[Specific immunotherapy in allergic bronchial asthma].
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Asthma↗
Biomedical subjects
Y Katz
Publications and source records attributed to Y Katz.
Cardiac arrest associated with flumazenil.
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Flumazenil↗
Testosterone prevents castration-induced reduction in peripheral benzodiazepine receptors in Cowper's gland and adrenal.
The effect of surgical castration of adult male Sprague-Dawley rats on peripheral and central benzodiazepine (BZ) receptors was studied. Following removal of the testes, a significant decrease in the density of peripheral BZ receptors (PBR) was observed in Cowper's glands (71%; P less than 0.005) and the adrenal (31%; P less than 0.01), but not in the heart. Administration of testosterone acetate (TA) prevented castration-induced PBR depletion. Orchiectomy per se, as well as TA administration to castrated rats, had no effect on central or peripheral BZ receptors in whole brain without the cerebellum. These results indicate the regulatory role of testosterone in the regulation of PBR in Cowper's glands and adrenal.
Adrenal Glands↗
Intellectual capacity of subjects exposed to methimazole or propylthiouracil in utero.
Antithyroid drugs, considered the treatment of choice for hyperthyroidism during pregnancy, may have an adverse effect on intellectual development of the offspring. We examined the intellectual capacity of 31 subjects aged 4-23 years, born to women with Graves disease who received antithyroid drugs throughout pregnancy. Methimazole 40-140 mg/week (n = 15) or propylthiouracil 250-1400 mg/week (n = 16) was given. I.Q. was assessed using the Wechsler test appropriate for age. Twenty-five unexposed siblings served as controls. The exposed and unexposed groups did not differ with respect to the total I.Q. Both groups scored equally in verbal and performance skills and in each of six main subcategories of the tests. There was no difference between exposure to methimazole and propylthiouracil or between the higher (greater than 40 mg/week and greater than 600 mg/week, respectively) and lower dosages. All children were euthyroid at birth and none had goitre. We conclude that exposure to methimazole or propylthiouracil during pregnancy in doses sufficient to control maternal hyperthyroidism does not pose any threat to intellectual capacity of the offspring.
Adolescent↗
Intraoperative assessment of blood flow to strangulated stomach by pulse oximetry.
A pulse oximeter was used to detect safe margins for resection of a strangulated stomach. The sensor probe was placed intraoperatively on various portions of the stomach, which herniated through a left lateral diaphragmatic defect. Failure to detect blood flow by this device in equivocally compromised tissue helped in the assessment of safe viable margins for resection.
Female↗
Inherited C3 deficiency and meningococcal disease in a teenager.
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Adult↗
Biochemical, physiological, and pathological aspects of the peripheral benzodiazepine receptor.
The PBR is a mitochondrial protein composed of at least two subunits, an approximately 30-kDa subunit that contains the site for BZs and an approximately 18-kDa subunit that binds isoquinoline carboxamide derivatives. Porphyrins and diazepam binding inhibitor are putative endogenous ligands for these receptors, which are under neural and hormonal control. Alterations in the density of PBR seem to be a sensitive indicator of stress: up-regulation after acute stress and down-regulation induced by repeated stress. PBR-specific ligands are involved in the control of cell proliferation and differentiation, and their binding is increased in some cancer tumors. Numerous studies in various endocrine organs have revealed that PBR are located in specific regions or tissues in the organs. Furthermore, PBR densities in various organs subject to hormonal control are regulated by organotropic hormones. At least in some cases, BZ ligands do not exert a specific effect in an organ, but rather modulate the well-documented effects of that particular hormone. To the best of our knowledge, BZ ligand action in peripheral tissues is dependent on recognition of PBR, which may suggest a receptor-mediated action.
Animals↗
Disulfiram and diethyldithiocarbamate are competitive inhibitors at the peripheral benzodiazepine receptor.
In the present study in vitro interactions of disulfiram (an agent used to induce ethanol intolerance in alcoholics), diethyldithiocarbamate (DDC), and metronidazole with central benzodiazepine receptors (CBR) and peripheral benzodiazepine (BZ) receptors (PBR) were investigated in rat tissues. Disulfiram displaced specific binding of [3H]PK 11195 from PBR in the cerebral cortex with an IC50 value of 5 x 10(-7) M. The binding of [3H]PK 11195 and [3H]Ro 5-4864 to PBR in the kidney was displaced by disulfiram with IC50 values of 7 x 10(-7) and 2 x 10(-7) M, respectively. DDC displaced [3H]PK 11195 binding to kidney membranes with an IC50 value of 5 x 10(-5) M. Binding of [3H] flunitrazepam to CBR in the cerebral cortex was not affected by either disulfiram or DDC. Metronidazole (up to 10(-4) M), a disulfiram congener, did not affect [3H]flunitrazepam (FNZ) and [3H] PK 11195 binding to CBR and PBR, respectively. Scatchard analysis of [3H]PK 11195 binding to kidney membranes, performed in the absence or presence of 7 x 10(-7) M disulfiram, decreased ligand affinity without influencing the maximal number of binding sites, suggesting a competitive inhibition. Beta-Mercaptoethanol (2 x 10(-2) M), which blocks the inhibitory activity of disulfiram and DDC at the acetaldehyde dehydrogenase, did not affect the inhibitory potency of disulfiram at the kidney PBR. Removal of disulfiram from kidney by repeated washing with Tris-HCl buffer resulted in the restoration of binding properties to control values, suggesting reversibility of disulfiram binding to PBR.
Animals↗
Testosterone and cyproterone acetate modulate peripheral but not central benzodiazepine receptors in rats.
Sixteen days of testosterone acetate (TA) treatment in male rats induced an increase in the densities of peripheral benzodiazepine receptors (PBR) in the adrenal and Cowper's glands and a decrease in PBR density in the testis. TA did not alter PBR density in the heart, cerebral cortex, or pituitary, or central benzodiazepine receptor (CBR) density in the cerebral cortex or hypothalamus. The antiandrogenic agent cyproterone acetate induced a decrease in PBR density in the testis, adrenal, and pituitary, but did not affect PBR density in Cowper's glands, heart, or cerebral cortex, or CBR density in the cerebral cortex or hypothalamus. In all of the above organs, affinity values did not change following the treatment with both agents. The receptoral changes may be relevant to the physiological and neurobehavioral effects of the chronic exogenous androgenic and antiandrogenic treatment.
Androgen Antagonists↗
Interactions of chloroquine with benzodiazepine, gamma-aminobutyric acid and opiate receptors.
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Animals↗
Synthesis of C1 inhibitor in fibroblasts from patients with type I and type II hereditary angioneurotic edema.
Patients with hereditary angioneurotic edema (HANE) have serum levels of functionally active inhibitor of the first component of complement (C1 INH) between 5 and 30% of normal, instead of the 50% expected from the single normal allele. Increases in rates of catabolism have been documented in patients with HANE and certainly account for some of decrease in C1 INH level. A possible role for a decrease in synthesis of C1 INH in producing serum levels of C1 INH below the expected 50% of normal has not been well studied. We studied the synthesis of C1 INH in skin fibroblast lines, which produce easily detectable amounts of C1 INH. In type I HANE cells, C1 INH synthesis was 19.6 +/- 4.0% (mean +/- SD) of normal, much less than the 50% predicted. In type II HANE cells, the total amount of C1 INH synthesis (functional and dysfunctional) was 98.9 +/- 17% of normal; the functional protein comprised 43% of the total. Thus, type II HANE cells synthesized functional C1 INH at a much greater rate than for the type I cells. In both type I and II HANE cells, amounts of steady-state C1 INH mRNA levels paralleled rates of C1 INH synthesis, indicating that control of C1 INH synthesis occurred at pretranslational levels. Both type I and type II fibroblasts synthesized normal amounts of C1r and C1s. These data suggest that the lower than expected amounts of functionally active C1 INH in type I HANE may be due, in part, to a decrease in rate of synthesis of the protein, and that the expressions of the normal C1 INH allele in HANE is influenced by the type of abnormal allele present.
Adult↗
Multiple therapy approach to juvenile periodontitis: a case report.
Various therapeutic techniques for the treatment of juvenile periodontitis are reported in the literature, with occasional contradictory results. One of the reasons for the contradictory results may be differences in patient selection and/or response to treatment. The following report describes the results of various treatment modalities, in different sites in the same individual, on localized juvenile periodontitis.
Adult↗
Identification and distribution of peripheral benzodiazepine binding sites in male rat genital tract.
In the present study we identified and characterized the distribution of high-affinity peripheral benzodiazepine binding sites (PBzS) in male rat vas deferens (whole, and prostatic and epididymal portions), prostate, seminal vesicles, and Cowper's glands. [3H]PK 11195, an isoquinoline carboxamide derivative, was used as a radioligand specific for PBzS. Scatchard analysis of saturation curves of [3H]PK 11195 binding in the whole vas deferens, the prostatic and epididymal portions of the vas deferens, the prostate, the seminal vesicles, and Cowper's glands yielded mean maximal numbers of binding sites of 1211 +/- 158, 1012 +/- 311, 1451 +/- 156, 1805 +/- 86, 865 +/- 51, and 2251 +/- 135 fmol/mg protein, respectively. The equilibrium dissociation constant values ranged between 1 and 3 mM in all the above tissues. The ability of various drugs to displace the specific binding of [3H]PK 11195 from PBzS in Cowper's gland membranes was also tested. The inhibition constants for Ro 5-4864, diazepam, and PK 11195 were 28, 330, and 4 nM, respectively, whereas clonazepam, Ro 15-1788, and testosterone were inefficient in displacing [3H]PK 11195. The presence of high densities of PBzS in the male genital tract suggests a functional role in these hormone-dependent organs.
Animals↗
Enhanced synthesis of factor B induced by tumor necrosis factor in human skin fibroblasts is decreased by IL-4.
IL-4 is a T cell-derived lymphokine that has multiple biologic functions, affecting B cells, T cells, mast cells, monocytes, macrophages, and hematopoietic progenitor cells. We report that IL-4 also affects human skin fibroblasts. These effects were primarily in modulating the effects of other mediators of inflammation on these cells, with IL-4 producing little or no effects by itself. Synthesis of C proteins in human skin fibroblasts is modulated by TNF and other mediators of inflammation. TNF increased synthesis of factor B by 18.6-fold; IL-4 reduced the TNF effect on factor B synthesis by 83%. This effect started with concentrations of IL-4 as low as 0.1 ng/ml. The effect of IL-4 on the TNF-induced increase in synthesis of factor B occurred after 2 h incubation, the time when the effects of TNF alone were first observed. IL-4 also abrogated the effects of IL-1 and LPS on factor B synthesis, but did not affect the increase in synthesis of factor B induced by IFN-gamma. In contrast to the pattern for effect of IL-4 on factor B synthesis, the TNF-induced rate of synthesis of C3 was augmented by IL-4. The specificity of the IL-4 effect was also apparent when comparing the effect of IL-4 on the TNF-induced synthesis of factor B to the effects on total protein synthesis (increased 1.5-fold) and the TNF-induced increases in synthesis in C1r, C1s, C1 inhibitor, C2, and factor H (no changes). The IL-4-induced decrease in synthesis of factor B was mediated at a pretranslational level and was dependent on synthesis of a new protein. This interaction between IL-4 and mediators of inflammation can potentially modulate the inflammatory response in the setting of activation of Th cells.
Cells, Cultured↗
Antiinflammatory effects of polypeptide growth factors. Platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor inhibit the cytokine-induced expression of the alternative complement pathway activator factor B in human fibroblasts.
The synthesis of complement components in human fibroblasts is modulated by mediators of inflammation such as cytokines. In particular, interleukin-1 (IL-1) and tumor necrosis factor (TNF) induce time- and dose-dependent increases in the synthesis of complement proteins factor B (FB), C3, and factor H (FH). Polypeptide growth factors are also soluble mediators released during inflammation and able to modulate many fibroblast functions. We have studied the effects of polypeptide growth factors platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF) on the synthesis of complement proteins in cultured human fibroblasts. PDGF, EGF, and FGF alone did not affect the level of synthesis of any of the complement proteins analyzed, but simultaneous incubation of PDGF, EGF, or FGF with IL-1 and TNF resulted in a dose-dependent inhibition of the cytokine-enhanced expression of FB. Inhibition of FB synthesis was observed between 4 and 8 h of exposure to PDGF and persisted for 4 h after the removal of the growth factor. Analysis of steady-state levels of specific FB mRNA suggested that PDGF-induced inhibition of FB synthesis is mediated at a pretranslational level and that it requires new protein synthesis. The effect of the growth factors was limited to FB, with marginal or no inhibition on the cytokine-enhanced synthesis of C3 and FH, excluding the possibility that the inhibitory effects of PDGF, EGF, and FGF on FB synthesis were due to a negative modulation of the growth factors on cytokine cell membrane receptors. Specific inhibition of cytokine-induced increases in FB synthesis by the growth factors may represent down regulation of the acute inflammatory process, further permitting progression to processes of tissue repair and remodeling. Study of the interactions between cytokines and growth factors in the regulation of synthesis of complement proteins may also provide a system for investigating mechanisms of signal transduction of both polypeptide growth factors and cytokines.
Anti-Inflammatory Agents, Non-Steroidal↗
Functional upper airway obstruction in adolescents.
Functional upper airway obstruction is an uncommon manifestation of a conversive reaction characterized by recurrent stridor attacks caused by adduction of the vocal cords during inspiration. The oxygen saturation never drops to pathologic levels. The stridor is not accompanied by an appropriate degree of anxiety and is not associated with other symptoms. Patients benefit from verbal reassurance and speech therapy, but stridor attacks tend to recur and psychiatric consultation seems necessary in most cases. We present the case histories of three adolescent patients with nonorganic upper airway obstruction and describe the features that may facilitate the diagnosis of this condition. Early diagnosis and intervention may prevent unnecessary and potentially harmful investigations and therapy.
Adolescent↗
Recurrent seizures in children with Shigella-associated convulsions.
Fifty-five children with Shigella-associated convulsions were followed prospectively to investigate their risk of subsequent febrile or nonfebrile seizures. The duration of the follow-up period was between 6.9 and 14.1 years (9.7 +/- 3.1 years). No case of nonfebrile seizures and only 2 cases (3%) of subsequent febrile seizures were observed during this period. We conclude that although febrile and Shigella-associated convulsions share many clinical features, the natural history of these two conditions seems to be distinctly different. Shigella-related convulsions are not associated with an increased incidence of subsequent febrile or nonfebrile convulsions.
Child↗
Increased density of peripheral benzodiazepine-binding sites in ovarian carcinomas as compared with benign ovarian tumours and normal ovaries.
1. Benzodiazepines are involved in the control of proliferation and differentiation of normal and malignant cells in vitro. This regulatory ability is probably mediated via peripheral benzodiazepine-binding sites. 2. In the present study we compared the binding characteristics of peripheral benzodiazepine-binding sites in human epithelial ovarian carcinoma with those in benign ovarian tumours and normal ovaries. 3. The affinity and density of peripheral benzodiazepine-binding sites in homogenate preparations of ovarian carcinoma as compared with benign ovarian tumours and with normal tissues (used as controls) were determined using a ligand specific for peripheral benzodiazepine-binding sites, [3H]PK 11195, an isoquinoline carboxamide derivative. 4. We observed a robust (three- to five-fold) increase in the neoplasm compared with benign ovarian tumours and normal tissues, without a concomitant change in affinity values. 5. This finding may reflect a change in the metabolic rates of ovarian cancer which is expressed as the alteration in the density of peripheral benzodiazepine-binding sites.
Adenocarcinoma, Papillary↗