[The ultrastructure of papillae filiformes of human tongue (author's transl)].

The fine structural morphology of the filiform papillae of the human tongue is investigated by transmission and scanning electron microscopy. Separation of the epithelium from the connective tissue by treatment with trypsin allows the demonstration of the three-dimensional structure of the primary and secondary connective tissue papillae and of the papillary epithelium. The distal surface of each primary connective tissue papilla is studded with secondary connective tissue papillae. Their lamellated surface structure corresponds with a complex system of cytoplasmic processes of the basal epithelial cells. The complicated surface architecture of the epithelial-connective tissue junction may suggest a close structural and functional relationship between the two types of tissues. There are two distinct cell populations forming the epithelial papilla, which differ in ultrastructural morphology from the basal cell layer to the surface of the epithelium. A dual pattern of keratinization, phylogenetically analogous to the hard and soft keratinization in rodent tongues, is found also in filiform papillai of the human tongue. The final product of epithelial differentiation is a type of keratin different from that in epidermal keratinocytes and in other regions of the oral cavity. The variability in size, shape and association with other organelles suggests the heterogenous nature of lingual keratohyaline granules. The predominance of Odland bodies of lamellated or of spoke type varies with the degree of keratinization of different regions of the papillary epithelium.


Vasodilating antihypertensive drug-induced aldosterone release--a study of endogenous angiotensin-mediated aldosterone release in the rat.

The vasodilatory drugs, minoxidil and hydralazine, induce renin release in the rat, man and the dog. Previous reports suggest that the rat adrenal cortex was insensitive to angiotensin stimulation. As a result these studies were designed to obtain evidence for or against the hypothesis that the control of aldosterone release in the rat is unique among mammalian species. Minoxidil and hydralazine induced a time-related increase in both serum renin activity and serum aldosterone. Minoxidil caused a dose-related, proportional increase in serum renin and aldosterone. This response was blocked by prior bilateral nephrectomy but was not affected by hypophysectomy. A competitive angiotensin antagonist, saralasin (1-Sar-8-Ala angiotensin II), impaired minoxidil-induced aldosterone release in a dose-related manner while potentiating minoxidil-induced renin release. Pretreatment with propranolol, a beta adrenergic blocking drug, impaired minoxidil-induced renin and aldosterone release. Only small changes in serum corticosterone occurred after minoxidil or hydralazine administration. These results indicate that minoxidil-induced aldosterone release was mediated by the endogenous angiotensin II formed from renin release. They also support the unanesthetized rat as an appropriate animal model for study of the renin-angiotensin-aldosterone axis and its modification by drugs.


Selective retrieving by maternal and nonmaternal female rats.

An earler study reported that nonpregnant females do not selectively retrieve a pup over a small plastic toy, while lactating mothers retrieve the pup more often than the toy. The present study was undertaken to see whether nonpregnant females made maternal by exposure to pups would act more like nonmaternal females than lactating mothers. The behavior toward a pup and a toy was studied in 1 group of nonmaternal virgins, 2 groups of maternal virgins, and 1 group of lactating mothers, during 7 daily 5-min. tests. Measures of the frequency and duration of retrieving-related behavior and analysis of behavioral sequences in relation to the pup and toy showed that pup-induced maternal virgins more closely resemble the lactating mothers than nonmaternal virgins.


The relationship of internality-externality, self-acceptance, and self-ideal discrepancies.

Internals (n=35) and externals (n=38) responded to Rotter's (12) I-E scale under two sets of instructions: standard (as the kind of persons they really were) and ideal-self instructions (as if they were the types of persons they would like to be) and the self-acceptance questionnaire (4). Results indicated (a) on both instruments the discrepancy between real and ideal-self was significantly larger in externals: (b) the external ideal-self includes an internal locus of control; (c) a significant discriminatory factor between internals and externals is their perceived control over their own destiny and not social institutions. The results were discussed in terms of the relationship of externality to maladjustment, neuroticism, and possible causes for this relationship.


Effect of training on the use of weight-bearing orthoses.

Weight-bearing orthoses have been disigned with the primary goal of reducing or eliminating weight bearing in skeletal structures.  In evaluating various designs and adjustments of these orthoses, we found that the training of the subject in the use of his orthosis was one of the most significant factors in controlling weight bearing.  Subjects fitted with instrumented ischial weight-bearing and patellar-tendon-bearing orthoses walked over a force plate which measured forces imparted to the floor.  The force data from the orthoses and force plate were computer-processed with single frame, multiple exposure photographic data to provide plots of axial loading in the orthosis and total axial loading imparted to the floor during the duration of the stance phase.  The difference between these two forces represents the load carried by the skeletal system.  Measurements were made first with subjects who had no specific instructions about the use of their orthoses.  The subjects were then instructed how to use their orthoses more efficiently.  In all cases, the effect of training produced a 30 to 50 percent increase in loading borne through the orthosis.


Postoperative ventilatory performance: dependence upon surgical incision.

Sixty-one patients undergoing elective surgery were evaluated in regard to the degree of depression in FVC and FEV1 that occurred in the postoperative period. Following a thoracotomy a reduction of about 75 per cent occurred, after a long midline incision 68 per cent, after an upper midline or paramedian incision 61 per cent, after a subcostal incision 53 per cent and after a lower midline incision 38 per cent. This information may be useful in determining which patients are at an increased risk for postoperative respiratory insufficiency.


Philadelphia's community based drug abuse program: broader medical and social concepts.

The rehabilitation of drug dependent people has undergone drastic changes since first attempts were made to curb the abuse of illegal drugs. The isolated law-enforcement model proved to be of no use in this area. So, too, the medical model, the psychological model and the public health model proved disappointingly low in their results. During the last ten years, a so-called "metabolic replacement model" has had its upsurge, creating a controversy still under discussion. The Drug Abuse Rehabilitation Programs of the West Philadelphia Community Mental Health Consortium, Inc. have been in the forefront with its treatment models. Established in 1968 as a purely methadone maintenance program, it has evolved into becoming a model, applying community mental health principles. This paper will explore this model further, describing the mechanics of its changes. From a municipal hospital-based methadone dispensing station, the program has developed into a multi-modality project. Three decentralized drug-free outpatient services are located in the midst of the community where the drug abuse problem is more accute. Outreach is emphasized and case-funding is applied. A possibly unique river-front motel was just acquired for the development of a community-based treatment modality. The 94 rooms were converted into a first-floor alcoholism program which also has a "highway safety program" and an intermediate care facility for alcoholics. The second floor of this facility contains outpatient services for the treatment of drug addicts, including a methadone maintenance program, counselling, family therapy and group therapy. The place where most of the emphasis has been placed is the Work Rehabilitation Center (a novel approach whereby patients will spend up to six hours in "partial hospitalization"). Clients will be tested for vocational aptitude and four workshops will be developed on the premises - carpentry, automotive, electricity and clerical. A huge cafeteria with a semi-automatic kitchen will allow further training in cooking and kitchen aids. The third floor of this renovated motel will include highly sophisticated clinical research area where computer utilization is already giving us very meaningful data. Clinical research is rapidly developing, and new drugs for the rehabilitation of drug addicts will be used. Further comments on the usefulness of methadone as a tool will be included in this paper and general comments as to the outcome of treatment further explored.


Effect of maternal heroin addiction on 67 liveborn neonates. Withdrawal symptoms, small body size, and small head circumference were frequent findings.

It is apparent that maternal addiction affects the fetus and causes serious problems in the neonatal period. Whether intrauterine exposure to heroin has far-reaching, long-term residual effects remains to be determined. We believe that prospective studies are indicated in order to evaluate the incidence of small head circumference, the pattern of intrauterine growth retardation, and the correlation of these findings with later neurologic and behavioral development.


Attempted suicide and suicide in functional psychoses.

A total of 2,243 first admissions to Gaustad Hospital between 1938 and 1961 diagnosed as functional psychotics were either followed up to the time of their death within 5 years, or observed over a period of 5 years, and then reexamined. Of these patients, 325 had attempted suicide prior to their admission. The frequency of attempted suicide was equal in both sexes. Men appeared to use more dangerous methods, and to have more serious intentions. The psychosis appears to have been of importance when considering whether, but not how the suicide should be attempted. The greatest risk of attempted suicide was to be found amongst patients with psychoses of a depressive nature. Twenty-eight of the 2,243 patients in this study committed suicide within 5 years following their discharge, and a further 20 took their own lives prior to the reexamination. A certain connection can be seen between attempted suicide and psychotic symptoms.


Methodology for a prospective study of suitability for psychoanalysis: the role of psychological tests.

A methodology for the use of psychological tests in the evaluation for suitability for psychoanalysis is described. Four variables--Reality Testing, Level and Quality of Object Relations, Affect Availability and Tolerance, and Motivation--were chosen for study and are discussed in detail. Data indicating a high degree of reliability between raters are presented.


The use of paraprofessionals in crisis intervention. Evaluation of an innovative program.

Single-session crisis services by paraprofessionals (graduate students and community volunteers) in the emergency room of a community hospital were offered to 293 clients. These clients were followed-up 6 to 12 months after their last contact and asked about: (1) the effectiveness of the service, (2) their use of referrals, (3) the major source of change in their crisis situation, and (4) their rating of improvement for their presenting problem. There were 104 clients who completed the follow-up. The results support the interpretation that timely intervention by paraprofessionals may have long-lasting results in specific problem areas. A model emphasizing the use of service deliverers as researchers is proposed.


Ureteral substitute by fallopian tube. Experimental study.

Experimental substitution of a long segment of ureter by a fallopian tube was performed in dogs. Three different techniques of proximal and distal anastomosis for reconstruction of the urinary tract were used in three groups of animals. Based on this, it is believed that the fallopian tube, as a pedicle graft, could serve in female dogs as the most approximate ideal substitute for ureter because of (a) anatomic proximity to the ureter permitting blood supply to the tube, (b) the fallopian tube's mucosa lining is not affected by urinary excretions, (c) does not allow absorption of electrocytes, (d) has a muscular wall with peristaltic activity, and (e) avoids the problems of antigenicity and/or foreign body reaction.


Vascular diseases in employed males: a perspective on preventive and remedial programs in industry.

Simple morbidity and mortality surveillance procedures have been applied at a large steel mill for several years. Analyses arising from these data are presented demonstrating, as a case in point, that vascular diseases are among the leading causes of absenteeism and are the leading cause of death among male employees. Furthermore, the strong association of hypertension with vascular mortality is clearly displayed. Finally, attempts to initiate treatment for hypertensive employees through referral to their family physicians met with rather disappointing success as only 22 of 200 referrals resulted in patient-physician interactions. Several suggestions and conclusions can be drawn from this work. First, simple surveillance procedures can be easily implemented in occupational settings and meaningful results derived. Industrial sites offer unique opportunities for epidemiologic studies. Second, vascular diseases have a devastating effect on working age males and it would appear that hypertension, as a controllable "risk factor", is a logical target for intervention programs. Third, while our information is rather limited, it would seem that traditional referrals of patients "at risk" to their family physicians is not an effective way to arrange for their treatment. For much the same reasons that industrial sites may be useful in epidemiologic studies, they may also provide a base for intervention programs for certain disease conditions. Before such programs are undertaken, however, research into their feasibility and effectiveness is required and we are hopeful that our own studies, now underway, will provide some insight in this area.


[Cerebral and cerebellar ependymomas in children].

Clinical analysis of 63 cerebral and cerebellar ependymomas in children aged up to 14 years showed that in the initial period of the disease the diagnosis based only on clinical manifestations may be difficult, before the appearance of signs of raised intracranial pressure eintraventricular or paraventricular ependymomas may cause attacks of vomiting, abdominal pains or signs of meningeal irritation. In every case with supposed brain tumour the child should be referred to a specialist since the results are better in earlier diagnosed and treated cases. Histological examination of biopsy material showed presence of 5 types of ependymonas: 1. with numerous cells (63%), 2 mixed (15%), 3 malignant (11%), 4 subependymal (4%), 5, epithelial (3%). In cases with subtotal removal of the tumour the mean survival is 12 months. After radical operation of the tumour the longest survival was 16 years.


Medical education in the People's Republic of China.

Medical education in the People's Republic of China is described as it was seen on a 10-week trip in 1973. The information was collected from five medical schools which were visited personally as well as from practitioners and citizens. An overview of the health care system indicates the relationships between education and practice. The three-year medical curricula from the five medical schools are reasonably similar; and in the state-controlled system of health care they are integrated with postgraduate training and continuing education. Goals of the educational programs, entrance procedures, and the medical school experience are discussed. The literature on medical education and practice in China is reviewed and compared with the data available during this recent visit. The lessons which might be learned are the methods of offering health care to massive populations and the organization of health professionals and paraprofessionals for such programs.


Serum I-K (immunoconglutinins) in Hodgkin's disease.

An increase of C'3 fraction, already observed in Hodgkin's disease has been confirmed, and is here described in a group of 33 patients at various clinical stages of Hodgkin's disease. It is consistently higher than those found in a group of 26 normal subjects. Conglutinins present in Hodgkin's disease patients, as far as their behaviour is concerned, may be considered as immunoconglutinins (I-K).


Folate transport by the choroid plexus in vitro.

Reduced folates are transported from blood into cerebrospinal fluid against a concentration gradient. In vitro, folates were transported into and released by isolated rabbit choroid plexuses. The choroid plexus uptake mechanism was specific for folates, energy dependent, and depressed by cold temperatures. In vivo, the choroid plexus may transport folates from blood to cerebrospinal fluid.


A new feeder system for quantitating actual toxicant consumption by mice during feeding studies.

A new mouse feeder system was described which enables mice to be utilized for long-or short-term feeding studies of chemical toxicants. Quantitative toxicant consumption can be obtained. The use of granulated feed of particle size, 500-1000 mu, prevents bridging, thus assuring a constant supply of diet to the experimental animals. Comparative weight gain in female BALB/c Nctr BR mice showed no significant differences between the groups fed 500 ppm 2-fluorenylacetamide, control granulated feed, or pellets.


The surface glycoproteins of a mouse melanoma growing in culture and as a solid tumor in vivo.

B16 melanotic tumors in various organs of mice were labeled with either [14C- or [3H]L-fucose or D-glucosamine. Glycopeptides derived from the membrane glycoproteins of these tumors were compared with those of normal tissues by double-label elution patterns from Sephadex G-50 columns. A marked increase of sialic acid-rich, fucose-containing glycopeptides (PEAK A) was found in the glycoproteins of the surface and internal membranes of melanotic cells. The glycopeptides from the melanoma cells could be reduced in size by treatment with neuraminidase. Comparison of the glycopeptide patterns of melanoma cells grown in culture and in mice revealed a greater complexity in in vivo material. Virtually all of the glycopeptides from melanoma cells grown in culture were of the larger type (Peak A) that correlates well with the malignant state. Comparison of two lines of B16 melanoma cells with greatly differing abilities to form tumors in lung revealed no significant, reproducible differences in their glycopeptide patterns.


The effect of Rauscher and Moloney leukaemia virus on amyloid development in casein-treated CBA mice.

Infection of adult CBA mice with Rauscher or Moloney leukaemia virus concomitantly with caseination significantly accelerated spleen amyloid development in irradiated, bone-marrow protected mice, but had no effect on untreated, adult thymectomized or thymectomized irradiated mice. Spleen tissue of mice infected with Moloney virus had the highest titre in the mice with accelerated amyloid development.


A profile for managing sensory integrative test data.

A concise method for compiling a data profile from a general sensory integrative test battery has been presented. Subtests from each test used were categorized according to the sensory integrative and motor functions being tested. These categories have been defined and include: tactile-kinesthetic perception, visual perception-figure ground, visual perception-constancy, ocular control, gross motor control, fine motor control, integration of function-two sides of the body, orientation in space, body awareness, and auditory discrimination. A method for converting the various scores into descriptive terminology is provided in which the test results are reported as above age expectancy, appropriate for age, somewhat deficient for age, and markedly deficient for age. The clinical implications of the technique are discussed.


Nuclide angiography in Paget's disease of the skull: Case report.

Early-appearing and persistent uptake on nuclear angiography in a patient with early Paget's disease of the skull is described. The diagnosis of subdural hematoma may be ruled out at the time of brain scanning.


[Studies on the influence of an artifically induced inflammatory reaction by creatinine, urea and guanidine injection (author's transl)].

The influence of creatinine, urea and guanidine injection on the course of an artifically induced inflammatory reaction has been studied in rats. The formalin and bolus alba edema served as inflammatory models. It was shown that the inflammatory reaction was not significantly altered by urea. By creatinine, however, the inflammation was diminished. If urea and creatinine were given together the course of the inflammatory reaction was not altered significantly, suggesting an inhibitory interrelation between these two substances. Guanidines showed the strongest inhibiting effect on inflammation. It is discussed that guanidines influence energy availability by inhibition of oxydative phosphorylation.


Histiocytosis X--comparison of three treatment regimens.

The three treatment regimens evaluated in this study (vinblastine alone versus prednisone and vinblastine versus prednisone and 6-mercaptopurine) proved to be about equally efficacious in children with histiocytosis x. Inasmuch as many physicians regard this disorder as one with a high mortality rate, it is worth emphasizing that 59 of the 83 patients (71% are living).


Early embryology and implantation in the California leaf-nosed bat, Macrotus californicus.

Female reproductive tracts from 84 bats were examined by light and/or electron microscopy to electron microscopy to observe early embryology and implantation in Macrotus. The earliest pregnancy was observed in October and by the end of October all bats were pregnant. Implantation had begun in most specimens from late October. In late November females were carrying implanted blastocysts in which differentiation of endoderm was noted. Reichert's membrane was first observed in November. In early December the trophoblast had begun to differentiate into cytotrophoblast and syncytiotrophoblast and by the end of January this differentiation was most evident. Reichert's membrane persisted until late January. Endoderm in the January sample completely surrounded the yolk sac cavity. By late February the embryos were at the embryonic disc stage had differenitated mesoderm. The uterine-fetal relationship was complex and an early placenta was recognized. In late March the embryos spanned a range of development from neural plate to limb-bud stages. Parturition occurred in June. This lengthy gestation period is characterized by an embryonic diapause of approximately four and one-half months. The roles of food supply and/or temperature in controlling this growth rate and the evolutionary implications of this development are discussed.


Sensitivity of DBLA-6 leukemia of rats to known antitumor agents in relation to their clinical effects.

Of 4 lines of myelogenous rat leukemias induced by N-nitrosobutylurea (NBU), DBLA-6 was selected as a screening model for antileukemic agents because of the following characteristics: a) High transplantability either by intravenous (i.v.) or intraperitoneal (i.p.) inoculation; b) linear relationship between inoculum size and survival time; c) marked increase of leucocyte counts in the peripheral blood as the tumor progresses after intravenous inoculation. To investigate reliability in its predicting clinical efficacy, its sensitivity to known antileukemics was studied. To determine the effects, a change of leucocyte counts in the peripheral blood together with the prolongation of life span was checked in the following systems; i.v.-i.v. (i.v.-inoculation, i.v.-injection), i.v.-i.p., i.p.-i.p., i.p.-i.v. Fifty percent cure was obtained with Vincristine, Vinblastine, Daunorubicin, 6-Mercaptopurine, and alkylating agent 838D or 864T. The success of treatment was measured by decrease of leucocytes. Methotrexate, cytosine arabinoside (Ara-C), and cyclophosphamide showed only poor effects, and Mitomycin C, L-asparaginase, and Bleomycin were ineffective. In addition, the chemotherapeutic effects of Vincristine and 864 on this leukemia were quite dependend both on the route of drug injection and on the site of tumor inoculation. Subsequently, our studies are being extended to cover the correlation between drug distribution and tumor localization or dissemination.


Genetic antecedents of altruistic behavior in Passeriformes.

On the basis of a theory for the establishment and increase of altruistic genes in animal populations a relationship was hypothesized to exist in an avian order between clutch averages (which were considered an index of "genetic investment") and prosocial behavior. The order Passeriformes was used, as clutch sizes were found to vary from one to 11 among the species, and the number of caretakers was also found to vary, falling into four categories: female only, female and male, both plus intraspecies helpers, and interspecies altruists. The positive correlations found in this research tend to support this theory.


Changes in galvanic skin response as affected by musical selection, sex, and academic discipline.

The present paper tested hypotheses that (a) music can influence anxiety; (b) differences in response to music may be found between males and females; and (c) differences in response may be found between music and nonmusic majors. Subjects included 100 music majors, (50 male and 50 female) and 100 nonmusic majors, (50 male and 50 female) randomly selected from students at North Park College, Chicago, Illinois. Test instruments included a pencil-maze, blindfold goggles, GSR apparatus, and a musical recording. All three hypotheses were substantiated in terms of levels of significance ranging from .01 to .05 for different Ss.


Potassim-aldosterone-renin interrelationships.

The present study was performed to assess the sensitivity of the renin-angiotensin-aldosterone axis to small changes in plasma potassium concentration within the physiologic range. Small increments in potassium levels were accomplished by graded constant infusions of potassium chloride over 2 h (0.17 meq/min; 0.33 meq/min; 0.5 meq/min) in 8 normal subjects on a 10 meq sodium-100 mgq potassium intake. Plasma levels of aldosterone, renin activity, angiotensin II, cortisol, potassium and sodium were measured at frequent intervals. There were no significant changes observed in plasma sodium, renin activity or angiotensin II levels while cortisol levels declined in the expected diurnal pattern. During the 0.17 meq/min (10 meq/h) infusion potassium levels did not increase significantly until 120 min while plasma aldosterone levels rose significantly at 30-60 min. The mean increment above control during the lowest infusion rate was 0.2 meq/liter (5%) for plasma potassium and 13 ng/100 ml (46%) for plasma aldostreone. Although there was a stepwise increase in the increments above control of both potassium and aldosterone levels as the rate of the infusion was increased, the most sensitive area of the dose response curve appears to be 0.1-0.5 meq/liter. in six normal subjects the potassium-lowering effect of glucose ingestion (0.25 g/kg/15 min over a 2-h period) was assessed. The mean maximal potassium decrement below control 0.3 meq/liter (8%) at 90 min was coincident with the mean plasma aldosterone decrement below control of 11 ng/100 ml (46%). Plasma aldosterone then rose to peak levels at 180 min (mean increment 22 ng/100 ml above nadir) while potassium levels remained below control. The rise in plasma aldosterone was associated with a parallel but more rapid rise in plasma renin activity, peaking at a level 108% above control. Ninety minutes after the termination of the glucose ingestion, plasma aldosterone returned to control levels but now in the setting of reduced levels of plasma potassium and elevated levels of plasma renin activity. The data support an important role for physiologic changes in extracellular potassium concentration in the control of aldosterone secretion and indicate that interpretation of studies assessing acute changes in plasma aldosterone must carefully consider minor simultaneous changes in plasma potassium levels. The data also document that acute changes in extracellular potassium concentration play a role in the regulation of renin secretion.


Influence of the hemodialysis on the half-life of practolol in patients with severe renal failure.

Practolol, a recent and more selective beta-adrenergic receptor blocking drug, was given orally as a single dose of 200 mg to seven healthy volunteers and to six patients suffering from severe renal impairment and submitted to the long-term hemodialysis program. The plasma drug decay was markedly slowed and the plasma half-life was prolonged sixfold in the uremic patients in comparison to healthy volunteers. Hemodialysis (8 hours) starting 48 hours after drug intake lowered plasma practolol significantly but transiently. The shorter half-life during hemodialysis and the detection of equally high values of practolol in the ultrafiltrates as in the plasma demonstrate that this drug is readily removable from the plasma. However, the ascending slope of the plasma drug concentration curve which appeared following hemodialysis is suggestive of an incomplete drug removal from the body.


Vinyl-chloride-induced liver disease. From idiopathic portal hypertension (Banti's syndrome) to Angiosarcomas.

Histologic examination of liver tissue (eight autopsy and 18 biopsy specimens) and five spleens from 20 workers with vinyl chloride polymerization showed hepatic angiosarcomas in 15. In addition, a peculiar pattern of progressive portal-tract, inconspicuous intralobular and conspicuous capsular fibrosis was observed in the five workers without angiosarconma, in all the seven patients with angiosarcoma from whom tumor-free portions of the liver were available, and in two tumor-free biopsies from patients subsequently found to have angiosarcoma. The fibrosis was accompanied by splenomegaly. Hypertrophy and hyperplasia of both hepatocytes and hepatic and splenic mesenchymal cells were also seen. The histologic similarity to chronic inorganic arsenical poisoning, in which angiosarcomas also occur, and to idiopathic portal hypertension (Banti's syndrome) suggests that the latter syndrome at times results from unknown toxic, possible environmental, chemicals.


Polarizing fucoid eggs drive a calcium current through themselves.

Calcium ions enter the prospective growth pole of polarizing Pelvetia eggs faster than the opposite pole and leave this antipode faster than the growth pole. The calcium current is greatest when first measured at 6 hours after fertilization and decreases as the time of final commitment to growth in a particular direction approaches.


Damage and repair of the peripheral myelin sheath and node of Ranvier after treatment with trypsin.

Cultures of whole fetal rat sensory ganglia which had matured and myelinated in culture were treated for 1-3 h with a pulse of 0.2% trypsin. The tissue was observed during the period of treatment and during subsequent weeks using both light and electron microscopy. Within minutes after trypsin addition the matrix of the culture was altered and the nerve fascicles loosened. Progressive changes included the retraction of Schwann cell processes from the nodal region the detachment of the myelin-related paranodal Schwann cell loops from the axon, and lengthening of the nodal region as the axon was bared. The retraction of myelin from nodal stabilized several hours after trypsin withdrawal. Breakdown of the altered myelin segments was rare. There were no discernable changes in neurons or their processes after this exposure to trypsin. The partial repair which occured over a period of several weeks included the reattachment of paranodal Schwann cell loops to the axolemma and the insertion of new myelin segments where a substantial length of axolemma had been bared. The significance of these observations to the characterization of the Schwann cell-axolemmal junctions on myelinated nerve fibers is discussed. The dramatic degree of myelin change that can occur without concomitant myelin breakdown is particularly noted, as is the observation that these altered myelin segments are, in part, repaired.


Growth of mammalian cells on substrates coated with cellular microexudates. I. Effect on cell growth at low population densities.

Mammalian and avian cells cultured on glass or plastic substrates produce microexudates of cellular macromolecules which remain bound to the substrate when the cells are detached. The gross macromolecular composition of microexudates from a range of diploid, heteroploid, and virus-transformed cells was determined with cells labeled with radioisotopes. Significant differences in the amounts of cellular glycoproteins, proteins, and RNA present in microexudates were found between different cell types and between cells of the same type at different stages of growth. Inoculation of cells onto substrates "coated" with microexudates altered their growth behavior. Microexudates from exponentially growing subconfluent homotypic and heterotypic cell populations enhanced the growth of mouse and chick embryo cells seeded at very low densities, but similar microexudates had no effect on the proliferation of cells seeded at higher densities. The enhanced growth of low-density cell populations seeded on microexudates was compared with the growth enhancement produced by feeder cell layers and conditioned medium.


Correlation of rhodopsin biogenesis with ultrastructural morphogenesis in the chick retina.

The developing chick retina from stages 39-45 has been examined by biochemical and electron microscope techniques. The levels of rhodopsin contained in the maturing chick retina were evaluated by detergent extraction and correlated with rod outer segment formation. It was found that the appearance of rhodopsin in significant levels preceded outer segment formation by at least 2 days, thus implying that rhodopsin is synthesized in the receptor cell inner segment and translocated to the outer limb when disk membrane biogenesis occurs. The level of rhodopsin continues to rise as the rod outer segment develops. Development of both rods and cones originates and proceeds most rapidly in the fundus or central region and proceeds toward the periphery. In general, rod outer segments were noted to develop far more rapidly than cone outer segments.


Regulation of DNA replication on subchromosomal units of mammalian cells.

The regulation of DNA replication at a subchromosomal level in mammalian cells has been investigated. DNA fiber autoradiographs were prepared from mouse L-929 cells pulse labeled with (3H)thymidine. Initiation events and subsequent chain growth occurring over short stretches (up to three replication units in length) of chromosomal DNA were analyzed. The results show that adjacent units usually initiate replication synchronously and that this synchrony is related to the proximity of initiation sites. In addition, adjacent units are of similar size and the rates of replication fork progression within units and on adjacent units are similar. The rate of fork progression increases with increasing replication unit size. Finally, no evidence for fixed termination sites for the units has been found. These observations suggest that despite large variations in size of replication units, timing of initiation events, and rates of fork progression found in chromosomal DNA as a whole, these processes are closely regulated within subchromosomal clusters of active replication units.


Isolation of a concanavalin A receptor from mouse L cells.

A cell surface glycoprotein receptor for concanavalin A (Con A) has been isolated from mouse L cells. The isolation procedure involved dissolving whole L cells in 0.3 M lithium diiodosalicylate and extracting with aqueous phenol. The Con A receptor, which was found in the aqueous phase of this extract, was further purified by affinity chromatography on a column of Con A-Sepharose; the receptor was adsorbed to Con A-Sepharose and eluted with 0.1 M methyl alpha-D-glucopyranoside or with 0.1 M methyl alpha-D-mannopyranoside, but not with other monosaccharides. The cell surface location of the Con A receptor purified in this way was confirmed by showing that it can be isolated from purified L cell plasma membranes and by demonstrating that it can be labeled from the exterior surface of intact L cells by the nonpenetrating galactose oxidase-KB3H4 system. Biochemical studies of the Con A receptor have shown that it migrates on sodium dodecyl sulfate-polyacrylamide gels as a single component having an apparent molecular weight of approximately 100,000. Its N-terminal amino acid is valine and it has carbohydrate attached at several (at least five) different sites along the polypeptide chain.


Inhibition of mitochondrial electron transport by hydroxy-substituted 1,4-quinones.

Mitochondrial electron transport from NADH, succinate, or duroquinol to oxygen is inhibited by 5-omega-cyclohexyl-n-pentyl-6-hydroxy-2,3-dimethoxy-1,4-benzoquinone and 2-omega-cyclohexyl-n-pentyl-3-hydroxy-1,4-napthoquinone. Assays of partial electron transport activities indicate a site of inhibition in the region between the site of duroquinol oxidation and cytochrome c reduction. Effects of the inhibitors on cytochrome spectra indicate the principle site of inhibition is between cytochromes of the b group and cytochrome c1. The quinones do not induce increased reduction of the b566 as does antimycin A. The benzoquinone can induce a partial antimycin insensitive bypass of the cytochromes b-c1 region. Uncoupling agents do not affect the extent of inhibition as has been reported for analogous naphthoquinone inhibitors.


Modification of histone binding in calf thymus chromatin by protamine.

When calf thymus chromatin is incubated with protamine, the protein binds to DNA, forming a chromatin-protamine complex. The binding reaches a saturating level at the weight ratio of protamine to DNA of approximately 0.5. Although the saturated binding of protamine to DNA does not cause major displacement of histones from calf thymus chromatin, examination of the dissociation profiles by salt in combination with urea of protamine-treated chromatin shows that the histone-DNA interactions are markedly altered by such binding. The dissociation of histones from the chromatin-protamine complex requires less NaCl but the same concentration of urea as that for untreated chromatin, suggesting that the electorstatic interactions between the histones and DNA are decreased as a result of protamine binding. When protamine concentration is increased beyond that required for saturated binding to DNA during in vitro exposure of calf thymus chromatin to protamine, lysine-rich histone is completely displaced.


Alteration of fatty acid composition of LM cells by lipid supplementation and temperature.

Alteration of the fatty acid composition of monolayer cultures of LM cells grown in chemically defined medium was achieved by supplementation with fatty acids complexed to bovine serum albumin. Phospholipids containing up to 40% linoleate were found in cells grown in medium containing 20 mu g of linoleate/ml. Incorporation of linoleate into phospholipids reached a plateau after 12-24 hr, and cells remained viable for at least 3-4 days. Although linoleic, linolenic, and arachidonic acids were incorporated into LM cells equally well, only the latter was elongated by these cells under these experimental conditions. Nonadecanoic acid was incorporated to a lesser extent than the polyunsaturated fatty acids. Phosphatidylcholine and phosphatidylethanolamine of LM cells had different fatty acid compositions; phosphatidylethanolamine contained more longer chain and unsaturated fatty acids. Cells were also grown in the absence of choline and presence of choline analogs such as N,N-dimethylethanolamine, N-methylethanolamine, 3-amino-1-propanol, and 1-2-amino-1-butanol. The analog phospholipids in these cells had fatty acid compositions which were intermediate between those of phosphatidylethanolamine and phosphatidylcholine of control cells grown in the presence of choline. Linoleate was found in both phosphatidylcholine and phosphatidylethanolamine of cells supplemented with linoleate. The sphingolipid fraction of these cells, however, did not contain significant amounts of linoleate. When linoleate was present in the phospholipids, compensatory decreases in the oleate and palmitoleate content of phospholipids were observed. Lowering of the growth temperature to 28 degrees produced an increase in unsaturate fatty acid content of the phospholipids. When linoleate was supplied to cells grown at 28 degrees, there was no further increase in the unsaturated fatty acid composition of the phospholipids. Using both fatty acid supplementation and lowered growth temperature, LM cell membranes can be produced which have phospholipids with vastly different fatty acid compositions.


The binding of tissue-specific adhesive molecules to the cell surface. A molecular basis for specificity.

Factors present in supernatants prepared from neural retina or cerebral lobe tissue cultures bind specifically to cells of the same type and promote cellular aggregation; the basis for the specificity of these factor-cell interactions has been investigated. Pronase digestion destroys binding of protein but not the carbohydrate portion of factors. Digestion with a mixture of protease-free glycosidases destroys both protein and carbohydrate binding. Purified beta-N-acetylhexosaminidase reduces binding of retina factor by 80%. The enzymatic activity which destroys binding of cerebral lobe factor to cerebral cells appears to be alpha-mannosidase activity. Further, paper chromatography of the enzymatic digestion products of the binding factors reveals that N-acetylgalactosamine residues are released from the retina factor while mannosamine residues are released from the cerebral lobe factor. Inhibition of binding of factors to cells by monosaccharides is consistent with the enzyme data. N-Acetylgalactosamine maximally inhibits binding of factor to retina cells while mannosamine inhibits factor binding to cerebral cells. These data suggest that the specificity of cellular adhesion is determined, at least in part, by the sequence of sugars in an oligosaccharide residue of a complex glycoprotein.


The activation of adrenal cortex mitochondrial malic enzyme by Ca2+ and Mg2+.

Adrenal cortex mitochondria prepared by a standard method do not exhibit malic enzyme activity. Addition of physiological concentrations of Ca2+ and Mg2+ enables these mitochondria to reduce added NADP+ by malate to form free NADPH. Half-maximum activation of the mitochondrial malic enzyme requires 0.3 mM Ca2+ and 1 mM Mg2+. Solubilized mitochondrial malic enzymes is independent of Ca2+ and has a K M of 0.2 mM for Mg2+. The Ca2+ effect is dependent on an initial period of active Ca2+ uptake which also causes other changes in respiratory properties similar to those observed with mitochondria from other tissues. After Ca2+ accumulation has taken place, free Ca2+, but not additional accumulation, is still required for malic enzyme activity. The requirement for Mg2+ can be met by Mn2+ (1 mM). This concentration of Mn2+ alone yielded only a slight activation of mitochondrial malic enzyme while higher concentrations of Mn2+ alone gave good activation of the mitochondrial malic enzy.e The NADPH generated by the Ca2+-Mg2+ activated malic enzyme effectively supports the 11beta-hydroxylation of deoxycorticosterone, whereas in the presence of malate, or malate plus Mg2+ but absence of Ca2+, the energy linked transhydrogenase supplies all the required NADPH. The activated malic enzyme appears to be more efficient than transhydrogenase in generating NADPH to support 11beta-hydroxylation. Cyanide and azide have been found to inhibit solubilized mitochondrial malic enzyme.


Planned splenectomy in treatment of idiopathic thrombocytopenic purpura.

The results of a policy of treatment in idiopathic thrombocytopenic purpura based on previous observations on the natural history of the disease and its response to corticosteroids are described. The results of splenectomy were better when the history was less than 100 days. Three patterns of response to splenectomy were observed: complete remission, symptomatic remission, and relapse. The prognosis can be determined by the level of the platelet count six weeks after splenectomy. Corticosteroid treatment for more than three weeks before splenectomy noticeably increased the incidence of complications after operation. Splenectomy can safely be performed in pregnancy. The decision to operate should be made on the maternal condition and its response to corticosteroids.


Teratogenic effects of diphenylhydantoin.

A child aged 24 months had multiple congenital abnormalities and delayed development. The 28-year-old mother had been treated since childhood with anticonvulsants. Her previous pregnancies had resulted in three early spontaneous abortions and one child with severe bilateral cleft lip and palate. This case report further suggests a relationship between maternal diphenylhydantoin use and fetal anomalies.


Malignant histiocytosis (histiocytic medullary reticulosis). I. Clinicopatholigic study of 29 cases.

The clinical records and histologic material from 29 cases of malignant histiocytosis (MH) have been reviewed, as well as autopsy findings in 14 cases. The mean age was 31 years, with a 2.2:1 male to female preponderance. Major physical findings included temperature elevation, lymphadenopathy, hepatomegaly, splenomegaly, and preterminal jaundice. Common laboratory findings were anemia, leukopenia, and thrombocytopenia. The median survival was 6 months, the mean 14 months, and the range from 1 month to 8 years. The histologic features observed in lymph nodes, liver, spleen, and bone marrow have been emphasized, as well as features useful in differential diagnosis. In contrast to our experience with the non-Hodgkin's lymphomas, bone marrow aspiration was superior to biopsy in assessing marrow involvement. Unusual manifestations included soft tissue infiltration in 5 cases; 2 of these patients presented with a soft tissue mass. The distinctive clinical as well as histologic findings warrant recognition and separation of MH from other hematopoietic disorders.


Comparison of the cellular DNA-bound products of benzo(alpha)pyrene with the products formed by the reaction of benzo(alpha)pyrene-4,5-oxide with DNA.

DNA isolated from mouse embryo cell cultures that had been treated with [3H]benzo(alpha)pyrene was degraded with enzymes to deoxyribonucleosides, and the hydrocarbon-deoxyribonucleoside products were isolated by chromatography on a Sephadex LH20 column eluted with a water: methanol gradient. The hydrocarbon-deoxyribonucleoside products were not identical to those found in similar chromatograms of enzyme digests of DNA that had been reacted with benzo(alpha)pyrene-4,5-oxide in aqueous ethanol solution. This finding suggests that the metabolic activation of benzo(alpha)pyrene that results in this hydrocarbon becoming covalently bound to DNA in mouse embryo cells in culture may be more complex than simply formation of a K-region epoxide and reaction of that compound with the cellular DNA.


A comparison of glycosyltransferase activities and malignant properties in normal and transformed cells derived from BALB/c mice.

The ability of suspensions of BALB/c cells to catalyze the incorporation of nucleotide sugars into complex polysaccharides has been compared. These cells have previously been characterized for concanavalin A-induced agglutinability, tumorigenicity, and malignancy. All of the cell lines tested catalyze transfer of the sugar moieties of cytosine 5-monophosphate N-acetylneuraminic acid, uridine 5-diphosphate galactose, uridine 5-diphosphate N-acetylgalactosamine, uridine 5-diphosphate N-acetylglucosamine, uridine 5-diphosphate glucose, and guanidine 5-diphosphate monnose into glycoproteins and glycolipids. While some transformed lines exhibit alterations in transferase levels, others cannot be distinguished from normal cells. Normal cells, transformed cells that cause tumors that regress, and transformed cells that cause tumors that kill an immunologically competent host show growth-dependent changes in transferase activities. Determining the ability to catalyze carbohydrate transfer is insufficient for predicting the tumorigenic and malignant properties of a cell line.


Comparative effects of three nitrosourea derivatives on mammalian cell cycle progression.

Three nitrosourea analogs, 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and 1-trans-(2-chloroethyl)-3-cyclohexyl-1-(4-methylcyclohexyl)-1-nitrosourea, were examined for effects on survival and cell cycle traverse capacity in exponentially growing (cycling) populations of line CHO Chinese hamster cells and in cultures arrested in G1 by isoleucine deprivation during treatment with drugs, then returned to the cycling mode by restoration of isoleucine (noncycling cells). Among parameters studied were survival, cell division, DNA initiation capacities, cell cycle distributions, and rates of cell cycle traverse in drug-treated cycling and noncycling cells utilizing a protocol combining autoradiography, cell number enumeration, and flow microfluorometry. The results obtained were in generally good agreement with results obtained in vivo in other studies and included the following. Cells treated with any of these agents accumulated preferentially in late S and G2, primarily the result of a gross increase in duration of these phases of the cell cycle. There was also a prolongation of doubling time during the early stages following drug treatment and return to the proliferating mode of cells which ultimately survived. All three drugs induced mitotic nondisjunction in cells capable of dividing and also induced polyploidy by allowing multiple rounds of progression through the cell cycle in the absence of an intervening cell division. In treated populations, the G2-arrested and polyploid cells were among the first cells to die. Treated, noncycling cells that were returned to cycle exhibited a lower survival capacity than did treated, cycling cells. Finally, 1-(2-chloroethyl-3-cyclohexyl)-1-nitrosourea and 1-trans(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea induced a dramatic alteration in clonal morphology and growth patterns in surviving cells that persisted for at least a week after drug removal. The results obtained suggest that our model system may be useful as a predictive guide for determining response of susceptible tumor cells to treatment with chemotherapeutic agents.


The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy.

The hormonal factors associated with converting a corpus luteum of estrous cycle into a corpus luteum of pseudopregnancy were studied by measuring LH and FSH prolactin, estradiol and progesterone levels in decapitated rats during the 4-day estrous cycle and a comparable time of pseudopregnancy (lights on 0600-0800 hr.). During the estrous cycle, prolactin, LH and FSH remained low and unchanging except on the afternoon of proestrus, when typical proestrous surges were observed. In contrast, estradiol levels began to increase on D-1, from baseline values of 7 pg/ml to approximately 15-20 pg/ml. These levels were maintained until the afternoon of D-2 when estradiol further increased to reach peak levels of 40-50 pg/ml by 0900 hr on proestrus. Estradiol then declined in relation to the increase in LH secreation and had returned to baseline by estrus. Progesterone secretion by the corpora lutea of the cycle also increased on the afternoon of D-1 and reached a maximum value of 25-30 ng/ml early on the morning of D-2. At this time, a precipitious fall in progesterone occurred, returning to baseline values of 5-1- ng/ml by 0700 on D-2 signifying the regression of the corpora lutea of the cycle. Progesterone remained low thereafter until the afternoon of proestrus when levels increased in response to the proestrus when levels increased in response to the proestrous surge of LH. Following cervical stimulation at 1900 hr on proestrus, no differences were noted, with respect to the estrous cycle, in LH, FSH or estradiol secreation through the afternoon of D-2. Surprisingly, progesterone levels did not differ in the cycle and pseudopregnancy until the early morning of D-29 instead of progesterone levels falling to baseline as they had during the cycle, the corpora lutea of pseudopregnancy were rescused, progesterone increasing dramatically to reach levels of 45-50 ng/ml by 1700 hr on that same day. The only difference in hormone secretion that was noted which could account for this marked divergence in progesterone secretion was the pattern of prolactin secretion following cervical stimulation. In contrast to the low levels seen during the estrous cycle, biphasio surges of prolactin secretion occured each day, one being nocturnal (0100-0900 hr) and the other diurnal (1500-2100 hr). The rescue of the corpus luteum occured in association with the nocturnal surge on D-2. These results suggest that nocturnal surge on D-2, PROLACTIN IS THE MAJOR Luteotropic stimulus which transforms and estrous cycle into pseudopregnancy by prolonging progesterone secretion from the corpus luteum. Moreover, if LH is important for progesterone secretion, no changes were observed in the pattern of LH secretion which can account for the rescue of the corpus luteum.


Observations on facilitation of the preovulatory rise of LH by estrogen.

Systemic levels of estradiol (E2) during the 4-day estrous cycle rise in a biphasic manner; slow elevations during diestrus II are followed by rapid increases during the early morning of proestrus (Kalra and Kalra, 1973). The relation of these alterations in systemic E2 levels to the proestrus surge of LH was investigated. Administration of progesterone (P 4 mg/rat) to rats at 2200 hr of diestrus II blocked ovulation and the surge of LH in the afternoon of proestrus. Injection of estradiol benzoate (EB, 5 mug/rat) 2 hr prior to, together with or following P treatment at 0300 hr of proestrus restored ovulation and the surge of LH. However, blockade of ovulation was not reversed if EB was administered at 0500 or 0800 hr of proestrus following P treatment on diestrus II. Similarly, bilateral ovariectomy at 2300 hr of diestrus II but not at 0300 hr or later on proestrus abolished the proestrus surge of LH. Apparently, the rapid rise in systemic E2 between 2300 hr of diestrus II and 0300 hrs of proestrus is crucial and serves to activate the neural "trigger" of preovulatory release of LH. The role of ovarian E2 secretion prior to 2300 hr of diestrus II in facilitation of neural "trigger" was studied. In the absence of endogenous E2 priming produced by ovariectomy at 0800 hr of diestrus II, EB injections at 2300 hr of the same day failed to restore the proestrus surge of LH. However, when ovariectomy was delayed to allow normal E2 priming through diestrus II, administration of EB shortly after ovariectomy at 2300 hr of diestrus II elicited the normal proestrus surge of LH. These results indicated that following the initial "priming" of central site(s) with low levels of circulating E2 during diestrus II, rapid elevations in ovarian estrogen secretion between 2300 hr of diestrus II and 0300 hr of proestrus facilitated the neural "trigger" of pituitary LH release during the critical period on proestrus.


Cytoplasmic glucocorticoid binding proteins in bone cells.

The binding of 3H-dexamethasone (3H-DM) was studied in the cytoplasmic fraction of bone cells isolated from fetal rat calvaria by enzymatic digestion. An high-affinity glucocorticoid binding protein resembling those described in other target tissues was demonstrated. Scatchard analysis revealed a single class of binding sites with an apparent dissociation constant for 3H-DM (0C) of 7 x 10-9M and a concentration of binding sites of 0.11 pmoles/mg cytosol protein. The number of cytoplasmic binding sites per cell was calculated at 6,000 which is probably an underestimate due to occupancy of some sites by endogenous steroids. The binding sites appeared protein in nature since incubation with pronase destroyed 100% of the binding. Nuclear transfer was demonstrated in a reconstituted system utilizing bone cytosol as donor and liver nuclei as the acceptor. Competitive binding analysis revealed corticosterone to be equivalent to DM in binding affinity; progesterone was 75% as potent as DM. Aldosterone and SC-26304 (a spirolactone analogue) had, respectively, 1


Adrenal and ovarian steroid secretion in the rat estrous cycle temporally related to gonadotropins and steroid levels found in peripheral plasma.

This study was undertaken to determine the patterns of estrogen and progestin secretion by the adrenal and the ovary and to relate these to the levels of steroids and gonadotropins found in peripheral plasma. A total of 70 rats were used in this study. Adrenal venous (ADVB) and ovarian venous blood (OVB) were collected by concurrent cannulation and peripheral blood (PB) was obtained from the abdominal aorta. Estrone (E1), estradiol (E2), PROGESTERONE (P) and 17alpha-hydroxyprogesterone (17alpha-OHP) were measured by radioimmunoassay. The concentration of E2 in general was higher in ADVB than in OVB. Although increased levels of E2 in ADVB were found on the afternoon of proestrus (1527-2634 pg/ml), they were not significantly different from those recorded at other times. In contrast E2 in OVB was lowest at 1000-1200 hr of estrus (225 pg/ml) and highest at 1000-2000 hr of proestrus (1190-1605 pg/ml). The E2 in PB followed the pattern seen in OVB; the values ranged from 80-211 pg/ml. P concentration in general was higher in ADVB than in OVB. The lowest concentration of P in ADVB was between 0200-0400 hr of estrus (183 ng/ml) and the highest between 1400-1600 hr of proestrus (580 ng/ml) and 1000-1200 hr of estrus (591 ng/ml). The lowest concentration of P in the OVB was between 1600-1800 hr of diestrus (42 ng/ml) and the highest between 0200-0400 hr of estrus (466 ng/ml). In the PB, P reflected changes in adrenal as well as ovarian secretion; the values ranged fron 7-25 ng/ml. E1 in ADVB was in general lower than in OVB, and there were no significant changes at any stage of the cycle. In the OVB, however, E1 showed a pattern similar to that of E2. Levels of E1 in PB were very low and failed to show any significant changes. 17alpha-OHP was high in ADVB, although there were no significant changes during the cycle; PB levels also did not show any significant changes. In the OVB a peak of 17alpha-OHP was recorded between 0200-0400 hr on the day of estrus. The LH and FSH levels showed increases after 1600 hr on the day of proestrus and this was in agreement with earlier studies. Since the adrenal secretes all of the 4 steroids studied, it is reasonable to assume that it does exert some effect in the pituitary-gonadal axis. A role of adrenal P for the facilitation of the preovulatory LH release has been indicated and the increased secretion of adrenal P between 1400-1600 hr of proestrus supports this possibility.


A daily signal for the LH surge in the rat.

We have demonstrated that a brief step-like increment in circulating estradiol concentrations to approximately 100 pg/ml, achieved by SC insertion of Silastic capsules containing estradiol-17 beta and their withdrawal after 29 1/2 hr, elicited a daily LH surge on 4 consecutive afternoons in rats ovariectomized 2 weeks previously. Since the duration of this stimulus was similar to that of the preovulatory increment in serum estradiol concentrations, it was postulated that the endogenous estrogen signal in intact rats might also trigger repetitive LH surges if ovulation and formation of corpora lutea were prevented. To test this hypothesis, rats were ovariectomized at 10:00 AM on proestrus (day 1) and blood samples were obtained at 12:30 and 5:00 PM on days 1 to 4. Although an LH surge occurred on proestrus, no subsequent LH discharges were observed. The absence of an LH surge on consecutive days could not be attributed to a difference between the endogenous estradiol stimulus and the exogenous stimulus which elicited repetitive LH surges in long-term ovariectomized rats. Rather, it was determined that in recently ovariectomized rats, in contrast to long-term ovariectomized rats, a daily LH surge occurred only if elevated serum estradiol concentrations were maintained. Thus, by leaving implants in place, an LH discharge was elicited on 10 consecutive days. These results support the concept that a neural signal for the LH surge is emitted each day throughout the estrous cycle of the rat, and that prolonged maintenance of elevated circulating estradiol concentrations is essential for the expression of these signals.


Micropuncture and microanalytic studies of the effect of vasectomy on the rat testis and epididymis.

Micropuncture techniques adapted for in vivo use in the male reproductive tract were used to study the effect of vasectomy on the concentration and morphology of spermatozoa in the seminiferous tubules and ductus epididymidis of the rat. Regardless of surgical technique, 85% of all rats which had previously under vasectomy developed a speratic granuloma at the proximal end of the ligated vas deferens. Vasectomy did not affect the weights of the ipsilateral (vasectomized) testes. Vasectomy without granuloma formation resulted in an elevation in the weight of the ipsilateral epididymis and an increase in the concentration of spermatozoa in the ipsilateral cauda. Vasectomy complicated by granuloma formation caused a significant increase in the ratio of the spermatocrit in the seminiferous tubule to that in the caput. In the vasectomized rat without granuloma, significantly more abnormal spermatozoa were in the caput than in the cauda; in the normal rat, the concentrations of abnormal spermatozoa in the two regions were not significantly different. Vasectomies with and without granuloma formation are distinct phenomena and should be investigated separately.


A respiratory valve for rapid switching between two gas mixtures.

We have devised a respiratory valve that facilitates rapid and silent breath-to-breath switching between two gas mixtures, under remote control. It utilizes two inspiratory Loven-type valve elements, one for each gas mixture, either of which can be held closed with an electromagnet. Any type of valve element can serve as the expiratory valve. We have used a small respiratory valve with goats and a larger model for both goat and human use.


Synthesis of glycolipids and phospholipids in hamster cells: dependence on cell density and the cell cycle.

Sakiyama et al. ('72) reported the isolation of a line of hamster cells (NIL 1c1) which contains only three glycolipids, hematoside, ceramide monohexoside and ceramide dihexoside. The incorporation of radiolabeled palmitate into hematoside during 24 hours was three fold higher in normal confluent, non growing cells than sparse, growing ones. Polyoma transformed cells did not exhibit this effect. We have continued studies with the untransformed cell line and have found that the higher incorporation of radiolabeled palmitate into hematoside by normal confluent cells is not due to a higher rate of turnover of hematoside at confluence but represents a true chemical increase. We have also found that this increase is not a gradual process during cell growth but instead occurs only when the cells become confluent and stop growing. The increase of hematoside at confluence is not due to a higher rate of synthesis of hematoside during G1, relative to the other phases of the cell cycle. We found the rate of synthesis of hematoside to be constant throughout the cell cycle. The rate of synthesis of phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol and sphingomyelin was also studied as a function of the cell cycle. We found no large differences in the synthetic rate of any given phospholipid species throughout the cell cycle although the rate of synthesis of the glycerophospholipids was somewhat higher during late G1 and S. We did, however, find major differences in the rates of synthesis of the different phospholipid species.


An epidemic of echovirus 18 meningitis.

The first reported outbreak of echovirus 18 meningitis in the United States occurred during the summer of 1972 in Durham, North Carolina. One hundred three cases of aseptic meningitis were seen at Duke University Medical Center over a period of four months. Most of the patients were less than 25 years old, black, and residents of Durham County or nearby counties.. Symptoms included headache (92%), fever (76%), nuchal rigidity (67%), and nausea and/or vomiting (51%). In contrast to previously published reports of echovirus 18 infection, diarrhea and rash were infrequent (6% and 5%, respectively). There were no deaths. Counts of white blood cells in the cerebrospinal fluid ranged from 0 to 1,540 cells/mm-3, but 90% of the patients had less than 500 cells/mm-3. Echovirus 11 was recovered from the cerebrospinal fluid of 55 of 78 patients, and echovirus 11 was isolated from two patients. Virus was recovered from the cerebrospinal fluid of 12 patients despite white blood cell counts in cerebrospinal fluid of less than 10 cells/mm-3.


Isobaric titration of readine monolayers: kinetics of hydrolysis of glycerides by pancreatic lipase B.

The rate of lipolytic enzyme-catalyzed reactions yielding water-soluble products can be measured by isobaric titration. The method is based upon the measurement of the amount of substrate that must be added to a monalayer to maintain constant surface pressure during the course of the enzymatic reaction. The rate constants determined for the hydrolysis of trioctanion and 1,2-diotanoin by pancreatic lipase were identical with those determined by the variable surface pressure method and by a radioactive substrate technique. This direct titrimetric method has a wider dynamic range and more versatility for following surface reactions that previously described systems.


Experimental studies on a lethal gene (1) in the Mexican axolotl, Ambystoma mexicanum.

1. Gene ł is a recessive lethal factor found in the white strain of axolotls. Animals heterozygous for the gene are phenotypically normal. When mated with each other they give offspring 25% of which exhibit the lethal effects of the gene. 2. The ł/ł homozygotes develop normally to an advanced embryonic stage (Harrison stage 40) before the effects of the gene are first manifested. They then come to display a characteristic combination of abnormalities, including a disproportionately small head, small and poorly developed eyes, abnormal poorly developed gills, undifferentiated limb buds, and reduced overall growth rate. They may feed briefly, but soon stop and invariably die within a few weeks of the time of hatching. 3. The action of gene ł has been analyzed by parabiosing mutant and normal embryos, and by grafting various organ primordia reciprocally between mutant and normal embryos. Parabiosis to normal embryos fails to correct the abnormalities of the mutants, although their survival may be somewhat prolonged. Grafts of mutant organ primordia (eye, limb, gill, pronephros, gonad, head) also invariably fail to show improved development or to survive on normal hosts; normal organ primordia develop normally on mutant hosts so long as the mutant survives. These experiments indicate that gene ł is a recessive autonomous cell lethal affecting all of the organ systems during late embryonic and early larval development.


One-way fluxes of alpha-aminoisobutyric acid in Ehrlich ascites tumor cells. Trans effects and effects of sodium and potassium.

One-way fluxes in the steady state and one-way influxes at zero intracellular concentrations were measured for alpha-aminoisobutyric acid (AIB) in Ehrlich ascites tumor cells at 32 degrees C. The one-way fulxes show trans effects in the concentration of AIB and are dependent on sodium levels. The one-way fluxes for initial influx and for the steady state were fitted with the equations derived for the frequently used two-state carrier model. Estimates of the parameters of these equations were obtained with use of nonlinear least squares. These gave relatively good fits of the flux data and the data on steady-state distribution ratios. The two-state carrier model predicted a trans inhibition of one-way influx and a trans stimulation of one-way efflux. The former phenomenon has been demonstrated for AIB transport in Ehrlich ascites cells and there is evidence, through less firm, for the latter.


Chronic subdural hematoma in adults. Influence of patient's age on symptoms, signs, and thickness of hematoma.

The relationship of age to clinical and pathological findings was analyzed in 109 adult patients operated on because of chronic subdural hematoma. A well-formed membrane on the inner and outer surface of the hematoma was used as the criterion for chronicity of the hematoma. Younger patients had more evidence of increased intracranial pressure; older patients had more evidence of mental deterioration and pyramidal tract lesions. The interval from trauma to operation was shorter in the young patients. The thickness of the hematoma as measured from angiograms increased with the age of the patient. The cause of this difference is discussed.


Digestibility of starches in infants and children.

The digestibility of various starches has been studied in normal infants of different ages. During balance periods of 3 days, while the infants were receiving known dietary quantities of the starch to be tested, the fecal content of lactic acid, glucose, dextrins, and starch was measured. After the first year of life, children were able to absorb almost completely 170 gm/m2 of body surface of cooked wheat starch given in the form of biscuit or macaroni. A lower absorption coefficient was found for potato starch given in the form of biscuit. Cooked wheat, tapioca, corn, rice, and potato starch in amounts of 45 and 85 gm/m2/day, respectively, for 1- and 3-mo-old infants, were almost completely absorbed. In 1-mo-old infants larger amounts (110 gm/m2/day) of cooked rice starch were well tolerated; it should therefore be possible to provide a large part of the carbohydrate requirements of infants from the first month of life with cooked starches.


Plasma membrane components of skin fibroblasts from normal individuals and patients with cystic fibrosis.

Plasma membranes have been isolated without proteolytic modification from fibroblast lines derived from patients with CF, from heterozygous parents, and from normal children. The cells had been grown in the presence of 3H- OR 14C- labeled L-leucine, D-glucosamine, and L-fucose. Membranes were mixed in suitable combinations to allow comparisons to be made between the different cell types. No differences in the plasma membrane composition, as revealed by divergence in 3H- or 14C-profiles, could be detected after gel electrophoresis. Identical protein and glycoprotein components were present in approximately similar amounts in all groups of cells;


The interaction of egg yolk and ram spermatozoa studied with a fluorescent probe.

The flourescent membrane marker, 1-anilinoaphtalene-8-sulphonate (ANS) was used to investigate the attachment of egg-yolk to the plasma membranes of ram spermatozoa. The degree of fluorescence was assessed using a subjective scoring system. It was found that egg yolk competes with ANS for sites on the plasma membrane. When the diluent contained 10% egg yolk, no ANS could be detected on the membranes. Egg yolk attached to the plasma membrane could be removed by washing twice with a yolk-free diluent. Loss of sperm motility in the presence of ANS was observed but some spermotozoa remained motile after incubation at 37 degrees C for 15 min with 2mM-ANS. Egg yolk protected spermatozoa against this loss of motility. It is suggested that egg yolk protects spermatozoa during chilling and freezing by its attachment to the sperm plasma membrane.


Production of carbon dioxide in vitro by blastocysts from intact and ovariectomized mice.

'Normal' and 'delayed implanting' mouse blastocysts were incubated in non-radioactive culture medium for various lengths of time (preincubation), and then placed in culture medium with (14-C)-glucose for 2 hr. The rate of embryonic CO-2 given off by the blastocysts. Normal embryos were unaffected by the length of preincubation. By contrast, 'delayed implantating' embryos had a low level of CO-2 production with short preincubations (i.e. less than 2 hr), but approached  the normal range with longer preincubations (i.e. more than 8 hr) and thus, were 'activated ' in vitro. Incubation of the 'delayed implanting' embryos with actinomycin D prevented the expected increase in CO-2 production, indicating that synthesis of new RNA  is necessary for their activation. Preincubation of normal and 'delayed implanting' blastocysts with oestradiol-17 beta and/ or progesterone had no effect on the level of CO-2 production, suggesting that the hormones do not directly stimulate or inhibit carbohydrate metabolism in the embryos.


Decryptification of acid phosphatase in arthrospores of Geotrichum species treated with dimethyl sulfoxide and acetone.

Decryptification of acid phosphatase in Geotrichum sp. arthrospores was accomplished using acetone or dimethyl sulfoxide treatment. Both dimethyl sulfoxide and acetone irreversibly destroyed the integrity of the spore membranes without solubilizing acid phosphatase.


Spoilage association of chicken breast muscle.

The ability of pure cultures of bacteria isolated from spoiling chicken breast muscle to produce strong off-odors was tested by using sterile breast muscle sections. The incidence of organisms capable of producing strong off-odors and changes in flora during storage of naturally spoiling muscle at 2 C was traced, and the relationship between bacterial type and off-odor production was noted.


Nature of the surviving plaque-forming unit of reovirus in water containing bromine.

The initial inactivation of reovirus in water containing 3 to 7 microns M bromine as HOBr was very rapid. Electron microscopy revealed extensive physical damage to the virions in as little as 1 min, but none were degraded beyond recognition. As treatment time continued, the reaction rate decreased toward a plateau of resistance, usually at about the 10-4 survival level; still no particles were lost. Progeny grown from these resistant plaque-forming units (PFU) were no more resistant to HOBr than the parent cultures. Small-number aggregation (adhering groups of two to ten virions counted by electron microscopy) had no detectable effect on the level of persistant PFU. Large aggregates seemed to be involved. Sonic treatment at 20 kHz after bromine exposure increased survival PFU titer 10- to 43-fold. Virus exposed to light centrifugation prior to bromine treatment did not show the plateau of resistance. Surviving PFU sedimented faster in a shallow sucrose gradient than single virions. Large aggregates were apparently too few to be counted by electron microscopy, but their penetration and inactivation must be achieved by any disinfectant chosen to rid water of reovirus.


Factors influencing the prognosis of vascular disease in insulin-deficient diabetes of long duration: a seven-year follow-up.

Fifty-one insulin-dependent nonobese diabetics with duration of disease from 15 to 40 yr were reassessed after 7 yr. Those presenting with clinical vascular disease, hypertension, or elevated fasting triglycerides initially were found to have a bad prognosis. Serum cholesterol fasting blood sugar, age, or duration of diabetes were not related to outcome, Acute insensitivity to intravenous insulin was correlated with presence of initial vascular disease and was significantly related to both death and clinical deterioration in either large or small vessels over the period of follow-up. Insulin sensitivity was reproducible and may be of value in predicting the progression of long-term vascular changes in the insulin-requiring diabetic.


Psychologic and neurologic consequences of partial and complete cerebral commissurotomy.

Preliminary psychologic testing was carried out on four patients who had undergone surgical sectioning of a portion or all of the corpus callosum and anterior commissure as a treatment for uncontrollable seizures. Results confirm earlier findings indicating the importance of the forebrain commissures in the interhemispheric exchange of a variety of sensory and motor information, and demonstrate that particular portions of the commissural system are responsible for transferring the information of specific sensory modalities. The patients also showed surprising abilities in performing complex tasks assumed to require integration of information from both hemispheres.


The spinal evoked response in infants and children.

Summated responses to peroneal nerve stimulation were recorded from surface electrodes placed over the spine of 60 infants and children. These potentials generally were greater in amplitude in infants than in older children. Over the cauda equina and rostral cord, initially positive triphasic potentials were recorded. Over the caudal cord, complex potentials were recorded in children less than three years of age. The conduction velocity of the response from midlumbar to lower cervical recording sites was less in infants than in older children and progressively increased with age, reaching adult values after the fourth year.


Judgment of the visual vertical and horizontal in patients with Parkinsonism.

Judgment of the visual vertical and horizontal in the upright body position was abnormal in 19 (29 percent) of 66 patients with Parkinson's disease. The magnitude of errors correlated with the degree of rigidity and of tremor in the limbs, but not with bradykinesia or other clinical features. The results suggest that the effect on visual perception of the vertical and horizontal coordinates in patients with parkinsonism is brought about by specific changes in the basal ganglia and is not, as in the case of other visual-motor tasks, determined merely by the overall severity of cerebral pathology.


Progressive nuclear ophthalmoplegia associated with mental deficiency, lingua scrotalis, and other neurologic and ophthalmologic signs in a family.

Six members of a family--the mother, three daughters, and two sons--have a unique syndrome consisting of congenital external ophthalmoplegia, bilateral facial weakness, lingua scrotalis, progressive chorioretinal sclerosis, and an intellectual deficit. Bilateral ptosis and almost complete ophthalmoplegia were found in three of the family members, bilateral facial weakness in two, and Parinaud's syndrome and convergence paresis in one. Electromyographically, a lesion of the lower motor neurons--"nuclear ophthalmoplegia"--was found. Three members of the family had different stages of progressive chorioretinal sclerosis and two had myopia. All the family members had lingua scrotalis, and all of those who had ophthalmoplegia had low IQs. Electroretinographic reactions were subnormal or absent in patients with chorioretinal degeneration. It was concluded that an extensive abiotrophic process, genetically conditioned, was a possibility.


Myasthenia gravis with features of the myasthenic syndrome. An investigation with electrophysiologic methods including single-fiber electromyography.

A 47-year-old woman had myasthenia gravis with only moderate weakness and a consistently poor response to anticholinesterase medication. She was investigated with routine electrophysiologic studies and single-fiber electromyography. The studies showed a limited effect of anticholinesterase medication. There was a decrement to 2 Hz stimulation of not less than 25 percent regardless of medication and administration of edrophonium. With faster rates of stimulation (10 to 20 Hz), there was a facilitation up to 190 percent. In addition, with postcontractive or post-tetanic potentiation the action potential in the abductor digiti minimi muscle was increased from the initial value of 2.5 mv or less to up to 6 mv. Single-fiber electromyographic investigations showed increased jitter and blocking with little response to drugs, as well as facilitation in a large number of motor end-plates in association with both voluntary activity and repetitive stimulation. The findings indicated a mixture of phenomena seen in myasthenia gravis and the myasthenic syndrome.


The syndrome of increased intracranial pressure without localizing signs: a reappraisal.

One hundred adult patients with headache, papilledema, and no localizing signs were evaluated prospectively and followed for up to 54 months. No patient with this syndrome who had a normal mental status, negative brain scan, and normal electroencephalogram was found subsequently to harbor a mass lesion. Benign intracranial hypertension was the final diagnosis in 71 percent of the patients studied. Lumbar puncture was a safe and helpful diagnostic procedure, and in no case was subsequent neurologic deterioration noted.


Multiple sclerosis and elevation of cerebrospinal fluid vaccinia virus antibody.

Thirty percent of 33 patients with a clinical diagnosis of multiple sclerosis and an elevation of cerebrospinal fluid (CSF) immunoglobulin G/albumin ratio greater than 2 standard deviations above the mean had elevation of the CSF vaccinia neutralizing antibody titer. Elevated titers were found in 1 of 23 patients with non-multiple sclerosis neurologic diseases and in none of the normal control patients. No linear correlation was found between the magnitude of the relative or absolute CSF immunoglobulin G concentration and the magnitude of the CSF vaccinia neutralizing antibody titers.


Hydatidiform mole: diagnosis, management, and long-term followup of 347 patients.

This report concerns 347 patients with primary hydatidiform moles studied during the first 6 years (1966-1972) of operation of the Southeastern Regional Trophoblastic Disease Center. Aside from a decreased incidence, molar pregnancy in the United States follows a pattern similar to that elsewhere in the world. Abnormal bleeding is the key to early diagnosis, and the frequent use of sensitive HCG assays is the key to proper followup. Twenty percent of patients with hydatidiform moles can be expected to develop subsequent malignant sequelae. Bilateral ovarian enlargement and/or a large-for-dates- uterus should alert the physician to a greater potential for this outcome. Spontaneous elimination of HCG from the circulation following moler pregnancy, as indicated by sensitive assay, would predict a benign postmolar course; no patient in the current series who once achieved undetectable levels of HCG developed malignant trophoblastic disease.


Ectopic endometrium in omentum. Uterine perforation by Lippes loop.

A case of ectopic endometrium in the omentum following perforation of the uterus by a Lippes Looptm is reported. Evidence is presented substantiating Sampson's theory of endometrial implantation.


Incidence of galactorrhea in ovulatory and anovulatory females.

The incidence of galactorrhea in 480 ovulatory females was compared to that in 383 anovulatory females. One percent of the ovulatory and 3.2% of the anovulatory patients had bilateral galactorrhea. The probability (P) of these two groups being from the same population was less than 0.02.


Radiological diagnosis of mass lesions within and adjacent to the foramen magnum.

Masses within or adjacent to the foramen magnum may present difficult clinical problems. They may sometimes be misdiagnosed as degenerative disease of the central nervous system, cervical spondylosis, or even cervical disk disease. In most cases, roentgenographyis necessary for proper diagnosis. The anatomy of the region of the foramen magnum is reviewed and 13 cases representing various diseases are presented. Alterations in the regional arterial and venous anatomy are emphasized.


Mercury levels in whole blood of Saskatchewan residents.

The study was undertaken to establish whole blood mercury levels in the Saskatchewan population and to identify characteristics of individuals with higher blood levels. The mean blood mercury level was 6.7 ng/ml, the median level 5 ng/ml and the range 1 to 42 ng/ml. Native persons living in northern Saskatchewan who had recently eaten local fresh-water fish had the higher levels. A greater consumption of fish and higher blood mercury levels were recorded during the fresh-water fishing season.


The relationship between mercury levels in maternal and cord blood.

The object of the study was to discover the relationship between mercury levels in maternal and cord blood. Paired whole blood samples, maternal and cord blood were analysed for total mercury content; 45 paired samples from non-fish-eating women in southern Saskatchewan demonstrated no significant differences in mercury levels between maternal and cord blood; 43 paired samples from fish-eating women in northern Saskatchewan demonstrated a significant difference, cord blood levels being higher. The significant is discussed.


Daily rhythm in human urinary melatonin.

The melatonin in urine samples from six healthy adult volunteers was concentrated on Amberlite XAD-2 resin, eluted with organic solvents, and quantitated by use of a bioassay technique (the dermal melanaphore response of larval anurans to melatonin in their bathing medium). The melatonin content of samples collected between 11 p.m. and 7 a.m. was, in each case, several times higher than that of samples collected between 7 a.m. and 3 p.m. or between 3 p.m. and 11 p.m.


Growth, behavior, and brain catecholamines in lead-exposed neonatal rats: a reappraisal.

Daily oral administration of lead to newborn rats has no adverse effect on their body growth. Lead-treated rats were more active than age-matched controls. Endogenous levels of brain dopamine were unchanged, whereas norepinephrine was increased, suggesting a possible relationship between lead exposure during earliest developmental periods, increased motor activity, and brain norepinephrine, and not brain dopamine as previously postulated.


Secretion of a nerve growth factor by primary chick fibroblast cultures.

Normal primary chick embryo fibroblast cultures product a nerve growth-promoting factor which cross-reacts with monospecfic antibody to pure male mouse submaxillary gland nerve growth factor (NGF). When taken together with the earlier demonstration that mouse L2 CELLS AND 3T3 cells also produce an NGF-like protein, these findings suggest that secretion of this factor may be a general property of fibroblast.


Morphine-dependent rats: blockade of precipitated abstinence by tetrahydrocannabinol.

Male rats were implanted subcutaneously with a pellet containg 75 milligrams of morphine base or placebo, and naloxone hydrochloride (4 milligrams per kilogram of body weight) was administered 72 hours later. Treatment with delta-9-tetrahydrocannabinol (2, 5, or 10 milligrams per kilogram) 1 hour before maloxone administration significantly reduced the intensity of abstinence; the two higher doses blocked the appearance of wet shakes and escapes, diarrhea, and increased defecation. delta-9-Tetrahydrocannabinol did not induce abstinence itself, and prior treatment with cannabidiol was ineffective in reducing naloxoneprecipitated abstinence in animals with morphine pellets. These data suggest that delta-9-tetrahydrocannabinol may be of value in facilitating narcotic detoxification.


The use of 6alpha-and 6beta-carboxymethyl testosterone-bovine serum albumin conjugates in radioimmunoassay for testosterone.

The synthesis of 6alpha- and 6beta-testosterone-bovine serum albumin (BSA) conjugates is described. 6beta-Carboxymethyl-4-androstene-3,17-dione was prepared by a route analogous to that described earlier for 6beta-carboxymethyl progesterone. Sodium borohydride reduction of the 3 and 17 keto groups and subsequent selective oxidation of the resulting 3beta, 17beta-diol using MnO2 provided 6 -carboxymethyl testosterone. Further acid catalyzed epimerization of the C-6 center gave the isomeric 6alpha-carboxymethyl testosterone. The 6alpha- and 6beta-testosterone derivatives were attached to BSA via a mixed anhydride coupling employing tributylamine and i minus-butylchlorocarbonate. For each molecule of BSA, the 6alpha- and 6beta-conjugates contained an average of 23 and 20 steroid residues, respectively. Antisera to the conjugates exhibited similar high specificities toward various steroids, the only incidence of serious cross-reaction being the expected case of dihydrotestosterone.


Considerations of delta 5-pregnenediol formation in ovarian tissue.

20Alpha-Hydroxypregn-4-ene-3-one (20alpha-DHP) in ovarian tissue could be formed directly from progesterone (Pathway 1) or from pregnenolone via a delta 5-intermediate, pregn-5-ene-3beta, 20alpha-diol (Pathway 2). The participation of Pathway 2 is demonstrated to the extent that pregnenediol can be formed from pregnenolone and that the delta 5-diol, in turn, can be a precursor to 20alpha-DH P in vitro, using ovarian tissue from cycling rats by both flask incubation and superfusion techniques. Pathway 2 would allow greater flexibility and local regulation with respect to potential steroid sulfate conjugates of delta 5-3beta-OH intermediates. The existence of two pathways leading to 20alpha-DH P could explain the occurrance of variable levels of this steroid without a necessary direct or inverse relationship to progesterone secretion levels at different stages of the estrous cycle.


Direct isolation of mycoplasmas and acholeplasmas from sera and kidneys of calves.

Kidneys and sera of calves from various farms and primary kidney tissue cultures were tested for mycoplasma and acholeplasma contamination. Altogether 24 strains belonging to Mycoplasma arginini and Acholeplasma axanthum were isolated from tissue cultures, kidneys and sera. The same species were detected from lungs and peribronchial lymph nodes of calves, together with A. laidlawii, A. modicum and M. bovirhinis species. There was a close correlation between the mycoplasma content of tissue cultures, sera and kidneys and the clinical picture observed in the farm, as well as between the quality of tissue cultures and the mycoplasma content of organs, sera and tissue cultures.


Life strengths and life stresses: explorations in the measurement of the mental health of the Black aged.

A study of Asian American patients receiving care in community mental health facilities suggests that rates of psychopathology among Asain Americans have been underestimated and that treatment facilities are not responding to the needs of this group.


Certain physiochemical properties of uterine tubal fluid, follicular fluid, and blood plasma in the mare.

Uterine tubal fluids were collected twice a day from mares for 5 consecutive estrous cycles between March 15 and September 1. Follicular fluids were aspirated from the follicles of exteriorized ovaries of 3 mares between days 2 and 5 of estrus. Uterine tubal fluid and follicular fluid were analyzed for osmolarity, dry matter, total lipids, total free fatty acids, glucose, fructose, and lactic acid. Blood samples were collected (jugular venipuncture) throughout the estrous cycle, and the same physical and biochemical analyses were made on blood plasma. A difference (P less than 0.01) was found for osmolarity between uterine tubal fluids collected during estrus and those collected during anestrus. The osmolarity of uterine tubal fluid during anestrus was greater than that of blood plasma; follicular fluid was similar in osmolarity to blood plasma. The dry matter in blood plasma was greater (P less than 0.01) than that in either uterine tubal fluid or follicular fluid. Cyclic variations in dry matter content were not observed in uterine tubal fluid. Total lipids in blood plasma and follicular were greater (P less than 0.01) than those in uterine tubal bluid. The concentration of total lipid in uterine tubal fluid was similar during estrus and anestrus. Myristic acid (C14:0) in blood plasma and myristoleic acid (C14:1) in uterine tubal fluid were the only free fatty acids that had cyclic variation. The fatty acids in the greatest concentration in uterine tubal fluid and blood plasma were palmitic acid (C16:0) and linoleic acid (C18:2). Concentrations of linoleic acid and stearic acid (C18:0) were greater (P less 0.01) in follicular fluid than in uterine tubal fluid or blood plasma. Only trace amounts of glucose were detected in uterine tubal fluid, whereas a considerable amount of glucose was found in follicular fluid. Fructose was not detected in any of the fluids. Lactic acid concentrations did not differ between estrus and anestrus. Lactic acid concentration was significantly greater (P less than 0.01) in uterine tubal fluids and follicular fluids than in blood plasma.


Relationship between Mycobacterium simiae and Mycobacterium habana.

Strains of the species Mycobacterium simiae give a positive niacin test. On the basis of their cultural and biochemical characteristics and by seroagglutination they can be classified into 2 subspecies. (1) The strains of serotype M. simiae 1 hydrolyze urea regularly and nicotinamide and pyrazinamide irregularly. They are photochromogenic after prolonged exposure to light. (2) The strains of serotype M. simiae 2 hydrolyze urea only. Three of 4 strains are scotochromogenic; the fourth has a pale pink pigment. Two of these strains possess alpha- and beta-esterase activity. The other two are negative in this test. Strains of M. habana are culturally and biochemically identical with the serotype M. simiae 1 and show the same serologic specificity as M. simiae 1. M. habana sera, after having been absorbed by M. simiae 1, retain a small amount of agglutinins specific for M. habana. We believe that the M. habana strains belong to the species M. simiae and are closely related to the serotype M. simiae 1.


Human pulmonary adiospiromycosis.

Emmonsia crescens, a fungus that causes granulomatous pulmonary adiospiromycosis, is an uncommon human pathogen. Histopathologic and ultrastructural evaluation of a new case of human adiospiromycosis from Guatemaia showed pulmonary granulomatosis in respose  to the inhaled spores of the fungus. The wall of each spore consisted of three zones. A fenestrated layer was clearly demonstrated within the middle zone. Neither budding nor endosporulation was detected. Our findings support the pathogenetic view that E crescens produces local changes by progressive enlargement of the inhaled spores and surrounding granulomas. Characteristically, the fungus does not propagate or disseminate within the lung


Ultrastructure of gonadoblastoma.

We examined, ultrastructurally, gonadoblastomas from two phenotypic females with a 46,XY and 46,XY/45, XO genotype, respectively. Ultrastructurally, germ cells of gonadoblastoma resembled immature gonocytes; it was not possible to classify them into exact developmental stages given for normal fetal testes or ovaries. In the dysgerminomatous part of the first tumor, germ cells showed ultrastructural signs of differentiation comparable to abortive spermatogenesis as seen in testicular but not ovarian dysgerminosa. The  sex cord cells resembled either Sertoli, granulosa, or ovarian stromal cells. The stroma surrounding the epithelial nests resembled the ovarian stroma and contained interstitial cells like Leydig or ovarian hilar cells or both. The epithelial nests of gonadoblastoma were surrounded by laminar multilayered basement membranes. The hyaline masses inside the tumor nests were composed of the same material.


Chromium-51 release from human blood platelets by anti A antibody.

Platelets were obtained by differential centrifugation from Group A donors and were incubated with Na2-51Cr04. After washing to remove excess chromium, the platelets were exposed for one hour to Anti A antibody which showed agglutinating activity only. Chromium release was no greater than that of controls. Hemolytic Anti A in the presence of rabbit complement released 15 percent more chromium than controls. Anti P1A1, a platelet specific antibody, when incubated with platelets in the presence of rabbit complement released 45 percent more chromium than controls. It appears that Anti A antibody is not as destructive to platelets as a platelet specific antibody is, even when the Anti A antibody shows hemolytic activity with red cells. These observations are in agreement with previous in vivo studies of ABO incompatible platelets.


Approach for an equation of state for adsorbed protein surfaces.

A surface equation of state for polymer interfaces is obtained by equating the chemical potentials of the solvent in the bulk and surface phases. This equation of state contains the fraction of the surface covered with polymer and the surface activity coefficient as parameters. These parameters may be obtained by measuring the thermodynamic modulus of elasticity. Moreover, if the amount of protein in the interface is known the degree of folding in the surface may be evaluated. The present theory was applied to adsorbed beta-lactoglobulin in surfaces. The results are in agreement with qualitative equations and results from other sources.


Hydrodynamic structure of bovine serum albumin determined by transient electric birefringence.

Birefringence relaxation studies on bovine serum albumin (BSA) reveal transient decay described by a double exponential process. The values of the relaxation times lead to estimation of the size of the equivalent ellipsoid of revolution for BSA. Previous measurements of transient birefringence for BSA have shown a single relaxation process, since the apparatus used in obtaining those data was not fast enough to detect the faster relaxation process.