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Biomedical subjects

S Harada

Publications and source records attributed to S Harada.

At least 379 records · Page 21Linked to original sources

Arterial baroreflex dynamics in normotensive and spontaneously hypertensive rats.

To investigate dynamic or frequency-dependent characteristics of arterial baroreflex control of efferent sympathetic nerve activity in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), we assessed the transfer function from aortic pressure (AP) to renal sympathetic nerve activity (RSNA) using a "white-noise technique." In pentobarbital sodium-anesthetized rats, we recorded RSNA as the output, while AP was randomly perturbed to impose input pressure changes with broad frequencies. We calculated the transfer function from AP to RSNA over the frequency range of 0.01-5 Hz through the spectral analysis of the input and output. The results indicated that the gain, phase shift, and coherence of the transfer function for SHR and for WKY were similar and statistically indistinguishable. The gain was relatively constant below 0.05 Hz but increased steadily by fivefold as frequency increased in the frequency range of 0.05-0.8 Hz. The phase was out of phase where coherence was high. The coherence was high (greater than 0.5) in the frequency range of 0.04-0.8 and 1.00-1.03 Hz but was low in other frequencies. These results suggest that dynamic or frequency-dependent characteristics of arterial baroreflex control of RSNA were not altered in SHR as compared with WKY.

Animals↗

Inefficient transmission of HTLV-I to MOLT-4 cells by cell-free virus and cocultivation.

Transmission of human T cell leukemia virus type I (HTLV-I) to a T cell line (MOLT-4#8) was studied using cell-free virus infection or cocultivation with an HTLV-I-transformed T cell line (MT-2). Immunofluorescence and FACS analyses showed that HTLV-I was efficiently adsorbed onto MOLT-4#8 cells. However, after adsorption, no extrachromosomal viral DNA in the cells was detected by the Southern blot method. In contrast, when MT-2 cells were cocultured with MOLT-4#8 cells, generation of extrachromosomal DNA was clearly observed. These data suggest that the cell-free HTLV-I may have difficulties in penetration, uncoating or reverse transcription. After cocultivation, MOLT-4#8 cells chronically infected with HTLV-I were cloned and analyzed. Only four provirus-positive cell lines were obtained. The transmission rate of the virus by cocultivation seemed to be low in our experimental system, although marked cell fusion was observed. Moreover, none of the cloned cell lines which harbored HTLV-I provirus expressed any viral protein. Inefficient integration and expression of the provirus might be hypothesized as compared with human immunodeficiency virus type 1 transmission.

Cell Fusion↗

Effects of OPC-21268, an orally effective vasopressin V1 receptor antagonist in humans.

An orally effective, nonpeptide vasopressin V1 receptor antagonist, OPC-21268 was produced for possible human use. We investigated the effects of OPC-21268 on the vascular effects of intra-arterially infused arginine vasopressin in human forearm vessels. The brachial artery was cannulated for drug infusions and direct measurement of arterial pressure. Forearm blood flow was measured by a strain gauge plethysmograph, and forearm vascular resistance was calculated. Arginine vasopressin was infused intra-arterially at doses of 0.02, 0.06, 0.09, 0.2, 0.6, and 1.2 ng/kg/min. The lower doses of arginine vasopressin increased, whereas the higher doses of arginine vasopressin decreased forearm vascular resistance (p less than 0.01). Intra-arterial infusion of phenylephrine at doses of 0.2, 0.4, and 2.4 micrograms/min increased forearm vascular resistance dose-dependently (p less than 0.01). OPC-21268 (50 mg for two, 100 mg for six, and 200 mg for two subjects) given orally did not alter resting arterial pressure, forearm vascular resistance, or heart rate. OPC-21268 decreased vasoconstrictor responses to arginine vasopressin at doses of 0.02 (p less than 0.02) and 0.09 (p less than 0.05) ng/kg/min and augmented vasodilator responses to arginine vasopressin at a dose of 1.2 ng/kg/min (p less than 0.01). However, the vasoconstrictor responses to phenylephrine were not altered by OPC-21268. These results demonstrated that OPC-21268 effectively and specifically antagonized the V1 receptor-mediated vasoconstriction in human forearm resistance vessels. These results suggest that OPC-21268 may be useful therapeutically to antagonize the vasoconstriction caused by arginine vasopressin in some pathological states.

Administration, Oral↗

Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients.

Animal studies suggest that some angiotensin converting enzyme inhibitors augment endothelium-dependent vasorelaxation. We aimed to determine if captopril augments endothelium-dependent vasodilation in middle-aged hypertensive patients. By using strain-gauge plethysmography, forearm vasodilation evoked with intra-arterial acetylcholine (4, 8, 16, and 24 micrograms/min) or nitroprusside (0.2, 0.4, 0.8, and 1.2 micrograms/min) was examined before and after captopril administration (25 mg per os). Before captopril, forearm vasodilation with acetylcholine was less in hypertensive patients (n = 12) than in age-matched (n = 7) or young (n = 7) normotensive subjects, but forearm vasodilation with nitroprusside did not differ among the three groups. Captopril improved forearm vasodilation in hypertensive patients (n = 7) with acetylcholine but nitroprusside did not. In contrast, nifedipine (10 mg per os) did not alter forearm vasodilation with acetylcholine or nitroprusside in hypertensive patients (n = 5). The decreases in mean blood pressure caused by captopril and nifedipine in hypertensive subjects were comparable. Captopril did not alter forearm vasodilation with acetylcholine or nitroprusside in young normotensive subjects (n = 7). These results suggest that captopril in hypertensive patients may acutely improve impaired endothelium-dependent forearm vasodilation that does not result from reduction in blood pressure per se.

Acetylcholine↗

Effects of L-arginine on forearm vessels and responses to acetylcholine.

This study was designed to investigate the effects of L-arginine (the substrate of endothelium-derived nitric oxide) in human forearm vessels. We examined whether intra-arterial infusion of L-arginine dilated forearm vessels and augmented vasodilatory responses to acetylcholine in young, healthy humans. The left brachial artery was cannulated for drug infusions and direct measurement of arterial pressure. Forearm blood flow was measured by a strain gauge plethysmograph. Intra-arterial infusions of L-arginine at 10, 20, 40, and 60 mg/min increased forearm blood flow from 4.7 +/- 0.6 to 4.9 +/- 0.5, 5.7 +/- 0.5, 7.2 +/- 0.8, and 8.2 +/- 0.9 ml.min-1.100 ml-1, respectively (n = 8, p less than 0.01), whereas D-arginine at the same doses did not alter forearm blood flow (n = 7). Intra-arterial infusions of acetylcholine (n = 7) (4, 8, 16, and 24 micrograms/min) and sodium nitroprusside (n = 5) (0.2, 0.4, 0.8, and 1.2 micrograms/min) increased forearm blood flow dose dependently (p less than 0.01 for both). Arterial pressure was not altered with infusions of these drugs. Responses to acetylcholine were augmented with simultaneous intra-arterial infusion of L-arginine at 10 mg/ml (p less than 0.01) but not with D-arginine. Responses to sodium nitroprusside were not altered by L-arginine. These results in human forearm resistance vessels support the notion that vasodilation induced by acetylcholine is a result of the conversion from L-arginine to endothelium-derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Dose-dependent enzyme suppression in spleen induced by GM1 (monosialoganglioside 1) administration to mice.

Our previous studies suggested that the administration of exogenous gangliosides to the body modulates enzymatic networks in the brain. In the present study, we tested whether that is the case with another organ, spleen. By testing the dose response relationship, we found that there is a optimum dose for the effect of enzymatic modulation of GM1 (monosialoganglioside 1) administration. Although the optimum level varied depending on each of the examined hydrolytic enzymes, it usually fell in the range around 50 micrograms/kg body weight. The findings led us to conclude that the enzyme-modulating actions of gangliosides come not merely from the bizarre actions in vivo of high molecular exogenous substances.

Animals↗

A patient with protein-losing enteropathy associated with systemic lupus erythematosus.

A 46-year-old woman previously diagnosed as having systemic lupus erythematosus presented with severe hypoalbuminemia and anasarca. She was demonstrated to have protein-losing enteropathy without any other active symptoms of SLE. Her bowel habit was normal and endoscopic examination revealed non-specific colitis and a small ulcer in the duodenum. Serum biochemistry showed an abnormal profile of the serum protein, including severe hyperlipoproteinemia and hyperfibrinogenemia. The process of protein-losing was not selective in terms of the molecular size. All of these symptoms and the abnormalities in laboratory data were improved by corticosteroid therapy.

Adrenal Cortex Hormones↗

Hypomagnesemia with increased metabolism of parathyroid hormone and reduced responsiveness to calcitropic hormones.

A patient with severe hypomagnesemia due to chronic alcoholism is presented who repeatedly exhibited marked hypocalcemia with a dissociation between radioimmunoassay findings for mid region of parathyroid hormone (PTH-M) and immunoradiometric assay findings of serum intact PTH (PTH-intact). Serum PTH-M was moderately elevated whereas serum PTH-intact was in a low normal range every time when her serum magnesium (Mg) concentration was markedly reduced. There was also a marked reduction in serum osteocalcin concentration. Supplementation of Mg resulted in a sharp increase in serum PTH level with a rapid disappearance of the dissociation between the two immunoassays of PTH. Shortly after serum PTH and 1,25(OH)2D levels reached their peak, serum osteocalcin started to increase, and was elevated into a supranormal level with normalization of serum Ca concentration. Mg is thought to act as a mimic/antagonist of calcium (Ca), and high extracellular Ca is shown to cause an inhibition of secretion with a stimulation of degradation of PTH. Thus, these observations are consistent with the hypothesis that Mg deficiency causes an increase in the metabolism of PTH and a reduction in the secretion of bioactive intact PTH by increasing the sensitivity of parathyroid cells to Ca. In addition, the fact that hypocalcemia disappeared concomitant with a marked increase of serum osteocalcin from undetectable levels suggest that refractoriness of bone to calcitropic hormones is present which plays a significant role in the development of hypocalcemia under hypomagnesemia, and that serum osteocalcin can be a good marker for the assessment of the responsiveness of bone to calcitropic hormones in these patients.

Alcoholism↗

Sperabillins, new antibacterial antibiotics with potent in vivo activity. Taxonomy, fermentation, isolation and biological activity.

A Gram-negative bacterium was found to produce new antibacterial antibiotics, sperabillins A, B, C and D, and the producing bacterium was characterized and identified as Pseudomonas fluorescens YK-437. Sperabillins were isolated by column chromatographies using cation-exchange resins, activated carbon and cation-exchange Sephadex, and preparative reverse-phase HPLC. Sperabillins showed antibacterial activity against Gram-negative and Gram-positive bacteria including antibiotic-resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. Sperabillin A inhibited DNA, RNA, protein, and cell wall biosynthesis in Escherichia coli. Sperabillins showed good protective effects in experimentally infected mice.

Amidines↗

Production and biological activities of a new antifungal antibiotic, TAN-950 A.

A novel antifungal antibiotic, TAN-950 complex, was isolated from the culture filtrate of Streptomyces platensis A-136 (IFO 14603, FERM BP-1786). The water-soluble amphoteric substances in this complex were purified by chromatography using ion-exchange resins, QAE-Sephadex and adsorptive resins and were designated TAN-950 A and TAN-950 A-E mixture. The molecular formula of TAN-950 A was determined to be C6H7N2O4Na for the sodium salt. This new amino acid antibiotic showed antifungal activity against Candida albicans in vitro and in vivo, and had low toxicity in mice.

Animals↗

Purification of bullous pemphigoid IgG subclasses and their capability for complement fixation.

The antibody reactivity and complement fixing capability of circulating IgG subclass antibodies of patients with bullous pemphigoid (BP) were investigated. Four subclasses of polyclonal IgG were purified from the sera of BP patients. The first stage of purification was a combination of chromatographies on DEAE Affi-Gel Blue and protein A-Cellulofine columns. The four polyclonal IgG subclasses were then isolated from the above-mentioned semi-purified subclass fractions using IgG subclass-specific immuno-affinity chromatographies. Using an immunohistopathological technique, IgG deposits were detected at the basement membrane zone (BMZ) in the normal skin incubated with IgG subclasses other than IgG3. C3 deposits were detected at BMZ in the skin incubated with IgG1. Neither IgG nor C3 deposits were in skin incubated with IgG3. These findings suggest that the subclasses of circulating BP antibodies are IgG1, IgG2 and IgG4, but not IgG3. Moreover, only the BP IgG1 subclass appears to fix complement.

Aged↗

[Application of FDA/EB staining for the detection of viable or non-viable mycobacteria in clinical specimens].

Two-hundred sputum specimens from tuberculosis patients were examined for viable or non-viable mycobacteria by a combination of fluorescein diacetate ethidium bromide (FDA/EB) staining, Ziehl-Neelsen staining, and the use of cultures in 3% Ogawa egg medium. The sputum specimens were treated with 3% NaOH for 10 min and washed in PBS. The bacteria was then harvested by centrifugation at 6,000 rpm for 5 min. Each sample was subjected to FDA/EB staining, Ziehl-Neelsen staining and cultures to compare the staining -method results and the results of colony formation. Ziehl-Neelsen staining method revealed acid-fast bacteria in the specimens, distributed from Gaffky 1 to Gaffky 8. The number of FDA-positive specimens and culture-positive specimens were identical in all Gaffky grades, suggesting that the FDA staining method well reflected the presence of viable mycobacteria in the specimens. We concluded that FDA staining is a valuable method to detect viable mycobacteria in sputum specimens on the first day of examination. It is therefore advantageous for doctors and patients to be immediately informed of culture results rather than waiting for several weeks.

Ethidium↗

[Recurrent fusiform aneurysm of the internal carotid artery; a case report].

A 61-year-old woman was referred to our department on February 12, 1991, due to a fusiform aneurysm of her left internal carotid artery (ICA). She had received aneurysm surgery twice in other hospitals in the past. The first operation, in June, 1980, was for an unruptured, symptomatic left internal carotid-posterior communicating aneurysm and the aneurysm disappeared completely after the neck clipping procedure was carried out by one of the authors. In November, 1990, she suffered from subarachnoid hemorrhage with a hematoma in the left frontal lobe. A ruptured anterior communicating aneurysm was clipped in another hospital, where abnormal dilatation of the left ICA was pointed out. She was referred to our department after a ventricular peritoneal shunt operation. Though the postoperative angiogram performed in 1980 had shown complete disappearance of the left IC-PC aneurysm, it was presumed that the fusiform aneurysm which she presented at our department was recurrent because it existed in almost the same place as the aneurysm which had been clipped. It was also in contact with a clip applied in 1980. In accord with the patient's desire to receive surgery, the fusiform aneurysm was operated on directly, and it was remarkably reduced in size by dome clipping. During a clip, a Sugita booster clip was useful for preventing a slip-out of the clip applied on the aneurysmal dome. The patient was discharged about 20 days after the operation and returned to her usual life. A recurrent fusiform aneurysm of the ICA arising after the neck clipping of IC-PC aneurysm has rarely been encountered.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneurysm↗

[Investigation of glutathione-S-transferase isozymes in human lenses].

Glutathione-S-Transferase (GST) isozymes in human lenses were investigated by the immunoenzymatic method using antibody against human liver GST2 and GST3 after polyacrylamide gel isoelectric focusing (western blotting method). Also, rocket immunoelectrophoresis was carried out for the detection of GST1. It was found that GST1 in lens also showed a polymorphism. The GST2 was not found in human clear lenses as well cataractous lenses. In addition, crossreacting materials against both antisera of GST2 and 3 were detected in the pH 6-7 area of the gel in all human lenses.

Blotting, Western↗

[Clinico-immunological study of the patients infected with Mycobacterium avium complex (MAC)].

Lymphocyte functions of the peripheral blood in the patients infected with MAC (MAC-pts) were evaluated comparatively with age-matched normal controls by using flow cytometry. The results obtained were as follows: 1) In normal controls, the number of total lymphocytes and the proportion and number of T lymphocyte subsets significantly decreased with age. The proportion of natural killer lymphocytes significantly increased in elder controls. 2) In MAC-pts, the number of total lymphocytes and T lymphocyte subsets were significantly lower and the proportion of natural killer lymphocytes were higher respectively than normal controls. 3) The lymphocyte proliferation induced by PPD-S stimulation in vitro in MAC-pts was significantly lower than the normal controls in both age groups of 50-69 and 70-89 years old. 4) The lymphocyte proliferation induced by PPD-S stimulation in MAC-pts was increased slightly by adding recombinant IL-2 and significantly higher by depletion of monocytes. By combination of both treatments, it recovered to the level of normal controls. From these results, we suggested that the decline of lymphocyte proliferation induced by PPD-S stimulation in MAC-pts was due to the decrease of IL-2 production by antigen committed lymphocytes and suppression by monocytes. 5) Lymphocyte proliferation induced by PHA stimulation in vitro was also significantly depressed in MAC-pts as compared with normal controls.

Adolescent↗

Surgical treatment for renal hyperparathyroidism--report of 23 cases.

The present study describes surgical resection in 23 patients under maintenance hemodialysis with hyperparathyroidism. Twenty-three patients under maintenance hemodialysis had subtotal parathyroidectomy (s-PTx, n = 12) or parathyroid gland transplantation combined with total parathyroidectomy (Tx, n = 11) performed from January 1979 to January 1991. Their ages ranged from 8 to 63 years. The PTH levels were elevated in all patients preoperatively from 2.5 to 120 times over the upper limit of normal. After s-PTx, PTH levels sharply declined in all but one patient. Clinical symptoms improved in 11 cases with PTH decrease. After Tx, an abrupt decline in PTH was observed after surgery in 10 patients. One patient was reoperated because of persistent hyperparathyroidism. Another patient showed a PTH increase 13 months after surgery. The transplanted parathyroid gland was subtotally resected. Five months after reoperation, the condition recurred and the patient underwent total resection of the transplanted parathyroid gland and its re-autografting into the forearm. In the patients with renal hyperparathyroidism, s-PTx or Tx improved clinical symptoms; this indicates the high reliability of both procedures in treating the disease. A long-term follow-up study must be conducted to check the possible postoperative recurrence of hyperparathyroidism from residual and/or autograft parathyroid gland.

Adolescent↗

Reproductive toxicity of the new quinolone antibacterial agent levofloxacin in rats and rabbits.

The reproductive toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was investigated in rats and rabbits. DR-3355 was administered orally prior to and in the early stage of pregnancy to male and female rats at doses of up to 360 mg/kg. No adverse effects on fertility or teratogenicity were noted at any dose. DR-3355 elicited no evidence of teratogenicity when administered during the fetal organogenesis period to pregnant rats at doses of up to 810 mg/kg, or to pregnant rabbits at doses of up to 50 mg/kg. However, female rats receiving 810 mg/kg showed salivation, soiled coats, soft stools and decreases in body weight and food intake. Rat fetuses in the 810 mg/kg group exhibited decreased body weight and retardation of ossification, and showed increases in mortality and skeletal variations. Decreases in maternal body weight and food intake were observed in rabbits in the 50 mg/kg group. No adverse effects were observed in perinatal and postnatal toxicity studies in rats using doses of up to 360 mg/kg.

Animals↗

Possible requirement of serum progression factors for transformation of BALB/c 3T3 fibroblasts by v-ras p21.

To form colonies in soft agar, ras-transformed 3T3 fibroblasts require serum. We examined what growth factors in serum were essential for ras-induced transformation. Temperature-sensitive (ts) v-Ki-ras-transfected BALB/c 3T3 cells were used to strictly control both the activity of the ras protein and the cell cycle. When G0-arrested ts cells were cultured with 10% serum at a permissive temperature, greater than 50% of cells formed colonies. A similar colony-forming activity was observed in the presence of 10% platelet-poor plasma, but not in the presence of 10% plasma isolated from hypophysectomized rats. Inhibitors of IGF signals attenuated colony formation in the presence of serum. These data suggest that progression factors, probably IGFs, are essential components in serum for ras-induced transformation of 3T3 fibroblasts.

3T3 Cells↗