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Biomedical subjects

M Hiruma

Publications and source records attributed to M Hiruma.

At least 91 records · Page 5Linked to original sources

The complement system in ischemic heart disease.

The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p less than 0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p less than 0.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r = 0.71) and inversely related to the ejection fraction (r = -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated.

Angina Pectoris↗

Polymyositis in mice experimentally inoculated with Getah virus.

Mice inoculated intracerebrally with parent, large-plaque (LP) and small-plaque (SP) strains of Kanagawa strain of Getah virus showed clinically recumbency and paralysis. The LP strain caused recumbency more rapidly and killed mice more early after inoculation than the parent and SP strains. Microscopically, skeletal muscles of the whole body were involved showing degenerative or inflammatory changes. In mice inoculated with the parent or SP strains, there were degeneration and necrosis of the muscle fibers with inflammatory cell infiltration and regenerative reaction. The lesions were particularly conspicuous in muscles of the hind legs. In mice inoculated with the LP strain, most of the muscle fibers revealed degeneration and necrosis, but reactive changes were poor. In addition, the periosteum and muscular connective tissue were thickened with karyorrhexis. Electron microscopically, virus particles were recognized mainly in cisternae of sarcoplasmic reticulum in skeletal muscle fibers of mice inoculated with the LP strain, while they were rare in those of animals injected with the parent and SP strains. From these finding, it was suggested that Kanagawa strain of Getah virus has the virulence to skeletal muscles of mice.

Alphavirus↗

[A case of systemic lupus erythematosus associated with cryptococcal meningitis which was successfully cured by the administration of massive dose of amphotericin B].

A case of SLE with moderately deteriorated renal function due to lupus nephritis developed cryptococcal meningitis. Long term administration of amphotericin B (cumulative dose 5 g) combined with 5-flucytosine eradicated this fungal infection. Throughout amphotericin B administration urinary excretions of Na and K, as well as plasma HCO3 concentration were monitored, and, Na, K and HCO3 were supplemented orally and intravenously so much as to replace their urinary losses. Neither prominent water-electrolyte disturbance nor severe azotemia, which are the most serious side effects of amphotericin B, did not ensue. This case study indicates that sufficient water.electrolytes supplementation is important to prevent the nephrotoxicity of amphotericin B.

Adult↗

Skin typing, sun exposure, and sunscreen use in a population of Japanese.

Distribution of Japanese skin types (JSTs), sun-exposure habits, and sunscreen use were surveyed in 379 new outpatients. The largest number of subjects belonged to JST class J-II (65%), J-I was second (24%), and J-III was third (11%). Eighty-eight percent of those studied had occasional or habitual sun exposure during the summer, and many were exposed for more than three hours per exposure day (80% of those with occasional exposure; 62% of those with habitual exposure). More younger persons had occasional sun exposure than older persons. More males had habitual sun exposure than females. Sunscreens were used by 41% of the subjects, but 77% of these used them without accurate understanding of the definition of the sun protection factor. More J-I subjects used sunscreens than J-II and J-III subjects. More females than males used them.

Adolescent↗

Effect of immunization and potassium iodide on polymorphonuclear leukocyte chemiluminescence in experimental murine sporotrichosis.

This study was undertaken to examine the effects of immunization with Sporothrix schenckii and oral potassium iodide (KJ) administration on the chemiluminescence (CL) response of mouse polymorphonuclear leukocytes (PMNs) in experimental murine sporotrichosis. When N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) particles were used as foreign bodies to be phagocytosed, the time to the peak CL response of the PMNs in an immunized group was shortened in comparison with a non-immunized control group, and the CL intensity was found to be prolonged. Whereas administration of KJ resulted in a reduction of the CL intensity in non-immunized mice, in immunized mice it caused a rise in CL intensity. When the foreign bodies used as targets for phagocytosis were Sp. schenckii, changes similar to the above occurred, but CL production was reduced.

Animals↗

Modification of glycosylation of renin in sodium-depleted and captopril-treated rats.

Concanavalin A (con A) chromatography of rat plasma revealed the presence of three differently glycosylated forms of renin, including the con A unbound form (renin C), the loosely bound form (renin A), and the tightly bound form (renin B). Rat renal cortical slices in vitro secreted all these forms. They had a different half-life in the plasma after ligation of both renal artery and vein (half-life of 21 +/- 1, 14 +/- 3, and 35 +/- 4 min for renin A, B, and C, respectively). Thus differently glycosylated forms of renin are released from the kidney into the blood circulation and disappear, with a different half-life. Rats were sodium-depleted and captopril-treated (40-60 mg.kg-1.day-1) for 2 wk, and the effects of these treatments on relative proportions of renin A, B, and C were investigated. These treatments elevated plasma renin concentration approximately 60-fold (from 24 +/- 3 to 1,406 +/- 128 ng angiotensin I.h-1.ml-1; P less than 0.01), in association with an increase in the relative percent of renin C in the plasma from 22 +/- 2 to 39 +/- 3% (P less than 0.01). Moreover, the relative proportion of renin C released from the renal cortical slices was significantly higher in the treated than in the control rats (42 +/- 9 vs. 16 +/- 3% of secreted renin, respectively; P less than 0.02). These results show that the predominant release of renin C, with the longest half-life (35 min) in the plasma, contributes to the increased plasma renin concentration in sodium-depleted and captopril-treated rats.

Animals↗

[Use of fosfomycin tablets in the treatment of purulent skin diseases].

Fourteen patients with purulent skin diseases were treated orally with fosfomycin (FOM) 1.5-3 g in the tablet form for 1 week to determine its efficacy and safety. The results obtained are summarized as follows. 1. The clinical efficacy rate was 71.4%. A bacteriological eradication rate of 71.4% was obtained. 2. As adverse reactions 3 patients experienced diarrhea and abdominal pain. But in all of these patients, symptoms were relieved with a reduction in dosage. 3. Taking the efficacy and the safety into account, utility rate was assessed to be 71.4%. From these results it is considered that FOM tablets are useful equally to conventional FOM capsules.

Adolescent↗

Heterogeneity of glycosylation of circulating active and inactive renin.

Concanavalin A chromatography was used to examine rat plasma and the incubation medium of rat renal cortical slices, the objective being to assess the heterogeneity of glycosylation of active and inactive renin. Inactive renin was measured by activation with trypsin. Concanavalin A chromatography could separate both active and inactive renin in the plasma into three forms, including the unbound form, the loosely-bound form and the tightly-bound form, thereby suggesting the presence of differently glycosylated forms of active and inactive renin in the plasma. Rat renal cortical slices secreted all these three forms of active and inactive renin, hence these forms are mainly of renal origin. These results suggest that differently glycosylated forms of active and inactive renin are released from the kidney into the blood circulation.

Animals↗

Differently glycosylated multiple forms of renin in the blood circulation of rats.

Serial lectin chromatography of rat plasma on concanavalin A and lentil lectin columns separated plasma renin into differently glycosylated multiple forms. To study the role of glycosylation in the clearance of circulating renin, three different forms of glycosylated renin (renin A, B-1 and B-2) were highly purified from rat kidneys. Renin A and B-1 were loosely and tightly, respectively, bound to concanavalin A, but did not bind to lentil lectin. Renin B-2 was bound to both concanavalin A and lentil lectin. Each form of renal renin, labelled with 125I and intravenously given to rats, disappeared from the blood circulation at different rates, and distributed in the liver and kidney to different extents. Deglycosylation of renin B-1 with endoglycosidase F led to reduced metabolic clearance rates and to a significant decrease in uptake by the liver. These results show the heterogeneity in the fate of circulating renin due to the heterogeneity of glycosylation.

Animals↗

Importance of glycosylation for hepatic clearance of renal renin.

Three differently glycosylated forms of renin (renin A, B-1, and B-2) were highly purified from rat kidneys by pepstatin-aminohexyl-Sepharose affinity chromatography and by serial lectin affinity chromatography on concanavalin A (con A) and lentil lectin-Sepharose, and the role of glycosylation of renin was investigated. Renin A and renin B-1 were loosely and tightly bound to con A, respectively, but did not bind to lentil lectin. Renin B-2 bound to both con A and lentil lectin. These three forms of renin were all similar in their physicochemical characteristics, including molecular weight, isoelectric point, specific activity, Km, optimum pH, and antigenicity. Each form of renin, labeled with 125I and given intravenously to anesthetized rats, disappeared from the circulation at different rates (metabolic clearance rates of 5.05 +/- 1.02, 17.1 +/- 2.5, and 36.0 +/- 4.1 ml.min-1.kg-1 for renins A, B-1, and B-2, respectively). Labeled renin A distributed to a similar extent in the liver and kidney (21.2 +/- 0.2 and 15.2 +/- 0.8% of the injected dose, respectively), whereas renins B-1 and B-2 were distributed predominantly in the liver (56.3 +/- 1.2 and 72.3 +/- 3.7% of the injected dose, respectively) and to a lesser extent in the kidney (4.3 +/- 0.3 and 2.1 +/- 0.2%, respectively). Deglycosylation of renin B-1 with endoglycosidase F resulted in no loss of its enzymatic activity or antigenicity but greatly reduced the metabolic clearance rate to 18% (from 17.1 +/- 2.5 to 3.09 +/- 0.17 ml.min-1.kg-1). Deglycosylation of renin B-1 greatly decreased its uptake by the liver (from 56.3 +/- 1.2 to 3.3 +/- 0.2%) and increased its uptake by the kidney (from 4.3 +/- 0.3 to 23.9 +/- 0.9%). These studies indicate the importance of glycosylation of renin for its hepatic uptake and metabolic clearance rate.

Animals↗

Fate of recombinant human renin administered exogenously to anesthetized monkeys.

Highly purified recombinant human renin (rh-renin), synthesized by Chinese hamster ovary cells, was labeled with iodine-125 and was given intravenously to pentobarbital-anesthetized common marmosets (Callithrix jacchus) to study the fate of the circulating renin. Specific anti-rh-renin antiserum was used to identify the 125I-rh-renin. Plasma disappearance of the exogenously administered 125I-rh-renin in marmosets (n = 6) showed two exponential components, with a half-life of 12.1 +/- 1.9 minutes for the rapid component and 120.3 +/- 16.4 minutes for the slow component. The metabolic clearance rate was 1.17 +/- 0.26 ml/min/kg. Thirty minutes after the injection of 125I-rh-renin, 43.1 +/- 0.9 and 3.5 +/- 0.5% of the injected dose had distributed to the liver and the kidneys, respectively. With time, the accumulated 125I-rh-renin in the liver and kidneys decreased. The accumulation of 125I-rh-renin was less than 1% of the dose injected in other organs such as lungs, heart, spleen, adrenal glands, testes, and ovaries. Analysis of liver and kidney extracts by high performance liquid chromatography at 30 and 120 minutes indicated that immunoreactive 125I-rh-renin decreased with time and was accompanied by an increase in nonimmunoreactive degradation products of a low molecular weight. The incubation of 125I-rh-renin with monkey or human plasma at 37 degrees C did not degrade the labeled renin. Therefore, rh-renin was rapidly cleared from the circulation by the liver and the kidney.

Anesthesia↗

Tinea faciei caused by Microsporum canis in a newborn.

A case of tinea faciei caused by Microsporum canis in a 14-day-old infant is reported. The incubation period was seen to be 1 week. This was a familial infection which also affected the infant's grandmother and their pet cat and dog. Topical treatment with clotrimazole controlled the infection in the baby. A review of 14 cases (including our own) of dermatophytosis in newborn infants reported in the Japanese literature showed that newborn infants might be infected by several of these agents.

Animals↗

Ultrastructural study of tissue reaction of mice against Sporothrix schenckii infection.

In the present study, in order to clarify the defense mechanisms against S. schenckii infections, we examined the tissue reactions of mice against the pathogen over a period of time by both light and electron microscopy. The histological features were, at an early stage, a mixed cell granuloma consisting of polymorphonuclear leukocytes (PMNs) and macrophages, and, later on, enlargement and vacuolation of the macrophages at the periphery. In electron microscopy, blastospores had been phagocytized by the PMNs and macrophages, and no extracellular blastospores were seen. PMNs taking up blastospores were phagocytized by other PMNs or by macrophages. After 3 or 4 months, the phagosomes of the macrophages had grown in size, and contained a number of blastospores. During the experiment, the ultrastructure of the blastospores was well preserved, and their viability was considered high. Of the defense mechanisms against S. schenckii infection, PMN phagocytosis is of great importance, but the fact that proliferation of this organism was observed within the macrophages, suggested that the macrophages were not able to destroy the organisms, but rather were responsible for the disease becoming chronic.

Animals↗

Ultrastructure of Sporothrix schenckii treated with iodine-potassium iodide solution.

The ultrastructural changes produced by iodine-potassium iodide solution on yeast cells of Sporothrix schenckii were investigated by transmission electron microscopy in order to clarify the mechanism of oral potassium iodide therapy for sporotrichosis. Yeast cells were dipped with solutions containing various concentrations of iodine. The rate of germination decreased markedly between the range of iodine concentrations from 0.63 microgram/ml to 5.0 micrograms/ml. No significant ultrastructural changes were seen at the concentration of the iodine of 1.25 microgram/ml (80% germination) or less. In the concentration of 2.5 micrograms/ml (50% germination), normal cells and degenerated cells coexisted. When the cells were treated with 5.0 micrograms of iodine per ml (0% germination) or more, their interior structures were completely destroyed. It is assumed that iodine treatment of the organism causes rapid destruction in the whole cell.

Iodine↗