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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 397 records · Page 22Linked to original sources

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↗

In vivo induction of IgG anti-DNA antibody by autoreactive mixed haplotype A beta z/A alpha d MHC class II molecule-specific CD4+ T-cell clones.

We characterized autoreactive T-cell clones derived from (NZB x NZW)F1 (B/WF1) mice. These autoreactive T-cell clones are shown to be CD4+ by immunofluorescence staining and to belong to Th2 type by cytokine release assay. Specificity analysis revealed the existence of mixed haplotype A beta z/A alpha d major histocompatibility complex (MHC) class II molecule-specific T-cell clones as well as A beta z/A alpha z- or A beta d/A alpha d-specific T-cell clones. Some but not all of the mixed haplotype A beta z/A alpha d-specific autoreactive T-cell clones showed strong activity to induce IgG anti-DNA antibody production upon transfer to young (4-month-old) B/WF1 mice, indicating that T cells with these specificities might be involved in B/WF1 autoimmunity.

Animals↗

Low density lipoprotein receptors in rat adipose cells: subcellular localization and regulation by insulin.

The distribution of LDL receptors within subcellular compartments of isolated rat adipose cells and the effects of insulin on their expression have been assessed. By immunoblotting with specific anti-rat LDL receptor antibodies, LDL receptors were 2.3- and 4.5-fold enriched in endoplasmic reticulum-rich high-density microsomes (HDM) and Golgi complex-rich low-density microsomes (LDM), respectively, compared to plasma membranes (PM). This distribution was similar in cultured cells in which total receptors were increased 2.5-fold compared to freshly isolated cells. After correction for enzyme recoveries, LDL receptors were distributed approximately 4% in HDM, approximately 73% in LDM, and approximately 23% in PM. Insulin decreased total LDL receptors in adipose cells approximately 44%, with a 48% and 49% decrease in HDM and LDM, respectively, without any changes in PM. In contrast, insulin caused an increase of glucose transporters in PM while also decreasing glucose transporters in LDM. When adipose cells were depleted of potassium to inhibit receptor-mediated endocytosis, insulin again caused a decrease of LDL receptors in LDM but now increased LDL receptors in PM. Insulin increased the rate of LDL receptor synthesis approximately 24%, but decreased their half life approximately 40%. Thus, in isolated adipose cells the majority of LDL receptors appear to be located in an intracellular compartment that co-sediments with the Golgi complex rather than located in the PM. The LDL receptors localized in intracellular compartments seem to be functionally regulated as insulin acutely diminishes the number of receptors by apparently accelerating their rate of degradation through, as yet, incompletely determined mechanisms.

Adipose Tissue↗

Quantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT.

UNLABELLED: A method was developed to calculate functional images of regional cerebral blood flow (rCBF) from a single scan using SPECT following intravenous 123I-N-isopropyl-p-iodoamphetamine (IMP) infusion. METHODS: A two-compartment model that includes two parameters of rCBF and regional distribution volume of IMP (Vd) was employed to correct for clearance of IMP from the brain. Using a given input function and a fixed Vd value (30 ml/ml according to an analysis on dynamic SPECT data), a unique value of rCBF was calculated for each pixel of the SPECT image according to the table-look-up procedure. This technique was applied to 15 human subjects, and the calculated rCBF values were compared with those measured by PET. RESULTS: A set of simulation studies demonstrated an optimal SPECT midscan time at 30 to 40 min postinjection of IMP, providing the minimal error sensitivity to the individual difference of the input function (rCBF values with an accuracy of +/- 10%). Another set of simulation suggested validity of fixing the Vd values, i.e., errors in calculated rCBF values were around +/- 7% for a change of Vd of +/- 10%. The measured rCBF values obtained from 15 human subjects were independent on the SPECT scan time. The calculated rCBF values also agreed well with those obtained by the nonlinear least-squares fitting analysis that were obtained from the dynamic SPECT scan and the frequent arterial blood sampling and measurement of lipophilic fraction for each sample (0.54 + 0.88x, r = 0.86), suggesting the validity of the simplified procedures in this method. CONCLUSION: These observations suggested the validity of this method as a clinical tool for quantitative measurement of rCBF.

Amphetamines↗

[Development of enzyme-linked immunosorbent assay for biliary apolipoprotein A-I and a diurnal change of apolipoprotein A-I concentration in human bile].

Enzyme-linked immunosorbent assay for measuring biliary apolipoprotein A-I was established. Utilizing this assay, a diurnal change of apolipoprotein A-I concentration in hepatic bile obtained from percutaneous transhepatic drainage was investigated. A biliary apolipoprotein A-I concentration changed from time to time, and correlations between apolipoprotein A-I and total protein concentration, cholesterol concentration and lithogenic index, r = 0.873, 0.863 and 0.567 respectively, were observed. Moreover, biliary total protein concentration was closely related with lithogenic index (r = 0.671). These data suggest that hepatic lithogenic bile may induce apolipoprotein A-I secretion into hepatic bile.

Apolipoprotein A-I↗

[Angiomyolipoma of the anterior mediastinum--a case report].

An asymptomatic 22-year-old female showed an enlarged mediastinal shadow in a chest X-ray mass screening. Computed tomogram indicated a tumor with a CT-number of 7-8 in her left anterior mediastinum, adjacent to the pericardium. With MRI the tumor showed a low signal intensity of T1 weighted images and a high signal intensity of T2 weighted images. Thoracotomy revealed that the tumor was yellow-whitish, and had a size of 7 x 7 x 1 cm. It was histologically composed of fatty tissue, smooth muscle, and vascular tissue, and was diagnosed as angiomyolipoma. Although angiomyolipomas are often found in the kidney, they are very rare in the mediastinum and difficult to diagnose by image analysis.

Adult↗