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Biomedical subjects

K Miyai

Publications and source records attributed to K Miyai.

At least 235 records · Page 13Linked to original sources

Studies on beta-lactam antibiotics VIII. Structure-activity relationships of 7 beta-[(Z)-2-carboxymethoxyimino-2-arylacetamido]-3-cephem- 4-carboxylic acids.

The synthesis, antimicrobial activity and oral absorptivity of 7 beta-[(Z)-2-carboxymethoxyimino-2-arylacetamido]-3-cephem-4- carboxylic acids are described. The [(Z)-2-(2-amino-4-thiazolyl)-2-carboxymethoxyimino]acetyl group was selected as the most suitable 7-substituent from seven 7-acyl groups for our further investigation of orally active cephalosporins.

Animals↗

Highly sensitive immunoenzymometric assay for human thyrotropin.

A sensitive assay procedure for immunoenzymometric assay of serum thyrotropin (TSH) was developed by making several modifications of the Enzymun-Test TSH kit (Boehringer, Mannheim GmbH). Serum samples were first incubated in plastic tubes precoated with monoclonal antibodies specific to the beta subunit of human TSH. After the tubes were washed, the TSH bound to the tubes was detected with peroxidase-conjugated polyclonal antibodies to TSH. The sensitivity of the assay was 0.2 milli-int. unit/L, and the intra-and interassay CVs were less than 10%. Analytical recovery was 96 to 106%. The normal basal range of TSH was 0.5 to 4.8 milli-int. units/L. The basal levels of TSH in all but one of 48 thyrotoxic patients with Graves' disease were less than 0.2 milli-int. unit/L, clearly different from those of normal subjects. Thyrotoxic patients in early normal pregnancy showed TSH concentrations of 1.7 to 2.9 milli-int. units/L by conventional double-antibody radioimmunoassay, possibly from cross reactivity with human choriogonadotropin, but undetectable TSH by this method. Measurement of basal TSH by this sensitive assay can be used as an initial screening test for thyroid dysfunction.

Adult↗

Enzyme immunoassay of free thyroxin in dried blood samples on filter paper.

We describe a double-antibody enzyme immunoassay for determination of free thyroxin (FT4) in dried blood samples on filter paper, with use of a T4-beta-D-galactosidase complex. The measurable range of FT4 concentration in two 3-mm blood discs, each of which contained about 2.7 microL of blood, was 1.9 to 93 ng/L, as determined by comparison with concentrations of FT4 in known serum standards. FT4 in blood samples dried on filter paper was stable for at least four weeks when kept dry at -20 degrees C, room temperature, or 37 degrees C. The mean coefficients of variation were 7.6% (within assay) and 6.4% (between assays). Results for FT4 by this method correlated well with those for serum determined by radioimmunoassay (r = 0.98). The proposed method can be used to differentiate persons with hyper- and hypothyroidism from normal subjects and those with abnormal concentrations of thyroxin-binding globulin. The procedure seems suited for screening studies.

Adult↗

Mesenteric venous thrombosis as sole complication of decompression sickness.

A 27-year-old male commercial diver developed massive mesenteric venous thrombosis following a dive. Symptoms at presentation included abdominal pain and diarrhea. A severe upper gastrointestinal bleed developed. Exploratory laparotomy demonstrated 130 cm of infarcted small bowel. The pathophysiologic events in decompression sickness predispose to vascular obstruction and venous infarction. This patient had a past history of possible thrombophlebitis and pulmonary embolism associated with diving but no identifiable coagulopathy.

Adult↗

Outcome in cirrhotic patients with acute alcoholic hepatitis after emergency portacaval shunt for bleeding esophageal varices.

Operative liver biopsy findings were reviewed in 164 consecutive, unselected patients with alcoholic cirrhosis who had bleeding from esophageal varices and underwent emergency portacaval shunt. The survival rate up to 10 years in 49 patients with acute alcoholic hepatitis and alcoholic cirrhosis was not significantly different from that of patients with alcoholic cirrhosis alone. The two groups of patients were compared with respect to 35 other preoperative clinical and laboratory variables, and no other difference between the groups was found that obscured an adverse effect of acute alcoholic hepatitis on survival. We have concluded that acute alcoholic hepatitis and the presence of Mallory bodies in the liver are not a contraindication to portacaval shunt and that there is currently no demonstrated role for preoperative liver biopsy in the evaluation of patients with alcoholic cirrhosis and bleeding esophageal varices.

Acute Disease↗

Fractionation of polyclonal antibody by isoelectric focusing--differences in cross-reactivity and affinity of rabbit clonotype anti-human thyrotropin antibody.

Immunoglobulin G (IgG) fractions prepared from three different batches of rabbit antihuman thyrotropin (hTSH) antisera were fractionated by agarose isoelectric focusing (IEF) in the pH ranges 3 to 10 and 5 to 8. Staining of protein in agarose gel after IEF showed that polyclonal IgG separated into more than 20 protein bands with isoelectric points (pIs) ranging from 6 to 9. The clonotype antibodies to hTSH were recovered from the fractions and subjected to radioimmunoassay for determination of the binding-affinity for hTSH and the cross-reactivity with human chorionic gonadotropin (hCG). The affinity constants of the antibodies recovered ranged from 6.4 X 10(9) M-1 to 3.1 X 10(10) M-1, and the cross-reactivities of the clonotype antibodies differed greatly. A good correlation was observed between the pIs of antibody molecules and their cross-reactivities: antibodies with higher pIs bound hCG more strongly than those with lower pIs. The correlation coefficients between the pIs and cross-reactivities were 0.83, 0.84, and 0.87 in three batches of antibody.

Animals↗

Streptozotocin-induced liver tumors in the Syrian hamster.

Streptozotocin was administered in a dose of 50 mg/kg body weight intraperitoneally on three consecutive days to 35 8-week old male Syrian golden hamsters. At sacrifice 16-36 weeks later, macroscopic liver tumors had developed in 27 of 29 surviving animals. The majority of animals had multiple hepatic nodules. Some tumors were already large (greater than 1 cm) 16 weeks after streptozotocin. By histologic criteria, five animals (17%) had hepatocellular carcinoma, 23 (79%) had adenomas with varying degrees of atypia, and one (4%) had a normal liver. No metastases to organs outside the liver were noted. No other primary tumors were observed. Sixteen of 29 animals had ascites. Twenty-five age-matched untreated animals showed no evidence of liver tumors. Although sporadic liver tumors due to streptozotocin have been reported in rats and mice, the high incidence of tumors and short latency period to tumor induction seem to be unique to the Syrian hamster. The development of liver carcinoma without the necessity for long-term administration of the carcinogen and without adjunctive procedures such as partial hepatectomy represents a potential improvement over other animal models of hepatic neoplasia.

Animals↗

HLA-A and -B antigens in Japanese patients with congenital hypothyroidism and their parents.

The frequency of HLA-A and B antigens were studied in 32 Japanese patients with congenital hypothyroidism due to thyroid dysgenesis, and in their parents. The incidence of the Aw24 antigen was significantly higher in 27 mothers of patients with ectopic thyroid (91.3%, corrected P less than 0.037) and it seemed to be slightly higher in patients (77.7%) than in controls (56.8%). The Aw24 antigen was also found in 4 patients with thyroid hypoplasia and their mothers. No difference was found in the incidences of the antigen in the fathers of patients and in controls. The haplotype frequencies were not significantly different in controls, patients and their parents. These findings suggest that the gene for susceptibility to congenital hypothyroidism due to thyroid dysgenesis is closely linked to the gene for the HLA-A locus of the patients' mothers.

Adolescent↗

Fluorometric assay of human serum carnosinase activity in normal children, adults and patients with myopathy.

A sensitive, accurate method has been established for the assay of serum carnosinase by measuring the fluorescence emitted from the L-histidine liberated on treatment with o-phthaldialdehyde. Using this method the serum values for normal adults, infants and children were measured. The mean value was very low in infants of less than 1 year old but increased with age, being almost the same in children aged 6 years or more as in adults. In adult men, the mean activity was 1.85 mumol/mL/h and in adult women it was 2.07 mumol/mL/h. Low activity was observed in patients with muscular dystrophy.

Adult↗

Semiautomated enzyme immunoassay of thyrotropin as a mass screening test for neonatal hypothyroidism.

A sensitive, simple, and rapid semiautomated sandwich enzyme immunoassay (EIA) was developed for measuring thyrotropin in dried blood samples on filter paper for use in screening for neonatal hypothyroidism. Good correlation was found between values for thyrotropin determined by this method and those determined by radioimmunoassay (RIA) (r=0.94). In pilot tests on 17,160 newborn infants in the general population, five cases of primary hypothyroidism were detected by both EIA and RIA. The recall rate was slightly highter in EIA than in RIA.

Autoanalysis↗

Relation of structural polarity to responses of cyclic 3', 5'-adenosine monophosphate accumulation and thyroid hormone release in cultured human thyroid follicles.

The relationship of structural polarity to functional activities was examined in cultured human thyroid follicles, which were isolated from the thyroid gland of patients with Graves' disease by collagenase treatment. Structural polarity was examined morphologically by electron microscopy, while the functional response to bovine TSH was examined by measuring intracellular cAMP accumulation and T3 release. In freshly isolated thyroid follicles, structural polarity was normal and TSH induced significant cAMP accumulation but no significant release of T3. After culture for 5 days the structural polarity of thyroid follicles became inverted in the absence of thyroid stimulators, but normal polarity was retained in the presence of TSH or dibutyryl cAMP [Bu)2 cAMP). The response to TSH of cAMP accumulation increased markedly after culture in either the presence or absence of TSH, suggesting that cAMP accumulation in response to TSH is not related to structural polarity. In contrast, thyroid follicles cultured without thyroid stimulators showed no significant T3 release in response to TSH, whereas those cultured with TSH or (Bu)2 cAMP showed significant T3 release in response to TSH. These data indicate that in cultured human thyroid follicles, the responses to TSH of cAMP accumulation and T3 release are not always correlated. Among many other explanations, the results were at least compatible with the idea that normal structural polarity is necessary for thyroid hormone release in response to TSH.

Bucladesine↗