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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 379 records · Page 21Linked to original sources

Converting enzyme inhibition improves congestion and survival in hypertensive rats with high-output heart failure.

The effects of angiotensin-converting enzyme (ACE) inhibitors in high-output heart failure have not yet been well established. We evaluated the effects of lisinopril (3 mg/kg/day) on hemodynamics, neurohormones, and survival in 10-week-old spontaneously hypertensive rats (SHR) with aortocaval fistula. Sham-operated treated and untreated SHR served as controls. Cardiac output (CO) was determined by thermodilution method, and renal blood flow (RBF) was assessed by laser-Doppler flowmetry. In sham-operated SHR, 2-week treatment with lisinopril decreased blood pressure (BP), left ventricular (LV) weight, and total peripheral resistance (TPR) (p < 0.01 each) and increased RBF and plasma renin activity (PRA) (both p < 0.05); CO and LV end-diastolic pressure (LVEDP) were unchanged. Fistula creation induced biventricular hypertrophy and high-output heart failure [increased LVEDP, CO, pulse pressure, and plasma norepinephrine (NE) and decreased RBF] with congestive signs (ascites, tachypnea). Lisinopril decreased LVEDP (p < 0.01), increased RBF, prolonged survival (both p < 0.05), and prevented ascites (0 vs. 46%) and increased PRA (p < 0.05) and attenuated the increase in plasma NE. Heart weight, BP, and CO were not affected by lisinopril. Thus, lisinopril ameliorated congestion and improved survival in SHR with fistula without compromising cardiorenal hemodynamics. Venous and renal dilatation and attenuation of vasoconstrictive systems may have contributed to the beneficial effects.

Animals↗

Identification of a second protein encoded by influenza C virus RNA segment 6.

Influenza C virus matrix protein (M1) is encoded by a spliced mRNA derived from RNA segment 6. Unspliced mRNA from this RNA segment, which has not been previously identified, can potentially encode a polypeptide that contains an additional 132 amino acids on the carboxy terminus of the M1 protein. Here the nucleotide sequences of RNA segment 6 of four influenza C strains, isolated in Japan between 1964 and 1988, were compared with the previously determined sequence of C/Ann Arbor/1/50. The results indicated that the deduced amino acid sequence of the carboxy-terminal 132 amino acid domain is conserved fairly well although it is more divergent than the M1 protein sequence. Examination of RNA segment 6-specific mRNAs also showed that unspliced mRNA is present, although in small quantities (approximately 13% of spliced mRNA), in influenza C virus-infected cells. To search for a polypeptide encoded by the unspliced mRNA, the extra carboxy-terminal domain was expressed in Escherichia coli as the glutathione S-transferase fusion protein, and rabbit immune serum was raised against the purified fusion protein. Immunoprecipitation experiments with this antiserum revealed that a previously unrecognized protein of apparent M(r) approximately 18,000, designated CM2, is synthesized in influenza C virus-infected cells.

Amino Acid Sequence↗

Genetic reassortment of influenza C viruses in man.

We reported previously that the antigenicity of the haemagglutinin-esterase (HE) glycoprotein of the human influenza C virus strain C/Nara/1/85 was indistinguishable from that of strain C/Nara/82. However, the ribonuclease T1-oligonucleotide map of total virion RNA of C/Nara/1/85 differed remarkably from the map of C/Nara/82, resembling instead the map of C/Nara/2/85, which has an HE antigenicity dissimilar to C/Nara/82 and C/Nara/1/85. This observation raised the possibility that C/Nara/1/85 might have arisen by reassortment from two viruses closely related to C/Nara/82 and C/Nara/2/85, respectively. Here, we compared the total nucleotide sequence of the HE gene and partial sequences of the other genes of C/Nara/1/85 with those of C/Nara/82 and C/Nara/2/85. The results suggest that C/Nara/1/85 has inherited HE and NP genes from a C/Nara/82-related virus and the PB2, PB1, PA, M and NS genes from a C/Nara/2/85-related virus.

Base Sequence↗

Parvovirus B19-associated haemophagocytic syndrome with prominent neutrophilia.

We describe a patient with both haemophagocytic syndrome and acute myocarditis probably associated with parvovirus B19 infection. The patient had a marked neutrophilia instead of neutropenia more usually observed in virus-associated haemophagocytic syndrome (VAHS). Endogenous serum concentrations of macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), and tumour necrosis factor-alpha (TNF-alpha) were higher than normal, suggesting that these cytokines may be involved in the genesis of the observed syndrome.

Acute Disease↗

Adult T-cell leukaemia with various abnormalities in endocrine and metabolic systems.

Adult T-cell leukaemia (ATL) is a unique type of T-cell malignancy closely associated with human T-cell leukaemia virus-1 (HTLV-1). Despite frequent descriptions of hypercalcaemia, cases accompanied by diabetes insipidus or syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) in ATL patients have rarely been reported. We present an unusual case of ATL with various abnormalities in his endocrine and metabolic systems involving anterior pituitary function, thyroid function, lipid metabolism and Ca metabolism. Some of these abnormalities were considered to arise from infiltration or leukaemic cells into systemic organs after elimination of the above symptoms. Clinical and haematological data showing improvement following chemotherapy are also presented.

Antineoplastic Combined Chemotherapy Protocols↗

Hemodialysis for lithium intoxication: preliminary guidelines for emergency.

In Japan, 9 cases of severe lithium intoxication have been treated by hemodialysis so far, and the usefulness and indications of this procedure are not yet understood fully. We have recently experienced a case of lithium intoxication treated by hemodialysis. Considering this case together with those reported previously, we have prepared some preliminary guidelines for the application of hemodialysis to patients with lithium intoxication. The blood concentration of lithium, renal function, the severity of consciousness disturbance and clinical symptoms such as somatic complications are, of course, important indices for the application of this therapy. We think that the signs of intoxication and the time interval between the onset and the beginning of treatment also serve as useful indices for application of hemodialysis.

Adolescent↗

Possible role of metallothionein in the cellular defense mechanism against UVB irradiation in neonatal human skin fibroblasts.

The role of metallothionein (MT) in protecting skin cells against UVB irradiation was investigated. Fibroblast strains from normal adult (HS-K) and neonatal (NB1RGB) human skins as well as keratinocyte strains from human skin (SV40-HSK) and newborn Balb/c mouse skin (Pam 212) were exposed to UVB irradiation. The sensitivity of HS-K and NB1RGB cells to UVB irradiation was similar; those of SV40-HSK and Pam 212 cells were two- and six-fold as sensitive to UVB irradiation as HS-K cells, respectively. The HS-K cells contained the greatest cellular reduced form of glutathione (GSH) levels compared to the three other skin cells: the levels were 13-, 7- and 6-fold of those in NB1RGB, SV40-HSK and Pam 212 cells, respectively. These results indicated that the sensitivity of skin cells to UVB irradiation was not always associated with their endogenous GSH levels. In particular, despite the fact that NB1RGB cells contained a relatively small amount of GSH, they were less sensitive to UVB irradiation. NB1RGB cells contained 4-30 times more MT than those in other skin cells examined. The sulfhydryl residues of MT molecules in the NB1RGB cells were estimated to be mostly unoccupied by metals, suggesting they act in a similar way to those of GSH. Moreover, NB1RGB cells in which the MT content was elevated by dexamethasone (1 microM) or Zn2+ (7 micrograms/mL) treatment were more resistant to UVB irradiation than nontreated ones. These results suggest that, at least in neonatal human skin fibroblasts, MT may play a role in protection against UVB irradiation.

Animals↗

Rheumatoid-susceptible alleles of HLA-DRB1 are genetically recessive to non-susceptible alleles in the progression of bone destruction in the wrists and fingers of patients with RA.

OBJECTIVE: To assess the relationship between HLA-DRB1 genotypes and the progression of bone destruction in Japanese patients with RA. METHODS: The HLA-DRB1 alleles were determined by polymerase chain reaction and allele specific oligonucleotide probe techniques in 160 Japanese patients with RA. HLA-DR 0101, 0401, 0404, 0405, 1001 and 1402 were regarded as susceptible alleles of RA according to previous reports. Patients were classified into three groups (S/S, S/N and N/N group), based on the possession of two, one or no susceptible factor. The grading of radio-graphic changes in the wrists and fingers were evaluated by Larsen's criteria. The radiographic grades were first compared with the results of genotyping in the 160 cross sectional cases. A retrospective study was then conducted on a subgroup consisting of 57 cases taken from the 160 cases used for the cross sectional study. RESULTS: In the scatter diagram of the 160 cross sectional cases expressing the relationship between the stage of bone destruction and duration of RA, the regression line and the 95% confidence intervals separated the S/S group from the S/N and N/N groups in the early phase of development of bone destruction. In the retrospective study on the 57 cases the median years taken to development to stage V in the wrists after the onset of symptoms were 13.1 in the patients in the S/S group, 22.7 in the S/N group and 23.0 in the N/N group. The difference observed between the S/S and S/N group, and between the S/S and N/N group were statistically significant (p < 0.01), but that between the S/N and N/N groups was not. Thus the bone destruction in the wrists and fingers progressed more rapidly in the S/S group than in the S/N and N/N groups; and the rheumatoid susceptible alleles of HLA-DRB1 can be considered to be genetically recessive to the non-susceptible alleles in the progression of bone destructions in the wrists and fingers. CONCLUSION: Genotyping of HLA-DRB1 can be a useful prognostic marker in the early phase of RA.

Adult↗

Control of sodium and chloride transport in the thick ascending limb in the avian nephron.

We previously reported that birds may concentrate urine by a countercurrent multiplier mechanism using single-solute (NaCl) recirculation, in which the thick ascending limb of Henle (TAL) of mammalian-type nephrons provides an energy source. The Japanese quail TAL has a higher lumen-to-bath Cl flux (JCl,lb) than that of mammals; the mechanism for maintaining the osmotic gradient along the medullary cone is unknown. We investigated whether salt delivery alters the NaCl reabsorption rate in the TAL dissected from both normal and salt-loaded Japanese quail, Coturnix coturnix, 3-7 wk old. When salt loading to the TAL was increased by increasing the perfusion flow rate (PFR), the lumen-to-bath Na and Cl flux coefficients (KNa,lb or KCl,lb, 10(-7) cm2/s) increased, respectively (P < 0.05), from 5.1 +/- 0.9 to 7.6 +/- 0.7 and from 6.8 +/- 0.9 to 8.9 +/- 1.4. Ouabain addition significantly reduced the KNa,lb. A significant correlation existed between PFR and JCl,lb (r = 0.69, P < 0.01) and PFR and JNa,lb. When the TAL was perfused at a low PFR, increasing Cl concentration in the perfusate and bathing medium from 125 to 175 (P < 0.05) or 225 mM (P < 0.01) increased JCl,lb but not KCl,lb, while decreasing Cl concentration decreased JCl,lb but not KCl,lb. Salt loading of intact birds (0.2 M NaCl drinking water) for 7 days increased the plasma Na level and the cloacal fluid-to-plasma osmolality ratio from 0.28 +/- 0.07 to 1.06 +/- 0.05 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Novel angiotensin receptor subtypes in fowl.

We reported previously that blood vessels of domestic fowl contain angiotensin (ANG) receptors on 1) endothelium, mediating vasorelaxation via endothelium-derived relaxing factor and guanosine 3',5'-cyclic monophosphate; 2) vascular smooth muscles, mediating neither relaxation nor contraction; and 3) presumably adrenergic nerve endings, transmitting vasopressor action via a release of norepinephrine. We aimed in the present study to determine fowl vascular ANG receptor subtypes and relate them to function. [Val5]ANG II (native fowl ANG II) increased mean arterial pressure of anesthetized, ganglion-blocker-treated fowl. The dose-pressor response curve for fowl ANG II was not altered by pretreatment (i.v.) with the ANG receptor subtype 1 (AT1) antagonist Dup-753 (losartan, 10 mg/kg) or the subtype 2 (AT2) antagonist PD-123319 (10 mg/kg). Furthermore, cumulative doses (1-20 mg/kg) of losartan or PD-123319 did not selectively inhibit ANG II-induced pressor responses. In reserpine- and prazosin-treated anesthetized fowl, [Val5]ANG II caused dose-dependent vasodepressor actions inhibited by neither losartan (10 mg/kg) nor PD-123319 (10 mg/kg). Likewise, [Val5]ANG II-induced vasorelaxation of fowl aortic rings in vitro was not inhibitable by PD-123319 or losartan (10(-5) M). Specific binding of 125I-labeled ANG II to the aortic endothelium was markedly displaced by ANG II, but not selectively by PD-123319 or losartan. Specific binding of 125I-ANG II ligand to the membrane fraction of aortic smooth muscles was displaced (50% inhibitory concentration) by [Val5]ANG II (3.3 x 10(-8) M) and slightly by PD-123319 (3.7 x 10(-5) M), but not by losartan or EXP-3174, an active metabolite of losartan.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Left ventricular function of the heart regressed by nifedipine in spontaneously hypertensive rats.

Left ventricular (LV) performance of the pharmacologically regressed heart in hypertension is still unclear. We compared LV function of the heart regressed by nifedipine with that of the hypertrophied heart in spontaneously hypertensive rats (SHR). Nifedipine (30 mg/kg/day in food) was given to 15-week-old male SHR for 20 weeks (n = 12). Age- and sex-matched SHR served as controls (n = 12). LV catheterization was performed using a micromanometer and cardiac output was determined by the thermodilution method. Hemodynamic studies were performed after washout of nifedipine (24 h), when blood pressure had returned to the untreated level. Peak pumping ability was assessed during acute volume loading with saline. Nifedipine significantly decreased blood pressure in conscious animals (222 +/- 11 to 201 +/- 12 mmHg, p < 0.01) and reduced LV weight (1.20 +/- 0.07 to 1.07 +/- 0.05g, p < 0.01). After washout of nifedipine, LV systolic and end-diastolic pressures, dp/dtmax and cardiac output determined under pentobarbital anesthesia were similar in the treated and untreated groups. Peak pumping ability during acute preload elevation was also similar in the 2 groups. Plasma norepinephrine was unaltered, and plasma renin activity was significantly lower in the treated rats (p < 0.05). These results indicate that nifedipine regressed LVH with a minimal reduction of blood pressure and without evidence of neurohumoral activation or volume retention. In conclusion, LV function of the heart regressed by nifedipine was preserved after a spontaneous rise in blood pressure and during acute preload elevation.

Animals↗

[Analysis of acute toxicity (LD50-value) of organic chemicals to mammals by solubility parameter (delta). (1) Acute oral toxicity to rats].

Acute oral toxicity (LD50-value) of organic chemicals to rats was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. Certain parabolic correlations were established between logarithm of LD50-value (mmol/kg body weight, rats) and delta c of all the collected chemicals (n = 144, R = 0.578), alcohols (n = 29, R = 0.587), ketones (n = 7, R = 0.962), aldehydes (n = 9, R = 0.621), ethers (n = 5, R = 0.890), acetates (n = 7, R = 0.670) and aromatics (n = 84, R = 0.736). Introducing molar volume (Vc) to the above equations could not improve the correlation. In the study, we assumed that as for acute toxicity, chemicals taken into the mammals through biological membrane first disturb the homeostasis, which causes certain biological reactions (i.e. death) and that amounts of the chemicals intaken are regulated by their solubility in the membrane. Based on the assumption, we drew a theoretical equation, which describes LD50 by a parabolic function of delta c. A regression analysis using the equation gave significant correlations as stated above, which incarnates the assumption. A solubility parameter of 2.30 x 10(4) (J/m3)1/2 was also determined for the biological membrane (absorption site) of rats. For comparison, log P was used to describe LD50 of all the chemicals, but no correlation was established (R = 0.164-0.443).

Acetates↗

[Analysis of acute toxicity (LD50-value) or organic chemicals to mammals by solubility parameter (delta) (2). Acute oral toxicity to mice].

Acute oral toxicity (LD50-value) of organic chemicals to mice was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. As it was observed in the previous study with rats, parabolic correlations were established between logarithm of LD50-value (mmol/kg body weight, mice) and delta c of all the collected chemicals (n = 85, R = 0.626), alcohols (n = 10, R = 0.683), ketones (n = 7, R = 0.631) and aromatics (n = 62, R = 0.645). Introducing molar volume (Vc) to the above equations did not improve the correlations. Although statistically significant correlations were not found in alcohols and ketones with mice, we successfully assured the theoretical equation regardless of species difference by establishing significant correlations with all the collected chemicals and aromatics. By analysis, we could determine the solubility parameter of 2.27 x 10(4) (J/m3)1/2 for the biological membrane (absorption site) of mice. As the delta c-values which dip the LD50-values are approximately the same for mice and rats, common deleterious effects and mechanism may be working at common target sites. In addition, no species difference in sensitivity (toxicity) was found for the aromatics. For comparison, log P was used to describe LD50 of all the collected chemicals, but no correlation was established (R = 0.004-0.418).

Acetates↗

[Analysis of acute toxicity (LD50-value) of organic chemicals to mammals by solubility parameter (delta) (3). Acute dermal toxicity to rabbits].

Acute dermal toxicity (LD50-value) of organic chemicals to rabbits was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. As it was observed in the previous studies with rats and mice, parabolic correlations were also established between logarithm of LD50-value (mmol/kg body weight, rabbits) and delta c of all the collected chemicals (n = 56, R = 0.498), alcohols (n = 19, R = 0.857), ketones (n = 7, R = 0.711), aldehydes (n = 7, R = 0.633) and aromatics (n = 20, R = 0.613). Introduction of molar volume (Vc) to the above equations did not improve the correlations. In the study, we assumed that chemicals absorbed dermally by the mammals similarly disturb the homeostasis, as in acute oral toxicities of organic chemicals to rats and mice. We successfully confirmed the theoretical equation regardless of species and routes of administration by establishing statistically significant correlations with all the collected chemicals, alcohols and aromatics. By analysis, we could determine the solubility parameter of 2.24 x 10(4) (J/m3)1/2 for the biological membrane (absorption site) of rabbits. As the dermal delta c-values which dip the LD50-values for rabbits are approximately the same as in acute oral toxicities with rats and mice, common deleterious effects and mechanism may be working at the common target sites. The regression curves of LD50-values of rabbits, however, are slightly higher than those of rats and mice, which may reflect the difference in amounts of the chemicals absorbed by the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Serial transcranial Doppler flow velocity and cerebral blood flow measurements for evaluation of cerebral vasospasm after subarachnoid hemorrhage.

Serial transcranial Doppler (TCD) and cerebral blood flow (CBF) examinations were performed in 73 patients with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysm to evaluate cerebral vasospasm. Twenty-six (35.6%) of the 73 patients developed ischemic neurological symptoms associated with cerebral vasospasm, which were reversible in all except four patients (5.5%) who demonstrated low-density areas associated with vasospasm on computed tomographic scans. In general, the flow velocities in the middle cerebral arteries began to increase soon after onset of SAH, reaching the maximum between days 8 and 10, subsequently decreasing gradually. There was no significant difference in the highest value and the time course of flow velocities between symptomatic vasospasm and asymptomatic vasospasm patients. Patients with symptomatic vasospasm demonstrated two typical time courses of flow velocities: rapid increases in flow velocities that preceded the clinical manifestations of vasospasm (16 patients, 61.5%), and no rapid increases in flow velocities despite the presence of ischemic symptoms (10 patients, 38.5%). In the latter, angiograms demonstrated vasospasm in segments distal to those evaluated by TCD examination. These results showed that the degree of cerebral vasospasm cannot be assessed only by the absolute flow velocities. CBF was measured two to 10 (mean 4.7) times within 3 weeks of SAH using the 133Xe intravenous injection method. The CBF value remained stable even during the period of major risk of vasospasm. However, the CBF was significantly lower in patients with symptomatic vasospasm on days 8, 9, 10, 13, 14, and 15, when compared with patients without symptomatic vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗