Social interaction, social competence, and friendship in children. The relationship between social skills, social interaction, and popularity was examined. The subjects were 198 children in third and fourth grades in middle- and low-income schools. The relationships between number of friends, socioeconomic status, and grade level were studied in a 2 times 2 times 2 factorial design with 2 sets of dependent measures: (1) social skills were assessed by an experimenter testing each child individually on a set of tasks which included measures of the ability to label emotions in facial expressions, knowledge of how to make friends, giving help, and role-taking ability; and (2) social interaction in the classroom was assessed using a naturalistic observational system. Popular and unpopular children differed in their knowledge of how to make friends and on the referential-communication task. In the classroom, popular children distributed and received more positive reinforcement than unpopular children and spent less time daydreaming. Both grade and social class factors were significant. However, different patterns of results contributed to the main effect of friends and the grade-level main effect. The importance of assessing social skills which are first validated by reference to a criterion such as sociometric position was noted.


[Clinical picture and pathomorphology of traumatic high-pressure oil injections, the so called "grease gun injury"]. On the basis of 3 personal observations the clinical picture, pathomorphology and therapy of the so-called "grease gun injury", are described. Clinically there is a difference between the acute stage, intermediary stage and chronic stage. In accordance with the course of disease are the pathomophological alterations, which are characterized by the development of an epithelioidcell-like granulation tissue. The injected oil is surrounded by histiocytic cell infiltrations, which, due to the chemico-toxic influence of this foreign substance are transformed into epithloidcells. Analogous to the pathogenesis of the tuberculoid granuloma this cellular metamorphosis is based on the action of long-chain fatty acids. It is important that the injured person is given immediate surgical treatment and operation. The aim of this being the entire removal of the oil or grease in order to avoid chronically granulating inflammation of the soft parts as well as the formation of scar tissue.


[Results of the synchronization therapy with vincristine and cyclophosphamide in lymphogranulomatosis, reticulum cell sarcoma and lymphosarcoma. A phase II study (author's transl)]. The effectiveness of synchronization therapy was tested on 88 patients who had already undergone some form of treatment for lymphogranulomatosis (stage III B and IV), generalized reticulum cell sarcoma or lymphosarcoma. This therapeutical concept is based on a partial synchronic increase in tumor cells induced by noncytocidal doses of vincristine, followed by cytostatic or cytocidal treatment with cyclophosphamide during DNA synthesis of the partially synchronized tumor cells. The therapeutic plan is similar to a single-agent therapy. In lymphogranulomatosis, complete remission could be achieved in 14 out of 19 cases (stage III B) and in 9 out of 24 cases (stage IV). The mean remission period during an orally administered cytostatic maintenance therapy was 15 1/2 months. The highest rate of remission was found in the mixed cell type of granulomas (23 out of 24 patients). In the non-Hodgkin's lymphomas, complete remission was achieved in 13 out of 30 cases (lymphosarcoma) and in 19 out of 15 cases (reticulum cell sarcoma). The mean remission period for orally administered cytostatic maintenance therapy was 16 months for lymphosarcoma and 11 1/2 months for reticulum cell sarcoma. These therapeutic results are comparable to those achieved by very effective schemes of combination chemotherapy but the toxic side-effects of synchronization therapy are considerably lower.


[Effect of slow-release aminophylline on pulmonary function in obstructive respiratory disease(author's transl)]. The effects on pulmonary function of a slow-release preparation of an oral broncholytic drug (containing 350 mg aminophylline, released over eight hours) was tested on 26 patients in a double-blind trial. There was a marked reduction of airway resistance and stimulation of breathing with decreased dynamic work of breathing. Distinctly improved alveolar function was demonstrated especially in a fall of arterial CO2 tension, but in some cases there was probably an increase in distribution abnormality. Central haemodynamic changes with a decreased in pulmonary artery pressure and changes in the other values lasted for more than ten hours on the first day of treatment, and were demonstrable on the fourth day even before the drug was taken that day. The criteria of an effective broncholytic slow-release drug with sustained effect were thus fulfilled.


[Fludrocortisone in the treatment of orthostatic hypotension: ophthalmodynamography during standing(author's transl)]. The effect of fludrocortisone (Astonin -H) in the management of orthostatic hypotension was tested in a double-blind trial of 30 patients who were receiving 0.3 mg fludrocortisone for seven days, a control group of 30 subjects receiving placebos. Systolic and diastolic brachial and ophthalmic arterial pressures, pulse amplitude and pulse rate were measured at rest, immediately after standing up and 10 minutes later. Comparing the treatment and placebo groups, the former had a higher systolic ophthalmic blood pressure on standing, a smaller fall of pulse volume and less of a rise in heart rate on standing up, and a raised systolic brachial artery pressure even in recumbency. At the same time there was an improvement in symptoms.


[Work-hygienic studies connected with the manipulation of silver-tin-mercury alloys at the dentists working place]. By means of a spectro-photometric measuring method, tests are made regarding the development of Hg vapors at the dental working place when processing amalgam. Depending on the step in amalgam processing and the location, more or less high Hg vapors concentrations, were measured. They are highest with high-speed, dry preparation of amalgam fillings, they decrease considerably with lower speed and more intensive colling (spray!).


Limbic system involvement in the increase in plasma prolactin following cortical spreading depression in gonadotropin-treated female rats. Cortical spreading depression (SD) was induced by applying 25% KCl to the frontal cerebral cortex in female rats under continuous ether anesthesia. Three weeks previously the animals had been subjected to sham operation, bilateral surgical "deefferentation" of the amygdala or transection of the dorsal columns of the fornix. During the week prior to experiment the rats were made "pseudopregnant" by treatment with PMS and hCG. Plasma prolactin was measured by radioimmunoassay in blood samples obtained from the peripheral circulation at 20 min intervals. After two control samples had been taken, KCl was applied to the cortex and sampling continued for another 100 min; In the sham-operated group prolactin levels increased with time following the application of KCl. Fornix-cut animals showed a similar, although briefer, increase with values significantly lower than those found in sham-operated animals at 80 min. The increase in plasma prolactin observed in sham-operated and fornix groups was completely abolished in amygdala-cut animals. These results indicate that limbic structures play a significant role in the mechanisms by which cortical SD elevates plasma prolactin levels under the present experimental conditions.


The effects of Methallibure (ICI 33,828) on the LH release in castrate male rats challenged with LHRH. Daily administration of 10 mg of Methallibure (ICI 33,828) for 6 days to male castrate rats resulted in significant depression of serum radioimmunoassayable luteinizing hormone (LH). Subsequent challenge with 100 ng of synthetic luteinizing hormone-releasing hormone (LHRH) showed these rats to release sufficient pituitary LH to achieve plasma levels equal to those of LHRH treated castrate controls. Although an effect at the level of the pituitary remains to be conclusively ruled out, these results suggest that the predominant in vivo effect of Methallibure in the castrate male rat is to suppress pituitary LH release due to diminished secretion of LHRH by the hypothalamus.


Recent research into the nutrition of the horse. The majority of recent experiments in equine nutrition relates to the metabolism of protein, non-protein nitrogen, carbohydrate, calcium and phosphorus. An understanding of the significance of the nitrogen cycle is emerging in which there is a two-way movement of compounds across the wall of the G.I. tract. Some quantitative estimates of the role of microflora in this process have been made for comparison with similar processes in ruminants. However, the pathway by which the microflora contributes to the nitrogen economy and the extent to which this occurs is not established in the horse. It is well established that both glucose and volatile fatty acids are common substrates in tissue metabolism; but in contrast to evidence in the ruminant the ratio of starch to fibre in the diet does not affect the efficiency fo fibre digestibility. This, and similar observations, are explicable in terms of the anatomy of the G.I. tract of the horse. There is a scarcity of information on the secretion of digestive enzymes by the horse and on the relationship between intestinal function and certain digestive upsets. Furthermore, there is an urgent need for accurate clinical evidence for the significance of calcium and phosphorus nutrition to the development of leg abnormalities in horses. The irrelevance, for diagnosing purposes, of estimates of serum Ca and P is concluded, especially where no other relevant information is available. Haematological procedures, of diagnostic value in this respect, are available for use at least in controlled clinical conditions.


Studies on the oxygen supply of heterotopic auxiliary liver grafts in rats. Heterotopic auxiliary liver transplantations were performed in rats using the method of Hess et. al. [6]. Oxygen pressure of liver tissue was measured with a Pt-surface electrode of Kessler and Lübbers [10]. After ligation of the hepatic artery, liver tissue PO2 decreased and remained low during further preparation. Only two of the seven lobes of the rat liver (= 30% of the parenchyma) were used as a graft. After revascularization and application of a gelatine plasma substitute, tissue PO2 of the graft increased to values of normal rat liver, although the graft was supplied with portal blood only. We suggest that one reason for this is the increase of portal perfusion rate, for the whole amount of portal blood perfuses only 30% of liver parenchyma. In the first month after transplantation PO2 of the graft parenchyma was low, but increased continually in the following months, reaching PO2 values of normal rat livers after 1 year.


Early recovery of albumin synthesis after liver transplantation. The delay necessary for an orthotopic transplanted liver to recover in normal activity has never been defined. This is of great importance whenever liver transplantation is considered in patients with severe liver insufficiency. This delay was studied in dogs using albumin synthesis and BSP clearance as tests of liver function. Albumin synthesis was normal as early as 2 h following graft revascularization while BSP clearance was not yet normal by this time. It is suggested that transplanted livers will be rapidly able to corect metabolic disorders and above all coagulation problems in patients with terminal hepatic failure.


Glucagon and insulin release from the allografted canine pancreas. Six previously pancreatectomized dogs were transplanted with duct-ligated, pancreatic allografts. Glucagon and insulin levels in the venous outflow from the graft and in the systemic circulation were determined during the first 60 minutes after transplantation. Two of the dogs were subjected to L-arginine stimulation 5 days after transplantation and the glucagon levels in the venous outflow from the graft were determined. The glucagon and insulin concentrations increased rapidly after transplantation, describing a biphasic curve. In response to L-arginine stimulation, an increased glucagon release was observed.


Measurement of erythropoiesis by radio-iron incorporation: influence of iron- and cell kinetic changes. 59Fe blood appearance curves have been obtained in mice by injection of the isotope at various times after 850 rad whole body X-irradiation and bone marrow grafting in order to produce different levels of erythropoiesis. The results demonstrate that measurements at 24, 48 and 72 hours are not comparable and lead to different interpretations. Standardization of the time at which 59Fe uptake measurements are made is therefore recommended.


The effects of antilymphocyte sera on bone marrow allograft rejection. Prior sensitization can be a problem in successful graft take in bone marrow therapy. Spleen weight and femoral marrow cellularity have been used as indices of successful graft take in lethally irradiated mice receiving bone marrow allografts. Recovery if poor in mice sensitized, at least 6 days before irradiation and bone marrow therapy, to an intraperitoneal injection of allogenic bone marrow cells. Rabbit anti-mouse lymphocyte serum, normal rabbit serum and pig anti-mouse lymphocyte serum but not normal pig serum partially ablate tis immunity when administered 8 and 10 days after sensitization. Normal rabbit serum is, however, ineffective when administratered 26 and 28 days after sensitization whereas rabbit anti-mouse lymphocyte serum completely ablates this immunity. These findings demonstrate the marked radioresistance of the secondary response to bone marrow allografts and further show the effectiveness of antilymphocyte sera in ablating this immunity.


Quantitative measurements on the haemopoietic systems of three strains of mice. Quantitative measurements on the haemopoiedic systems of SAS/4, 3H and RFM mice have been used to calculate the distribution and population sizes of haemopoietic cells in the bone marrow, spleen and peripheral blood. Considerable strain differences have been found in the sizes of haemopioetic stem cell populations and in the distribution of these cells within the haemopioetic system, although the incidence of CFU-S was shown to be uniform throughout skeletal sites of haemopioesis. The seeding efficiency of colony forming cells in the spleen, measured by the 'f" factor 24 hours after irradiation and transplantation, also differs between strains and between the bone marrow and spleen of the strains investigated.


Children born to women denied abortion.

Children born to women denied abortion. 'Compulsory childbearing has varied and sometimes unfavorable consequences for the subsequent life of the child.... The higher incidence of illness and hospitalization..., slightly poorer school marks and performance, somewhat worse integrationin the peer group--all point to a higher risk situation for the (unwanted) child and the family, as well as for society.... Boys born from unwanted pregnancies are more endangered in the development of their personalities than girls'.


Physical dependence on alcohol in mice.

Physical dependence on alcohol in mice. Although it has not yet been possible to construct a complete model of alcoholism in experimental animals; some aspects of the disease can now be studied with satisfactory laboratory systems. Production of physical dependence requires a period of continuous intoxication; brief intervals of sobriety allow the accrued dependence to disappear. Administration of ethanol by inhalation, with daily injections of pyrazole, allows maintenance of stable blood alcohol levels in mice. In this model, physical dependence arises to its maximum in a week or two and can decay in less than a day. Sedative drugs suppress the mouse withdrawal reactions but drugs that intefere with catecholamine or gamma-aminobutyric acid pathways facilitate withdrawal seizures. Susceptibility to withdrawal seizures is controlled in part by genetic factors.


Direct effects of ethanol on the nervous system. Neurophysiological, neurochemical and behavioral studies of the effects of ethanol on the nervous system have so far failed to identify specific, direct, primary mechnisms of action that may account for the typical pattern of alcohol intoxication in vivo. Electroencephalogram and evoked response studies indicate biphasic effects in the intact subject, which may correlate better with the level of arousal than with a specific drug action. Effects on spinal reflexes are also biphasic, probably representing the net result of direct influence on resting membrane potential, primary afferent depolarization, and neurotransmitter release. With the exception of its inhibitory effect on release of oxytocin, vasopressin and possibly other hypothalamic peptides, ethanol does not appear notably different in its spectrum of effects from a wide range of other hypnotics, anesthetics and minor tranquilizers. Interpretation of the findings is complicated by the fact that functional alteration of any given neuronal system by ethanol in vivo may reflect a) direct local action of ethanol on the cells under study, b) change in the input to those cells because of an action elsewhere in the nervous system, c) effects of ethanol metabolites, or d) indirect consequences of decreased blood flow, oxygen or metabolite supply, hormonal action, or hypothermia, due to disturbances of homeostasis in the whole body as a result of deep intoxication. To date, attempts to circmvent b, c and d by the study of brain tissue in vitro have shown consistent effects of ethanol only at concentrations well above those that are meaningful in vivo. Relatively specific patterns of action of different drugs in vivo may prove to be largely dependent on their customary rates and routes of administration, and on summation of minor differences in the dose-response curves with different types of neuron, even though the basic types of molecular action may be essentially similar.


Ethanol and brain ribosomes.

Ethanol and brain ribosomes. The effects of chronic ethanol intake by mice and rats have been determined on brain ribosomes. Under conditions of ethanol administration, when physical dependence on ethanol either does or does not develop in rats, significant inhibition of polypeptide synthesis was observed in comparison with animals not receiving ethanol. In both rats and mice drinking a 10% ethanol solution, in vitro protein synthesis was found to be diminished more in the free than membrane-bound polyribosomes (polysomes) when compared to similar fractions obtained from control animals. Addition of exogenous amino acids stimulated protein synthesis of free polysomes to a greater extent than that of bound polysomes obtained from both groups of micemin vivo incorporation of [5-3H]-orotic acid into RNA was more inhibited in polysomes than ribosomes of ethanol-drinking mice, suggesting that ethanol affects messenger RNA. In addition, chronic ethanol ingestion produced a decreased in vivo incorporation in ribosomal RNA of a mixed population of ribosomes and polysomes. Chronic ethanol ingestion by mice led also to a differential effect on the polysomal population of the brain. It decreased the amount and the incorporation of precursor label into RNA of free polysomes while exerting an opposite effect on bound polysomes. The significance of these findings relative to brain metabolism is discussed.


Supersensitivity-like phenomena in the central nervous system. The are numerous supersensitivity-like changes in the central nervous system associated with denervation and disuse. There is little evidence, however, for increases in postjunctional sensitivity exactly parallel to that which occurs in disused effector organs. As we learn more about the mechanisms responsible for supersensitivity in effector organs, it becomes evident that the operation of such mechanisms in neurons may have reverberations in all spheres of cellular function, including transmitter release and energy control as well as receptor function.


Use of synthetic luteinizing hormone-releasing hormone in induction of ovulation in amenorrheic patients. Luteinizing hormone-releasing hormone (LH-RH), administered to normal women in divided intrramuscular doses or by intravenous infusion, resulted in a prolonged release of luteinizing hormone and follicle-stimulating hormone from the pituitary gland, reliably resulting in ovulation during the late follicular phase. LH-RH was administered 6 days after clomiphene to 18 amenorrheic, anovulatory, infertile women in whom clomiphene therapy had failed previously. When LH-RH was administered intramuscularly in two divided doses, ovulation occurred in six of eight women and in 11 of 22 woman-months of stimulation (50%). One pregnancy occurred. When LH-RH was administered by intravenous infusion, ovulation occurred in nine of ten women and in 16 of 26 woman-months of stimulation (61.5%); three of the ten women became pregnant. Pregnancy also followed treatment withLH-RH in one patient with irregular menses and functional sterility.


The presence of peptidases in the rabbit hypothalamus capable of inactivating luteinizing hormone-releasing hormone. The presence of peptidases in the rabbit hypothalamus capable of inactivating luteinizing hormone-releasing hormone (LH-RH) was investigated with the use of a sensitive and specific radioimmunoassay for the releasing hormone. Enzymes acting on LH-RH were found in two fractions from rabbit hypothalami, a particulate fraction and a supernatant fraction, which very rapidly inactivated the decapeptide. Peptidase activity in the particulate fraction from male and female rabbits was approximately the same, but the supernatant fraction from female animals had significantly greater peptidase activity than that from male animals. These findings confirm the hypothesis that rabbit hypothalamus contains peptidases which inactivate LH-RH, and give some indication that the enzymes may be involved in the control by the central nervous system of reproductive function.


Psoriasis: a review. II.

Psoriasis: a review. II. Notwithstanding the intense interest in systemic cytotoxic therapy in recent years, the great majority in psoriatics are likely to go on needing topical therapy with tar, dithranol or corticosteroids, and a welcome trend is the spreading of interest in day care centres such as those in Paris (GRUPPER), Stockholm (THYRESSON), Stanford (FARBER) and San Francisco (CRAM) evolving from the out-patient regimes advocated by INGRAM in Leeds a generation ago.


Effect of glucose and anti-insulin serum on insulin released from adult rat isolated islets of Langerhans in long-term organ culture (fourteen days). Isolated islets of Langerhans from adult male rats were cultured in media containing either basal (1 gm./ml.) or high glucose (3 mg./ml.), and the media were changed every two days for fourteen days. The insulin released in each medium was measured by a back-titration radioimmunoassay. Insulin secretion was fairly constant in the basal glucose medium and a consistent three-to-sevenfold increase was observed in the alternated or continuous presence of high glucose. Addition of an excess of anti-insulin serum did not change significantly the basal or stimulated release of insulin. The electron microscopic appearance of the islets after fourteen days of incubation showed well-preserved islets both with or without anti-insulin serum. Anti-insulin serum did not alter the ultrastructural aspects of the islets in either basal or high glucose media.


Effect of lectins on hormone release from isolated rat islets of langerhans. Lectins from Agaricus bisporus and Agaricus campestris stimulate insulin and glucagon release from isolated rat islets in the presence of 2 mM glucose. In the case of insulin release, maximal stimulation was observed at lectin concentrations above 58 mug. per milliliter (approximately 1 muM).A. bisporus PHA-B-stimulated insulin release was independent of a source of metabolic energy but was abolished by deuterium oxide. The lectin did not alter islet glucose oxidation to CO2 or incorporation of [3H] leucine into trichloracetic acid-precipitable material nor did it modify rates of insulin secretion induced by 20 mM glucose. None of nine other lectins tested stimulated insulin release, whereas stimulation of fat cell glucose oxidation was a general property of the lectins. Binding of 125I-labeled A. bisporus PHA-B to islets increased with time up to one hour and after attainment of equilibrium was very slowly reversible. Binding was directly proportional to islet number and the estimated Kdiss of the binding reaction was 17 mug per milliliter. The total number of A. bisporus PHA-B binding sites per islet was approximately 2 times 10(10). Binding of A. bisporus PHA-B to the islets and A. bisporus PHA-B-stimulated insulin release were inhibited in parallel by a glycopeptide containing the oligosaccharide receptor for the lectin, suggesting that lectin binding is essential for the expression of insulin-releasing activity. It is proposed that the specific interaction between mushroom lectin and its receptors may lead to conformational changes in the structure of the membranes of the islet A2- and B-cells that facilitate exocytosis.


Effects of cyproheptadine on insulin secretion by isolated perifused rat islets. The effects of cyproheptadine on basal and glucose-induced insulin release by isolated rat islets was studied by use of a perifusion system. A forty-five minute preincubation of islets with a medium containing both 34.3 mug./ml. (10(-4) M) cyproheptadine and 1.0 mg./ml. glucose completely abolished the biphasic pattern of increased insulin secretion normally obtained after islets are stimulated with a medium containing 3.0 mg./ml. glucose. In another series of experiments, similar results were obtained when the cyproheptadine and 3.0 mg./ml. glucose were presented together. Here, however, the inhibition of the first phase of insulin secretion did not achieve statistical significance and some recovery of the islets' secretory capacity was observed late during the second phase. In studies designed to investigate the influence of cyproheptadine on basal insulin secretion, no obvious effect was observed. These results are discussed in relation to the species-specific alterations in pancreatic beta-cell morphology that have been reported in rats after the oral administration of cyproheptadine.


The tropic action of gastro-intestinal hormones. There is evidence that under various physiological circumstances long-term adaptation of structure and function of the gut occurs. The mechanisms of these changes are not clear but gastro-intestinal hormones may be involved. In particular, gastrin which has been shown experimentally to stimulate growth and development of parts of the gut, probably has a role in maintaining the structure of the normal upper alimentary tract. Cholecystokinin may be of major importance in producing adaptive changes in the pancreas in response to dietary modifications and enteroglucagon is possibly concerned with maintaining a normal small intestinal structure. The importance of the 'trophic' action of gatrointestinal hormones is becoming more widely recognised and as new gastro-intestinal hormones become established, this aspect of their physiological importance as well as their acute effects, will deserve attention.


Hepatic veno-occlusive disease in a renal transplant patient receiving azathioprine. Central vein phlebitis and occlusion developed in a patient who was receiving immunosuppressive therapy with azathioprine (Imuran) and prednisone after renal transplantation. He had been well for 1 year before evidence of liver disease was noted; once begun, it progressed to hepatocellular failure in spite of a change in immunosuppressants from azathioprine to cyclophosphamide. Several known causes of venoocclusive disease and the possible causes in this patient are discussed.


The problems of abdominal operations in elderly patients. In a series of 152 patients aged 65 years or older who underwent abdominal operations between January 1 and December 31, 1971, the total mortality was 17 percent. Pulmonary pathologic conditions were responsible for the majority of the deaths. Use of IPPB did not significantly influence the postoperative course. This study suggests that meticulous preoperative preparation of patients; deliberate, clean, and efficient surgical techniques; and intensive postoperative care are of utmost importance in surgical treatment of the elderly.


Aspects of the effect of metiamide on pentagastrin-stimulated and basal gastric secretion of acid and pepsin in man. This study has examined the inhibition produced by metiamide on the gastric secretion of acid and pepsin in 13 patients with duodenal and three with gastric ulcer. The effect of metiamide on the response to a range of doses of pentagastrin in three normal individuals was determined, as was the interaction of metiamide and atropine on prolonged basal secretion. Metiamide inhibited the secretion of acid more than pepsin and the gastric secretion of patients with gastric ulcer more than duodenal ulcer. Metiamide inhibited both the maximal secretory response attainable with pentagastrin and decreased the sensitivity to pentagastrin. Atropine augmented and prolonged the action of metiamide.


Development of host resistance to Fasciola hepatica after the elimination of primary infection with diamphenethide. We studied the specificity of the individual developmental stages of Fasciola hepatica for evoking immune response of the host to reinfection with this parasite, whereby the primary infection was eliminated by a dose of 150 mg/kg diamphenethide administered in various intervals. In rats we observed a state of hypersensitivity demonstrated by retarded migration and growth of the flukes and the reduction in the number of sexually developed parasites. The changes were most marked, if the elimination of the immunizing infection followed 8-10 weeks after primary infection.


Effects of various cerebral metabolic activators on glucose metabolism of brain. The effects of various metabolic activators on the glucose metabolism of the perfused cat brain have been investigated.  (1) When the perfusion is done with the blood containing cytidine monophosphate, the glucose metabolism of the brain is enhanced, as compared to the perfusion with the blood without cytidine monophosphate.  There is no marked change in the cerebral metabolic rate and in the contents of intermediate metabolite of glucose in the brain.  (2) Citicoline enhances the incorporation of blood glucose into the brain and its metabolism in the brain.  It increases slightly the cerebral blood flow rate and decreases the accumulation of lactate in the brain.  (3) Either Pyrithioxin or Meclophenoxate has no effect on the glucose metabolism of the brain nor on the cerebral metabolic rate.


[Symptom-centered group therapy for phobias--the problem-oriented workshop in psychotherapy]. Short term psychotherapy is increasingly recognized as a socioeconomic necessity. Problem-oriented treatments, particularly if applied in problem-homogenous groups, are one means of economizing and sometimes even improving psychotherapy. They also require a re-evaluation of the nature of the patient-therapist dyad. The "task-oriented small group" as a basic field of human interaction has been studied intensively in experimental social psychology. Nevertheless, group psychotherapy and behavior therapy have largely neglected group-specific aspects of such variables as cohesion, task-orientation, modelling, mutual self-help, risk-taking, motivation and insight. This paper outlines some recent changes in this respect, and discusses in particular the "symptomoriented peer workshop" as a treatment milieu. The general therapeutic potential of the peer workshop is briefly assessed with regard to the application of the above mentioned group variables in peer self-help groups, rehabilitation programs for the chronically hospitalized, symptom or depth-treatment in short-term psychotherapy, and in re-education programs for problem-children. The main concern is with its specific application to the treatment of phobias. Phobias are comparatively easy to define, yet are often connected with other personality problems. This has made them a model-problem in the arguments about symptom-substitution between "psycho"- and "behavior" -therapists, and it has stimulated discussion as to how behavior-focused treatments affect cognition and emotion, and to what extend depth and insight-oriented therapies change behavior. The interaction between treated and non-treated problems, and the behavioral, cognitive and emotional effects of differential treatment ingredients are discussed with special reference to the first controlled study in behavior therapy, that applied behavior-focussed confrontation with reality (flooding in vivo) under the sociodynamics of the small gsoup. Problem-focussed retraining under real-life conditions (reality testing) as group-therapeutic fieldwork can be a means of treatment in its own right may open up the patient for subsequent attempts to tackle more complex problems, or may just be an adjuvant in a multi-level approach. This certainly applies for phobias and can probably be generalized to other problems.


Induction of pseudopregnancy in the rat by electrochemical stimulation of the brain. Electrochemical stimulation of the neocortex, VMH-arcuate hypothalamus, medial preoptic area, corticomedial amygdala, and dorsal hippocampus was performed under pentobarbital anesthesia to determine the brain regions involved in prolactin release as evidenced by pseudopregnancy. Stimulation occurred on the day of vaginal estrus, followed 4 days later by uterine traumatization. All animals were sacrificed 8 days after brain stimulation. Medial preoptic sitmulation resulted in an 83% incidence of pseudopregnancy while VMH-arcuate stimulation resulted in 43% incidence. Amygdaloid and hippocampal stimulation resulted in a lower incidence of pseudopregnancy (20 and 24%, respectively). Stimulation of the neocortex or sham stimulation of the five brain regions did not induce pseudopregnancy. These data indicate that the MPOA and VMH-arcuate hypothalamus are areas which may facilitate the release of prolactin necessary for the development of pseudopregnancy. The lower incidence of deciduomata formation resulting from electrochemical stimulation on the amygdala and hippocampus suggest that these areas have a minor effect on stimulating the induction of pseudopregnancy.


Twenty-five years of hospital and community psychiatry: 1945-1970. The author, the first medical director of the American Psychiatric Association and APA president in 1964-65, presents a historical review of the 25 years between 1945 and 1970, a period in which there was a reawakening of interest in the mentally ill and mentally retarded after years of neglect. He lists major landmarks in mental health care during those years, describes the first Mental Hospital Institiute held by the American Psychiatric Association in 1949, and presents an anecdotal footnote about the Joint Commission on Mental Illness and Health.


Further characterization of antigen-dependent migration inhibition factor in mice. Antigen-dependent MIF was produced in inbred mice. Lymph node cells from mice sensitized to tubercle bacilli were incubated with small quantities of antigen. The supernatant contained antigen-dependent MIF and its activity when tested on mouse and rabbit spleen was minimal unless PPD was added to the supernatant. The production of the antigen-dependent MIF was T cell-dependent, as shown by the use of anti-theta serum. Its molecular weight was in the range of 50--100,000 and it was concluded that the factor is different from conventional antibodies or antigen-antibody complexes.


The recovery of the B-cell population in adult thymectomized, lethally irradiated and bone marrow-reconstituted mice. The recovery of the B-cell population in adult thymectomized, irradiated and bone marrow-reconstituted mice (T X BM mice was estimated at various times after bone marrow transplantation. The spleen cells to be tested were mixed with dexamethasone-resistant thymocytes (DRT) and sheep red blood cells (SRBC) and transferrred to irradiated recipients. The number of plaque-forming cells (PFC) in the spleen of the recipients was determined 7 days later. Using this functional B-cell assay a sequential appearance of the precursors of IgM-, IgG- and IgA-PFC in the spleen of T X BM mice was observed. The precursors of IgM-PFG (IgM-B cells) were present immediately after transplantation. The first IgG-B cells could be detected at 13-16 days after transplantation and the IgA-B cells finally appeared at 22 days after transplantation. The number of B cells reached a constant and normal level at 30 days after transplantation. The IgM-, IgG- and IgA-B cell development in sham-thymectomized, irradiated and bone narrow-reconstituted mice (ST X BM mice) was virtually the same as in T X BM mice.


Levels of lysosomal enzymes in tissues of mice infected with Mycoplasma fermentans. The effects of a toxic dose of Mycoplasma fermentans on levels of lysosomal enzymes in mice were examined. Washed cell suspensions (approximately 10(10) colony-forming units) of a recent isolate of M. fermentans were injected intraperitoneally into 3- to 4-week-old BALB mice, and levels of acid phosphatase and beta-glucuronidase were monitored in liver, spleen, thymus, and serum. Levels of acid phosphatase remained essentially normal, but levels of beta-glucuronidase were markedly evevated in serum and to a lesser extent in liver and thymus. The peak response of serum beta-glucuronidase was noted at 8 h postinjection, with a level of 30 mug of phenolphthalein released per ml per h, representing a six-fold increase over control levels. Pretreatment with BCG did not potentiate the effect as it did with endotoxin. The implication of this increased lysosomal enzyme activity in "lethal toxicity" is that that the increase may be secondary to some other cytotoxic event, or that the affinity of mycoplasmas for biological membranes may be involved. The data suggest that the role of lysosomal enzymes in other models of mycoplasma-induced disease should be evaluated.


Sequential appearance of salivary antibodies after oral immunization of axenic mice. The purpose of the present investigation was to examine the production of specific salivary antibodies after oral immunization of axenic mice (ICR/CD-1) with formalinized Escherichia coli (ATCC 11775). Three aspects of the humoral response were studied: (i) the sequential appearance of anti-E. coli antibodies; (ii) classes of antibodies produced in response to the antigen; and (iii) antibody specificity. Antibody levels were determined by passive hemagglutination with soluble lipoplysaccharide and bacterial agglutination, using preparations of somatic O and flagellar H antigens. A short latent period of 1 to 3 days was observed when saliva samples were assayed for anti-lipopolysaccharide and anti-O antibodies. The salivary antibody titers peaked at 11 days after initiation of the immunization regimen. Only two of six mice exhibited a change in serum antibody levels against these antigens. The predominant class of early antibody in saliva was immunoglobulin (Ig)G; however by 7 days IgA WAS found to comprise the major portion of specific immunoglobulins. Serum antibodies directed against falgellar antigenic determinants were primarily of the IgM class, whereas the salivary antibodies were IgG in nature.


In situ separation of bacterial trapping and killing functions of the perfused liver. CF-1 mice cleared and killed 80% of a 1.2 x 10(9) intravenous dose of Salmonella typhimurium after 30 min. The perfused mouse liver trapped 70% of a similar dose of S. typhimurium in a single pass, but in the perfusion model no significant killing of the trapped organisms was observed. The perfused rat liver also avidly trapped bacteria. Because of its larger size, we have been able to devise techniques to experimentally distinguish between the bacterial trapping and killing functions of this organ. When the liver was washed free of blood with sterile M-199, over 70 to 80% of a 10(6) to 10(10) dose of viable S. typhimurium was trapped after a single pass, but no significant bacterial killing was observed. When blood or plasma was added to the perfusion medium, over 50% of the trapped bacteria were killed in 15 to 30 min. Phase contrast and electron micrographs of perfused livers showed extensive extracellular trapping of bacteria in the sinusoids. Our data show that humoral factors are apparently not necessary for efficient trapping of live Salmonella by the perfused rat liver but are an absolute requirement for bacterial activity of the organ.


The Fédération Dentaire Internationale, 1900-1975. The author presents an historical survey of the development of the Fédération Dentaire Internationale. Beginning with its foundation by Charles Godon in 1900 he describes the growth of the Federation as an organization of the dental profession which continued despite the interruption of two world wars. The most important aims and events of the first 50 years are presented in chronological sequence. In the period of the last 25 years--after the London Congress of 1952---the main emphasis is placed on describing the present structure and objectives of the Federation. Brief reflections on the Federation of today conclude the article.


The mystery bridges of Martin Bormann's alleged Berlin skull--key clues for forensic identification or another Piltdown case? Dental records prepared by Martin Bormann's dentist Dr Hugo Blaschke in 1945 have been examined in the Captured Military Record Branch of the US National Archives in 1972 and compared with the direct evidence from examination of skeletal remains unearthed in Berlin in 1972 at a site next to Lehrter RR station where Bormann is known to have been seen alive for the last time on May 2, 1945. There is adequate qualitative and quantitative concurrence between all available antemortem and postmortem dental data to ascertain that the forensic identification of Martin Bormann can be considered established.


Lymphokines in sensitized rats. I. Migration inhibitory factor(s) from specifically stimulated thymocytes in vitro. Cell-mediated immune responses were studied in Wistar rats by migration inhibition factor (MIF) assays in vitro of lymphoid cells derived from thymus, spleen and peripheral blood and peritoneal exudates and by delayed cutaneous hypersensitivity reactions in vivo. Using PPD and purified diphtheria toxoid as soluble test antigens it appeared that significant migration inhibition was observed only when sensitized thymus and peritoneal exudate cells were used in the direct capillary migration system. Indirect MIF assays, using both capillary and agarose techniques, showed that migration inhibitory activity was found in thymus culture supernatants as well as in spleen culture supernatants of sensitized animals. The MIF activity in thymic cell culture supernatants seemed to be antigen-independent, although in this respect no definitive conclusions can be drawn from the present results. Migration inhibition in direct and indirect techniques always correlated with a positive delayed-type skin reaction. It is suggested that a population of thymus cells of sensitized animals is able to produce MIF on specific antigenic stimulation in vitro. This might support the idea that a cell population within the thymus possesses characteristics of peripheral T cells.


Lymphokines. I. Use of insoluble concanavalin A for the production of migration inhibitory factor in guinea pig lymphocyte cultures. Incubation of guinea pig lymph node lymphocytes with insoluble concanavalin A (Con A) in serum-free medium yields sizable amounts of migration inhibition (MIF) and mitogenic factors (MF). Various controls confirmed that the activities detected in supernatants from such cultures are not due to free soluble Con A released during culture. Whereas guinea pig MIF does not act upon human and horse monocytes, guinea pig MF stimulated human but not horse lymphocytes. Upon stimulation by insoluble Con A, guinea pig MIF and MF appear to be produced essentially by T lymphocytes. The technique proposed for producing lymphokines appears convenient for further purification and biochemical characterization of culture supernatants.


Regulation of antibody formation in chickens escaping from tolerance to human serum albumin. The immune capacity of chickens made tolerant to human serum albumin just after hatching was studied after a primary and secondary challenge at 7--14 weeks of age, of either 1 mg/kg or 100 mg/kg. The class and avidity of antibody produced by birds "escaping" from tolerance was similar to normal controls. The escaping chickens made a normal peak antibody response to a high dose but not to a low dose (except that the response to a low secondary dose after priming with a high dose was normal); but the decline of the antibody titer was abrupt, indicating inability to maintain the response. It is concluded that the antibody-forming capacity of B cells is normal, but regulation of antibody formation is impaired in previously tolerant chickens.


Behaviour of local and systemic immunoglobulins in patients with lung cancer. Tissue blocks from lung parenchyma in the vicinity of primary lung cancer and regional lymph nodes were collected during surgery from 22 patients. Cryostat sections were assessed for the presence of five five immunoglobulin classes by means of immunofluorescence. Imprints made from surfaces of freshly resected tumours were used for indirect immunofluorescent reaction to detect anti-tumour antibodies in the autologous system sera of patients after surgery. Also, sera of 60 lung cancer patients were assessed for IgG, A, M levels. It has been found that the direct vicinity of primary lung cancer and regional lymph nodes was a site of intensive immunoglobulin synthesis is plasma cells, with a predominance of the IgA and IgG classes. Serum anti-tumour antibody was found in 3 cases out of 22. There were significantly elevated serum immunoglobulin levels with predominance of IgA and IgG. Inoperable patients had higher immunoglobulin levels then those who underwent surgery.


Yoshida ascites sarcoma grown in mice.

Yoshida ascites sarcoma grown in mice. Xenogeneic Yoshida ascites sarcoma grows well in the abdominal cavity of thymectomized, irradiated mice reconstituted with syngeneic bone marrow. These animals displayed a 100-percent mortality. In control sham-thymectomized, irradiated mice reconstituted with syngeneic bone marrow mortality was significantly lower. The tumor growth could be neutralized by means of single intravenous injection of nonimmune spleen cells inoculated at the same time as the tumor. Tumor cells grown in mice killed normal rats and were rejected by normal mice.


Organization and unionization of health workers in the United States: the trade union perspective. Recent legislation in Washington opened the door to organization and unionization of health workers in voluntary hospitals and highlighted the poor pay and unorganized status of this enormous work force of at least 1.5 million persons, many of whom are women, black, or Spanish-speaking. The authors, who are senior officials of District 1199 of the National Union of Hospital and Health Care Employees, chart the factors associated with the low priority given over the years to organizing hospital workers, and the first breakthroughs, in New York City hospitals, in 1958. From a start with lowest income hospital workers, the subsequent inclusion of technical and professional workers and linkages with the highly publicized hospital workers' strike in Charleston, South Carolina in 1969. The benefits of unionization and the broader social goals of the union are discussed.


Unionization, strikes, threatened strikes, and hospitals--the view from hospital management. The history of union organizing efforts in the hospital field is discussed in this article, along with the factors judged necessary for successful union organizing. The role played by labor legislation in the unionization of hospital workers is shown, and the influences of the National Labor Relations Act, the Taft-Hartley amendments, and labor legislation at the local level are described. Management has largely resisted unionization because of the social nature of hospitals. Competitive market forces do not confront the not-for-profit hospitals, which are dependent upon third-party reimbursement. While strikes are an integral and essential part of collective bargaining in industry, they are, in fact, detrimental to hospitals because of these institutions' concern with human life. Despite laws and assurances from labor leaders that strikes will not occur, strikes have been used as a method for resolving disputes, through they are basically inconsistent with the economic characteristics and objectives of the hospital. The authors conclude that arbitration awards should be made by arbitrators appointed from outside of the local region of the hospital involved, ant that, because of the catastrophic effect of strikes upon patients as well as employees, arbitration awards should be required, should be binding upon both parties, and should be federally enforced.


The chemotherapy of infections due to nocardia. Recent studies in vitro have revealed marked susceptibility of Nocardia asteroides to minocycline and to the synergistic combination of ampicillin plus erythromycin. Sulfonamides remain as the proven and well-used agents for this potentially fatal infection seen commonly in the compriomised host.


Clomacran in the treatment of schizophrenic patients: a comparison of two assessment methods. In an uncontrolled clinical trial clomacran, the chlorpromazine analogue of the acridane series, was found to be therapeutically effective in the treatment of newly admitted schizophrenic patients. There was essentially no difference in the sensitivity of the two assessment instruments, i.e. BPRS and PAF, in the detection of therapeutic changes. On the other hand, the PAF, a 123-item scale, was found to be more sensitive for the description of a schizophrenic patient population than the BPRS, an 18-item scale.


The effect of methylphenidate on cardiovascular sensory differentiation on the hyperkinetic syndrome. In the present study, the action of methylphenidate on mean heart rate was studied while hyperkinetic children were attending to monosensory, bisensory and trisensory stimuli presentations. Neither children receiving methylphenidate nor those receiving placebo exhibited a significant shift in tonic heart rate during relaxation periods. While attending to sensory stimuli, heart rates were higher for children receiving placebo than for those receiving methylphenidate in all experimental conditions for the high and moderate degrees of hyperkinetic behavior. A drug reversal effect was demonstrated in mildly hyperkinetic children.


Effect of quinacrine, chloroquine and primaquine on the multiplication of Mycobacterium leprae in mice. Quinacrine administered in 100 mg per kg body weight to mice had a bacteriostatic activity on M. leprae in the mouse, chloroquine at 15 mg per kg and primaquine at 0.25 mg per kg were without activity. These findings could point to the presence of a functioning direct oxidative pathway of glucose catabolism in M. leprae.


Separation of Mycobacterium lepraemurium from the subcutaneous tissues of the rat. In an effort to obtain cell suspensions free from blood cells which interfere in spectrophotometric studies, a method was devised by which relatively large quantities of whole cell suspensions of M. lepraemurium are obtained for experimental purposes. We have routinely employed this procedure which is quite reliable, technically simple, moderate in equipment requirements, and in a matter of five minutes it can be ascertained whether or not the preparations are free from contaminants which render the purified bacillary suspensions unsuitable for studies involving spectrophotometric technics. However, in this procedure, certain points are essential in order to obtain large quantities of purified bacillary suspensions. It is important to homogenize the lepromata for only a few seconds at brief intervals. Excessive homogenization may cause considerable damage to the bacilli and it may be difficult to separate the bacilli from the host tissues. It is also important to use transparent bottles and tubes during centrifugation as the material can be seen and thus each fraction can be separated easily. Very few bacilli are lost in the discarded material and we have repeatedly obtained 2.5 to 3 gm wet weight of M. lepraemurium from one leproma weighing 25 gm to 30 gm.


Acid mucopolysaccharide metabolism in leprosy. 3. Hyaluronic acid mycobacterial growth enhancement, and growth suppression by saccharic acid and vitamin C as inhibitors of beta-glucuronidase. A series of pilot studies are presented utilizing mouse and human infections with M. leprae and mouse infections with M. lepraemurium relating to the previously reported finding that hyaluronic acid seems to be a major nutrient substrate for these bacilli. The "feeding" of hyaluronic acid to the bacilli enhanced the growth of M. leprae in mouse abdominal walls and increased the Morphologic Index of M. lepraemurium infection. Saccharic acid, an inhibitor of beta-glucuronidase previously reported as present in these leprosy bacilli, caused marked regression of advanced M. lepraemurium infection, inhii. Ascorbic acid (vitamin C), also an inhibitor of beta-glucuronidase, given at a level of 1.5 gm/day for 4.5 months to one lepromatous patient without other treatment and for up to 24 months to four other lepromatous patients receiving DDS, was accompanied by lesion regression and changes in bacillary morphology similar to those seen in the inhibitor treated mice. If these observations are confirmed the possible use of beta-glucuronidase inhibitors as a useful adjunct to other leprosy therapy is raised as is also the likelihood of developing new therapies.


Chlorpromazine-induced electrocardiogram abnormalities. The aim of our clinical investigation was to evaluate the electrocardiographic abnormalities in patients receiving only chlorpromazine, and to assess the role of sex, age and length of illness in these abnormalities. 96 schizophrenic patients (48 male and 48 female patients) satisfying study criteria were selected for inclusion and changed from their old medication to a fixed dose of 125 mg chlorpromazine daily. This uniformization period lasted two weeks, during which the electrocardiograms were taken after an overnight fast. Five patients were excluded because their electrocardiographic changes revealed the possibility of an organic heart disease. The electrocardiograms were found to be normal for 65.9% of the patients and abnormal for 34.1%. 11% of patients were classified as demonstrating Grade I repolarization abnormalities, 14.3% of patients as Grade II, and 8.8% as Grade III. Chi square (X2) tests revealed no significant differences between sexes, age groups or lenghts of illness as regards ECG normality and grade of abnormality.


Thiosemicarbazones and hydrazones of alpha-methylchalkone as potential chemotherapeutic agents. The effectiveness of chalkones and derivatives as antibacterial and antifungal agents stimulated our interest in the possibility of coupling this type of compound with certain hydrazines and thiosemicarbazides to determine the potential chemotherapeutic activity of these combinations as anticancer and antimalarial agents. Accordingly, 18 hydrazine and thiosemicarbazide derivatives of alpha-methylchalkone (dypnone) have been synthesized for study as potential antitumor agents in animal tumor systems against Walker 256 carcinosarcoma (intramuscular) and leukemia L-1210 and for antimalarial activity against Plasmodium berghei in experimentally infected mice. Of the series of chalkone derivatives, significant inhibition in preliminary tests against the Walker 256 carcinosarcoma (intramuscular) rat tumor system was exhibited by alpha-methylchalkone-1,4-phthalazinediyldihydrazone and showed activity in the leukemia 1210 mouse tumor system. The guanylhydrazone of alpha-methylchalkone showed good inhibition with confirmed activity against Plasmodium berghei in experimentally infected mice.


A comparative evaluation of bacteriologic and morphologic indices of Mycobacterium leprae in skin, lymph node, bone marrow, nerve and muscle. This study elicits the comparative evaluation of the Bacteriologic Index (BI) and Morphologic Index (MI) of the skin, lymph node, bone marrow, nerve and muscle tissues of 15 untreated leprosy patients. The findings of comparable or even higher BI's and MI's in lymph nodes than skin are of considerable interest, especially the presence of a significant percentage of viable bacilli during reaction states when MI of skin and nerve tissue was found to be negative. Evaluation of the BI's and MI's of lymph nodes has been suggested to be of utmost importance for follow-up studies of patients being treated with antileprosy drugs.


Statistical problems in interpreting comparative bioavailability trials. The basic purpose of a comparative bioavailability is to determine whether or not a new formulation of a drug is equivalent in its in vivo behavior to some standard formulation. Statistical analysis of the blood or urine concentrations of the drug plays a critical role in this determination, and two major problems are in deciding what to analyse and what statistical methods to use. It is proposed that the analysis usually employed, namely, hypothesis-testing, is largely irrelevant to the problem and should be replaced by an approach based on confidence intervals. Secondly, it is suggested that only those characteristics of the bood or urine-level sequence that have a meaningful relationship to the therapeutic use of the drug, should be analysed.


Bioavailability studies and the clinical pharmacologist: correlation of drug distribution with clinical effects. Bioavailability studies can be interpreted only when clinical information is available which correlates drug distribution with both efficacious and toxic clinical effects. The clinical pharmacologist should be instrumental in the development of safe and effective drug therapy by the systematic application of well designed clinical trials, the clear definition of therapeutically desirable clinical responses, and the development and application of improved techniques of measuring these effects.


Toxoplasmosis and the compromised host.

Toxoplasmosis and the compromised host. A high percentage of population shows antibodies to Toxoplasma gondii yet clinical manifestations of primary infestations are rare. Congenital and secondary forms (chorioretinitis) are serious medical conditions. An outburst in a compromised host is always serious and may be fatal. Therefore, patients subjected to immunosuppressive therapy or with pathologic immune suppression should be clinically and serologically screened and, when toxoplasmosis is diagnosed, treated for the entire period of immunosuppression.


Tinea versicolor hypopigmentation: histochemical and therapeutic studies. One hundred and thirty-four patients with tinea versicolor were divided into 3 treatment groups: (1) 30% sodium thiosulfate application, (2) 30% sodium thiosulfate application plus ultraviolet light, and (3) 30% sodium thiosulfate application, ultraviolet light, and meladinine tablets (amoidin 0.01 g and amidin 0.005 g). Analysis of the 79 patients who completed the 6-week study showed no statistical difference. Therefore, topical treatment should be instituted as quickly as possible to prevent pigmentary changes. Ultraviolet light should be used only after the fungus has cleared in order not to darken the skin further.


Diagnostic significance of the immunofluorescent pattern in dermatitis herpetiformis. Despite significant clinical, histologic, immunopathologic and other differences between typical cases of dermatitis herpetiformis (DH) and bullous pemphigoid (BP), the differential diagnosis may be difficult. Our direct immunofluorescent studies in 59 cases of DH and 134 cases of BP indicate the diagnostic value of immunopathologic studies.


Urea creams in the treatment of dry skin and hand dermatitis. Two randomized, double-blind comparison studies were conducted to evaluate the efforts of 2 emollient dry skin creams containing urea in the management of dry skin in atopic patients. Cream with 10% urea was shown to be effective in the management of dry skin and hand dermatitis. The cream with a pH of 6 caused less burning.


Psychoanalysis as a theory of therapy.

Psychoanalysis as a theory of therapy. The development of psychoanalytic theory is traced from its origins in Freud's early thinking in terms of his advancing clinical experience. While the influence of clinical experience on the modifications of theory has long been accepted, little attention has been paid to the broad spectrum effects of changing theoretical perspectives on the technique of clinical psychoanalysis. This development is traced through the emergence of ego psychology and the dominance of the structural theory to more current developments having to do with object relations and the theory narcissism. The residual theoretical ambiguities and clinical perplexities are illustrated in two clinical cases. The development of psychoanalytic theory and the correlative aspects of technique are seen as manifesting an organic developmental process which has led to an increasing sophistication of analytic intervention and a broadening capacity for dealing with increasingly difficult and less classical types of cases. The conclusion is drawn that therapeutic lestening is equivalently an informed listening, and it is theory that lends understanding and sensitivity to the hearing process. It is theory that is to be put in the service of listening, rather than listening to be put in the service of theory.


Side effects of tricyclic antidepressand drugs with particular reference fo dothiepin. Fifteen patients on dothiepin and 20 on other tricyclic compounds were compared for side effects by self-rating. The high incidence of complaints beforehand and overall reduction during 2 weeks treatment, correlating with clinical improvement, shows that comparison of side effects is unreliable unless pretreatment incidence is recorded.


The Hamilton rating scale. An assessment bases on a dothiepin ("prothiaden") versus imipramine ("Tofranil") clinical trial. The Hamilton Rating Scale for Depression is in common use, particularly in durg trials. The authors compared this scale with a system of psychiatric assessment and recording designed by M. Sim. They found that there was closer agreement with the full assessment of the Sim method than with the single diagnostic area for depression. This suggests that the Hamilton Scale for depression is more general than specific in its application.


Contingent naloxone (N-allylnoroxymorphone) treatment of the paroled narcotic addict. This is a presentation of the results of pilot and controlled research on the effectiveness of the contingent (upon narcotic drug use) administration of 500-2,000 mg daily, of the narcotic antagonist, naloxone (N-allylnoroxymorphone), to paroled narcotic addicts enrolled in a urine monitoring program conducted in a metropolitan-based outpatient clinic. Criteria of effectiveness, which include clinic attendance, the extent of narcotic drug usage, and final disposition at the end of a 6-month treatment period, are viewed in relation to already established baseline results with  a sample of patients processed through the same clinic over a 5-year period prior to the introduction of naloxone treatment. Although results of the pilot study are encouraging, indicating longer patient involvement and less reinstitutionalization than baseline values, the results of the controlled evaluation reveal no benefit from contingently administered naloxone beyond placebo reactivity, which appears to be substantial in the contingent approach. The results are discussed in terms of given sample characteristics, and suggestions are offered regarding the development of new narcotic antagonist treatment approaches.


Effects of control techniques on therapeutic outcome in a controlled clinical trial. Undertaken in the context of a controlled drug trial involving newly admitted psychiatric hospital patients, this study compared the effectiveness of a "Doctor's Choice" (DC) method of administering psychotropic drugs versus an experimentally determined treatment regimen employing random assignment and double-bline procedures. The 32-day drug trial sought to determine the comparative effectiveness of thioridazine-placebo, thioridazine-chlordiazepoxide, and thioridazine-imipramine, with the daily dosage of openly administered thioridazine ranging from 100 to 900 mg and dosages for chlordiazepoxide and imipramine, administered in a double-blind fashion, fixed at daily dosages of 30 and 75 mg, respectively. DC medication, consisting of a choice (by a research physician) of any of the three experimental medications determined on the basis of judged clinical need, was added as a fourth treatment category for present purposes. Criteria of effectiveness included standarized psychiatric rating scales and global measures of imporvement completed by research team members and ward physicians. Outcome results for the DC group compared to those for a single control group made up of individuals matched with DC patients on the basis of drug assignment indicated an essentially similar clinical effectiveness under both DC and control treatment conditions. Generalization of the finding was limited by the fact that the main treatment effect, attributable to thioridazine, overshadowed the more subtle action of the ancillary drugs.


[Severe light dermatosis following photo therapy in a newborn infant with congenital erythropoietic urophyria]. A newborn infant with hemolytic anemia and hepatosplenomegaly was treated by phototherapy for early jaundice. After 18 h, a dark brown pigmentation of the skin was noticed, leading to the assumption of a bronze baby syndrome. Indeed, the child was suffering from a severe disturbance of liver function. 4 days later, a severe bullous dermatosis with blody imbibition developed, covering all exposed parts of the body surface and reoccurring in many bursts over several weeks despite protection against light. A severe hemolytic anemia was constantly present. The baby died on the 50th day. The diagnosis of erythropoietic porphyria was suggested immediately after the onset of the bullous exanthema and proved by laboratory data as follows: uro- and coproporphyrin in the urine were extremely high, uroporphyrin being mainly of type-I isomer. In red cells, increased amounts of uro-, copro- and protoporphyrins were detected. Massive red fluorescence of erythroblasts (so-called porphyroblasts) in the bone marrow and in the blood could be observed. At autopsy, the liver showed multiple blood-forming areas and severe diffuse hemosiderosis, which is to be explained by a long existing, i.e. fetal hemolysis. Erythropoietic porphyria is such a rare disease that there is no reason to consider it as a general contraindication for phototherapy.


Catalytically inactive sucrase antigen of rabbit small intestine: the enzyme precursor. By immunofluorescence microscopy using a specific antibody to the active rabbit sucrase-isomaltase complex, a catalytically inactive sucrase antigen was discovered on the small intestinal mucosa of young rabbits still lacking sucrase activity. In adult rabbits, the same antigen was demonstrated on enterocytes of mucosal crypts devoid of sucrase. Catalytically inactive antigen was isolated by means of immobilized antibody to active sucrase, and it was compared with the active sucrase-isomaltase complex. From structural similarities between the 2 proteins and from the fact that active sucrase succeeds the inactive antigen in both the maturing and the mature rabbit, it is concluded that the inactive antigen is the enzyme precursor. In some patients with hereditary sucrase-isomaltase deficiency, abnormal persistence of sucrase precurosr due to a faulty activation mechanism may be the underlying defect.


Streptomycylamines: difference in activity and mode of action between short-chain and long-chain derivatives. A homologue series of aliphatic streptomycylamines (SM-amines) have been prepared and tested in vitro (binding to 70S ribosomes) and in vivo (MIC).  The short-chain SM-amines act as streptomycin (SM) but are less active than SM.  They are inactive towards a SM-resistant Escherichia coli, our strain 042.  The long-chain SM-amines are active both towards our sensitive and resistant E. coli, our strains 079 and 042.  Their activities are not pH-dependent in contrast to that of SM.  However, the higher homologues of the aliphatic amines (C10 Congruent TO C10) are considerably active per se although two to four times less than the corresponding SM-amines.  Further, the amines do not compete with the SM-amine for the binding to the ribosomal particles.  The binding affinities of these long-chain SM-amines to ribosomes are considerably smaller than that of SM.  The binding is however specific as a typical isotope dilution curve can be obtained.  We conclude that the long-chain SM-amines have a mode of action different from that of SM.


Determination of ammonia inhibition in fabric impregnated with antimicrobials. A new method is described for determining the presence or absence of ammonia produced by urealytic microorganisms, using fabric which has been treated with an antimicrobial. Circular disks of fabric treated with various concentrations of an antimicrobial are placed in the bottoms of snap-on lid petri dishes. Nutrient medium containing urea, an indicator, and a dilution of an overnight culture of Proteus mirabilis is applied to the fabric disks. The lids are snapped on and the dishes are incubated at 37 degrees C. By examination of the fabric disks at regular intervals of time for a color change from white to red, one may determine whether the concentration of antimicrobial in the fabric is sufficient to inhibit the production of ammonia by a urealytic microorganism.


Computerized Electroencephalogram. A model of understanding the brain function in childhood psychosis and its treatment. Computer analysis of the electroencephalogram (CEEG) in psychotic children before and after pharmacotherapy, normal children of schizophrenic mothers, and matched normal children of normal parents indicated significant intergroup differences. The psychotic children had more slow, as well as very fast, EEG waves. With drug therapy the EEG showed a partial "normalization," as fast EEG activity decreased. The EEG and auditory evoked potential of children of schizophrenic mothers were strikingly similar to those of psychotic children and schizophrenic adults, with significant decreases of the average EEG amplitude and the evoked potential latencies. Psychotic children were distinctly differentiated from the normal children by discriminant function analysis of the EEG and EP. Quantitative analysis of brain functions in the mentally ill can help determine the neurophysiological correlates of behavior, a more scientific diagnostic classification, prognosis, and selection of therapy.


Methionine-and S-adenosyl methionine-mediated repression in a methionyl-transfer ribonucleic-acid synthetase mutant of Saccharomyces cerevisiae. A Saccharomyces cerevisiae mutant strain unable to grow at 38 C and bearing a modified methionyl-transfer ribonucleic acid (tRNA) synthetase has been studied. It has been shown that, in this mutant, the percentage of tRNAmet charged in vivo paralleled the degree of repressibility of methionine biosynthetic enzymes by exogenous methionine. On the contrary, the repression mediated by exogenous S-adenosylmethionine does not correlate with complete acylation of tRNAmet. Althought McLaughlin and Hartwell reported previously that the thermosensitivity and the defect in the methionyl-tRNA synthetase were due to the same genetic lesion (1969), no diffenence could be found in the methionyl-tRNA synthetase activity or in the pattern of repressibility of methionine biosynthetic pathway after growth at the premissive and at a semipermissive temperature. It appears that the mutant also exhibits some other modified characters that render unlikely the existence of only one genetic lesion in this strain. A genetic study of this mutant was undertaken which led to the conclusion that the thermosensitivity and the other defects are not related to the methionyl-tRNA synthetase modification. It was shown that the modified repressibility of methionine biosynthetic enzymes by methionine and the lack of acylation of tRNAmet in vivo follow the methionyl-tRNA synthetase modification. These results are in favor of the idea that methionyl-tRNAmet, more likely than methionine, is implicated in the regulation of the biosynthesis of methionine.


Derepression in Saccharomyces cerevisiae can be dissociated from cellular proliferation and deoxyribonucleic acid synthesis. A method has been developed that permits precise control of release from catabolite repression in Saccharomyces cerevisiae. It consists of transferring cells growing exponentially on 5% glucose to derepression medium at high cell density. Derepression then proceeds with reproducible kinetics and is complete within 6 to 7.5 h for various intra- and extramitochondrial markers, in the absence of any substantial increase in cellular dry weight or protein. Nuclear (and mitochondrial) deoxyribonucleic acid synthesis can be interrupted in certain thermosensitive (cdc) mutants at the nonpermissive temperature; a shift to this temperature before the onset of derepression has no effect on its outcome.


Transition of R factor NR1 in Proteus mirabilis: molecular structure and replication of NR1 deoxyribonucleic acid. The structure of R factor NR1 DNA in Proteus mirabilis has been studied by using the techniques of CsCl density gradient centrifugation, sedimentation in neutral and alkaline sucrose gradients, and electron microscopy. It has been shown that the nontransitioned form of NR1 DNA isolated from P. mirabilis cultured in drug-free medium is a37-mum circular deoxyribonucleic acid (DNA) with a density of 1.712 g/ml in a neutral CsCl gradient. This circular molecule is a composite structure consisting of a 29-mum resistance transfer factor containing the tetracycline-resistance genes (RTF-TC) and an 8-mum r-determinants component conferring resistance to chloramphenicol (CM), streptomycin/spectinomycin, and the sulfonamides. There are one to two copies of NR1 per chromosome equivalent of DNA in exponential-phase cells cultured in Penassay broth. After growth of PM15/NR1 in medium containing 100 mug of CM per ml, the density of the NR1 DNA increased from 1.712 g/ml to approximately 1.718 g/ml and the proportion of NR1 DNA relative to the chromosome is amplified about 10-fold. The changes in R factor DNA structure which accompany this phenomenon (termed the transition) have been studied. DNA density profiles of the transitioned NR1 DNA consist of a 1.718 g/ml band which is skewed toward the less dense side. The transitioned NR1 DNA consists of molecules containing the RTF-TC element attached to multiple copies of r-determinants DNA (poly-r-determinant R factors) and multimeric and monomeric autonomous r-determinants structures. Poly-r-determinant R factors have a density intermediate between the basic composite structure (1.712 g/ml) and r-determinants DNA (1.718 g/ml). These species presumably account for the skewing of the 1.718-g/ml DNA band toward the less dense side. When transitioned cells are subsequently cultured in drug-free medium, poly-r-determinant R factors and autonomous poly-r-determinants undergo dissociation to form smaller structures containing fewer copies of r-determinants. This process continues until, after prolonged growth in drug-free medium the NR1 DNA returns to the nontransitioned state which consists of an RTF-TC and a single copy of r-determinants.


Denaturation mapping of R factor deoxyribonucleic acid. The R factor NR1 consists of two components: a resistance transfer factor which harbors the tetracycline resistance genes (RTF-TC) and the r-determinants component which harbors the other drug resistance genes. Using partial denaturation mapping it is possible to distinguish the RTF-TC region from the r-determinants region of the composite R factor NR1 DNA which has a contour length of 37 mum and a density of 1.712 g/ml. The r-determinants region was a relatively undenatured 8.5-mum segment of the molecule when the deoxyribonucleic acid was partially denatured at pH 10.7. An RTF-TC genetic segregant of NR1 which had lost the r-determinants component had a contour length of 28.7 mum and a density of 1.710 g/ml. Characterization of an RTF-TC using partial denaturation mapping at pH 10.7 confirmed that the relatively undenatured 8.5-mum r-determinants segment of the composite R factor had been deleted. Circular, transitioned NR1 DNA molecules (1.716 to 1.718 g/ml), whose contour lengths were consistent with an RTF-TC plus an integral number of tandem copies of r-determinants, were also characterized by denaturation mapping. The relatively undenatured region in these molecules had a length equal to an integral number of copies of r-determinants and was located at the same site in the partially denatured RTF-TC as the single copy of r-determinants in the 37-mum composite NR1. This indicates that there is a unique integration site for r-determinants in the RTF-TC component. The R factor UCR122, a TC deletion mutant of NR1, was also characterized by denaturation mapping. The translocation of the TC resistance gene(s) on the denaturation map permitted the alignment of the denaturation map with the heteroduplex map of Sharp et al. (u073). Linear and circular monomeric and presumed multimeric r-determinants DNA molecules (p = 1.718 g/ml) were partially denatured at a higher pH (11.10). The r-determinants multimers showed a repeating 8.3-mum (monomeric) partial denaturation pattern indicating a head-to-tail arrangement of monomers in these poly-r-determinant molecules.


Isolation of specialized transducing bacteriophage lambda carrying genes of the L-arabinose operon of Escherichia coli B/r. A heat-inducible lysis-defective phage lambda (lambdacI857S7) has been integrated at multiple sites within the L-arabinose region (araCOIBAD) of a strain of Escherichia coli K-12 deleted for the normal lambda attachment site (lambdaattdelta). The lambda phage has become integrated with opposite orientations at two different loci within the aratb gene and with the "normal" orientation (clockwise N-RA-J) at a single site in the araC gene. The burst size, spontaneous-curing frequencies, and number of prophage harbored by each of the ara secondary-site lysogens have been determined. From these secondary-site lysogens it has been possible to generate plaque-forming ara-transducing phage (lambdapara) and defective ara-transducing phage (lambdadara), as well as defective leucine-transducing particles (lambdadleu). The construction and characterization of these lambdaara-transducing phage and their derivatives which carry genetically defined portions of the L-arabinose region are presented.


Role of pyrimidine dimer excision in loss of potential streptomycin resistance mutations of ultraviolet-irradiated Escherichia coli on phosphate-buffered agar. The frequency of ultraviolet (UV)-induced mutations to streptomycin resistance dropped rapidly when starved Escherichia coli strains WP-2 B/r and B/r T- were incubated on phosphate-buffered agar (PBA), but was reduced only slightly in a WP-2 hcr- mutant. During postirradiation, incubation viability remained approximately constant. Cells given an optimal recovery treatment with photo-reactivating light showed no further recovery if subsequently incubated on PBA. At least 70% of the mutations induced to streptomycin resistance by UV could be repaired. The loss of potential streptomycin-resistant mutants was markedly reduced in strain B/r T- when 5 mug of acriflavin or 700 mug of caffeine per ml was added to PBA. The excision of UV-induced thymine-containing dimers from E. coli tb/r T- was investigated. Dimer excision progressed more slowly when the cells were incubated on PBA containing acriflavin or caffeine. There was no congruity between the kinetics of dimer excision and the kinetics of mutant loss. Our results indicate that removal of potential streptomycin-resistant mutants is considerably faster than the excision of pyrimidine dimers.


N-terminal amino acid sequences of D-serine deaminases of wild-type and operator-constitutive strains of Escherichia coli K-12. The N-terminal amino acid sequences of the D-serine deaminases from strains of Escherichia coli K-12 that harbor wild-type and high-level constitutive catabolite-insensitive operator-initiator regions are identical: Met-Ser-GluNH2-Ser-Gly-Arg-His-Cys. This result indicates that the operator-initiator region is probably distinct from the D-serine deaminase structural gene.


Structural and biochemical alterations of Nocardia asteroides cell walls during its growth cycle. Analysis of Nocardia asteroides 14759 cell walls were done to determine the chemical and structural composition during the growth cycle. It was found that the ultrastructural profiles of the cell wall become altered as the cultures aged. Chemical analysis revealed corresponding shifts in cell wall components as the culture went from lag to logarithmic to stationary phases of growth. The peptidoglycan from lag-phase cells (5 h) represented 15% of the total cell wall weight, and the percentage of peptidoglycan progressively increased so that, in 1-week stationary-phase cells, it represented approximately 40% of the total wall weight. In lag-phase cells it was found that 36% of the cell wall weight was lipid in nature, whereas stationary-phase cells had only 7% lipid in their wall. The overall sugar composition of the walls remained relatively constant at about 28 to 31% however, the arabinose to galactose ratio changed from approximately 1:1 in lag-phase to 2:1 in stationary-phase cells. Gas-liquid chromatography demonstrated that the fatty acids making up the cell wall lipids changed relative to one another as the cells aged. Based upon the removal of lipids by ethanol-ether, chloroform, and alkaline methanol extraction, it was shown that the classes of loosely and firmly associated lipids changed as the cells aged. Further, it was found that a carotenoid-like pigment associated to a C22 fatty acid increased in the cell wall as the culture stopped growing. Peptidolipid or lipoprotein was found to make up a significant part of the cell wall. This component increased in amount and varied in amino acid content as the culture aged. Analysis of the totally extracted basal layer of the cell wall (peptidoglycan plus arabinogalactan) showed that it too changed as the cells grew and fragmented. The data presented established that the cell wall of N. asteroides was structurally and chemically complex and that a progression of chemical and physical processes occurred within the wall as the cells developed through their growth cycle.


Deletions fusing the hisG and hisD genes in Salmonella typhimurium. Frameshift mutation hisD497 occurs in the operator-proximal portion of the Salmonella typhimurium gene coding for the dimeric protein, L-histidinol dehydrogenase (HDH). Rare revertants of hisD497 are deletions fusing the hisD gene to the adjacent preceding structural gene, hisG (adenosine 5'-triphosphate-PR transferase). HDH purified from one revertant, hisGD4908, contains subunits of approximately normal molecular weight but with no clearly demonstrable unique amino-terminal sequence. We propose that a combined inactive G-D polypeptide is synthesized and then cleaved at a number of closely juxtaposed sites by endoproteolytic activity. At least some of the resulting fragments then participate in formation of active HDH dimers.


Isolation of a hybrid F' factor-carrying Escherichia coli lactose region and Salmonella typhimurium histidine region, F42-400 (F' ts114 lac+, his+): its partial characterization and behavior in Salmonella typhimurium. Episome F' ts114 lac+ (F42-114) was transferred into Salmonella typhimurium carrying an F'his+ (FS400) episome, and fused episome F' ts114 lac+, his+ (F42-400) was obtained. Episome F42-400 could be transferred to S. typhimurium, Escherichia coli and Klebsiella pneumoniae. Identification of the episome was based on: (i) temperature sensitivity of the Lac+ and His+ phenotypes; (ii) the fact that F- segregants, obtained after temperature curing or acridine orange curing, were simultaneously Lac- and His-; and (iii) linkage of lac+ with his+ in episomal transfers to E. coli and S. typhimurium. The frequency of episome transfer was influenced by the genotype of the donor. Plasmid LT2, prevalent in S. typhimurium LT2 strains, was suggested to be responsible for the low fertility of S. typhimurium donors. Episome F42-400 was capable of chromosome mobilization, and the extent of chromosome mobilization was not influenced by the presence or absence of the histidine region on the donor chromosome. Growth in a defined medium with acridine orange was able to cure F42-400. The frequency of curing was increased (the frequency of His+ cells was 0.0001%) if the cells were grown at 40 C in the presence of acridine orange. Selection for temperature-resistant Lac+, His+ derivatives in a strain without histidine deletion yielded Hfr strains. However, similar and stronger selections in strains without the chromosomal histidine region failed to yield Hfr strains. Our inability to obtain Hfr's in strains without the chromosomal histidine region was explained by assuming that the episome F42-400 has lost the F sites involved in integration into the S. typhimurium chromosome.


Behavior of a hybrid F' ts114 lac+, his+ factor (F42-400) in Klebsiella pneumoniae M5a1. Episome F' ts114 lac+, his+ (F42-400) was transferred from Salmonella typhimurium to Klebsiella pneumoniae. From the progeny, a strain of K. pneumoniae able to retransfer the episome was obtained. The His+ phenotype in this strain is temperature sensitive. Escherichia coli female-specific phages phiII, W31, and T3 were shown to plate on K. pneumoniae. From phiII we obtained two derivatives; phiIIK, which plates only on K. pneumoniae, and phiIIE, which plates only on E. coli. Growth of phages T3 and phiIIK was inhibited by F42-400 in K. pneumoniae. Growth in presence of acridine orange in a defined medium at 40 C resulted in a high level of curing. The frequency of His+ cells after growth in acridine orange at 40 C was 0.001%. An extensive search to detect chromosome mobilization by F42-400 in K. pneumoniae, under different experimental conditions, was negative. We cannot exclude the possibility that the low transfer efficiencies prevented our detection of chromosome mobilization. A search among temperature-resistant, acridine orange-curing-resistant, or galactose-resistant derivatives of the K. pneumoniae donor strain failed to reveal any chromosome transfer. Our failure to detect Hfr's may be a result of: (i) the peculiarity of episome F42-400, (ii) the peculiarity of K. pneumoniae chromosome, or (iii) low transfer efficiency. K. pneumoniae-modified F42-400 and phage 424 were restricted by E. Coli K-12. E. coli K-12-modified episome F42-400 and phage 424 were restricted by K. pneumoniae. E. coli C failed to restrict F42-400 modified with K. pneumoniae specificity. The ability of K. pneumoniae to accept F42-400 is less, by about a factor of 50, than that of E. coli C. As an explanation for the differences in the behavior of E. coli C and K. pneumoniae in ability to receive F42-400 it was suggested that recipient bacteria have specific sites for interaction with the F-pilus tip; these are present in E. Coli C, leading to high transfer efficiency, whereas they may not be present (or if present, are not accessible) in K. pneumoniae, leading to low transfer efficiency.


Differences in coupling of energy to glycine and phenylalanine transport in aerobically grown Escherichia coli. Differences exist in the coupling of energy to transport of glycine and phenylalanine in aerobically grown cells of Escherichia coli. Energy derived from respiration, although involved in both uptake systems, is not employed identically as shown by kinetic effects of cyanide and anoxia and by temperature dependencies. Additional evidence for aerobic differences was provided by the effects of azide which greatly decreased initial rates of uptake of glycine but not phenylalanine. The effect on glycine uptake was not due to uncoupling of oxidative phosphorylation or to a decrease in respiration rate. Evidence for anaerobic differences was provided by the addition of either glucose or ferricyanide to cell suspensions containing glycerol, thereby maintaining anoxic uptake of phenylalanine, but not glycine, at the aerobic level. Ferricyanide stimulation required a functional Ca, Mg-adenosine 5'-triphosphatase and involved cell metabolism. Ferricyanide was also found to produce differential stimulation of other amino acid transport systems; tyrosine, tryptophan and leucine uptakes were stimulated whereas those for alanine, proline, threonine, and glutamine were relatively unaffected.


Kinetic studies on the specificity of chelate-iron uptake in Aspergillus. Three strains of the fungus Aspergillus, Aspergillus quadricinctus (E. Yuill), A. fumigatus (Fresenius), and A. melleus (Yukawa), each producing different iron-chelating compounds during iron-deficient cultivation, were used for 55Fe3+ uptake measurements. Iron from chelates of the ferrichrome-type family was taken up by young mycelia of all strains tested, irrespective of the ferrichrome-type compound these strains predominantly produce in low-iron cultures. Ferrichrysin-producing strains, however, seem to favor ferrichrysin iron uptake, whereas ferrichrome, ferricrocin, and even ferrirubin showed similar iron transport properties in all of these strains. Compared to iron uptake from ferrichrome-type compounds (Km approximately 4 uM) iron uptake from fusigen revealed completely different kinetic values (Km approximately 50 to 80 muM). Iron from exogenous chelates, e.g., from coprogen produced by Neurospora crassa for ferrioxamine B produced by Streptomyces pilosus, can obviously not be taken up by Aspergillus, confirming the pronounced specificity of chelate-iron transport in fungi.


Specificity of the Escherichia coli proline transport system. The presence of both the carbonyl portion of the carboxyl group at position 2 of the pyrrolidine ring and a secondary amine was essential for uptake of a compound by the proline permease of Escherichia coli. The permease possessed a high affinity for azetidine-2-carboxylic acid and for compounds with ring structures smaller than the pyrrolidine ring. Pipecolic acid, the higher homologue of proline, and its derivatives were not transported. Cis- and trans-3,4-methano-prolines, also six-membered ring structures, behaved anomolously in that they possessed a high affinity for the permease. The difference between the methano-prolines and other six-membered ring structures probably resides in the fact that the former exist in the "boat" configuration whereas the latter possess the "chair" configuration. In general, substituted prolines in the cis configuration displayed a higher affinity for the permease than did corresponding trans isomers, though the affinity for substituted prolines was influenced by the position, size, and polar or nonpolar nature of the substituent group. At O C many analogues with affinity for proline permease exchanged with intracellular proline, but some analogues, notably trans-3-methyl- and trans-4-methyl-L-prolines, though possessing high affinity for the permease, showed an almost complete inability to exchange with intracellular proline.


Inhibition of Escherichia coli isoleucine biosynthesis by isoleucine tetrazole. Growth of a derivative of Escherichia coli K-10 was strongly inhibited by 2 times 10(-4) M L-5(1-amino-2-methylbutyl)-tetrazole (isoleucine tetrazole). Growth inhibition was reversed by isoleucine, threonine, glycyl-L-isoleucine, or glycyl-L-threonine, and, in a valine-resistant mutant, by L-valine. Partial reversal of growth inhibiton was effected by L-leucine, L-methionine, or L-homoserine. The tetrazole inhibited the activity of the biosynthetic threonine deaminase (EC 4.2.1.16 L-threonine hydrolyase [deaminating]), the inhibition being relieved by L-valine. The tetrazole also inhibited isoleucyl-transfer ribonucleic acid (tRNA) synthetase (EC 6.1.1.5 L-isoleucine: tRNA ligase [adenosine monophosphate]), but was without effect on the activities of alpha-isopropylmalate synthetase or acetohydroxy acid synthetase. One class of isoleucine tetrazole-resistant mutants produced biosynthetic threonine deaminases which were no longer subject to feedback inhibition by either isoleucine or the tetrazole.


Attachment of lipoprotein to murein (peptidoglycan) of Escherichia coli in the presence and absence of penicillin FL 1060. In vivo studies on the attachment of lipoprotein to the murein (peptidoglycan) of Escherichia coli showed that it takes several generations of growth until the amount of lipoprotein on newly made murein is equilibrated. The technique used involves degradation of the sodium dodecyl sulfate-insoluble murein-lipoprotein complex (sacculus, rigid layer) with lysozyme and separation of the labeled products on paper. No lipoprotein was found on murein subunits incorporated during a pulse of [3H]diaminopimelate for 1 min in logarithmically growing cells at 37 C. Even after one doubling of the cell mass, only 4 to 8% of the labeled murein was isolated as bound to lipoprotein. With uniformly labeled murein, 30% remains bound to lipoprotein after lysozyme treatment, corresponding to three murein subunits. Therefore it can be concluded that during pulse labeling either no lipoprotein is incorporated into the newly synthesized murein or no murein subunits are inserted into existing murein around lipoprotein attachment sites. Longer pulse and pulse-chase experiments argue for the latter interpretation. It is therefore concluded that incorporation of murein subunits into the growing murein polymer is not at all a random process. Instead, quite large areas of murein, on which lipoprotein is situated, seem to be preserved. Under the influence of penicillin FL 1060 murein synthesis is 50% inhibited. The rate of lipoprotein attachment is less affected so that increasing amounts of lipoprotein become attached during spheroplast formation. By the time the stationary growth phase has been reached, the lipoprotein content of the murein has doubled. Diaminopimelate auxotrophic mutants require, in the presence of penicillin FL 1060, more diaminopimelate for full growth than in the absence of penicillin FL 1060. This finding and the fact that murein synthesis is always inhibited by 50% over a wide range of penicillin concentration (1 to 1,000 mug/ml) point to the inhibition of an enzymatic step of murein synthesis which can be partially bypassed by a second enzyme, less efficient but resistant to penicillin FL 1060.


Accumulation of arginine precursors in Escherichia coli: effects on growth, enzyme repression, and application to the forward selection of arginine auxotrophs. The accumulation or ornithine, citrulline, and possibly acetylornithine by Escherichia coli K-12 arginineless mutants provided with acetylarginine as source of arginine causes severe growth inhibition. This occurs under conditions where comparable derivatives of E. coli W (Bollon and Vogel, 1973) show little or no growth inhibition. The same conditions, which have been reported to cause noncorrelative synthesis of acetylornithinase and argininosuccinase in E. coli W (Bollon and Vogel, 1973), do not alter the correlative pattern of enzyme synthesis observed in E. coli K-12. Moreover, previously reported effects of ornithine and citrulline on repression of the arginine regulon in E. coli W are not observed in the K-12 strains examined. The bearing of these observations on possible differences between the mechanism of enzyme repression operating in the two types of strains cannot yet be fully evaluated; it is, however, clear that considerable care should be exercised before extrapolating the results obtained with one type of strain to the other one. The particularly strong inhibition of acetylarginine utilization exerted by ornithine in E. coli K-12 allows the forward selection of several classes of arginine auxotrophs from strains deficient in carbamoylphosphate biosynthesis and thus capable of ornithine accumulation. Possible applications of this technique to the genetic analysis of the bipolar argECBH operon are discussed.


Role of the cell surface in bacterial mating: requirement for intact mucopeptide in donors for the expression of surface exclusion in R+ strains of Escherichia coli. Two derivatives of the F-like R factor R1drd19 carrying mutually exclusive resistance determinants were used to study the role of the mucopeptide in the expression of conjugal functions. The use of metabolically active penicillin spheroplasts in R+ times R- matings had no effect on the ability of the cells to donate or accept a plasmid. However, in R+ times R+ matings it was found that surface exclusion was totally abolished if the donor, but not the recipient, was a spheroplast. This result implies that the traS gene, expressed by the excluding plasmid, is dependent for its action on an intact mucopeptide layer in the donor cell, and that this interaction is independent of the transfer ability of the excluding plasmid.