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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 631 records · Page 35Linked to original sources

Large neurons in the tuberomammillary nucleus in patients with Parkinson's disease and multiple system atrophy.

To investigate whether the histaminergic neurons degenerate in Parkinson's disease (PD) and multiple system atrophy (MSA), we studied the number of large-sized neurons in the tuberomammillary nucleus in patients with PD, patients with MSA, and age-matched controls. The number of large-sized neurons in the tuberomammillary nucleus in PD patients was not altered compared with controls, and Lewy bodies were rarely present in the tuberomammillary nucleus. In contrast, the number of large-sized neurons in the tuberomammillary nucleus in MSA patients was significantly decreased compared with controls. Thus, the central histaminergic neurons are affected in MSA and preserved in PD.

Aged↗

Functional transformation of microbodies in higher plant cells.

In germinating fatty seedlings, microbodies are functionally transformed to leaf peroxisomes from glyoxysomes during greening, and then converted to glyoxysomes from leaf peroxisomes during senescence. Immunocytochemical studies revealed that glyoxysomes can exchange directly into leaf peroxisomes during greening and leaf peroxisomes are once again directly converted to glyoxysomes during senescence. The reversible transformations of microbodies are regulated at various levels, such as gene expression, splicing of the mRNA and degradation of microbody proteins. The regulatory mechanisms underlying this organelle differentiation are described.

Biological Transport↗

Hepatic local disposition of a drug with high protein binding and high hepatic clearance using BOF-4272 as a model drug.

The local disposition of a drug, which is efficiently eliminated by the liver in spite of very high binding with serum albumin, was investigated using BOF-4272 as a model drug in the hepatic perfusion system. Bovine serum albumin (BSA) labeled with Evans Blue was used as the marker of hepatic blood space. The perfusion experiments were carried out at 37 degrees C and at 4 degrees C to evaluate the local disposition in active and inactive livers, respectively. The perfusates included 0, 0.25, 0.5, 1.0 and 4.0% of BSA in the injection of BOF-4272, and 0 and 1.0% of BSA in the injection of Evans Blue. After an instantaneous injection of BOF-4272 or Evans Blue (labeling reagent of BSA), the outflow time profile from the liver was analyzed by curve-fitting based on two-compartment dispersion model. All estimated parameters of BSA were almost the same between 37 degrees C and 4 degrees C, which showed that the blood space in the liver was unaffected by perfusate temperature. The recovery ratio (FH) and the mean transit time (FH) of BSA were 100% and about 0.1 min, respectively, both with BSA (1.0%) and without BSA in the perfusate. FH of BOF-4272 increased from 20% to 50% with an increase in the perfusate BSA at 37 degrees C, whereas FH was almost constant (90%) regardless of BSA concentration at 4 degrees C. FH of BOF-4272 was almost 0.1 min regardless of BSA concentration at 37 degrees C, whereas FH decreased from 0.29 min to 0.17 min at 4 degrees C with an increase in the perfusate BSA. A large elimination (10%) of BOF-4272 was noticed even at 4 degrees C in the presence of perfusate BSA, which demonstrates that the passive transfer of BOF-4272 from BSA to the hepatic tissues is considerably rapid. This efficient transfer is responsible for the large hepatic clearance of BOF-4272 with very high binding with BSA.

Animals↗

Electrocardiographic observation on spontaneously occurring arrhythmias in chickens.

In order to clarify the spontaneous occurrence of arrhythmias in chickens, electrocardiograms using standard bipolar limb leads were recorded for 461 chickens of 7 breeds, including 3 pure breeds: Rhode Island Red (RIR, n = 125), Japanese Game (JG, n = 101), and White Leghorn (WL, n = 52); and 4 crossbreeds of RIR: the first filial generation (F1) obtained by mating RIR with JG (RIR x JG, n = 44), the backcross obtained by mating the Fl of RIR x JG with the parental JG ((RIR x JG) x JG, n = 10), the F1 obtained by mating RIR with WL (RIR x WL, n = 73), and the F1 obtained by mating RIR with the commercial hybrid chicken, Dekalb Amber Link (DAL)(RIR x DAL, n = 56). Nine types of arrhythmias were observed in 107 chickens (23.2%, 107/461): 66 had sinus arrhythmia, 19 had atrial premature contraction, 9 had ventricular preexcitation syndrome, 7 had ventricular premature contraction, 2 had second-degree atrioventricular block. 1 had atrial fibrillation, I had aberrant ventricular conduction. I had intraventricular conduction disturbance, and 1 had ventricular electrical alternans. Except for sinus arrhythmia, the incidence of other arrhythmias in RIR was significantly high, compared with that in pure breeds other than RIR (p < 0.001) and that in crossbreeds of RIR (p < 0.01). Arrhythmias other than ventricular premature contraction and sinus arrhythmia will be the first to be described as spontaneously occurring arrhythmias in chicken. Although the reason for both the highest incidence of sinus arrhythmia in WL and the predominance of other arrhythmias in RIR were obscure, the present results suggest the possibility of using chickens, especially RIR which shows a high incidence of arrhythmias, as a relevant animal for studying arrhythmias.

Animals↗

A rapid and easy electrophoretic method for detecting biochemical loci of rat (Rattus norvegices).

Methods for electrophoresis for the analysis of biochemical marker genes, which are used widely for genetic monitoring of inbred strains of rats, have been complicated by the variation of the gel and electrode buffer and electrophoretic conditions with the enzyme or the protein to be examined. To simplify the methods, we performed electrophoresis under fixed conditions of 200 V and 30 min using cellulose acetate membrane as the gel and veronal solution as the gel and electrode buffer. Good results were obtained concerning 12 loci, namely, Amy1, Cs1, Es1, Es2, Es3, Es4, Fh1, Gc, Hbb, Ldr1, Mup1, and Svp1. This method was applied to 8 inbred strains of rats and confirmed to be practical.

Animals↗

Analysis of pathogenesis of autoimmune insulitis in NOD mice: adoptive transfer experiments of insulitis in ILI and NOD nude mice.

In an effort to study the pathophysiological events in the development of insulitis in NOD mice, we have developed ILI- and NOD-nu/nu mice. ILI mice are a nondiabetic inbred strain but are derived from the same JcI:ICR mouse as NOD mice and share the same H-2 allotype with NOD mice. Splenocytes and CD4+ cells from diabetic NOD mice appeared to transfer insulitis to ILI-nu/nu mice, suggesting that ILI mice already express autoantigen(s) responsible for insulitis. But reciprocal thymic grafts from NOD mice into ILI-nu/ nu mice and those from ILI mice into NOD-nu/nu mice failed to allow the development of insulitis, implying that ILI mice possess neither precursor T cells nor the thymic environment responsible for the development of insulitis. In addition, splenocytes from ILI mice appeared to contain regulatory cells which suppress the development of diabetes but not that of insulitis in NOD mice. The use of these nude mice should provide more information on the products of insulitis-susceptibility genes of NOD mice.

Adoptive Transfer↗

[Resolution of psoriasis vulgaris following allogeneic bone marrow transplantation for aplastic anemia].

A 36 year-old man had suffered from psoriasis vulgaris for about 25 years. He had received corticosteroids ointment and PUVA therapy with partial response. In 1987, he was diagnosed as having aplastic anemia (AA) and treated with various medications, but failed to respond. He received an allogeneic bone marrow transplantation (BMT) from his histocompatible sister in 1993. Conditioning regimen of BMT consisted of total lymphoid irradiation (7.5 Gy) and cyclophosphamide (200 mg/kg). Cyclosporin A and methotrexate were given for prophylaxis of graft-versus-host disease. On day 24, bone marrow examination disclosed normocellular marrow and karyotypic analysis completely confirmed the donor's origin. Before BMT, he had systemic psoriatic plaques with scales, together with nail involvement. After BMT, psoriatic plaques disappeared and nail deformity improved. He has remained in remission of his AA and completely free of psoriasis in the absence of immunosuppressive or other treatments. The cause of psoriasis is thought to be an immune-mediated disorder. Our case supports the observation that changing the host's immune system through allogeneic BMT can achieve remission of psoriasis. It is suggested that allogeneic BMT may be one strategy for the treatment of intractable immune-mediated disorders.

Adult↗

Endogenous nitric oxide production is augmented as the severity advances in patients with liver cirrhosis.

1. Since endothelium-derived nitric oxide (NO) is a potent vasodilator and degraded into nitrous ions, we measured the serum nitrate ion (NO3-) and the amount of urinary excretions of NO3- as an index for endogenous NO to ascertain whether NO formation is augmented in patients with chronic liver diseases. 2. Using inpatients suffering from chronic liver diseases, serum levels and urinary excretions of NO3- were measured by using high-performance liquid chromatography with an anion exchange column. 3. Among the four patient groups of normal controls, and those with chronic liver diseases such as chronic active hepatitis, compensated cirrhosis, and decompensated cirrhosis the serum level of NO3- showed the highest level in a patient group with decompensated cirrhosis. The amount of urinary excretion of NO3- was significantly increased in both groups of patients with liver cirrhosis compared with the control group and patients with chronic active hepatitis. Patients with chronic active hepatitis did not show any difference between the normal control group. The amount of urinary excretion of NO3- correlated significantly and negatively with the level of serum albumin (P < 0.05) and counts of platelets (P < 0.01) in patients with compensated cirrhosis. 4. These findings suggest that the production of endogenous NO is augmented in patients with liver cirrhosis, particularly in a decompensated subgroup. Increases in the production of endogenous NO correspond to the progress of liver cirrhosis, but not in patients with chronic hepatitis.

Adult↗

[Cardiac arrhythmias caused by electrolyte imbalance].

Cardiac arrhythmias are known to be caused by many factors. Among them, electrolyte imbalance is the most important because of electrical activity of the heart is composed of transmembrane fluxes of Na+, Ca2+ and K+. In this review article, we describe the effects of high or low concentrations of these electrolytes on the active and passive electrical properties of the membrane in the cardiac tissues, and the mechanisms by which these electrolytes cause abnormal impulse formation and conduction in the heart. Antagonism and synergism of electrolytes and pathological conditions such as digitalis intoxication and ischemia are discussed with respect to not only cardiac electrophysiology but also cellular metabolism. A pathophysiological role of Mg2+ to maintain normal excitation and conduction of the heart is also pointed out.

Action Potentials↗

[Diurnal alteration of platelet-free Ca2+ in subjects with normal renal function and patients undergoing CAPD].

We examined the relation of diurnal alteration of platelet-free Ca2+ to blood pressure and plasma vasoactive substances in 6 subjects with normal renal function (N group) (with both normal GFR and normal urine concentration, and with the renal biopsy finding of minor glomerular change) and 7 patients undergoing CAPD (CAPD group), then evaluated the pathophysiological difference in diurnal variations between both groups and the effect of native kidney function. Diurnal values of platelet basal-free Ca2+ concentration in N showed a positive correlation with the corresponding PRA levels. On the other hand, in CAPD they showed a positive correlation with the corresponding levels of plasma AVP. The larger increases in platelet-free Ca2+ concentration due to thrombin stimulation were observed in the daytime and the smaller increases in the nighttime in the N groups. The thrombin-induced changes showed a positive correlation with the diurnal levels of mean blood pressure in N (p < 0.004). However, in contrast, in CAPD the increase in platelet-free Ca2+ due to thrombin tended to be larger in the nighttime and showed a negative correlation with the daily mean blood pressure levels (p < 0.004). These findings suggest that there might be differences in the regulation of intracellular-free Ca2+ dynamics and the diurnal variation between subjects with normal renal function and patients undergoing CAPD. Those differences could affect the progression of vascular disturbance in CAPD patients.

Adult↗

Donor leukocyte transfusions and discontinuation of immunosuppressants to achieve an initial remission after allogeneic bone marrow transplantation in a patient with primary refractory acute leukemia.

We present a female patient who received an allogeneic bone marrow transplantation for primary refractory Philadelphia-positive acute biphenotypic leukemia. Since leukemic blasts were persistently present in peripheral blood and bone marrow, in spite of the evidence for engraftment of male donor hematopoiesis, we performed donor leukocyte transfusions and discontinued immunosuppression. An initial complete remission was obtained 15 weeks after allogeneic bone marrow transplantation, and lasted for 24 weeks. We concluded that the prominent mechanism for the eradication of the refractory leukemic clone in the patient was the graft-versus-leukemia effect.

Adult↗

[The combination therapy with vinca-alkaloid slow infusion and cholchicine was effective to refractory idiopathic thrombocytopenic purpura. The patient could receive femoral head replacement in safety].

A 46-year-old man with idiopathic thrombocytopenic purpura (ITP) refractory to corticosteroid, splenectomy and other drugs was admitted to our hospital in August, 1994, because of aseptic necrosis of the right femoral head. Although high-dose intravenous gamma-globulin was ineffective, the platelet count was increased within two weeks by the combination therapy that consisted of 0.02 mg/kg vincristine alternating with 0.1 mg/kg vinblastine by slow infusion at a 1-week interval, and oral 1.5 mg/day colchicine. He subsequently underwent the femoral head replacement. This combination therapy seems to be useful for refractory ITP in preparation for surgery.

Colchicine↗

[Atlantoaxial dislocation with ventilatory insufficiency--report of two cases].

We performed electromyography and polysomnography in two cases of atlantoaxial dislocation with ventilatory insufficiency to determine the patients' respiratory patterns. The results showed that hypertrophic sternocleidomastoid muscles (SCMs) played an important part in their respiration. The diaphragm and intercostal muscles did not display marked electromyographic (EMG) activity, but the SCMs showed a great deal of phasic inspiratory activity during the daytime that decreased or disappeared during sleep. A 6-year-old boy with atlantoaxial dislocation related to spinal abnormalities was chiefly dependent on the SCMs for respiration and required mechanical ventilation when a sleep because the SCMs were completely inactive. A 4-year-old girl with atlantoaxial dislocation as the result of an automobile accident was partially dependent on the SCMs. She had no trouble breathing during the daytime, but polysomnography recordings showed recurrent hypopnea and desaturation during the night synchronous with decreased EMG activity of the SCMs. She also required mechanical ventilation to improve her long-term prognosis. Polysomnography should be performed in severe cases of atlantoaxial dislocation with respiratory failure in addition to routine respiratory function tests.

Atlanto-Axial Joint↗

Relapse and elevation of blood urea nitrogen in acute fenitrothion and malathion poisoning.

We observed 6 patients with severe fenitrothion and/or malathion poisoning necessitating artificial ventilation and intensive care monitoring. Three developed relapse following acute cholinergic crisis. In these patients the blood urea nitrogen (BUN) abnormally elevated before the development of relapse and the initial high concentration of plasma organophosphate (OP) decreased only gradually. However, the patients who did not develop relapse showed no elevation of BUN and a relatively low concentration of plasma OP. This observation was confirmed in a retrospective search of 14 patients. In addition, erythrocyte cholinesterase (EChE) activities were more helpful to diagnose the development of relapse than plasma cholinesterase activities. Therefore, careful monitoring of BUN in addition to plasma OP concentration may be useful to predict the development of relapse.

Blood Urea Nitrogen↗

Arteritis in a novel congenic strain of mice derived from MRL/Lpr lupus mice: genetic dissociation from glomerulonephritis and limited autoantibody production.

An MRL/Mp strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop systemic vasculitis and glomerulone phritis in the same individual, and both have been thought to be associated with an increase in circulating immune complexes and autoantibodies. However, the genetic basis of these diseases is poorly understood. A novel recombinant congenic mouse strain, McH5-lpr/lpr, which was established by rearrangement of the genetic background of MRL/lpr mice by hybridization with C3H/HeJ-lpr/lpr mice, developed severe granulomatous polyarteritis, as did the MRL/lpr strain, but not glomerulonephritis. Serum levels of anti-DNA and anti-myeloperoxidase antibodies in these mice were significantly reduced, as compared with MRL/lpr mice, although rheumatoid factors were not. These results indicate that each of these two diseases, arteritis and glomerulonephritis, is under the control of different background gene(s), suggesting a different pathological basis of these diseases, and that anti-DNA and anti-myeloperoxidase autoantibodies appear to have a limited pathogenic role in granulomatous arteritis in the mouse strain described.

Animals↗

Kimura disease: CT and MR findings.

The lesions of Kimura disease showed slightly high and very high intensity on T2-weighted MR, and low and intermediate intensity, respectively, on T1-weighted images. The degree of enhancement also differed between the two cases. These discrepancies may be attributable to differing degrees of fibrosis and vascular proliferation.

Adolescent↗