Serotonin and the control of ventilation in awake rats. In awake, unrestrained, intact rats, reserpine, para-chlorophenylalanine, 6-fluorotryptophan, and para-chloroamphetamine depleted whole brain serotonin and produced a substantial and sustained hyperventilation as evidenced by a 5--9 torr drop in PaCO2. Administration of 5-hydroxytryptophan to rats treated with para-chlorophenylalanine partially alleviated the hyperventilation. No change in ventilation was observed after alpha-methyltyrosine. 5,7-Dihydroxytryptamine produced contradictory results. On the basis of these pharmacological studies, we propose that some serotonin-mediated nerve transmissions might function under physiological conditions to inhibit the central nervous system output which controls normal breathing.


The MMPI as a predictor of response to conservative treatment for low back pain. Studies that used the MMPI to predict the response of chronic low back pain patients to standard medical treatment have not produced definitive results. Patients seen in a university hospital orthopedic back pain clinic were given the MMPI before treatment, and 6 to 12 months later 76 patients completed follow-up forms that indicated their level of intensity during the previous week and their ratings of the success of treatment in relieving their pain as well as in enabling them to return to normal activities. Predictions of poor response were made in terms of either single MMPI scales or code types. Patients with poor outcome on two of the three criteria (level of pain intensity and ability to return to normal activities) had significantly higher scores on the Hs scale. The predicted high risk code types very accurately identified patients with poor response on the same two criteria; however, the code-type procedure overpredicted poor response in the good outcome group.


Clinical limitations of the Low Back Scale. Administered the Low Back (Lb) Scale, a special derivative of the MMPI, to 20 patients with functional low back pain and 20 patients with verifiable organic evidence for their low back complaints. The Social Desirability Scale also was administered in order to assess the test-taking attitudes of the patients. The two groups of patients were equated in terms of age and sex. The results revealed no significant differences between the functional and organic patients in scores on the Lb Scale and on the Social Desirability Scale. The findings, which were consistent with other recent studies of the Lb Scale, strongly suggested that the clinical usefulness of this scale is highly questionable.


A quantitative study of lipofuscin accumulation with age in normals and individuals with Down's syndrome, phenylketonuria, progeria and transneuronal atrophy. The amount of lipofuscin in neurons of two brainstem nuclei, the inferior olivary nucleus (ION) and the lateral geniculate nucleus (LGN), was measured in the brains of 1 progeric, 2 phenylketonuric, 5 Down's syndrome and 13 normal individuals. Aggregations of lipofuscin granules in cresyl violet stained sections were examined with epi-fluorescent illumination, drawn with a camera lucida, and measured with a planimeter. The proportion of lipofuscin to cell size was a linear function of age over the age range examined, 14 to 92 years. There was no difference between progeric, phenylketonuric, Down's and normal brains in the amount of lipofuscin accumulated with age, nor was there a marked within-individual correlation between amounts of lipofuscin in the two nuclei when these amounts were subtracted from the regression line values to control for age. The proportion of lipofuscin to cell size was the same in neurons of the LGN showing transneuronal atrophy in response to right eye pathology as it was in non-atrophic neurons.


Autonomic dysfunction in tetanus: the effects of a variety of therapeutic agents, with special refernce to morphine. Sympathetic overactivity in tetanus is a common event and may be difficult to control. This report demonstrates the efficacy of morphine in this clinical situation and also discusses the sympathetic effects of 3 muscle relaxants, pancuronium, d-tubocurarine and alcuronium.


Complications related to the administration of general anesthesia in 600 developmentally disabled dental patients. A total of 600 handicapped patients had dental rehabilitation under general anesthesia during an eight-year period. Handicaps included mental retardation, cerebral palsy, Down syndrome, seizure disorders, autism, cystic fibrosis, osteogenesis imperfecta, and muscular dystrophy. No significant complications developed in the majority of patients. This is attributed to thorough preoperative evaluation, appropriate anesthetic management, and vigilant postoperative observation.


[The myectomy of the small oblique muscle with a thread operation on the rectus superior muscle on the eye with ptosis (author's transl)]. Cuppers and Thomas, in 1975, imagined that in the presence of unilateral ptosis with paresis of the rectus superior muscle only, on this side, it was advisible to place a thread on the rectus superior adelphi muscle, in order to expect an improvement, even a recovery from ptosis, by provoking an elevation impulse of the levator muscle and of the rectus superior muscle on the eye with ptosis. The first four operations were unsuccessful. On the order hand, during the fifth operation, we were led, in addition to placing the thread, to procede on the same side, to a myectomy of the small oblique muscle. The result was excellent. Two more cases of ptosis operated in the same way have been healed too. We publish here the detailed case reports, we have tried to explain them, and to specify their indications.


[Retinal detachment and argon laser prophylactic treatment (author's transl)]. We have studied 6 retinal detachments which hapened after a preventive photocoagulation with argon laser in 6 patients who had already had a severe retinal detachment on the other eye (2 anatomical success on 5 operated cases). This preventive photocoagulation was done on eyes which at the term were free of any retinal dehiscence. In this group of 6 we notice 2 giant tears (greater than 70 degrees) or 33% and 3 large tears (between 20 degrees and 70 degrees) or 33%. These high amounts do not correspond to what has been noticed before: - on the non photocoagulated fellow eyes (neither giant nor large tear) - on the whole lot of operated retinal detachments during the same period of time in our unit (2% of giant and 5,7% of large tears). We think that the responsability of laser in the development of these large lesions in predisposed eyes must be thought about. Studies on a larger scale will be necessary to have a more definite idea on this subject.


[Trabeculitis and Besnier-Boeck-Schaumann disease (author's transl)]. The trabeculitis is a nodular infiltration of the trabeculae. His visualization is made after gonioscopy for hypertony or systematic examination of the angle. The alone etiology known is sarcoidosis and the treatment is corticosteroid.


[A new method of lacrymal derivation in the canalicular obstruction (author's transl)]. The authors believe that in their experience the best method of lacrymal derivation in the canalicular obstruction is the Jone's technique. However, the post operatoire complications are numerous in this method and therefore they are looking for a new procedure of lacorhinostomy: - the type of tube is a silicone tube which has the great advantage of not irritating the tissues; - the silicone tube is introduced into the lacrymal duct. After having used this technique for four years the authors are convinced that this is the best method.


[Corneal changes in Scheie disease. (Mucopolysaccharidosis type I S) (author's transl)]. Bilateral keratoplasty performed on a 39-year-old patient with Scheie disease gave the opportunity to study the histological, histochemical and ultrastructural lesions of both corneas. The patient showed all the characteristics signs of Scheie disease with bilateral corneal opacities, thick face, synophrys, mitral and aortic valve stenosis, bilateral carpal tunnel syndrome, stiff joints, and was of normal intelligence. 24 hours urines revealed a marked excretion of mucopolysaccharides. Histology showed scarring of the superficial stroma. Histochemistry revealed an accumulation of acid mucopolysaccharides in the keratocytes throughout the stroma. Electron microscopy showed vacuoles or pleomorphic inclusions in the keratocytes compabible with abnormal lysosomes deficient in alpha-L-iduronidase.


[Adenine-arabinoside in the treatment of idu-resistant herpes simplex keratitis (author's transl)]. Fifteen cases of herpes simplex epithelial keratitis, which failed to heal following IDU therapy, were treated with Ara-A 3% ointment applied fives times daily. Epithelial disease resolved in fourteen cases with Ara-A and mean healing time was 6,6 days. No sign of ocular or adnexal toxicity were noted.


[Biomicroscopy of the fundus in retinal detachment surgery (author's transl)]. Biomicroscopy of the fundus during retinal detachment surgery has the same advantages as indirect ophthalmoscopy. In addition to this, it offers three main advantages over indirect ophthalmoscopy: the observation of the fundus, in an optical cross section of the tissues, the high variation of magnification available, and the observation of the fundus without switching off the light of the operating room. Since 1976--biomicroscopy of the fundus during retinal detachment surgery has been easily performed with the surgical mobile slit lamp manufactured by the firm Zeiss. The angle of the surgical slit lamp can be reduced to 5 degrees. The slit lamp can be used either with the Zeiss OPMI 1 operating microscope or with the Zeiss OPMI 6 operating microscope. The microscope, the contact lens and the surgical instrumentation specialy fitted for biomicroscopy of the fundus during retinal detachment surgery are described. The surgical technique is dealt with, pointing out the practical details which allow for overcoming the own difficulties of biomicroscopy of the fundus during surgery.


Interaction between T cells and non-T cells in suppression of cytotoxic lymphocyte responses. Generation of cytotoxic T lymphocytes (CTL) in mixed leukocyte cultures was suppressed by a factor elaborated by alloantigen-activated T cells. This suppressor factor, CTL-TsF, in contrast to a factor that suppresses proliferative responses in mixed leukocyte reactions (MLR-TsF), was effective only when added during the first 24 hr of a 6-day-culture period. Moreover, removal of CTL-TsF 24 hr after culture initiation failed to restore CTL responses. CTL activity could be rescued from suppressed cultures, however, by addition of 2-mercaptoethanol on days 3 or 4. Similarly, transfer of nonadherent cells at 3 or 4 days from cultures treated with CTL-TsF to cultures of adherent cells initiated in control factor restored CTL responses. Mixing experiments with cells pulsed with CTL-TsF for 4 hr at culture initiation identified a target of CTL-TsF as a Thy-1 negative cell that was adherent to plastic and to Sephadex G-10. Suppression was not due to interference with physiologic accessory cell function, but more likely was accomplished via a negative signal from CTL-TsF-pulsed cells. The results thus suggest that CTL-TsF acts early, but reversibly, in the CTL differentiative process via a second suppressor effector cell, possibly a macrophage.


Suppressor T cells regulate the cytolytic T lymphocyte response to syngeneic tumors induced by murine sarcoma virus (MSV) in the mouse. Studies were designed to analyze the immune activities of spleen cells from mice previously injected with murine sarcoma virus (MSV) and undergoing the processes of MSV tumor growth and rejection. Fractionation of MSV-primed spleen cells according to cell size by velocity sedimentation at unit gravity showed that MSV-specific cytolytic T lymphocytes (CTL) generated in vivo underwent an apparent transition in size from large to small cells as the tumor regressed. The majority of CTL precursors, however, were invariably recovered among small to medium-sized MSV-immune cells, as revealed to CTL generation in vitro in secondary mixed leukocyte-tumor cell cultures (MLTC). Evidence was obtained for the existence in MSV-immune spleens of two suppressor cell populations capable of inhibiting CTL generation in vitro: one population probably consisted of macrophages and could be removed by treatment with carbonyl iron; the second population was comprised of T cells and inhibited the differentiation of tumor-immune CTL precursors in a selective manner. These results provide a preliminary overview of the mechanisms regulating the generation, differentiation, and activity of tumor-specific CTL in a syngeneic model system.


Induction of allograft tolerance after total lymphoid irradiation (TLI): development of suppressor cells of the mixed leukocyte reaction (MLR). We searched for the presence of suppressor cells of the MLR in C57BL/Ka leads to BALB/c chimeras. The chimeras were made with total lymphoid irradiation (TLI) and marrow transplantation. Spleen cells from the old chimeras inhibited the MLR of BALB/c responder cells against C57BL/Ka stimulator cells. Inhibition was specific for the stimulator cells, since no effect on the MLR was observed with C3H or BALB.C3H stimulator cells. Maximal inhibition was achieved when the responder cells in the MLR shared the H-2 haplotype of the chimeric recipient. Spleen cells obtained from chimeras young 30 to 40 days after BM transplantation inhibited the MLR nonspecifically, since similar marked inhibition was observed regardless of the H-2 haplotype of the responder or stimulator cells. The finding of antigen-specific and nonspecific suppressor cells is similar to that observed in mice rendered tolerant to bovine serum albumin after treatment with TLI.


Serum eosinophil chemotactic factor levels in patients with bullous pemphigoid, drug reactions and atopic eczema. The sera of 4 patients with bullous pemphigoid, of 5 patients with drug reactions and of 13 patients with atopic eczema were examined for the occurrence of low molecular weight eosinophil chemotactic factor (ECF) by fractionation on a Sephadex G 25 column. Almost all patients had a peripheral eosinophilia, and many had raised total serum IgE levels. ECF was demonstrated in the sera of all 4 patients with bullous pemphigoid and in 4 of 5 patients with systemic drug reactions. In contrast, the sera of the 13 patients with atopic eczema did not contain any ECF activity, nor did the 13 control sera. These findings suggest that the ECF from phagocytosing polymorphonuclear leukocytes (PMN) and/or the mast cell derived ECF-A contribute to the elevated serum ECF levels in patients with bullous pemphigoid and drug reactions. A correlation between serum ECF and IgE levels and peripheral eosinophilia could not be established.


A new operation for repair of large ventral hernias following giant omphalocele and gastroschisis. An operation is described for repair of skin-covered large anterior abdominal wall defects, using the patient's own tissues, without synthetic materials, and its use in three patients is reported.


The use of peritoneoscopy in the diagnosis and treatment of complications of ventriculoperitoneal shunts in children. Abdominal complications of ventriculoperitoneal shunts used for hydrocephalus have been diagnosed and treated by peritoneoscopy in six instances. In four children, lost catheters were retrieved, and in two cases malfunction was treated. This technique was curative in each instance, thus avoiding total shunt replacement and formal laparotomy.


The role of the periodontal ligament in overdenture treatment. The results of this experiment suggest that the periodontal ligament plays a role in the efficiency of muscular activity during chewing in patients wearing overdentures. A masticatory index as an indicator of the efficiency of masticatory movement is proposed in this research.


Stereotypes concerning normal and handicapped children. Individuals' attitudes were assessed toward various groups of children. In study 1 the respondents were 65 male and female teachers from across the state of Kansas. In study 2 the respondents were 89 men and women in attendance at the 1978 International Conference of the Association for Children with Learning Disabilities. In both studies the evaluations of the labels "gifted children," "normal children," and "physically handicapped children" were found to be significantly more positive than the evaluations of the labels "mentally retarded children," "learning disabled children," and "emotionally disturbed children." These results seem to indicate that definite negative stereotypes are held toward the latter three groups of children. In study 1 these findings were found to occur generally regardless of the respondents' sex, age, educational level attained, and amount of previous mainstreaming experience.


L-Chlorozotocin.

L-Chlorozotocin. L-Chlorozotocin (2-[[[2-chloroethyl)nitrosoamino]carbonyl]amino]-2-deoxy-L-glucose) was synthesized in seven steps from L-arabinose for comparison with chlorozotocin, which is the D enantiomorph and an antineoplastic agent with clinical potential. Purification of the intermediate 2-amino-2-deoxy-L-glucose as the Schiff's base formed with 4-methoxybenzaldehyde ensured complete separation from the manno epimer. Comparative screening against leukemia L1210 with concurrent toxicity controls revealed no significant difference between D- and L-chlorozotocin in either activity or toxicity.


Purification and characterization of the 45,000-Dalton fragment from tryptic digestion of (Ca2+ + Mg2+)-adenosine triphosphatase of sarcoplasmic reticulum. Tryptic digestion of (Ca2+ + Mg2+)-ATPase from sarcoplasmic reticulum of rabbit skeletal muscle has previously been shown to cleave the enzyme initially into a 55,000-dalton fragment and a 45,000-dalton fragment. In the present study the two fragments are solubilized in sodium dodecyl sulfate (SDS) and separated by preparative polyacrylamide gel electrophoresis. The 45,000-dalton fragment is found to be a relatively nonselective, divalent cation-dependent ionophore when incorporated into an oxidized cholesterol membrane (BLM). Ionophoric activity of this fragment is inhibited by low concentrations of LaCl3, HgCl2, and various reducing agents. There appears to be one or two relatively inaccessible disulfide bonds in the 45,000-dalton fragment that are essential for transport. Addition of reducing agents inhibits the ionophoric activity of the succinylated undigested enzyme and the 45,000-dalton fragment, but has no effect on the 55,000-dalton fragment. These experiments imply that the 45,000-dalton fragment and the 55,000-dalton fragment are in a series arrangement in the membrane.


Intra-abdominal injuries in nonpenetrating gunshot wounds of the abdominal wall: two unusual cases. Intra-abdominal injuries of the bowel, mesentery, and mesenteric vessels were found at laparotomy in two patients with nonpenetrating gunshot wounds of the abdominal wall. The mechanism of wounding is thought to be the temporary cavity around the wound tract. The importance of complete angiographic investigation and early exploratory laparotomy is stressed.


Reiter's aortitis with pericardial fluid, heart block and neurologic manifestations. A man who presented with Reiter's triad and keratoderma blenorrhagicum followed by cardiac manifestations is reported. He developed mild aortic insufficiency, A-V block and pericardial effusion. Painful ophthalmoplegia occurred 5 months later with exacerbation of the cardiac complications as corticosteroids were being tapered. Retreatment with high dose corticosteroids resulted in a remarkable remission of the neurologic complications and stabilization of his cardiac manifestations now maintained for 3 years.


Idiopathic retroperitoneal fibrosis: a systemic connective tissue disease? Renal histology of a patient with idiopathic retroperitoneal fibrosis demonstrated a proliferative crescentic glomerulonephritis with intramembranous electron-dense deposits. These findings were interpreted as being consistent with an immune complex glomerulonephritis. Serologic studies revealed a positive antismooth muscle antibody titer of 1:80 and a weakly positive antinuclear antibody titer of 1:40. No distinct systemic disease was identified. While fibrosis of the retroperitoneum can occur in association with a number of distinct pathologic conditions and pharmacologic agents, the mechanism responsible for the development of the idiopathic variety of retroperitoneal fibrosis remains unclear. Our observation of an immune complex glomerulonephritis and the cumulative data on idiopathic retroperitoneal fibrosis are consistent with the concept that the fibrosis may be a local expression of an immunologically mediated systemic disease.


Office uroflowmetry using a maximum flow rate purge meter. The use of a purge size rotameter for the determination of maximum urinary flow rates represents an inexpensive and non-invasive method to detect obstructive or neurogenic lower urinary tract abnormalities. We have used the device to identify successfully selected patients with such abnormalities.


Presence of natural killer cells in specific-pathogen-free chickens. Spleen cells of normal specific-pathogen-free N, P, and 15 X 7 chickens were cytotoxic in vitro for target cells of Marek's disease lymphoma line MSB-1. The natural killer (NK) cell activity, best expressed in chickens over 7 weeks old, varied among several genetic lines of chickens tested. The NK cells were thermolabile, and incubation of the cells at 37 degrees C for 30--60 minutes resulted in substantial loss of cytotoxicity. The specificity of NK effector cells was directed against common antigen(s) on tumor cell lines of diverse origin but not on normal adult or embryonic cells.


[Effect of chorionic gonadotropin on the urinary excretion of testosterone and other androgens in healthy men and those with coronary arteriosclerosis]. The results of studying the excretion of testosterone and other androgens with the urine after a chorionic gonadotropin load in patients with ischemic heart disease and in persons who had suffered from acute myocardial infarction are discussed. In choriogonin load stimulating the gonads, there is noticeable variability in the excretion of testosterone and epitestosterone, androstenedione, and 7-keto-dehydroepiandrosterone in the urine. The data obtained are evidence of reduced functional reserves of the sex glands in some of the patients.


Studies on adjuvants for human prophylactics. II. Influence of the route of injection on the activity of adjuvants to tetanus toxoid in guinea pigs. The effects of the route of the injection and adjuvants on the immune response of guinea pigs were investigated at various stages of immune response to tetanus toxoid. Delayed-type hypersensitivity (DH) was observed as the first immune response to the toxoid before initiation of antitoxin production. The DH reaction was weak when plain toxoid was administered subcutaneously. Water-in-oil in water (w/o/w) enhanced greatly the reactivity of the immunized animals; pertussis vaccine, endotoxin and aluminium showed adjuvanticities in this order. The foot pad (fp) injection of plain toxoid promoted remarkably the induction of DH. The reactivity was enhanced considerably by w/o/w and to a less extent by aluminium. However, pertussis vaccine showed an adverse effect on DH by the fp route. Active cutaneous anaphylaxis (ACA) induced by the subcutaneous route was enhanced by w/o/w, endotoxin, pertussis vaccine and, to a less extent, by aluminium. The fp route compared with the sc route enhanced ACA by plain toxoid; w/o/w and aluminium but not endotoxin and the vaccine showed adjuvanticities. The influences of adjuvants and the route of injection on Arthus reactions were inconsistent. The effect of adjuvants on antitoxin production was quite different from that on DH when antitoxin was produced abundantly. Aluminium showed consistently a potent adjuvanticity, but activities of w/o/w, endotoxin and pertussis vaccine were inconsistent 4-6 weeks after the primary stimulus by the subcutaneous route. The adjuvant effect became less significant in the secondary response. The fp route was more favorable for antitoxin production than the subcutaneous route with most adjuvants except pertussis vaccine added to tetanus toxoid. Antitoxin production by plain toxoid was very poor when administered intraperitoneally; aluminium and w/o/w but not endotoxin showed a remarkable adjuvanticity for the antitoxin production.


[Radiologic findings in newborns with group B streptococcal septicemia: clinical importance of heart size and lung manifestations (author's transl)]. Chest radiographs of thirteen neonates with group B streptococcal septicemia were evaluated for signs of early diagnosis. Six of the neonates had chest radiographs as seen in idiopathic respiratory distress syndrome (RDS). Seven patients had radiologic findings consistent with neonatal pneumonia. The children with RDS were in general smaller and born prematurelly, but three neonates with x-rays resembling RDS had normal birth weights and thus were mature. Cardiomegaly was observed in a high percentage with a prevalence in children with RDS. Heart size increased in two of the three children who died, but became normal in patients recovering from infection. Three patients had pleural effusions.


[The regulation of protein synthesis in heart muscle. Biochemical data, stimulative and inhibitory factors and their clinical significance (author's transl)]. The regulation of protein synthesis in heart muscle has been investigated by many authors under both normal and pathological conditions. This review summarizes the evidence for the dependence of normal heart protein synthesis from normal serum levels of insulin, amino acids, fatty acids and glucose. A decreased serum concentration of these substances causes an inhibition of heart muscle protein synthesis by 30--60%. Various drugs and other chemical lead to similar impairments of heat muscle protein synthesis. The resulting imbalance between synthesis and degradation of myocardial proteins with their half-times of 5--12 days gradually leads to a decrease in their myocellular concentration with a consequent impairment of myocardial function. Finally, the biochemial sequences are described which represent the important pathogenetic mechanisms in the development of heart muscle hypertrophy and in the adriamycin-induced cardiomyopathy.


Comprehensive urinary screening for inborn errors of complex carbohydrate metabolism. A rapid and comprehensive urinary screening programme is presented by which most of the "heteroglycanoses" can be identified. The diagnoses obtained on a total of 44 patients with different storage disorders shows the usefulness of the method.


[Hodgkin's disease. Results in diagnosis and treatment (author's transl)]. Optimal treatment in Hodgkin's disease requires the knowledge of the stage the disease has reached. Laboratory tests, x-ray and scintigraphy, usually, are not sufficient, but biopsies of bone marrow and liver are necessary, in special cases supplemented by laparoscopy or explorative laparotomy with splenectomy. As treatment of choice, irradiation is favored for disease restricted to lymph nodes, and cytostatics for disease complicated by severe symptoms or by organ involvement. Diagnosis and therapy should be adapted to the individual patient. New therapeutic approaches must be compared with the sometimes excellent results obtained by several institutions.


Properties of (Mg2 + Ca2+)-ATPase of erythrocyte membranes prepared by different procedures: influence of Mg2+, Ca2+, ATP, and protein activator. Erythrocyte membranes prepared by three different procedures showed (Mg2+ + Ca2+)-ATPase activities differing in specific activity and in affinity for Ca2+. The (Mg2+ + Ca2+)-ATPase activity of the three preparations was stimulated to different extents by a Ca2+-dependent protein activator isolated from hemolysates. The Ca2+ affinity of the two most active preparations was decreased as the ATP concentration in the assay medium was increased. Lowering the ATP concentration from 2 mM to 2-200 microM or lowering the Mg:ATP ratio to less than one shifted the (Mg2+ + Ca2+)-ATPase activity in stepwise hemolysis membranes from mixed "high" and "low" affinity to a single high Ca2+ affinity. Membranes from which soluble proteins were extracted by EDTA (0.1 mM) in low ionic strength, or membranes prepared by the EDTA (1-10 mM) procedure, did not undergo the shift in the Ca2+ affinity with changes in ATP and MgCl2 concentrations. The EDTA-wash membranes were only weakly activated by the protein activator. It is suggested that the differences in properties of the (Mg2+ + Ca2+)-ATPase prepared by these three procedures reflect differences determined in part by the degree of association of the membrane with a soluble protein activator and changes in the state of the enzyme to a less activatable form.


Gastrointestinal carcinoids: extrahepatic metastases and symptomatology following resection. Of 49 patients with midgut and hindgut carcinoids, second primary distinct carcinomas occurred in 12. The most aggressive carcinoids were the 24 that arose in the distal small bowel and cecum. Of the patients affected, 15 had lymph node metastases and eight had liver metastases at the time of diagnosis. That only five patients were completely relieved of symptoms following resection was partially explained by autopsy findings in 15 patients, six of whom had metastatic extra-abdominal carcinoid without liver metastases (most commonly, bone metastases).


Long-term results after surgical correction of Ebstein's anomaly: report of two cases. Two patients with Ebstein's anomaly had valve replacement with Starr-Edwards cloth-covered valves 11 and 8 years ago. They have been asymptomatic and very active despite the absence of anticoagulation. These cases provide some of the long-term results needed for proper evaluation of the different methods of operative treatment of Ebstein's anomaly.


Ageing of Neurospora crassa. IX. Microviscosity properties of mitochondrial membranes during normal and abnormal growth and development of an inositol auxotroph. Microviscosity of mitochondrial membranes of an inositol auxotroph of Neurospora was measured by the method of Shinitzky, employing the fluorescent probe diphenyl-hexatriene. With high concentration of inositol, growth, morphogenesis, and cellular and biochemical phenotypes of the auxotroph are normal; whereas with low concentrations, these characteristics become abnormal and cellular and clonal senescence ensue. During normal growth and development, the critical temperatures of phase transition, the energies and volumes of fusion (delta E, V), and the microviscosities (n) at low and high temperatures changed in a cyclical "gaussian" manner; whereas the microviscosity at 25 degrees C remained constant. The normal developmental changes of the microviscosity properties were consistent with Brody's molecular packaging hypothesis, whereby the biochemical properties of conidia are pre-determined in conidiogenic hyphae. The microviscosity properties and their developmental change were closely correlated with other biochemical and biological properties such as the critical extremities of growth temperature, activity of membrane-bound cytochrome oxidase, and the stages of cellular differentiation. The thermodynamic properties of the membrane microviscosity support the genetic hypothesis that conidia and conidiogenic hyphae are more highly differentiated than growing hyphae. During abnormal growth and development, delta E and V of the liquid-crystalline phase underwent a precocious, but otherwise normal change at an early age; whereas subsequent cellular and mitochondrial senescence was accompanied by an abnormal increase of microviscosity and abnormally small delta E and V. With the results of other experiments and by analogy to proposed structural determinants of microviscosity properties of other biological membranes, a tentative interpretation of the molecular basis of the microviscosity properties and their normal and abnormal changes is derived. The effects of phospholipase treatment indicated that electrostatic interaction of phospholipid polar groups with membrane proteins may restrict mobility, increasing microviscosity and decreasing energies of fusion. Abnormal development or ageing of the membranes, leading to abnormally large n and small delta E, is probably a consequence of excessive lipid peroxidation and related abnormal changes of their structure.


Ageing of Neurospora crassa. VIII. Lethality and mutagenicity of ferrous ions, ascorbic acid, and malondialdehyde. Ferrous ions were highly lethal and mutagenic to germinated conidia of Neurospora crassa. At comparable survival, treatment with 0.2 mM ferrous ions was 14- and 50-fold more mutagenic than ultra-violet irradiation or X-rays, respectively, in the reversion of an inositol auxotroph. Ascorbic acid alone (2 mM) was not reproducibly lethal and inhibited both the lethality and mutagenicity of ferrous ions. Bovine superoxide dismutase (SOD) completely inhibited the residual lethality of ferrous ascorbate. Protection by ascorbic acid and SOD indicates that superoxide radicals, generated by oxidation of Fe(II), are directly or indirectly mutagenic and lethal. Malondialdehyde (MDA) was lethal and appeared to be mutagenic; however, its action is probably different from that of superoxide. Therefore, superoxide-mediated production of endogenous MDA by way of peroxidation of polyunsaturated fatty acids is probably not an alternate mutagenic pathway, at least in the reversion of the allele of the inl locus examined. These results and the demonstration of superoxide-mediated decrease in the synthetic fidelity of DNA polymerase in vitro (Rana and Munkres, in preparation) warrant additional exploration of the hypothesis that endogenous cellular free radicals, generated by pre- and post-senescent metabolism, may enter into lethal and mutagenic reactions.


The relevance of growth control (chalones) to the aging process. A large amount of data suggests that a wide variety of cells and tissues contain cell-specific endogenous inhibitors of mitosis which are non species-specific. Increasingly, it appears that these chalone inhibitors are actually relatively small polypeptides capable of complexing with large molecular weight anionic molecules. The purification and chamical characterization of these inhibitors has been rendered extraordinarily difficult and the results have been very slow in forthcoming because of this ability to form complexes with anionic polyelectrolytes. Our recent understanding of this behavior should markedly accelerate our understanding and knowledge of chalone biochemistry in the future. If, in fact, chalones are ubiquitously important to the control of cell proliferation, then they will be important to our understanding of the development of post-mitotic cells and to our concepts of programmed senescence; both in turn might be important to our knowledge of the aging process.


Chalones: concepts and results.

Chalones: concepts and results. Control of cell proliferation is executed, in part, by means of negative feedback, utilizing cell-line specific messenger substances called chalones. Although knowledge of chalone chemistry is still in its infancy, the reality of the concept can no longer be reasonably questioned. In particular, it has recently been shown that chalones are even capable of causing tumour regression both in animals and in man. In addition to overviewing the chalone concept, we show here that the chalone-induced tumour regression is readily explained in simple and plausible terms.


Role of peritoneoscopy in the postoperative evaluation and treatment of adenocarcinoma of the exocrine pancreas. Our experience with peritoneoscopy in the postoperative staging and evaluation of ten patients with locally unresectable adenocarcinoma of the exocrine pancreas is presented. In contrast to the German experience with previously unexplored patients, the pancreas was visualized only 30% of the time and biopsy was not possible for technical reasons. Based on our experience in these ten patients, postoperative peritoneoscopy for staging or for following the effectiveness of treatment is of limited value in carcinoma of the pancreas. Preoperative evaluation of this technique deserves greater attention.


[Rate of DNA synthesis and the size of replication units in cell culture of Drosophila melanogaster]. The rate of DNA replication and the size of replication units was examined by means of pulse-labeling with 3H-thymidine and DNA autoradiography in the chromsomes of Drosophila melanogaster  synchronized cells culture in vitro. The center-to-center distance between adjacent labeled section of DNA fibers was taken for a size of replication unit, i.e. replicon. DNA synthesis was revealed to start simultaneously in most replicons. The rate of elongation of labeled sections of DNA fibers is about 25 mu per hour (75 kb per hour). Taking into consideration bidirectinal DNA replication the rate of DNA replication per growing point is 12.5 mu per hour (38 kb per hour). The mean size of replicon is about 60 mu (130 kb) in cell culture of Drosophila melanogaster and most of these replicons vary from 20 to 80 mu. Calculation suggests that one replicon may consist of six chromomeres each being known to be formed by a segment of DNA molecular 10 mu long on average.


[Description of the kinetics of the two substrate reactions S1+S2 goes to and comes from S3+S4 by a generalized Monod, Wyman, Changeux model]. A number of mathematical models, generalizations of the Monod, Wyman, Changeux model, have been derived describing the kinetics of two substrate reactions S1+S2 (formula: see text) S3+S4. Protomers of the olygomeric enzyme E(R, T) undergo concerted conformational transitions of the type R in equilibrium T. Cases of ordered and random substrate and product binding to the active sites of the enzyme have been considered. The models have been shown to account for the isosteric substrate activation (sigmoidal curves upsilon (S1) and upsilon(S2) and substrate inhibition of the enzyme as well as activation by one substrate and inhibition by the other. Products can exert both activating and inhibiting isosteric effects on the enzyme. Relative advantages of the two main methods of parameter estimation, experimental-kinetic and mathematical, have been discussed. The second method has been illustrated by fitting one of the models to experimental data for substrate saturation of human platelet phosphofructokinase.


[Modern views on mechanism of ATP hydrolysis by myosin (on the 40th anniversary of myosin enzymatic activity discovery)]. Literature data and the author's materials concerning the intermediate stages of ATP hydrolysis by myosin and actomyosin are reviewed. The scheme of hydrolytic stages based on the application of fluorescent and UV spectroscopic stop-flow and 18O exchange methods is discussed. Some unsolved problems of the hydrolytic mechanism and its relation to energy transduction in the mechanochemical act are also considered.


The influence of the gamma system on cross-correlated activity of Ia muscle spindles and its relation to information transmission. In the decerebrate cat during static or slowly varying (less than 0.3 Hz) muscle stretches, the activity of muscle spindle (MS) pairs was poorly correlated and such correlation was not changed after ventral root sectioning. With slightly faster sinusoidal stretches (0.3-20 Hz) activity in pairs of MS was also poorly correlated. However, sectioning of the ventral roots produced preferential firing frequencies in the same muscle spindle pairs and increased their degree of correlation. The increase in correlation between MS activity detected after suppressing the gamma bias appeared to arise from extrinsic 60 Hz power line vibration in the range of micrometers. Nevertheless, activation of the gamma system could suppress such phase locking. When frequencies above 20 Hz were used, the gamma system could not decorrelate the MS pair activity since the two units became locked to their common input signal. It is suggested that decorrelation of MS activity by gamma influence may improve the fidelity of the information transmitted by the Ia MS ensemble by filtering distortion harmonics, as well as damping tremor oscillations in the stretch reflex loop.


Laparoscopy: induction of pneumoperitoneum via transfundal puncture. One of the most troublesome features of laparoscopy is the establishment of pneumoperitoneum. This report discusses a very simple and direct way of establishing pneumoperitoneum via transfundal puncture.


Low back pain in patients with and without demonstrable organic disease. Pain descriptors of patients with low back pain were analyzed to determine their usefulness in identifying patients without demonstrable organic disease. Using a standardized back pain questionnaire which scales qualities of pain along 7 independent factors, it was possible to make clear distinctions between the subjective reports of patients with and without demonstrable organic disease of the lower back. Pain described by patients with demonstrable organic disease tends to be consistent and specific; whereas pain described by patients without demonstrable organic disease tends to be more variable and diffuse. Pain reported by the latter group was also more intense. Factors which may underlie these findings were discussed.


Myosin synthesis and enzymatic properties during thyroxine intoxication in rabbits. Hyperthyroidism has been induced to rabbits by a daily subcutaneous injection of D-L thyroxine (0.3 mg/kg). The ventricular myosin Ca2+ ATPase was increased after one week and reached + 100 % after two weeks while the K+ EDTA ATPase remained normal. During the same period, the heart weight, and the myosin incorporation of 3H-lysine after a four hour period of labelling had increased in parallel. The enhancement of both the Ca2+ ATPase and the labelling of myosin correlate, which suggests the appearance of a new molecule during the course of intoxication. This biochemical abnormality was unchanged after treatment with propranolol.


The relationship of a decline in myofibrillar ATP-ase activity to the development of severe left ventricular hypertrophy in the rat. Abdominal aortic coarctation in the rat led to a modest degree of cardiac hypertrophy associated with normal ATPase activity of myofibrills. The addition of aortic incompetence was accompanied by the development of severe hypertrophy (approx. 75 %). During the course of this latter increase in heart weight, the Ca++ ATPase of myofibrils progressively declined to a level 36% below controls. This occurred at a time when protein synthesis was stimulated as evidenced by increased incorporation of H3 lysine into myofibrils. Results are compatible with the hypothesis that the abnormal ATPase activity reflects the synthesis of an abnormal myosin molecule.


[Sub-umbilical laparotomy by supra-pubic disinsertion of the abdominal rectus muscles (Cherney's incision). 220 cases (author's transl)]. Used in pelvic surgery in women, supra-pubic disinsertion of the rectus muscles, combining a satisfactory aesthetic result, comfort and the possibility of enlargement, was associated with a minimum of complications (4 haematomas, 4 hernias and 2 cases of breakdown) and would be suitable as a routine approach in surgery of this type.


[Subclavian-femoral bypass: New course (author's transl)]. An unusual course for subclavian-femoral bypass was made by tunnelisation underneath the abdominal wall rather than the skin in an elderly patient with a huge incurable incisional hernia which required the wearing of an abdominal support belt. The prosthesis passed behind the sternum and the deep surface of the abdominal wall when the belt was worn.


Nucleotide sequence and conserved features of the 5.8 S rRNA coding region of Neurospora crassa. The nucleotide sequence of Neurospora crassa 5.8 S rDNA and adjacent regions has been determined. The deduced 5.8 S rRNA sequence of Neurospora differs from the 5.8 S rRNA sequence of Saccharomyces cerevisiae at 13 of 158 residues. Nine of these differences are clustered in a segment capable of forming a short hairpin secondary structure thought to be involved in the 28 S - 5.8 S rRNA complex. These differences occur in pairs such that the potential secondary structure is preserved.


Local cutaneous allergy to monocomponent insulin. A case is described of a patient who developed local cutaneous hypersensitivity soon after commencing treatment with monocomponent insulins (MCI). This appears to be the first record of such a case.


[The bronchospasmolytic and protective effects of fenoterol, ipratropium bromide, theophylline ethylenediamine and disodium cromoglicicum in inhalation challenge tests; a comparative study (author's transl)]. Two series of tests were carried out with 0.5 milligrams of fenoterol, 0.25 milligrams of ipratropium bromide (both by inhalation) and with 240 milligrams of theophylline (intravenously) in persons with extrinsic bronchial asthma. In the first series (A) the broncholytic effects of the drugs were studied by administering them after inhalation provocation tests. In series B the protective effects of the drugs were studied by giving them before the tests. Untreated probands served as controls; in series B 20 milligrams of disodium cromoglicicum were given in addition. The results in series A showed that fenoterol had significantly higher bronchospasmolytic efficacy than the other drugs which were only slightly effective. In series B, however, all four drugs had an equally potent protective action. The results indicate that regular administration of these agents benefits persons with allergic bronchial asthma whereas in acute asthmatic attacks prompt and adequate bronchospasmolysis can be induced only by sympathomimetic drugs with beta-effects.


[Immunological examination of lymphocytes in patients with sarcoidosis and bronchial asthma (author's transl)]. Blood lymphocytes of 31 patients with bronchial asthma and of 20 patients with sarcoidosis were isolated and investigated for the following surface markers: E-receptors (E-rosettes, a T cell characteristic), Fc-receptors (EA-rosette assay), C3-receptors (EAC-rosette assay), surface immunoglobulins (immuno-fluorescence technique). In addition, the reactivity against allogeneic lymphocytes was tested in mixed lymphocyte culture (MLC). MLC properties were defined by homozygous reference cells (so-called LD-typing). HLA-typing was performed simultaneously. The results, so far, indicate in both disease groups a series of remarkable alterations of the lymphatic subpopulations. A marked diminution of circulating T lymphocytes was encountered in some cases. The immunological results are discussed in relation to pathogenetic aspects of the diseases.


[Silicotuberculosis in Austria and the industrial injuries act (author's transl)]. The case material comprising all persons who developed silico-tuberculosis since it was listed as an occupational disease almost 50 years ago is analysed. The relationship between various occupations and the incidence of silicosis is reviewed with special reference to the most exposed group: the wokers in the granite quarries of Upper Austria. The changes in the clinical picture of the lesion, legal aspects, diagnostic difficulties in distinguishing between silicosis with or without complicating tuberculosis are discussed.


Inhibition of myosin ATPase by vanadate ion. Inhibition of the myosin ATPase by vanadate ion (Vi) has been studied in 90 mM NaCl/5 mM MgCl2/20 mM Tris-HCl, pH 8.5, at 25 degrees C. Although the onset of inhibition during the assay is slow and dependent upon Vi concentration (kapp approximately 0.3 M-1 s-1), the final level of inhibition approaches 100%, provided the Vi concentration is in slight excess over the concentration of ATPase sites. Inhibition is not reversible by dialysis or the addition of reducing agents. The source of this irreversible inhibition consists of the formation of a stable, inactive complex with the composition M . ADP . Vi (where M represents a single myosin active site). The complex has been isolated, and its mechanism of formation from M, ADP, and Vi has been studied. Omission of ATP increases the rate of formation by about 35-fold (kapp approximately 11 M-1 s-1), yet this rate is still low in comparison with the rates of simple protein-ligand association reactions. This slowness is interpreted in terms of a rate-limited isomerization step that follows the association of M+, ADP, and Vi: M+ . ADP . Vi leads to M+. ADP . Vi (+ indicates the inactive product of the isomerization). The properties of M.ADP.Vi are compared with those of the ATPase intermediate M**.ADP . Pi, and the possible role of Vi as an analog of Pi is discussed.


Morphine potentiation of tonic immobility: effects of naloxone, PCPA, and 5,6-DHT. The duration of tonic immobility in chickens, a catatonic-like state produced by brief restraint, was greatly potentiated by a single 1.0 mg/kg injection of morphine. Naloxone by itself, however, had no effect on tonic immobility, and only an exceptionally large dose of naloxone blocked the morphine potentiation. Pretreatment with PCPA and 5,6-dihydroxytryptamine completely eliminated the morphine enhancement. The effect of morphine on tonic immobility may be mediated by a central serotonergic-raphe system.


Defective splicing of mitochondrial rRNA in cytochrome-deficient nuclear mutants of Neurospora crassa. Recent studies have shown that the gene encoding the large (25 S) mitochondrial rRNA of Neurospora crassa contains an intervening sequence of 2-2.5 kilobases that is not present in the mature 25S mitochondrial rRNA. Earlier studies had provided evidence that mitochondrial rRNAs in Neurospora are synthesized via a 32S precursor RNA that contains sequences for both the mature 19S and 25S RNA species. The present work shows that the intervening sequence is not present in 32S RNA. However, we have identified two temperature-sensitive nuclear mutants that fail to excise the intervening sequence at the nonpermissive temperature (37 degrees C). When grown at 37 degrees C, the mutants show decreased ratios of 25S to 19S RNA and accumulate a novel 35S RNA that appears to consist of 25S RNA plus most or all of the intervening sequence. The mutants are allelic but can be distinguished in temperature shift-up experiments, mitochondrial rRNA processing turning off more rapidly in one than in the other. These mutants should provide powerful new tools for studying RNA processing in eukaryotic cells.


Brain serotonin metabolism with relation to the head twitches elicited by lithium in combination with reserpine in mice. Lithium alone, which scarcely induced head twitches, did not affect brain 5-hydroxytryptamine (5-HT) levels but increased 5-hydroxyindoleacetic acid (5-HIAA) levels. However, the combined use of lithium chloride (2 mEq/kg x 5, SC) and reserpine (5 mg/kg, SC) administered hourly markedly elicited the head twitches, together with the pronounced decrease of 5-HT levels and increase of 5-HIAA levels as similarly seen by reserpine alone. Pretreatment with p-chlorophenylalanine (PCPA) strongly potentiated the twitches elicited by the combined administration of lithium and reserpine, along with inducing the significant decrease of 5-HT levels and no change of 5-HIAA levels as compared with those levels in the PCPA-treated mice. The results imply that lithium produces the head twitches in the presence of reserpine, and an increase of 5-HIAA or a decrease of 5-HT levels do not necessarily interfere with the incidence of the twitches, and that the receptor sensitivity to 5-HT is strongly involved in the incidence of the head twitches.


Facilitation of avoidance acquisition in rats produced by P-chlorophenylalanine or P-chloroamphetamine. The effects of reducing brain serotonin using p-chlorophenylalanine (PCPA) were examined as a follow up to our previous report that reducing serotonin with p-chloroamphetamine (PCA) facilitated Y-maze avoidance acquisition and reduced open field activity. In the current work, PCPA was also found to facilitate Y-maze avoidance acquisition, while open field activity, although reduced, was not reduced significantly. In a second experiment, we re-examined PCA, except that the apparatus was changed in order to test the generality of the effect of PCA on avoidance performance in a task other than the Y-maze. Testing was also run at varying shock intensities to determine if this was a significant determinant of the effect. PCA reliably facilitated shuttle-box avoidance acquisition and did so at all shock intensities tested. Finally, in a third experiment, the time course of the onset of the PCA-induced avoidance facilitation was examined and found to develop 8--10 hours following drug treatment and not at a shorter drug to test interval of 4 hours. The present data, in conjunction with our previous data support the concept that lowered brain serotonin content facilitates avoidance acquisition regardless of the specific method used to reduce serotonin or to assess avoidance acquisition.


Surgery and postsurgical management of the patient with low back pain. The role of surgery in the care of back pain and sciatica is discussed. Surgery's role in this case is relatively minor considering the overall problems of back disorders. The history, signs, and symptoms of various diagnostic categories are reviewed. Factors in deciding on the need for surgical care are analyzed. An algorithm that displays the diagnostic approach as well as various treatment plans helps in the decision-making process. Various exercise programs for postsurgical care are outlined. Details of the surgical procedures are also presented to explain the degree of tissue damage created by surgery itself.


Clinical anatomy of the lumbosacral complex. The clinical anatomy of the lumbosacral region has been presented to show the complexity of spinal pathology. Individual structures are described, but emphasis is placed on understanding the concept of the entire functional unit and how alteration can lead to pain and disability.


Physical examination of the lumbosacral complex. Examination is the foundation upon which effective treatment rests. The importance of a methodical step-by-step process is stressed. The manner in which the examination findings are used to assess the efficacy of the treatment techniques is illustrated. This paper outlines one method of examining the lumbosacral complex.


Mobilization of the spine.

Mobilization of the spine. This article presents spinal dysfunction (as opposed to disease) as being an altered state of mechanics demonstrating either an aberrant motion or an increase or decrease from the expected range. Examination techniques, including passive intervertebral motion testing, are outlined, as is the grading system for recording results. Mobilizations and positional distraction are advocated for treating restricted range, and the neurophysiological and mechanical effects are explained along with their indications and contraindications. Pain is presented as a misleading symptom that cannot be relied upon to monitor the results of treatment. The author considers that exercise routines have no place in the treatment of spinal dysfunction, although selected exercises may be given for the patient's particular requirements. Walking is advocated to maintain mobility and function, but running, cycling, and swimming are generally discouraged.


An innovative program for the restoration of patients with chronic back pain. The literature on conventional medical procedures for restoring high-risk patients having chronic low back pain reveals that these procedures are ineffective and may even be iatrogenic. An alternative, noninvasive approach, which takes into consideration the critical role of cognitive and emotional factors, is practiced at Casa Colina Hospital for Rehabilitative Medicine. Details of the approach as well as comments confirming its efficacy are presented.


Plasma insulin, carbohydrate, and free fatty acid changes in newly born infants of diabetic and non-diabetic mothers after loading with glucose, fructose, and galactose. Changes in the concentration of blood glucose, fructose and galactose and their disappearance rate, concentration of plasma insulin, free fatty acids, blood lactate and pyruvate after intravenous glucose, fructose and galactose loads (1 g/kg) were studied in 23 infants of insulin treated diabetic mothers (IDM). The control group consisted of 42 infants of healthy mothers (IHM). The disappearance rate of these monosaccharides was higher in IDM that in IHM (P less than 0.01). All monosaccharides enhanced plasma insulin levels, but the plasma insulin concentration varied considerably. The highest insulin response with difference between IDM and IHM occurred after loading with glucose. Fructose was the least effective insulin stimulator which did not increase glucose levels. All monosaccharides decreased free fatty acid levels. Lactate levels and lactate:pyruvate ratio in IHM were increased after fructose loading. The results of this study suggest that galactose is of some physiological importance for maintaining glucose levels and that the islet apparatus of newborns of diabetic mothers is less loaded with galactose than with glucose.


Macromolecular synthetic activity in mice regenerating liver after ethylnitrosourea injection. The present report is a continuation of our previous studies on the biochemical mechanisms of carcinogenesis; studying the nature of interactions taking place between Ethylnitrosourea and DNA, RNA and protein of various stages of their synthetic activity. As a model system we chose partially hepatectomized mice live 36 hrs after surgery. Synthetic macromolecule activity in the remaining liver segment was determined by means of 3H-thymidine, 3H-uridine and 3H-leucine. We observed complete depression of DNA synthetic activity (immediately after Ethylnitrosourea administration it remained depressed almost through out the whole period of our observations) while protein synthetic activity was highly elevated. Qualitative changes of soluble proteins which were analyzed by isoelectric fractionation on 5% polyacrylamide after previous 3H- and 14C-leucine incorporation, could not be detected. Our biochemical data are correlated with histological studies and with the tumour incidence following the Ethylnitrosourea treatment of partially hepatectomized mice in the course of long-term experiments. The results provide guideline for further analysis, which should be modified according to the information concerning Ethylnitrosourea carcinogenesis induced 36 hours after partial hepatectmoy.


A study of the effect of dietary factors and various exercises on the swimming performance of the albino rat. In Experiment 1 a double-phase test diet (high-protein low-carbohydrate phase (HP): 5 days, high-carbohydrate phase (HC): 2 days) was compared to a normal diet by measuring all-out performance in rats trained by steady or interval swimming exercise. The tests carried out on the 8th day showed the swimming performance to be improved to a similar extent by the two training procedures, to be further improved by the test diet in the exercised animals; changes in liver glycogen, blood glucose and serum corticosterone reflected especially in the influence of exercise which in some cases was potentiated by the test diet. In Experiment 2 the 5 days of high protein intake were treated separately from the effect of the double-phase test diet as a whole in order to study the mechanism. These aminals were exercised by treadmill running of 7 days. Cytochrome P450 content of the liver rose under the effect of exercise as well as the HP phase, thus supplying additional evidence for the enzyme inducer effect of physical exertion. Glycogen decreased both in the muscle and liver during the HP phase and returned to normal after the HC phase. Liver glycogen rose to an even higher level than normal in the trained groups, but muscle glycogen values remained lower, this may be related to the shortness of training and to an accelerated rate of turnover. High protein intake associated with a depletion of carbohydrate stores was found to have an effect of its own which, when followed by replenishment of calories reserves, might be used to advantage in improving physical performance.


Inactivation of bradykinin by placental peptidases. Normal human placental eluate (0.15 M NaCl) has very high capacity for inactivating synthetic bradykinin (its specific activity is 20--50 times higher than that of normal human serum). In chromatography on DEAE-Sephadex A 50, several fractions with bradykinin-inactivating capacity were recovered. On Cbo-Phe-Arg synthetic substrate, one fraction with kininase activity was identified as carboxypeptidase N. This is not identical with serum (pregnancy) carboxypeptidase N and does not therefore pass into the blood stream. The properties of other fractions with kininase activity were studied. Aminopeptidase activity degrading L-lysine-p-nitranilide and L-arginine-beta-naphthylamide was separate from kininase activity.


Use of the periodogram in the analysis of high frequency basal blood sugar oscillations in healthy subjects. Twenty-four triplicate samples of the morning blood sugar of 17 fasting healthy women were taken from the cubital vein with a cannula at 15-sec intervals. The mean value was 4.44+/-0.69 mmol/l and the mean variation range 22.4+/-9.2%. Variability within the sets of three samples was 1.7+/-0.9%. In 23.5% of the cases, statistically significant periodicities (p less than 0.05) were detected by computing the periodogram. In 29.4%, several periodic components (2--4) were detected simultaneously. After deducting harmonic components, the residual scatter fell by an average 43.9%. In four cases the drop was significant in the F test at 1% and in one case at 5% level. The periodic components of the observed oscillations could be due to oscillation in feedback control circuits and the main role in the random component was evidently played by inadequate glucose blending in the circulation.


[Modification of the ovarian cycle, ovulation and reproduction in rat by administration of p-chlorophenylalanine in the pre and post ovulation period (author's transl)]. The effect of p-Chlorophenylalanine (PCPA) administered in pre and post-ovulation phases on ovulation reproduction and ovarian cycle was studied in rats. Vaginal smears, number of ovules, mature follicles and ovaric histologic features were evaluated. PCPA administered in the periods after follicular rupture prolongs the diestrus phase from 2 to 10 consecutive days and totally inhibits the reproductive conduct. When administered in the periods just prior to follicular rupture, PCPA prolongs the estrus phase from 2 to 4 consecutive days and does not totally inhibit reproduction. A progressive increase in reproduction took place as treatment time approached ovulation, to such an extent that the number of inseminated and fertilized rats when treated at the ninth hour of the proestrus phase, was superior to the control group. PCPA administered in periods after and before follicular rupture totally inhibits ovulation in all cases. Ovaries present many mature follicles, as many as in the controls sacrificed at the 18 hour of the proestrus, just before ovulation.


[Supression by copulation of the inhibitory effect of p-chlorophenylalanine on rat ovulation (author's transl)]. The effect of copulating on reflex ovulation was studied in rat. The effect of PCPA (300 mg/kg, i.p.) on ovulation and reproduction was compared by evaluating number of oocytes in tubes, histologic features of ovaries, vaginal cycle, insemination, fertilization and number of embryos per rat. PCPA, administered on 9th and 16th h of the estrus phase, totally inhibits ovulation, stimulates reproductive behaviour and prolongs the estrogenic phase. When the animals are kept in copulatory conditions for 16 or 46 hours, the inhibition induced in ovulation disappears to the extent that 60% of the rats become pregnant though the number of embryos is under that of the control group. The farther the treatment with PCPA within the same cycle in the ovulatory period, the greater the inhibitory effect on ovulation is and the lesser the neutralizing effect produced by reflexes related to copulation. Administration of PCPA at the 16 hour of the diestrus causes a greater increase in the average number of embryos-as compared to administration at the 9 hour. In periods longer than 48 hours before ovulation, the inhibition brought about by PCPA is not suppressed by copulatory conditions kept for 16 or 24 hours and is only neutralized if they are kept during a complete cycle. Those treated with PCPA in the diestrus phase and maintained in copulatory conditions for 46 hours, present a higher average of embryos than those maintained in similar conditions for 16 hours.


[Transportable communication and environmental control device for the profoundly handicapped (author's transl)]. At the centre for the physically handicapped in Weingarten/Württemberg (Federal Republic of Germany) a multidisciplinary approach has been made to develop a experimental model of a communication device for the profoundly handicapped, which is transportable and can easily be handled and adapted to motor and cognitive abilities. This tool is available free of charge for a test period after which the user is required to give a report of his experiences, which will provide the basis for models which will be marketed.


Restimulation in secondary MLC by autologous non-T cells. Lymphocytes sensitized in mixed leucocyte culture (MLC) were restimulated with non-T or complete cells. Cells primed against autologous non-T cells and restimulated with autologous cells gave responses with the kinetics of a secondary response. In contrast, cells primed against either type of autologous cell responded to restimulation by allogeneic cells with the kinetics of a primary MLC response. Following priming against alloantigens good secondary responses against both complete and non-T allogeneic restimulators were seen. Restimulation with autologous non-T cells, but not autologous complete cells, also led to secondary responses. The observation of different responses to antigens expressed on non-T autologous lymphocytes, in comparison to complete cells, implies that the secondary MLC involves more than response against alloantigens. Allogeneic and autologous MLC may be qualitatively different phenomena, the latter representing the recognition of identifying structures between interacting populations of cooperating cells.


Human leucocyte interferon: analysis of effect on MLC and effector cell generation. Mixed lymphocyte cultures (MLC) showed decreased thymidine incorporation when interferon (IF) had been added to the culture medium. The cell-mediated lympholysis (CML) potential generated in mixed lymphocyte cultures grown in the presence of IF was substantially augmented at a certain concentration range. Highly purified leucocyte IF also had this effect, whereas mock preparations did not. The CML-augmenting property was found in the antiviral fraction after separation of semipurified leucocyte IF (by the method of Dahl & Degree). The possibility that the effects were due to a shift in kinetics after culturing in the presence of IF has been excluded. The killer-enhancing properties of IF did not seem to be due to an enhanced expression of histocompatibility antigens, the selective inhibition of CML suppressor cells, or a change in the specificity of recognized target cells. The results of secondary in vitro MLC-CML experiments, in which primary MLC had been carried out in the presence or absence of IF, indicated that the compound acts (in vitro) through preferential selection of cells that are less sensitive to inhibition by IF and more likely to kill.


Activation of abdominal muscles during some physiotherapeutic exercises. The aim was to evaluate the theoretical efficiency of some abdominal muscle exercises for strength training. Sit-up with rounded back (curl-up) from the supine position up to 45 degrees activates the straight and oblique abdominal muscles to 50% of the values for maximum isometric contraction measured as integrated EMG. This exercise was compared with two previously suggested exercises: curl-up with simultaneous activation of the plantar-flexors of the ankle activated the abdominal muscles to the same level and curl-up from a position with dorsally extended spine did not activate the muscles more. Curl-up with lateral rotation of the trunk gave a high activation of the oblique muscles. This exercise was compared with two completely isometric exercises suggested for patients with back pain: only somewhat lower activation was obtained during an exercise in supine position with lateral resistance to the knees, but with lateral resistance against the elevated forearms there was only little activation.


A cytogenetic study of a mentally retarded population in South Africa. The entire population of the Umgeni Waterfall Institution for mentally retarded Whites was karyotyped using aceto-orcein and ASG banded preparations. Of the 512 subjects, 376 were males and 136 were females. Their ages ranged from 1 to 72 years and mental retardation ranged from borderline to profound. Altogether 11,1% had chromosome abnormalities, of which 8,2% had trisomy-21, 1,9% had other autosome abnormalities, and sex chromosome anomalies occurred in 1%. Normal variant chromosomes were seen in 4,5% of the population. Problems that arose in the course of the survey were mainly due to inadequate family histories and the high proportion of cases in which contact with the family had been lost, thus precluding proper follow-up studies.


Chromosome abnormalities in South African mental retardates. Standard and differential staining techniques were employed in this cytogenetic study of mentally retarded Whites at the Umgeni Waterfall Institution. All of the 512 patients were karyotyped and 57 were found to have chromosome abnormalities. Of these, 42 had trisomy-21; there were 3 subjects with 5p deletion (cri-du-chat) syndrome, 3 had supernumerary small marker chromosomes, and 2 had complex structural rearrangements. Gonosomal aneuploidies were less common than the autosomal defects and only 2 poly-X males and 1 poly-X female were identified. Long Y chromosomes were found in 11 males and 4 others had deleted Y chromosomes. One abnormal chromosome, a deletion of the terminal region of 11q, was missed in unbanded karyotypes. Banding is essential to the identification of structurally abnormal chromosomes.


Resistance and sphincter-like properties of the cystic duct. The canine cystic duct, like that in man, has an extremely thin layer of muscle deep to the mucosal layer, surrounded by a dense layer of collagen fibers. The resistance to flow through the duct was studied in 16 anesthetized dogs by perfusing the duct with saline solution at constant pressure and recording the flow rate of the solution. The flow rate varied with respiratory movements, but there were also nonrespiratory variations which might be due to spontaneous sphincter-like contractions. Significant reductions in flow through the duct followed systemic intravenous or local intra-arterial injections of morphine or pharmacologic concentrations of adrenaline or cholecystokinin. It was concluded that an extremely small amount of muscle in the wall of the duct was capable of sphincter-like activity. The resistances to flow were the same in either direction through the duct, an indication that the prominent mucosal folds, valves of Heister, did not function as unidirectional valves. In view of the high resistance to flow through the duct and the possibility that sphincter-like activity may also occur under physiologic conditions, the function of the duct requires more attention than it has received in the past.


Noninvasive hemodynamic evaluation in selection of amputation level. Various noninvasive techniques of hemodynamic evaluation have been used to determine the optimal level of amputation. Noninvasively obtained measurements of pressure and blood flow in the lower extremity have been found to be reliable in predicting the probable healing of an amputation. In patients with severely calcified noncompressible arteries, noninvasive electromagnetic flowmeter measurements of peak pulsatile flow provide a more accurate indication of the vascular status of the patient than do blood pressure measurements which, in such patients, frequently exceed 300 millimeters of mercury. Skin thermistor thermometry does not appear to be applicable in patients with extensive severe ischemia of the leg. The need for a reliable method of determining the lowest possible level of amputation is well recognized. Such factors as wound edge bleeding and clinical judgment too often lead to above the knee amputation when, frequently, a more distal amputation could have been possible. Our experience has shown that noninvasive techniques for hemodynamic evaluation are a valuable aid to clinical judgment in determining accurately the lowest level for successful limb amputation.


Macrophage-related suppressor cells in human renal transplant recipients. In this study 66 renal transplant recipients were studied by in vitro immunologic monitoring assays in an attempt to delineate some immune reactivity parameters which migh explain the successful long-term survival of HLA incompatible allografts. Ninety percent of the recipients were found to be responsive to their specific donors in one-way mixed lymphocyte culture assays, indicating the presence of antigen reactive proliferating T cells. In contrast, studies of the in vitro generation of cytotoxic T cells showed that 73% of the long-term recipients demonstrated a marked hyporesponsiveness to the donor in cell-mediated lympholysis (CML) assays. Longitudinal studies indicated that specific CML hyporesponsiveness to the donor developed after transplantion. In the majority of recipients, CML hyporesponsiveness could be related to a suppressor cell phenomenon, since recipient mononuculear cells specifically suppressed the CML reactivity of third-party cells to the donor. Recipient CML hyporesponsiveness to the donor could be abrogated by removal of recipient adherent cells, most of which were monocytes or macrophages. The suppressor cell effect on CML is postulated to be related to macrophages which are either acting independently or under the regulation of suppressor T cells. These studies are among the first to suggest that suppressor cell regulation of relevant effector T cell activity may be important in the facilitation of successful human renal transplantation.


The RhLA complex of rhesus monkeys. XI: Positive MLC reactions between identical sibs caused by alloimmunization. D-locus identical pairs of monkeys were alloimmunized. An exchange of skin and blood between initially MLC-negative unrelated monkeys frequently led to strong mutual reactivity in mixed cultures. This was not the case when RhLA identical siblings were similarly (mutually) immunized. These data led to the postulation of a second RhLA-linked MLC locus, named D', which exerts its influence only after alloimmunization. Interestingly, strong MLC responsiveness between the RhLA identical siblings could be provoked after further immunization with tissue from a thired party animal. This unexpected MLC-reactivity is ascribed to the in fluence of minor non MHC linked loci which express themselves if the responder has been sensitized against a disparate D'-product. It is suggested that the postulated D' locus has a "helper function" in that it assists in triggering proliferative responses in mixed cultures against the products of these non MHC loci.


Different stimulating capacity of monocytes and B lymphocytes in mixed leukocyte cultures: a dose response study. Cell fractions highly enriched either for monocytes of for B lymphocytes were separated from human peripheral blood. They were tested for their capacity to stimulate allogeneic lymphocytes in mixed leukocyte cultures, using dose-response titrations. Neither population could be stimulated to proliferate by allogeneic cells, but both proved strong stimulators. In this respect monocytes were more efficient than B cell preparations. Differences were pronounced at the lower numbers of stimulating cells but were no longer significant with large amounts of cells.


Aromatization of androgens by human breast cancer. The metabolism of dehydroepiandrosterone and testosterone by human mammary tumor was investigated. Estrogen synthesis from dehydroepiandrosterone was observed in 9 of 10 estrogen-receptor-negative tumors and only in 2 of 8 receptor-positive tumors (p less than 0.025). Conversion of testosterone to estrogens was observed in 7 of 8 receptor-negative and 2 of 7 receptor-positive tumors. Tumors which are capable of transforming dehydroepiandrosterone to estrogens were also able to aromatize testosterone suggesting that the presence of the aromatase enzyme is inherent to certain tumor cells. No estrogen formation was detected by the mitochondrial-microsomal fraction of normal breast cells while fractions from both fat cell and tumor cell showed estrogen synthesis. Estrogen formation by tumor cell fraction ranged from 5 to 190 times that observed for fat cells. The physiological significance of these results in the neoplastic tissue and its relationship to hormone dependence are discussed.


Changes in mixed lymphocyte culture-reactive lymphocytes following alloimmunization of single lymph nodes in sheep. When an "isolated" single lymph node is challenged with irradiated allogeneic lymphocytes, there is a change in the reactivity of the lymphocytes flowing out of the node when they are cultured in vitro in unidirectional mixed lymphocyte cultures (MLC) against the immunizing lymphocytes. These changes in the reactivity of the recipient lymphocytes are shortlived, follow a set time sequence in relation to the cell traffic changes accompanying the immune response, are the property of small lymphocytes and not blast cells, are exhibited by surface Ig-negative cells, and they are specific for the donor lymphocytes. It is suggested that antigen causes the selective retention of antigen-specific lymphocytes within the stimulated node followed by the proliferation and differentiation of large numbers of antigen-specific cells, which then leave the lymph node as small lymphocytes.


Atopy.

Atopy. Atopy should be considered an immunological disorder that may result in several clinical conditions including respiratory disease, allergic dermatitis, food allergy dermatitis, and perhaps flea allergy dermatitis. The clinical course of the disease tends to fluctuate from season to season, which makes objective evaluation of injection therapy difficult. The disease is subject to both familial and environmental influences, and dogs maintain the atopic state throughout their life. The disease cannot be cured; however, a combination of symptomatic and specific injection therapy usually provides adequate control of the clinical signs. Owners of atopic dogs should appreciate that their pet has inherently itching skin, a cure for which is unlikely to be found.


[Protein and lipid metabolic characteristics of persons in a hot climate]. A comparative investigation of the total protein, its fractions, total lipids, cholesterol, carotinoids, retinol, tocopherol in the blood serum of practically healthy persons (donors) was effected in different periods of the year. The proteinic and lipids metabolism rates in persons residing in conditions of a hot climate were found to change substantially, depending upon the season of the years. It is possible that, to a certain degree, this is due to a change in the nature of the nutritional pattern of these people under the effect of climate factors.


[Properties of the influenza viruses isolated in 1976 from gulls in Astrakhan Province]. Investigation of a number of properties of influenza viruses isolated from Laridae birds in the Astrakhan region showed that in one epizootic focus avian influenza viruses with different hemagglutinins and identical neuraminidase may circulate among Laridae birds. Among viruses with the antigenic formula Hav5Nav2 clear-cut differences in virulence and plaque-forming capacity were demonstrated.


[Virological and serological examination of the patients in a period of influenza A1 outbreak in Aktyubinsk]. In October--December, 1977, an epidemic outbreak of influenza predominantly among young people of an organized community was recorded in Aktyubinsk. For decifering the outbreak virological and serological examinations of 325 subjects in foci of the disease as well as hospitalized patients were carried out. The etiology of influenza was confirmed clinically, epidemiologically, and by laboratory examinations in 150 patients. In chick embryos, 53 strains of influenza A1 virus were isolated. Investigations of the strains causing the influenza outbreak in autumn 1977 confirmed that they were influenza A (HINI) viruses. Antihemagglutinating antibodies to the new influenza A1 virus isolate were demonstrated in patients and normal subjects. A detailed analysis of antibody levels to 5 serotypes of influenza virus revealed a rise in antibody titers to the homologous serotypes A2 and to the new A1 isolate. In the acute stage of the disease and in convalescence the geometric mean antibody titer to the new A1 isolate was comparatively lower than to other serotypes.


[Chim virus, a new arbovirus isolated from ixodid and argasid ticks collected in the burrows of great gerbils on the territory of the Uzbek SSR]. Five strains of hitherto unknown arbovirus designated Chim by the place of primary collection of ticks was isolated from Ixodid and Argasid ticks collected in the Uzbek SSR in burrows of great gerbils. The virus has no antigenic relationships with arboviruses previously isolated from ticks, its size varies from 100 to 220 nm, it contains RNA and has a lipid-containing envelope. Chim virus is pathogenic only for suckling mice by the intracerebral route and exerts cytopathic effect in continuous L, Rh, BHK cell lines.


[Left ventricular relaxation and filling abnormalities in patients with HOCM and left ventricular pressure overload (author's transl)]. In order to test the hypothesis that delayed mitral valve opening (MO) with regard to endsystolic dimension (t DS-MO) is specific for hypertrophic obstructive cardiomyopathy (HOCM), LV echograms of patients with different forms of LV hypertrophy due to chronic pressure overload (CPO; aortic stenosis + arterial hypertension, n = 24) and hypertrophic obstructive cardiomyopathy (n = 24) were recorded, digitized and compared with those of normals (N :n = 28(. In patients with HOCM (93 +/- 37 ms; p less than 0.0001) and CPO (66 +/- 31 ms; p less than 0.0001) the time t DS-MO was significantly delayed compared with N (13 +/- 15 MS), due to abnormal relaxation. This prolonged relaxation time resulted in an abnormal diameter increase (delta D) during the isovolumic relaxation phase (HOCM: 4.0 +/- 2.2 MM/CPO: 3.0 +/- 1.8 mm; p less than 0.0001/N:0.6 +/- 0.5 mm) and the rapid filling phase (HOCM 7.6 +/- 2.7 mm; p less than 0.0001/CPO 9.2 +/- 2.9 mm; p less than 0.05 / N: 10.7 +/- 2.2 mm). The echocardiographical signs of an abnormal relaxation are not specific for HOCM, they can be seen in different forms of secondary LV hypertrophy and are accompanied by changes in the diastolic filling pattern.


[A model analysis on the effects of left ventricular hypertrophy and dilatation on pump function and myocardial force and shortening (author's transl)]. The effects of hypertrophy and dilatation on myocardial force and shortening were analysed using Wong's formula for equatorial midwall stress in a thick-walled ellipsoid of revolution. Wall thickness, chamber volume and ejection fraction were treated as independent variables. An isolated increase in wall thickness reduces wall stress and, to a lesser extent, myocardial fiber shortening, i.e. myocardial function is overestimated from ventricular pressures and ejection fraction. Ventricular dilatation without a proportional increase in myocardial mass leads to an increase of myocardial force and shortening, i.e. myocardial performance is underestimated from ventricular function. A decrease of ejection fraction increases total systolic myocardial force considerably, leading to a shift to the right on the inverse relation of force and shortening. Therefore the efficiency of myocardial contraction is reduced and myocardial performance is better than ventricular pump function would indicate.


[Echocardiographic diagnosis of subpulmonic obstruction in hypertrophic cardiomyopathy (a case report) (author's transl)]. The echocardiogram of a patient presenting with a systolic ejection murmur and ECG evidence of left ventricular hypertrophy revealed asymmetric septal hypertrophy but no abnormal systolic anterior motion of the mitral valve as in IHSS. Her pulmonary echo disclosed small A waves, partial valve closure in early systole and coarse systolic fluttering. This motion pattern--which is similar to that of patients with infundibular pulmonary stenosis and which resembles the aortic valve motion pattern in discrete subaortic stenosis--led us to the diagnosis of hypertrophic cardiomyopathy with subpulmonic obstruction, which was later confirmed by cardiac catheterization.


Amanitin content and toxicity of Amantia verna Bull. The alpha-, beta-, and gamma-amanitin content of 11 samples of Amanita verna Bull., collected during 1975--1978 in Germany and Switzerland, has been determined by high performance thin-layer chromatography (HPTLC) of crude methanolic extracts. The toxicity (i. v. LD50 for mice of defatted, lyophilized, methanolic extracts) of 3 samples has been compared with that of A. phalloides from the same site of collection. The amanitin content of A. verna ranged from 2250 to 4570 mg/kg dry weight; the fungi contained almost as much beta- as alpha-amanitin, whereas the gamma-amanitin content amounted to about 12% of the total amanitin. A verna contained less amanitin (65% on the average) than A. phalloides from the same collection site, but it was not significantly less toxic, since the phallotoxins contributed to the toxicity of either species in our tests.


[Absorption, body distribution, metabolism, and excretion of dieldrin in non-human primates and other laboratory animals (author's transl)]. Using 14C-labelled dieldrin, the resorption, body distribution, and rate of excretion as well as the metabolism was investigated qualitatively and quantitatively. The experiments with mice, rats, rabbits, Rhesus monkeys, and chimpanzees were performed under identical conditions to obtain reliably comparable results.


A 1H NMR study of the syn-anti dynamic equilibrium in adenine nucleosides and nucleotides with the aid of some synthetic model analogues with fixed conformations. The syn-anti equilibrium about the glycosidic bond in adenosine and some related analogues was studied by means of 1H NMR spectroscopy, with the aid of several model analogues fixed in given conformations either by intramolecular bonding, or by introduction of a bulky substituent. A model unambiguously and exclusively in the syn conformation is 8- (alpha-hydroxyisopropyl) adenosine; while one fixed in the anti conformation is 8,5'-anhydro-8-oxoadenosine. A new analogue, fixed in the high anti conformation, is 8,2-'O-isopropylidenearabinofuranosyladenine. Several additional new model compounds were synthesized and their properties are described. With the aid of these models, the syn-anti dynamic equilibrium was examined for adenosine and some related compounds in different solvent systems, and the conformer populations evaluated quantitatively. The validity of the procedure applied, and the accuracy of the results are critically examined, and compared with findings obtained by other procedures. Available literature data on the syn-anti equilibrium in other 8-substituted adenosines are re-analyzed in the light of the present results. An analysis is also presented of the interdependence of the various conformational parameter, i. e. conformation about the glycosidic bond and those of the sugar ring and exocyclic carbinol group, in adenosine and 2',3'-O-isopropylidenadenosine.


Separation of the S-adenosylmethionine: 5- and 8-hydroxyfuranocoumarin O-methyltransferases of Ruta graveolens L. by general ligand affinity chromatography. Two S-adenosyl-L-methionine:furanocoumarin O-methyltransferases of R. graveolens, acting at the 5- and 8-hydroxyl of the psoralen nucleus, were completely resolved by adsorption on a general affinity ligand, 5-(3-carboxypropanamido) xanthotoxin, followed by specific desorption by bergaptol and xanthotoxol, respectively. The 5-O-methyltransferase was purified 450-fold by this procedure, the 8-O-methyltransferase 112-fold, and both enzyme fractions were electrophoretically homogeneous. No resolution could be achieved of the activity against two 5-hydroxypsoralens or of the activity against two 8-hydroxypsoralens, and conclusive evidence is presented for the existence of only one 5-O-methyltransferase and only one 8-O-methyltransferase acting on linear furanocoumarins.


Improved synthesis and rapid isolation millimole quantities of adenylysulfate. An improved enzymatic method for the synthesis of adenylysulfate (APS) from adenosine 5'-phosphate using APS-reductase from Thiobacillus denitrificans is described. Isolation of millimole quantitities of this sulfur nucleotide is achieved rapidly by means of ion exchange chromatography on a strongly basic ion exchange resin. A facile and reproducible desalting procedure is described.


Drug-protein interaction: 8-methoxy psoralen as photosensitizer of enzymes and amino acids. For a better insight of the molecular basis of the photobiological effects of furocoumarins, the relevance of proteins oxydation by singlet oxygen produced by these substrates under irradiation with long u. v. light was studied. Complex oligomeric as well as simple monomeric purified enzymes with high or low molecular weight and different properties and simple amino acids were irradiated under oxygen in presence of 8-methoxy-psoralen. The effects on both proteins and amino acids were compared with those obtained under similar conditions with typical photosensitizers as methylene blue and Rose Bengal. The results indicated that the photooxydation of proteins, although possible, appears to play a minor role, if any, in the mechanism of action of furocoumarin.


Action of citrinin on liposomes.

Action of citrinin on liposomes. Citrinin, a mycotoxin, was studied for its effect on artificial membranes (liposomes). Of the three (net positive, negative and neural) liposomal preparations tested, the membrane carrying a net positive charge was preferentially acted upon by citrinin and in this case even the lowest concentration was found to be sufficient for causing a high degree of damage. This is the first report of evidence that citrinin has a direct effect on membranes. It was shown to exhibit concentration dependency in its lytic activity on artificial membranes leading to leaching of trapped 45Ca2% ions.


Comparative studies on the dodecameric and hexameric forms of yeast aminopeptidase I. Yeast aminopeptidase I, when purified from autolysates of brewer's yeast, is obtained in two molecular froms a) the enzymatically active dodecameric complex (Mr = 640,000, s20,w = 22 S) and b) inactive hexamers (Mr = 320,000, s20,w = 12 S). Although the amino acid composition of the 12 S protein is very similar to that of the active enzyme,the hexamers behave differently in ionic exchange chromatography and during electrophoresis on polyacrylamide gels. Moreover, the antigenic properties of 12 S and 22 S aminopeptidase forms suggest a considerable degree of structural diversity. Several strains of Saccharomyces cerevisiae did not contain hexameric forms although their 22 S aminopeptidase was immunologically indistinguishable from brewer's yeast aminopeptidase. It is proposed that the hexameric protein is the result of "unproductive" aggregation of aminopeptidase subunits.


[Sequence complexity of transcribed unique DNA sequences in genome of mouse P815 mastocytoma cells (author's transl)]. The sequence complexity of nuclear RNA from mouse liver, mouse spleen and highly malignant P815 mastocytoma was measured by nRNA driven hybridization to unique DNA sequences of P815 cells. The unique DNA sequences represent 63% of the total nuclear DNA of P815 cells and their availibility in hybridization experiments was found to be 76%. Of these sequences 7.8% formed hybrids with nuclear RNA of this cell, about 11.5% with mouse spleen and about 14.5% with mouse liver nuclear RNA. Assuming an asymmetrical transcription, the complexities of these transcripts are 2.8 X 10(8) nucleotides for mouse P815 mastocytomas, 4.3 X 10(8) for mouse spleen and about 5.3 X 10(8) nucleotides for mouse liver. Cellular specifity of the transcribed information was analyzed in additivity experiments, in which unique DNA sequences, not complementary to the nuclear RNA of one cell were annealed to the nuclear RNAs of the two other tissues/cells. In these experiments most of the nuclear RNA sequences of P815 cells were found to be also present in the nucleus of mouse liver and spleen. Only a small portion of the unique DNA sequences of P815 mastocytoma (about 1.2% corresponding to 4.4 X 10(7) nucleotides) was found to be complementary only to P815 mastocytoma nuclear RNA.


Effect of mechanical traumatization on rate and constancy of oxygen uptake of isolated diaphragms. Diaphragms of mice were traumatized by division parallel or transversally to the muscle fibres. The extent of traumatization was varied by the degree of subdivision. Oxygen uptake was measured by the Warburg technique. Undivided diaphragms as control displayed constant oxygen uptake for the four hours of observation. With divided diaphragms oxygen uptake was unstable. Division parallel to the muscle fibres resulted in continuous decrease of oxygen uptake after a normal initial phase; the decline was significantly steeper was increasing extent of traumatization. Division transversally to the muscle fibres resulted in an initial increase of oxygen uptake followed in a second phase by a continuous decrease. The initial increase as well as the final decrease of oxygen uptake was more pronounced with higher extent of subdivision.


The influence of spermine, spermidine and various sera on T-lymphocyte and granulocyte colony growth in vitro. Using T-lymphocyte (T-LC) and granulocyte colony (GC) assays with truly proliferating cells, the dose-response relationships of spermine and spermidine, fetal calf (FCS), calf (CS), horse (HS) and human AB serum (ABS), and of the polyamines in the presence of selected does of the sera were analyzed. In contrast to earlier observations using [3H]thymidine uptake masurements it was found that the polyamines as well as the sera themselves inhibit T-LC and GC growth in the presence of autologous HS and ABS, respectively. The polyamines also inhibit in the presence of additional HS and ABS, yet most effectively with added FCS and CS. Thus the previously reported species-specificity of the serum-dependent polyamine inhibition has here been shown to be more quantitative than qualitative. These studies stress the significance of assays utilizing truly dividing cells and broad dose-response relationship in order to assess specific biological effects in vitro.


[Temperature-dependence of biological process (author's transl)]. Temperature dependence of biological processes is described by the modified Arrhenius equation, in which the constant is replaced by a temperature-variable coefficient. The theoretical foundation for this replacement is given and experimentally verified.


Free-running human circadian rhythms in Svalbard. The body temperature, activity-rest time, electrolytes of urine samples and mood was measured in two persons a 19 day period under continuous light conditions in the arctic (vicinity of Ny Alesund, Svalbard-Spitsbergen). For temperature recording a new thermoprobe and a portable printer was used. Possible week Zeitgeber of the 24 hour day did not synchronize the circadian system, since circadian rhythms of about 26 hours were found. These results open up the possibility to study effects of drugs on the circadian system of humans under Svalbard conditions.


[A fluorometic test for microsomal monooxygenase activity in the rat liver with scoparone as substrate (author's transl)]. A sensitive fluorometric test for the determination of monooxygenase activity in liver microsomes from rats is described. The assay is based on the O-demethylation of 6,7-dimethoxycoumarin (scoparone) to 7-hydroxy-6-methoxycoumarin and 6-hydroxy-7-methoxycoumarin. Pretreatment of rats with phenobarbital or polycyclic hydrocarbons (benzo[a]pyrene, 3-methylcholanthrene) causes a significant increase in the amount of microsomal dealkylation activity.


Down's syndrome in Nigeria: dermatoglyphic analysis of 50 cases. Dermatoglyphic analysis was carried out on 50 cases of Down's Syndrome and 100 normals. It involved the digital patterns, axial triradius and palmer crease on the hands. 94.6% of the digital patterns in Down's Syndrome were the Ulnar loop type against 62.5% in the normals. No arch was reported in Down's Syndrome. There were more whorl patterns in the normals (31.1%) than in the Down's Syndrome group (4%). The mode of the distribution of the digital indices in the Down's Syndrome was at +3.58. More than 84% of the 50 cases of Down's Syndrome have digital index of +3.58 compared to only 12% in the normals.


Some characteristics of sulphate uptake into synaptosomes. Incorporation of Na235SO4 by ovine brain Ficoll-prepared synaptosomes were studied as a function of time, temperature and substrate concentration. The rate of uptake obeyed Michaelis-Menten kinetics and apparent Km value of 4.4 mM Na2SO4 was determined. In the presence of p-hydroxymercuribenzoate a reduction in sulphate uptake was noted which suggests that thiol groups may possibly be implicated in the uptake mechanism.