/mmol TBH/d) was calculated through subtraction of the non-erythron turnover (NET) from the total plasma iron turnover (PIT). ET was significantly higher (0.05 greater than P greater than 0.01) in group A (39 +/- 21) than in group B (20 +/- 8). The conclusion drawn from the finding of significant increases in VCO and ET without and concomitant significant decrease in red cell survival in the anaemia group is that ineffective erythropoiesis, i.e. bone marrow haemolysis, seems to play an important role in the anaemia of Hodgkin's disease.


[Chylous ascites. Report of a case following the rupture of Pecquet's cistern]. The first case in the national literature of chylous ascites following traumatic rupture of Pequet's cistern, confirmed through lymphography is reported. The technique employed and concomitant bone changes are discussed.


Carbon monoxide production in patients with breast carcinoma. Total haem catabolism has been studied through measurement of endogenous production of carbon monoxide (VCO) in 19 patients treated for breast carcinoma. The subjects were divided into three groups. Group A included six patients with haemoglobin (Hb) concentration greater than 11.5 g/dl and considered free from disease. Group B consisted of seven patients with distant metastases and Hb concentration greater than 11.5 g/dl and group C of six patients with distant metastases and anaemia (Hb concentration less than 11.5 g/dl). VCO in group A was 10.3 +/- 3.7 (mean +/- 1 SD) and in group B 9.0 +/- 2.5 mumol/mmol total body haem (TBH)/d. These values are not different from our normal values of 10.8 +/- 2.8 mumol/mmol TBH/d. In group C VCO was 21.1 +/- 3.1 (an increase of 100%). VCO was compared to daily catabolism of circulating red cell haemoglobin haem (Vhaem-c) in the VCO/Vhaem-c quotient. Vhaem-c was calculated from total circulating red cell haemoglobin haem (TBHb-c) and red cell survival. In group A and group B this quotient was 1.3 +/- 0.6 and 1.1 +/- 0.2, respectively, and in group C was 2.5 +/- 0.9. The difference between group A and B on one side and group C on the other side was significant (P less than 0.001). The 'extra' CO produced in patients with anaemia and disseminated disease (group C) was thought to originate from increased turnover of bone marrow haem, reflecting considerable ineffective erythropoiesis with destruction of haemoglobinized immature red cells. The results confirm earlier findings of a high VCO/Vhaem-c quotients in patients with anaemia secondary to Hodgkin's disease.


Haemolytic effect of two sulphonamides evaluated by a new method. A technique to investigate drugs which could cause haemolysis in subjects deficient in glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase; G6PD) has been developed. The method is based on the technique of 14CO2 evolution during the incubation of normal erythrocytes in the presence of [I-14C]glucose and their own serum, the latter containing the active metabolites of the drugs received by normal subjects. By this method agents causing a stimulation of the hexosemonophosphate pathway of normal erythrocytes should be regarded as potentially haemolytic for G6PD-deficient subjects. Two sulphonamides, sulphormethoxine and sulphalene, of which until now no haemolytic effects have been reported, together with chloroquine, have been investigated. While chloroquine does not affect the hexosemonophosphate shunt of normal erythrocytes, the two sulphonamides stimulate this pathway. THE RESULTS ARE CONFIrmed by the reduction of the half-life of 51Cr-labelled G6PD-deficient red cells (Mediterranean variant), after administration of the two sulphonamides.


Oxidation of human and animal haemoglobins with ascorbate, acetylphenylhydrazine, nitrite, and hydrogen peroxide. Partially purified haemoglobin solutions of man, horse, car and dog were oxidized with ascorbate, acetylphenylhydrazine, nitrite, and H2O2 at 25 degrees C and with ascorbate and acetylphenylhydrazine at 37 degrees C. Haemoglobins of the carnivores were more easily oxidized with ascorbate, nitrite, and H2O2 than equine and human haemoglobins. Feline haemoglobin, in general, appeared more susceptible to oxidation, particularly oxidative denaturation, than those of the other species. In addition, results of the incubations at 37 degrees C suggest that feline haemoglobin B might be more susceptible to  oxidative denaturation than feline haemoglobin A. Equine haemoglobins appeared to be the least susceptible to oxidation with ascorbate and nitrite, but were more easily oxidized with acetylphenylhydrazine than those of the dog or man. It is apparent, therefore, that because a haemoglobin is more susceptible to oxidation with one oxidant does not mean that it will be more susceptible to oxidation with all oxidants. Results from the present study support the concept that an oxidant intermediate(s) is more important than H2O2 in drug-mediated oxidation of haemoglobin.


The morphological classification of red cells using an image analysing computer. Image analysis provides a potential method for automation in the examination of blood films. In order to assess the applicability of this technique to red cell morphology, a scheme has been defined for the classification of red cells into six categories, namely, round cells, elongated cells, tear drop poikilocytes, helmet cells, irregular cells and spherocytes. A study was carried out to determine the consistency which observers classified red cells according to this scheme. Measurements of area, perimeter, maximum diameter and integrated optical denisty of fixed, Romanowsky-stained red cells were made using an image analysing computer. A multivariate classifier based on parameters derived from these measurements, namely cell area and the quotients of integrated density over area, area over the square of perimeter and perimeter over maximum diameter was also used to classify red cells into the above categories. It was found that the inherent error of the machine-based classifier was of the same order as the degree of inconsistency encoutered between trained observers. The significance of these findings is discussed.


Function and ultrastructure of platelets of neonates: enhanced ristocetin aggregation of neonatal platelets. We have investigated platelet morphology and function in human maternal-newborn pairs. Fibrinogen concentration and factor-VIII activity in plasma were also determined. Our results showed that, compared to maternal platelets, neonatal platelets were poorly responsive to adenosine diphosphate, adrenaline and collagen. Uptake of labelled serotonin by neonatal and maternal platelets was the same, but release of the radioactivity was reduced in the former. Phagocytic activity of neonatal platelets, demonstrated with latex particles, was similar to that of maternal platelets. Although the ultrastructure of neonatal platelets approximated that of maternal platelets, immature appearing platelets were occasionally found in the neonatal samples. An unanticipated finding was that platelet aggregation induced by ristocetin was more vigorous in neonatal than in maternal platelet-rich plasma samples. Furthermore, neonal -lasma, which had lower fibrinogen and factor-VIII content than maternal plasma, facilitated maternal platelet aggregation by ristocetin and showed a greater ability than maternal plasma to promote ristocetin-induced aggregation of platelets of a patient with von Willebrand's disease. These results indicate that the plasma of neonates contains large quantities of the ristocetin-dependent platelet aggregation factor (RAF), probably more than is in maternal plasma, despite the higher levels of factor-VIII procoagulant activity in the latter. Thus, in the newborn, there is a clear dissociation between factor-VIII clotting activity and the RAF activity.


Role of vitamin B12 in folate coenzyme synthesis. Normal red cells in man were found to contain predominantly folate pentaglutamates with smaller amounts of tetra- and hexapolyglutamates. There was no change in the type of polyglutamate present in red cells from patients with vitamin B12 deficiency and primary folate deficiency. In contrast to the fall in red cell polyglutamate concentration in vitamin B12 deficiency, there was a marked fall in short-chain folates in early folate deficiency (treated non-anaemic epileptics) and a fall in both short chain and long chain polyglutamates in patients with severe folate deficiency and megaloblastic anaemia. These differences in folate distribution within cells exclude a primary failure to transport methylfolate into cells as the lesion in vitamin B12 deficiency. The failure of folate polyglutamate synthesis in ivtamin B12 deficiency arises either from a failure to provide the proper substrate for polyglutamate synthesis or to a direct requirement for vitamin B12 for polyglutamate synthesis.


Factor VIII and factor-VIII-related antigen in multiple myelomatosis and related conditions. Factor VIII and factor-VIII-related antigen (FVIIIRA) were estimated in 19 patients with paraproteinaemia. The FVIIIRA levels were above the normal range in 12 cases with II of these showing an abnormal FVIII/FVIIIRA ratio. The patients could be subdivied into three groups according to their FVIIIRA levels: normal levels, levels greater than normal but less than 200%, greater than 200%. This subdivision correlated with the degree of bone involvement as assessed by radiological skeletal survey.


Prostaglandin E2 potentiation of platelet aggregation induced by LASS endoperoxide: absent in storage pool disease, normal after aspirin ingestion. Patients with storage pool disease and normal subjects who ingest aspirin show diminished collagen-induced platelet aggregation and an absent second wave of aggregation with ADP or adrenaline. These 'second-phase' aggregation responses are thought to be mediated by cyclic endoperoxide ('labile aggregation stimulating substance', LASS) that is derived from arachidonic acid and is the precursor of prostaglandin E2 (PGE2) and PGE2alpha. Furthermore, although PGE2 does not directly aggregate platelets, it markedly potentiates LASS-induced aggregation. The platelets of six patients with storage pool disease were capable of converting arachidonic acid to LASS, but the potentiation of LASS-induced aggregation by PGE2 was markedly diminished. In contrast, PGE2-potentiation of LASS aggregation was not reduced after aspirin ingestion. The effects of aspirin can be attributed entirely to its ability to block the enzymatic conversion of arachidonic acid to LASS and PGE2. These findings explain why a mutual correction of the aggregation defects is often seen when aspirin-treated platelets are mixed with storage pool-deficient platelets. This is because 'aspirin platelets' aggregate to the mixture of LASS and PGE2 produced by the storage pool-deficient platelets, which are themselves unresponsive. The findings in storage pool disease support previous conclusions that prostaglandin sensitization of platelets to the pro-aggregatory effects of LASS is an important factor in irreversible aggregation, and could be clinically important.


The effect of trimethoprim on cellular transport of methotrexate and its cytotoxicity to human lymphoblastoid cells in vitro. A study has been made of the effects of the antifolate drug trimethoprim (2,4-diamino-5-(3'4',5'-trimethoxybenzyl)pyrimidine) on the cellular transport of natural folates and of methotrexate in a human lymphoblastoid cell line grown in culture. The results indicated that cellular uptake of 5-methyltetrahydrofolate, folic acid and methotrexate could be inhibited by trimethoprim; the inhibition, for methotrexate at least, was competitive, but it was in every case rather weak. Calculations showed that under conditions used during therapy with methotrexate, trimethoprim could be employed as an antibacterial agent without the cellular uptake of methotrexate being impaired by more than 1%. The cytotoxic effect of trimethoprim against the cell line used was 2000 times less, on a molar basis, than that of methotrexate. However, the degree of growth inhibition caused by the two agents in combination was greater than the sum of the individual toxicities. Again, this effect was not large at clinically useful concentrations of trimethoprim.


Investigation of quercetin binding sites on chloroplast coupling factor 1. The quercetin binding sites on spinach chloroplast coupling factor 1 (CF1) have been investigated using direct and competitive binding, stopped-flow, temperature-jump, and fluorescence resonance energy transfer measurements. It was found that 8-anilino-1-naphthalensulfonic acid (ANS) competes with quercetin binding at two sites on the solubilized enzyme which are distinct from the two tight nucleotide binding sites and the 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) reactive site. The bimolecular association of quercetin with CF1 is too fast to measure directly and is followed by two slower conformational changes. The distances from the tight nucleotide sites to the quercetin-ANS sites were estimated as 40-48 A by fluorescence resonance energy transfer using 1,N6-ethenoadenosine diphosphate and 1,N6-ethenoadenylyl imidodiphosphate as donors and quercetin as the acceptor. The distance from the quercetin-ANS site to the NBD-C1 reactive site was found to be about 30 A using ANS as a donor and NBD-C1 reacted with a tyrosine group on CF1 as the energy acceptor. A model is proposed for the relative location of these sites on CF1.


On the free-energy changes in the synthesis and degradation of nucleic acids. Standard free-energy changes for reactions involving single- and double-stranded nucleic acids have been related to that for polynucleotide synthesis from ribonucleoside diphosphates for which deltaG degrees' approximately O. For polynucleotide formation from triphosphates this quantity is about -1 kcal. In the replication reaction the base pairing interactions are quantitatively of comparable importance. Production of a hydrolytic break in a double strand is substantially less favorable than in a single strand. The resealing of breaks utilizing ATP and NAD+ have similar free-energy changes and are entropy driven processes. The highly exergonic hydrolysis of pyrophosphate is maintained to be of significance for both in vivo and in vitro polymerizations.


Stereospecific binding of diastereomeric peptides to salmon sperm DNA. Studies of the interaction specificities of L-lysyl-L-phenylalaninamide (1) and the diastereomeric dipeptide amide, L-lysyl-D-phenylalaninamide (2), with salmon sperm DNA reveal distinct differences in the binding site of the aromatic ring of the phenylalanine residue. The results of 1H nuclear magnetic resonance (NMR), spin-lattice relaxation rates, viscometric, and flow dichroism studies indicate the aromatic ring of 1 is "partially" inserted between base pairs of DNA whereas the aromatic ring of 2 points outward toward the solution. The terminal L-lysyl residue presumably interacts stereospecifically with DNA helix thus dictating the positioning of the aromatic ring of the C-terminal phenylalanine residue. In the accompanying paper (E. J. Gabbay et al. (1976), Biochemistry, following paper in this issue), the interaction of several oligopeptide amides (containing the N-terminal L-Lys-L-Phe residue) with DNA is examined. The results are found to be consistent with stereospecific binding of the terminal L-lysyl residue, and in addition, the evidence suggests that oligopeptides may bind to DNA via a modified single-stranded beta-sheet structure which is wrapped around the nucleic acid helix in a manner similar to that described by M. H. F. Wilkins (1956), Cold Spring Harbor Symp. Quant. Biol. 21, 75).


Pre-proparathyroid hormone: analysis of radioactive tryptic peptides and amino acid sequence. The amino acid sequence of bovine pre-proparathyroid hormone has been partially determined by analysis of the polypeptide labeled selectively with radioactive amino acids. Analysis of tryptic peptides containing methionine or lysine indicated that parathyroid hormone, proparathyroid hormone, and pre-proparathyroid hormone had several common peptides. Two lysine-containing peptides present in proparathyroid hormone but not in parathyroid hormone were also present in pre-proparathyroid hormone. In addition, pre-proparathyroid hormone contained several additional lysine- and methionine-containing peptides not present in parathyroid hormone or proparathyroid hormone. Analysis by repetitive Edman degradation of the polypeptide labeled with lysine, methionine, and other amino acids indicated that pre-proparathyroid hormone contained 25 additional amino acids at the amino terminus of proparathyroid hormone; the identities of 17 of the 25 amino acids have been established. An unusual feature found was the presence of methionyl-methionyl at the amino terminus and the presence of 5 methionines within the first 14 amino acids.


The interaction specificity of peptides with DNA. Evidence for peptide beta-sheet-DNA binding. Proton magnetic resonance studies (1H NMR) of the interaction of oligopeptide amides of defined sequence (and containing the amino acid, phenylalanine) with salmon sperm DNA are reported. The extent of upfield chemical shifts, deltasigma, and signal line broadening of the aromatic protons (in the presence of excess DNA) are found to depend on the primary sequence and stereochemistry of alpha carbons of the amino acids in the oligopeptide amides. The results obtained with 21 different di-, tri-, tetra-, penta- and hexapeptide amides are found to be consistent with a model whereby the peptide assumes a slightly modified single-stranded beta-sheet structure which is wrapped around the nucleic acid helix in a manner similar to that described by M. H. F. Wilkins (1956), Cold Spring Harbor Symp. Quant. Biol. 21, 75).


Configuration of unsheared nucleohistone. Effects of ionic strength and of histone F1 removal. Nucleohistone solubilized from rabbit thymus nuclei by an endogenous nuclease has in 0.15 M salt an exceptionally low intrinsic viscosity and very high sedimentation velocity. A fully reversible expansion of configuration occurs on lowering ionic strength. When [eta] is plotted against I-1/2 and extrapolated to high I, [eta] = 0 is reached at I = 0.4-1 M and [eta] at I = infinity is negative, contrary to the behavior of DNA and of the great majority of polyelectrolytes, which extrapolate to a positive [eta] at I = infinity. This behavior demands that the configuration of nucleohistone depends not only on electrostatic expansive forces but also on contracting forces which are not electrostatic and do not go to zero in any accessible configuration. Intramolecular hydrophobic bonds might provide such contracting forces. Increasing I above 0.15 M leads to precipitation near 0.3 M and redissolution with dissociation of F1 and expansion in 0.6 M. The expansion is largely but not completely reversed on return to 0.15 M. Much further expansion occurs in I = 1.2 M. Nucleohistone exposed to 1.2 M could not be redissolved in the original medium. Nucleohistone depleted of F1 exhibits a similar expansion as ionic strength is reduced, at higher viscosities throughout. On extrapolation to I = infinity both positive and negative viscosities were observed, on different lots, perhaps reflecting variable extraction of other histones. Circular dichroism spectra are very little affected by ionic strength (0.6 M and lower) or F1 removal, despite tenfold changes in viscosity.


Complete retention of phospholipid acyl groups by mammalian cells in culture. Radiolabeled phosphate, acetate, and glycerol are incorporated into strain L-fibroblast phospholipids. The acetate and glycerol specifically label the fatty acid and glycerol moieties, respectively, of the phospholipids. To study the metabolic fate of the various moieties of phospholipids, cells incubated with the above radiolabeled compounds were transferred to unlabeled medium, and the rate at which phospholipid radioactivity per 10(6) cells decreased was determined. The rate of decrease expected on the basis of cell division alone was estimated either by monitoring increases in cell number, or by measuring the rate at which radiolabeled DNA per 10(6) cells decreased. Both phospholipid phosphorus and glycerol are lost at a rate greater than can be accounted for by cell division alone. By contrast, nearly all phospholipid acyl chains were retained by the cell to the same extent as radiolabeled DNA. While presence of nonradioactive glycerol in the medium increased the rate at which glycerol was lost from phospholipid, the addition of exogenous fatty acid was without effect on the retention of phospholipid acyl groups. The acyl-glycerol bond of phosphatidylcholine is metabolically more labile than that of phosphatidylethanolamine. Together the data suggest that although L-fibroblast phospholipids undergo deacylation-reacylation reactions, the acyl chains do not equilibrate with either extracellular or intracellular pools of unesterified fatty acid.


Pre-proparathyroid hormone: fidelity of the translation of parathyroid messenger RNA by extracts of wheat germ. Pre-proparathyroid hormone is the major protein synthesized in wheat-germ extracts in response to addition of an 8-15S fraction of parathyroid RNA. The accuracy of the translation of the mRNA from parathyroid tissue was examined by analysis of the carboxyl-terminal tryptic peptide and the amino-terminal amino acid of the protein, by analysis of the size distribution of the mRNA, and by translation of the mRNA in a second cell-free extract. When 8-15S RNA was fractionated on a sucrose gradient containing formamide, RNA that supported the synthesis of pre-proparathyroid hormone was present in a single symmetrical peak, suggesting that it was homogeneous. Analyses by paper chromatography and electrophoresis of the proline-containing tryptic peptides of pre-proparathyroid hormone indicate that they are identical with the corresponding proline-containing peptides of parathyroid hormone. Because the COOH-terminal tryptic peptide of parathyroid hormone contains proline, the data indicate that the COOH termini of pre-proparathyroid hormone and parathyroid hormone are identical. Methionine from initiator [35S]Met-tRNAfMet was rapidly incorporated into pre-proparathyroid hormone by the wheat-germ extract, and a single-step Edman degradation selectively removed almost all of the initiator [35S]methionine present in pre-proparathyroid hormone. Translation of the 8-15S RNA in a cell-free extract from Krebs-II ascites cells resulted in a protein that comigrated with pre-proparathyroid hormone on sodium dodecyl sulfate-acrylamide gel electrophoresis. These data support the conclusion that the wheat-germ system accurately translates the mRNA for parathyroid hormone, and they strengthen the contention that pre-proparathyroid hormone is the initial biosynthetic product.


Purification, characterization, and partial amino acid sequence of nerve growth factor from cobra venom. The nerve growth factor (NGF) from Naja naja (cobra) venom has been purified and its structure compared to the NGF from mouse submaxillary gland. A two-step purification procedure has been devised, consisting of a gel filtration step in 1 M acetic acid followed by chromatography of the active pool on carboxymethylcellulose at pH 5. The molecular weight of the native protein was found to be 28000, and this value was reduced by approximately one-half under denaturing conditions. These values are comparable to those obtained for mouse 2.5S or betaNGF. Tryptic peptide maps of S-[14C]carboxymethyl NGF gave the number of labeled peptides expected for a structure composed of two identical or very similar subunits. Thus, the quaternary structures of mouse and cobra NGF are the same. Cyanogen bromide (CNBr) treatment of Naja naja NGF produced three fragments, of which two were purified to homogeneity. These fragments and the whole protein were analyzed in the automated protein Sequencer. The amino-terminal CNBr fragment of the protein was also subjected to digestion by thermolysin and the resultant peptides were purified and characterized. These data plus those from the characterization of the tryptic peptides provided the basis of the construction of a tentative primary structure of Naja naja NGF which is approximately 60% identical with mouse NGF.


Isolation of a 32P-labeled polypeptide of low molecular weight from phosphorylated human erythrocyte membranes. The incorporation of 32P into well washed human erythrocyte membranes was studied in a medium containing [gamma-32P]ATP, Mg2+, and EGTA. Following phosphorylation, the membranes were completely solubilized in 1% sodium dodecyl sulfate and subjected to gel electrophoresis in dodecyl sulfate polyacrylamide. A large incorporation of radioactivity was observed in a band which migrated faster than component 7 (nomenclature of T. L. Steck, (1972), J. Mol. Biol. 66, 295) but slower than the bromophenol blue tracking dye, and did not stain with Coomassie Blue. Isolation of this band by preparative gel electrophoresis revealed that 41% of the radioactivity was associated with a 32P-labeled polypeptide. This polypeptide was further purified by gel chromatography on Sephadex LH-20 in chloroform-methanol-HCl, and Bio-Gel A 1.5m in dodecyl sulfate. Its amino acid composition is characterized by a high content of acidic residues. The calculated minimal molecular weight is 15084. Based upon the recovery of amino acids, the polypeptide fraction comprises at least 1.8% by weight of the total erythrocyte membrane proteins. An apparent molecular weight of 15000 was estimated by gel chromatography in dodecyl sulfate, while a range of 14000-16000 was estimated by electrophoresis in dodecyl sulfate polyacrylamide. The state of phosphorylation of this peptide may reflect a physiological function in the intact red cell.


A method for the separation of hybrids of chromatographically identical oligomeric proteins. Use of 3,4,5,6-tetrahydrophthaloyl groups as a reversible "chromatographic handle". Hybridization experiments with variants of an oligomeric protein often provide important information regarding subunit structure, function, and interactions. In some systems, however, the variants are so similar electrophoretically and chromatographically that purification of individual hybrids is not feasible. Therefore a method was developed for preparing hybrids by using 3,4,5,6-tetrahydrophthalic anhydride as a reversible acylating agent for protein amino groups. The technique involved acylating about 30% of the amino groups at pH 8 to give a derivative with a markedly altered net charge, formation of the hybrid set with unmodified and modified species, separation of the individual components by ion-exchange chromatography, and finally removal of the tetrahydrophthaloyl groups from the desired hybrid by incubation for about 1 day at pH 6 and room temperature. Experiments with model compounds and two enzymes showed that the anhydride was sepcific for amino groups. The extent of modification of proteins was measured by the spectral change at 250 nm, the loss of free amino groups, and the change in electrophoretic mobility of the polypeptide chains in polyacrylamide gels containing 8 M urea. Deacylation of modified, inactive aldolase and the catalytic subunit of aspartate transcarbamylase led to the restoration of the enzyme activity and electrophoretic mobility of the unmodified proteins. Both intra- and inter-subunit hybrids of aspartate transcarbamylase were prepared and isolated by using the tetrahydrophthaloyl groups as a reversible "chromatographic handle". Prior to deacylation the inter-subunit hybrid containing one acylated and one native catalytic subunit (and negative regulatory sub-units) exhibited no homotropic cooperativity and after deacylation the characteristic allosteric properties of the enzyme were regained. Similarly the ligand-promoted conformational changes associated with the allosteric transition were resotred upon deacylation of the intra-subunit hybrid containing one acylated and two native chains in each catalytic subunit. Criteria are described which must be satisfied if a reversible "chromatographic handle" is to be effective in hybridization experiments and it is shown that, despite some heterogeneity in its reaction with protein amino groups, 3,4,5,6-tetrahydrophthalic anhydride shows considerable promise for studies of oligomeric proteins.


Vespulakinins: new carbohydrate-containing bradykinin derivatives. Two structurally similar and highly active glycopeptides have been isolated from extracts of yellow jacket venom sacs by ion-exchange and droplet countercurrent chromatography procedures. Vespulakinin 1 (heptadecapeptide) and vespulakinin 2 (pentadecapeptide) are both highly basic and contain the nonapeptide bradykinin at their carboxy termini. Most unique is the presence of carbohydrate. Vespulakinins are the first reported naturally occurring glycopeptide derivatives of bradykinin and the first reported vasoactive glycopeptides.


The monomers and oligomers of ferritin and apoferritin: association and dissociation. We have reinvestigated the association and dissociation of ferritin and apoferritin in phosphate buffer (pH 7.2, I = 0.05). When oligomer-enriched solutions of horse spleen ferritin were mixed with more concentrated, but unenriched solutions of horse spleen apoferritin, there was dissociation of the ferritin oligomers, as determined by polyacrylamide gel electrophoresis and from iron/protein ratios. Some evidence was also obtained for association of monomers in the mixture of ferritin and apoferritin after pelleting and redissolution of pellets in minimal volumes of the phosphate buffer. Monomer-enriched, biosynthetically labeled rat liver ferritin was pelleted, redissolved in minimal volumes of phosphate buffer, and separated by polyacrylamide gel electrophoresis; the fractions were isolated and counted. The results revealed that an association of monomers of the rat liver ferritin had taken place which doubled the concentration of dimers. However, our results also indicate that association by concentration was limited to a fraction of monomers.


Thermodynamic equilibria of cholesterol-detergent-water. Cholesterol monomer is incorporated into alkyl sulfate micelles with a unitary free energy of -10.3 kcal/mol. This experimental free energy is in good agreement with that predicted by our previous determination of the hydrophobicity of the sterol suggesting that the partitioning is primarily hydrophobic with little or no contribution to the free energy from head group interactions in this system. The intrinsic hydrophobicity of cholesterol is shown to be insufficient for effective partitioning of the sterol between micelles (or bilayers) and its own self-associated form. This finding strongly supports a model of phospholipid-cholesterol interaction involving significant free energy contributions from head group effects such as alterations in hydrogen bonds or hydration. Since these head group contributions are not observed in the cholesterol-alkyl sulfate system, one concludes that there is a high degree of specificity of interaction between the sterol OH and polar moieties of other amphiphilic molecules.