Familial amyloidotic polyneuropathy in an Indian family.
An Indian female with familial amyloidotic polyneuropathy is reported. The literature with regard to recent advances in the field is reviewed.
Biomedical subjects
Publications and source records attributed to S Roy.
An Indian female with familial amyloidotic polyneuropathy is reported. The literature with regard to recent advances in the field is reviewed.
A randomised study of the efficacy, duration of action and side-effects of two analgesic regimens following lower abdominal surgery is described. Patients received extradural pentazocine 30 mg or extradural buprenorphine 0.3 mg to provide postoperative analgesia. Interval for the next analgesia was significantly greater after extradural buprenorphine (18.96 hours) than after extradural pentazocine (8.39 hours) (p less than 0.001). No serious side-effects were reported.
OBJECTIVE: To determine the effect of pentoxifylline on early reproductive performance in an animal model for endometriosis. DESIGN: Preclinical blinded study in a rodent model. SETTING: Animal research laboratory. PARTICIPANTS: Sexually mature female golden hamsters. INTERVENTIONS: At laparotomy, groups of hamsters were subjected to: (1) excision of the right uterine horn and (2) excision of the right uterine horn with explantation of four 2-cm2 uterine fragments onto the left uterine mesentery. Six weeks later, surgically treated hamsters and nonsurgically treated controls were subjected to ovulation induction with pregnant mare serum gonadotropin and human chorionic gonadotropin; subsequently, hamsters were divided into groups for periovulatory treatment with either pentoxifylline (2.5 mg/kg) or vehicle given subcutaneously every 8 hours. All hamsters were mated with proven males and killed after 48 hours. MAIN OUTCOME MEASURES: Numbers of unfertilized oocytes and embryos recovered from the left uterine horn at 48 hours after mating. RESULTS: Fertilization rates in surgical and nonsurgical control groups exceeded 90%. Fertilization was significantly impaired in saline-treated animals bearing uterine explants (mean of 2.3% +/- 1.9%). Administration of pentoxifylline dramatically reversed this effect (99.0% +/- 0.7% mean fertilization rate). CONCLUSION: These data suggest that periovulatory treatment with pentoxifylline abrogated the adverse influence of endometrial explants on fertilization in the rodent model. Periovulatory administration of nonteratogenic immunomodulatory agents may provide an alternative to conventional treatment for endometriosis.
Although present consensus holds that endometriosis-associated subfertility is the result of an adverse effect of hyperactivated macrophages on early reproductive events, most treatments for endometriosis are directed at the suppression of endometriotic implants. We hypothesized that periovulatory immunomodulation of macrophage activation and inflammatory mediator production might be a more effective approach to this problem. In this experiment, heterologous transfer of activated peritoneal inflammatory cells within a syngeneic strain of mice was used as an in vivo model for the peritoneal inflammatory environment of the endometriosis patient. Intraperitoneal transfer of hyperactivated macrophages, but not basal state macrophages, significantly inhibited fertilization. This activity was reversed by periovulatory pentoxifylline treatment. Immunomodulation of peritoneal inflammatory cell hyperactivation with pentoxifylline may represent a new modality for the treatment of endometriosis-associated subfertility.
Recombinant Protein A was immobilized on a cellulose and acrylic composite matrix through Schiff base formation. Various factors that could affect the binding of immunoglobulin by the Protein A molecules immobilized on the solid matrix were studied to achieve optimum affinity purification. The spacer arm length and ligand concentration of Protein A were verified as factors crucial to optimized IgG purification. Liquid-phase environmental conditions such as pH and salt concentration also play important roles in adsorption capacity by affecting the molecular interaction between IgG and the immobilized Protein A. The rate of interaction between Protein A and IgG is rather fast, with minimal differences observed at 10-fold increases in the cartridge loading rate. This paper describes a cellulose/acrylic composite matrix for immobilizing Protein A, at an optimized ligand concentration, installed on a spacer arm of adequate length, to purify immunoglobulins from animal plasma. The fast-flow property of the cartridge made from such a matrix and its simplicity in operation provide effective means for purifying immunoglobulins on a relatively large scale.
A group of 15 postmenopausal women who had not recently received estrogen replacement were enrolled in a study during which they received 0.625 mg of conjugated equine estrogen and 2.5 mg of medroxyprogesterone acetate daily from Monday through Friday of each week for six months. No treatment was given on the weekend. Endometrial biopsy specimens at the end of therapy revealed minimal growth of glands and stroma and a low mean mitosis count. Of the 12 women who completed the trial, 5 were completely amenorrheic, and only 4 of the 15 bled beyond the second month of treatment. Of those four, two spotted for only a few days. In the 12 women who completed the trial there was a significant increase in high density lipoprotein cholesterol and a nonsignificant lowering of low density lipoprotein cholesterol. The results of this study indicate that comparative trials between this regimen and one in which the two drugs are given daily for seven days a week are warranted.
The tat-responsive region (TAR) of the human immunodeficiency virus-1 (HIV-1) exhibits a trans-inhibitory effect on translation in vitro by activating the interferon-induced 68-kilodalton protein kinase (p68 kinase). Productive infection by HIV-1 was shown to result in a significant decrease in the amount of cellular p68 kinase. The steady-state amount of p68 kinase was also reduced in interferon-treated HeLa cell lines stably expressing tat, as compared to the amount of the kinase in interferon-treated control HeLa cells. Thus, the potential translational inhibitory effects of the TAR RNA region mediated by activation of p68 kinase may be downregulated by tat during productive HIV-1 infection.
A new continuous coupled fluorimetric assay is described for ATPases in general. Thus phosphate released from ATP hydrolysis is coupled to the nucleoside phosphorylase reaction using 7-methylguanosine as a fluorescent substrate for the nucleoside phosphorylase reaction. The hydrolysis of 7-methylguanosine leads to 7-methylguanine, which has lower quantum yield and hence can be used to monitor ATP hydrolysis continuously. The method has the potential to be extended to GTPase and nucleotidyltransferase assays.
The nature of Rosenthal fibres (RF) was investigated in eight cases each of low-grade astrocytoma and reactive gliosis using immunohistochemical (IH) staining for glial fibrillary acidic protein (GFAP), electron microscopy (EM) and immunoelectron microscopy (IEM) by immunogold labelling technique. By IH under light microscopy (LM), three types of RF were seen, uniformly positive (type I), rim positive (type II) and completely negative (type III). EM showed variation in structural pattern of RF. Some RF contained large amount of glial filaments (GF) intermingled with RF while others with a large amount of electron dense material and less GF. Thus, the presence and amount of GF in RF appear to be responsible for the different types of IH staining under LM. IEM showed that all RF including the ones consisting of entirely amorphous material possess immunoreactivity for GFAP. It is suggested that RF formation is a two-stage process, starting with excessive accumulation of GF within astrocytic processes followed by their gradual alteration into electron-dense amorphous material under the influence of some unknown metabolic or other factors. The quantitative analysis of different types of RF suggests a difference in the rate of formation of RF in neoplastic and reactive conditions.
Changing perspectives in 95 children with poststreptococcal acute glomerulonephritis (PSAGN) in our hospital between 1979 and 1988 are reported. Between 1961 and 1970 an average of 31 +/- 6.3 patients/year with PSAGN were treated and 70% had antecedent pyoderma. In the present study antecedent pharyngitis was observed in 59 children and pyoderma in 36. In comparison to the decade ending in 1970 our data show: (1) a marked decline in the prevalence of PSAGN (P = less than 0.0005), (2) a predominance of antecedent pharyngeal infection (P = 0.044), (3) a decline in urban and an increase in rural patients with PSAGN (P = 0.0483); and in the last decade: (1) a predominance of antecedent pharyngeal infection in children over 6 years of age (P = 0.0009) and (2) a predominance of antecedent pyoderma in black children (P = 0.0004).
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We describe a patient with peripheral neuropathy, polymyalgia, arthralgia and cervical vertebral osteosclerosis who was subsequently diagnosed to have fatal multiple myeloma with IgG gammopathy and lambda urinary chains. The initial presentation and clinical features are discussed.
Menstrual data of 13 control subjects and 88 subjects immunized with three beta-hCG-based vaccine formulations were analysed. Immunization did not change the menstrual regularity; bleeding days were normal (3-7 days) and 89% of the menstrual cycles were within the normal range of 22-35 days. Irregular (short or long) cycles were observed in both immunized and control groups. These were, however, unrelated to prevailing anti-hCG antibody titres or to cross-reactivity of antibodies with hLH.
Comparative phase I clinical trials were carried out in 5 centres with three formulations of beta-hCG-based vaccines inducing antibodies against human chorionic gonadotropin. The objectives of these trials were to determine their relative immunogenicity, duration, reversibility and safety. A total of 116 tubal ligated women volunteers were enrolled in the study and 101 subjects were followed-up for one year or more until the antibody titres declined to near zero levels. Every woman receiving the vaccine produced anti-hCG and anti-tetanus antibodies. Clinical examination carried out at intervals of 4-6 weeks revealed no abnormality. No serious side effects or adverse reactions were reported with any of the formulations during primary immunization with three monthly injections of the vaccine. Eleven women, however, demonstrated hypersensitivity to test dose at the time of the booster injection. The reaction was to tetanus toxoid; gonadotropin subunits conjugated to another carrier did not evoke any such reaction. Progesterone in bleeds taken at midluteal phase, as well as complete progesterone and estradiol done in two immunized women, indicated normal ovulatory cycles. Immunization with these formulations had no significant effect on haematological, clinical chemistry and other metabolic parameters. In summary, the results indicate that none of the three beta-hCG-based contraceptive vaccines had any adverse effects clinically, on endocrine status and metabolic parameters. Formulations A and B induced comparatively higher anti-hCG titres than M. Thus, further work can be undertaken to study the efficacy of these vaccines in humans for preventing pregnancy.
There is limited information on the metabolism of levonorgestrel, norethindrone and structurally related contraceptive steroids. Both levonorgestrel and norethindrone undergo extensive reduction of the alpha, beta-unsaturated ketone in ring A. Levonorgestrel also undergoes hydroxylation at carbons 2 and 16. The metabolites of both compounds circulate predominantly as sulfates. In urine, levonorgestrel metabolites are found primarily in the glucuronide form, whereas norethindrone metabolites are present in approximately equal amounts as sulfates and glucuronides. Of the progestogens structurally related to norethindrone, norethindrone acetate, ethynodiol diacetate, norethindrone enanthate, and perhaps lynestrenol, undergo rapid hydrolysis and are converted to the parent compound and its metabolites. There is no convincing evidence that norethynodrel is converted to norethindrone. Of the progestogens structurally related to levonorgestrel, it appears that neither desogestrel nor gestodene are transformed to the parent compound. However, there is evidence that norgestimate can be, at least partly, converted to levonorgestrel. Further studies on the metabolism of these progestogens are required before we can understand their mechanism of action.
Bile acids are major determinants of canalicular bile secretion, and there are indications that choleretic bile acids increase bile canalicular contractions, in isolated rat hepatocytes. Therefore, we examined the influence of various bile acids on the rate of actin polymerization in vitro. The free forms of cholic acid, ursodeoxycholic acid, and chenodeoxycholic acid, as well as their taurine and glycine conjugates, were incubated with purified muscle actin, at a concentration of 100-300 nmoles/mg actin. The rate of actin polymerization was measured by viscometry and the fluorescence of the pyrene probe, linked to actin. Results showed that all bile acids slow the rate of polymerization, and that the effect was dose-dependent. However, the reduction by chenodeoxycholic acid was greater than that caused by the other bile acids. The results indicate that bile acids, particularly in high concentrations interact with actin, a finding that may be related to the increased bile canalicular contractility, and altered canalicular membrane morphology, induced by choleretic bile acids.
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