Modeling static and dynamic human cardiovascular responses to exercise. A human performance model has been developed and described [9] which portrays the human circulatory, thermo regulatory and energy-exchange systems as an intercoupled set. In this model, steady state or static relationships are used to describe oxygen consumption and blood flow. For example, heart rate (HTRT) is calculated  as a function of the oxygen and the thermo-regulatory requirements of each body compartment, using the steady state work values of cardiac output (CO, sum of all compartment blood flows) and stroke volume (SV, assumed maximal after 40% maximal oxygen consumption): HTRT=CO/SV. The steady state model has proven to be an acceptable first approximation, but the inclusion of transient characteristics are essential in describing the overall systems' adjustment to exercise stress. In the present study, the dynamic transient characteristics of heart rate, stroke volume and cardiac output were obtained from experiments utilizing step and sinusoidal forcing of work. The gain and phase relationships reveal a probable first order system with a six minute time constant, and are utilized to model the transient characteristics of these parameters. This approach leads to a more complex model but a more accurate representation of the physiology involved. The instrumentation and programming essential to these experiments are described.


An inverse correlation (dose-response between 5-methyl-cytidine and the fate of spontaneous tumours in mice. Tumour-bearing mice, 248 in number, have been injected with 5-methyl-cytidine dissolved in physiological salt solution. The mice were divided into 5 series depending upon the amount of 5-methyl-cytidine they received. Mice of a successive series received 43.2, 28.8, 14.4 and 7.2 mg/kg body weight. There was a progressive increase in the percentage of mice showing regression of tumours in the successive series, as follows: 45%, 50%, 65%, 60%, and 67.8% respectively, giving an average percentage of regressions of 59.7%. The incidence of mice developing multiple primary tumours increased in the same successive series respectively as follows: 25%, 43.8%, 58.3%, 73.3%, and 70%, thus giving an average of 58.3%. The evidence obtained indicates an inverse correlation (dose-response) between the amount of the 5-methyl-cytidine injected and the percentage of regressions of spontaneous tumours.


Studies on the cytogenetic activity of some common fungicides in higher plants. Seeds of barley and secondary roots of Vicia faba were exposed to treatments with 23 of the most commonly used fungicides with a view to discovering the effect of these fungicides on the germination, seedling injury and chromosome abnormalities in the former, and the spectrum and frequency of chromosomal aberrations in the latter. Sixteen fungicides reduced the percentage of seed germination, induced seedling injury and produced cytological anomalies of varying degrees in barley. More potent fungicides were further tested in the secondary roots of Vicia faba which were found to produce a significant amount of chromosomal aberrations in the form of chromatid and isolocus breaks and exchanges of chromatid type. Based on theseo bservations, fungicides Dexon, Benlaté, Cerasan, Copperson, Lonocol, Morestan, Hexasan and Karathane could be classified as strong radioimimetic agents. Their role as environmental mutagens in enhancing the spontaneous mutation rate has been discussed and it has been concluded that these constitute genetic and environmental hazards of great magnitude to the eco-system where they are released.


Ultrastructural aspects of infertility.

Ultrastructural aspects of infertility. Organ culture studies have demonstrated that 17beta oestradiol can cause the rapid deterioration and dissolution of pre-existing nuclear channel systems in the human endometrial glandular cell. The importance of the nuclear channel system in implantation is emphasized and the implications of secretory activity in the endometrium of an infertile woman are discussed.


Long-term results of continuous oxygen therapy at sea level. Twelve patients with hypoxemia associated with severe chronic obstructive pulmonary disease were treated with continuous portable oxygen therapy and have been followed up for a mean period of 25.2 months at sea level. Pulmonary function testing has revealed no further significant deterioration at long-term follow-up (17 months). After oxygen therapy was initiated, arterial carbon dioxide tension increased slightly, but decreased to pretreatment levels when patients were allowed to breathe room air. The electrocardiogram, which was unchanged at one month, has shown some reversal of cor pulmonale in five patients. Six patients have died, yielding a 56 percent survival rate at two-and-one-half years by the life table analysis. Five patients were autopsied, with possible oxygen toxicity being present in only one. The quality of life in our patients was improved and was especially represented by a reduction in hospital admissions for respiratory illness. We believe that continuous oxygen therapy is beneficial and worthwhile economically in certain patients.


Depression of hypoxic and hypercapnic ventilatory drives in severe asthma. Because of the previous finding of an attenuated hypoxic ventilatory drive in a teenager with severe asthma, the ventilatory responses to hypoxia and hypercapnia were examined during remission in 16 patients with the history of severe asthma. Spirometric and body plethysmographic pulmonary functions were normal or nearly normal just prior to ventilatory drive testing. The ventilatory responses to progressive isocapnic hypoxia and to hyperoxic hypercapnia were studied. Both hypoxic and hypercapnic drives were significantly depressed in the asthmatic patients. Factors known to blunt the ventilatory drives were not present in this group of patients. Hence, the etiology of these changes is unclear. In some patients, these depressed respiratory drives might contribute to hypoventilation, to severe hypoxemia, and to respiratory failure during severe asthma.


Determinants of survival following cardiac operations in elderly patients. Ninety-four cardiac operations were performed on 92 patients 65 years of age and over at the Peter Bent Brigham Hospital, Boston, from July 1970 to July 1974. There were 39 aortic valve replacements, 11 mitral valve replacements, 14 double valve operations, 16 coronary revascularizations, five repairs of aortic dissections, and one atrial septal defect closure. The operative mortality was 11 percent in elective cases and 40 percent in the emergency cases, an overall mortality of 17 percent. There were no hospital deaths following elective double valve operations or coronary bypass procedures. Combined hospital and late mortality of ventricular aneurysmectomy approached 100 percent. Myocardial infarction accounted for eight of the 16 hospital deaths. The overall late mortality has been 7.5 percent. Ninety-seven percent of surviving patients are functional class 1 or 2 with a follow-up of 4 to 48 months. These data suggest that any necessary cardiac surgery, excepting ventricular aneurysmectomies, may be performed electively with low risk and a high likelihood of satisfactory rehabilitation in the elderly age group. The major determinants of mortality are the urgency of the intervention and associated coronary artery disease.


Indications for prophylactic preoperative insertion of pacemakers in patients with right bundle branch block and left anterior hemiblock. To determine the need for prophylactic temporary pacing in bifascicular block during surgical and other procedures, a retrospective analysis was carrried out in 38 patients who underwent a total of 74 procedures. The male:female sex ratio was 3.2:1 and mean age was 74 (range 48-96) years. Known organic heart disease was absent in 45 percent of the total group. Patients were divided into four groups on the basis of their preoperative electrocardiograms. Of the 74 procedures, 19 were carried out under general, 22 under spinal and 29 under regional anesthesia; four endoscopic procedures were done without anesthesia. There was only one complication relating to deterioration of AV conduction. It is concluded that asymptomatic patients with right bundle branch block and left anterior hemiblock do not require prophylactic preoperative pacemaker insertion. Though experience is limited, the same may be true of patients with the additional finding of prolongation of PR interval.


Treadmill exercise test in aortic stenosis and mitral stenosis. The incidence of positive submaximal treadmill exercise tests was evaluated in patients with mitral stenosis and aortic stenosis, no electrocardiographic evidence of left ventricular hypertrophy, and normal coronary arteries on angiography. Seven of 19 patients (37 percent) with aortic stenosis (53 to 80 mm Hg gradient across the aortic valve) had greater than or equal to 1.0 mm of ischemic S-T segment depression during or after a submaximal treadmill test. Three of 15 patients (20 percent) with mitral stenosis (11 to 22 mm Hg mean gradient across the mitral valve) had greater than or equal to 1.0 mm of ischemic S-T segment depression during or after a submaximal treadmill exercise test. Patients with significant valvular disease, no electrocardiographic evidence of left ventricular hypertrophy, and normal coronary arteries may have a positive submaximal treadmill exercise test due to an unfavorable balance between myocardial oxygen supply and myocardial oxygen demand.


Intrapleural tetracycline for malignant pleural effusions. After drainage by closed-tube thoracostomy, tetracycline was instilled in seven patients with malignant pleural effusions. None of the patients had clinically significant recurrence of effusion, even though four patients worsened while receiving systemic chemotherapy and died.


Rapid diagnosis of primary influenza pneumonia. Primary influenza pneumonia is a disease of high mortality. Differentiation between a bacterial and viral etiology for the pulmonary infiltrates frequently presents a diagnostic dilemma. Rapid diagnosis is essential; and once established, the patient requires careful supportive therapy. This report describes two patients with primary influenza pneumonia complicated by severe respiratory failure. Early diagnosis of the pulmonary infiltrates was accomplished by obtaining bronchial secretions with fiberoptic bronchoscopy and staining them with influenza-A fluorescent conjugate. One patient died of the complications of this illness, despite maximal supportive therapy. The other patient survived the illness and at the time of hospital discharge was showing marked improvement in his exercise tolerance. There was subsequent gradual return of ventilation and gas transport function to normal values.


P-A interval: lack of clinical, electrocardiographic and electrophysiologic correlations. P-A interval is measured from the onset of the P wave to the onset of the low right atrial electrogram during His bundle recording. The significance of this interval was evaluated in 214 patients with intact A-V conduction and bundle branch block. One hundred fifty-eight patients had normal P-A (NPA) 27 +/- 9, mean +/- SD, and 56 had prolonged P-A (PPA). The NPA and PPA patients were similar (P greater than .10) in regard to sex, age, cardiac functional class, and P-R. PPA patients had significantly (P less than .05) greater P duration (mean +/- SEM, PPA vs NPA) 106 +/- 2 msec vs 100 +/- 1 msec), slower heart rates (72 +/- 2 vs 79 +/- 1), and longer sinus recovery times (1104 +/- 44 msec vs 980 +/- 38 msec). A-H was slightly shorter in PPA than in NPA patients suggesting that a systematic error in measruement of PA due to a relatively distal recording site may have been responsible for PA prolongation in some patients. Patients were prospectively followed for 16-56 months (mean 21.9 +/- 0.8 months). PPA was associated with only minor increase in P wave duration and decrease in sinus automaticity. PPA did not predict future occurrence of significant atrial dysrhythmia.


Effect of aging on lung mechanics in healthy nonsmokers. The purpose of the present investigation was to determine the effects of aging on air flow limitation. In 22 healthy nonsmoking subjects, we constructed maximum expiratory flow-static recoil pressure curves. Analysis indicates that with aging there was a progressive increase in the critical transmural pressure. The conductance of the S segment was not dependent on age, with the exception of a significant increase in the oldest group. This is probably due to a more peripheral location of the equal pressure point secondary to a loss of lung recoil or to increased resistance, or both.


Assessing left ventricular filling pressure with flow-directed (Swan-Ganz) catheters. Detection of sudden changes in patients with left ventricular dysfunction. The accuracy with which pulmonary pressures reflect sudden changes in left ventricular (LV) pressures was studied in 15 patients without mitral disease. Mean pulmonary artery (PA), pulmonary artery end-diastolic (PAd), mean pulmonary capillary (PC), and pulmonary capillary "a" wave (PCa) pressures were compared with simultaneous LV diastolic pressures measured before (LV pre "a") and after atrial systole (LVEDP). Recordings were made at rest and after angiography. There were significant correlations (r greater than 0.75, P less than 0.01) between LV diastolic pressures and each of the pulmonary pressures. The LVEDP and PCa related most closely (r = 0.98). Differences of 5 mm Hg or more between LVEDP and either PAd or PC occurred in more than 50 percent of the observations and were due to large LV "a" waves. The PC, and to a lesser degree the PAd, were more closely related to LV pre "a" than to LVEDP. Changes (delta) in PCa after LV angiography approximated deltaLVEDP, whild deltaPAD and deltaPC reflected deltaLV pre "a" more closely than deltaLVEDP. In conclusion, PCa reflects the LV "a" wave and, thus, is the most accurate index for LVEDP and deltaLVEDP in patients with LV dysfunction. The PC reflects LV pre "a" (mean LV filling pressure) but is an unreliable index of LVEDP. The PC is more easily measured than PCa and, with proper interpretation, should remain the most useful measurement for patient monitoring.


Vectocardiography in tetralogy of Fallot before and after operation (palliative and corrective surgery). Vectorcardiograms from 55 patients with diagnosed tetralogy of Fallot were studied and divided into the following three groups: A, 35 nonoperated cases; B, 23 with systemic-pulmonary shunt (nine studied preoperatively and also in A); and C, ten after total correction. In group A, two different types of QRS loop occurred in the horizontal plane (HP); 23 clinically and hemodynamically severe cases had right anterior position with clockwise (C) rotation, and 12 less severe cases had right posterior position with counterclockwise (CC) rotation or figure-8 morphology. In the frontal plane the QRS loop was located inferiorly and to the right, with C rotation (80 percent); two cases had the left anterior hemiblock (LAHB) pattern, and another two severe cases had CC rotation and right superior position. Group B had an evident increase of left ventricular forces in the HP, compared with group A; group-B rotation was preferentially CC or figure-8 morphology. Group C had a pattern of right bundle-branch block in nine cases (classic in one and uncharacteristic in eight); four cases also had LAHB.


Repair of tetralogy of Fallot after catheterization-induced complete heart block. The case of a four-year-old boy with tetralogy of Fallot who developed complete heart block during cardiac catheterization and subsequently underwent surgical repair in the presence of heart block is presented. Return to normal sinus rhythm occurred on the 11th postoperative day, and the manner in which increased atrioventricular conduction appeared was documented with the use of a continuous Holter monitor. Placement of a temporary transvenous pacemaker, systemic heparinization in the preoperative period, and the insertion of a permanent epicardial wire during surgery were performed.


Acute pulmonary hypersensitivity to carbamazepine. Acute pulmonary hypersensitivity to carbamazepine (Tegretol) is reported, manifested by diffuse pulmonary infiltrates, skin rash, and eosinophilia. The reaction cleared on cessation of the drug. A lymphocyte transformation test was reactive to carbamazepine.


Malfunctioning electrocardiographic monitor simulating sinus arrest. A 64-year-old patient was admitted to the hospital with a history of two syncopal episodes. The results of the physical examination, resting electrocardiogram and His-bundle study were all normal. Study with a 24-hour ECG monitor (Holter) was at first interpreted as demonstrating periods of sinus arrest. However, more careful examination revealed that these actually represented transient speeding of the monitor tape, perhaps secondary to a semiconductor malfunction. Such monitor malfunction may stimulate severe rhythm disturbances.


Anomalous aortic origin of the right and left pulmonary arteries in a normally septated truncus arteriosus. The first reported case of anomalous origin of the right and left pulmonary arteries with a normally septated truncus arteriosus is presented. Embryologic mechanisms are discussed, and a possible explanation for the development of the anomaly is advanced. Surgical correction was unsuccessful in this case, but is feasible and mandatory for long-term survival.


Intralobar pulmonary sequestration infected with a mycobacterium of the Battey-avium complex. A 24-year-old man with an intralobar pulmonary sequestration infected with a Mycobacterium of the Battey-avium complex is presented and discussed.


Reactivation of pulmonary tuberculosis due to trauma. A 53-year-old man developed pulmonary tuberculosis, presumably reactivation, with ten days of sustaining multiple fractured ribs. Tuberculous bronchopneumonia developed in the right lung adjacent to the site of injury and spread to the contralateral lung. Sputum smears were positive for acid-fast bacilli three weeks after trauma. Theories for the reactivation of pulmonary tuberculosis secondary to trauma are reviewed.


Chyliform pleural effusion. An unusual manifestation of hepatothoracic echinococcus cysts. A case of hepatothoracic echinococcosis with the unusual manifestation of a large, right, chyliform pleural effusion is presented. The possible etiology, the pathogenesis, and the origin of this chyliform fluid are discussed, and the methods used to differentiate chyliform fluid from true chyle and pseudochyle are described.


Superior vena cava syndrome caused by bronchogenic cyst. A patient with superior vena cava syndrome due to an infected benign mediastinal bronchogenic cyst is reported. Although bronchogenic cyst is a rare cause of the superior vena cava syndrome, it should be considered because it is a potentially treatable lesion. Patients with bronchogenic cysts should have elective surgery before major complication develop.


Right cervical aortic arch associated with a ventricular septal defect. A patient with a right cervical aortic arch and ventricular septal defect is presented. This is the second reported case to have this rare combination of defects and the first to have survived corrective surgery. The x-ray film findings are discussed, and the similarity to the right posterior aortic arch is stressed.


Functional anatomy of cranial synostosis. An understanding of how sutural growth processes relate to the totality of cranial growth is necessary to cure the cause and not just the symptoms of cranial synostosis. There is no direct genetic determination for the origin, growth, size, shape or maintenance of bones. Rather, phenotypic expression of skeletal tissues is regulated via genetic information encoded in the cells of functional matrices. The primary morphogenetic event in neurocranial growth is the volumetric expansion of the neural mass, which causes the surrounding neurocranial capsule to expand. Calvarial bones arise at widely separated ossification centers and spread centrifugally towards each other. Premature synostosis of the human metopic suture was noted as a frequent characteristic of the cleft-palate skull. Primary morphological event associated with premature synostosis was a cranial base malformation. Cranial sutures permit passage of the neonatal head through the birth canal, permit slight relative variations between adjacent bones while keeping these same bones relatively approximated. All morphological attributes of carnial bones and of their sutures are extrinsically determined and regulated, including both the normal and premature synostosis of the cranial sutures. It seems reasonable to the author that premature synostosis originates in the early embryonic prosencephalic head organizer, which makes it developmentally understandable.


Coordinated investigation of cystic astrocytomas by nuclear medicine and neuroradiological techniques. Astrocytomas are the most common intracranial neoplasm in children. It is necessary to demonstrate preoperatively the location and extent of a possible neoplastic cyst and to differentiate it from the part that is solid. This is achieved through brain scans, computer axial tomography and angiography. Though of considerable help, brain scan and computer axial tomography are insufficient in providing the neurosurgeon with the complete character and geography of the neoplasm necessary for successful surgical treatment. Demonstration of these features can only be elucidated by contrast angiography. Consequently, the coordination of these three techniques permits the precise evaluation of the presence, nature, and operative and postoperative course of cystic astrocytomas.


Surgical treatment of hydatid cysts of the central nervous system in the pediatric age (Dowling's technique). Single hydatid cysts of the brain are rarely seen by pediatric neurosurgeons who do not reside in certain countries, i.e. Australia, Uruguay, and Argentina. It is, however, of considerable importance that every pediatric neurosurgeon be aware of the manner of diagnosis of this condition and surgical management of these patients. Out of 35 cases of hydatidosis of the CNS and its covering observed over a 42-year period, there were 29 hydatid cysts of the brain and one of the spinal cord. Emphasis is placed on the former. Surgically, the hydatid cyst can be removed intact. The essential steps of the technique are: (1) a large flap; (2) careful handing during all the operative steps avoiding monopolar coagulation; (3) opening of the atrophic cortex overlying the cyst over an area whose diameter should be no less than three quarters of the diameter of the cyst, and (4) letting the cyst come out by just lowering the head of the operating table and instillating warm saline between the cyst and surrounding brain. In this series of hydatid cysts of the CNS, there was no operative mortality. The 20 cases in which the cyst was removed unbroken with Dowling's technique are alive and only two have sequelae of the preoperative lesion (blind). In the 11 cases in which Dowling's technique was not used and the cyst broke during ventriculography (3) or surgery (7, one broke spontaneously), only 7 are alive and well and there were 4 late deaths.


Freeze-fracture study of human brain tumors. This freeze-fracture study was performed in 3 astrocytomas, 6 glioblastomas, 2 ependymomas, 3 medulloblastomas, 1 cerebellar sarcoma, 3 germinomas, and 1 medulloepithelioma. The number of nuclear pores/mum2 nuclear membrane was not correlated with biological malignancy. Fracture faces A and B were discernible in nuclear, Golgi and rough endoplasmic reticulum (ER), mitochondrial surface, and plasma membranes. Fenestrae were evident in Golgi and ER membranes. The transitional zone of cristae from the inner surface membrane appeared as a circular hole and broken-off neck on faces A and B of the inner surface membrane, respectively. The decrease in number of membrane particles in the plasma membrane seemed to correlate with the frequency of metastases, and, in addition, the membrane particles appeared to cluster in glioblastoma, medulloblastoma, and medulloepithelioma. The gap junctions were abundant in astrocytomas, moderate in number in ependymomas and germinomas, and rare in glioblastomas, cerebellar sarcoma, and medulloepithelioma. Tight junctions were often found in germinomas and medulloepithelioma, and rarely in ependymomas.


Cerebral artery aneurysms in infancy, childhood and adolescence. From this series of 16 cerebral artery aneurysms in the paediatric age group the following points can be made: (a) aneurysms in the paediatric age group may be found in unusual locations, more peripherally than usually seen in the adult population, (b) in seven patients, the aneurysm was of giant size; two of these produced symptoms by mass effect, (c) in two patients with subacute bacterial endocarditis the aneurysm was mycotic; the inflammatory fusiform dilatation of the entire circle of Willis in one case was associated with generalized candidiasis, (d) an antecedent head injury in a child may so prejudice the initial clinical assessment that the possibility of haemorrhage from aneurysm is overlooked, and (e) gradual vertebral artery ligation, to reduce the pressure-head in fusiform aneurysms, is well tolerated by the young patient, even when done bilaterally.


Perspectives in paediatric neuroradiology. At The Hospital for Sick Children, there is a sufficient number of children who require neuroradiological procedures as to warrant a separate unit for Paediatric Neuroradiology. It functions within the Department of Radiology but is mostly involved with neurosurgery and neurology. Children under 15 kg in weight demand somewhat different technical procedures. Pneumoencephalography must be performed in a specially designed chair allowing isocentric position of the head, vertical 360 degrees rotation and side-to-side movements for tomography. Percutaneous femoral catheter cerebral angiography requires very small needles, guidewires, and catheters, so that vessels of 100 mum can be demonstrated. 2:1 magnification and subtraction are esential. Myelography is used to delineate the geography and the character of the noraml and abnormal central nervous system in infants. These studies permit accurate diagnosis of most neurosurgical and neurological diseases.


Acute subdural hematoma in infancy and childhood. 27 cases of acute posttraumatic subdural hematomas diagnosed and treated by the authors from 1968 to 1972 are presented. Five were newborns, 18 were infants, and three were toddlers. The youngest patient was 38 h and the oldest 5 years old. The most common age was between 1 and 3 months. Falls were the most frequent cause of injury, parental or familial abuse was next. A correlative analysis of the different clinical pictures in each of these age groups is made. We stressed that the presence of hemorrhages in the fundi, and convulsions, in the infant who has suffered a head injury, are indications for contrast studies. A critical analysis of subdural taps, as a method of diagnosis and treatment, is made: we seriously doubt that subdural taps are of any real value in the clinical management of a child with acute head injury. Comparative analysis of the surgical treatment and results is made. Twelve patients were treated with repeated subdural taps, 15 with craniotomy. Of the former group, 41.6% developed a chronic subdural whereas only 13% of the latter group developed this complication. Five out of the 27 patients died. Comparative psychological evaluation of these two groups, surgical and nonsurgical, is presented. In the surgical group 72.7% had an IQ over 80 and in the nonsurgical group only 25% had an IQ over 80. A correlative analysis of the clinical picture, method of diagnosis, surgical result, and psychological tests are analyzed.


Cystic cavum veli interpositi associated with normal or low pressure hydrocephalus. A new clinical syndrome, characterized by progressive increase in head size (without intracranial hypertension), variable delay in milestones, moderate ventricular dilation, and the presence of a cavum veli interpositi is herein described. The arteriographic and venographic signs are suggestive, but not diagnostic, of the presence of a cavum veli interpositi. Pneumoencephalography, with adequate filling of the subarachnoid spaces and ventricles, is essential to confirming the diagnosis. Cerebrospinal fluid shunting appears to result in an improvement, but the results cannot as yet be considered definitive since only 10 of our 29 patients were shunted.


Treatment of infected ventricular shunts. 25 shunt infections following 23 vascular and 2 peritoneal shunts are reviewed, thus enlarging a previous review. Intraventricular administration of antibiotics are essential to reach the CSF beyond the blood-SF barrier, the tubing and the valve. Methicillin in dosages of 25-50 mg/day, intraventricularly combined with systemic therapy, have been used most often in this series. The only death in this series occurred when the infection was cured. The remaining 24 have no evidence of residual infection following 6 months to 5 years. Only 14 have had shunt removal. The results indicate that shunt removal should not be the initial means of treating infected shunts.


Ventriculovenous shunt to the proximal segment of a ligated neck vein. A new surgical technique for shunting the cerebrospinal fluid to the venous circulation (preliminary report). The author proposes ventriculovenous shunts to a ligated neck vein (external jugular or facial) for the treatment of hydrocephalus. He postulates that the ligated neck vein is filled with CSF and becomes an extension of the shunt tube, which prevents venous thrombosis. The pressure of the shunt at the venous tube was shown to be about 90 mm H2O avoiding excessive ventricular decompression. Reflux of blood to the ventricle can occur if the infant's cranium is compressible and must be prevented by protecting the cranium from external pressure with a bandage or helmet or by incorporating a one-way valve into the shunt. 31 cases of advanced hydrocephalus were thus treated during a 4-year period. Ages ranged from 15 days to 55 years, the cranium was rigid in 13 and compressible in 18. A valve was used in only two cases. Shunts were patent 7-10 days after surgery, as shown at autopsies in two early postoperative deaths. In two cases meningitis occurred, one of them died. The shunt was removed in one case on account of meningitis and in 4 cases due to cervical CSF leakage. The former and three of the latter were reoperated with success. Three cases had distal shunt obstruction, two due to kinking of the tube, and one due to reflux of blood. One of the former died. 23 patients benefited from the operation, 5 of which were operated on twice. The follow-up period was from 0.5-44 months (average 11.5 months). The last two cases were operated on using one-way valve and a spiral wire in the venous segment of the tube. They are well 2 and 3 months, respectively, following surgery.


Lateral asymmetry in human constitutive heterochromatin. Human lymphocytes were grown for one replication cycle in BrdU, stained with 33258 Hoechst, exposed to UV light and subsequently treated with 2 x SSC and stained with Giemsa. This technique differentially stains the constitutive heterochromatin of chromosomes 1, 9, 15, 16, and the Y. In the heterochromatin of chromosome 9 both sister chromatids stained darkly and symmetrically but in the other four chromosomes the heterochromatin showed lateral asymmetry, one chromatid being darkly stained while its sister chromatid was a pale or paler than the rest of the chromosome. The lateral asymmetry is presumed to reflect an underlying asymmetry in distribution of thymine between the two strands of the DNA duplex in the satellite DNA component of the chromosomes. In some number 1 chromosomes compound lateral asymmetry was seen; darkly staining material was present on both sister chromatids although at any given point lateral asymmetry was maintained so that if one chromatid stained darkly the corresponding point on the sister chromatid was very pale. The pattern of compound lateral asymmetry varied among the number 1 chromosomes studied but was constant for any one homologue from one individual. This technique reveals a previously unsuspected type of polymorphism within the constitutive heterochromatin of man.


Chromosomes and DNA of Mus: terminal DNA synthetic sequences in three species. The DNA replication patterns of the terminal S phase of three species of Mus were analyzed by tritiated thymidine autoradiography. The centromeric heterochromatin of M. fulvidiventris is the latest component to finish DNA synthesis. The Y chromosome finishes replication earlier than the centromeric heterochromatin. The centromeric heterochromatin of M. musculus, on the other hand, is not the latest component to finish DNA synthesis. At the very late S phase, grains are found in the euchromatic arms instead of the heterochromatic areas. The "hot X" and the "hot Y" can be identified in the majority of, but not all, cases. The heterochromatic short arms of the autosomes in M. dunni finish DNA replication earlier than many areas in the euchromatic long arms and the heterochromatin of the sex chromosomes. This indicates that in M. dunni there are at least two types of heterochromatin. The late-replicating zones in the euchromatic long arms are distinctly banded. This banded grain pattern can be seen in all Mus species observed, but in M. dunni it is most exaggerated. Late-replicating chromosome segments can be demonstrated also by 2+ cycles of BUdR incorporation and Giemsa staining.


Molecular properties of orthopteran DNA. DNAs from three grasshopper species and three locust species (Family Acrididae, Order Orthoptera) have been characterised by a variety of biochemical techniques as part of a general investigation of their molecular evolution. Base compositions were inferred from thermal denaturation profiles and analytical CsCl and Cs2SO4 pcynography. Repeated sequence content of the genomes was studied by renaturation kinetics incorporating absorption measurements. Relative genome size was measured by microdensitometry of nuclear preparations.


The location of 5S (ribosomal) RNA genes in Drosophila hydei. The location of the 5S ribosomal RNA cistrons in band 2-23B1,2 of the polytene (salivary gland) chromosomes of Drosophila hydei was indicated by in situ hybridization of tritiated low molecular weight RNA fractionated from total in vivo synthesized larval RNA or from in vitro synthesized salivary gland RNA and competition of the hybridization of this RNA by 5S RNA obtained from calf lens ribosomes. -- At the submicroscopic level, band 2-23B1,2 in salivary gland chromosomes shows a compact organization. The adjacent region, 23B2, is slightly puffed and displays typical RNP particles, some of which may be observed close to band 2-23B1,2.


Segregational mechanisms of sex chromosomes in Spongilla-flies (Neuroptera: Sisyridae). Evolutionary loss of the Y chromosome has occurred in Climacia areolaris (Hagen) of the neuropteran family Sisyridae. The diploid set comprises 6 pairs of autosomes, plus 2 X chromosomes in the female and 1 X in the male. The Y is retained in Sisyra vicaria (Walker) of the same family: its chromosome number is 14 in both sexes including 2X chromosomes in the female and 1X plus Y in the male. Two alternative pathways for the segregation of the sex chromosomes-distance segregation and sex bivalent formation-co-exist in the latter species in a ratio of approximately 1 to 6; the possible phylogenetic significance of this feature is discussed.


The synaptic behaviour of the X and Y chromosomes in the marsupial Monodelphis dimidiata. The pairing behaviour of the X and Y chromosomes of Monodelphis dimidiata was studied with light and electron microscopy. Pairing of the sex chromosomes is delayed with respect to autosome synapsis. Both the X and the minute Y chromosome show an axis attached by its two ends to the nuclear envelope. Synapsis of the sex chromosomes occurs by the joining of the chromatin sheaths that surround the axes and by a small, three-layered structure close to the nuclear envelope. The X and Y chromosomes remain joined to each other during the diffuse stage and diplotene-diakinesis but they do not show a synaptonemal complex. During the diffuse stage a dense plate is formed at the boundary between the X-Y body and the nuclear envelope. During early metaphase a folded sheet is attached to the periphery of the X-Y body. This sheet is formed by a piece of the nuclear envelope carrying the dense plate and it shows transverse fibrils and a central element similar to synaptonemal-complex remains. No evidence of a non-chiasmate segregation mechanism was observed. Polarization of the axial ends of the sex chromosomes is observed after X-Y synapsis. These important departures from the X-Y pairing pattern of eutherian mammals are discussed and assumed to present a special mechanism for holding the minute Y joined to the X chromosome in this marsupial.


Interphase chromosome arrangement in Anopheles atroparvus. The arrangement of chromosomes in interphase nuclei of Anopheles atroparvus has been inferred from an analysis of: 1. The early stages of mitosis as seen following Quinacrine staining, and 2. The reversible effects on the chromatin pattern obtained following the treatment of living cells with various NaCl solutions, and the following conclusions have been reached: (a) The chromatin is connected to the nuclear membrane, (b) Homologous chromosomes show close side-by-side somatic pairing, (c) The long arms of the sex chromosomes form a fluorescent peripheral body, (d) The autosomes are strongly reflexed at the centromeres, (e) The autosomal centromeric regions are polarized towards the peripheral body, (f) The telomeric regions of all the autosomes are closely apposed.--A ring-shaped pattern of interphase chromatin is constantly and reversibly induced by NaCl 0.15 to 0.18 M solutions.--These relationships indicate a peripheral arrangement of the interphase somatic complement.--The distribution of the chromosomes in polytene nuclei and at the beginning of meiosis resembles that suggested above for somatic interphase cells. This distribution may apply more widely in the Diptera.


The organization of interphase chromatin in drosophilidae: the self adhesion of chromatin containing the same DNA sequences. Cytological evidence is presented which shows that for Drosophila virilis and Samoaia leonensis at least, each satellite DNA is condensed into a distinct heterochromatic mass during interphase. This is seen as just one example of a general phenomenon in which chromatin containing a particular DNA sequence binds to other chromatin containing the same sequence. It is proposed that DNA sequence specific proteins can account for this phenomenon.


5-Methylcytosine in heterochromatic regions of chromosomes: chimpanzee and gorilla compared to the human. Fixed metaphase chromosomes of gorilla and chimpanzee were UV-irradiated to produce regions of single-stranded DNA and then treated with antibodies specific for the minor DNA base 5-methylcytosine (5 MeC). An indirect immunofluorescence technique was used to visualize sites of antibody binding. In the gorilla six pairs of autosomes contained major fluorescent regions, indicating localized regions of highly methylated DNA. These corresponded, with the exception of chromosome 19, to the major regions of constitutive heterochromatin as seen by C-banding. The Y chromosome also contained a highly fluorescent region which was located just proximal to the intense Q-band region. In the chimpanzee no comparable concentrations of highly methylated DNA were seen. Smaller regions of intense 5 MeC binding were present on perhaps six chimpanzee chromosomes, including the Y. Five of these corresponded to chromosomes which were highly methylated in the gorilla.--There is diversity among the human, gorilla and chimpanzee in both the size and location of concentrations of 5 MeC, supporting the idea that satellite DNA evolves more rapidly than DNA in the remainder of the chromosome.


Binding of quinacrine to the human Y chromosome. Human chromosome spreads were stained with 3H-quinacrine and their fluorescence observed. The exact location of specific spreads on each slide was noted and photographs taken. Autoradiographs were then prepared so that the quinacrine fluorescence of any specific chromosome could be compared directly with the distribution of grains over the same chromosome on the autoradiograph. The Y chromosome fluoresced much more intensely than any of the other chromosomes, but there were no more grains over the Y chromosome than over the other chromosomes. Therefore the enhanced fluorescence of the human Y chromosome is not due to an increased binding of quinacrine.


Causes and consequences of Robertsonian exchange. At least two types of Robertsonian exchange are now known in the acrocentric chromosomes of man. Both types involve breakage in the arms adjacent to the centromere. Evidence is presented for a third type of exchange, one involving breakage within the centromere itself, in the grasshopper Percassa rugifrons. In this species, which is regularly homozygous for a single fusion metacentric, the eighteen rod autosomes have small but pronounced granules at the centric end of the chromosome. When C-banded these granules show differential Giemsa staining and appear to represent centromeric chromomeres; these chromomeres are lacking in the metacentric fusion product. Equivalent fusions may have occurred in some mammal species too and possible examples of this are discussed in sheep and mice. The Percassa fusion has led to a modification in both the frequency and the distribution of chiasmata as judged by a comparison of these properties in the metacentric relative to the two next smallest rod equivalents. Comparable modifications are known to occur in other naturally occurring fusions but these changes are certainly not automatic consequences of fusion since they are not shown in at least some newly produced fusion mutants.


Anaphase transport of akinetochoric fragments in tipulid spermatocytes. Electron microscopic observations on fragment-spindle interactions. Akinetochoric chromosomal fragments in spermatocytes of mutant Pales ferruginae are transported polewards in anaphase. During migration their surfaces form radial lamellar projections between which non-kinetochoric spindle microtubules become arranged in an orderly fashion. The same morphological features had been observed earlier in intact chromosomes in late anaphase. It is assumed that the fragments are transported by some kind of poleward directed "streaming" force of the anaphase spindle, which is applied to the fragment's surface. Non-kinetochoric microtubules are thought to be engaged in the generation or, at least, in the transmission of this spindle force. Due to the morphological similarities with akinetochoric fragments, extra-kinetochoral application sites for anaphase spindle forces can be also suggested for chromosomes possessing kinetochores.


The location of repeated DNA sequences in the chromosomes of Chironomus tentans. Polytene chromosomes of Chironomus tentans were hybridized in situ with in vivo labelled nuclear and chromosomal RNA. Nuclear RNA formed hybrids preferentially in five distinct regions considered to contain clustered, repeated DNA sequences. These are the two nucleolar organizer regions, Balbiani ring 1 and 2, and the 5 S RNA genes in region 2A of chromosome II, which together comprised almost 70% of the total number of grains over the complement. The remaining grains were diffusely distributed over the chromosomes. There was a significant difference in the distribution of grains when RNA from different chromosomes was used for hybridization. Chromosome I RNA hybridized preferentially with chromosome I, and chromosome II+III RNA preferentially with chromosome II+III. Some regions within the chromosomes hybridized significantly more chromosomal RNA than other regions. A considerable cross-hybridization of RNA from one particular type of chromosome with the other chromosomes was also found. It is concluded that repeated DNA sequences which hybridize with heterogeneous chromosomal RNA in C. tentans are widely dispersed in the genome. Some of these sequences have a delimited localization, others are dispersed, and some sequences which are transcribed in one particular chromosome are present also in the other chromosomes.


Autoradiographic demonstration of DNA replication in ultrathin sections of plastic-embedded tissues using an exogeneous DNA polymerase. A DNA-dependent DNA polymerase isolated from regenerating rat liver can mediate the incorporation of tritiated nucleoside triphosphates into acid-insoluble polydeoxyribonucleotides using the DNA contained in ultrathin sections of glycol methacrylate-embedded crab testis as initiator-template. (Summary see p. 186).


Evidence for a subunit structure of chromatin in mouse myeloma cells. If micrococcal nuclease is allowed to digest chromatin as it exists inside intact nuclei isolated from mouse myeloma tissue culture cells, more than 60% of the DNA can be isolated as a homogeneous fragment on a sucrose gradient. Analytical ultracentrifugation indicates that the protected DNA is native, unnicked, and about 140 +/- 10 base pairs long. After less extensive nuclease digestion, the protected DNA migrates in gels in lengths which are integral multiples of this 140 base pair "monomer" band. A submonomer band, 105 "/- 10 base pairs long, can also be detected. Similar digestion patterns were obtained by two different nuclear isolation procedures and even when intact cells were gently lysed directly in the digestion medium. These results confirm and extend the chromatin digestion studies of previous investigators and provide support for a subunit model for eukaryotic chromatin. The single strand specific S1 nuclease did not digest intranuclear chromatin under the conditions used.


An open study of mesoridazine (Serentil) in chronic schizophrenics. Mesoridazine besylate (Serentil) was evaluated in an eight-week open-label trial in 12 male and 41 female patients with chronic schizophrenia who had ceased to progress beyond a certain level of functioning despite continued psychotropic medication not including Serentil. After a ten-day washout period the patients received Serentil in I.M. doses of 25-150 mg daily on the first ten study days, followed by daily tablet doses ranging from 25 to 400 mg until the final day of the study. Observations were made before and after the washout period as well as on days 3, 10, 14, 28 and 56 of the study, and results were expressed in terms of the Nurses' Observation Scale for Inpatient Evaluation (NOSIE) and the Brief Psychiatric Rating Scale (BPRS). The NOSIE ratings showed that the patients were significantly "less mentally ill" at the end of the washout period and underwent a statistically highly significant further improvement in the course of the Serentil treatment. These improvements occurred in irritability, manifest psychosis, retardation, and depressive manifestations, and social competence. Only two BPRS items improved significantly during the washout period. Treatment with Serentil led to improvement in thinking disturbances as well as in psychomotor, paranoid and depressive disturbances. In fact, between baseline and day 56 of the treatment period, all BPRs items except guilt feelings and all BPRS factors were improved to a highly significant (p less than 0.01) degree. Rating for mental illness from study day 10 onward showed that patients in a subgroup of depressive disturbances showed significantly greater improvement than patients in another subgroup, psychomotor disturbances. Adverse reactions were experienced by a total of 13 patients; in 7 of these a dosage adjustment became necessary for this reason. All patients completed the study program.


A neglected modality in psychiatric treatment--the monoamine oxidase inhibitors. The monoamine oxidase inhibitors are at present being used relatively infrequently in my opinion because of reports of severe and dangerous side effects such as toxic hepatocellular damage and hypertensive crises and also on account of several studies which have not given a very encouraging picture regarding the efficacy of this group of drugs. The purpose of this article is to demonstrate that this group of antidepressant drugs is very useful when the proper indications for their employment are observed and are relatively safe provided that appropriate precautions such as the avoidance of cheese and other foods high in tyramine content are taken by the patients being treated with these compounds. The history, pharmacology, side effects, and indications for their use are reviewed, and it is indicated that the MAO inhibitors are the therapeutic agents of choice in atypical depressions associated with anxiety, phobic and hysterical symptoms, and depressive illnesses (including endogenous depressions) which have failed to respond satisfactorily to tricyclic antidepressants. It is then demonstrated both from a review of the literature relating to these drugs and also from my own clinical experience that these compounds are very effective when used in the treatment of the psychiatric conditions for which they are indicated and are also relatively safe when the appropriate precautions are conscienciously observed.


[Radio-iodine therapy of toxic adenoma of the thyroid (author's transl)]. Between 1963 and 1971, radioiodine (133I) treatment of a toxic thyroid adenoma was performed in 229 patients, in 70% the dosage being 30000 rd. In 188 patients the results were checked an average of 2 1/2 years later. Subjective improvement or freedom from symptoms was achieved in 76% (in 85% within 3-6 months), body weight increased, serum cholesterol level rose significantly, while pulse rate, pulse amplitude, PB127I and index of free thyroid hormones significantly fell. The 131I two-phase test was inconclusive. 72% of toxic adenomas were inactivated and 88% of patients with still active adenomas were improved or free from symptoms. Clinical improvement apparently preceded the scanning results. Corresponding to the index of free thyroid hormones, 94% were euthyroid, 0.6% hyperthroid, and 2.8% suspected of being hypothryoid. In combination with other findings, especially isotope scanning, 1.7% of patients were suspected of having T3 hyperthyroidism after treatment. A recurrence was observed in 2.1%. The success rate increased with rising radiation dose up to 30000 rd.


[Chronic secondary hypoparathyroidism and pseudo-brain tumour (author's transl)]. A 31-year-old man developed chronic secondary hypoparathyroidism after removal of goitre. Asymmetric cerebral oedema occured and a classical picture of pseudo-brain tumour with severe cerebral involvement developed which regressed merely on administration of calcium ions. The patient has remained well for over a year on dihydrotachysterol maintenance.


[Vitiligo, hepato-splenomegaly, and goitre after working with paratertiary butylphenol (author's transl)]. In three men vitiligo-like skin changes, enlargement of liver and spleen and diffuse goitre (grade II) with increased TSH secretion developed within one to two years of their having started work in a factory producing paratertiary butylphenol. These observations also tend to confirm the often discussed pathogenetic connection between vitiligo and thyroid disease.


[Attempt at classification and orientation of prescriptions using an index of psychotropic drugs in computers]. We designed a method of rational classification of psychotropic drugs belonging to neuroleptic class. Standard profiles were determined along BELSON'S Method (partially modified). Neuroleptic population is analysed according to two leading variables : desinhibiting action and powerful sedative action. The remaining variables are graded depending upon their binding with leading variable, we called them explanatory variables. Profile of drug is found along these explanatory variables. Results are set out with : list of decomposition with clauses, list of variables selected by method, dichotomic graphic, identification of drugs. Our purpose is to find objective tests, for classification of these therapeutic drugs. It must enable a best evaluation of indications and contra-indications, practice in every day.


[Use of a rating scale in transcultural psychiatry]. The Psychopharmacological Studies Group of Fann, Dakar, considered the cultural expression of mental illness as it would help for a new definition of the nosographic frames, and inside of them, the appreciation of symptoms. This new definition would be applied "universally" if it may be considered that some symptoms are "culture-free" and others deeply marked by the discourse held by the person or by his social group. The use of valuation scales for symptomatic change during a treatment (here anti-depressive one) become harder by the undifferenciation of these two types of symptoms. Further, it may exist nosographic masks which can hide more curable substructures ; as often happens here, in masked depressions when the presented symptoms are those of acute or chronic psychotic manifestations. The efficacy of depressive treatment is then remarkable.


[Self-rating of mood using a list of adjectives, Zersen's Befindlichkeits-Skala (BS)]. The ZERSSEN Mood Scale or " Befindlichkeits-Skala " is the only self-rating scale that is altogether specific (adjectives on mood states essentially), actual and therefore sensitive (lack of adjectives on the habitual state, on personality traits), bipolar (possible detection of a manic or depressive shift), easy to administrate and analyze, existing under 2 statistically equivalent forms. Each BS and BS' form contains 28 pairs of antonymic everyday adjectives, whose French translation has been checked by back-translation. The subject has to cross if he feels right now " rather... ", " rather... " or " neither nor ". The French translation was tested on 100 depressed and 6 manic newly hospitalized patients, on 30 depressed patients in the course of a 6-week antidepressant trial, and on 46 academic and administrative members of the staff. Various calculations on the validity, reliability and sensitivity of the scale confirm the original German data. The product-moment correlation between BS and BS' (split-half reliability) reaches .89 in the control group, .79 in the newly hospitalized depressives and .93 to .96 in the anti-depressant trial, a p less than .001 in all three studies. The correlation does not reach a significant level in neurotic depressives, who are a mean 11 y. younger than psychotic depressives and score significantly lower than the latter. Age, sex and sequence of administration do not influence the means, the standard deviations and the correlation between BS and BS'. The original German studies and our original French ones give convergent results as for means and extreme scores of the main mood levels, with a cutting score for mania at 6 and for depression at 27 : (see article) Thanks to their high intercorrelation, the BS and BS' scales may be given independently, thus allowing a daily or even twice daily administration. The range of application of the ZERSSEN Mood Scale is not limited to psychiatry but includes numerous medical, surgical and psychological fields.


[Pharmacoclinical value of the study of lithium cycles during 24 hours]. One cannot base a posology only upon morning lithiemy which turns out to be an unreliable criterion. It is useful to appreciate therapy equilibration through lithiemic cycle i.e. and every two hours dosage among patients on lithium carbonate or gluconate. Certain patients with quite an insufficient lithiemic morning level may be well equilibrated during day time. Lithiemy variations during the day are constantly reliable with the same patient. The study of nycthemeral variations among lithium salts treated patients allows us to understand some pathological subphenomena : intermittent tremor, subconfusional transitory onsets. Lastly lithiemic cycles allow comparison between lithiemy variations in manic or depressive relapses.


A study of indoles which inhibit pineal antigonadotrophic activity in male hamsters. Blinding adult male golden hamsters led to involution of the testes and accessory sex organs (seminal vesicles and coagulating glands) and to a regression in pituitary prolactin levels within 8 weeks. The subcutaneous implantation of either melatonin or 6-hydroxymelatonin (1 mg/wk in beeswax) prevented the atrophy of the reproductive organs and the decrease in the stores of pituitary prolactin. Two other indoles, N-acetylserotonin and 5-hydroxytryptophol, failed to counteract the reproductive effects of blinding. Both melatonin and 6-hydroxymelatonin significantly elevated plasma LH titers.


Uptake and conversion of progesterone and testosterone to 5alpha-reduced products by enriched gonadotropic and chromophobic rat anterior pituitary cell fractions. Monodispersed cells from anterior pituitaries of male rats were prepared by Pronasedissociation and incubated with [3H]progesterone or [3H]testosterone. The cells were then separated into enriched fractions consisting of gonadotropic, somatotropic or chromophobic cells by velocity sedimentation at unit gravity for 4 h. The uptake of [3H]progesterone and [3H]testosterone by the gonadotropic enriched cell fraction was 1.8 to 3.2 times greater than the somatotropic and chromophobic enriched cell fractions. The gonadotropic and chromophobic enriched cell fractions metabolized [3H]progesterone and [3H]testosterone appreciably. The principal metabolites were identified and quantitated by reverse isotopic dilution. After incubation with [3H]progesterone, the principal metabolite was [3H]5alpha-dihydroprogesterone which ranged from 11.5% for the gonadotropic cells to 7.6% for the chromophobic cells. Smaller amounts of 3alpha-hydroxy-5alpha-pregnan-20-one (3.7 to 4.8%) and 20alpha-dihydroprogesterone (2.1 to 4.3%) were also identified. After incubation with [3H]testosterone, the principal metabolite was 5alpha-dihydrotestosterone which ranged from 12.6% for the gonadotropic cells to 10.3% for the chromophobic cells. Smaller amounts of 5alpha-androstane-3alpha, 17beta-diol (4.1 to 5.5%) and androstenedione (1.8 to 3.0%) were identified. After incubation with [3H]progesterone or [3H]testosterone the same metabolites were also identified in the somatotropic cell fraction but were thought to be present because of contamination with gonadotropic cells. Dissociated pituitary cells from orchidectomized rats had a 2-fold increase in the uptake of [3H]testosterone and a greater metabolism of [3H]testosterone to 5alpha-dihydrotestosterone as compared to pituitary cells from intact rats (12.6 vs 25.7%).


The effects of intracerebroventricular administration of renin on drinking and blood pressure. The aim of the present investigation was to (a) determine if renin-substrate (angiotensinogen) is present in cerebrospinal fluid; (b) investigate the effects of intracerebroventricular administration of renin on drinking and blood pressure; and (c) determine if such effects are mediated via the formation of angiotensin II. Angiotensinogen concentration in cerebrospinal fluid was measured in 15 dogs and averaged 205 +/- 34 ng/ml. This value was approximately 1/5th of the corresponding plasma angiotensinogen concentration but the ratio of angiotensinogen:total protein in cerebrospinal fluid was approximately 15 times greater than in plasma. Intraventricular injection of hog renin (0.1 Goldblatt units) stimulated drinking in each of 8 dogs; the mean volume drunk in the 15 min period following the injection was 485 +/- 84 ml. When the renin was preceded by intraventricular saralasin acetate, a specific antagonist of angiotensin II, the drinking response was reduced to 8 +/- 6 ml. In eight pentobarbital anesthetized dogs, intraventricular dog or hog renin (0.05-0.25 Goldblatt units) increased systolic pressure from 152 +/- 10 to 168 +/- 10 mm Hg (P less than 0.001) and diastolic pressure from 101 +/- 8 to 116 +/- 7 mm Hg (P less than 0.001). This response, which lasted from 30 min to more than 3 h, was also abolished by saralasin acetate. These data indicate that centrally administered renin increases drinking and blood pressure and that these effects are mediated via the formation of angiotensin II.


Effects of the octapeptide of cholecystokinin on insulin and glucagon secretion in the dog. The effects of intravenous infusion of synthetic C-terminal octapeptide of cholecystokinin (OP-CCK) on concentrations of insulin and glucagon in peripheral venous plasma of conscious dogs were studied. Both hormones increased in response to 160 and 480 ng/kg/h of OP-CCK. The increases to 480 ng/kg/h were larger than those to 160 ng/kg/h. Peripheral venous concentrations of glucose and intestinal glucagon-like immunoreactivity were not altered by OP-CCK. OP-CCK, 160 ng/kg/h, did not enhance insulin and glucagon responses to intravenous infusion of amino acids. The results suggest that insulin- and glucagon-releasing actions of porcine cholecystokinin preparations should not be attributed entirely to gastric inhibtory polypeptide or other impurities contained in these preparations since the synthetic active fragment of cholecystokinin alone increases insulin and and glucagon concentrations in peripheral plasma.


Effects of hyper- and hypothyroidism on serum LH and FSH levels in intact and gonadectomized male and female rats. The effects of hypo- and hyper-thyroidism on serum LH and FSH were determined in both intact and castrated male and female rats. Thyro-parathyroidectomy (Tx) for 30 days in rats with intact gonads resulted in a significant reduction in serum LH and FSH, and also in a decrease in serum testosterone in males. Administration of 2.5 mug thyroxine (T4)/100 g BW to Tx rats of both sexes returned serum LH and FSH levels to those of intact rats, and in males also restored normal serum testosterone levels. Tx superimposed upon castration resulted in a significantly greater increase in serum LH and FSH than produced by castration alone. Administration of 2.5 mug T4/100 g body weight to castrate-Tx rats reduced serum LH and FSH values to those of castrate rats, whereas 10 mug T4/100 g BW evoked a further decrease in serum LH but no additional reduction in serum FSH. When both 2.5 mug T4/100 g BW and 2 mug estradiol benzoate were injected into Tx-ovariectomized rats, the decrease in serum LH and FSH was much greater than produced by T4 alone. These observations indicate that hypothyroidism results in decreased release of LH and FSH in rats with intact gonads, and in increased release of LH and FSH in castrate rats of both sexes. Administration of a replacement dose of T4 can restore LH and FSH release to normal in Tx rats with intact gonads, and to castration levels in Tx-castrate rats.


Interrelationships between alpha and beta-anomers of glucose affecting both insulin and glucagon secretion in the perfused rat pancreas. II. Temporal and quantitative relationships between the alpha and beta anomers of glucose on insulin and glucagon secretion were studied in two surgical preparations of the in vitro perfused rat pancreas. Alpha-Glucose was a more effective stimulator of insulin release. Beta-Glucose, however, though less effective, was a positive modulator when admixed with alpha-glucose. Dose-response studies showed that alpha-glucose probably had a smaller apparent Km for insulin secretion, while the Vmax for the two anomers was the same-the effects of the two anomers being indistinguishable at high glucose concentrations (300 mg/dl). Alpha-Anomeric stereospecificity was demonstrable equally on both phases of insulin release and was maintained throughout 60-min perfusions. Spontaneous or arginine-stimulated glucagon release was also preferentially inhibited by alpha-glucose. Since others have shown that glucose uptake and phosphorylation in islets are not alpha-stereospecific, the data suggest that the initial signal for the first and second phases of insuulin release and glucose suppression of glucagon secretion is at the level of a glucoreceptor prior to, or indedendent of, major pathways of glucose metabolism.


The biological effects of injected antibodies to estradiol-17 beta and to progesterone in pregnant rats. Estradiol-17 beta (E2) and progesterone (P) levels have been effectively reduced in pregnant rats by injecting them with antibodies which bind E2 or P (A-E2- or A-P) with high specificity. Before, and at daily intervals after treatment with A-E2 or A-P, blood was collected sequentially from the tail vein and the levels of circulating A-E2, A-P total E2 (E2t) and total P (Pt) determined. Having established the relationship between A-E2, E2t, bound E2 (E2b) and unbound E2 (E2u), as well as between A-P, Pt, bound P (Pb) and unbound P (Pu), the concentrations of E2u and Pu could be calculated reliably. Treatment of gestating rats with A-E2 and A-P lowered E2u and Pu levels significantly (P less than 0.001). In comparison with the 14 controls, the 17 A-E2 treated (and thus E2u-deficient) animals showed significant increases in placental weight (P less than 0.001). This effect of A-E2 was readily prevented by replacement therapy with diethylstilbestrol (DES), since A-E2 does not bind DES. In 21  pregnant rats, treatment at day 10 of gestation with only 2 ml A-P (total "Binding Capacity" = 6 mug P) critically lowered the Pu levels and provoked abortion. In contrast, the same treatment in 12 rats at day 6 of gestation (when the P levels are higher than at day 10) failed to provoke the appropriate degree of P-withdrawal (Pw) and abortion, illustrating the quantitative nature of the relationship between effective A-P treatment, Pw and the termination of pregnancy.


The purification and characterization of rat placental lactogen. A method has been developed for the purification of rat placental lactogen employing a specific radioreceptor assay (RRA). The method involves precipitation with ammonium sulfate, gel filtration on Sephadex G-100, ion-exchange chromatography on DEAE-cellulose and CM-Sephadex, and preparative isoelectric focusing. The isolation precedure results in a 1300-fold purification and a 10% yield of rat placental lactogen. Potency estimates by RRA indicate that the purified hormone is 41% as active as the ovine prolactin standard (25 I U/mg), but 169% as active as the NIH human placental lactogen preparation. Polyacrylamide gel electrophoresis at pH 8.9 annd analytical isoelectric focusing of the rat placental lactogen reveal 2 major and 2 minor components, all of which are active in the RRA.


Androgen binding protein as a biochemical marker of formation of the blood-testis barrier. Androgen binding protein (ABP) was measured during postnatal development in normal and irradiated rats to determine whether development of a blood-testis barrier and formation of a continuous lumen from testis to epididymis is correlated with entry of ABP into the caput epididymis. ABP is found in normal testis as early as 14 days postnatally (0.2 pmol/mg), at which time no blood-testis barrier is observed by the peroxidase perfusion technique. Previous findings have shown a close correlation of blood-testis barrier development and lumen formation. Indeed, ABP is not detectable in the epididymis until 18-20 days of age (1.0 pmol/mg) at which time blood-testis barrier formation and lumen development is complete. Whole body irradiation (125 rads) of pregnant rats at 19-20 days of gestation produces male offspring with seminiferous tubules remarkably free of germinal epithelium and containing essentially only Sertoli cells. These Sertoli cell-enriched (SCE) testes produce normal amounts of ABP between 14 and 21 days postnatally. However, between 21 and 30 days of age the specific activity of ABP is significantly higher in the SCE tests (2.8 pmol/mg protein) than in normal testis (0.5 pmol/mg protein). In the SCE testis neither blood-testis barrier development nor lumen formation are complete until 30 days of age, at which time ABP is first detectable in epididymis of the irradiated rat. Thereafter there is a gradual decline of ABP in the SCE testis-and a dramatic increase in the epididymis. NIH-FSH-S-10 (200 mug/rat) injected SC into 14-day-old normal rats stimulated ABP in the testis from control levels of 0.15 pmol/mg to 1.46 pmol/mg within 4 h after injection. However, no ABP was detectable in the epididymis of either the control or the FSH-stimulated rats. These findings suggest that entry of ABP into caput epididymis is an index of blood-testis barrier formation and lumen development.


Comparison of somatomedin activity in rat serum and lymph. A chick embryo fibroblast (CEF) assay has been used to measure the somatomedin activity in serum and lymph from normal rats. Lymph contains about one-half the SM activity found in serum. The somatomedin activites in serum and lymph have identical elution volumes on Sephadex G-50 in 1N acetic acid. Chromatography at neutral pH demonstrates that somatomedin peptides are bound to large proteins in both normal rat serum and lymph. The relative restriction of somatomedin to the intravascular space may be due to this protein binding.


Age-dependent loss of sensitivity of female urogenital sinus to androgenic conditions as a function of the epithelia-stromal interaction in mice. The ability of the female urogenital sinus to respond to androgens in forming prostate was determined by growing 13- to 18-day old embryonic female urogenital sinuses and vaginas from 1- to 30-day old mice as grafts to male hosts. All embryonic unrogenital sinuses as well as vaginas from 1-day old mice were responsive to androgens and formed prostate, whereas vaginas from mice 5- or more days old never formed prostate. To determine which tissue, the epithelium or stroma, accounts for the age-dependent loss in responsiveness of the vagina to androgens in forming prostate, recombinations composed of epithelium and stroma from 16-day old embryonic urogenital sinuses and vaginas from 1- to 20-day old mice were grown as grafts to male hosts. The developmental response of these recombinants demonstrated that the age-dependent loss in responsiveness of the intact vagina to androgens results from an age-dependent loss in the ability of vaginal stroma to participate in prostatic morphogenesis. These data emphasize the importance of stromal factors during prostatic morphogenesis and the relationship of temporal factors to developmental properties of urogenital stroma.


Reversal by vasotocin of pinealectomy and constant light effects on the pituitary melanocyte-stimulating hormone (MSH) content in the mouse. A single injection of 1 pg synthetic arginine vasotocin (AVT) into the third ventricle of the mouse completely prevented the pituitary MSH increase which occurs seven days after pinealectomy or 24 h after exposure to constant light. The same concentration of AVT injected into the third ventricle of normal mice markedly decreased the pituitary MSH content at 20 min following the injection. The present results suggest that AVT injected into the third ventricle of the mouse inhibits synthesis and/or release of MSH-release inhibiting factor (MIF).


Iodoacetate and iodoacetamide-induced alterations of pancreatic alpha- and beta-cell responses. Iodoacetate and iodoacetamide were compared as to their capacity to block islet glycolysis and interfere with glucose inhibition of glucagon release and glucose stimulation of insulin release. Glycolysis was measured in isolated rat islet by the rate of lactate formation from 27 mM glucose. Hormone release was investigated by perfusing isolated rat pancreas with a 10 mM mixture of 19 amino acids, with and without 5 mM glucose. In perfusion experiments, lactate (2.5 mM) and pyruvate (0.5 mM) were present to provide alternate source of energy independent of glycolysis. Iodoacetate was about twice as potent as iodoacetamide in blocking glycolysis in islets, 0.2 and 0.5 mM, respectively being needed for complete inhibition of lactate production. Levels of either agent lower than 0.05 mM did not affect lactate accumulation. Iodoacetate, at the level which completely inhibited glycolysis did not interfere with the permissive action of glucose for insulin release. In contrast, iodoacetamide at a level (0.05 mM) which had no effect on lactate production, changed the response of the beta-cell dramatically: amino acids now released insulin even in the absence of glucose and insulin release by 5 mM glucose alone was greatly augmented. Both thiol reagents at 0.025 mM concentration completely prevented glucose from suppressing amino acid stimulated glucagon release, iodoacetamide being more potent than iodoacetate. These data indicate that the opposite physiological actions of glucose in alpha and beta-cells are in each case dissociable from the fuel function of the sugar molecule, and the results best support the concept that glucose and thiol reagents effect insulin and glucagon secretion by acting on sulfhydryl groups related to receptor sites in the alpha-and beta-cell membrane.


Effects of testosterone propionate or dihydrotestosterone propionate on plasma FSH and LH levels in neonatal rats and on sexual differentiation of the brain. The present study tests the hypothesis that the effects of perinatal androgen administration on the development of the brain are brought about indirectly by a suppression of plasma gonadotropin (GTH) titers. Both castrated male and intact female rats were treated neonatally with 5 alpha-dihydrotestosterone propionate (DHTP) or testosterone propionate (TP) throughout the first ten postnatal days of life and the corresponding effects on neonatal plasma FSH and LH levels and the subsequent ability of the adult to exhibit cyclic GTH release and female sex behavior (lordosis) were determined. In males castrated within 24 h of birth, subcutaneous injections of DHTP (60 or 180 mug per 100 g average body weight) or TP (60 mug/100 g) given on day 2, 4, 6, 8 and 10 reduced plasma levels of FSH and LH as determined by radioimmunoassay 48 h following the first and last injections. However, TP but not DHTP masculinized the development of the regulation of GTH release as mesured by luteinization of subcutaneous ovarian grafts, and also suppressed the ability of adult neonatally castrated male primed with estradiol benzoate and progesterone to display lordosis behavior. In intact females, the same neonatal DHTP and TP injection regime lowered FSH and LH plasma levels following the last injection (day 12), while DHTP lowered LH, but not FSH, following the first injection (day 4). All TP treated females had ovaries devoid of CL by 45 days of age and showed prolonged vaginal cornification. However, DHTP failed to masculinize the pattern of GTH release in females since DHTP-treated females, like oil-treated females, possessed CL(days 45 and 100) and exhibited vaginal cycles (days 80-100). Lordosis quotients of females treated neonatally with DHTP were as high as those of oil-treated females and significantly  higher than those of TP-treated females. These results demonstrate that the ability of TP to induce maculine differentiation of the neural regulation of GTH release and female sex behavior does not depend on its ability to depress circulating LH and FSH levels in the neonatal male, or LH levels in the neonatal female rat.


The relationship between the rat of testosterone infusion and gonadotropin secretion. Prepubertal and young adult male rats were castrated and continuous intravenous infusions of testosterone were administered for 2-3 days. Blood samples were obtained at various intervals and serum concentrations of FSH and LH were determined. In 43-day-old males a dose of approximately 57 mug/day was required to suppress serum LH to levels observed in intact controls, and FSH was also suppressed at this dose. Within one day after termination of infusions serum LH and FSH concentration had returned to (or exceeded) the levels observed in castrates infused with vehicle only. This was true even after a very large dose of testosterone had been administered (918 mug/day). In 59-day-old males serum LH was suppressed somewhat by 40 mug testosterone/day and further by 200 mug/day. FSH did not appear to be suppressed as readily in these rats as compared to the younger animals. Further experiments in which castrated rats were injected with testosterone or testosterone propionate revealed marked differences in the magnitude and time course of the action of these compounds upon LH release. It is suggested that the rate of metabolism of these steroids is important in limiting their effects, especially when administered by single daily injections. Furthermore, it appears that "recovery" of the hypothalamic-pituitary system from exposure to high concentrations of testosterone is rapid following clearance of the steroid from the blood.


3Beta-hydroxy-20-oxo-pregn-5-ene-16 alpha-carbonitrile, a potent catatoxic steroid devoid of an abortifacient effect. PCN (3beta-Hydroxy-20-oxo-pregn-5-ene-16alpha-carbonitrile), a potent catatoxic steroid devoid of all other classic hormonal properties, given in doses amply sufficient to induce hepatic drug-metabolizing enzymes and inhibit the anesthesia caused by massive amounts of progesterone in pregnant rats, did not modify: 1. the pregnant:mated ratio, 2. the length of gestation, 3. the number of implantation sites, and 4. the size of the litter. The viability and postpartum development of the offspring were normal, as judged by gross macroscopic examination. PCN had no adverse effects on pregnancy after hypophysectomy (day 12), or ovariectomy (day 8) in rats treated with maintenance doses of progesterone and estrone. It would therefore appear that the pregnancy-maintaining capacity of endogenous or exogenous steroids (administered as substitution therapy following the glandular extirpations) was not altered by PCN and that hypothalamo-hypophyseal regulatory mechanisms were not responsible for the failure of the steroid to provoke abortion. As judged by our in vivo experiment, this pure hepatic microsomal exzyme inducer does not modify the steady state of steroid-dependent physiologic functions.


Thyroid hormone regulation of the pulsatile discharges of luteinizing hormone in ovariectomized rats. The pulsatile discharges of luteinizing hormone (LH) were characterized in ovariectomized rats in the presence or absence of thyroid hormone. LH secretion in ovariectomized rats with intact thyroid glands and thyroidectomized-ovariectomized rats receiving daily physiological doses of thyroxine (2 mug/100 g BW/day for 8 days) showed equivalent periodic discharges with frequencies between 15 and 45 min. Though the frequency of the plasma LH rhythm in untreated athyroid-ovariectomized rats was normal, the maximum and minimum concentrations were 2- to 3-fold higher than those of euthyroid-ovariectomized animals. On the other hand, treatment of athyroid-ovariectomized rats with a daily hyperthyroid dose of thyroxine (20 mug/100 g BW) for 8 days, attenuated pulsatile discharges of LH. The LH measured in the sera of these animals each gave dose-response curves by radioimmunoassay which were identical to the authentic rat LH reference preparation. Furthermore, neither the molecular profile nor the metabolic clearance rate of LH was affected by alterations in thyroid status. These results suggest that altered thyroid status does not influence the synthesis and metabolism of LH but does exert a profound effect on the secretion of this hormone by presumably acting directly on the hypothalamo-pituitary axis.


The effect of basal hypothalamic deafferentation on the nycthemeral rhythm of plasma TSH. Basal hypothalamic deafferentation abolished the nycthemeral rhythm of both plasma TSH and corticosterone.


The effect of somatostatin on platelet aggregation. Somatostatin was infused intravenously over two hours to rabbits in a dose of 1.5 mug/kg min with an initial loading dose of 50 mug/kg. This dose inhibited platelet aggregation in response to both ADP and collagen. Lower doses of SRIF had no effect. The addition of SRIF in vitro to either human or rabbit platelet rich plasma also had no effect on collagen or ADP-induced platelet aggregation.


Demonstration of C-peptide immunoreactivity in various body fluids and clinical evaluation of the determination of urinary C-peptide immunoreactivity. C-peptide immunoreactivity (CPR) was demonstrated not only in plasma, but in urine, ascites, cerebrospinal fluid and pleural effusion. The concentration of  CPR in urine was very high compared with that in the other body fluids and was easy to assay. CPR in urine after glucose administration or tolbutamide injection increased parallel to the change of CPR in plasma and also to that of IRI in normals or diabetics without renal disturbances. The result suggest that the determination of CPR in urine before and after stimulation of insulin secretion could serve as a simple indicator of insulin secretory function of pancreas.


Physical and radiological findings specific for medullary carcinoma of the thyroid gland. Preoperative physical and radiological findings, if specific to a certain extent, are important for detecting patients with sporadic form of medullary thyroid carcinoma and especially for the first patient in the family having a hereditary form of medullary thyroid carcinoma and pheochromocytoma syndrome. To delineate clinical features of medullary thyroid carcinoma, a total of 9 patients with this tumor were reviewed retrospectively. In most patients, the thyroid lesions were located in the upper two thirds of the lobe, which was determined by careful palpation or 131I scintiscanning of the thyroid. The primary lesion in the thyroid could be felt more or less as a round, sharply demarcated nodule with fairly good mobility. These findings suggested rather a benign thyroid nodule when there was no lymph node involvement. However, it could be considered a sign suggesting medullary thyroid carcinoma when accompanied by marked lymph node metastasis. In our recent 2 cases, the diagnosis of medullary thyroid carcinoma was strongly suspected on these clinical bases, one of the cases being presented in detail. In 4 patients, lymph node metastasis in the central neck extended to either submandibular or upper mediastinal regions or both. In about one third of the patients, calcified deposits were shown in the cervical roentgenograms. With the use of soft tissue roentgenography, grossly punctate calcific deposits associated with psammoma-like shadows were recognized and the pattern was a criterion for definitive diagnosis of medullary thyroid carcinoma.


Effects of x-ray irradiation on the subsequent gonadotropin secretion in normal and neonatally estrogenized female rats. Female rats were irradiated with 190R of X-rays at 10 days of age and sacrificed 4, 7 or 12 months later. Their ovaries were histologically examined and serum levels and pituitary contents of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined by radioimmunoassay. Both serum levels and pituitary contents of LH and FSH rose significantly 4 and 7 months after irradiation, although the ovaries were markedly reduced in weight. On the contrary, 12 months after irradiation, the ovaries increased in weight and consisted mostly of polyhedral, hyperplastic interstitial cell masses, and both LH and FSH in the serum and pituitary were reduced to normal levels. These characteristic changes in the ovarian weight and histological appearance could not be observed in the similarly irradiated animals which were received daily injections of estrone for the first 30 days of postnatal life, i.e., daily injections of 50 mug for the first 10 days, 100 mug for the middle 10 days and 200 mug for the last 10 days. Serum LH levels of the estrogenized irradiated rats at 7 or 12 months of age did not elevate although those of FSH were significantly higher than the non-irradiated intact levels. From these results, a rise in the blood levels of LH and the FSH may be attributed to the increase in weight and the histological changes in the ovaries of the irradiated female rats, and the elevation of only FSh level may not result in the abnormal growth of the irradiated ovaries.


Female lordosis pattern in the male rat induced by estrogen and progesterone: effect of interruption of the dorsal inputs to the preoptic area and hypothalamus. Lordosis behavior was very rare in castrated male rats which had been pretreated with 50 mug estradiol benzoate (EB) for successive 2 days and 1 mg progesterone (P) 6-8 hr prior to testing on the third day. Only one out of 8 rats displayed lordosis in response to mounts by the sexually matured males. However, the occurrence of lordosis behavior was markedly increased in similarly treated castrated males in which the dorsal afferents to the preoptic area (POA) and hypothalamus were removed by the surgical cut. Twelve out of 19 rats of the group showed lordosis response. The incidence was less frequent in rats receiving sham deafferentation. These results suggest that the dorsal inputs to the POA and hypothalamus may exert a tonic inhibitory influence on the lordosis mediating system in the male rat.


Serum T3 level in the patients with hyperthyroidism after therapy. Serum T3 level in various thyroid diseases was determined in unextracted serum with the Dainabot kit for T3 RIA. The serum T3 level in 33 normal subjects was 0.8-1.6 ng/ml. It was 5.7 +/- 3.5 ng/ml (mean +/- S.D.) in 36 hyperthyroid patients, and undetectable to 0.8 ng/ml in 21 hypothyroid patients. Generally the serum T4 and serum T3 decreased  in parallel after radioiodine therapy for hyperthyroidism. However, in some cases the serum T3 level remained high in spite of normalized serum T4 after radioiodine therapy. This state indicated "T3-toxicosis", and hyperthyroidism was apt to recur. When thyroid function was observed for 2 years following radioiodine treatment, the ratio of serum T3 (T3 level before treatment/T3 level after treatment) decreased more significantly as compared with the ratio of serum T4 in euthyroid cases. Serum T3 provides a more sensitive index of thyroid function than serum T4 in euthyroid states after radioiodine or anti-thyroid drug therapy. The present data indicate that the serum T3 level and the T4/T3 ratio are valuable aids in the estimation of prognosis of hyperthyroid patients after various treatments.


The size of the corpus luteum during pseudopregnancy and pregnancy in the rat. The corpus luteum in mature Sprague Dawley rats was weighted at the various stages of pseudopregnancy and pregancy. The average size of these corpora lutea was 1.0 +/- 0.10 mg, 1.61 +/- 0.69 mg, 1.90 +/- 0.25 mg, 3.69 +/- 0.36 mg, and 4.37 +/- 0.50 mg on day 2 of diestrus, on days 10-15 of psuedopregnancy, on days 9-10, 14, and 20 of pregnancy, respectively. The fact that the average size of the corpus luteum on days 10-15 of pseudopregnancy was larger than that on day 2 of diestrus is thought to drive from prolonged exposure of the corpus luteum to prolactin. The average size of the corpus luteum on days 9-10 of pregnancy had a tendency to be larger than that on days 10-15 of pseudopregnancy and this seems to demonstrate that the placenta secreted placental lactogen by this stage of pregnancy. The average size of the corpus luteum on day 14 of pregnancy was larger than that on days 9-10 of pregnancy. This phenomenon might be attributed to the presence of large amounts of placental lactogen secreted from the placenta between days 10 and 14 of pregnancy. Furthermore, it was noted that the size of the corpus luteum on day 20 of pregnancy was larger than that of day 14, which suggests that further secretion of placental lactogen continued after day 14 of pregnancy. As there was a remarkable decrease in the number of fetuses on day 20 of pregnancy when overiectomy was performed on day 14 of pregnancy, the ovary was considered indispensable in maintaining pregnancy in the rat.


Synthesis of two lactogenic proteins by the mouse placenta in vitro. The culture medium of mouse placental tissues was analyzed on acrylamide gel electrophoresis to localize lactogenic substances. Placental explants from 12- or 14-day-pregnant BALB/cHe mice were organ-cultured for 6 days in leucine-free Way-mouth's medium supplemented with 3H-leucine (10 mu/Ci/ml) and insulin (0.12I.U./ml). The medium was collected every other day and subjected to acrylamide gel electrophoresis. The electrophoretic pattern of radioactive leucine incorporated into proteins was examined on stained 7% gels. Five protein bands were associated with high radioactivity. The location of lactogenic activity on acrylamide gel was when investigated by the technique of organ culture of mouse mammary tissues. Placental explants from 12- to 14-day-pregnant BALB/cHe mice were organ-cultured in Waymouth's medium supplemented with insulin for 2 days. After electrophoresis, proteins were eluted by keeping the segment of acrylamide gel in phosphate buffer, dialyzed and dissolved in tissue culture medium 199 supplemented with insulin and cortisol. Mammary tissues from 8-day-pregnant KA2 mice were cultured for 3 days in the medium containing each eluate. Mammary glands always responded to eluted proteins from two positions of 7% gel, as judged in histological sections. The data suggest the presence of two lactogenic substances in the mouse placenta.


Long-term effect of vasectomy on the biochemical composition of testes and sex accessory organs of the Indian desert gerbil, Meriones hurrianae Jerdon. A long-term vasoligation operation in gerbils, Meriones hurrianae Jerdon did not reveal any consistent change in the weights of androgen dependent organs such as seminal vesicles, ventral prostate, epididymes and perineal complex (levator ani muscle and penis). Histological structure of the testis and caput epididymis remains normal after vasectomy. There was no effect of bilateral vasectomy on androgen production of the testes as reflected by fructose content of coagulating gland. No compensatory hypertrophy of the contralateral testis was observed in unilaterally vasectomized gerbils. The RNA content of the testis and epididymis and ascorbic acid content of adrenal gland did not show appreciable change. No change in protein content of the testis was found but a significant increase was observed in the protein content of epididymis after the operation.


[Influence of neonatally administered gonadotropin on the sexual function of adult rats]. Male and female rats were daily injected with 10 IU HCG plus 10 IU FSH from the 1st to 14th day of life in order to investigate the influence of neonatal gonadotrophin administration on the sex-specific differentiation of the brain. When adult, the males showed hypogonadism associated with approximately normal sexual activity. In the females, precocious puberty, indicated by premature vaginal opening and spontaneous estrus, occurred. Furthermore, bisexuality with a tendency towards more male behavioural patterns was observed, but no impairment of ovarian cyclicity. Thus, hypergonadotrophic hypergonadism during the hypothalamic differentiation phase gave rise to bisexual behaviour in adult female rats associated with normal ovarian cycles. The question of a direct or indirect influence of gonadotrophins on the sex-specific brain differentiation is discussed.


[An ultrastructural study of the adrenal cortex in Cushing's syndrome without and with hyperaldosteronism]. This paper reports ultrastructural comparision of the adrenal gland zones of a rare case of a combination from Cushing's syndrome and hyperaldosteronism with a pure Cushing's syndrom and with a normal human adrenal gland. Whilst between the zona glomerulosa of the normal adrenal gland and of the Cushing's syndrom there are no differences, the morphological state of the glomerulosa cells of the Cushing's syndrom in combination with hyperaldosteronism is interpreted as an inhibition of the activity of these cells. In the cells of the hyperplastic zona fasciculata of Cushing's syndrom in combination with hyperaldosteronism, there are no electronmicroscopical characteristics, who are morphological equivalent of the production of aldosterone. The abundant quantity of steroid producing organells in these cells point to a high function. The cells of the adenoma of Cushing's syndrom contain abundant vacuols of lipids, in which presumable are stored steroid hormones.


[Diurnal rhythms of thyroid hormones in rooster chicks (Gallus domesticus). 1. Studies on the colloid epithelium portion, the radioiodine accumulation in the thyroid gland and the plasma radioiodide concentration]. Four and five week old White Leghorn cockerels were investigated concerning diurnal changes of thyroidal activity. They were kept under normal conditions, including the changes in day light (light from 5.00 am to 8.00 pm). In the thyroid maxima of the per cent amount of colloid were found at 3.00 am and at noon. The values differed significantly from the intermediate ones (2P less than 0.001) which reached only 22 per cent of the maxima. The thyroidal uptake of radioiodine had also a maximum at 3.00 am (51 percent and 78 percent resp., 90 min. or 24 hours p.i.). The 24-h uptake at 3.00 am was significant different from the corresponding uptakes between 6.00 am and 6.00 pm (53-61 percent; 2P less than 0.05). The plasma radioiodide increased at afternoon and in the evening. The 9.00 pm concentration differed significantly from the 9.00 am concentration (2P less than 0.001). Since in the afternoon most of the food is ingested the thyroid can take up a greater amount of untracered iodide and therefore the radioiodide concentration of plasma may remain high. The above observations may be explained in the following way: (1) The thyroidal iodine uptake is increased in the afternoon corresponding to the increase in colloid; however these increase is not detectable by measuring the radioiodine uptake because of dilution effects (during the night the increase in colloid coincidences with the increase in iodine uptake); (2) looking at the daily changes of colloid and radioiodine uptake the thyroid may be stimulated in the early morning and in the evening.


[Diurnal rhythms of thyroid hormones in rooster chicks (Gallus domesticus). 3. Studies on the changes in deiodination rate of thyroxine-I-131]. As a measure for the availability and efficiency of the so-called free hormone to repress the thyreotropin-secretion (Mouriz et al., Endocr. 79, 248-260 (1966) we investigated the deiodination of thyroxine-I-131 (T4-I-131). This was done with special regard to a possible cyclic variation. By means of the reutilisation we could measure the removed radio-iodide in the thyroid 1-1/2 hours after T4-I-131 application. Using I-125 as a reference-isotope for the radioiodine uptake we could specify the actual extent of deiodination. The deiodination had a diurnal variation: The minimal values at 9 am and 9 pm ("deiodination" 10 or 9 percent) were significantly different (2 P less than 0.025) from the maximal values at 3.00 am and 3.00 pm ("deiodination-rate" about 17 percent). We propose the following explanation: 1) While the deiodination is decreasing in the morning and evening the pituitary releases more thyreotropin; 2) Thereby the thyroid releases more hormone and so the protein-bound iodine and the so-called free hormone raises. This would be in good agreement with our prior investigations.


[Determination of plasma progesterone using thin layer chromatography during pregnancy and normal menstrual cycle]. Plasma progesterone levels were measured during pregnancy and the normal human menstrual cycle by thin-layer densitometry of a specific fluorescence reaction for delta4-3-ketosteroids. 94 determinations were carried out from the 7th week of pregnancy until term. 84 plasma progesterone concentrations were estimated between day 16 and day 26 and other 10 during the preovulatory phase of the normal menstrual cycle.


[The mechanism of insulin secretion following oral glucose administration. 4. Inhibition of the early reflectoric phase of plasma insulin increase through atropine]. In the first phase after on oral glucose load or after sham-feeding of glucose in conscious intact or on the oesophagus fistulated dogs respectively, the peripheral venous plasma insulin concentration increases independently of any blood glucose alteration. After previous intravenous atropin injection, this reflectoric insulin secretion cannot be observed. The N. vagus is involved in the afferent and/or efferent side of the reinforcing mechanism of insulin secretion basing on the entero-insular axis. Additionally the enteral glucose absorption is inhibited.


Pulmonary response to polyurethane dust. Weanling and 9 months or older rats were exposed to particles of an aged (PUF I) or freshly prepared (PUF II) rigid polyurethane foam by intratracheal intubation. The dose was 5 mg of particles. The response of the lung tissue was examined morphologically by serial sacrifices. Inflammation and macrophage activity were the initial responses. Fibrosis developed after 6 months. Nodular scars and perifocal emphysema were seen after 12 months. Four rats had a papillary adenoma in a major bronchus after 18 months exposure to PUF II.