Cytology of the pineal gland: changes produced by various treatments.

The cytological appearance of the pineal body is related to stage of development or age, time of day, exposure to illumination, season of the year, and reproductive state. Experimental manipulations that alter the normal cytology of the pineal include hypophysectomy, administration of any of several hormones or drugs, blinding, denervation and exposure to stressful influences such as heat or cold. The effects of blinding are similar to the effects of continuous darkness on the pineal's cytology. Ultrastructural examinations reveal a number of changes in the organelles, especially an increased number of vesicles and complex membranous whorls. These features suggest heightened activity and generally are coincident with sexual quiescence. Membranous whorls also may be induced by cold exposure. Prolonged or continuous illumination leads to a reduction in the size of pinealocytes and to changes in their organelles that suggest reduced activity. Such alterations can often be correlated with heightened sexual activity. Sympathetic denervation of pineal glands also results in atrophy of the pinealocytes. Reproductive condition is reflected in the appearance of the pinealocytes. The estrous cycle, pregnancy, castration and the administration of gonadotropins or gonadal steroids affect pinealocyte structure. A feedback system involving the gonads and pineal gland is indicated.


Melatonin in humans physiological and clinical studies.

Studies are reported of the variation of melatonin in serum, plasma urine and cerebrospinal fluid in normal subjects and in patients with various diseases. The diurnal variation of plasma and urine melatonin found in healthy controls on a regular dark-sleep pattern persisted when the subjects slept in light. The effect of sleep deprivation and of rapid light exposure at night is reported. There was a correlation between melatonin in morning urine and plasma at 2 a.m. Four hours of extended darkness in the morning as well as a 9-hour shift of sleep and activity cycles following travel affected the melatonin rhythm. The night increase in plasma melatonin preceeded both the cortisol and prolactin rise. A single oral dose of 4.3 X 10(5) nmol of melatonin given to a 44-year-old healthy male gave a peak plasma value of 624 nmol/l after 30 min. Plasma melatonin was not affected by electroconvulsive therapy, TRH-injection, L-Dopa or bromoergocryptine orally. Patients with alcoholism, migraine, postoperative pinealoma, panhypopituitarism, hereditary dystonia and schizophrenics on propranolol exhibited a decreased amplitude of their diurnal rhythm of melatonin. Two patients with pituitary tumors had occasional high levels of plasma melatonin. The change in melatonin secretion in human is apparently controlled by a mechanism which is at least party influenced by environmental lighting conditions, drugs and different disease states.


Pineal research: the decade of transformation.

In a little more than a decade (1954--1965), the pineal gland was demonstrated to be an active neuroendocrine transducer in contrast to a functionless vestige as earlier supposed. The two major contributions which laid the groundwork for the development of modern pineal science were Kitay and Altschule's book The Pineal Gland (1954) and Lerner's isolation and structural work on melatonin (1958). After Lerner's discovery, biochemists, anatomists, and physiologists determined much about the structure and function of the pineal gland. In 1965, Wurtman and Axelrod tied this earlier work together by characterizing the pineal as a neuroendocrine transducer.


Neural control of pineal function in mammals and birds.

Pineal function in mammals is regulated by a system with four major neural components. The first is a retinohypothalamic projection from the ganglion cells of the retina to the suprachiasmatic nucleus of the hypthalamus. The suprachiasmatic nucleus appears to function as a circadian oscillating system projecting into the hypothalamus and this represents the second component. The third component is constituted of a brainstem pathway from the lateral hypothalamus to the intermediolateral cell column of the upper thoracic spinal cord. The fourth component is the preganglionic and postganglionic sympathetic system arising from the upper thoracic cord to innervate the superior cervical ganglion which, in turn, innervates the pineal gland. No direct neural control of the pineal gland has been demonstrated in birds.


Six month evaluation of thiopropazate hydrochloride in tardive dyskinesia.

Using a blind evaluation of cinematographic films of patients suffering from tardive dyskinesia we found that thiopropazate hydrochloride in a dosage up to 30 mg daily was effective in reducing the severity of the dyskinesia in most patients. The overall improvement in the group of patients studied was not significant after one or three months of therapy but was significant after six months of treatment. The administration of thiopropazate hydrochloride over a six month period did not appear to aggravate the underlying pathophysiology so that the drug could be considered likely to be safe for long-term use. The anticholinergic antiparkinsonism agent benztropine mesylate aggravated the dyskinesia to a significant degree.


Stereological approach to the study of synapse morphometry with particular regard to estimating number in a volume and on a surface.

The paper presents a system of stereological formulae which are suitable for the quantitative ultrastructural characterization of synapses. Attention is given first to the question of deciding which synaptic feature to adopt as the basis for measurement. Three counting units can be recognized on electron micrographs: the bouton, the total zone of apposition of pre- and postsynaptic membranes, and the zone of paramembranous density. These may provide different numerical results. Possible units of reference are considered also and whilst emphasis is given to a volume of nervous tissue and a membrane surface of postsynaptic element, interesting alternatives are presented for the sake of completeness. Stereological parameters available for quantifying synapses (for example boutons per tissue volume, paramembranous dense zones per soma surface) are described. In addition, some new and previously neglected possibilities are included and some errors found in the literature are corrected. Worked examples of the estimation of synaptic densities are provided.


Clinical endocrinological approach to hypothalamic-pituitary disease.

The authors review the present knowledge of the hypothalamic-pituitary endocrine axis. The physiology and pathophysiology are discussed along with outlines of standard approaches to diagnosis of disorders. An appendix of useful provocative tests is included.


Dexamethasone and severe head injury. A prospective double-blind study.

A prospective double-blind study of the effects of dexamethasone administration on the outcome of patients with severe head injuries was performed. Patients were stratified for severity of neurological injury and were treated with placebo, low-dose dexamethasone (16 mg/day), or high-dose dexamethasone (96 mg/day) for a period of 6 days. Outcome was evaluated at 6 months following injury. Of the 76 patients available for analysis, a good outcome was achieved in 37% of placebo-treated patients, 44% of low-dose-treated patients, and 29% of high-dose-treated patients. These differences are not statistically significant. Similarly dexamethasone administration had no statistically significant effect on intracranial pressure patterns or serial neurological examinations during hospitalization. Gastrointestinal bleeding occurred in only one patient. Good outcome was associated with age under 10 years, lighter depth of coma on admission, and the preservation of brain-stem reflexes upon admission. A recalculation of data in previous clinical series purporting to show an improvement in outcome as a result of corticosteroid therapy shows no significant difference in outcome when steroid- and placebo-treated patients are compared. In our series, 90% of all deaths were caused by recurrent intracranial hematomas, medical complications, or diffuse brain injuries with parenchymal hemorrhage and tissue disruption -- causes of death which cannot be affected by corticosteroid therapy. The study suggests that dexamethasone in either high or low dosages has no significant effect on morbidity and mortality following severe head injury.


Free transplantation of lyophilized dura for vestibuloplasty: a clinical and histological study.

Covering epithelial defects in the oral cavity is often neccessary in maxillofacial surgery. Special problems arise in preprosthetic surgery because requisites for function and quality of epithelial grafts must be satisfied. Using free heterologous lyophilized dura grafts for vestibular sulcoplasty in 23 patients, we observed a good clinical and histological healing process. Considering the necessity of a second operation for skin or mucosal grafts (and the limited source of mucosa), we believe that the lyophilized dura can be used successfully in preprosthetic surgery.


The elective retention of vital roots for alveolar bone preservation: a pilot study.

A technique for retaining alveolar bone beneath complete dentures involving sumergence of vital canine roots below the level of the alveolar bone is reported. Early or late complications occurred in five of the eight roots retained. Radiographic and histologic examination showed the continuance of pulpal vitality and an absence of resorption of roots during the test period. The clinical at the end of 20 months' observation indicated that the procedure may provide a practical means of retaining alveolar bone for some individuals.


Delayed hypersensitivity reactions in guinea-pigs using cotton pellets; demonstration of macrophage migration inhibition activity in the cell free exudate.

Subcutaneous implantation of cotton pellets containing PPD into CFA sensitised guinea-pigs produced a reaction of having many characteristics of the delayed hypersensitivity (DH) reaction, together with less conspicuous features of a non-immunological response. The time course of the cellular response in the reaction showed a slow onset, attaining maximum levels between 18 and 24 hr. Mononuclear cells dominated the reaction from 18 to 48 hr. In animals treated with ALS the reaction diminished to the level of a non-immunological reaction. The model made it possible to detect macrophage migration inhibition factor (MIF) activity in the skin exudates. From 6--48 hr high molecular weight antigen-dependent MIF activity was found associated with immunoglobulin. At 18 hr, two types of low molecular weight MIF activity were demonstrated. One was antigen-dependent and the other was antigen-independent. Treatment of sensitised guinea-pigs with ALS abolished the appearance of these factors, suggesting that they might be related to cell-mediated immunity. At 48 hr, the low molecular weight antigen-dependent MIF activity was still evident whereas the low molecular weight antigen-independent activity was not detected. High molecular weight antigen-independent MIF activity was also found at 18 hr. No MIF activity was demonstrated in any of the control exudates.


Electron microscopy of cerebral malaria in golden hamsters (Mesocricetus auratus) infected with Plasmodium berghei.

Transmission and scanning electron microscopy of hamster cerebral malaria show that haemorrhages occur following vessel necrosis in animals with low parasitaemias. There is no concurrent thrombosis nor packing of capillaries with parasitised erythrocytes. Small vessels contain numerous monocytes which have phagocytosed erythrocytes and smaller particles of similar electron density. The monocytes attach to and migrate through the endothelium but then remain in close proximity to the vessels. Irregular dense deposits are present in the basement membrane of some animals 14 days after infection. These may be immune complexes. The pathogenesis of cerebral malaria is discussed in relation to these findings.


Fused suprarenal glands in association with central nervous system defects in the first half of foetal life.

Fifty-two abortuses with CNS defects, delivered during the first half of gestation, were examined for the presence of fused suprarenal glands. Three cases were found, the first in an 8 week embryo aborted spontaneously; the second and third in 18 and 20-week foetuses terminated for suspected CNS abnormality. All three had severe vertebral pathology in addition to the fused suprarenals and the CNS defects. It is suggested that the anomaly may be part of a widespread embryonal distortion secondary to disturbance in the vertebral axis. Since going to press, a further case of fused suprarenals has been found in a 22 week female foetus which had anencephaly and complete spina bifida, severe scoliosis and kyphosis, a small omphalocele, absence of the right kidney, a polycystic left kidney and a unicornuate uterus. This case was found among 12 further abortuses with CNS defects.


Experimental murine amyloidosis: experience with Candida albicans as an amyloidogenic agent and liver biopsy as a diagnostic tool.

We describe a method of inducing experimental amyloidosis in mice using injections of Candida albicans. Both viable and non-viable Candida produced amyloid and we compare the results with each method. Diagnosis was by liver biopsy, a technique of value in assessing the natural history of the disease. Once the amyloid had been induced, the disease always progressed until the animals died of generalised amyloidosis. This experimental model should, therefore, be suitable to use in assessing the treatment of amyloidosis.


Cystic fibrosis and malnutrition.

Cystic fibrosis as a specific disease entity has been known to be associated with malnutrition for almost half a century. The importance of the malnutrition in the disease process remains unknown, as does much information about specific nutritional deficiencies in CF. Supplements for children with CF should include extra energy as fat or carbohydrate, a form of linoleic acid that can be absorbed, hydrolyzed protein, fat-soluble vitamins with vitamins A and E in a water emulsion, vitamin B12, probably B vitamins and vitamin C, and trace minerals. Routine measurements of nutritional status, particularly in children with growth failure, should be made at regular intervals and should include a three-day diet record and a simultaneous 72-hour stool fat determination. If fat malabsorption is not controlled by pancreatic enzymes, the use of antacids or cimetidine should be considered. The true role of nutrition in patients with CF will not be known until the appropriate studies are completed.


Side effects of phenobarbital in toddlers; behavioral and cognitive aspects.

Cognitive and behavioral effects of phenobarbital in toddlers were assessed in a randomized, placebo-controlled study of patients who had had a febrile seizure. There were no significant differences in IQ (Binet or Bayley Scales) between placebo and phenobarbital groups after eight to 12 months of therapy. However, detrimental effects of phenobarbital were found in memory, for which serum level influenced scores, and in comprehension, in that length of treatment time affected performance. Hyperactivity was not seen. Behavioral changes, reported by parents, were increased fussiness and a characteristic disturbance of sleep. These changes varied in severity and were classified as transient, dose related, or unacceptable. After 12 months in the study, most parents could not distinguish between phenobarbital and placebo. Our data suggest that although most toddlers do not have major side effects from phenobarbital therapy when treated for a year, serum levels and length of time on phenobarbital should be kept at a minimum to reduce negative cognitive and behavioral effects.


Disturbed fat absorption following infectious gastroenteritis in children.

Fat absorption was studied in 10 patients recovering from an episode of acute infectious gastroenteritis who failed to gain weight despite adequate caloric intake. Three patients restudied after clinical improvement and three other infants with failure to thrive, unrelated to gastrointestinal problems, served as control subjects. Fat balance studies during the ingestion of a formula containing long-chain fatty acids demonstrated significant degrees of steatorrhea in patients (mean CFA 70.6 +/- 10.7 compared to 90.3 +/- 2.4 in control subjects). The administration of a test meal demonstrated a marked deficiency of duodenal bile acid concentration and of fat incorporation into the micellar phase in patients. Fecal bile acid excretion was significantly increased in patients (mean 33.9 +/- 11.6 microM/kg/day) as compared to control subjects (mean 13.5 +/- 3.1 microM/kg/day). Bacterial overgrowth and abnormalities of the small intestinal mucosa were not constant. Ileal dysfunction and associated bile acid loss are possible causes of disturbed fat assimilation following acute intestinal infection in children.


Brain abscess and cystic fibrosis.

Brain abscess has only recently been considered a complication of cystic fibrosis. Three patients are reported here and a fourth cited from the literature. All of our patients were young adults with advanced pulmonary disease. The bacteria involved were mouth organisms and were found in the sputum culture in only one of the patients. Resistance was present to previously given antibiotics. As patients with cystic fibrosis survive into adulthood, the risk of developing a brain abscess appears to increase.


Epidemiology of the group B streptococcus: maternal and nosocomial sources for infant acquisitions.

Repeated bacteriologic observations were made in 462 newborn infants and correlated with similar data from their mothers to evaluate the relative contributions of the birth canal  and the hospital environment to acquisition of group B streptococci in the first few days of life. Fifty-eight percent of infants whose mothers were intrapartum carriers acquired streptococci in comparison with 12% of those whose mothers were noncarriers. Acquisitions from the birth canal were not influenced by the route of delivery or the time between membrane rupture and birth, but could be related to the quantity of streptococci in maternal cultures. Observations in ten cohorts of infants, including serotyping and bacteriophage susceptibility of group B isolates, demonstrated clear-cut streptococcal spread among infants in two cohorts. Infants appeared to harbor larger numbers of streptococci at more body sites following acquisition from the birth canal than after acquisition from the hospital environment.


Functional analysis of neutrophil granulocytes from healthy, infected, and stressed neonates.

Neutrophil granulocyte function was assessed in 17 well term infants, 14 stressed infants, and eight infants with group B streptococcal infection. Chemiluminescence production elicited by opsonized zymosan or by a wild strain of type III group B streptococci, as well as phagocytosis and killing of streptococci, were measured. Chemiluminescence production by PMNs of term neonates in response to opsonized zymosan or group B streptococci was equal to that of adult controls. In contrast, six of nine stressed or infected neonates had depressed CL responses upon zymosan challenge. When opsonized type III group B streptococci were used to elicit CL, seven of ten stressed or infected infants had markedly depressed responses. Phagocytosis, as determined by a radiolabeled bacterial uptake technique, was normal in the healthy and stressed neonates. Depressed CL production by the PMNs of stressed or infected neonates was associated with impaired intracellular bactericidal activity, however. These studies indicate that stressed or infected neonates have impaired leukocyte metabolic activation that may be associated with depressed bactericidal activity. Such impairment may contribute to the morbidity and mortality observed in serious neonatal infections.


Infant care: cache or carry.

To test the hypothesis that a characteristic infant-care pattern existed during most of human history, contemporary hunter-gatherers in a representative sample of world cultures were examined. Numerically coded measures of infant care revealed a uniform pattern. Mothers are the principal caregivers, providing extensive body contact day and night and prolonged breast-feeding. When not carried, the baby of hunter-gatherers has complete freedom of movement. Care is consistently affectionate, with immediate nurturant response to crying. Nonetheless, in most groups, children achieve early independence and by 2 to 4 years spend more than half the time away from the mother. In the United States this pattern of carrying that endured for one to three million years has been replaced by one resembling nesting or caching. Infants spend little time in body contact with caregivers and their movements are restricted by playpens, high chairs, or cribs. Of the minority who are breast-fed, half are weaned within a few weeks. Separate sleeping arrangements and delayed response to crying are regularly recommended. These remarkable transformations may profoundly alter infant development and maternal involvement.


The effect of an alexidine mouthwash on plaque and gingivitis.

A clinical study was conducted on the effects of an alexidine or placebo oral rinse on plaque and gingivitis. Forty-two male subjects rinsed for 54 days while continuing toothbrushing. This was followed by 4 days of mouthrinsing only. The alexidine mouthrinse significantly reduced the plaque index when used in conjunction with toothbrushing and also when brushing was discontinued. The gingivitis results were inconclusive.


A rapid chairside test for the severity of periodontal disease using gingival fluid.

A study was done in an attempt to develop a simple test for the severity of periodontal disease. Gingival fluid collected on filter paper was tested for protein content, and the resulting color was compared to standard color filters. Tissue was excised and prepared for histologic examination. The inflammatory cell infiltrate on each slide was graded on a scale of zero to three. Zero was least and three was the highest number of inflammatory cells. The results indicate that the white cell infiltrate graded 0 or 1 on the histologic inflammatory index has a color index of B 1/8 TO B1 whereas the tissue graded 2 or 3 HII has a range of B2 to B6 on the color scale. This test can give the dental practitioner a general idea of the severity of the inflammation.


Hand instrumentation versus ultrasonics in the removal of endotoxins from root surfaces.

In this study, the average net total endotoxin in the solubilized extracts from each sample were healthy teeth, 1.46 ng/ml; periodontally diseased teeth, 169.5 ng/ml; ultrasonically scaled teeth, 16.8 ng/ml; root planed teeth, 2.09 ng/ml. The material that was extracted and assayed was not conclusively proven to be endotoxin, but recent studies suggest it was. Meticulous root planing as performed in this study produced values similar to those for unerupted periodontally healthy teeth. Ultrasonic scaling resulted in endotoxin values approximately eight times greater.


The infrabony pocket and its relationship to trauma from occlusion and subgingival plaque.

The role of trauma from occlusion and subgingival plaque in the pathogenesis of the infrabony pocket as observed in the radiograph was studied in 48 teeth which had to be extracted because of advanced periodontal disease. Prior to extraction the teeth were examined with regard to the degree of mobility and the direction of the horizontal components of the masticatory forces. Following extraction, the teeth were stained and examined under the stereomicroscope. When the tooth is adequately stained, the subgingival plaque and the remaining attachment fibers can be distinguished easily from the area of the junctional epithelium. The observations which were made on the extracted teeth were then correlated with what could be seen in the radiograph. The following major observations were made: In the depth of the infrabony pocket there was a close congruence between the front of the subgingival plaque and the borderline of the remaining attachment fibers, the distance varying between 0.2 and 2.0 mm. There was also a close relationship between the front of the subgingival plaque and the alveolar crest adjacent to the tooth as well as between the surface of the subgingival plaque and the opposite vertical wall of the infrabony pocket, the distances ranging between 1 and 3 mm. The horizontal forces were mainly or exclusively oriented bucco-lingually, whereas the infrabony pockets were located mesially or distally, i.e. parallel to the direction of the force and not at a right angle to it as observed in experimental studies. The mobility of the teeth adjacent to which infrabony pockets developed was normal in 42% of the cases, slightly increased in 31%, and only in 11% of the cases was it excessively increased. In 19 cases the infrabony pocket was located on one of the roots of lower molars which were removed by hemisection. In eight of the 12 cases, which were observed for periods from 1 to 10 years, the remaining root functioned well without further development of angular bone defects or infrabony pockets. All of them became markedly firmer as a consequence of successful periodontal treatment. Three of the four remaining roots were extracted because of periapical problems. There was no evidence to indicate that trauma from occlusion had been involved in the pathogenesis of the infrabony pockets.


Mouse pancreatic beta-cells: tetraethylammonium blockage of the potassium permeability increase induced by depolarization.

1. Membrane potentials and input resistance were measured in beta-cells from mouse pancreatic islets of Langerhans in the presence or absence of D-glucose. 2. Tetraethylammonium (TEA) (a specific blocker of the K permeability increase induced by shifts in membrane potential from negative to positive values) was externally applied and its effects on potentials and input resistance evaluated. 3. In the absence of glucose, addition of TEA up to 20 mM to the perifusion medium did not affect the resting potential and the input resistance, the selectivity ratio PK/PNa (calculated from the constant field equation) remaining unchanged at about 30. 4. The characteristic response of the beta-cell membrane potential, in the presence of glucose, is a fluctuation between a silent phase at about -50 mV and an active phase at about -40 mV giving rise to a train of spikes. TEA abolishes this pattern and very much reduces the graded response of spike frequency normally seen with different concentrations of glucose. 5. Addition of glucose in the presence of up to 20 mM-TEA induces an increase in membrane resistance of about 4.10(7) omega. 6. TEA lowers the glucose level required to trigger the electrical activity from about 5.6 to about 4.6 mM. 7. TEA blocks the repolarization phase of action potentials induced by the addition of glucose or by depolarizing intracellular current injection. 8. In the presence of 11.1 mM-glucose and 20 mM-TEA the action potentials frequently crossed the zero line, the membrane potential reaching up to 25 mV during the peak of the spikes.


Potassium permeability activated by intracellular calcium ion concentration in the pancreatic beta-cell.

1. Membrane potentials and input resistance were measured in beta-cells from mouse pancreatic islets of Langerhans in a study designed to assess the role of a K permeability specifically blocked by quinine or quinidine and activated by intracellular calcium ion concentration ([Ca2+])i-activated PK). 2. Addition of 100 microM-quinine to the perifusion medium resulted in a 10--30 mV depolarization of the membrane and an increase in the input resistance of ca. 4.10(7) omega. 3. In the absence of glucose, 100 microM-quinine induced electrical activity. 4. In the presence of glucose, 100 microM-quinine abolished the burst pattern of electrical activity and very much reduced the graded response of spike frequency normally seen with different concentrations of glucose. 5. Addition of mitochondrial inhibitors, KCN, NaN3, DNP, CCCP, FCCP, to the perifusion medium containing glucose rapidly hyperpolarized the beta-cell membrane, inducing a concomitant decrease in input resistance. 6. In the presence of glucose, these mitochondrial inhibitors reversibly blocked electrical activity; upon removal of the inhibitor, recovery of electrical activity followed a biphasic pattern. 7. The effects of mitochondrial inhibitors were partially reversed by 100 microM-quinine. 8. It is proposed that the membrane potential of the beta-cell in the absence of glucose is predominantly controlled by the [Ca2+]i-activated PK. It is further suggested that this permeability to K controls the level for glucose stimulation and leads to the generation of the burst pattern.


Effects of progesterone and 17-beta-oestradiol treatments on the pancreatic B cell castrated  female rats. Biochemical variations.

The biochemical effects of progesterone and/or oestradiol treatments on castrated female rats have been compared to those of control olive-oil injections. 1. The steroid treatments used produced physiological concentrations of the two hormones in peripheral plasma, comparable to those obtained during pregnancy. 2. Glycemia remains within a normal range for all the treatments. 3. Circulating immunoreactive insulin (IRI) increases in the steroid-treated rats and the values reach those of the pregnant animals. 4. It was concluded that the biochemical modifications that occur during the steroid treatment (especially with the combined treatment) are quite comparable to what happens during pregnancy and explain, at least in part, the altered carbohydrate and lipid metabolism, and the hyperactivity in the B cell, resulting in an increased insulin secretion.


Vasopressin in fetal sheep: a review.

Advance in fetal sheep surgery has allowed investigation of vasopressin physiology at the end of gestation (100 to 140 days). In the fetus of that age, vasopressin is present in the pituitary and in the blood. The hormonal secretion is stimulated by hypotensive and hyperosmolar stimulus. Hypoxemia is also reported as being a potent stimulus of vasopressin secretion and may have an important effect on blood pressure control.


The effect of LH-RH administration on LH release in the female rabbit.

Intracarotid infusion of LH-RH to female rabbits stimulated a significant increase in plasma LH concentration in the jugular vein. This response varied with the reproductive state of the animal, with a greater release occurring in oestrous (spontaneous or oestrogen-induced) and non-receptive does than in pseudopregnant or ovariectomized animals. If ovariectomized rabbits were pretreated with oestrogen, the pituitary response to LH-RH was restored. These findings suggest that there is little change in pituitary sensitivity to LH-RH infusion between oestrous and non-receptive rabbits, although pseudopregnancy (high physiological levels of progesterone) or ovariectomy inhibit its ability to respond to a releasing-hormone stimulus.


Genetic and environmental variation in the LH response of ovariectomized sheep to LH-RH.

The influence of breed and season on the sensitivity of the pituitary gland of sheep to LH-RH was assessed. Ovariectomized ewes of 3 breeds (Finnish Landrace, Scottish Blackface and Tasmanian Merino) with differing normal breeding seasons and with differing ovulation rates were injected (i.v.) with 3 doses of LH-RH (1.56, 6.25 or 25.0 micrograms) at 3 different times of the year covering the anoestrous and the breeding seasons of intact ewes; 9 ewes of each breed (3 per sub-class) were examined on the first and third occasions, 6 (2 per sub-class) on the second. The response was measured in terms of the concentration of LH in peripheral plasma 20, 40, 60 and 80 min after injection. Time of year, but not the breed of sheep, affected the magnitude of the response; the data indicated that the duration of LH secretion was greater during the breeding season than during anoestrus. It was concluded that changes in the spontaneous activity of the hypothalamus/hypophysis could contribute to seasonal changes in LH secretion independently of the modifying effects of gonadal steroids. Such variation in unmodulated activity apparently does not contribute to the differences in ovulation rate among the 3 breeds.


Male reproductive patterns in nonhibernating bats.

Knowledge relative to the reproduction of nonhibernating bats is reviewed. Events in the male, as they are now understood, are summarized for all families for which data exist. Attention is given to the wide species diversity of male accessory sex oragns in respect to gross structure and glandular complement. Stability or variability or organization of the male reproductive system is noted. Functional relationships between primary and accessory sex organs are considered and any synchrony between these organs and their functional cyclicity identified. Various frequencies of male reproductive cycles are examined for each species within families. Factors influencing male reproductive evens in nonhibernating Chiroptera are briefly considered. It has long been speculation that reproductive cycles under natural conditions are strikingly related to the environment, with such features as temperature, moisture, length of day and available food all implicated. These cues, however, appear to be filtered through varied genetic potential and physiological patterns, since not all species respond similarly, even though residing together in a homogeneous environment. Variation between certain species in frequency and length of the oestrous cycle seem to be accommodated to by parallel adjustments in the male, including extended sperm production or storage and continued secretory activity of accessory sex glands.


Reproductive asymmetry and unilateral pregnancy in Chiroptera.

Bats are noteworthy in that anatomical and/or functional asymmetries of the female reproductive organs are far more frequent and profound than recorded for any other mammalian Order, being observed in representatives of all 13 familis so far examined. Asymmetry is expressed as a unilateral dominance of an ovary, the uterus, or both. Dextral dominance is most frequent, but cases of sinistral dominance are recorded. In general 6 basic patterns of asymmetry are recognizable. These are briefly described. Physiological factors which may condition expressions of asymmetry in specific cases are discussed, and some avenues for future research are suggested.


The anterior pituitary and reproduction in bats.

This contribution is a review of investigations on the role(s) of the anterior pituitary in chiropteran reproduction. Information on this subject has come mainly from histological studies of cytological changes during the annual cycle and mostly from hibernating temperate-zone species. Although direct evidence is unavailable, it appears that variations in the temporal synchronization of specific endocrine functions of the pars distalis are involved, at least in part, in several of the numerous reproductive specializations found in bats. Mention is also made of recent studies on the anterior pituitary of Macrotus californicus and its possible involvement in delayed development.


Endocrine physiology of the breast.

Endocrine physiology of the breast is discussed in regard to both the development and functional aspects. The interaction of hormones at the mammary gland level is presented from the fetal stage through the reproductive era. The mechanisms of galactopoiesis and lactation are discussed. Finally, physiology of prolactin and the influence of this hormone upon the breast in physiologic and pathologic states is presented.


The teaching of medical ethics in the Federal Republic of Germany.

Eduard Seidler sets his discussion of the teaching of medical ethics in the Federal Republic of Germany against an historical background. Immediately after the Second World War the freshness of the memory of the 'Nuremberg Medical Trials' influenced the way in which moral dilemmas were treated in Germany. At the present time no systematic instruction in medical ethics is provided in either undergraduate or postgraduate or continuing medical education. As a result of this, an inquiry was set up in 1977/78. Questionnaires were sent out with a view to collecting information on how subjects referring to medical ethics are treated during medical training. The inquiry showed that no special discipline can claim to be the only competent one for medical ethics, but that everyone has something to contribute. Dr Seidler concludes by stating that basic curricula related to the problems of medical ethics would have to be developed and should be carried on continuously within the training programme.


Sib risk of neural tube defect: is prenatal diagnosis indicated in pregnancies following the birth of a hydrocephalic child?

Recurrence frequencies of central nervous system malformations in sibs of probands with anencephalus or spina bifida range between 1% and 7%. The frequency of hydrocephalus among sibs of such probands is low (0.21%) but, nevertheless, is increased 2 to 5-fold when compared to general population frequencies. Anencephalus and spina bifida cystica were observed in 1.65% of sibs of children with hydrocephalus, a 2- to 8-fold increased over the population frequencies. These data indicate that some aetiological factors may be common to all three malformations. The risk figure of 1.65% for anencephalus and spina bifida in sibs born after the birth of a hydrocephalic proband constitutes sufficient indication for prenatal diagnosis by alphafetoprotein determination of the amniotic fluid.


Neural tube malformations: complex segregation analysis and calculation of recurrence risks.

Familial data on neural tube malformations in Great Britain were submitted to segregation analysis under the mixed model. Maternal and fetal factors cannot be discriminated in the absence of substantial bodies of data on spina bifida survivors who reproduce or on half-sibs. Early abortion studies would allow differential mortality in utero to be taken into account. After fitting the mixed and generalised single locus models, it is concluded that the multifactorial model can provisionally be used for calculation of recurrence risks. Pathogenic hypotheses implicating twinning seem to rest on little evidence.


May spina bifida result from an X-linked defect in a selective abortion mechanism?

It is suggested that the major genetic factor in determining the birth of children with neural tube defects may be a single X-linked gene. It acts as an X-linked dominant, not by producing neural tube defects, but by enabling the affected fetus to survive selective spontaneous abortion. This mechanism, mediated at the deciduoplacental junction, may be under the control of both maternal and fetal genes. With more mutant alleles, survival would become more likely, reaching a maximum in the homozygous affected female fetus of a homozygous affected mother. The female excess in anancephaly is greater than that in spina bifida because of its prenatal severity, thus requiring relatively more mutant alleles for survival.


Programs developed from concerns for women in medicine.

Since the Medical College of Pennsylvania, formerly the Woman's Medical College of Pennsylvania, became coeducational in 1969, there has been a continued effort to maintain the commitment of the institution to its heritage of women in medicine. An office has the role of coordinating and stimulating the establishment and maintenance of programs relevant to women in medicine throughout the institution. These programs are now available to men as well but particularly serve women's needs. They include the Summer Premedical Program, the Summer Health Policy Program, a restraining program for inactive physicians, a demonstration child care project, archives and special collections related to women in medicine, a women in medicine oral history project, and a bibliography of the literature on women physicians. The Medical College of Pennsylvania will continue its interests in the present and future needs of women physicians.


Biotyping and colicine typing of Salmonella typhimurium strains of phage type 141 isolated in Scotland.

Cultures of Salmonella typhimurium (551 strains) of phage type 141 isolated in Scotland from 1965 to 1977 were examined for biotype and colicine type. Three main biotype clones were recognised: If (30 strains), 9f (507 strains) and 31bd (11 strains) with subtype variants 9bf (1 strain), 9cf (1 strain) and 31b (1 strain). The contribution made by each biotype clone to outbreaks in Scotland was analysed. The findings confirmed the distinctness of the three biotype clones within the single phage type and indicated possible origins of strains of biotypes of 9f and 31bd.


Assay of the heat-labile enterotoxin of Escherichia coli in infant rabbits.

Infant rabbits were shown to respond to Escherichia coli heat-labile enterotoxin by a consistent increase in intestinal fluid content, which was maximal 5 h after oral dosing. Infant rabbits could be used in a simple quantitative assay for heat-labile E. coli enterotoxin based on the ratios of gut weight to remaining body weight 5 h after oral dosing. Infant rabbits remained responsive to heat-labile enterotoxin up to 14 days of age, after which their gastric pH became low enough to destroy the enterotoxin. Rabbits that had been deprived of food before being dosed had a reduced gastric pH and a reduced response to the enterotoxin. Lincomycin andmitomycin C were found not to increase th  e yield of heat-labile enterotoxin from E. coli strain P307.


Observations by immunofluorescence microscopy and electron microscopy on the cytopathogenicity of Naegleria fowleri in mouse embryo-cell cultures.

The destruction of secondary mouse-embryo (ME) cells by Naegleria fowleri was studied by indirect immunofluorescence with ME-cell antiserum as a specific label to trace the fate of mammalian-cell cytoplasm. The appearance of naegleria-induced cytopathic effect in the cultures coincided with the accumulation of discrete particles containing granules of ME-cell antigen within the cytoplasm of amoebae, suggesting that the organisms ingested host-cell material. In cultures containing cytochalasin B, a non-lethal inhibitor of phagocytosis by N. fowleri trophozoites failed to acquire any granular fluorescence and were not cytopathogenic. The engulfment of mammalian-cell cytoplasm by the organisms was confirmed when thin sections of naegleria-infected ME-cell cultures were examined by electron microscopy. Amoebae were seen in the process of detaching portions of cytoplasm from whole ME cells by means of distinctive ingesting pseudopodia, and fragments of mammalian-cell cytoplasm were identified within the food vacuoles of trophozoites. There was no evidence for cytotoxic disruption of ME cells before or during engulfment of these fragments. It is concluded that N. fowleri trophozoites attack and destroy cultured ME cells by a phagocytosis-like mechanism alone, without the aid of any amoeba-associated cytotoxic or cytolytic agents. The possible significance of these findings with respect to the in-vivo pathocity of N. fowleri is discussed.


Oscillations of membrane potential in L cells. IV. Role of intracellular Ca2+ in hyperpolarizing excitability.

Effects of divalent cations on oscillations of membrane potentials (i.e., spontaneous repetitive hyperpolarizing responses) and on hyperpolarizing responses induced by electrical stimuli as well as on resting potentials were studied in large nondividing L cells. Deprivation of Ca2+ from the external medium inhibited these hyperpolarizing responses accompanying slight depolarization of the resting potential Sr2+ or Mn2+ applied to the external medium in place of Ca2+ was able to substitute for Ca2+ in the generation of hyperpolarizing responses, while Mg2+, Ba2+ or La3+ suppressed hyperpolarizing responses. The addition of A23187 to the bathing medium or intracellular injection of Ca2+, Sr2+, Mn2+ or La3+ induced membrane hyperpolarization. When the external Ca2+, Sr2+ or Mn2+ concentration was increased, the resting potential also hyperpolarized, in a saturating manner. The amplitude of maximum hyperpolarization produced by high external Ca2+ was of the same order of magnitude as those of hyperpolarizing responses and was dependent on the external K+ concentration. In the light of these experimental observations, it was deduced that the K+ conductance increase associated with the hyperpolarizing excitation is the result of an increase in the intracellular concentration of free Ca2+ mainly derived from the external solution.


Immunopathological studies of Plasmodium berghei infected mice: (effect of carbon particles).

An attempt was made to block the role of the macrophages in the immune response by saturating them with carbon particles. The experiment was performed on Swiss albino female mice injected intraperitoneally with 10(5) P. berghei berghei. These mice were injected with carbon particles of 20 mgs on the day before the inoculation and again 10 mgs on day 4 and day 9 after the inoculation. The degree of parasitaemia was slightly higher throughout the experiment in the infected mice treated with carbon than in those untreated. By direct immunofluorescent method the free floating form of malaria antigen was detected in the infected organs (liver, kidney and spleen) on day 3 of infection onwards. The antigen was more intense in the carbon treated mice than in the untreated ones. The granular form of the antigen in the walls of glomerular capillaries of the kidney, in the Kupffer cells of the liver and in the reticulo-endothelial cells of the spleen, the malarial antibody and the immune complex (malaria antigen, antibody and mouse beta 1 C globulin) in the kidney were detected later on (day 11).


Development, growth rate, degree of malignancy, and chromosome pattern of Morris transplantable hepatomas.

A spectrum of chemically induced transplantable adenocarcinomas of the rat hepatocyte was developed in inbred strains of rats. For the most part, the tumors showed remarkable stability in growth rate between 1973 and 1976, as determined by months between transfers. A few tumors were slower-growing in 1976 than in 1973, and a few tumors of intermediate growth rate were somewhat slower-growing in 1973 than in 1976. Percentage distributions of chromosomes of six aneuploid hepatoma are presented. The most homogeneous cell lines were a haploid and a hyperdiploid line. The karyotype of each hepatoma had a consistent number of abnormal chromosomes. Lung metastases were observed in almost all cell lines.


Amino acid and sugar transport in Escherichia coli (ColIb) during abortive infection by bacteriophage T5.

T5 bacteriophage cannot replicate in Escherichia coli containing the colicinogenic factor ColIb. We show that active transport of proline and glutamine begins to decline at about 10 min after infection, the same time at which macromolecular synthesis stops during abortive infection. Uptake of alpha-methylglucoside is stimulated, however, and this change is evident even by 5 min after infection. These changes in membrane function do not occur during infections that are productive because of mutations on the plasmid or phage. The results suggest that the abortive infection is caused by membrane depolarization.


Are class I (pre-early) proteins of bacteriophage T5 sufficient to induce abortive infection of ColIb+ Escherichia coli?

When T5 bacteriophage infect a colicin Ib-containing host, a variety of membrane changes and inhibition of macromolecular synthesis occur. This work shows that all these changes also occur when a mutant of T5 that can only inject 8% of its DNA is used. This indicates that all the information necessary for the abortive infection is present on this 8% (first-step-transfer) DNA.


Kupffer cell suspensions and cultures as a tool in experimental carcinogenesis.

Approximately one-third of the cells in the liver are nonhepatocytes. Of these, the Kupffer cells, or phagocytes lining the sinusoids, are of particular significance since environmental carcinogens must first traverse a Kupffer cell barrier before reaching the liver parenchyma. Phagocytosis and subsequent degradation of carcinogens by Kupffer cells lead to their permanent removal. Factors such as membrane receptors, which determine the avidity of Kupffer cells for various substances, would consequently have a decisive role in the primary interaction between carcinogens and Kupffer cells. Likewise, the intracellular lysosomal apparatus, which determines the ability of these cells to degrade various substances, would determine whether these substances can persist in an active form. In vivo data on Kupffer cell clearance of various substances are plentiful. However, to dissect the complex problem of Kupffer cell interaction with carcinogens, a clear-cut in vitro system would certainly be useful. A system for separating Kupffer cells from other types of liver cells and maintaining pure Kupffer cell cultures has been achieved in recent years. Some basic cell biological studies--such as studies of membrane receptors and lysosomal enzyme apparatus--have already been carried out. It could now be rewarding to adopt the system for in vitro studies of Kupffer cell interactions with carcinogens.


Transduction of bacteriophage lambda by bacteriophage T1.

When bacteriophage T1 was grown on bacteriophage lambda-lysogenic cells, phenotypically mixed particles were formed which had the serum sensitivity, host range, and density of T1 but which gave rise to lambda phage. T1 packaged lambda genomes more efficiently both when the length of the prophage was less than that of wild-type lambda and when the host cell was polylysogenic. Expression of the red genes of lambda or the recE system of Escherichia coli during T1 growth enhanced pickup of lambda by T1, whereas packaging was reduced in recB cells. If donors were singly lysogenic, the expression of transduced lambda genomes as a PFU required lambda-specified excisive recombination, whereas lambda genomes transduced from polylysogens required only lambda- or E. coli-specified general recombination to give a productive infection.


Impaired renal allograft function: a comparative study with angiography and histopathology.

We reviewed 47 renal transplant recipients who had undergone angiography and transplant biopsy to evaluate impaired allograft function. Angiographic criteria for rejection were seen in all allografts with hyperacute rejection, accelerated rejection and chronic rejection, and in 13 of 17 allografts with acute cellular rejection. Angiography was normal in allografts with vasomotor nephropathy or transplant glomerulopathy. Angiography is an accurate method for the diagnosis of most causes of post-transplant dysfunction.


The significance of cancer after renal transplantation.

Cancer developing after renal transplantation is a well documented event that has clinical importance and immunologic implications. The incidence and severity of these malignancies are not of the magnitude to discourage the use of transplantation as major treatment for chronic renal failure. Suppression of the immune surveillance system has been believed to be the cause of cancer after transplantation but recent data suggest that cancer after transplantation does not constitute acceptable evidence for the immune surveillance theory.


Dissociation of urethral and anal sphincter activity in neurogenic bladder dysfunction.

In 53 patients with suspected neurogenic bladder dysfunction carbon dioxide cystometry was done in combination with urethral and anal sphincter electromyography. Complete dissociation between the reflex activity of the 2 sphincters was found in 25 per cent of the patients and only 58 per cent of the patients had identical reflex activity. It is concluded that anal sphincter electromyography is highly unreliable in the diagnosis of urethral sphincter dysfunction.


Use of full thickness patch graft in urethrovaginal fistula.

A full thickness free graft of labium minor was used to repair a large urethrovaginal fistula that could not be bridged otherwise. A successful result was obtained with relief of incontinence and a normal caliber urethra 14 months postoperatively. The question is posed as to the applicability of this technique in vesicovaginal fistulas.


A direct hepatotoxic effect of valproic acid.

Nine patients treated with valproic acid had low plasma fibrinogen concentration and other liver function abnormalities. Several patients also had a low platelet count and prolonged bleeding time. The abnormal values returned promptly to normal when the drug therapy was discontinued or the dosage reduced. The liver function abnormalities are consistent with a direct, dose-related hepatotoxicity.


Myths, morbidity, and mortality in asthma.

Persistence of outmoded concepts or "myths" concerning the diagnosis and treatment of asthma probably is responsible for large economic losses, overutilization of hospital beds, and many preventable deaths. There have been many worthwhile studies refuting these myths, leading to the following conclusions: Asthma consists of much more than wheezing and in many cases must be treated long after wheezing stops. There is no convincing evidence relating the chronic pulmonary changes of asthma to the psyche. Modern methods of prescribing theophylline have not made it universally effective and safe. Intermittent postive-pressure breathing is rarely justified in asthma. Respiratory acidosis may be corrected only by improving alveolar ventilation. Corticosteroids are usually essential for control of severe asthma and may be used safely. Severe asthmatics need careful monitoring because sudden respiratory failure may occur.


[Sensitivity of frequent-occurring isolates in outpatients to routinely-used antibiotics (author's transl)].

The susceptibility of microorganisms (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, E. coli, Klebsiella pneumoniae, Salmonella spp. and Haemophilus influenzae) frequently occurring in outpatients (treated by practitioners) to six kinds of antibiotics [ampicillin (ABPC), cefazolin (CEZ), erythromycin (EM), minocycline (MNC), gentamicin (GM) and thiamphenicol (TP)] was determined by the standard method established by the Japan Society of Chemotherapy. 1) There were few multiple-antibiotic-resistant urine isolates from patients with a simple urinary tract infection, whereas urine isolates from patients with a complicated urinary tract infection contained many multiple-antibiotic resistant organisms. 2) Isolates from patients with a respiratory tract infection (sputum and tonsillar secretions isolates) and isolates from patients with acute purulent otitis media (purulent discharge isolates) contained few multiple-antibiotic-resistant organisms except for EM-resistant Streptococcus pyogenes. 3) Superficial pus isolates contained many multiple-antibiotic-resistant organisms, while bile isolates were relatively free from multiple-antibiotic resistant organisms. 4) When the results of the previous8,9) and present investigations were compared with the reports of other Japanese investigators1,5,6), suggestive evidence was provided that organisms resistant to macrolides and chloramphenicol showed a tendency to decrease, whereas organisms resistant to penicillins, cephalosporins and aminoglycoside antibiotics were on the increase.


Pathological studies in experimental Candida endocarditis.

Mycotic endocarditis was produced in rabbits by indwelling intracardiac catheters filled with a suspension of Candida albicans. Grossly, cardiac lesions consisted of massive fungoid valvular vegetations and/or "sleeve thrombi" surrounding the catheter. Microscopically, platelet-fibrin aggregates were observed to be loosely attached to the valvular cusps. With time, the vegetations became organized and more firmly attached against the endocardium. Also observed was a heavy neutrophylic collar often containing Candida cells which infiltrate the subendothelial tissues of the valvular cusps. Sterile endocardial lesions were produced by retained catheters. The lesions consisted of discrete, glistening, hemispherical nodules in the right heart; and similar elevated plaques on the mural endocardium of the left ventricle. Microscopically, these lesions consisted of fibrous connective tissues devoid of inflammatory cells. The lesions in the left ventricle were more extensive, extending into the myocardium.


Dry up method as a revised Limulus test with a new technique for gelatin inhibitor removing.

To detect endotoxins, Limulus test, especially its tube method, is recently used most widely. But this method has shortcomings considerably, for example, the lack of the objectivity on the judgement, the necessity of long handling time and the requirement of relatively large amount of Limulus lysate. To revise these shortcomings we established a new method. In our method, sample and Limulus lysate are mixed on a silicone coated slide glass and incubated at 37 degrees C for 30 min, then heated to dry up for the judgement. In samples which contain protein, the pretreatments with (NH4)2SO4, dilution and boiling are performed to remove gelation inhibitor. It was proved that this method could be applied to such samples as physiological saline, plasma, urine, transudate, exudate, cerebrospinal fluid (CSF) and suspension of Escherichia coli (E. coli). This method has advantages in its (1) objectivity of the judgement because of the clear difference of the dry up patterns between positive reaction and negative, (2) shortness of the handling time (results can be obtained within 2 hr from sampling), (3) requirement of little amount of sample and of Limulus lysate (a fifth volume of sample and a tenth volume of lysate are needed compared with the conventional method) and (4) sensitivity (0.1 or 0.5 ng/ml of lipopolysaccharide (LPS)).


[Chromosome changes induced by industrial chemicals (author's transl)].

Radiation-induced chromosome damage has been widely recognized and intensively studied. Recently, attention is placed on chromosome changes induced by various industrial chemicals. In case of occupational exposure to ionizing radiation, chromosome breaks are characterized as one of the most sensitive biological effects. Chromosome breaks among industrial workers who dealt with benzene, vinyl chloride monomer or styrene have also been reported. Moreover, relationship between chromosome changes and exposure to environmental lead, cadmium and mercury compounds have been studied. Ionizing radiation, benzene and vinyl chloride monomer are known also as industrial carcinogens and attention is now placed on carcinogenicity of clastogens or chromosome breaking agents. In the present paper, our studies on in vitro chromosome breakage induced by benzene and its metabolites as well as cadmium, lead, and chromium compounds are reviewed. Also, inhibition of repair of radiation-induced chromosome breaks by clastogens is reported. Significance of cytogenetic studies in industrial medicine is also discussed.


Characteristics of adrenocortical function, gastrin release and gastric secretion in duodenal ulcer etiology.

Measurements of serum cortisol and gastrin along with gastric acid-pepsin secretion in the resting state were carried out in gastric and duodenal ulcer patients. Increased basal corticosteroid concentrations were observed in patients with duodenal ulcer and gastric ulcer. Higher concentrations of the hormone were observed in the former group (P less than 0.05 for the latter). Fasting gastrin levels were significantly higher in gastric ulcer patients where gastric secretion is low than those in duodenal ulcer patients (P less than 0.001). These results suggest that the effect of adrenal cortical hormone on lowering the threshold of oxyntic gland cell reactivity against gastrin is an important factor in duodenal ulcer etiology. Extra-antral control mechanism(s) of gastric acid-pepsin secretion should not be overlooked.


Treatment of metastatic endocrine-unresponsive carcinoma of the prostate gland with multiagent chemotherapy: indicators of response to therapy.

Eighty-eight patients with metastatic and hormonally unresponsive carcinoma of the prostate gland were treated with a multiagent chemotherapy protocol. Because of the difficulty in evaluating the response of patients to therapy, data were collected in a prospective fashion and analyzed for clinical or laboratory changes that correlated with improved survivorship. Decrease of initially abnormal values of either acid or alkaline phosphotase into the normal range was associated with prolonged survival; weight gain of more than 10% was also associated with improved survival. Thirty-three patients demonstrated a fall of acid or alkaline phosphatase into the normal range or they increased their weight by at least 10%. The median survival time for this group of patients was 76.1 weeks as compared to 28.2 weeks for patients who failed to exhibit these changes. In future studies of the treatment of metastatic prostate cancer, these changes might be used as criteria of response to therapy.


Cell surface glycoproteins of human tumor cell lines: unusual characteristics of malignant melanoma.

Cell surface glycoproteins of human tumor cell lines (melanomas and astrocytomas, and ovarian, bladder, stomach, cervical, laryngeal, and renal cancers) were studied by labelling with 1) neuraminidase-galactose oxidase-[3H]borohydride, 2) galactose oxidase-[3H]borohydride, and 3) dilute periodate-[3H]borohydride. The labeled components were examined by polyacrylamide gel electrophoresis and fluorography. Each tumor type had a distinctive pattern of labeled glycoproteins when the results from both procedures 1 and 2 were considered. Cell surface glycoproteins of malignant melanoma could not be labeled by procedure 2, whereas the other cell lines had at least two major glycoproteins that could be labeled by this method. Very similar profiles of melanoma glycoproteins were labeled by procedures 1 and 3. From these results the conclusion was reached that cell surface glycoproteins of melanomas are substituted with sialic acid so that their D-galactose and/or N-acetyl-D-galactosamine residues are available for oxidation by galactose oxidase only after neuraminidase treatment. An alternative explanation that these sugars are sterically accessible to galactose oxidase only after neuraminidase treatment also has to be considered. All melanoma lines studied were characterized by having two major cell surface glycoproteins with molecular weights of 110,000 and 90,000, respectively. Lines, however, varied considerably in their expression of other components. In particular, heterogeneity was shown in the expression of gp220, a component identified as fibronectin by immunoprecipitation with a specific antiserum, and in the expression of gp37/32, a pair of glycoproteins having the characteristics of la-like antigens. Of the other cell lines studied, astrocytomas most closely resembled melanoma in their glycoprotein profiles. The brain tumors, however, had two or three glycoproteins, including gp110, which could be labeled by galactose oxidase-[3H]borohydride without neuraminidase treatment.


Binding of carcinogenic halogenated hydrocarbons to cell macromolecules.

Ethylene dibromide (EDB), a known stomach carcinogen, and ethylene dichloride (EDC), which is carcinogenic to the liver, have been shown in in vitro experiments to bind covalently to stomach and hepatic microsomal proteins and to salmon sperm DNA. The binding of EDB or EDC with proteins was not significant when denatured microsomes were used or when DNA was used in the absence of microsomes. The binding of EDB to these macromolecules was augmented with increasing concentrations of microsomes. SKF-525A, an inhibitor of the microsomal metabolism of various substrates, significantly inhibited the binding of EDB to protein and DNA. These findings suggest that metabolic activation of EDB and EDC is required for their covalent binding to macromolecules. Glutathione and 1-methyl-2-mercaptolmidazole markedly decreased the binding of EDB, which indicated that a reactive electrophilic intermediate(s) of EDB is (are) involved in the binding. The binding of EDC to liver proteins of (C57BL/6 X C3//He)F1 mice, which are susceptible to liver tumor induction by EDC and to DNA, was significantly higher than the corresponding binding for Osborne-Mendel rats, a species not susceptible to liver tumor induction by this compound.


Anti-inflammatory effect of spontaneous lymphoma in SJL/J mice.

Histiocytic lymphomas develop spontaneously in about 80% of SJL/J mice between the ages of 8 and 14 months. These animals were used for the determination of whether spontaneously arising cancers compromise monocyte function similar to the monocyte defects described during growth of transplanted tumors. SJL/J mice with tumors accumulated significantly fewer macrophages than did age-matched animals without tumors either on sc implanted filters or in peritoneal exudates induced by phytohemagglutinin. There was no corresponding defect in polymorphonuclear neutrophil responses. Whereas no apparent correlation existed between tumor size and degree of inhibition, animals without demonstrable tumors had no inflammatory defects. Aging did not alter the inflammatory response to implanted filters but increased both the resident peritoneal macrophage population and the total macrophage yield to phytohemagglutinin provocation. When given transplants of histiocytic lymphomas, young SJL/J mice developed similar inflammatory defects. This study represents the first demonstration that spontaneous tumors, in addition to transplanted tumors, produce abnormalities in monocyte inflammatory responses.


Adamantinoma of the appendicular skeleton.

Adamantinoma is a slowly developing tumor originating in the bones of the extremities and containing cells that resemble amelioblasts but do not produce enamel. Anamantinoma's clinically and histologically benign appearance is deceptive, for the recurrence rate is high unless surgical extirpation is complete. Thus, aggressive surgical excision of the involved area of bone should be performed at the time of diagnosis. Allograft substitution may be an effective alternative to amputation.


Free hypothenar full-thickness grafts for distal digital defects.

The application of free full-thickness grafts of palmar skin from the hypothenar area is advocated for full thickness digital tip defects too large for open treatment. The traditional objection to this site as a donor for full-thickness skin on the basis of sensitivity and pain has not been confirmed. Strict, meticulous attention to detail is required for success in utilizing this technique. Other methods of treatment are reviewed and indications, advantages, and disadvantages of the free full-thickness graft of hypothenar skin are discussed.


[Neuroblastoma in children. Clinical staging and management (author's transl)].

Sixty-four children with neuroblastoma stage I to III c are presented. The coordinated management utilizing surgical excision, irradiation (2--5.000 rad) in stage II and III and multiagent chemotherapy is described. Favorable sites were abdomen (30) and thorax (22). In ten cases the primary site was unknown. The prognosis is influenced by several factors: Patients under 1 year of age without evidence of bone or bone marrow metastases have a favorable outcome (13/15). Nearly all patients with lesions of bone or generalized tumor in bone and/or bone marrow (stage III b and III c) failed to attain long term disease free survival despite combination chemotherapy and the use of radiation therapy (33/34). No relation between histological or biochemical characteristics and prognosis could be found. Biochemical determinations however are useful as an index of response to treatment. Prognosis was independent from sex. A review of the literature and on attempt to improve the therapeutic efficancy in stage III are reported.


[Cell receptor defects as the cause of endocrine and metabolic diseases (author's transl)].

The following pathogenetic mechanisms, exemplified by three diseases (diabetes mellitus, hyperthyroidism and familial hypercholesterolemia), are discussed: 1. The impaired interaction between a chemical signal and a specific receptor can be the cause of a disease. 2. The cause for an imparied interaction can be a defect of the receptor, i.e., a reduced number of receptors or an altered receptor affinity, or a wrong signal. 3. A defect of the receptor can be induced by exogenous influences or it can be determined genetically. 4. The receptor and the signal can be modified by their interaction: the number of receptors is reduced by high concentrations of the chemical signal or by increased degradation due to binding to the receptor. 5. The receptor concept opens new perspectives for the pathogenetic understanding, diagnosis and therapy of some diseases.


[Soluble mediators as a means of communication between lymphozytes in immune reactions (author's transl)].

Soluble mediators play an important role in the positive and negative regulation of immune reactions. This has been particularly well documented for T-B-cooperation in the humoral immune response to T-dependent antigens. T-helper cells produce a T-cell replacing Factor (TRF) upon mitogenic or antigenic stimulation. It provides the signal to antigen triggered B-cells to begin with active antibody synthesis and secretion and thus it is a positively regulating mediator. Additional functional and some structural characteristics of TRF are described. Antigen specific and non-specific suppressor factors seem to be involved in the negative regulation of immune responses. Thus, the communication between cells of the immune system is largely conducted via soluble signal substances.


Characterization of human pepsin I obtained from purified gastric pepsinogen I.

Immunochemical homogeneous human pepsinogen I-group (PgI) was purified by solid immunoadsorbent and by DEAE-chromatography from gastric mucosa. PgI contained five electrophoretic distinct bands at pH 8.2 but only four bands at pH 5.6. After acid activation human pepsin (PI) was separated from the inhibitory peptide by affinity chromatography using poly-L-lysine. Purified PgI contained 9-16% of the inhibitory peptide. The yield of PI was 64 to 85%. A 65% increase of specific activity was observed. PI demonstrated three bands in agar gel electrophoresis at pH 5.6. The pH range of PI was rather wide, showing two maxima at pH 2.0 and pH 3.0 with hemoglobin as substrate. Irreverisble inactivation of PI was observed at pH 7.0 and at a temperature of 60 degrees C. The Km-value of PI was 0.170 mmol as determined with N-acetyl-L-phenyl-alanyl-L-3,5 diiodotyrosine. The specific activity was 9.6 IU/mg (hemoglobin substrate) and 0.032 IU/mg (dipeptide substrate). Porc pepsinogen (PPg) and its activated pepsin (PP) was used for comparison. PP showed indentical elution patterns in affinity chromatography. In AEE PPg and PP demonstrated both two components at pH 5.6 with different electrophoretic mobilities. The pH optimum of PP was observed at pH 2.0. PP was slightly more sensitive in alkali and heat inactivation than human P. A higher Km-value of PP of 0.082 mmol and higher specific activity as compared to human PI was observed.


Characterization of human pepsin II obtained from purified gastric pepsinogen II.

Human pepsinogen II (PgII) was purified from human gastric mucosa by immunoadsorbents using anti-PgII antiserum. Contaminating pepsinogen I (PgI) was adsorbed by a subsequent anti-PgI immunoadsorbent. PgII was further purified on DEAE-Sphadex A50. By agar gel enzyme electrophoresis (AEE) at pH 8.2 PgII was separated into five proteolytic bands, demonstrated upon acidification and incubation with hemoglobin. PgII was converted to pepsin II (PII) by acidification at pH 2.0 and was immediately separated from its inhibitory peptide and from other substances by DEAE chromatography. Purified PII showed two bands in AEE at pH 5.6 and was immunochemically identical with PgII. The "gastricsin" and "pepsin" purified from acid gastric juice by classical procedures proved to be identical with PII and pepsin I (PI), respectively. PII showed a broad pH range with one maximum at pH 2.9. PII in contrast to PI did not hydrolize N-acetylphenylalanyl-3,5-diiodotyrosine and proved to be more alkali-stable than PI. A modified nomenclature is proposed for the human pepsinogen system.


Shifting perspectives on the alcoholism treatment movement 1940--1955.

Relationships between the Yale Center of Alcohol Studies, considered to be representative of the alcoholism treatment movement, and various temperance groups, clergy and spokesmen for the alcoholic beverage industry are examined.


Total joint arthroplasty. Biologic causes of failure.

Hypersensitivity reactions and deep sepsis are the primary forms of biologic failure of total joint arthroplasty. Hypersensitivity reactions appear to be related to metal debris associated with metal articulating with metal arthroplasties. Although the incidence of deep sepsis following total joint arthroplasty is lower than initially feared, it remains a serious problem for both the patient and the surgeon. Fixation of prosthetic devices with methyl methacrylate appears safe. However, improved methods of fixation which are more compatible with osseous tissue are currently under study. The advantages of porous materials and the results of laboratory studies are reviewed.


Non-enzymatic, post-translational, amino acid modifications in ageing. A brief review.

Accumulated evidence implicates two non-enzymatic, post-translational, amino acid modifications -- deamidation of asparagine and glutamine, and racemization of aspartic acid -- as potentially important reactions in cellular and organismal ageing. Rates of deamidation can be genetically regulated over a range of at least six days to ten years, and this release of ammonia from amides causes molecular conformational changes, loss of activity, and age-related alterations in a number of proteins in vivo. Racemized aspartic acid amasses with age, especially in croslinked and partly degraded proteins of the normal ageing human lens and yellow cataracts. In both cases, modification of amino acids could account for the accumulation of altered proteins observed with ageing in the cells of certain organisms.


Autoantibodies in healthy subjects of different age groups.

Autoantibody determinations in 1284 healthy Caucasian subjects of various age groups were made by indirect immunofluorescence for anti-nuclear, anti-gastric, and anti-thyroglobulin antibodies. A sex-dependent relationship between age and prevalence of anti-gastric and anti-thyroglobulin antibodies was found. No association was found between age and anti-nuclear antibodies.


[Zollinger-Ellison syndrome: comparative and critical review of international and national bibliography (author's transl)].

Since Zollinger and Ellison described two cases of this disease in 1955 which would later recieve their names (ZED), more than 1,000 cases have been published in the world literature up to date. In our area around 28 cases have been reported in a period of 14 years (1964--1976). The author reviews this disease, evaluating and comparing results obtained in this small series, with regard to prevalence, clinical manifestations and histopathologic lesions, against those obtained in series of large scope. Mean age was 46 years, ranging from 18 to 63 years, and the male-female ratio was 7:5. Ulcers and diarrhea were present in 100 percent and in 35 percent of the cases, respectively. The incidence of AEM-1 was 25 percent. In 85 percent of the cases the existence of a gastrinoma was demostrated, being pancreatic in 78 percent and extrapancreatic in 7 percent. In 10 percent of the cases there was a diffuse hyperplasia of the islet cells, and in one case, there was hyperplasia of the G-cells of the antrum. These results are very similar to those obtained by different authors.


The surgical management of extracranial and intracranial occlusive disease.

The role of surgery in preventing transient ischemic attacks and stroke in certain occlusive vascular lesions is well-established. This is well-established when carotid endarterectomy for carotid stenosis with transient ischemic attacks is used. The overall surgical results are best achieved by the frequent performance of the procedure and meticulous attention to technical as well as medical features of this group of patients at risk. Continuing medical care of these patients is essential. The long-term mortality rate is augmented by the high incidence of myocardial infarctions. Complete cardiac evaluation and good medical care, at the time the patient is initially treated, should subsequently minimize this event. Although the microvascular bypass procedures are technically feasible and associated with a low mortality rate, their exact role in the medical management of patients with intracranial occlusive lesions is unproven. However, the procedure offers great promise and an exciting future for neurosurgery in stroke therapy.


Anticoagulant treatment to prevent cerebral infarction.

The indications for anticoagulant treatment to prevent cerebral infarction or progression of cerebral infarction are now clear. The indications are: (1) Prevention of recurrent embolization from a cardiac source (long-term anticoaguland treatment). (2) Transient ischemic attacks (particularly vertebrobasilar system) if a surgically accessible causative lesion, polycythemia, and thrombocytosis are not present (anticoagulants for a few months.) (3) Progressing stroke in either systme assuming that the neurological defect is partial and CT scan shows no evidence of bleeding (anticoagulants for a few months.) (4) Rarely, completed stroke (long-term).


The effect of rifampicin upon the transcription of RNA polymerase beta-gene in Escherichia coli.

We studied the rate of synthesis of beta-and beta'-subunits of DNA-dependent RNA polymerase and the rate of beta-polypeptide mRNA synthesis in rifampicin-treated bacteria. The chosen antibiotic doses did not significantly inhibit the total RNA and protein synthesis in rifampicin-sensitive bacteria. For RNA-DNA hybridization experiments a pOD162 plasmid was constructed carrying a fragment of the rpoB gene and no other chromosome DNA regions. It was found that low doses of rifampicin cause an absolute and a relative increase in the rate of synthesis of the specific mRNA for the beta-subunit, suggesting a stimulation of the corresponding gene transcription and excluding the possibility of a less pronounced inhibition of the rpoB gene expression compared to that of most other genes. However the relative acceleration of transcription is substantially higher than the absolute one. The stimulating effect of rifampicin on the beta-polypeptide synthesis is also demonstrated in a coupled system of transcription and translation directed by lambda rifd47 DNA. The possible mechanisms of the rifampicin action are discussed.


Genetic evidence for the creation of a reinitiation site by mutation inside the yeast ura 2 gene.

The ura 2 gene of yeast codes for two enzymatic activities which are translated from a unique messenger RNA in the order carbamoyl-phosphate synthetase (CPSase), aspartate transcarbamylase (ATCase) (Lacroute, 1968; Denis-Duphil and Kaplan, 1976). Nonsense mutations in the CPSPase region cause a complete loss in ATCase activity by a total polar effect, characteristic of eukaryotic mRNA translation, and due to the unique site of protein initiation present on each messenger (Shaffer et al., 1969). A triple nonsense mutant in the CPSase has been constructed by recombination and ATCase+ revertants have been selected from it. Among seventeen revertants obtained, three had a deletion covering the three nonsense mutations relieving thus the polar effect (Fink and Styles, 1974) but fourteen others examined had retained all the CPSase DNA including the three nonsense mutations; this can be explained in the present state of knowledge only by the creation by mutation of reinitiation site either for transcription or for translation in the region of the ura 2 gene distal to the last nonsense mutation.


Development of a system useful for studying the formation of unstable alleles of IS2.

IS2-induced deletions of the gal control region were isolated in a plasmid carrying gal OP-308::IS2-7. This contains a 54 basepair long, unstable mini insertion within IS2, thus allowing constitutive expression of the gal structural genes. Deletion PPI is 11.9 kilobasepairs (kb) long and is Gal+ because it has retained the mini insertion. In PP4 7.2 kb DNA material including markers gal OP, chlD and pgl are deleted. PP4 has lost the mini insertion and is therefore Gal negative. DNA sequencing of the newly formed junction in PP4 reveals that the deletion terminates precisely at nucleotide 1 of IS2 and that no DNA sequence homology is involved in this IS2-mediated deletion formation. PPI segregates Gal- clones due to the loss of the mini insertion. One such segregant PPIS and PP4 both give only constitutive Gal+ revertants, which consist of the previously known mini insertions and also a new class of "supermini" inserts within IS2 of about 10 to 20 basepairs long. Therefore, PPIS and PP4 can be used to study various parameters involved in the formation of mini insertions.


Tn10 mediated integration of the plasmid R100.1 into the bacterial chromosome: inverse transposition.

Upon integration into the bacterial chromosome the drug resistance plasmid R100.1 often loses its tetracycline resistance character. We have analyzed an Hfr strain formed by such an integration and an R-prime plasmid derived from it. We find that integration took place within the Tn10 transposon, that the two IS10 sequences were retained, but that at least 80% of the transposon segment located between them, and carrying the tetracycline resistance genes, had been lost. We suggest that integration of R100.1 was mediated by an inverse transposition using the IS10 sequences.


Expression of Escherichia coli ribosomal protein and RNA polymerase genes cloned on plasmids.

Fragments of lambda drifd 18 DNA with different end-points within the set of structural genes of ribosomal proteins L11 (RPLK), Li (rplA), L10 (rplJ) and L12 (rplL) as well as the beta (rpoB) ANd beta' (rpoC) subunits of RNA polymerase have been cloned on plasmids. These plasmids were transformed in host cells which were mutant for each of the genes, enabling expression of both wild-type (plasmid-borne) and mutant (chromosomal) genes to be differentiated. On the basis of these results we propose the following genetic structure for the region: rplK and rplA are in one operon; rplL, rpoB and rpoC are in a second. Our data suggest the possibility that rplJ is by itself in an operon situated between the other two.


Inactivation of E. coli RNA polymerase by polyriboinosinic acid: heterogeneity of RS complexes.

Polyriboinosinic acid (poly I) inhibits initiation of transcription by binary complexes formed between Adenovirus 2 DNA and E. coli RNA polymerase holoenzyme. In the presence of poly I, just as in the presence of rifampicin, initiation of transcription exhibits a sigmoidal dependence on the temperature at which the binary complexes are formed. This indicates that I (closed) complexes between Ad 2 DNA and RNA polymerase are rapidly inactivated by poly I, but that RS (open) complexes are relatively resistant. However, even among the RS complexes, at least two classes can be distinguished on the basis of the degree to which they are resistant to poly I: RS-1 complexes are somewhat sensitive to poly I (half-time of inactivation approximately 10 min) while RS-2 complexes are almost completely resistant to the inhibitor (half-time of inactivation approximately 10 h). For both types of RS complex, the degree of sensitivity to poly I is ionic strength-dependent.


The unstable sensitivity of yeast cells to lethal and mutagenic action of nitrous acid.

Fifty-two cultures grown under standard conditions from separate subclones of haploid Saccharomyces strain X2180-1A were exposed to standard treatment with nitrous acid (NA). When the duration of NA-treatment was the same:a) cell survival varied markedly and the frequency distribution of its values differed significantly from the normal one; b) the overall frequency of induced ade1- and ade2-mutants (OMF) and the proportion of complete mutants among them (PCM) also displayed significant subclonal variation, apparently co-ordinated with the variation in survival. In the same experiments several different types of dependence of the OMF and PCM on the duration of NA-treatment were found. Thus the characteristics of the action of NA on yeast cells appeared to be unstable. Subclones with pronounced and reproducible differences in sensitivity to the lethal action of NA were isolated from X2180-1A without any induction or enrichment technique. This fact proves the genetic nature of the instability discovered, i.e. this instability appears to reflect the behavior of unstable genetic factors playing, along with the stable ones, a role in the control of NA-sensitivity of X2180-1A cells.


The peculiar behaviour of coliphage P1vir mutants on restricting hosts.

The sensitivity of two vir coliphage P1 mutants, to the host-specificity systems A, K, RII, and B of Escherichia coli, and to the newly identified host-specificity systems Mir and 59 of Klebsiella pneumoniae has been studied. Both 1 vir phages were completely resistant to the E. coli K, but were restricted 10(-5) by the B, mir and 59 systems. The P1 parent, on the contrary, was restricted 10(-2) by all of the above mentioned hosts. The possible role of phage coded proteins in the altered sensitivity of the vir strains has been studied by analysing the sensitivity of both P1, and P1vir to the various systems in the presence of chloramphenicol. Protein synthesis inhibition by chloramphenicol did not significantly influence the sensitivity of P1 and P1vir to various restricting hosts. It is concluded that the altered sensitivity of vir mutants depends on the different affinities of the mutated phage DNA sequence for the enzymes of the various restriction and modification systems. The possibility that the phage repressor contributes to the regulation of the restriction and modification enzymes is also discussed.


Stress and disease: the missing link. A vasospastic theory. I. Acute myocardial infarction - a potentially reversible event?

A review of the evidence in acute myocardial infarction indicates that it might well be initiated by coronary artery spasm, and that coronary thrombosis, although important in tipping the balance between severe damage and death of heart muscle, may merely be secondary to the spasm-induced reduction in coronary blood flow.


Comparison of metoprolol and pindolol in the treatment of mild to moderate hypertension: a double-blind crossover study.

Matched doses of metoprolol and pindolol were administered to 31 hypertensive outpatients in a double-blind randomized crossover trial, which was designed to compare the antihypertensive efficacy and pattern of side effects of the two drugs. Twenty-nine patients completed the study. A tenfold difference in dose (25 +/- 2 mg/day of pindolol and 234 +/- 22 mg/day of metoprolol) was required to produce a similar antihypertensive effect. There was a significantly greater fall in pulse rate during metoprolol treatment. Complaints of dry mouth, mild Raynaud's phenomenon, and eye discomfort were more frequent during treatment with metoprolol; and sleep disturbances and abnormal dreaming patterns were more frequent during treatment with pindolol.


[Attachment of Sulfobacillus thermosulfidooxidans cells to the surface of sulfide minerals].

The behaviour of Sulfobacillus thermosulfidooxidans cells in cultures growing at 50 degrees C in the autotrophic conditions with intensive stirring of the medium was studied by phase-contrast and electron microscopy. The following compounds (at a concentration of 1%) were used as an energy source: pyrite, chalcopyrite, arsenopyrite, antimonite, galenite, sphalerite, and copper-zinc-pyrite ore. A considerable part of cells was found to be attached to the surface of crystals in the course of oxidation of the above sulfide minerals. Adhesion of cells to the surface of minerals was accomplished by means of abundant slime formation. The cell produced slime at the highest rate by those parts of its surface which was adjacent to the mineral. Apparently, the chemoreceptor apparatus of the cell was involved in the process of adhesion. Appendages of an unknown nature were found in cells growing on pyrite. Presumably, cells are anchored to the surface of minerals by these structures.


Stress and disease: the missing link. A vasospastic theory. II. The nature of degenerative arterial disease.

An analysis of the evidence indicates that the initiation and progress of atherosclerosis might well be explained by repeated bouts of arterial constriction in relation to life stresses, through increased blood flow velocity and turbulence at points of constriction, and consequent endothelial damage, plasma insudation into the wall, and intimal smooth muscle cell - connective tissue proliferation.


Stress and disease: the missing link. A vasospastic theory. III. Stress, vasospasm and general disease.

The potential importance of vasospasm, with or without consequent thrombosis, as a mechanism in general disease is discussed and the evidence examined in one organ, namely the brain. It is concluded that vasospasm might be important in a number of neurological disorders, including migraine, epilepsy, and even some of the schizophrenia-like illnesses. Repeated ischaemic cell damage from vasospasm is also discussed as a possible factor initiating autoimmune disease and cancer. The similarities between viral transformation and neoplasia have led to the proposition that much cancer might be explained if as a species we have evolved by the gradual build-up of viruses.


Theorectical mechanisms for synthesis of carcinogen-induced embryonic proteins: III. The tRNA methylases; methylation mechanism and function.

It is contended that redundant repressed tRed) with carcinogens in adult cells. Supportive evidence, especially from molecular model building, is presented for a mechanism of tRNA methylation. In this mechanism the adenine moiety of S-adenosyl-L-methionine base-pairs with uracil for all tRNA methylations. Furthermore it is proposed that such methylations are required during the transcription of a tRNA molecule in order to limit the number of possible conformers that can occur before further development of the molecule takes place. This theory of the function for methyl groups is discussed in the light of the properties found for hypomethylated tRNAs.


The role of cardiac valves in artificial heart performance.

The criteria for the design, selection of materials, and fabrication of a total artificial heart have evolved over several years. As these criteria have become more sophisticated and exact, they have optimized the performance of all components within the system. A pump with sufficient volume and pressure output that fits in the available anatomic space was a primary objective. Concomitantly, a nonthrombogenic, durable material that was nondegradable in body fluids was being developed. The most easily managed energy source selected to date has been pulsed, compressed air programmed for gentle but effective systole and diastole. The evolution of good cardiac valves has been of major importance to the artificial heart effort. The historical development of the artificial heart has often centered around existing prosthetic valves which are currently an integral component of the complete system. A detailed analysis of the performance of the total artificial heart clearly identifies the role of the cardiac valve.


As it was in the beginning . . .the British Medical Association (Victorian Branch).

Branches of the British Medical Association arose throughout the Commonwealth, one of the later being in Victoria, one of the smaller and thickly populated of the States. There were the usual causes. Dissatisfaction led to cliques, views of ethics varied with age and position and ambitions clashed. But the immediate causa causans was the blackballing of a candidate whose merits were his own, but whose ancestory was condemned. His "fidus Achates", with many traits in common who had been 20 years the mainstay, and 18 years the Editor, of the existing and repellant Medical Society of Victoria, promptly resigned, and refused repeated offers to return even at the price of a testimonial. SoDr Neild and Dr Louis Henry came together and between them ran the Branch for years and in process of time took prominent positions medically, musically and many ways.


Prevention of duodenal ulcer relapse by cimetidine: a one-year double-blind trial.

Fifty-one patients with duodenal ulcer which was healed by a six-week course of cimetidine completed a one-year double-blind study to compare the effects of cimetidine and placebo on the prevention of ulcer relapse. Patients were allocated at random to receive either 400 mg of cimetidine twice daily or placebo. Ulcer relapse was assessed by regular clinical follow up and endoscopy. A total of six of the 24 cimetidine-treated patients (25%) suffered a relapse compared to 25 of the 27 of placebo-treated patients (92.6%). Out of this total number of relapses, asymptomatic relapse with ulceration discovered by routine endoscopy at six months or one year, occurred in three patients receiving cimetidine and eight patients receiving placebo. Cimetidine prevents recurrence in patients with duodenal ulcer disease.


Craniofacial surgery.

The historical development of craniofacial surgery for congenital abnormality is reviewed. The work of a second Australian unit of craniofacial surgery which has been formed in Brisbane is described, current indications for surgery are defined, and the preoperative preparation is outlined. The treatment of six children with hypertelorism, Crouxon's disease, Apert's syndrome, and bicoronal craniostenosis is described and the postoperative results and complications are outlined. There is a case for early surgery.


Evaluation of a new antihelminthic for trichuriasis, hookworm, and stronglyloidiasis.

Mebendazole was tested in a double-blind trial for its efficacy in the treatment and control of enteric helminths. One hundred and twenty-two children from a community near the Gulf of Carpentaria, and from a community in Cape York Peninsula in northern Queensland were divided into two equal groups to receive a course of either mebendazole or placebo after the identification of one or more intestinal helminths in a single pretreatment specimen of faeces. Between the tenth and twentieth days after a four-day course of treatment, three specimens of faeces were collected from each child. Mebendazole cured trichuriasis in 75% of cases, and over-all egg reduction rate was 96%. The drug also cured hookworm in 13 out of 15 cases and Strongyloides sterocoralis infestation in 14 out of 21 cases. Mebendazole was ineffective against Hymenolepis nana. No cases of Ascaris lumbricoides infestation were present. No side effects or adverse reactions to the drug were noted and patient acceptance was excellent. Mebendazole appears to be a safe drug for use in the treatment of human parasitic intestinal nematode infestations, and should be especially useful in the treatment and control of trichuriasis.


[Diagnostic relevance of thermography in renal transplantation (author's transl)].

During a followup period of 18 months 75 renal transplant recipients were examined by thermography according to Tricoire. Thermography is a not invasive, quickly available and reproduceable method. Because of the high incidence of 85% exact diagnoses this investigation is a helpful additional test in kidney transplantation for evaluation of graft function as well as for diagnosis for evaluation of graft function as well as for diagnosis of pathological intrarenal or perirenal disorders. Thermography is especially recommendable for transplant patients, if postoperative haemodialysis is necessary. In these cases information can easily be obtained whether postoperative olig-anuria is caused by acute tubular necrosis or by primary insufficient vascularisation of the transplant.


[Echinococcosis.--Current problems of diagnosis and epidemiology (author's transl)].

The indirect hemagglutination-test (IHA) and the indirect immunefluorescence-test are two modern methods for the serological diagnosis of an echinococcosis. If both tests are employed, the disease can be diagnosed with great reliability. A titer of 1 : 128 in the IHA makes the diagnosis of an echinococcosis very likely; a titer exceeding 1 : 1000 is significant. Serological tests of 36 patients with E. cysticus and  E. alveolaris are evaluated; the interpretation of the results is discussed. In all patients the diagnosis was established between October 1977 and October 1978. In Germany the complement fixation test is commonly used to diagnose an echinococcosis. This test, however, is unreliable and fails in one third of all cases. It should be--as well as the Casoni skin-test--replaced by more sensitive and specific reactions. If the complement fixation test is positive, it might be used for postoperative controls. Compared to previous years the disease-rate among Germans is rising. The main reason seems to be the increasing tourism to foreign countries. Serological tests in small laboratories are unreliable and make an evaluation difficult. The diagnosis should be established in specialized centres.