[Use of danger analysis in the projection stage].
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Accidents, Occupational↗
Biomedical subjects
R Lang
Publications and source records attributed to R Lang.
Modulation of immune response and tumor development in tumor-bearing mice treated by the thymic factor thymostimulin.
Thymostimulin (TS), a partially purified thymic factor, has a significant impact on tumor development in C57B1/6 mice inoculated with Lewis lung carcinoma (3LL) cells, as judged by its effect on time of tumor appearance after tumor cell transplantation. In a previous study, we determined the conditions under which survival rate of the tumor-bearing mice can be significantly increased by TS treatment. In the study communicated here we analyzed host defense mechanisms that are modified by TS treatment in the tumor-bearing mice. In general, immune parameters that were increased or stimulated by the presence of the tumor were further increased in the TS-treated animals (number of lymphoid spleen cells, their response in mixed lymphocyte tumor cultures, their natural killer cell activity, and their ability to produce colony-stimulating factor), or reached earlier maximum levels (spontaneous [3H]thymidine incorporation, a reflection of in vivo spleen cell activation). Responses which reflect tumor-induced immunosuppression (proliferative response induced by phytohemagglutinin or concanavalin A stimulation) were restored to normal level by TS. Specific tumor-related reactions (specific cell-mediated cytotoxicity) were preserved in the TS-treated animals. The wide spectrum of TS effects had, nevertheless, certain elements of selectivity; e.g. colony-stimulating factor, but no interferon production is enhanced by TS in the tumor-bearing mice in diametric contrast to TS effect in Mengo virus-infected mice. The spectrum of TS effects was also dependent on the type of tumor cell used. The results indicate that the significant effect of TS on 3LL tumor development in mice is associated with a strong, multifaceted effect of TS on the immune system.
Animals↗
Fine specificity and T-cell receptor beta-chain gene rearrangements of five H-2Db-specific cytotoxic T-cell clones.
A panel of cytotoxic T lymphocyte clones that recognize H-2b target cells has been established. Six different clones were distinguished according to the following criteria. First, the fine specificity of the clones was determined by testing proliferation and cytotoxicity on target cells of recombinant mice. Clone 221 recognized H-2Kb, and five other clones recognized H-2Db. Clone 433 distinguished itself from the other five Db-specific clones by cross-reacting with an antigen on H-2k cells. Second, the presence of an idiotypic determinant as defined by the 3F9 clone-specific monoclonal antibodies was investigated in cytotoxicity inhibition experiments. One of the Db-specific clones, 653, was inhibited by these antibodies and was therefore clearly different from the other Db-specific clones. The third criterion involved the rearrangement pattern of the DNA coding for the beta chain of the T-cell receptor. Southern blot analysis showed that each clone had a unique pattern. Interestingly, clone 653, which expresses the same idiotypic determinant as clone 3F9, had deleted the C beta 1 gene cluster, whereas this gene is functionally expressed in clone 3F9.
Animals↗
Atenolol vs. amiloride-hydrochlorothiazide in the treatment of mild to moderate hypertension: a double-blind, crossover, placebo-controlled study.
The antihypertensive effect of atenolol 100 mg was compared to that of amiloride HCl 5 mg + hydrochlorothiazide 50 mg (AHCZ) in a double-blind, crossover, placebo-controlled study of 128 patients. Both drugs were given once daily. Atenolol produced a significant decline in lying, standing, and postexercise blood pressure and pulse rate values. The corresponding values on AHCZ were not significantly different from placebo. Both the beta-blocking agent and the thiazide diuretic with amiloride were relatively well tolerated. More than half of all adverse effects were nonspecific and also observed in patients on placebo. In the population studied, atenolol proved to be a superior antihypertensive agent to AHCZ.
Adult↗
Central catecholamine-neuropeptide Y interactions at the pre- and postsynaptic level in cardiovascular centers.
Central catecholamine (CA)-neuropeptide Y (NPY) interactions and their regulation by glucocorticoids have been analyzed in vivo and in vitro, especially in the dorsal cardiovascular center of the medulla oblongata, including the nucleus tractus solitarius (nTS), using immunocytochemical, receptor autoradiographical, biochemical, and physiological techniques. Intraventricular (i.v.t.) injections of NPY in a low (7.5 pmol) or a high (1.25 nmol) dose increased adrenaline levels 4 h later in the caudal part of the dorsomedial medulla. Furthermore, NPY immunoreactivity (IR) tended to decrease in the rostral part of the dorsomedial medulla 5 min after injection of clonidine (1 microgram) in the alpha-chloralose anaesthetized rat. Thus, presynaptic interaction between NPY and adrenaline (A) mechanisms may exist in the dorsal cardiovascular center taking place at the network local circuit level or the membrane level of the NPY/A costoring synapses of the dorsomedial medulla. In vitro NPY (10 nM) reduced the affinity of the alpha 2-adrenergic agonist binding sites in the nTS, and clonidine (10 nM) reduced the 125I-NPY binding in the dorsomedial medulla. These results indicate the existence of postsynaptic receptor-receptor interactions between alpha 2-adrenergic and NPY receptors in the dorsal cardiovascular center. This interaction may in part take place at the level of the Ni protein, since NPY (300 nM) inhibited cyclic AMP (cAMP) accumulation in slices of the dorsomedial medulla. However, the interactions also probably take place at the proteins carrying the recognition sites, since NPY and adrenaline together given i.v.t. significantly antagonized the hypotensive effects of one another. Thus, the reduced affinity of the alpha 2-adrenergic receptor induced by NPY may reflect a reduced efficiency of this receptor and not an increased coupling of Ni protein to the adenylate cyclase. Thus, the postsynaptic interaction between the two receptors represents inter alia a sensitivity regulation of the two receptors. Evidence is also presented for the existence of a glucocorticoid regulation of NPY IR neurons, especially of those innervating the locus coeruleus, since after 2 weeks adrenalectomy reduced NPY IR in this area. Furthermore, glucocorticoid receptor IR was demonstrated in the nuclei of NPY nerve cell bodies of the nTS. Thus, glucocorticoids exert direct actions on cardiovascular NPY/CA costoring neurons, actions that may contribute to their hypertensive effects in humans.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
[Renal and adrenal function following acute administration of urapidil in hypertensive patients with normal and impaired renal function].
The effects of i.v. injection of urapidil (Ebrantil) (25 mg) on arterial blood pressure, renal function and renin-aldosterone system were studied in a group of patients with hypertension and normal renal function, in patients with hypertension and chronic renal failure and in normotensive controls. The pharmacokinetics of urapidil were evaluated simultaneously by measuring blood levels of the compound and its main metabolite. In the controls and in patients with hypertension, systolic and diastolic blood pressure were lowered few minutes after injection. Minimal blood pressure values were reached after 15-20 min. Hypotensive action was more pronounced in hypertensive patients as compared to controls. In contrast, increment in heart rate was greater in the controls. Despite the fall in blood pressure, renal plasma flow and glomerular filtration rate remained unchanged. Following the injection of urapidil, plasma renin activity increased with no change in plasma aldosterone levels. Plasma half-life of urapidil averaged 1.96 +/- 0.17 h in controls, 3.31 +/- 0.75 h in patients with hypertension and normal renal function and 2.52 +/- 0.46 h in patients with hypertension and chronic renal failure. Urapidil effectively lowers arterial blood pressure in patients with normal and impaired renal function with no deterioration in renal function.
Adrenal Glands↗
Characterization of an Lyt-2+ alloreactive cytotoxic T cell clone specific for H-2Db that cross-reacts with I-Ek.
An alloreactive cytotoxic T cell clone (433) possessing the L3T4-, Lyt-2+ phenotype is described that shows a double specificity. It has been derived from unprimed BALB/c (H-2d) spleen cells by repetitive in vitro restimulation with C57BL/6(H-2b) cells. The specificity of clone 433 was determined in cytotoxicity and proliferation experiments. One specificity was for the class I antigen H-2Db and the second was for the class II antigen I-Ek. Inhibition of cytotoxicity with monoclonal antibodies confirmed these results. Cold target competition experiments demonstrated that the two specificities were mediated by the same cell population. Anti-Lyt-2 antibodies inhibited only the H-2Db- but not the I-Ek-specific lysis, suggesting a higher affinity of the antigen receptor for I-Ek than for Db. To our knowledge, this is the first description of a T cell clone that is specific for a class I antigen and cross-reacts heteroclitically with a class II antigen.
Animals↗
Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability.
A convenient way to estimate the number of viable cells growing in microtitre tray wells is to use a colorimetric assay and an automatic microplate scanning spectrophotometer. One such assay, developed by Mosmann, depends on the reduction by living cells of tetrazolium salt, MTT, to form a blue formazan product. However the original technique has several technical limitations, namely a less than optimal sensitivity, a variable background due to protein precipitation on adding an organic solvent to dissolve the blue formazan product, and a low solubility of the product. These problems have been overcome by the following modifications: avoidance of serum in the incubation medium, thus overcoming precipitation problems in the organic solvent; avoidance of phenol red in the incubation medium, thus avoiding the use of acid in the final solvent which altered the spectral properties of the formazan; elimination of the medium containing MTT after the reaction and subsequent use of pure propanol or ethanol to rapidly solubilize the formazan; use of a higher concentration of MTT; use of half-area microtitre trays to increase the spectrophotometer readings from a given amount of formazan; use of a more judicious reference wavelength in a dual wavelength spectrophotometer. With these modifications the reliability and sensitivity of the test have been increased to the point where it can in many cases replace the [3H]thymidine uptake assay to measure cell proliferation or survival in growth factor or cytotoxicity assays. Examples of its use in IL-2 assays are given.
Animals↗
Immunohistochemical evidence for extrinsic and intrinsic opioid systems in the guinea pig superior cervical ganglion.
Immunohistochemical localization of the opioid peptides alpha-neo-endorphin (alpha-neo-END), dynorphin A (DYN) and leu-enkephalin (leu-ENK) in the guinea pig superior cervical ganglion (SCG) was studied following central denervation, peripheral axotomy, and after application of the depleting drug reserpine and of the neurotoxin 6-hydroxydopamine. The paraganglionic cells of the SCG are shown to form an intrinsic opioid--(alpha-neo-END, DYN, leu-ENK)--immunoreactive system being not visibly responsive to the experimental procedures. Leu-ENK-immunoreactive fibres ascend in the preganglionic trunk and supply fibre baskets to defined clusters of postganglionic neurones. Principal ganglion cells of the SCG containing alpha-neo-END- and DYN-immunoreactivity project to extraganglionic targets via the postganglionic nerves. These findings are indicative of a sympathetic alpha-neo-END-ergic and DYN-ergic innervation of effector organs. They also point to a modulatory function of opioids on neuronal activity in a paravertebral ganglion.
Animals↗
Fibrogenesis imperfecta ossium with early onset: observations after 20 years of illness.
Fibrogenesis imperfecta ossium is a rare, acquired disorder of bone mineralization characterized by a morphologic abnormality of bone collagen that presents with bone pain and tenderness and usually results in the patient becoming bedridden. Onset of symptoms in the six previously reported cases of this disorder occurred in patients over 50 years of age. We report a case of fibrogenesis imperfecta ossium with symptoms starting at age 39 where the diagnosis was not made even after three bone biopsies because of the failure to recognize the characteristic morphologic abnormality of collagen. Elevated serum alkaline phosphatase, increased urinary hydroxyproline, and numerous osteoclasts on a bone biopsy are compatible with increased bone turnover. There was no apparent abnormality of vitamin D metabolism contributing to this disorder. Treatment with sodium fluoride, synthetic salmon calcitonin, and 24,25-dihydroxyvitamin D did not result in any apparent benefit.
24,25-Dihydroxyvitamin D 3↗
Altered functions of peripheral blood monocytes in homosexual males and intravenous drug users with persistent generalized lymphadenopathy.
Persistent generalized lymphadenopathy (PGL) is observed predominantly in subjects at risk of developing AIDS. Twenty-seven individuals belonging to such groups: twelve homosexual males and fifteen intravenous drug users, were investigated for immunological abnormalities with particular attention to monocyte functions. They were compared with five AIDS patients. Twenty out of twenty-two individuals had anti-LAV/HTLV-III antibodies and most had abnormalities characteristic of AIDS: polyclonal hypergammaglobulinemia, decreased cell-mediated immunity, inverted T-cell helper/suppressor ratio and histological alterations of lymph nodes. As for peripheral blood monocyte functions, phagocytic capacity and production of O2- were normal and bactericidal capacity was decreased. Monocytes cultured in the presence of concanavalin A produced less PGE2 and more IL-1/MCF than normal monocytes. Similar abnormalities were found using monocytes from AIDS patients. These data suggest that monocytes from patients with PGL have functional alterations that may be either intrinsic or secondary to lymphocyte dysfunction(s); these alterations do not account for the decreased capacity of lymphocytes to respond to mitogens but may explain the uncontrolled activation of B cells.
Acquired Immunodeficiency Syndrome↗
Pharmaceutical error resulting in fatal diabetic ketoacidosis.
A 41-year-old male with a 25-year history of diabetes mellitus requiring 25 to 30 units of neutral protamine hagedorn (NPH) insulin daily was found dead at home. Recent history revealed that he was well until the last four days of life when he had the onset of nausea, vomiting, and anorexia coinciding with procurement of a new bottle of insulin from his pharmacist. Pertinent autopsy findings included coronary and aortic atherosclerosis, a peptic ulcer, and diabetic glomerulopathy. Chemical analysis of the vitreous humor, including glucose (813 mg/dL) and acetone (40 mg/dL), revealed that he died of diabetic ketoacidosis. Further investigation revealed that the pharmacist had accidentally substituted regular insulin, with a duration of action of up to 6 h as opposed to 24 to 28 h, for NPH. Cultures of blood and of the regular insulin yielded no growth. Analysis of this case emphasizes the importance of obtaining a careful medical and medication history and the usefulness of vitreous electrolytes when investigating a sudden death in a diabetic.
Adult↗
[Estimation of the future demand for orthodontic services and of the appropriate number of orthodontists for the 1984-1994 period in Switzerland].
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Forecasting↗
Braces are for the birds.
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Animal Diseases↗
History of medicine. The Department of Dermatology, University of Cape Town, 1922-1962.
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Dermatology↗
Treatment of diabetic perforating ulcers (mal perforant) with local dimethylsulfoxide.
Perforating foot ulcers constitute a major problem in diabetics with peripheral neuropathy for which no specific therapy is available. Twenty patients with chronic, resistant mal perforant were treated by local application of dimethylsulfoxide (DMSO) solution. Complete healing of the ulcers was achieved in 14 patients following 4-15 weeks of daily treatment. Partial resolution was observed in another four patients, and in the remaining two there was no effect. A control group, equal in number, was treated conventionally. Complete healing of the ulcers took place in only two patients. The therapeutic effect of DMSO most probably results from an increase in tissue oxygen saturation via a combined mechanism of local vasodilatation, decreased thrombocyte aggregation, and increased oxygen diffusion. Local DMSO is effective, simple, devoid of systemic side effects, and inexpensive. It should be employed for diabetic foot ulcers prior to the consideration of surgical measures.
Aged↗
Favorable response to aggressive chemotherapy in a patient with primary plasma cell leukemia.
Primary plasma cell leukemia was diagnosed in a previously healthy 58-year-old man. The unusual presentation with concomitant multiple osteolytic lesions and hepatosplenomegaly, the favorable response to aggressive chemotherapy with COAP, and the relatively long survival of 22 months prompted this report. This and several other cases recently reported should encourage an aggressive therapeutic approach to this disease.
Antineoplastic Combined Chemotherapy Protocols↗
Analgesic effect of ceruletide compared with pentazocine in biliary and renal colic: a prospective, controlled, double-blind study.
The analgesic effect of ceruletide in biliary and renal colic was evaluated by a randomized, double-blind study in 82 patients. Ceruletide was compared with pentazocine, a well-established analgetic agent. Rapid and effective analgesia was obtained by intramuscular injection of ceruletide 0.5 micrograms/kg in 56 patients with biliary colic. The analgesic effect of ceruletide compared well with pentazocine 0.5 mg/kg im, and was associated with remarkably fewer side effects. In 26 patients with renal colic, ceruletide was significantly inferior to pentazocine. These data support the recommendation of ceruletide as a first-choice analgetic agent for biliary colic.
Adult↗