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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 1,099 records · Page 61Linked to original sources

Sex difference in the biliary excretion of digoxin and its metabolites in aging Wistar rats.

The biliary excretion of digoxin (Dg3) and its metabolites was studied in both young (3-month-old) and old (25- and 30-month-old) Wistar rats of both sexes. The 2 h biliary recovery (% of the dose) of intravenously injected [3H]Dg3 (0.01 mg/100 g) radioactivity was similar between young male and female rats, while the first 10 min excretion was significantly higher in females. In old (25-month-old) male rats, the 2 h biliary recovery of radioactivity was significantly lower than the corresponding young value. This was primarily due to the drastic decrease with age in excretion of bis-digitoxoside. On the other hand, in old female rats (25- and 30-month-old) the 2 h recovery value was not significantly different from the corresponding young (3-month-old) value. This was due to the much higher percentage (more than 80% of the total) of Dg3 in the female bile radioactivity which did not significantly decrease with age. The results suggest that the rate of stepwise cleavages of the sugar chain of Dg3 decreases with age more rapidly in male than in female rats as has been previously shown by the authors for digitoxin. Large sex differences observed in the age-dependent alteration in Dg3 metabolism and its biliary excretion raise a caution against a generalization of the data obtained from a single sex in this animal species with regard to the effect of aging.

Aging↗

Superoxide anion generation by polymorphonuclear leukocytes enhanced in a patient with colony-stimulating activity-producing lung cancer.

We examined superoxide (O-2)-generating activity of polymorphonuclear leukocytes (PMN) from a patient with lung cancer in whom there was a marked granulocytosis. There was a high level of colony-stimulating activity (CSA) in both the serum and the supernatant of the culture of the primary tumor. The PMN from the patient produced almost three times more O-2 than did the PMN from healthy donors and other patients with lung cancers but with no granulocytosis. The binding of wheat germ agglutinin (WGA), used as a stimulus for O-2 generation, to the surface membrane of cells and the protein content in the cells were about double that noted in the case of healthy donors. Following total extirpation of the tumor, the level of CSA in the serum decreased, as did activity of PMN for O-2 generation, and the binding of WGA to the cells reverted to normal levels.

Blood Proteins↗

The breakdown of an emergency system following a gas explosion in Osaka and the subsequent resolution of problems.

Osaka, a modern urban metropolis in Japan, experienced a tragic gas explosion in 1970 when the dispatch room of the City Fire Department was in the process of being moved to a new building. Many unforseen problems arose during this disaster: eg, there was an overall lack of leadership, confusion of communication, a need for triage, and lack of control of mass media. The Osaka Medical Association organized a committee to resolve these problems. Their conclusions and recommendations were that a control headquarters be established at the scene of disaster, the number of ambulances and EMTs be increased, disaster tags be utilized, a special radio frequency be created, and a computer-aided command and control system for fire fighting and ambulance services be introduced. These recommendations have all been followed.

Adolescent↗

Aqueductal stenosis--results of vestibular function tests.

A case of aqueductal stenosis is reported. The patient was a 14-year-old Japanese girl who was suffering from bilateral tinnitus and unsteadiness of gait. A series of neuro-otological tests revealed prolonged acoustically evoked brain stem response (ABR) latency, disturbed standing reflex, inhibited optokinetic nystagmus (OKN) and ataxic eye tracking test (ETT). Marked distension of the lateral and third ventricles was noticed on CT examination of the brain. A positive contrast ventriculogram using iotalamic acid showed occlusion of the cerebral (Sylvian) aqueduct. All of these results are suggestive of benign, non-neoplastic aqueductal stenosis with associated hydrocephalus. The patient underwent ventriculo-peritoneal shunt and, following the surgery, the results of neuro-otological, including radiological, re-examination indicated a remarkable recovery.

Adolescent↗

Zinc, copper, manganese, and selenium metabolism in patients with human growth hormone deficiency or acromegaly.

This study was designed to evaluate trace metal metabolism in patients with known abnormalities of human growth hormone (hGH). The mean concentration of zinc in plasma and urine decreased in patients with hGH deficiency after hGH injection, whereas, after adenomectomy, in patients with acromegaly, zinc increased in plasma, remained the same in erythrocytes, and decreased in urine. There was a negative correlation between plasma zinc and serum hGH levels and a positive correlation between urinary zinc excretion and serum hGH levels in acromegaly. In hGH deficiency, the copper content remained unchanged in plasma and erythrocytes and rose in urine after treatment; however, in acromegaly, the copper content increased in plasma and remained unchanged in erythrocytes and urine after surgery. The mean concentration of erythrocyte manganese did not change significantly after treatment in patients with hGH deficiency or acromegaly, but the pre-hGH treatment level of erythrocyte manganese in hGH deficiency was lower than in the controls. Plasma selenium concentrations were decreased in hGH deficiency and increased in acromegaly patients after therapy. These results suggest that hGH affects the metabolism of zinc, copper, manganese, and selenium.

Acromegaly↗

Biological activities of lipopolysaccharide fractionated by preparative acrylamide gel electrophoresis.

Lipopolysaccharide from a smooth strain of Salmonella minnesota was fractionated into two major fractions and one intermediate fraction by using sodium dodecylsulfate-polyacrylamide gel electrophoresis. On the basis of the study by Hitchcock and Brown, it was deduced that the top fraction was mainly long O-side chain LPS and the bottom fraction was O-side chain-less LPS. The middle fraction was a mixture of both short O-side chain LPS and O-side chain-less LPS. The antigenic properties and biological activities were not altered in this fractionation procedure. Comparison of the biological activities of the top fraction with those of the bottom fraction revealed that the bottom fraction had higher activity in polyclonal B-cell activation and spleen-swelling effect and that there was no significant difference in adjuvant activity, ability to render macrophages cytotoxic, induction of colony-stimulating factor and the ability to induce the Schwartzmann reaction. It was suggested that O-side chain makes no contribution to the latter biological activities including adjuvant activity of S. minnesota LPS.

Adjuvants, Immunologic↗

Adjuvant activity of Klebsiella O3 lipopolysaccharide: inhibition of the adjuvant activity by concanavalin A.

Klebsiella O3 lipopolysaccharide (KO3 LPS) was found to exhibit extraordinarily strong adjuvant activity in augmenting antibody responses and delayed-type hypersensitivity (DTH) to protein antigens in mice. The O-specific polysaccharide chain of KO3 LPS consists of alpha-mannoside. We investigated the effect of concanavalin A (Con A) or succinyl Con A, which is known to bind to alpha-mannoside, on the adjuvant activity of KO3 LPS in augmenting DTH to ovalbumin. When KO3 LPS was mixed with Con A prior to injection, the strong adjuvant activity of KO3 LPS in augmenting DTH was inhibited and the degree of inhibition depended upon the dose of Con A. An equal amount of Con A elicited nearly complete inhibition of the adjuvant activity of KO3 LPS, Con A at 1/10 the amount of LPS elicited partial inhibition, and Con A at 1/100 the amount of LPS showed no inhibition. An equal amount of succinyl Con A, which induced less marked aggregation of KO3 LPS than Con A, elicited inhibition of the adjuvant activity of KO3 LPS to an extent similar to that by Con A. On the other hand, Con A or succinyl Con A bound to KO3 LPS did not impair in any way the lethal toxicity of KO3 LPS for mice which is known to be due to the lipid A moiety. From these findings it is concluded that the strong adjuvant activity of KO3 LPS does not solely depend upon the lipid A moiety but the O-specific polysaccharide moiety plays an important role in expression of the adjuvant activity.

Adjuvants, Immunologic↗

Formation of a hexagonal lattice structure by an R-form lipopolysaccharide of Klebsiella: comparative study of preparations extracted by the phenol-water and the phenol-chloroform-petroleum ether methods.

An R-form lipopolysaccharide (LPS) extracted from Klebsiella strain LEN-111 (O3-:K1-) by the phenol-chloroform-petroleum ether method was compared with that extracted by the phenol-water method in the ability to form a hexagonal assembly. The LPS which was extracted by the phenol-water method and dialyzed against tap water to remove phenol showed ribbon-like structures, and it formed a hexagonal lattice structure with a lattice constant of 14.5 +/- 0.3 nm when it was precipitated by addition of two volumes of 10 mM MgCl2-ethanol. The LPS which was extracted by the phenol-chloroform-petroleum ether method and lyophilized consisted of ribbon-like structures and their fragments and it often formed small pieces of a hexagonal lattice, although the LPS before lyophilization did not form such a lattice. When the LPS extracted by the phenol-chloroform-petroleum ether method was precipitated by addition of two volumes of 10 mM MgCl2-ethanol, it formed essentially the same hexagonal lattice structure as that formed by the LPS extracted by the phenol-water method. From these results it is concluded that the ability of the LPS to form a hexagonal lattice structure does not depend upon the method of its extraction from bacterial cells.

Chemical Phenomena↗

Formation of a hexagonal lattice structure by an R-form lipopolysaccharide of Klebsiella: relationship between lattice formation and uniform salt forms.

Various uniform salt forms of an R-form lipopolysaccharide (LPS) extracted from Klebsiella strain LEN-111 (O3-:K1-) were prepared and their ultrastructure was examined. The LPS, which was extracted by the phenol-water method, freed from contamination with RNA by treatment with RNase, and precipitated by addition of two volumes of 10 mM MgCl2-ethanol, was used as the original preparation for uniform salt forms. The original LPS preparation formed a hexagonal lattice structure with a lattice constant of 14.9 +/- 0.2 nm. The LPS after electrodialysis retained the ability to form a hexagonal lattice structure, although its lattice constant was large (18.7 +/- 0.5 nm) and the lattice structure of the electrodialyzed LPS was labile at pH 8.0 in contrast to that of the original LPS preparation. The magnesium salt form of the LPS formed essentially the same ordered hexagonal lattice structure (lattice constant of 15.0 +/- 0.2 nm) as that of the original LPS preparation. The calcium and ammonium salt forms formed a hexagonal lattice structure, but the lattice constants of the calcium and ammonium salt forms were larger (18.6 +/- 0.6 nm and 19.3 +/- 0.4 nm, respectively) than that of the magnesium salt form. The sodium and potassium salt forms consisted of freely branching ribbon-like structures with an average width of 13 nm and an average thickness of 9 nm. The triethylamine salt form consisted principally of short rods (10 nm X 9-13 nm).

Calcium↗

Formation of a hexagonal lattice structure by an R-form lipopolysaccharide of Klebsiella sp.

We extracted an R-form lipopolysaccharide (LPS) by the phenol-water method from Klebsiella sp. strain LEN-111 (O3-:KI-) and followed the changes in ultrastructure of the LPS during the extraction procedure. When the LPS was obtained from the water phase of an extract by addition of 2 volumes of 10 mM MgCI2-ethanol, it consisted of membrane pieces with a hexagonal lattice structure with a lattice constant of 14 to 15 nm. The lattice structure of the LPS was disrupted into short rods with sodium dodecyl sulfate, but the same hexagonal lattice structure was again formed by precipitation with 2 volumes of 10 mM MgCI2-ethanol. The LPS preparation after two cycles of treatment by the phenol-water method, which contained no detectable amounts of proteins, kept an unaltered ability to form the hexagonal lattice structure. Extensive treatment with pronase and extraction with chloroform did not impair the ability of the LPS preparation to form the lattice structure. When the other salts, NaCI, CaCI2 or Zn(CH3COO)2, were used for precipitation of the LPS with ethanol in place of MgCI2, the LPS did not form the hexagonal lattice structure. However, if the LPS precipitated with NaCI-ethanol was converted to the magnesium salt form after it was electrodialyzed, it formed the same hexagonal lattice structure as the LPS precipitated with MgCI2-ethanol. From these results, it was concluded that the R-form LPS has the ability of in vitro self-assembly into a hexagonal lattice structure in the presence of Mg2+ without the help of other components such as proteins and free lipids from outer membrane.

Bacterial Outer Membrane Proteins↗

False lumens in type III aortic dissections: progress CT study.

The fate of false lumens in 13 patients having Type III aortic dissections was studied using computed tomography (CT). Contrast media filled false lumens with or without thrombosis were observed in ten patients; the false lumens of three patients were entirely thrombosed at initial examination. Follow-up CT studies showed shrinkage or disappearance of the false lumens with thrombosis in four patients, progression of thrombosis in two patients, and enlargement of the false lumen in one patient who subsequently required surgical repair. No change was observed in the remaining six patients during our observation period. CT study provides useful information for evaluating the efficacy of medical treatment and the timing of surgical intervention during follow-up evaluation of medically treated Type III aortic dissections.

Adult↗

Tauroursodeoxycholate prevents biliary protein excretion induced by other bile salts in the rat.

Biliary excretion of various proteins (5'-nucleotidase, alkaline phosphatase, lactate dehydrogenase, and albumin) was investigated in pentobarbital sodium-anesthetized rats infused with different bile salts [taurocholate (TC), taurochenodeoxycholate (TCDC), and tauroursodeoxycholate (TUDC)]. A TCDC infusion at 0.4 mumol . min-1 . 100 g body wt-1 caused much higher increases in the biliary excretion of these proteins compared with the respective values in rats that received an infusion of TC at a threefold higher rate (1.2 mumol . min-1 . 100 g body wt-1). In contrast, a TUDC infusion at 1.8 mumol . min-1 . 100 g body wt-1 showed the minimum effect on these protein leakages. A combined infusion of TCDC (0.4 mumol . min-1 . 100 g-1) and TUDC (0.6 mumol . min-1 . 100 g-1) resulted in drastic (8- to 20-fold) decreases in excretion of these enzymes and albumin compared with respective values in rats infused with TCDC alone. Similar preventive effects were observed with the addition of TUDC to the infusion of TC (1.2 mumol . min-1 . 100 g-1). These results suggest that the hepatic cytotoxic effects of TC and TCDC can be prevented by the simultaneous infusion of TUDC in rats.

5'-Nucleotidase↗

Evaluation of left ventricular function using digital subtraction angiography.

To evaluate function of the left ventricle and myocardial perfusion images, digital subtraction angiography (DSA) was performed in 45 patients with ischemic heart disease. Validity of the technique was compared with data obtained from cine left ventriculogram in all patients and 201 T1 myocardial images in 20 patients. End-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) calculated from DSA were correlated closely with those from cine left ventriculogram (r = 0.92, r = 0.94 and r = 0.86, respectively). Regional contractility at the antero-lateral wall of the left ventricle, assessed by DSA, was also correlated well with cine left ventriculogram (r = 0.75). Evaluation of the inferior wall motion showed less correlation in both procedures (r = 0.68). Phase and amplitude analysis with the same technique with radionuclide cardiac angiography was successfully applied in left ventriculogram obtained by DSA. The procedure seems to be helpful for objective evaluation of the left ventricular wall motion. Myocardial perfusion image, obtained with modified Radtke's technique, showed good coincidence with 201 T1 images. Thus, DSA is applicable for evaluation of function of the left ventricle and myocardial perfusion in patients with ischemic heart disease.

Angina Pectoris↗

Comparative studies on antitumor activity of Klebsiella O3 lipopolysaccharide and its polysaccharide fraction in mice.

The antitumor activity of the polysaccharide fraction (OPS) obtained by the acid hydrolysis of Klebsiella O3 lipopolysaccharide (KO3 LPS) isolated from the culture supernatant of the decapsulated mutant strain LEN-1 (03: K1-) against both allogeneic tumor and syngeneic tumor systems in mice was compared with that of KO3 LPS. OPS prolonged the life span of MM2-bearing C3H/He mice by intraperitoneal (i.p.) pre- and post-treatment at the doses of 100 and 1000 mg/kg. However, large amounts of OPS were needed to show the antitumor activity as compared with KO3 LPS. OPS showed no growth inhibitory activity against Meth-A sarcoma in BALB/c mice by i.p., intravenous (i.v.) or intratumoral (i.t.) administration. When 1000 mg/kg of OPS was i.p. administered once a day for 10 days, OPS significantly inhibited the tumor growth of Sarcoma-180 solid type tumor. On the other hand, KO3 LPS significantly suppressed the growth of Meth-A tumor by i.t. administration at the doses of 0.3 and 1.0 mg/kg and showed complete regression in 8 and 9 out of 10 mice, respectively. In MM2 tumor, KO3 LPS also showed complete regression in all mice post-treated by i.p. administration at the dose of 1.0 mg/kg. These results suggest that OPS has antitumor activity on the tumors used in this study, but the activity was less than that of KO3 LPS.

Animals↗

Growth hormone responses to growth-hormone-releasing hormone and thyrotropin-releasing hormone in diabetic patients with and without retinopathy.

Growth hormone (GH) responses to growth-hormone-releasing hormone (GRH) and thyrotropin-releasing hormone (TRH) were studied in 17 diabetic patients. Ten patients (group 1) had retinopathy corresponding to stage III-V (Scott's classification), and the remaining seven patients (group 2) had no retinopathy despite longer duration of diabetes in comparison with the patients in group 1. There were no differences in age, percent of ideal body weight, and serum HbA1 levels between the two groups. Basal serum GH levels were 1.9 +/- 0.4 ng/ml (mean +/- SEM) in group 1, and not different from the values in group 2 (1.6 +/- 0.7 ng/ml). However, GH responses to synthetic human GRH-44 (1 micrograms/kg body wt, i.v. bolus) were significantly greater in group 1, as judged by the maximal response or integrated GH secretion after the administration of GRH. There were no differences in serum insulin-like growth factor I (IGF-I) levels between group 1 (262 +/- 35 ng/ml) and group 2 (232 +/- 30 ng/ml), and no significant correlation was found between serum IGF-I levels and GH responses to GRH in either of the two groups. Paradoxical GH responses to TRH (500 micrograms, i.v. bolus) were found in only one patient in each group. We have thus demonstrated that GH responses to GRH are more pronounced in diabetic patients with retinopathy than in patients without this complication, although it remains to be determined whether or not greater GH responses to GRH are causally related to the development of diabetic retinopathy.

Blood Glucose↗