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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 1,189 records · Page 66Linked to original sources

C3b receptor (CR1) on erythrocytes in various diseases.

Complement receptor for C3b (CR1) on erythrocytes was investigated in various diseases by immune adherence hemagglutination (IAHA) using aggregated human IgG. In normal controls, 21 out of 312 (6%) revealed defective CR1 reactivity, and there was no difference in the prevalence of defective CR1 reactivity between female (11/157, 7%) and male (10/155, 6%). Among diseases examined significantly high prevalence of defective reactivity of CR1 on erythrocytes was seen in systemic lupus erythematosus (SLE) (22/30, 73%) and malignancy of hematopoietic system, especially in acute myelogenous leukemia (AML)(6/11, 55%).

Connective Tissue Diseases↗

Rationale for a novel immunotherapy of cancer with allogeneic lymphocyte infusion.

A simple method of cancer immunotherapy has been developed which achieves marked objective response in 20-30% of patients with disseminated disease. Each course consists of a low dose of chemotherapy followed two days later by intravenous infusion of allogeneic lymphocytes. Courses are repeated on a monthly basis as needed. The function of the chemotherapy--too mild to significantly influence tumor growth directly--appears to be depletion of suppressor T cells, which sensitizes the patient to the immunostimulant action ("allogeneic effect") of the subsequently infused lymphocytes. The rationale for this method is discussed in the context of a review of past attempts at lymphocyte immunotherapy. We are now attempting to improve response rates by combatting anergy with nutritional immunopotentiators, and by preventing prostaglandin-mediated or -dependent immunosuppression with prostaglandin synthetase inhibition. By understanding and counteracting the various specific and general means by which a growing tumor induces host tolerance, it should prove possible to achieve immune-mediated tumor regression in a high proportion of patients. Best results may be seen when allogeneic lymphocyte therapy is initiated at an earlier stage of the disease, and is used in conjunction with surgery, radiotherapy, short-course intensive chemotherapy, or hyperthermia-based methods.

Combined Modality Therapy↗

Meningoencephalitis due to serratia marcescens infection in neonates.

Six autopsy cases of Serratia meningoencephalitis were reported. The symptoms of this infection become apparent at an early stage in neonates; the meningoencephalitis in these six cases was severe, with or without inflammatory lesions in other organs. Serratia marcescens was originally described as a nonpathogenic organism; however, it is believed that after entering the blood stream of neonates, it becomes pathogenic, especially to the central nervous system. Meningoencephalitis due to Serratia marcescens is very severe and takes a rapid and progressive course against which no antibiotics have been found effective. Prevention of this infection is therefore considered of crucial importance.

Cerebrospinal Fluid↗

Islet-activating protein (IAP)-induced adrenergic modulation of pancreatic A and B cell in dogs.

Islet-activating protein (IAP) is a substance purified from the culture medium of Bordetella pertussis, and its main action is characterized by the enhancement of secretory response to glucose and other stimuli in pancreatic islet. In this experiment, the effect of IAP on epinephrine-induced secretion of immunoreactive insulin (IRI) and glucagon (IRG) was investigated in normal dogs. Epinephrine suppressed IRI secretion and it had a little increment to IRG secretion in control group, while IRI and IRG secretions were significantly increased by epinephrine in IAP pretreated group. Using beta-blocker (Propranolol) with epinephrine, these increments of IRI and IRG secretions in IAP pretreated group were abolished. However, using alpha-blocker (Phentolamine) with epinephrine, these secretions of IRI and IRG in IAP pretreated group were much more increased than epinephrine alone induced secretions. Blood glucose levels were lower in IAP pretreated group than in control group throughout the loading tests in all of the experiments. These findings suggest that (1) IAP decreases blood glucose level and (2) IAP enhances epinephrine-induced secretion of insulin and glucagon by acceleration of beta-adrenergic effect and by reduction of alpha-adrenergic suppression in dogs.

Animals↗

Chromosome aberrations induced by 7,12-dimethylbenz[a]-anthracene in bone marrow cells of spontaneously hypertensive rats (SHR) and control Wistar Kyoto (WKY) rats: time course and site specificity.

The frequency of chromosome aberrations (CA) induced by iv injection of 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6] was examined with the use of control Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). SHR appear to be analogous to hypertensive humans, since evidence has been reported of a difference in tumor susceptibility between SHR and WKY strains. Injection of DMBA evoked CA in bone marrow cells of both SHR and WKY rats. The frequency of CA in SHR was significantly higher than in WKY rats at 12 and 18 hours after DMBA treatment. With regard to the relative frequencies of aberrations in SHR and WKY rats, chromosomes 1 and 2 were more susceptible to DMBA-induced CA. The proportion of breaks that occur in the "hot spot" at 6 hours after DMBA treatment was distributed nonrandomly at a site approximately 40% of the total length from the centromere in chromosome 1 and at lengths of approximately 30 and 55% in chromosome 2. The specific distribution of CA seemed to be caused by a cell cycle-specific effect. These results, confirming nonrandom CA induced by DMBA in bone marrow cells of WKY rats, are similar to previous reports in which Long-Evans rats were used. Thus they indicate that a common mode of action by DMBA at the chromosome level in rat bone marrow cells was observed in different strains and that SHR were more sensitive than WKY rats to CA induced by DMBA.

9,10-Dimethyl-1,2-benzanthracene↗

Occurrence of galactosamine-6-phosphate as a constituent of Bacillus megaterium spore coat.

Galactosamine-6-phosphate was identified as a component of the coat of the Bacillus megaterium QM B1551 spore. It was one of the main constituents of the outermost layer of the spore coat, but it was absent from the other integuments including the cortex. These findings suggest that galactosamine-6-phosphate comprises the phosphorus-containing skeleton structure of the spore coat.

Bacillus megaterium↗

Platelet cyclo-oxygenase deficiency in a Japanese.

A case of platelet cyclo-oxygenase deficiency in a Japanese was investigated. There was a marked decrease of aggregation with collagen and absence of aggregation with epinephrine and arachidonic acid. The platelet response to a labile aggregation stimulating substance (LASS) was normal. There was no biosynthesis of prostaglandin endoperoxides from arachidonate. The platelets, including granular volume, showed no ultrastructural abnormalities. The responses to various inducers of platelet aggregation, except for arachidonate, were different from the cases described by others. It is concluded that the defective platelet function, due to a deficiency of platelet cyclo-oxygenase, is heterogeneous.

Adult↗

Effect of low dosage of interferon on natural killer activity in patients with HBsAg-positive chronic active hepatitis.

The effect of human leukocyte interferon (IFN) on natural killer (NK) activity in 7 patients with HBsAg-positive chronic active hepatitis was investigated. Human leukocyte IFN was intramuscularly given once a week for 4 consecutive weeks (10 X 10(5), 5 X 10(5), 2 X 10(5) and 1 X 10(5) U). 1 week after the initial injection, NK activity showed a significant rise compared with the preinjection levels (p less than 0.001) and remained elevated during the 1-month treatment, while it fell after the cessation of IFN therapy. 4 of 5 patients showed a marked decrease in Dane particle-associated DNA-polymerase activity. Serum HBeAg disappeared in 3 of 6 patients and serum transaminase levels markedly improved in all patients. Only a transient reduction in HBsAg was observed in 2 patients after the treatment period. The findings indicate that a low dosage of human leukocyte IFN such as 18 X 10(5) U, administered in decreasing doses, enhances NK activity in patients with HBsAg-positive chronic active hepatitis, and that the effect of IFN is involved in the immune mechanisms associated with natural cytotoxicity.

Adult↗

Selective inhibition of type I collagen synthesis in osteoblastic cells by epidermal growth factor.

We have investigated the effect of epidermal growth factor (EGF) on collagen metabolism in clonal MC3T3-E1 cells, an osteoblastic cell line derived from newborn mouse calvaria. EGF significantly increased DNA synthesis, but decreased collagen production. We analyzed the amount of total collagen synthesis and degradation products of collagen together with the level of the enzyme responsible for extracellular collagen degradation, to investigate whether the decreased collagen production was due to a decrease in total collagen synthesis or to an increase in collagen degradation. Total collagen synthesis, determined by total hydroxyproline synthesized, was significantly decreased in cells cultured in medium containing EGF, but the amount of collagen degradation products and the level of animal collagenase activity were not increased. Analysis of the collagen type produced by the cells in the absence of EGF showed that 95% of the collagen recovered was type I and 3% was type III. The decreased level of collagen accumulated by cells cultured in the presence of EGF was explained only by the decreased rate of type I collagen synthesis. These results indicate that EGF selectively inhibits type I collagen synthesis in the clonal osteoblastic cell line, MC3T3-E1.

Animals↗

Assessment of viable myocardium within infarct zone by exercise thallium-201 scintigraphy.

The viability of the myocardial regions corresponding to pathologic Q waves was evaluated. Thirty-four patients with prior myocardial infarction underwent serial thallium-201 scintigraphy during treadmill exercise testing. On the delayed images, 8 of the initial 85 segmental defects (8 patients, 9%) showed total redistribution (RD) and 11 (6 patients, 13%) showed partial RD. In contrast, 66 segments showed persistent defect. The segments with total RD were more likely to be associated with normal or hypokinetic wall motion than the segments with persistent defect (p less than 0.05). Six of the 38 segments (13%) with collateral vessels showed total RD and 10 (21%) showed partial RD. However, 35 of 38 segments (92%) without collateral vessels showed persistent defect. There was a significant difference (p = 0.02) in myocardial thallium uptake patterns when the segments with and without collateral vessels were compared. It is concluded that (1) exercise-induced thallium RD may occur in patients with prior myocardial infarction, and myocardial infarct regions with total RD are highly associated with good contractility; these suggest the presence of viable but jeopardized myocardium within the infarct zone, and (2) collateral vessels may play a role in limiting infarct size.

Adult↗

Immune responsiveness and phagocytic activity of macrophages in streptozotocin (SZ)-induced diabetic mice.

We succeeded in inducing different severities of diabetic state in C3H male mice by repeated intraperitoneal injections of various doses of SZ. SZ-induced diabetic mice were divided into four groups as follows: Group A, B, C and D. SZ, respectively, 3, 5 doses of 45 mg/kg, 5 doses of 60 mg/kg on consecutive days and one of a dose of 200 mg/kg BW. The degree of hyperglycemia and glycosuria were mild in group A and D. Group B was moderate and group C severe with ketonuria and loss of body weight. We investigated the immune response to anti-sheep red blood cells (SRBC) and the phagocytic activity of macrophages in the above mentioned various SZ-induced mice. Antibody forming activities (values of anti-SRBC plaque-forming cells (PFC) and serum agglutinin) were markedly depressed in all of SZ-diabetic groups. The degree of the suppression of antibody response to SRBC in SZ-diabetic mice corresponded with the severity of the diabetic state (C greater than B greater than A = D). However, the phagocytic activity of peritoneal macrophages in SZ-diabetic mice was as high as or higher than that in normal controls, using both latex beads and immune complex as test particles. Moreover, we observed that insulin treatment reversed the defect in the immune response in SZ-diabetic mice. These results indicate that the phagocytic activity of peritoneal macrophages was retained but the antibody response was impaired in the SZ-diabetic mice, and this suggested that the impaired antibody response may be a contributing cause of increased susceptibility to infections in a diabetic state.

Animals↗

A simple and sensitive method for determination of human urinary kallikrein activity (kininogenase activity), using human low molecular weight kininogen.

Human low molecular weight kininogen was partially purified and applied to the measurement of human glandular kallikrein as a substrate. The prepared human low molecular weight kininogen did not contain any significant amounts of kinin generating or destroying enzymes. When ethanol was added to the assay tube to stop the enzyme reaction, the substrate was almost completely removed from the incubation solution. Moreover, less than 1.25% ethanol had no effect on the kinin radioimmunoassay. These data suggest that the measurement of generated kinin can be done directly after the addition of ethanol. In this assay system, control tubes were unnecessary since the small volume of the urine samples (0.5 to 2.0 nl) contained negligible amounts of endogenous kinin. In a comparison of the availability as a substrate for human urinary kallikrein among human, dog and bovine low molecular weight kininogens, the enzyme activity was 5 or 100 times as high in the human substrate as in the dog and bovine substrates, suggesting that a human substrate is best for the human enzyme. A significant correlation was found between our previous method using bovine substrate and this method for human urinary kallikrein activity. In both methods, urinary kallikrein excretions were significantly lower in patients with essential hypertension and higher in those with primary aldosteronism, respectively. This simple, specific and sensitive kininogenase assay system seems to be very useful for investigating the physiological or pathophysiological role of the renal kallikrein-kinin system in hypertensive and renal diseases.

Animals↗

Cephabacins, new cephem antibiotics of bacterial origin. IV. Antibacterial activities, stability to beta-lactamases and mode of action.

Cephabacin F group antibiotics with a 7-formylamino substituent showed antibacterial activity against a wide variety of bacteria including beta-lactamase-producing clinical isolates and anaerobic bacteria. Cephabacin H group antibiotics without the substituent showed more potent activity against Gram-positive bacteria than cephabacin F group antibiotics, but were not active against Gram-negative bacteria producing beta-lactamases. Cephabacin F group antibiotics were highly resistant to hydrolysis by various types of beta-lactamases and showed strong inhibitory activity against a cephalosporinase of Proteus vulgalis GN 4413 due to the 7-formylamino substituent. Mode of action of cephabacin F1 and H1 was examined using Escherichia coli and Bacillus subtilis as the test organisms. They showed strong lytic activity against these organisms and inhibited their peptidoglycan synthesis. Cephabacin F1 had the highest affinity for penicillin-binding protein (PBP) 1 in E. coli and PBP 4 in B. subtilis. Cephabacins showed a protective effect in experimentally infected mice.

Bacteria↗

Relevance of in vitro antibacterial activities and pharmacokinetic properties of antipseudomonal beta-lactam antibiotics to their therapeutic effects on urinary tract infection caused by Pseudomonas aeruginosa P 9 in mice.

The therapeutic effects of seven antipseudomonal beta-lactam antibiotics on experimental urinary tract infection caused by Pseudomonas aeruginosa P 9 in mice were compared, and the results were analyzed in relation to their in vitro antibacterial activities and pharmacokinetic properties. The CD50 values were (mg/kg): cefsulodin, 6.19; cefoperazone, 162; sulbenicillin, 167; ticarcillin, 184; azlocillin, 121; mezlocillin, 390; and piperacillin, 227. Cefsulodin was more active than the other antibiotics not only in therapeutic effects but also in in vitro antibacterial effects evaluated according to growth inhibitory, bactericidal, and bacteriolytic activities. It also penetrated and persisted well in the kidney of mice. The therapeutic effects of cefoperazone, azlocillin, and piperacillin were much less than expected from their in vitro antibacterial activities; the CD50 values were more than 18-fold as large as that of cefsulodin, whereas the differences of their MIC values were less than four-fold.

Animals↗