[Antilymphocyte globulin treatment in children with aplastic anemia].
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Biomedical subjects
Publications and source records attributed to K Miyamura.
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We describe a family from Japan displaying the mutant insulin syndrome with hyperinsulinaemia and an increased insulin: C-peptide molar ratio. Serum insulin isolated from several family members showed reduced in vitro biological activity, and analysis by high performance liquid chromatography revealed a peak co-eluting with human insulin and a second species of increased hydrophobicity co-migrating with the previously reported Insulin Wakayama. The insulin genes from the propositus were cloned and sequenced, revealing one normal allele; the second allele, encoding a leucine for valine amino acid substitution at position 3 of the insulin A chain, was similar to that previously described for Insulin Wakayama. Synthesized [LeuA3] insulin showed 0.14% of receptor binding activity on rat adipocytes and a 10-fold prolonged half-life in a somatostatin-infused dog compared with human insulin. The finding of the same mutant gene in two unrelated Japanese families suggests that Insulin Wakayama may be discovered in additional Japanese families with hyperinsulinaemia and/or diabetes.
To evaluate the function of the central nervous system of patients with occupational vibration disease, electroencephalograms and auditory brainstem responses (ABR) were recorded in 20 male subjects with occupational vibration disease whose age ranged from 46 to 67 years (mean 57.4 yr). All the subjects had operated chain saws from 10 to 25 yr (mean 15.2 yr) and had frequently complained of many subjective symptoms induced by central nervous system disturbances such as headache, head heaviness, tinnitus, vertigo, and insomnia, which corresponded to stage 3 in the diagnostic criteria of Andreeva-Galanina. Twenty-six healthy men whose age ranged from 40 to 67 yr (mean 53.0 yr) were selected as controls. Electroencephalograms were recorded with a 12-channel electroencephalograph, using unipolar and bipolar leads. Auditory brainstem responses were recorded by signal averaging technique using 100 microseconds alternating clicks. The stimuli were presented at 70 dB above threshold (SL) with a rate of 10 per second. The following results were obtained. 1. By electroencephalography, the incidence of diffuse alpha pattern, slow alpha wave and drowsy pattern was 32%, 32%, and 42%, respectively. 2. Click thresholds in the patients were obviously higher than those in the healthy controls. 3. The occurrence rate of wave II of ABR in the patients (61.8%) was significantly lower than that in the healthy controls (85.0%) (p less than 0.05). 4. The interpeak latencies I-V and III-V of ABR in the patients were significantly longer than those in the healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to evaluate the functions of the peripheral somatic nerve and autonomic nerve in patients with occupational vibration disease objectively and quantitatively, four examinations were performed on twenty 44-63 yr old patients with occupational vibration disease and their total operating time ranged from 5,000 to 43,750 h. 1) Motor nerve conduction velocities (MCV) and sensory nerve conduction velocities (SCV) of the ulnar and median nerves were measured using conventional methods. 2) Electrogustatory thresholds under the controlled area of the chorda tympani nerve were measured by Tomita's method using an electrogustometer (610-M, M.E.C.). 3) Dopamine-beta-hydroxylase (DBH) activity in blood was assayed by the photometric assay of Nagatsu and Udenfriend. 4) Coefficient of variation of R-R interval in ECG (CVR-R) was measured after 15-min-resting in supine position by using a R-R interval analyzer (Autonomic R 100, M.E.C.). The results of these examinations were compared with those of special examinations for the diagnosis of vibration disease. In patients with occupational vibration disease, MCV and SCV of the ulnar and median nerve were lower in value than those in age-matched healthy controls. In particular, MCV of the ulnar nerve, MCV and SCV of the median nerve were significantly lower in the patients than in the controls. Nerve conduction velocities were significantly correlated with skin temperature and nailpress test, though diminished nerve conduction velocities observed in vibration disease patients were considered to be attributable to peripheral circulatory disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)
A seroepidemiologic study to detect class-specific antibody against hepatitis A virus (HAV) was made with 831 randomly collected sera (415 in 1973 and 416 in 1984) from healthy Japanese. Competitive-inhibition, IgG, IgA, and IgM anti-HAV enzyme-linked immunosorbent assays (ELISA) were used. Both collections showed a low prevalence of IgG anti-HAV in young age groups and it increased rapidly at middle age and plateued at greater than or equal to 94% prevalence in the older age groups. However, two age groups spanning ages 25-34 demonstrated statistically lower IgG anti-HAV age prevalences in 1984 vs 1973 (P less than 0.001), with an average 10-year prevalence shift. These data suggest that there has been no significant level of HAV infection to alter antibody prevalences in Japan from 1973 to 1984. The markedly decreased incidence of HAV infection in Japan has created a presently large and growing population of HAV susceptibles.
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A 43-year-old patient with adult T cell leukemia (ATL) was treated with mega-dose cyclophosphamide and total body irradiation (TBI) followed by bone marrow transplantation (BMT) from his HLA-identical sibling who was not a carrier of ATL virus. After BMT, ATL cells rapidly decreased and disappeared, and the engraftment of marrow was confirmed on day 20. The patient showed normal hematologic recovery. However, he died on day 205 with interstitial pneumonitis caused by cytomegalovirus infection. Neither autopsy findings nor serologic and cytologic examinations showed any evidence of ATL relapse after BMT. This pilot study suggests that mega-dose chemotherapy and TBI followed by allogeneic BMT should be considered for such treatment of ATL.
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Nystagmus, head-deviation, and hearing loss were provoked by Type I allergy induced in guinea pigs with passive sensitization and specific antigen challenge. Mast cell degranulation, edema of connective tissue of the endolymphatic sac and endolymphatic hydrops were histologically observed. These findings indicated that Type I allergy can be induced in the inner ear, and that symptoms analogous to Meniere's disease may be induced by this response.
The data of large RNase T1-resistant oligonucleotide mapping of enterovirus 70 (EV 70) previously reported (Takeda et al., Virology 134, 375-388, 1984) were subjected to further genetical analysis to estimate the evolutionary rate of genome RNA of EV 70 and to clarify the phylogenetic relationship among isolates. A proportion of common spots between strains decreased as the year elapsed and eventually, only seven spots were common to all the 16 isolates tested, indicating that the substitution is scattered throughout the genome. On the other hand, some specific sets of spots were conserved among geographically or epidemiologically related strains. Base sequence variation of the isolates was deduced according to Aaronson et al. (Nucleic Acids Res. 10, 237-246, 1982) from pariwise comparison of the common spots and used as a genetic distance between them. The base substitution rate of virus genome was estimated by regression analysis of the genetic distance of the isolates against the sampling time. A fairly constant and rapid rate was obtained; it was 1.83 X 10(-3)/base/year. Based on the substitution rate, genetic distance and sampling time of the strains, the phylogenetic tree of EV 70 was constructed using Unweighted Pair Group Method Using Arithmetic Averages (UPGMA) (Nei, Molecular Population Genetics and Evolution, North Holland, Amsterdam, 1975). The tree supports the previous hypothesis that evolution of EV 70 started from a single common ancestor. The time of its emergence was estimated to be 1967 +/- 15 months. The virus branched into many strains early during the first pandemic and has evolved in a divergent fashion, yielding genetically polymorphic viruses in the world.
The clinical usefulness of calcium antagonists was studied in four patients with reactive hypoglycemia including two with alimentary and two with idiopathic. All patients had hyperresponses of plasma insulin (IRI) and C-peptide (CPR) during an oral glucose tolerance test (OGTT). A calcium antagonist (diltiazem 90 mg/d, or nifedipine 30 mg/d, or nicardipine 60 mg/d) was administered orally for about two months. After two months of treatment, plasma IRI and CPR responses during the OGTT were clearly suppressed in all patients and symptomatic reactive hypoglycemia disappeared. One month after the discontinuation of the treatment in two patients, plasma IRI and CPR responses during the OGTT became higher again and symptomatic reactive hypoglycemia recurred. In addition, an intravenous glucose tolerance test was performed before and after two months of the treatment with calcium antagonists in the two patients with reactive hypoglycemia and seven patients with hypertension, who were free from glucose intolerance and were also treated with a calcium antagonist. In these patients, plasma IRI and CPR responses were also reduced after the treatment compared with those before the treatment. These results suggest that calcium antagonists are useful as therapeutic agents for the treatment of reactive hypoglycemia associated with hyperinsulinemia, and that one of the main mechanisms of action of calcium antagonists is a direct action on the pancreatic B-cell to inhibit glucose-induced insulin release.
The distribution of Properdin factor B (Bf) phenotypes and their gene frequencies were investigated in four Asian populations (Chinese, Filipino, Thai and Japanese). The frequency of the BfS phenotype in Filipinos (0.717) was significantly lower than that in Chinese (0.900) and Thai (0.889) (p less than 0.01), but not different from the Japanese (0.840). One variant, BfF 0.65 S, was identified in a Japanese subject. Thus, in the Asian populations studied, Bfs frequencies were high and the frequency of variants other than F and S were low.
We have identified a non-insulin-dependent diabetic patient with fasting hyperinsulinemia (90 microU/ml), an elevated insulin:C-peptide molar ratio (1.68; normal, 0.05-0.20), normal insulin counterregulatory hormone levels, and an adequate response to exogenously administered insulin. Insulin-binding antibodies were absent from serum, erythrocyte insulin receptor binding was normal, and greater than 90% of circulating immunoreactive insulin coeluted with 125I-labeled insulin on gel filtration. The patient's insulin diluted in parallel with a human standard in the insulin radioimmunoassay, confirming close molecular similarity. The patient's insulin was purified from serum and shown to possess both reduced binding and ability to stimulate glucose uptake and oxidation in vitro. Analysis of the patient's insulin by high-performance liquid chromatography (HPLC) revealed two products: 7.3% of insulin immunoreactivity coeluted with the human standard, while the remaining 92.7% eluted as a single peak with increased hydrophobicity. Family studies confirmed the presence of hyperinsulinemia in four of five relatives in three generations, with secretion of an abnormal insulin documented by HPLC in the three tested. Leukocyte DNA was harvested from the propositus and the insulin gene cloned. One allele was normal, but the other displayed a thymine for guanine substitution at nucleotide position 1298 from the putative cap site, resulting in a leucine for valine substitution at position 3 of the insulin A chain. Insulin Wakayama is therefore identified as [LeuA3] insulin.
Follicular fluid from small porcine follicles was filtrated through an Amicon XM-50 membrane to obtain a filtrate less than 50,000 MW. The filtrate was eluted through a Sephadex G-25 column (1.5 X 70 cm) using 0.01 N CH3COOH, pH 4.0, as elution buffer, and divided to five fractions. To test the inhibitory activity of these fractions on the in vitro estradiol and progesterone secretion, each fraction was added into a rat granulosa cell culture with FSH and testosterone in the medium. Two of five fractions exerted a significant inhibitory activity on the estradiol and progesterone secretions by the granulosa cells. They were in a range of low molecular weight fractions (MW 1,000-3,000) on the elution profile. Whether the in vitro active fractions are capable of inhibiting the in vivo estradiol and progesterone secretions by the ovary was assessed using the hypophysectomized DES-treated immature rat with hMG stimulation and the testosterone-treated immature rat with PMSG stimulation. The administration of the fractions to the former animal significantly suppressed the increases due to gonadotropin in the ovarian and serum estradiol concentrations. The administration of the fractions to the latter animal significantly suppressed the increases due to gonadotropin in the estradiol and progesterone concentrations of the ovary and serum. These results suggest that a low molecular weight substance from porcine small follicular fluid is capable of inhibiting the estradiol and progesterone biosyntheses in the follicle of the rat ovary.
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