Synthesis and study of glutaryl-S-(omega-aminoalkyl)-L-cysteinylglycines as inhibitors of glyoxalase I. Glutaryl-S-(8-aminooctyl)-L-cysteinylglycine and glutaryl -S-(10-aminodecyl)-L-cysteinylglycine have been prepared by a seven-step procedure as potential ligands for affinity chromatography purification of mouse liver glyoxalase I. Both compounds exhibited nonlinear, mixed-type inhibition of the enzyme. The decyl derivative was a more effective inhibitor than was the octyl analog.


Analogs of camptothecin.

Analogs of camptothecin. Several compounds having portions of the camptothecin ring system were prepared. These compounds were screened against L1210 lymphoid leukemia with negative results. Two of the analogs which contained the pyridine and hydroxylactone D and E rings were also screened for inhibition of DNA and RNA syntheses in HeLa cells. Each of these analogs had decreased activity as compared with comptothecin and there was no degradation of DNA in the HeLa cells. This suggest that the D and E rings are not a sufficient requirement for camptothecin-like activity.


Biologically active polycycloalkanes. 1. Antiviral adamantane derivatives. Convenient methods for the synthesis of 1-substituted 3-adamantyl chlorides and bromides (2), 1-adamantylphenols and -cresols (3), and 1-adamantylacetic (6) as well as 1,3-adamantanediacetic (11) acids are described.  Several novel derivatives were synthesized from these key intermediates: adamantylcyclohexanols (4) and -cyclohexanones (5) from adamantylphenols (3), and esters (7,12, and 22), amides (13 and 18), thioamides (9 and 16), amidine (10), nitrile (15), and amines (14 and 17) from 1-adamantanecarboxylic (19) and -acetic (6) acids and 1,3-adamantanediacetic acid (11).  Some adamantylpyrimidines (24) and -purines (25 and 26) were also prepared.  Antiviral activities of the compounds obtained in this work and a series of new 1-adamantyl alkyl ketones synthesized before, together with those of some known adamantane derivatives, were tested in vitro on monolayer culture of chick ambryo fibroblasts against Newcastle disease virus.


Synthesis and antiviral activity of certain 5'-monophosphates of 9-D-arabinofuranosyladenine and 9-D-arabinofuranosylhypoxanthine. A number of 5'-phosphates of 9-D-arabinofuranosyladenine and 9-D-arabinofuranosylhypoxanthine were prepared and tested against a variety of DNA viruses in tissue culture. The syntheses of the antiviral agent 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate (6) and a series of related nucleotides, 9-beta-D-arabinofuranosyladenine 5'-O-methylphosphate (3), 9-beta-D-arabinofuranosylhypoxanthine 5'-O-methylphosphate (7), 9-beta-D-arabinofuranosylhypaxanthine cyclic 3',5'-phosphate (13), and 9-alpha-D-arabinofuranosylhypoxanthine 5'-monophosphate (17), are described. The concepts underlying the development of these antiviral agents are discussed. Comparison of the anti-DNA viral activity is made with 9-beta-D-arabinofuranosyladenine (ara-A). Reproducible antiviral activity against three DNA viruses in vitro at nontoxic dosage levels is demonstrated by 3,6, and other related nucleotides.


Primary care career choices and medical student learning styles. The study reported here focused on the influence of medical students' learning styles (that is, how they prefer to receive and use information in learning and problem-solving situations) on (a) their choice of a medical career type and (b) their sources of information and influence in making that choice. The results suggest that those students with learning styles that are associated with primary care careers are also those who are dissatisfied with a traditional basic science curriculum and are influenced more than the average student by concrete work experiences, as well as identification with role models, in making a career decision. Among the implications of these results for medical school admissions, curricula, and faculty is the possibility that more students might consider primary care careers if more primary care experiences and role models were available in medical school.


A preliminary study of Mexican-American medical students. The results of a 1973 mail questionnaire survey of Chicano medical students are reported. A response rate of 50 percent was achieved, and the results indicate that this group of medical students is similar to the majority of medical students in some respects but diverges widely in other areas, for example, parental socioeconomic status and language use. Differences in ethnic identification within the group were also found. California and Texas are educating the majority of the Chicano students surveyed.


Support groups for women in medical school: a first-year program. This report presents a workable model for a support system for first-year women medical students at the University of North Carolina School of Medicine. The students met in small groups at weekly intervals with women faculty members from the Department of Psychiatry throughout the academic year. Role conflicts which confront these young women professionals entering a "masculine" field as a minority group are described. There is an elaboration of those factors, both personal and institutional, which serve either to promote or deter conflict resolution and the acquisition of a satisfactory professional and female identity. A discussion of group formation and processes and a year-end evaluation are included. Both students and faculty assessed the program as having provided a needed and constructive setting in which to explore the problems and identities of women professionals and to develop close supportive relationships with women colleagues.


Electromyography and mechanics of mastication in the albino rat. The masticatory apparatus in the albino rat was studied by means of electromyography and subsequent estimation of muscular forces. The activity patterns of the trigeminal and suprahyoid musculature and the mandibular movements were recorded simultaneously during feeding. The relative forces of the individual muscles in the different stages of chewing cycles and biting were estimated on the basis of their physiological cross sections and their activity levels, as measured from integrated electromyograms. Workinglines and moment arms of these muscles were determined for different jaw positions. In the anteriorly directed masticatory grinding stroke the resultants of the muscle forces at each side are identical; they direct anteriorly, dorsally and slightly lingually and pass along the lateral side of the second molar. Almost the entire muscular resultant force is transmitted to the molars while the temporo-mandibular joint remains unloaded. A small transverse force, produced by the tense symphyseal cruciate ligaments balances the couple of muscle resultant and molar reaction force in the transverse plane. After each grinding stroke the mandible is repositioned for the next stroke by the overlapping actions of three muscle groups: the pterygoids and suprahyoids produce depression and forward shift, the suprahyoids and temporal backward shift and elevation of the mandible while the subsequent co-operation of the temporal and masseter causes final closure of the mouth and starting of the forward grinding movement. All muscles act in a bilaterally symmetrical fashion. The pterygoids contract more strongly, the masseter more weakly during biting than during chewing. The wide gape shifts the resultant of the muscle forces more vertically and moreposteriorly. The joint then becomes strongly loaded because the reaction forces are applied far anteriorly on the incisors. The charateristic angle between the almost horizontal biting force and the surface of the food pellet indicates that the lower incisors produce a chisel-like action. Tooth structure reflects chewing and biting forces. The transverse molar lamellae lie about parallel to the chewing forces whereas perpendicular loading of the occlusal surfaces is achieved by their inclination in the transverse plane. The incisors are loaded approximately parallel to their longitudinal axis, placement that avoids bending forces during biting. It is suggested that a predominantly protrusive musculature favors the effective force transmission to the lower incisors, required for gnawing. By grinding food across transversely oriented molar ridges the protrusive components of the muscles would be utilized best. From the relative weights of the masticatory muscles in their topographical relations with joints, molars and incisors it may be concluded that the masticatory apparatus is a construction adapted to optimal transmission of force from muscles to teeth.


Epidermal downgrowths in regenerating rabbit ear holes. Rabbits are unique among mammals in that their ears can regenerate tissues from the margins of full thickness holes which grow in and completely fill the opening in about two months. The circular blastema that forms around the edges of the hole differentiates a new sheet of cartilage as it regenerates in a centripetal direction. Similar holes in other mammals fail to regenerate and form scar tissue instead of a blastema. Histological studies of the healing around the edges of rabbit ear holes reveal that during the second week, when the epidermis is completing its migration across the wound from the opposite sides of the ear, conspicuous tongues of epidermal cells grow down into the underlying tissues at the edges of the wound. These epidermal downgrowths are situated between the original intact dermis of the skin and the more central tissues which give rise to the blastema. Such downgrowths are of a transient nature, and are no longer found once the blastema rounds up toward the end of the second week. Since they are not found in the healing of similar wounds in rabbit ears prevented from regenerating by prior removal of their cartilaginous sheets, nor in the naturally nonregenerating ears of sheep and dogs, it is considered that these downgrowths of healing epidermis may play a role in the unusual regenerative response of ear tissues in the rabbit.


Some applications of bloodmeal identifications in relation to the epidemiology of vector-borne tropical diseases. No attempt has been made to give a complete review of the value of bloodmeal identifications of haematophagous arthropods in relation to the epidemiology of disease but rather to choose certain topics of current interest. A brief review of the current techniques for bloodmeal identification is given with particular reference to recent studies on mosquitoes and sandflies using the haemagglutination inhibition test. New data on mixed feeding by Anopheles gambiae (a mixture of species B and C) collected in Ethiopia confirm the earlier work with A. sacharovi that interrupted feeding is important. Details of current attempts to measure the cryptic portion of multiple meals using blood-typing techniques are given. Information collected on the feeding patterns of Culex univittatus group and Mansonia uniformis from Kenya demonstrates that caution must be shown in interpreting blood meal analyses since sampling techniques as well as several other factors can affect the results. A recent survey of sandflies in West Bengal suggest that a dangerous situation now exists and an outbreak of visceral leishmaniasis could occur.


The impact of health care and nutritional education on an urban community in Zambia through the under five clinics. A social survey was carried out on 60 surviving children who suffered from severe kwashiorkor, using 60 "normal" peers drawn from the same socio-economic area. The impact of local under five clinics in the area with regard to health education and health care was assessed and found to be inadequate, despite the large number of clinics available. The replacement of these under five clinics by "at risk" clinics for children of all ages within the framework of a community health centre was suggested.


[Urethral profile: study of a technique (author's transl)]. The different methods used for the measurement of urethral resistance were critically reviewed. Experimental studies were carried out to standardize pressure profile measurements. A catheter with 8 side holes was found to give the best results. The various parameters which can influence the measure were studied. Strict specifications of the procedure are proposed.


Fish rhabdoviruses: comparative study of protein structure. Proteins from four fish rhabdoviruses have been studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The viruses were: trout viral hemorrhagic septicemia (VHS), infectious hematopoietic necrosis virus (IHN), spring viremia virus of carp (SVC), and the pike fry rhabdovirus (PFR). For the two salmonid viruses (VHS-IHN), gel electrophoresis indicated the proteins, with molecular weights estimated to be 190,000, 80,000, 38,000, 25,000, and 19,000, respectively. The electrophoretic profile of the two other viruses (SVC-PFR) revealed four major proteins with molecular weights of 190,000 80,000 42,000 and 21,000, respectively. In this case a minor component with 50,000 daltons was found. For each virus only one protein was found to be glycosylated, i.e., the one with a molecular weight of 80,000. A major protein (molecular weight between 38,000 and 42,000) was found to be associated with the nucleocapsid. All these results revealed marked similarities in protein structure between the four fish rhabdoviruses and the previously well-characterized members of rhabdovirus group. However, one can distinguish two groups of viruses: the first one is composed of salmonid viruses (VHS and IHN) with a protein structure comparable to that of rabies virus and potato yellow dwarf virus; the second one is composed of carp and pike viruses, having a protein structure very similar to that of vesicular stomatitis virus.


Abortive infection of L cells by influenza virus: absence of virion RNA synthesis. Influenza virus multiplies productively in chick cells and abortively in L cells. The infecting influenza virus RNA genomes are less stable in infected L cells than in infected chick cells. However, transcription of the virus genome in L cells, while reduced in rate, is not decreased in extent. There is no detectable synthesis of virion RNA in L cells, and this is the most likely cause of the abortive infection.


Proteins synthesized by Semliki Forest virus and its 16 temperature-sensitive mutants. The proteins synthesized in chicken embryo fibroblasts infected with wild-type Semliki Forest virus and 16 temperature-sensitive mutants derived from it were studied by polyacrylamide gel electrophoresis. In addition to the structural proteins, five nonvirion proteins (NVP) with molecular weight of 130,000, 97,000, 86,000, 78,000 and 62,000 were found varying amounts in cells infected with the different RNA+ mutants and also in the wild-type-infected cells. Pulse-chase experiments suggested that NVP 130, NVP 97, NVP 86, and NVP 62 are precursors presumably of the structural proteins. The amount of NVP 78 was not affected by the chase, and it may represent a translational product of the nonstructural part of the genome. The NVP 130 was shown to be a common precursor of the structural proteins by tryptic peptide mapping. Kinetic evidence from one of the mutants (ts-3) suggested that NVP 86 is one of the precursors of the capsid protein. A common feature of all the RNA+mutants was the inability to cleave the NVP 62 into E2 and E3, suggesting that this cleavage is a crucial reaction in the virus maturation.


Structure and chemical-physical characteristics of lactate dehydrogenase-elevating virus and its RNA. Lactate dehydrogenase-elevating virus (LDV) was purified from culture fluid of infected primary cultures of various mouse tissues (peritoneal macrophage, bone marrow, spleen, and embryo) and from plasma of infected mice. Electron microscopy of negatively stained virus and positively stained sections of LDV revealed spherical particles of uniform size with a diameter of about 55 nm, containing an electron-dense core with a diameter of about 30 nm. During sample preparation the envelope had a tendency to slough off and disintegrate to form aggregates of various sizes and small hollow particles with a diameter of 8 to 14 nm. Two strains of LDV exhibited a density of 1.13 g/cm3 in isopycnic sucrose density gradient centrifugation whether propagated in primary cultures of the various mouse tissues or isolated from plasma of infected mice. A brief incubation of LDV in a solution containing 0.01% Nonidet P-40 or Triton X was sufficient to release the viral nucleocapsid, whereas a similar treatment had no effect on Sindbis virus. The nucleocapdis of LDV exhibited a density of 1.17 g/cm3, was devoid of phosphatidylcholine, and contained only the smallest of the viral proteins, VP-1, which had a molecular weight of about 15,000. The envelope contained two proteins. VP-2 with a molecular weight of 18,000 and a glycoprotein, VP-3, which migrated heterogenously (24,000 to 44,000 daltons) during polyacrylamide gel electrophoresis. When compared to the sedimentation rate of 29S rRNA, the RNAs of LDV and Sindbis virus sedimented at 48 and 45S, respectively, whether analyzed by zone sedimentation in sucrose density gradients containing low or high salt concentrations or denatured by treatment with formaldehyde. Our results indicate that LDV should be classified as a togavirus, but that LDV is sufficiently different from alpha and flaviviruses to be excluded from these groups.


Studies on the budding process of a temperature-sensitive mutant of murine leukemia virus with a scanning electron microscope. The scanning electron microscope was used to study the budding process of the wild-type Moloney murine leukemia virus and one of its temperature-sensitive mutants, designated ts 3. A considerably larger number of budding particles was observed on TB cells infected with ts 3 at the nonpermissive temperature (39 C) than at the permissive temperature (34 C). No apparent difference was noted between the number of particles on ts 3-infected cells at (34 C) and wild-type-infected cells at 34 or 39 C. Virions were detected at the cell membrane of ts 3-infected cells at 39 C as early as 8 h postinfection. Virion density increased progressively up to 48 h after which no increase was observed. An average of 1,600 virus particles was observed at the cell surface at the peak of virus production. The distribution of these on the cell membrane appeared to be random. The maximum proportion of the cell surface occupied by the viral particles did not exceed 10%. After temperature shift from 39 to 34 C, approximately 90% of the particles had dissociated from the cell membrane within 1 h.


Meatal advancement for distal hypospadias without chordee. A simple 1-stage procedure is described for correction of distal hypospadias in patients with a mobile ventral penile shaft skin.


The wild turkey as a host for Heterakis gallinarum and Histomonas meleagridis. Freshly embryonated eggs of Heterakis gallinarum gathered from naturally infected domestic turkeys and chickens developed the first 4 weeks essentially as well in young wild turkeys as in domestic poults, but then became progressively retarded and failed in most birds to result in females with fertile eggs. There was no significant difference in the prevalence or progress of infections with Histomonas meleagridis in the two kinds of turkeys, both of which differed from chickens only in that the latter had neither liver involvement nor mortality. In a second test, heterakids hatched from eggs stored 5-6 months at 4 C (comparable to overwintering) sustained very heavy losses in all birds, with greatly accelerated liberations of H. meleagridis, Few worms reached maturity and still fewer produced fertile eggs. In turkeys, and especially in wild turkeys, replacement of infective stages was so poor, that these birds were of no importance in contaminating the soil.


Effects of magnesium and temperature during the recovery process from the potassium contracture of the pregnant rat myometrium. Effects of external ions (Na, K, Mg) on the recovery from K-contracture of the pregnant rat myometrium were investigated in Ca-free media. Relaxation was faster, when the external concentration of Na and K ions was higher. The time course of relaxation within a limited range of 60-20% of the mechanical output followed a single exponential function. The rate of relaxation, given by the reciprocal of the period during which the contraction decayed to 1/e, was 0.3-0.5 min-1 at 34-35 degrees C in isotonic Na solution. Low temperature caused prolongation of the relaxation, and the activation energy estimated on the rate of relaxation was 3-4 kcal-mol-1. Relaxation became faster when Mg (0.5-20 mM) was added to the relaxation media. Relaxation in isotonic K media was slower than in isotonic Na media, and the addition of Mg caused a slight acceleration of the relaxation. Low temperature caused an acceleration of the relaxation, irrespective of the presence or absence of external Mg ions. In low K media, where K ions were replaced by isomolar sucrose, addition of Mg caused a significant acceleration of the relaxation. Activation energy ranged between 13-15 kcal mol-1 in the solutions containing Mg. This favors the existence of a relaxing system in pregnant rat myometrium that is Mg- and metabolism-linked.


The metabolic and phagocytic activities of leukocytes from patients receiving corticosteroid and radiation therapy, and patients with bacterial infections. Peripheral blood leukocytes from patients given corticosteroid or radiation therapy, as well as patients with bacterial or viral infections, were studied with regard to the selected enzyme activities of the hexose monophosphate shunt (HMS). Glucose-6-phosphate dehydrogenase (G-6-PD), 6-phosphogluconate dehydrogenase (6-PGD) and reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase were assayed spectrophotometrically on mixed leukocyte suspensions in isotonic glycerol. Enzyme activities of G-6PD and NADPH oxidase in patients receiving corticosteroid or radiation therapy were significantly lower than the enzyme activity of 6-PGD. In patients with bacterial infections, activities of the three enzymes increased but in patients with viral infections, only the activities of NADPH oxidase and G-6PD were slightly decreased. Nitroblue tetrazolium (NBT) dyereducing activities of neutrophils from patients receiving corticosteroid or radiation therapy were attenuated which coincides with the reduced activities of HMS enzymes. From these results, it is likely that the reduced activities of intraleukocytic HMS enzymes of patients receiving corticosteroid or radiation therapy are correlated with intracellular bactericidal activities which might result from the attenuated level of hydrogen peroxide production.


Sources of variation in preweaning weight of mice. The effects of body weight of dam after parturition (D), litter size at birth (N), and birth weight (B) on the weight of mice at 12 da of age (M) were examined in 3 experiments under different conditions: Experiment 1, cohabitating of breeders at 3 wk of age, a sexually immature stage; Experiment 2, cohabiting of breeders at 9 wk of age, a mature stage; and Experiment 3, cohabiting of breeders at 9 wk of age plus cross-fostering at birth. In all experiments, litter size was standardized to 8 at birth. Standard partial regression coefficients of M on D, N, and B were .325 +/- .036, .298 +/- .038, and .483 +/- .034 in Experiment 1; .204 +/- .045, .161 +/- .044, and .370 +/- .043 in Experiment 2; and .375 +/- .098, .074 +/- .097, and --.137 +/- .287 in Experiment 3. The variation in M attributable jointly to all independent variables (D, N, and B) was 49, 22, and 17% in Experiments 1, 2, and 3, respectively. It was concluded that when sexually mature mice at nearly the same age are cohabited for reproduction, the effects of D, N, and B on an indirect measure of milk production (M) are not large. The potential for genetically improving milk production under the condition of Experiment 3 was discussed.


Experimental respiratory infection with Pasteurella multocida and Bordetella bronchiseptica in rabbits. Eight-to-10-wk-old offspring of a colony of specific pathogen free [Eda:(NZW x FG)F1BR] rabbits were exposed to cultures of Pasteurella multocida and Bordetella bronchiseptica. Two groups of 9 animals each were exposed to cultures of either species of bacteria intranasally and killed 2, 7, 14, and 21 da postinoculation. Five of 9 rabbits in each group developed a mucopurulent nasal discharge 4-7 da postinoculation. The remaining 4 rabbits in each group failed to develop clinical signs. The gross and microscopic lesions did not differ in character or distribution among the inoculated rabbits. The infection was characterized by an acute upper respiratory syndrome accompanied by a mild bronchopneumonia.


Fetal mouse heart in organ structure: ultrastructure. The fetal mouse heart can be maintained in organ culture for days while it retains its capacity to beat rhythmically; however, degenerative changes eventually occur. In this study, the ultrastructure of the hearts fixed immediately after removal from the fetus without incubation often revealed some swelling of organelles,suggesting that early ischemic alterations may occur during the time required for removaland fixation.  Within 2 days in organ culture, most of the cells reverted to normal, indicating that the injury was reversible.  However, a few cells had undergone necrosis.An interesting finding in some cells was the presence of autophagic vacuoles containing damaged mitochondria and occasionally,myrofibrils.  These vacuoles were usually surrounded by a single layered membrane, but occasionally a double membrane was present.  The occurrence of these vacuoles in an otherwise normal appearing cell suggests that focal cytoplasmic injury had occurred and the damaged elements were being sequestered anddigested within the vacuoles.  An alternative possibility is that these cells were adjusting their cytoplasmic contents to a new level of homostasis. In as much as this phenomenon is not often seen in adult myocytes, it may suggest that fetal cells have agreater capacity to resist injury than adult cells and thus can isolate and digest damaged components without undergoing complete necrosis.


Derivation of type 1 epithelium from type 2 cells in the developing rat lung. Renewal of squmous alveolar epithelium following injury probably occurs by division of type 2 cells with subsequent transformation to type 1 epithelium.  The present morphologic and cytodynamic studies of developing rat lung provide further evidence that this mechanism reflects the normal process of cell renewal in the alveolar epithelium.  From gestation days 18to 20, the epithelium was composed of glycogen-laden cuboidal cells which by day 20 contained lamellar bodies.  In this period of high DNA synthesis in thelung, about 50 per cent of 'H-thymidine-labeled pulmonary cells were type 2, and mitoseswere frquently seen in these cells.  On day 22, when many type 1 cells were first seen,over-all labeling was much reduced and was predominate in interstitial cells; type 2 labeling fell to about 10 percent.  (he labeling index of type 1 cells, about 1 per cent atthis time, did not increase subsequently and mitotic figures were not seen in this celltype.  Cells intermediate in formbetween type 2 and type 1 were observed after day 21, and, postnatally, the normal mixed population of epithelium cells lined the alveoli.  The findings of maximal DNAsythesis and cell division when the alveoli were lined exclusively by type 2 cells, low labeling and the absence of mitotic figures in type 1 epithelium, and the observation of intermediate cell forms provide additional evidence that the type 2 cell is the progenitorof type 1 epithelium.


Ultrastructure of platelets in Bernard-Soulier syndrome. The platelets of a patient with the Bernard-Soulier syndrome were studied by electron microscopy.  The main abnormalities were the presence of giant and often round platelets, hypertrophic and frequently widely dilated open canalicular system, disorganized microtubules, and platelets with sparse or absent granulation.  Although well defined, these ultrastructural morphologic aberrations are not considered diagnostic or pathognomonic of the syndrome.


Panel on epidemiology and etiology of laryngeal carcinoma. Ours is a developing country. We have still not controlled the common infectious diseases which are extinct in the West; therefore, our limited resources are spent on study  of epidemiology of infectious diseases. My conclusions on epidemiology of cancer of the larynx are drawn from observations made of the clinical material over a period of 25 years. I have come to the conclusion that the smoked tobacco and the slaked lime in the Indian "Pan" are the two important carcinogenic agents. Poor nutrition appears to be carcinogenic. It requires study and confirmation at a cellular level. Misuse of voice does seem to be the cause of laryngeal cancer. Racial, genetic and other environmental factors, including pollution have not contributed to the increased incidence of laryngeal cancers. The common histological types of laryngeal cancer are known. My observations on certain biological behavior of the tumor have been helpful. 1. An exophytic growth is less infiltrative; its metastatic mass reflects the same characteristics. 2. Certain anaplastic tumors can flout all laws of cancer spread and metastasize in distal organs. 3. Presence of reticular hyperplasia in peripheral lymph nodes is of good prognostic value.


Emotionality changes in rats following chronic exercise. The effect of chronic endurance exercise on the emotionality of male albino rats was studied in five experimental groups: Controls, Runners, Walkers, Swimmers and Waders. Runners and Swimmers were trained for 8 weeks using programs which produced significant bradycardia and cardiac hypertrophy. Walkers and Waders received comparable handling and exposure to the psychological aspects of the treadmill running and swimming routines but were not physically trained. The Control group was allowed only home cage activity. After 8 weeks all animals were tested for their level of emotionality using the tunnel emergence test and the open field test. The emergence test was judged to be too stressful for the Sasco rat strain used in this study since many rats failed to emerge in one hour. Three measurements in the open field: urination, defecation and central squares also lacked power to discriminate emotionality because of their very low level of occurrence. The Control rats had significantly longer latency times, which indicates that the additional handling received by the other groups reduced their emotionality. The significantly larger number of total squares entered by the Runners and Swimmers supports the hypothesis that chronic physical exercise does function to lower emotionality in the rat.


Fungal endocarditis: analysis of 24 cases and review of the literature. Fungal endocarditis occurs in heroin addicts, patients who have undergone cardiovascular surgery, and patients who are treated for prolonged periods with intravenous fluids and broad spectrum antibiotics. The organisms associated with endocardial infection differ in each of these groups. Candida parapsilosis is the fungal species most commonly isolated from narcotics addicts, Aspergillus species are most frequently found in patients after cardiovascular surgery, and Candida albicans occurs most frequently in patients who have received prolonged courses of intravenous fluids and antibiotics. Despite the availability of antifungal antibiotics and surgery, over 80% of patients with documented fungal endocarditis die of this infection. Thus, early diagnosis of fungal invasion and prevention of established endocardial infection are essential. Antifungal therapy and/or careful followup should be considered in patients in whom "transient fungemia" is documented by blood culture and serological and untrasonic techniques should be further evaluated as a means of early diagnosis.


Adrenal function in the carcinoid syndrome: effects of the serotonin antagonist cyproheptadine. Results of evaluations of adrenal function in 11 patients with carcinoid tumors are presented. Nine patients had tumors that made and secreted serotonin resulting in elevated 5-hydroxyindoleacetic acid (5-HIAA), elevated serum serotonin, and the carinoid syndrome; while two patients had tumors that did not make serotonin and that did not cause elevated 5-HIAA excretion or elevated serum serotonin. All of the patients had normal 24-hr 17-hydroxycorticosteroid excretion. In the group of patients with tumors actively secreting serotonin, the correlation between 17-hydroxycorticosteroid and 5-HIAA excretion (r = 0.44) was not significant. Six of these patients pretreated with cyproheptadine (CYPRO), a serotonin antagonist, experienced a 36% mean decrease in 17-hydroxycorticosteroid excretion, a finding that was not present when three of them were treated with triprolidine (TPRO), an antihistamine. Serum cortisol at 8 a.m. was normal in all patients except two whose values were mildly elevated, and these two patients showed evidence of suppression of ACTH secretion secondary to dexamethasone treatment. There was a significant positive correlation between serum-cortisol concentrations and 5-HIAA excretions (r = 0.73, p less than .05). Normal diurnal variation was present in six patients in whom it was determined. The serum-cortisol response to insulin-induced hypoglycemia in six patients who had carcinoid tumors actively secreting serotonin was not statistically different from that of 12 normal volunteers. Comparisons between these two groups were difficult because the carcinoid patients' fall in blood sugar was 50%, whereas that of the control group was to 38% of the fasting glucose concentration. Six patients with actively secreting carcinoid tumors responded to standard metyrapone testing with a mean increment of 22.8 +/- 2.5 mg/day in 17-hydroxycorticosteroids. This response was statistically different from the increment of 13.8 +/- 5.3 mg/day in 17-hydroxycorticosteroid excretion found in 34 age-matched hospitalized control patients. When the tests were repeated in four of the patients with carcinoid tumors after pretreatment with CYPRO, the increment in 17-hydroxycorticosteroid excretion was reduced well below the mean increment of the control group. Peak serum 11-deoxycortisol (Compound S) values during the test were also reduced. This decrease in the metyrapone response after CYPRO pretreatment was not due to changed peripheral cortisol metabolism, altered adrenal responsiveness to ACTH, interference with recovery of 17-hydroxysteroids by the Porter-Silber reaction, altered metyrapone metabolism, or reduced renal clearance of Compound S. These changes in adrenal response to metyrapone were not seen when the patients were pretreated with TPRO. Our data suggest that the alterations in adrenal function in our patients may be related to elevated serum serotonin. If CYPRO acts by antagonizing serotonin, these data may give support to the idea of serotoninergic control of cortisol secretion.


[Oral iron therapy in infancy and childhood (author's transl)]. In pediatric practice iron deficiency is the most common nutritional deficiency. Infants between 6 months and 2 or 3 years are predisposed, especially if they were pre- or dysmature newborns or gemini. The frequency of iron deficiency--prelatent, latent or manifest anemia -- can be understood from the peculiarities of iron metabolism in this early period of life. Influencing factors are the body iron content of the newborn and the amount of postnatal iron intake. The discrepancy between a low iron content in the average baby's formula and high requirements in the rapidly growing organism have also to be considered. Low values of hemoglobin and serum iron, and an increased intestinal iron absorption in a normal baby of 4--6 months or a prematurely born baby of 2--3 months indicate depleted iron stores. A longterm oral iron therapy is indicated in pre- or dysmature babies, in newborns with perinatal blood loss, and in infants with recurrent infections. In this study 40 infants and children were treated with a liquid ferrogluconate preparation (Athensa-Ferro-Saft). Controls of several parameters of red blood cells, serum iron and iron binding capacity showed a good or excellent therapeutic effect. No serious side effects were seen. Because the preparation is well tolerated and can be administered in individual doses, it may be recommended for pediatric use.


The induction by X-rays of chromosome aberrations in male guinea-pigs, golden hamsters and rabbits. II. Properties of translocations induced in post-meiotic stages. Translocations induced by X-rays in post-meiotic germ cells of male guinea-pigs, golden hamsters and rabbits were studied cytologically in the F1 sons of the irradiated males. The percentage of spermatocytes displaying multivalent configurations varied with the translocation, but the average percentage appeared to depend on the species: fewer quadrivalents were observed in hamster than in guinea-pig heterozygotes and most were recorded for rabbit heterozygotes. Chain quadrivalents were more abundant than ring quadrivalents at meiosis for the guinea-pig and hamster, in contrast to the mouse. Too few translocation heterozygotes were examined to determine which meiotic configuration was the more prevalent in the rabbit. In all three species, as in the mouse, translocations were found which caused male sterility, due to partial or complete failure of spermatogenesis, although most translocations caused semi-sterility. For these semi-sterile males both the frequency and time of embryonic death in the progeny appeared to be the same as in the mouse. It is concluded that similar types of chromosome aberrations are induced by X-rays in post-meiotic germ cells of male guinea-pigs, rabbits, golden hamsters and mice.


The induction by X-rays of chromosome aberrations in germ cells of male guinea-pigs, golden hamsters and rabbits. I. Dose response in post-meiotic stages. The induction by X-rays of translocations in post-meiotic germ cells of the guinea-pig, golden hamster and rabbit was studied by cytological analysis of male offspring of the irradiated animals. As reported previously for the mouse, the pattern of sensitivity to dominant lethal induction, as indicated by litter-size, was similar to that for translocation induction in both the guinea-pig and golden hamster. In both speciesspermatids were more sensitive than spermatozoa, and in the golden hamster spermatocytes gave a lower yield than spermatids. The translocation frequency among post-meiotic germ cells treated with 600 rad was higher in the rabbit than the guinea-pig, and both were above that for the golden hamster. However, for spermatozoa, species differences with respect to the recovered translocation yield appeared to depend on dose. In the hamster, the translocation frequency after 600 rad, as measured in the female offspring, was similar to that obtained in the male offspring. A small amount of data on the induction of sex-chromosome aneuploidy by 200 rad in golden hamsters suggested that the hamster might be as sensitive as the mouse.


Arthroderma benhamiae infection in the Central African hedgehog Erinaceus albiventris, and a report of a human case. The occurrence of ringworm caused by Arthroderma benhamiae Ajello & Cheng is reported in Central African hedgehogs (Erinaceus albiventris Wagner), caught near Nairobi, Kenya. Of the 45 animals examined, 10 were positive on culture, including a litter of 4 young. Six infected animals were without lesions, and 2 littermates showed scaly areas similar to those described in E. europaeus L. caused by Trichophyton erinacei (Smith & Marples) Padhye & Carmichael. No correlation with mite infestation or mange lesions was evident. Ringworm-like lesions were found which were repeatedly negative on culture. A human infection by A. benhamiae was contracted from the hedgehogs.


Effects of tentoxin on enzymic activities in cucumber and cabbage cotyledons. Tentoxin, produced by Alternaria alternata (Fr.) Keissl. causes severe variegated chlorosis in germinating seedlings of certain dicotyledonous species. However, it does not impair radicle and hypocotyl elongation or cotyledon expansion. Effects of the toxin on the activity of selected enzymes from both chloroplasts and cytoplasm were determined. Cucumber (Cucumis sativus L.), which is highly sensitive to tentoxin and cabbage (Brassica oleracea L.), which is resistant, were used as test plants. The activities of chloroplastic, but not cytoplasmic, enzymes were decreased by treatment of cucumber cotyledons with tentoxin. Neither group of enzymes was affected by the toxin in cabbage cotyledons. The decreased enzymic activities are probably related to reported inhibition of photophosphorylation by tentoxin.


The constriction of the trapping rings in Dactylaria brochopaga. The mechanism of ring constriction of a nematophagous fungus has been studied in vitro. The process of ring constriction in vivo normally requires less than one second. However, precise observations of the mechanism are difficult due to this rapidity, as well as the obstruction of the ring by the nematode. A method of initiating ring constriction without the use of an inert mechanical stimulus is described. With this method it is also possible to retard the constriction of the rings so that accurate observations of the entire process can be made. An explanation of the possible physiological mechanism is also presented.


Isolation of Emmonsia crescens Emmons et Jellison 1960 from small mammals in Bulgaria. Authors examined a total of 3849 specimens of mammals included in 36 species from different region of Bulgaria. Adiaspiromycosis was detected microscopically in 18 mammals species. Strains of Emmonsia crescens Emmons et Jellison 1960 was isolated from 6 species--Apodemus flavicollis, Apodemus sylvaticus, Clethrionomys glareolus, Microtus arvalis, Musmusculus and Rattus norvegicus.


The isolation of keratinophilic fungi from soils in Israel. A preliminary report. One hundred and fourteen soil samples collected from various areas of Israel were screened for the presence of keratinophilic fungi. Five species were isolated from the 59 positive samples, viz: C. keratinophilum--22 strains, C. evolceanui--18, C. serratus Eidam--10, M. gypseum--T. terrestre--4. Most of the geophilic organisms were recovered from garden soil, road-side and sandy-soil specimens. The importance of these findings is briefly discussed.


[Free and bound sterol content of sunflower, soy bean and maize oils]. The amounts of free sterols, steryl esters and steryl glycosides in sunflower, soya and maize oils as well as in the phosphatides of the same oils were determined. The refinement byproducts were enriched with sterols. The highest contents of total sterols and steryl glycosides (2,68 and 1,9%, respectively) were established in soya phosphatides followed by those in sunflower oil phosphatides (2,03 and 1,68%, respectively) and maize oil phosphatides (0,81 and 0,54%, respectively).


[Fat-stabilizing properties of phosphatides. 1. Response of selected phosphatides to oxygen]. The authors investigated the formation of hydroperoxides and carbonyl compounds in raw phosphatides from soya-beans and rape-seeds during storage at 50 degrees C. According to the results obtained, the chemical deterioration of the raw phosphatides depends upon their intrinsic contents of prooxidative and antioxidative compounds and upon the consituent fatty acids. Purified preparations are considerably more stable as comparable fatty acid methyl esters; and phosphatides containing nitrogenous bases are less sensitive to atmospheric oxygen than their nitrogen-free analogues.


[Fat-stabilizing properties of phosphatides. 2. Antioxidative properties of selected phosphatides]. The authors study the effects of selected phosphatides on the oxygen uptake of methyl linolate. According to the results obtained, the antioxidative properties of such compounds are to be attributed not to their specific molecular structures, but to accompanying substances such as tocopherols, amino acids or Maillard products.


Uptake and disappearance of 4-methyl-alpha-ethylmetatyramine in relation to its releasing action on 5-hydroxytryptamine in the brain. 4-Methyl-alpha-ethylmetatyramine (H75/12) was given intraperitoneally to mice and rats. At various time intervals the animals were killed and the concentration of H75/12 and 5-hydroxytryptamine (5-HT) in the brain and of H75/12 in the heart and, in some cases, in plasma was determined. H75/12 was rapidly taken up by the heart and then disappeared bi- or multiphasically. A maximum concentration of about 6 mug/g was obtained in the brain 30--60 min after the administration of 25 mg/kg. H75/12 disappeared from the brain with a half-life of 1.0 and 1.5 hrs in the mouse and rat, respectively. In the mouse the relative uptake of H75/12 increased with the dose given, i.e. the dose-uptake curve had an upward bending. Significant release of 5-HT in the brain was obtained after a single injection of 25 and 100 mg/kg in the rat and mouse, respectively. The 5-HT release was prevented by tricyclic, antidepressive agents, particularly by chlorimipramine. However, these agents had no certain effect of the uptake of H75/12 in the brain. Moreover, it was not possible to demonstrate a decreased uptake of H75/12 in the rat brain after a chronic, transverse cerebral hemisection, although the monoamine-containing neurones had degenerated as indicated by a complete disappearance of 5-HT. It is concluded that only a minor part of the H75/12 measured is located in monoaminergic neurones. The uptake of H75/12 in the rat brain appeared to be increased in starving animals, possibly indicating decreased metabolism of the drug.


Demonstration and isolation of phallolysin, a haemolytic toxin from Amanita phalloides. Phallolysin, a high-molecular weight, thermo- and alcohol-labile toxin with haemolytic activity, was demonstrated in Amanita phalloides. Phallolysin was isolated from cold aqueous toadstool extracts by precipitation with 40% ammonium sulphate, ion-exchange chromatography on DEAE cellulose, gel chromatography on Biogel P-30 and electrofocussing in Ampholine. Electrofocussing in a flat pH gradient resulted in the separation of the gelchromatographically homogeneous phallolysin into phallolysin A (I.P. 8.06) and phallolysin B (I.P. 7.49). Phallolysin A exhibited 70% purity with respect to its behaviour on polyacrylamide gel electrophoresis when stained with Coomassie Brilliant Blue. On the average 0.62 mug, at least 0.20 mug of protein was equivalent to 1 haemolytic unit (HU). The i.p. LD50 for mice was found to be 1060 (930--1210) HU/kg.


[Urinary excretion of 17-hydroxycorticosteroids and 17-ketosteroids in women with epileptic seizures during the premenstrual period]. The authors determined the amounts of free and total 17-hydroxycorticosteroids (17-OHCS) and 17-ketosteroids (17-KS) in the urine of 11 women in whom epileptic seizures occurred most frequently on the 2nd and 1st day before menstruation and in 7 women with seizures showing no such correlation with the menstrual cycle. A statistically significant decrease of 17-KS was demonstrated in women with premenstrual seizures. In both groups of women the amounts of free 17-OHCS were near the lower normal range, while the amounts of total 17-OHCS were reduced and the obtained results compared with the accepted normal values showed statistically significant differences (p less than 0.01). The obtained results are, however, insufficient for assuming that these hormones play an important role in the mechanism of seizure release in premenstrual period. The authors think, on the other hand, that the statistically significant fall in 17-KS in women with premenstrual seizures may play some role among other factors in the mechanism of seizure release.


[Urinary excretion of estrogen fractions, alpha and beta pregnanediol and pregnanetriol in women with epileptic seizures during the premenstrual period]. The authors determined the amounts of oestrone, oestradiol, oestriol, alpha and beta pregnanediol, and pregnanetriol in 24-hour urine of 11 women with epileptic seizures occurring two and one day before the onset of menstruation, and in 7 women with seizures not dependent on the menstrual cycle. Determinations of these hormons were done during three successive menstrual cycles on the 2nd and 1st day before the onset of bleeding. In both groups a significant decrease was observed in the urinary levels of oestradiol and oestriol as compared with normal values. On the other hand, the amount of excreted oestrone was only slightly lowered in relation to the amount of this hormone excreted by controls. A significant decrease in the amounts of alpha pregnanediol (the difference being statistically significant at p less than 0.01 level) was observed two days before menstruation. On the other hand, pregnanetriol was decreased only in women in whom the seizures showed no temporal correlation with the stage of the menstrual cycle. The authors suggest that the observed reduction in the metabolites of progesterone in both groups was associated with an increased seizure readiness of the brain on the days preceding menstrual bleeding.


Familial poliodystrophy, mitochondrial myopathy, and lactate acidemia. In two siblings with limb-girdle muscle weakness and episodic headaches and vomiting from early childhood, progressive neurologic degeneration later developed, and both children died. In one child, corticosteroids induced improvement in both cerebral and muscular symptoms that lasted 1 year. This patient had elevated blood, urine, and spinal fluid lactate levels, together with increased cardiac output and oxygen consumption at rest. Several muscle fibers were characterized by a "ragged red" appearance with the trichrome stain. Subsarcolemmal and intermyofibrillar excess of mitochondrial oxidative enzyme reaction product was correlated with abnormal mitochondrial aggregates by electron microscopy. The brain revealed focal areas of cortical degeneration and necrosis with adjacent gliosis or edema. Ferrocalcific deposits were prominent in the globus pallidus. The other sibling had similar changes in the brain at autopsy. This familial multisystem disorder especially involving the brain, skeletal muscle, and heart appears to represent a defect in some mitochondrial oxidative mechanism.


A pharmacologic study of the stiff-man syndrome. Correlation of clinical symptoms with urinary 3-methoxy-4-hydroxy-phenyl glycol excretion. We have investigated hypotheses that link the stiff-man syndrome to an imbalance of neurotransmitter systems. No evidence was found to support the concept of defective synaptic transmission at either cholinergic input to Renshaw inhibitory elements or at glycinergic inhibitory input to motoneurons from spinal interneurons, since neither physostigmine nor glycine altered symptomatology. Urinary excretion of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenyl glycol showed a high correlation with clinical status. This suggests the involvement in the stiff-man syndrome of a central norepinephrine neuronal system that has net excitatory effects upon motoneurons, a system whose activity can be increased slightly by levodopa and decreased markedly by diazepam, with corresponding changes in stiffness.


The syndrome of Gogi (word meaning) aphasia. Selective impairment of kanji processing. In 1943, Imura described an aphasic syndrome shown by Japanese patients and designated it as Gogi ("word-meaning") aphasia. Salient features are selective impairment of processing kanji or Chinese characters and difficulty in finding access to the lexicon in both production and reception, with preservation of processing kana or phonetic signs, and fluent oral repetition. A patient with this syndrome is presented, with emphasis on the nature of his kanji impairment. Cases of Gogi aphasia in the literature are reviewed and contrasted to cases of Broca's aphasia with selective impairment of kana processing. The implications  for a neurolinguistic model of language processing in aphasia are discussed.


"Encephalomyeloneuritis" in the absence of cancer. An elderly man presented with signs and symptoms indicating a rapidly progressive central and peripheral nervous system disease, which led to death within 3 months. The pathologic picture was that of a "paraneoplastic" encephalomyelitis and neuritis, but no cancer could be found. Supratentorial predilection for the limbic structures correlated well with an observed limbic dementia. Arguments favoring a direct toxic or metabolic effect of cancer as a cause for this syndrome was less convincing in view of this report.


Neuromuscular complications of acromegaly. Seventeen consecutive acromegalic patients were evaluated for evidence of neuromuscular dysfunction and followed for 1 year after hypophysectomy. Before treatment, four patients had both a myopathy and the carpal tunnel syndrome, five had myopathy alone, four had carpal tunnel syndrome alone, and four had neither. The myopathy was caracterized by mild, strictly promixal weakness and flabbiness of muscles; electromyography revealed typical myopathic abnormalities, but serum enzymes and muscle biopsy usually were normal. The presence of myopathy or the carpal tunnel syndrrome could not be correlated with the magnitude of growth hormone elevation or any secondary endocrine derangement, but myopathy was associated with a longer duration of acromegaly. Carpal tunnel symptoms usually improved in the first 6 weeks after hypophysectomy, while myopathy improved more slowly and sometimes was detectable 1 year later.


Increased cerebral blood volume in benign intracranial hypertension. In two patients with benign intracranial hypertension, the regional cerebral blood volume was markedly elevated (mean of 85 percent) while regional cerebral blood flow was slightly reduced (mean of 10 percent). Reduction of cerebrospinal fluid pressure by removal of cerebrospinal fluid reduced the mean values of regional cerebral blood volume by 13 percent without significant change in regional cerebral blood flow. The abnormal regional volume and regional flow returned to normal concurrent with the clinical improvement. Vinous engorgement and increased intracranial blood volume appear to play an important part in the pathophysiology of increased intracranial pressure in benign intracranial hypertension. A unified concept of the pathogenesis of benign intracranial hypertension is proposed.


Chronic cerebellar stimulation in the monkey. Electron microscopic and biochemical observations. The effects of chronic electrical stimulation to the surface of cerebellum in the Macaca mulatta monkey were studied with morphologic and biochemical techniques. There was considerable damage and loss of Purkinje cells in all specimens examined, including an area without electrodes, but the greatest changes appeared in tissue beneath the cathode and anode. Despite the damage, normal appearing synapses persisted in the molecular layer of all specimens. Fibrous glial processes were more numerous beneath the cathode. There were abnormalities in gamma-amino butyric acid (GABA) and polyamine concentrations in virtually all specimens, consistent with the morphologic evidence of widespread tissue damage.


"Alpha-like" rhythms in electroencephalograms in coma after cariac arrest. Electroencephalograms (EEGs) of 12 comatose patients showed "alpha-like" rhythms after cardiac arrest. Four patients revealed a stage II sleep pattern and two patients showed signs of reactivity in their EEGs. One patient recovered with minimal impairment of memory, one patient lived for 3 months, and 10 died 3 ot 30 days after cardiac arrest. Examination of the brain demonstrated the usual anoxic lesions in three patients and "respirator brain" in one. In three patients with ventral pontine syndrome, a somewhat similar EEG pattern, but with distinct differences in topography and reactivity, was observed. In order to recognize alpha-like rhythms in comatose patients after cardiac arrest, EEGs should be recorded daily for several days.


Progressive multifocal leukoencephalopathy: a complication of immunosuppressive treatment. Progressive multifocal leukoencephalopathy developed in a patient with rheumatoid arthritis after treatment with an immunosuppressive agent (chlorambucil). We fell that this case lends further support to the concept that an altered immunologic state is important in the appearance of this infection, which is probably viral in origin.


Local alterations of hemostatic-fibrinolytic mechanisms in reforming subdural hematomas. Multiple chemical and coagulation determinations were undertaken on the subdural hematoma fluid from the reformed effusions of two patients. It was found that plasma or blood repeatedly reentered the subdural cavity. Coagulation studies compared the in vitro effects of subdural fluid with those of cerebrospinal fluid, serum, and a buffer control. Despite some chemical differences, the subdural fluids from both patients behaved similarly by (1) accelerating the intrinsic clotting system, (2) producing defective clot formation, and (3) accelerating the fibrinolytic system. It is presumed that these continuous hemostatic-fibrinolytic alterations, acting in the subdural sac, may have important implications in the growth and reformation of subdural hematomas, and a hypothesis of the mechanisms involved is presented.


"Saccadic nystagmus" in cerebellar cortical atrophy. An ocular dyskinesia designated "saccadic nystagmus" was observed in a patient with cerebellar cortical atrophy. Saccadic nystagmus is a sustained ocular dyskinesia present during visual fixation and abolished by eye closure. It is difficult to distinguish visually from either pendular or jerk nystagmus without eye movement recordings. The oscillations are horizontal and rapid and may be influenced by direction of gaze. Caloric nystagmus (eye closed) and optokinetic nystagmus were normal in our patient. Visual fixation abolished caloric nystagmus, which was replaced by saccadic nystagmus.


Parkinsonism: effects of levodopa treatment on concept formation. Concept formation was compared in 71 parkinsonian patients and 35 controls matched for age and WAIS vebal IQ. It was found that the patients formed significantly fewer concepts, as measured by the Wisconsin Card Sorting Test (WCST). The patients had difficulties in shifting sets and were unable to attend to the completion of a concept. Levodopa-treated patients were able to produce more correct responses, but were still unable to maintain the correct responses to produce more correct concepts than non-levodopa-treated patients. The behavior of the parkinsonian patients on the WCST is similar to that of patients who have undergone frontal lobectomy. In addition, the results indicate that levodopa therapy may improve "vigilance", without increasing the patient's overall cognitive ability.


Nervous system neoplasms and primary malignancies of other sites. The unique association between meningiomas and breast cancer. To determine whether nervous system neoplasms are associated with primary malignancies elsewhere, we studied the frequency of multiple primary tumous in patients in whom at least one of the primary tumors was within the nervous system. The patients were Conneticut residents with tumors diagnosed between 1935 and 1964. Of 135 patients, 130 had two primary tumors, four had three primary tumors, and one had four primary tumors. Only with multiple primary tumors involving the brain and breast did the number of observed cases significantly exceed the number of expected cases; eight patients who had a meningioma associated with a breast cancer accounted for this excess. Patients with breast cancer presenting with signs or symptoms of an intracranial neoplasm should be carefully evaluated, for the intracranial lesion may be a potentially curable meningioma.


Schwann cells and regenerated peripheral myelin in multiple sclerosis: an ultrastructural study. Tissue of a multiple sclerosis plaque in the brachium conjunctivum of the pons known to contain peripheral myelin by light microscopic studies were removed from the paraffin block and processed for electron microscopic studies. The cells related to the peripheral myelin possessed the ultrastructural characteristics of Schwann cells, with basement membranes and associated collagen fibers. No continuity was seen with the peripheral within the central nervous tissues by selective maturation of multipotential primitive reticular cells, a phenomenon consistent with the view that Schwann cells are mesenchymal in character.


Stroke in a 15-year-old girl secondary to terminal carotid dissection. A 15-year-old girl died 14 days after hemiplegia suddenly developed. On arteriography, intimal separation of the middle cerebral arteries showed as a long attenuated column of dye--the "string" sign. Pathologic examination showed intimal separation starting at the distal bifurcation of the right internal carotid artery and extending into the middle and anterior cerebral arteries. The arteriographic string sign as evidence of dissection may aid diagnosis of this cause of childhood hemiplegia.


Cicutoxin poisoning (water hemlock).

Cicutoxin poisoning (water hemlock). A 54-year-old man had a severe case of cicutoxin poisoning following the ingestion of water hemlock (Cicuta maculate). The administration of thiopentone sodium by continuous intravenous infusion proved the optimum method of controlling the gross and irregular body movements and of managing the metabolic acidosis and the cholinergic crisis characteristic of this type of poisoning. This report includes a detailed neurologic and biochemical assessment of the condition.


Silent period measurement in the differentiation of central demyelination and axonal degeneration. The investigators recorded the silent period from the abductor pollicis brevis and gastrocnemius soleus muscles in normal subjects and in patients with multiple sclerosis and motor neuron disease. In the multiple sclerosis group the termination of the silent period recorded from the leg was significantly delayed, and the arm and leg silent period differences were increased threefold as compared with normal subjects. Silent period measurements in the motor neuron disease group were normal. The silent period probably participates in a "long loop reflex", and its delay in multiple sclerosis could therefore be due to a block in central conduction resulting from demyelination. This would not occur in motor neuron disease, in which axonal degeneration is the primary lesion. The techniques used are relatively simple and are a valuable means of differentiating central demyelination from axonal degeneration in man.


Cerebral responses to electrical tooth pulp stimulation in man. An objective correlate of acute experimental pain. The pulp of individual teeth of 17 normal adult volunteers was electrically stimulated via pairs of electrodes implanted into dentine. Computer-summated responses recorded from the surface of the head were composed of two concurrent sequences of events, one of which was seen maximally over midline areas and the other over the lower portions of the postcentral regions. Appropriate tests demonstrated that these wave forms represented cerebral tooth pulp-evoked potentials. Because tooth pulp-evoked potentials represent objective, quantifiable, nonverbal concomitants of central events associated with the perception of noxious stimuli, they may prove helpful in investigating acute experimental pain in man.


Arterial stationary wave phenomenon in Tolosa-Hunt syndrome. In a patient with Tolosa-Hunt syndrome, serial cerebral angiograms showed arterial stationary wave phenomenon and persistent deformity of the carotid siphon. Stationary arterial waves are noted in only 0.3 percent of cerebral angiograms and have not been reported in Tolosa-Hunt syndrome. In accordance with theories proposed by Theander and New, we felt that the intense stenosis of the carotid siphon produced by the periarteritis in our patient caused relative obstruction and high resistance, giving rise to resonance of arterial pressure waves and creation of the arterial stationary waves.


Olivary hypertrophy without palatal myoclonus associated with a metastatic lesion to the pontine tegmentum. A 46-year-old man had metastasis to the central tegmental tract of the pons with ipsilateral olivary hypertrophy. Although the phenomenon of palatal myochlonus has been repeatedly correlated with the finding of olivary hypertrophy, no palatal myoclonus was noted on repeated examinations. The clinical pathologic correlates and literature of similar cases are reviewed.


Vascular malformations of the pons in children. Three children reported here and an additional five patients from the literature with angiomas of the pons had a total of 19 clinical episodes of neurologic "illness." Thirteen of these episodes were ictal and six were progressive in onset. The progressive onset was identical with that occurring in patients with tumors of the brain stem. Laboratory and radiographic studies were not uniformly helpful in differentiating this disorder from the more common brain-stem glioma. The survival of these patients varies from several hours to 15 years.


Frequency of nerve fiber degeneration of peripheral motor and sensory neurons in amyotrophic lateral sclerosis. Morphometry of deep and superficial peroneal nerves. Among 10 patients with amyotrophic lateral sclerosis who had combined biopsy of muscle and cutaneous nerves, two had a history of paresthesia that suggested involvement of peripheral afferent neurons. Of four patients without paresthesia, two had unequivocal abnormalities of touch-pressure sensation of the toe. On morphometric evaluations of lateral fascicles of deep peroneal nerve, one nerve had an abnormally low myelinated fiber density and seven of 10 had abnormally high frequencies of teased-fiber abnormalities. Teased fibers in which myelin was degenerating into linear rows of myelin ovoids and balls occurred in 10.5 percent of fibers in amyotrophic lateral sclerosis nerves as compared with 1.7 percent in control nerves (0.01 less than p less than 0.025). Estimates of density of myelinated fibers were less sensitive than estimates of the frequency of various changes in teased fibers for detecting abnormality.


Response of generalized penicillin epilepsy in the cat to ethosuximide and diphenylhydantoin. The effects of ethosuximide and diphenylhydantoin sodium on feline generalized penicillin epilepsy, a model of human generalized corticoreticular (centreccephalic) epilepsy, were significantly reduced following administration of ethosuximide with plasma levels of 60 mug per milliliter, and there was a linear correlation between the plasma level and antiephilepileptic effect (p less than 0.01). Diphenylhydantoin produced a lesser reduction in epileptic activity, and there was no correlation between the plasma level and effect. Four cats that received both drugs successively responded well to ethosuximide, while only two responded to diphenylhdantoin. The good response to ethosuximide is in accord with clinical experience in human generalized corticoreticular epilepsy.


Serum linoleic acid in multiple sclerosis. Total serum fatty acids were analyzed in 30 patients with multiple sclerosis and in 33 controls. No significant decrease in linoleic acid was found in the patients with multiple sclerosis. A disturbance in linoleic acid metabolism is not inevitably associated with this disease.


Myotonic dystrophy: opportunities for prenatal prediction. Prenatal prediction of the inheritance of myotonic dystrophy in a family with affected individuals feasible in special cases when analysis of linkage to the secretor gene (determing ABH substances) can be carried out. We report a large kindred having multiple members affected with variable degrees of severity of myotonic dystrophy and having several matings for which linkage analysis is feasible. Even though this approach is not applicable for most families and although the process of genetic recombination complicates the analysis, in individual cases the use of linkage in prenatal or postnatal prediction of myotonic dystrophy may be very helpful for early diagnosis, more precise genetic counseling, and family planning.


Acute overdose with levodopa. Clinical and biochemical consequences. A 61-year-old parkinsonian patient ingested up to 100 gm of levodopa during a period of 12 hours. Signs of parkinsonism were completely alleviated. Adverse effects included initial hypertension followed rapidly by hypotension of a few hours' duration, prolonged symptomatic postural hypotension, sinus tachycardia, mental confusion, insomnia, and anorexia. The effects of the overdose gradually subsided over 1 week. Analyses of serum and urine for dopa and its metabolites confirmed the overdose, which biochemically resulted in apparent saturation of two enzymatic pathways that inactivate dopamine: conjugation with sulfuric acid and O-methylation.


Value of the Gravlee Jet Washer in the diagnosis of endometrial cancer. in 220 women with gynecologic symptoms, endometrial washings were obtained with the Gravlee Jet Washer-in 135 outpatients before office curettage without anesthesia or analgesia; in 85 hospitalized patients before fractional dilatation and curettage under anesthesia. The method was simple, inexpensive, virtually painless, and free of complications. Endometrial adenocarcinoma was present in 12 patients; the jet washing samples were diagnostic in 6 of these. Reported variations in diagnostic accuracy for endometrial carcinoma and precancerous phases raise doubts as to the value of this technic in asymptomatic patients. It is valid for screening symptomatic patients provided results other than normal or positive are further evaluated. Laboratory handling and interpretation must be improved if jet washing is to succeed in mass screening programs.


Thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura. The patient reported here is the twentieth reported case of thrombotic thrombocytopenia purpura (TTP) occurring in pregnancy, the third survivor, and the first to be delivered by cesarean section. Diagnosis of TTP is usually made on the basis of the pentad of anemia, thrombocytopenia, renal disease, neurologic abnormalities, and fever. A peripheral smear showing microangiopathic hemolysis can be confirmatory and may even be regarded as a definitive test in questionable cases of thrombocytopenia. Although splenectomy, steroids, heparin, and early delivery have been recommended, splenectomy is the only treatment showing a statistically significant improvement in survival rate; 60% of infants born at or beyond 33 weeks' gestation have survived.


Translocation of the Dalkon Shield into the broad ligament. Perforation of the uterus is a serious complication in users of intrauterine devices for contraception. The incidence varies with the type of device. The perforation can occur in different parts of the uterine wall. Perforation into the broad ligament is rare; only 4 cases have been described. Two additional cases, both occurring with the Dalkon Shield, are reported here.


Tunable lasers in ophthalmology.

Tunable lasers in ophthalmology. The present status of laser application in clinical ophthalmology is breifly reviewed. The potentials of tunable dye lasers as retinal photocoagulators are discussed. Selective irradiation of ocular tissues over the full visible spectrum and the simplicity and reliability of recently developed waveguide lasers are the most attractive features of these lasers. Waveguide dye lasers have permitted to set up very compact and simple retinal photocoagulators, with improved output intensity stability and nearfield distribution uniformity. Preliminary results obtained with pulsed Rhodamine 6G laser show that good retinal photocoagulations are obtained at very low output energies.


Evaluation of two kinds of smallpox vaccine: CVI-78 and calf lymph vaccine. II. Clinical and serologic observations of response to revaccination with calf lymph vaccine. Revaccination with standard calf lymph vaccine was performed on 26 children who had received a primary vaccination with an attenuated smallpox vaccine, CVI-78, and 22 children who had received primary vaccination with standard calf lymph. Revaccination resulted in a vesicular reaction in 96 percent of those who had been vaccinated previously with CVI-78 and 73 percent of those vaccinated previously with standard calf lymph. All children had a positive hemagglutination-inhibition (HI) antibody titer either after primary vaccination or revaccination. Only 65 percent of those initially vaccinated with CVI-78 vaccine had positive neutralizing antibodies after revaccination. All children who received primary vaccination with standard calf lymph had postrevaccination neutralizing antibodies. The children who had neither a dermal nor a serologic response after primary vaccination responded as primary vaccinees on challenge with standard calf lymph.


Inhibition of RNA synthesis by acetyl salicylate and actinomycin D during early development in the mouse. Experiments were designed to ascertain and compare the effects of acetyl salicylate and actinomycin D on RNA synthesis in mouse oocytes in vitro and in vivo. After exposure to the drugs the effects on RNA synthesis were measured by incorporation of [3H]uridine and autoradiography. The results indicate that acetyl salicylate inhibits RNA synthesis in the treated oocytes as does actinomycin D. The only difference in the effects of these two drugs is that salicylate inhibits RNA synthesis to a much lesser degree than does actinomycin D. Effects from a short exposure to salicylate may be reversible; the same effects with actinomycin D cannot be reversed. In utero exposure of the female fetus may lead to partial or total sterility (depending on the dose and time of exposure) of that fetus and/or abnormal development of the progeny from those mice (F2). These results suggest that RNA synthesis in early oogenesis is a vital part of later development of the oocytes in adult mouse ovary. Inhibition of RNA may be one of the causes of malformations and sterility.


Kinetics of inactivation and recovery of the slow inward current in the mammalian ventricular myocardium. In order to study the kinetics of inactivation and recovery of the slow inward current in the mammalian ventricular myocardium voltage clamp experiments using the double sucrose gap technique were performed on isolated trabeculae and papillary muscles of cats. The separation of the slow inward current from the fast Na current was achieved by use of the conditioning clamp procedure. 1. The decay of the Ca current reflects the inactivation which develops due to depolarization. The rate of inactivation depends upon the membrane potential. Excess Ca (8.8 mM) accelerates the inactivation speed indicating that Ca ions not only act as charge carrier of the slow inward current but might influence in addition the kinetics of the slow membrane channel. In the presence of a lowered temperature a deceleration of inactivation (Q10 2.3) occurs. 2 If the membrane is repolarized a recovery process takes place restoring the availability of the slow membrane channel. As the inactivation the recovery rate depends upon the membrane potential. Excess Ca causes an acceleration whereas a decrease in temperature diminishes the recovery speed (Q10 2.3). Consequently, the Ca supply to the myocardial cell can be modified not only by changes of the transmembrane Ca concentration gradient or by an alteration of the Ca conductance of the slow channel but also by changes in the degree of recovery after a preceding Ca current. 3. Compared with the inactivation the recovery proceeds very slowly. Assuming that this slow recovery represents an inherent kinetic feature of the slow channel the kinetics of inactivation and removal of inactivation are not describable by a single inactivation variable (called as f by Reuter, 1973) which is of the Hodgkin-Huxley type. If a second inactivation variable (called as l) would be introduced additionally a formulation of the inactivation-recovery process of the slow membrane channel on the basis of the Hodgkin-Huxley model becomes feasible.


[Influence of heart work and substrate uptake on the regulation of pyruvate dehydrogenase activity in isolated guinea pig hearts (author's transl)]. In isolated guinea pig hearts performing a defined stroke work, the influence of heart work and substrate uptake on the interconversion of pyruvate dehydrogenase (PDH) was studied. When hearts from fasted animals are perfused with a salt solution containing 10mM glucose, an increase in cardiac output and aortic pressure effects an increase in active PDH from 50 to 74% of total PDH activity and a decrease in tissue content of energy-rich phosphates. Pyruvate turnover calculated from oxygen consumption corresponds with PDH activity. Under these experimental conditions, PDH activity might either represent the rate limiting step of oxidative glucose breakdown, or it might be adjusted to a flux rate controlled by other factors. In fed animals, PDH activity exceeds the pyruvate turnover. However, an increase of heart work raises the active PDH from 76 to 95%. Addition of 10 mM acetate to the perfusion medium decreases PDH activity and glucose uptake. In fed animals, an increase of heart work raises the active PDH from 43 to 59% only, whereas in fasted animals this effect is abolished. The effect of changes in heart work on PDH interconversion might be explained by changes in energy-rich phosphate concentrations. However, substrate uptake and nutritional state may interfere or even abolish this effect.


[Studies on the degree of hypoxic and pharmacological coronary dilation (author's transl)]. On 11 isolated dog hearts, perfused with arterial blood of a donor dog, the degree of hypoxic dilatation and the maximum coronary blood flow achieved by adenosine were compared. The maximum coronary blood flow under adenosine infusion amounted to 455ml/minx100g, that means an increase of about 600% of the normal flow. If coronary venous pO2 was below 5mm Hg coronary blood flow was increased to 420ml/minx100g, which is 93% of the pharmacologically achieved maximum increase of the coronary blood flow. The difference between the maximum hypoxic and the maximum pharmacological dilatation is due to the method; it is caused by an increase of the extravascular component of coronary resistance under the influence of catecholamines in the case of hypoxic dilatation. It is pointed out that in order to achieve a maximum hypoxic dilatation oxygen pressure has to be below the critical value. It can be concluded that the intravascular component of coronary resistance is as low under hypoxic as under pharmacological dilatation.


[Method for the continuous measurement of the phase relation between heart beat and respiration (author's transl)]. A simple method for the continuous analysis of the phase relation between heart beat and respiration is described. By means of an analog computer the timing of the R wave of the ECG within the respiratory cycle is graphically displayed. In contrast to other investigations, the onset of the inspiration is used as starting signal. The results obtained with the analog computer were completed by a digital computer program, which allowed in addition to calculate histograms of the events. In order to evaluate our method we used an analog model of two coupled oscillators. Responses obtained at different coupling characteristics were compared with measurements in four subjects. The results indicate a mutual interaction between heart action and respiration as cause of the coupling of these two systems.


Responses of neurons of lizard's, Lacerta viridis, vestibular nuclei to electrical stimulation of the ipsi- and contralateral VIIIth nerves. Field and intracellular potentials were recorded in the vestibular nuclei of the lizard following stimulation of the ipsi- and contralateral vestibular nerves. The field potentials induced by ipsilateral VIIIth nerve stimulation consisted of an early negative or positive-negative wave (presynaptic component) followed by a slow negativity (transsynaptic component). The spatial distribution of the field potential complex closely paralleled the extension of the vestibular nuclei. Mono- and polysynaptic EPSPs were recorded from vestibular neurons after ipsilateral VIIIth nerve stimulation. In some neurons early depolarizations preceded the EPSPs. These potentials may be elicited by electrical transmission. Often spikelike partial responses were superimposed on the EPSPs. It is assumed that these potentials represent dendritic spikes. Contralateral VIIIth nerve stimulation generated disynaptic and polysynaptic IPSPs in some neurons and EPSPs in others. The possible role of commissural inhibition in phylogeny is discussed. In a group of vestibular neurons stimulation of the ipsilateral VIIIth nerve evoked full action potentials with latencies ranging from 0.25-1.1msec. These potentials are caused by antidromic activation of neurons which send their axons to the labyrinth.


Transcellular ion route in rabbit gallbladder. Electric properties of the epithelial cells. The intracellular potential in gallbladder epithelial cellsis about minus 59 mV with respects to both mucosal and serosal media. It is a diffusion potential mainly due to K+;Na+ conductance seems to be very low. Entrance of Cl- into cellsappears to be coupled with Na+ a neutral carrier and exit towards blood side seems to be due to a NaCl neutral pump.


Osmotic thirst suppression during 2,4-dinitrophenol (DNP) hyperthermiain the dog. The effect of generalized body hyperthermia elicited by intravenous infusion of 2,4-dinitrophenol (DNP) on the reactivity of the thirst mechanism to osmotic stimuli was examined in conscious dogs. DNP increased deep body temperature by 1.53 +/- 0.18 degrees C in 18 out of 20 experiments. Impairement of thrist sensation was observed at the same time. The animals did not drink enough water to compensat for its total and evaporative loss. In cosequence water deficit developed, reaching maximum value of 2.7 plus 0.6% of body weight. The deficit was accompanied by an increase in plasma osmolarity, plasma protein concentration and hematocrit. A significant correlation between evaporative water loss and water deficit as well as between increase in deep body temperature and water deficit was found. The cellular dehydration developed in the course of DNP hyperthermia was higher by 3.3 +/- 0.6% of intracellular water (P less than 0.001) than that which was necessary to elicit drinking under conditions of normothermia. It is concluded that DNP hyperthermia changes the osmotic reactivity of the thirst mechanism so that the body fluids osmolarity is regulated at a higher level. This finding is discussed with regard to voluntary dehydration.


Dynamic characteristics of heart-rate responses to sine-function work-load patterns in man. Dynamic characteristics of heart rate in response to sinusoidal variations of work load were analysed in 8 male and 3 female untrained students exercising in a sitting position on a bicycle ergometer. The mean work load was 90 watt in men and 60 watt in women, the amplitudes being 50 and 30 watt respectively. Nine different frequencies were used, the periods varying from 0.5 to 15.0 min. By means of harmonic analysis, the fundamental components in the response of the heart rate have been shown to prevail over the 2nd and 3rd harmonics, indicating a mainly linear behaviour of the control system in the work-load range studied. A comparison of the frequency response of untrained males and females observed in this study and of trained sportsmen, investigated by wigertz (1970), reveals differences between the groups. The individual and ensemble mean frequency responses have been described by several transfer functions, the best fit having been obtained with functions containing two time constants including one with a highly damped oscillating element. The dominating dynamic parameter is a time constant of about 20 to 30 sec. This time constant tends to be shorter and its portion of the frequency response diminishes in order from the untrained females and males to the trained sportsmen. The individual time constant decreases as the PWC170 increases, and is therefore a suitable criterion for estimating the physical performance of individuals under dynamic conditions.


Influence of electrical stimulation of the posterior hypothalamus on musculocutaneous and renal circulation in anesthetized dogs. Hypertension and tachycardia were consistently induced by electrical stimulation of the median posterior hypothalamus in dogs under chloralose anesthesia, curarized and artificially ventilated. When renal and femoral vascular beds were perfused at a constant blood flow, the renal perfusion pressure markedly increased, whereas only minor variations of the femoral perfusion pressure occurred. When the renal and femoral vessels were perfused by the heart at the prevailing blood pressure, peri-arterial electromagnetic flow measurements revealed that renal flow decreased and that femoral flow increased during hypothalamic hypertension, both before and after vagotomy. In the same animals, no significant changes of renal or femoral flow occurred during reflexogenic hypertension induced by carotid occlusion. These marked hemodynamic differences between the reflexogenic and the hypothalamic type of hypertension were consistently and repeatedly observed. The indications that baroreflex counter-regulation and ganglionic inhibition due to elevated catecholaminemia contribute to the relative lack of femoral vasoconstriction during hypothalamic hypertension, are discussed.


Free thiamine as the likely precursor of endocellular thiamine phosphates in everted rings of rat jejunum. Labeled and unlabeled (endogenous) free and phosphorylated thiamine were measured in isolated everted rings of rat jejunum in vitro during short incubation periods (1-10min). Shortly after the addition of thiamine-14C to the incubation medium, the intracellular specific activity of the free form was higher than the specific activity of the phosphorylated fraction. In the course of time this difference diminished and finally the two specific activities became equal. The conclusion was reached that free thiamine is the likely precursor of intracellular phosphorylated thiamine. Moreover evidence is presented which indicates that free thiamine entered actively into intestinal epithelial cells. Since free thiamine was modified into phosphorylated form inside the cells, its movement against the endocellular concentration gradient was noticeably favoured.


The oxygen pressure histogram in the left ventricular myocardium of the dog. Myocardial PO2 in its relation to arterial and coronary venous PO2 was measured in anesthetized open-chest dogs by means of polarographic methods. At normal arterial O2 supply, there exists a broad PO2 spectrum in the myocardium, ranging from about 0 Torr to arterial values (mean 19.3 Torr, median 14 Torr). 60% of the values are below the mean coronary venous PO2 of 18.8 Torr, the maximum is in the class of 0 to 5 Torr. Neither the shape of the histogram nor the mean coronary venous PO2 are significantly changed under moderate arterial hypoxemia (mean arterial PO2 63.7 Torr). Also increases in arterial PO2 to more than 300 Torr cause no distinct change in coronary venous PO2, whereas myocardial PO2 shows heterogeneous reactions. Myocardial as well as coronary venous PO2 seem to be well regulated over a wide range of arterial PO2.


Urea handling by the renal countercurrent system: insights from computer simulation. The renal handling of urea has been investigated with the aid of a computer model of the countercurrent system in which active electrolyte reabsorption occurs along the entire ascending limb of Henle's loop. In this model, summarized in Fig.9, the buildup of a corticopapillary gradient for urea is optimized if there is net addition of urea to loops of Henle only in the outer medulla. This added urea remains within the tubular system until it is reabsorbed from collecting ducts in the inner medulla. Thus, a net transfer of urea from outer to inner medulla is accomplished (via distal tubule and cortical collecting duct). There is no net addition of urea to loops of Henle within the inner medulla; in this region, the loops act simply as countercurrent exchangers for urea. Computer simulation of systematic variation in the urea permeabilities of each nephron segment shows that interference with any element of the above schema results in impairment of the medullary accumulation of urea relative to plasma. Simulation of varying rates of urinary urea excretion demonstrates that this model can account for the ability of the kidney to excrete substantial amounts of urea without an accompanying osmotic loss of water. The major insight gained from this study is that net addition of urea to loops of Henle in the outer medulla greatly enhances the medullary accumulation of urea, whereas, net addition of urea to loops within the inner medulla tends to defeat such accumulation and hence the urinary concentrating process. This general principle applies also to an alternate model of the countercurrent system, in which electrolyte reabsorption from thin ascending limbs of Henle is passive.


Salt appetite during the early phase of renal hypertension in rats. In male Sprague-Dawley rats the left renal artery was constricted by a 0.2mm silver clip while the contralateral kidney was left untouched. 10 days after clipping the animals were offered, in addition to water, 0.9% saline as drinking fluid for 6 days. Hypertensive animals drank twice as much saline as did control rats throughout the period of observation. In the hypertensive animals, 24-hrs saline intake during the first day of the self-selection study was quantitatively related to the actual height of blood pressure and to the preceding blood pressure increase. After 6 days on the self-selection regimen, plasma angiotensin II concentrations in the hypertensive rats were elevated by 50% when compared with control rats. On the basis of these and previously reported findings (i.e. an increased activity of the renin-angiotensin-aldosterone system and sodium retention) it is suggested: a) despite sodium retention salt appetite is enhanced, indicating a disordered regulation of sodium balance during the early phase of renal hypertension in rats; b) elevated plasma concentrations of angiotensin II and aldosterone could have enhanced salt appetite; c) despite greater salt intake than in control rats the activity of the renin-angiotensin system remains elevated in renal hypertensive rats, thereby possibly inducing a sustained high saline intake.


Frequency dynamics of arterial autoregulation. In anesthetized dogs the low-frequency input impedances (0.001 to 0.1 Hz) of different arterial beds were measured. The following arteries were perfused with blood by a servocontrolled pump in different experiments: Femoral, renal, superior mesenteric, and circumflex branch of the left coronary artery. Step and sinusoidal flow changes were used as input patterns. Furthermore, in the femoral artery the high-frequency input impedance was calculated from pulsatile pressure and flow. The pressure reactions to flow changes were interpreted by assuming a lead-lag autoregulatory control system consisting of two opposing components. The time constants of the two components were found to have characteristic values in different arterial beds and may vary depending on the condition of the experiment. The magnitude of the response usually depends on the mean perfusion pressure, indicating a nonlinear behaviour of the system. Furthermore in the renal artery a characteristic delayed pressure increase was observed after short flow impulses. It is interesting to compare the general pattern of the pressure reaction to the input flow with the force response to stretch which, according to the literature, can be observed in certain striated muscle preparations. The mechanisms underlying the autoregulatory reactions described in this study appear to be, at least in part, a general feature of contractile tissues.


Bulbo-spinal neurons activated by baroreceptor afferents and their possible role in inhibition of preganglionic sympathetic neurons. In paralyzed cats under chloralose-urethane anaesthesia the medulla oblongata was searched with dye-filled microelectrodes for neurons responding to electrical stimulation of the carotid sinus nerve (CSN) and distension of the isolated carotid sinus (CS). 89 cells localized in the solitary tract nucleus and in the reticular formation ventrally and ventrolaterally to the nucleus exhibited mainly an excitatory input from the CSN. 16 could be also antidromically excited from the cervical spinal cord at C4 level. 11 of these were shown to be excited by a pressure rise in the CS. The latencies of the antidromically driven units ranged from 1.2-2.8 msec and the calculated conduction velocity of the descending fibres was 29 plus or minus 5.2 m/sec. The possibility of involvement of these bulbo-spinal neurons in the inhibition of the preganglionic sympathetic neurons at the spinal cord level is discussed.


Simultaneous perfusion of both coronary arteries and drainage of the coronary sinus in the dog heart in situ. A technique is described for perfusion of the entire coronary arterial system of the dog heart in situ and for drainage of the coronary sinus blood. Both coronary arteries are cannulated without ligation of major ventricular branches and disconnected from the aorta. The cannulas are connected to an extracorporeal system allowing perfusion under controlled pressure, without ill effects to either the heart or the blood. The arterial perfusion system is fed from the femoral arteries of the dog. The coronary sinus is cannulated for draining the blood to a venous reservoir against a controlled pressure. From the reservoir the blood is pumped into a femoral vein. Thus a preparation is obtained in which the interdependency of coronary circulation and performance of the heart has been discontinued. Under careful monitoring of pressures and flows, and of blood temperature, blood gases and plasma electrolytes, the preparation has been kept in excellent condition for up to 7 hrs.


A mathematical model of the ventilatory control system to carbon dioxide with special reference to athletes and nonathletes. The ventilatory response curve (VRC) as a function of alveolar and arterial pCO2 was recorded in 6 high-performance athletes and 6 nonathletes. The best fit to the data points could be found for an equation of the form (see article) showing that the results are strongly related to a Gaussian probability density function (PDF). After normalizing the equation to a form (see article) (M = mean value of PDF), sigma, A and M could be determined for both groups. Sigma and A are smaller in the athletic group, whereas M did not show any systematic difference. Regarding the respiratory center consisting of functional "elements" responding indirectly to variable pCO2 it can be concluded that the frequency distribution of the different active elements is greater and spread over a wider pCO2 range in the nonathletes with the same mean value in both groups. Using Loeschcke's model (1960), the open loop gain factor for different V CO2 as a function of p(A)CO2 was computed; the gain factor showed a maximum in the physiological range of pCO2.


Effect of azide on the ERG of the isolated mammalian retina. Azide, which is known to affect the pigment epithelium strongly may be assumed to cause damage to the receptors, which are functionally connected to the pigment epithelium. To check this hypothesis the effect of azide on the ERG was investigated. An isolated retina preparation was used as in this preparation the P III component, which contains considerable receptor contribution, can be isolated. In 2 series of experiments the effects of azide on the P III and the complete ERG were investigated. Depending on the concentration azide was shown to abolish the b-wave, to cause delay and amplitude diminution of the P III and enhance a positive component in the off-effect. A number of plausible sites of origin of these azide effects on the ERG changes are discussed.


The transport of D-glucose, L-glucose and D-mannose across the isolated guinea pig placenta. Studies were carried out on the transport of 3H-D-glucose, 14C-L-glucose and 3H-D-mannose across the isolated artificially perfused guinea pig placenta and the inhibition of these transports by phloretin was investigated. 1. In 10 out of 13 placentas the transfer of D-glucose exceeds that of L-glucose. 2. In 10 out of 13 placentas the transfer of D-mannose exceeds that of L-glucose. 3. Phloretin (1 times 10 minus 3 M/1) decreases the transport of D-glucose and of D-mannose, it does not decrease the transport of L-glucose. The inhibition is not complete. The characterization of the washing-out curves permits the assumption that some placentas (6 out of 21) cannot discriminate between D- and L-hexoses, because a non specific transfer (simple diffusion) covers the specific one.


Renal phosphate transport: inhomogeneity of local proximal transport rates and sodium dependence. The standing droplet method has been used in combination with the peritibular perfusion of blood capillaries to determine the build up of transtubular concentration differences of phosphate (Piota) in the renal proximal convoluted tubule of parathyroidectomized rats. Electron probe analysis was used to estimate Piota. At zero time both the intraluminal and the contraluminal Piota concentration was 2 mM. The time dependent decrease of the intraluminal Piota concentration was approximately 4 times faster in the early than in the late proximal convoluted tubule. After 45 sec an intraluminal steady state concentration of 0.20 mM Piota was achieved in the early part. In the late part the intraluminal Piota concentration approached a steady statevalue of 0.54 mM at 123 sec. When sodium free solutions were used the intaluminal Piota concentration increased to 2.22 mM in the earlier and to 2.76 mM in the late part. The data indicate that in the proximal convoluted tubule 1. the rate of phosphate reabsorption is greater in the early part than in the later part, and 2. phospate reabsorption might occur as co-transport with Na+ ions.