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Biomedical subjects

S Baba

Publications and source records attributed to S Baba.

At least 901 records · Page 50Linked to original sources

[Clinical studies of S6472 in otorhinolaryngologic infections].

A multicenter cooperative clinical trial was carried out on S6472 (a long-acting preparation of cefaclor (CCL)) to evaluate its effectiveness and safety in the treatment of infectious diseases in the field of otorhinolaryngology. The results are as follows: The clinical efficacy of the drug could be evaluated in 114 patients. An efficacy rate of 65.8% was obtained. The efficacy rate for each disease was found to be 60.0% for acute suppurative otitis media, 12.5% for chronic suppurative otitis media and 44.4% for acute exacerbation of chronic suppurative otitis media. The overall efficacy rate for all cases of suppurative otitis media was 46.4%. The efficacy rate for acute tonsillitis was found to be 93.1%. In the treatment of acute exacerbation of chronic tonsillitis, the efficacy of the drug was rated as excellent or good in all cases. The overall efficacy rate for all cases of tonsillitis was found to be 93.9%. In the treatment of other infectious diseases, the efficacy was rated as excellent or good in all cases. When the cases by resistant organisms to CCL were excluded from the evaluation, the overall efficacy rate of the drug was found to be 74.2%. The bacteria could be identified in 106 cases. Regarding the bacteriological efficacy of single infections, its bacterial elimination rate was found to be 81.1% for Gram-positive bacteria including S. aureus, S. epidermidis, etc., while it was 42.9% for Gram-negative bacteria. The overall elimination rate of bacteria in single infections was 73.1%. The bacterial elimination rate for mixed infections was found to be 85.7%, whereas it was 76.8% when the single and mixed infections were combined. Regarding side effects, 1 case each of diarrhea, soft stool and rash, or 3 cases in total (2.4%), were recorded in a total of 123 patients. However, the severity of each side effect was mild. Regarding abnormal laboratory findings, there were 1 case each of an increase in S-GPT, leukopenia and complication of eosinophilia and thrombocytopenia, or 3 cases in total (7.0%). Each of these adverse reactions was, however, transient in nature, and no serious cases were observed. On the basis of the above results, it was concluded that S6472 can provide sufficient clinical efficacy when it is administered at daily dosage of 750 mg or 1,500 mg in 2 divided doses after the breakfast and dinner.

Administration, Oral↗

Serum pancreatic secretory trypsin inhibitor in pancreatic disease.

The clinical usefulness of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic diseases was evaluated. The mean serum PSTI level of 41 healthy normal persons was 9.4 ng/ml (ranging from 5.2 to 16.7 ng/ml). Serum PSTI levels were abnormally raised in all patients with acute pancreatitis ranging from 35.0 to 4500 ng/ml, but were almost within normal range in patients with chronic pancreatitis, pancreatic cyst, acute abdominal emergencies such as perforated ulcer and intestinal obstruction, and macroamylasemia. There was no correlation between serum PSTI levels and total or pancreatic-type isoamylase activity. Patients with acute pancreatitis in whom the elevation of serum PSTI was transient and occurred after that of serum amylase activity had relatively mild symptoms and recovered along with normalization of serum PSTI levels. On the other hand, patients whose serum PSTI values became increased coincidentally with serum amylase activity and remained elevated, had severe clinical symptoms and unfavorable clinical outcome. Of 2 patients who underwent partial pancreatectomy, the serum PSTI level increased markedly in one who developed postoperative pancreatitis but not in the other without pancreatitis. In contrast to patients with acute pancreatitis, the serum response to the secretin stimulation in patients with chronic pancreatitis, was only small and transient, reaching the maximum at 10 min after administration of secretin. These results suggest that measurement of serum PSTI concentration may be useful in the diagnosis of acute pancreatitis and that the degree of rise and the duration of the elevated levels of serum PSTI are closely related to the severity of acute pancreatitis.

Acute Disease↗

Increased fructose-lysine of nail protein in diabetic patients.

Fructose-lysine, which is formed by binding glucose to lysine, is degraded on acid hydrolysis into furosine. Furosine was determined by high-performance liquid chromatography according to the method of Schleicher et al. Furosine values were significantly higher in diabetic patients than in healthy subjects, and significantly correlated with haemoglobin A1 (HbA1) values. These results suggest that furosine, like HbA1, may become an indicator of long-term blood glucose control in diabetic patients and be useful in investigating diabetic complications on the level of tissue.

Blood Glucose↗

Revised method for the quantitative determination of 5-hydroxytryptamine in human plasma by gas chromatography--mass spectrometry--selected ion monitoring.

To estimate the 5-hydroxytryptamine level in human plasma by gas chromatography--mass spectrometry--selected ion monitoring (GC--MS--SIM), a recovery method from plasma and derivatization conditions with pentafluoropropionic anhydride were investigated. By heating 5-hydroxytryptamine at 140 degrees C for 4 h in the presence of pentafluoropropionic anhydride the peak intensity of derivatized 5-hydroxytryptamine increased more than three times in comparison with the reported method. There was a marked difference in the plasma levels of 5-hydroxytryptamine obtained using the GC--MS--SIM method compared to those obtained using fluorometric assay.

Carbon Radioisotopes↗

[Insulin degrading system on isolated rat hepatocytes; enzymatic and immunologic characteristics of insulin-degrading activities].

Insulin degradation by isolated rat hepatocytes was investigated. Using the preincubation method, the extracellular insulin-degrading activity was removed from the medium over 120 min at 15 degrees C and 60 min at 37 degrees C. The degradation of insulin was assayed by the ability of binding to specific receptors on isolated rat hepatocytes (rebound method) and the precipitability with trichloroacetic acid (TCA method). The degrading activities measured by the rebound method showed twice those by the TCA method, however, a positive correlation with high coefficient (r = 0.87, P less than 0.001) was demonstrated between both methods. The insulin-degrading activity by hepatocytes depended on time, temperature and cell concentrations, and the optimum pH was 7.0. As a result of kinetic analysis of insulin binding and degradation, the degradation velocity of 125I-insulin was inhibited by 50% at native insulin concentration of 7 X 10(-8) M, whereas the half-maximum inhibition of 125I-insulin binding was demonstrated at that of 4 X 10(-9) M. The Km for insulin degradation was 170 nM. In order to characterize the enzymatic properties of insulin-degrading activity by isolated hepatocytes, the effects of various compounds and anti-insulin-degrading enzyme (IDE) rabbit serum on insulin degradation were examined. N-ethylmaleimide and anti-IDE serum significantly inhibited the insulin-degrading activity, while dithiothreitol stimulated it, whereas chloroquine and NH4Cl had little effect on insulin-degrading activity. Finally, the immunoenzymatic labelling of hepatocytes by anti-IDE serum showed the presence of cell surface IDE on isolated hepatocytes. These results suggest that most of insulin-degrading activity by isolated rat hepatocytes is identical to pig muscle IDE. Therefore, it would seem that IDE plays an important role in insulin metabolism by isolated rat hepatocytes rather than lysosomes.

Animals↗

High-performance liquid chromatographic determination of serum aliphatic amines in chronic renal failure.

A high-performance liquid chromatographic method has been introduced for the determination of aliphatic amines in serum as their 2,4-dinitrophenyl derivatives. The method has been applied to the estimation of ethanolamine, methylamine and dimethylamine in serum from patients with chronic renal failure undergoing maintenance haemodialysis. Significant differences in the levels of both methylamine and dimethylamine were obtained between normal subjects and uraemic patients both predialysis and postdialysis. After a dialysis treatment, the levels of these two amines were reduced to approximately 55% in the patient group. Their mean values, however, were found to be about six times the values of the normal group. The degree of removal of these substances during haemodialysis was smaller than those for urea nitrogen and creatinine. On the other hand, the mean ethanolamine level before dialysis was close to that of controls, and yet a 2.3-fold increase was observed after dialysis.

Adult↗

Application of high-performance liquid chromatography with synchronized accumulating radioisotope detector to analysis of glyceryl trinitrate and its metabolites in rat plasma.

A new, sensitive, and specific high-performance liquid chromatographic method for the quantitative analysis of [14C]glyceryl trinitrate and its four metabolites in plasma is described. The drugs are extracted from 0.05 ml of plasma with methanol and analyzed by high-performance liquid chromatography using a synchronized accumulating radioisotope detector. The limit of detection is 0.2 ng per injection. The within-day coefficient of variation is 5.9% at a concentration of 27.0 ng per ml of plasma. The method was applied to single-dose pharmacokinetics of glyceryl trinitrate in rat.

Animals↗

Comparative light and scanning electron microscopic observations of nasal cavity carcinogenesis in rats treated with 1,4-dinitrosopiperazine.

Epithelial lesions in the nasal cavity of male F344 rats appeared as papillary and nodular hyperplasias progressing to invasive carcinomas during administration of 1,4-dinitrosopepirazine (DNP) at a dose of 0.01% in the drinking water. Observations with specific attention to the cells covering the luminal surface of the mucosa were made by scanning electron microscopy at 10-week intervals. After administration of DNP for 20 and 30 weeks three different types of light microscopically identifiable focal lesions, i.e., papillary hyperplasia, nodular hyperplasia and papilloma, of the epithelium in the nasal cavity were distinguished, and after 40 and 50 weeks areas of squamous cell carcinomas were also observed. In the scanning electron microscope, papillary hyperplasia appeared as a nodular elevation of the surface with a smoother appearance than the surrounding nonnodular areas. Areas of nodular (inverted) hyperplasias had irregularly shaped indentions of the surface. Papillomas appeared as pedunculated projections of the surface. Carcinoma presented as a protrusion of irregular cell masses. The surface cells in the areas of papillary and nodular hyperplasias and of papilloma had numerous short microvilli rather uniform in shape (short-uniform microvilli), unlike the normal epithelium in the nasal cavity, which possesses cilia or olfactory vesicles. The microvilli of carcinoma cells were more irregular in shape and size than those of hyperplastic cells (pleomorphic microvilli).

Animals↗

Exocrine and endocrine secretion from isolated perfused rat pancreas with islet cell tumors induced by streptozotocin and nicotinamide.

Pancreatic exocrine and endocrine function in the rat with islet cell tumors induced by streptozotocin and nicotinamide was studied in the in vitro isolated perfused pancreas. The tumor-bearing pancreas secreted significant amounts of insulin even at 2.8 mM glucose stimulation. Further, insulin response to 8.3 mM glucose stimulation was greater in the tumor-bearing pancreas than in the control. Not only endocrine, but also exocrine, disorders were found in the rat pancreas bearing islet cell tumors. In contrast to the increased response of insulin, amylase output in response to 0.1 ng/ml cerulein was significantly lower in the tumor-bearing than in the control pancreas, although there was no difference in pancreatic juice flows from both groups. These results suggest that enzyme secretory function of the pancreas with islet cell tumors may be suppressed in the presence of some interrelationship between the exocrine and endocrine portion of the pancreas with islet cell tumors.

Adenoma, Islet Cell↗

An attempt to produce an antibody of histamine and histamine derivatives.

Three conjugates of different histamine derivatives to bovine serum albumin were prepared, and an attempt was made to determine whether antibody against histamine and histamine derivatives could be produced in rabbits by immunization with these conjugates. Antibody produced by immunization with bovine serum albumin-succinylhistamine conjugate could not recognize the hapten moiety of the immunogen. Immunization of rabbits with conjugate of bovine serum albumin and p-[2-(N alpha-trifluoroacetylhistamine)azo]benzoic acid resulted in the production of antibody to N alpha-trifluoroacetylhistamine. The antibody had a specificity for histamine metabolites and their derivatives. However, the antibody also showed a small but not negligible affinity for trifluoroacetylated serotonin, norepinephrine and aniline, indicating that the antibody specificity was directed mainly to the trifluoroacetamide group. After immunization of rabbits with bovine serum albumin and p-[2-(N alpha-propionylhistamine)azo]benzoic acid conjugate, antibody against N alpha-propionylhistamine could be produced. However, the antibody had a very low affinity even for N alpha-propionylhistamine. Specific antibody to histamine and histamine derivatives could thus not be produced by immunization with the present hapten-carrier conjugates.

Animals↗

Amylase inhibitor from wheat: its action and clinical application.

The electrophoretic and column chromatographic characteristics of an amylase inhibitor of wheat origin were investigated. Further, the clinical usefulness of this inhibitor for determining the ratio of pancreatic to salivary isoamylase activity in serum was evaluated. Amylase inhibitor inhibits the action of salivary alpha-amylase by making an amylase-inhibitor complex, which is easily separated into its individual component during electrophoresis with full recovery of amylase activity. Using the specific inhibitory effect of this inhibitor on salivary alpha-amylase activity, the ratio of pancreatic to salivary isoamylase activity (P/S) in serum was determined. There was a good correlation in P/S ratio in serum between the results obtained with the inhibitor method and those with electrophoretic method. The P/S ratio in sera from patients with acute pancreatitis was over 8.0, whereas that in sera from patients with salivary-type hyperamylasemia such as mumps, pulmonary diseases and following surgery was less than 0.1. However, hyperamylasemia due to macroamylase or renal failure could not be identified by the inhibitor method.

Amylases↗

Carbamylation of hemoglobin in renal failure and clinical aspects.

It was revealed that in renal failure hemoglobin A1 (HbA1) was formed by the binding of substances other than glucose to Hb. It was elucidated that the formation of HbA1 increased in urea-added medium and further increased in media containing urea either stored at 37 degrees C for 1 week or heated at 100 degrees C for five minutes. The increment of HbA1 was proportional to the amount of cyanic acid produced by the treatment of the medium after the addition of urea. We found that there was the best correlation between the HbA1 level and the BUN level of 1 to 2 weeks before. Therefore, it appeared that HbA1 could be an indicator of the state of renal failure of 1 to 2 weeks earlier in patients with renal failure without impaired glucose tolerance, especially in patients on hemodialysis.

Blood Urea Nitrogen↗

Synthesis of deuterium labeled 17-methyl-testosterone.

The synthesis of two forms of selectively deuterated 17-methyl-testosterone is described. 17-Methyl-d3-testosterone was prepared by the Grignard reaction of dehydroepiandrosterone with deuterium labeled methyl magnesium iodide followed by an Oppenauer oxidation. 17-Methyl-d3-testosterone-19,19,19-d3 was prepared by treating 3,3-ethylenedioxy-5,10-epoxy-5 alpha, 10 alpha-estran-17-one with deuterium labeled methyl magnesium bromide followed by hydrolysis and dehydration of the 5 alpha-hydroxyandrostane derivative.

Chemical Phenomena↗

Effects of glycosylation on physiological and biological activities of substances.

Hemoglobin A1 (HbA1) increases in old erythrocytes. These erythrocytes with increased HbA1 had decreased oxygen dissociation ability, resulting in decreased function. L-Triiodothyronine (T3) underwent glycosylation to form glycosylated T3. The biological activity of glycosylated T3 was assayed utilizing the metamorphosis of tadpoles. It was found that glycosylated T3 was less than one-tenth as biologically active as T3.

Aging↗

Effect of short-term peroral administration of synthetic trypsin inhibitor on endocrine secretion in the isolated perfused rat pancreas.

The effects of peroral treatment with synthetic trypsin inhibitor on endocrine secretion in response to four different stimuli were investigated in the isolated perfused rat pancreas. After 10 days' treatment pancreatic wet weights and protein and amylase contents in the pancreas were significantly increased. On the other hand, total contents of IRI and IRG in the T.I.-treated and control pancreas were nearly the same. In spite of the lack of alteration in hormone contents, a lower initial phase of IRI response to 8.3 mM glucose, glucose plus 0.1 ng/ml caerulein or 20 mM arginine was observed in the T.I.-treated pancreas. Furthermore, the IRI response to 10 mM theophylline was both slower and the most reduced in the T.I.-treated pancreas. From these observations, it is suggested that short-term peroral administration of synthetic trypsin inhibitor not only has no trophic effect on pancreatic B-cell and A-cell in the rat but also may affect some pathway of insulin secretion from the B-cell to reduce IRI responses to secretagogues.

Amylases↗

Amylase secretion by isolated pancreatic acini after acute cholecystokinin treatment in vivo.

A single dose of synthetic cholecystokinin octapeptide (CCK8, 5 micrograms/kg) in a depot carrier was injected subcutaneously into rats 2 and 14 h before the removal of the pancreas and the preparation of isolated pancreatic acini. CCK8 treatment induced no significant change in body weight or total amount of pancreatic DNA, but pancreatic weight, total pancreatic protein and amylase, and the concentration of amylase and total protein relative to DNA were significantly decreased. In acini prepared from CCK8-pretreated rats, responsiveness to maximal and supramaximal concentrations of CCK8 was significantly increased, irrespective of whether the amount of amylase released was expressed relative to DNA or calculated as a percentage of the acinar content. The dose-response curves for CCK8 were similarly shaped in both CCK8-pretreated and control rats but shifted threefold toward higher concentrations of CCK8 2 or 14 h after CCK8 treatment. Specific 125I-CCK binding was significantly increased only for high-affinity binding sites. Although these observations suggest that alterations in pancreatic amylase release could be due to changes at the cholecystokinin receptor, the secretory responsiveness to maximal and supramaximal concentrations of carbachol was also increased without any change in the sensitivity. Moreover, in contrast to the cholecystokinin receptor, there was no change in the number of muscarinic receptors or in their affinity for either agonists or antagonists measured with [3H]quinuclidinyl benzilate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗