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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 847 records · Page 47Linked to original sources

Histochemical localization of copper in the intestine and kidney of macular mice: light and electron microscopic study.

Menkes' disease is an X-linked recessive disorder characterized by accumulation of copper in various organs and cells, such as the intestine, kidney, and cultured fibroblasts. Light and electron microscopic localization of Cu was investigated in the intestine and kidney of macular mice, an animal model of Menkes' disease, by a modified sulfide-silver method. Cu was accumulated in the cytoplasm of the absorptive epithelial cells, the vascular endothelium, and secretory granules of the Paneth cells. In kidney the distal tubule cells and glomeruli of both macular and control mice stained faintly, whereas the organelle-free cytoplasm in the proximal tubule cells of macular mice stained more intensely than those of controls. The nuclei, mitochondria, and lysosomes of the cells of macular mice hardly stained at all. These findings indicate that Cu is concentrated in the organelle-free cytoplasm of the affected cells of macular mice. This suggests that the Menkes' mutation affects Cu transport from the cytosol to the organelles in the cell.

Animals↗

Sequence comparisons of HTLV-I from HAM/TSP patients and their asymptomatic spouses.

We amplified and sequenced portions of the human T-lymphotropic virus type I (HTLV-I) (U3), pol, env, and pX provirus regions (1212 bp per person) from peripheral blood lymphocytes (PBL) of two married couples (case 1 and case 2). Both husbands are patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and the wives are asymptomatic HTLV-I carriers. We selected these regions because the LTR and env regions of murine retrovirus models have been involved in determining tissue tropism. In addition, the predominant immunogenic epitope for HTLV-I-specific cytotoxic T cells obtained from circulating PBL of HAM/TSP patients was localized in the HTLV-I pX region. Our aim was to examine variations in these HTLV-I regions between affected and asymptomatic spouses. In the HTLV-I regions studied, we detected no sequence variation between each couple. These data do not favor the hypothesis that neurotropic mutants of HTLV-I are involved in the pathogenesis of HAM/TSP.

Base Sequence↗

[A study on acute organophosphorus poisoning--changes in the activity and isoenzyme patterns of serum cholinesterase in human poisoning].

Various organophosphorus compounds with low acute toxicity levels are widely used as insecticides. Human acute poisoning by organophosphates has often occurred accidentally. We determined the activity and isoenzyme patterns of serum cholinesterase (ChE) obtained from 13 human patients who attempted suicide with various organophosphates, i.e. Fenitrothion, Malathion, Isoxathion, Pyridaphenthion and Trichlorfon, and studied on the changes in the activity and isoenzyme patterns of serum ChE after ingestion. The following results were obtained. 1) Twenty ChE isoenzyme bands from normal human serum were detected by electrophoretic separation on polyacrylamide gradient gel. The main bands in the ChE isoenzyme pattern in normal serum were bands 4 and 5 which had the highest activity of acetylcholinesterase (AChE) with a molecular weight of 600,000-800,000, and bands 7, 12, 14, 17 and 18. 2) Inhibition of serum ChE activity was more severe as the amount ingested increased in patients who took Fenitrothion and Malathion. Reactivation of serum ChE activity was very slow in patients treated with PAM (2-pyridine aldoxime methiodide) in the late stage of ingestion or whose symptoms reappeared. 3) There were no differences in the patterns of serum ChE isoenzyme by organophosphorus compound. Band 7 disappeared in the serum ChE isoenzyme of almost every patient, and bands 12, 18, 14 and 17 of the serum ChE isoenzyme disappeared successively with the decline of serum ChE activity. Only band 5 of the isoenzyme remained in cases who had serum ChE activity lower than 5% of normal. 4) All 13 patients were treated with PAM and atropine immediately after being admitted to hospitals. We could not clearly determine the efficacy of PAM on reactivation of serum ChE activity and isoenzyme, because it was impossible in human poisoning to compare PAM efficacy with no treatment and with pre- and post-PAM treatment. 5) The activity and isoenzyme patterns of serum ChE recovered rapidly after combined hemoperfusion and hemodialysis treatment (HP-HD treatment) of the patients poisoned with Malathion. But HP-HD treatment had no effect on poisoning by Fenitrothion and Isoxathion. These findings demonstrated the changes in the activity and isoenzyme pattern of serum ChE in patients poisoned with several organophosphates after PAM and HP-HD treatment.

Acute Disease↗

Liver cirrhosis with severe hypoxemia and paradoxic pulmonary vascular response to graded inspiratory oxygen tension.

We present the findings in a patient with liver cirrhosis who showed oppositional pulmonary vascular responses to various alveolar oxygen tensions. In this case the pulmonary artery constricted on exposure to hyperoxia and then gradually dilated during progressive hypoxic inhalation. Such a paradoxic response must result in severe arterial hypoxemia because of severe V/Q mismatching.

Dyspnea↗

Possible compensatory role of parathyroid hormone-related peptide on maintenance of calcium homeostasis in patients with non-insulin-dependent diabetes mellitus.

Recent studies have revealed that altered mineral and vitamin D metabolism is observed in diabetic patients with the complication of osteopenia. In order to elucidate the role of parathyroid hormone-related peptide (PTHrP) on calcium homeostasis in diabetes, we have measured the serum level and urinary excretion of PTHrP as well as other serum calcium-regulating hormones in 106 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 43 control subjects. The serum concentration of intact PTH was 2.34 +/- 0.13 (mean +/- SEM) pmol/l in NIDDM patients, which is significantly lower than the value of 3.11 +/- 0.14 pmol/l in the controls (p < 0.01). Both serum calcium and calcitonin, however, were not statistically different from controls. On the other hand, circulating PTHrP in NIDDM was 40.1 +/- 1.4 pmol/l, which is significantly elevated when compared to 27.3 +/- 1.3 pmol/l in the controls (p < 0.01). Moreover, urinary excretion of PTHrP also was significantly higher in NIDDM (p < 0.01). In the present study, the circulating calcium level was well preserved in NIDDM patients, although the PTH levels were shown to be decreased. The elevated serum PTHrP might, therefore, have a physiologically compensatory role on the calcium regulatory systems in NIDDM. Furthermore, this elevation is most likely due to the excess production of this peptide and not to the decrease in urinary excretion.

Adaptation, Physiological↗

Morphometric profiles of the mandible of SMXA recombinant inbred strains of mice and strain identification on the basis of mandible measurements.

SMXA recombinant inbred (RI) strains were derived from the F2 generation of a cross between two progenitor inbred strains, A/J and SM/J, which differ considerably with respect to many characters. In order to determine the morphometric profiles of the mandible of SMXA RI strains and to identify these strains, principal component and discriminant analyses (mandible analysis) were carried out using 11 mandible measurements. Principal component analysis revealed that the mandibles of each strain have their own characteristic size and shape. The RI strains, however, were roughly divided into 15 groups based on the morphometric profile of their mandibles. Discriminant analysis showed the probability of erroneous discrimination to be 6.49% (20/308) for the males and 8.06% (27/335) for the females. In both sexes, most of the erroneous discrimination (13 in the male, 17 in the female) occurred between RI strains having comparatively similar morphometric profiles. This suggested that all of the SMXA RI strains examined could be regarded as genetically homogeneous within each strain.

Animals↗

A secondary amyloidosis associated with systemic lupus erythematosus.

Secondary amyloidosis associated with systemic lupus erythematosus has rarely been reported. A 57-year-old female had been diagnosed as having possible systemic lupus erythematosus, although her clinical course was not typical. About one year after the diagnosis, treatment was begun with prednisolone because of progressive renal dysfunction, thrombocytopenia and low serum levels of complements. Recurrent diarrhea and gastrointestinal bleeding soon developed, then amyloidosis was revealed in the stomach and duodenum. Postmortem examination confirmed systemic amyloidosis. We discuss the significance of this rare association of systemic lupus erythematosus and secondary amyloidosis.

Amyloidosis↗

Hearing recovery in sudden deafness patients using a modified defibrinogenation therapy.

Ninety-eight patients with idiopathic sudden deafness were treated with a modified defibrinogenation (DF) therapy including batroxobin, low molecular dextran, vasodilators and vitamins. Hearing improvement was evaluated with two methods: categorical judgement and improvement rate (%). By categorical judgement, 60 patients (61% of the total) were classified into recovery or good improvement categories. The improvement rate was calculated for each of the 93 patients, and the average value was 64%. Modified DF therapy was effective especially for patients with severe hearing loss of 70-90 dB with flat audiogram. Although serum fibrinogen significantly decreased after batroxobin administration there was no correlation between the concentration of fibrinogen and hearing recovery. When prognostic factors were studied, the interval between the onset of hearing loss and start of treatment, initial hearing level, and the existence of vertigo all had significant correlation with the degree of hearing recovery.

Adenosine Triphosphate↗

Role of insulin in the pathogenesis of hypertension associated with glucose intolerance.

The role of insulin in the pathogenesis of hypertension was explored in normal men and male patients with impaired glucose-tolerance. They were classified as normal (n = 94), borderline (n = 164), impaired tolerance (IGT, n = 104), or diabetes mellitus (n = 100) according to their response to an oral 75g glucose challenge. Besides routine laboratory examinations, fasting immunoreactive insulin and post-glucose insulin levels at 30 minutes were measured. Patients with impaired glucose tolerance were older and more obese than the normal subjects. Serum cholesterol and triglyceride concentrations increased with severity of the glucose tolerance impairment. However, renal function, as estimated by blood urea nitrogen levels did not differ among these four groups. Multiple regression analysis revealed that blood pressure correlates significantly with the obesity index, blood glucose, serum cholesterol and serum insulin in all four groups. Among these groups, the partial F ratios for the obesity index were the greatest in both normal and diabetic groups, but in both borderline and IGT groups those for insulin were the greatest. These results indicate that in patients with impaired glucose tolerance is hypertension associated more closely with hyperinsulinemia than it is in normal subjects or diabetic patients.

Adult↗

R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. III. Pharmacological properties and antitumor activities.

R1128 B (1,3,6-trihydroxy-8-n-butylanthraquinone), a new antibiotic produced by Streptomyces sp. No. 1128, inhibited estrogen binding to its receptor. The IC50 value of R1128 B for partially purified rat uterine cytosol receptor was 1.2 x 10(-7) M. However, the IC50 value of R1128 B against androgen-receptor binding was about 50-fold greater than that against estrogen-receptor binding. R1128 B was a competitive inhibitor against estrogen-receptor binding. R1128 B inhibited the growth of estrogen-responsive human mammary adenocarcinoma MCF-7 cells in soft agar. This inhibition, however, was reversed when estradiol was added to the culture medium. R1128 B showed antitumor activities against MCF-7 both xenografted to nude mice and implanted in subrenal capsule of mice (SRC assay). The potency of R1128 B was about 8-fold lower than that of tamoxifen both in vitro and in vivo.

Androgen Receptor Antagonists↗

Cloning and sequencing of cDNA for glycolate oxidase from pumpkin cotyledons and northern blot analysis.

A cDNA clone for glycolate oxidase (EC 1.1.3.1) was isolated by an immunochemical method from a cDNA expression library constructed from poly(A)+-RNA of green pumpkin cotyledons. The analysis of in vitro transcription-translation products of the cDNA insert revealed that the cDNA clone contained the complete coding region for glycolate oxidase. The entire insert of the cDNA was 1,440 nucleotides in length and encoded 367 amino acid residues, equivalent to a molecular mass of 40,353 daltons. The amino acid sequence of the C-terminal tripeptide was Pro-Arg-Leu, which is slightly different from the proposed signal for targeting to microbodies, Ser-Lys/Arg/His-Leu. Characteristic hydrophilic domains observed in the C-terminal regions of most microbody proteins were found in the deduced sequence of glycolate oxidase by hydropathy analysis. Immunoblot analysis showed that the amount of glycolate oxidase was low in dark-grown cotyledons and increased during greening of pumpkin cotyledons. Northern blot analysis showed that the probe could hybridize with a single 1.5-kb species of mRNA from pumpkin cotyledons and that the amount of the hybridizable mRNA increased dramatically during greening of the cotyledons. This observation indicates that the induction of glycolate oxidase during greening of the cotyledons is due to an increase in the level of the mRNA.

Alcohol Oxidoreductases↗

Effects of the immunosuppressant FK506 on a penetrating keratoplasty rejection model in the rat.

PURPOSE: The immunosuppressive effects of FK506 on allogeneic corneal transplantation were tested in a rat model. METHODS: Inbred-strain Lewis rats were used as recipients, and Fisher rats were used as donors. Intraperitoneal injection of FK506 (0.3, 1.0, and 3.0 mg/kg per day) was administered for 2 weeks, and the grafts were inspected by clinical evaluation. Mixed lymphocyte culture assay, using lymphocytes from recipients of penetrating keratoplasty as responder cells and irradiated splenocytes from naive Fisher or Brown Norway as stimulator cells, was used to identify allogeneic stimulation. The rejection process was studied by histology and immunohistochemistry. RESULTS: The rat strain combination developed 100% graft rejection in about 2 weeks after the penetrating keratoplasty. FK506 prolonged the graft survival in a dose-dependent manner, as observed by clinical evaluation. In mixed lymphocyte culture assay, Lewis rats that had been primed to allogeneic stimulation at the time of cornea transplantation presented significant proliferation to Fisher stimulator splenocytes. FK506 suppressed this primed lymphocyte proliferation. Immunohistochemical and histologic studies confirmed the clinical evaluations. Untreated rat corneas, at the second postoperative week, presented a large number of helper/inducer T cells, macrophages, IL-2 receptor-expressing cells, and Ia-antigen-expressing cells. In the same period, FK506-treated rats appeared normal and had no cellular infiltration. Corneas rejected after FK506 cessation had less intense cell infiltration than the control corneas. CONCLUSIONS: These data indicate that FK506 prolonged the corneal graft survival and can be a potentially useful drug in the immunotherapeutic arsenal to suppress corneal graft rejection.

Animals↗

[Effects of inhaled beta-adrenergic and anticholinergic drugs on respiratory function and arterial blood gases in patients with pulmonary emphysema].

We studied the effects of inhaled anticholinergic (oxitropium bromide, 0.2 mg) and beta-adrenergic (fenoterol 0.4 mg) drugs on respiratory function and arterial blood gases in fourteen male patients with pulmonary emphysema (age 63 +/- 8 years; FEV1/FVC 1.41 +/- 0.73 L) using a three day, randomized, double-blind placebo-controlled design. Each day, spirometry and arterial blood gas analyses were performed before and 45 min after inhalation. Both fenoterol and oxitropium bromide significantly improved FEV1 by 21% and 16%, respectively, although there was no significant difference between the two drugs. However, the mean value of PaO2 significantly decreased from 74.5 +/- 2.6 to 69.3 +/- 2.7 Torr with fenoterol, but not with oxitropium and placebo. Change of PaO2 with fenoterol was significantly correlated with %FRC, but not with FEV1 nor change of FEV1. We therefore conclude that an anticholinergic inhalant bronchodilator is more favorable for patients with COPD than a beta-adrenergic agent.

Adrenergic beta-Agonists↗

[A case of intrathoracic dumb-bell ganglioneuroma and a surgical approach using spinal evoked potentials (SEP)].

A successfully treated case of a seven-year-old girl with a left intrathoracic Dumb-bell ganglioneuroma is reported. The tumor was 10 cm in diameter. Preoperative angiography revealed that the location of tumor was very close to the Adamkiewicz artery. In order to prevent the artery from damaging, spinal evoked potentials (SEP) was used during the surgery and was very useful for monitoring the spinal cord. Although SEP has often been employed in spine surgery, the literature on the use of it for posterior mediastinal tumor is scarce. It is considered that SEP is very useful for not damaging the feeding artery to the spinal cord, and for preventing the postoperative neurologic complications.

Child↗

[Late deterioration of functional abilities in adult cerebral palsy].

Clinical characteristics of late deterioration in adult cerebral palsy were reported with detailed neurological evaluations and analyses. 10 adult cases, 9 male and 1 female, with cerebral palsy (CP) were included aged from 24 to 58 years on admission. Without marked mental retardation all had been ambulant and completely independent of ADL with residual spasticity and/or dyskinesia of minimal degree until the second or third decade. Late deterioration of functional abilities starting with numbness or pain in upper extremities at age 24-45 (mean: 36.2 y), associated with profound atrophy of the shoulder girdle and hand muscles. Dyskinesia and spasticity markedly aggravated with urinary and respiratory dysfunctions, resulting in tetraplegia in a couple of years. Mentality is generally unaffected, however, severe dementia occurred in one case. Intensive clinical examinations revealed no particular abnormalities except for mild segmental neurogenic changes by needle EMG. Neuroradiological surveys revealed a marked narrowing of upper to middle cervical spinal canal with deformity and shrinkage of the corresponding cord in most cases. Cranial CT scans and MRI were unremarkable except for diffuse cortical atrophy and ventricular dilation. These studies showed that in adult CP an unexpectedly severe deterioration of sensory, motor and/or mental functions may appear even in previously well achieved cases. These dramatic changes of the clinical features of CP after middle age might be suggestive of the degenerating process and precocious aging of the CNS.

Adult↗

[Respiratory outcome in extremely premature infants following general anesthesia].

This study was aimed to predict the need of postoperative tracheal intubation in premature infants following anesthesia using volatile anesthetics by means of the scoring system derived from our former study of ketamine anesthesia. The subjects consisted of 14 infants (birth weight: 719 +/- 130 g and weight at operation 1882 +/- 312 g) needing cryotherapy for retinopathy and anesthetized with less than 1 MAC of volatile anesthetics. Respiratory outcome was successfully predicted in 9 patients (64%) while no infant was predicted incorrectly to be ready for tracheal extubation. The incidences of postoperative ventilatory support were 28% and 32% after anesthesia with volatile anesthetics and ketamine anesthesia, respectively. However, general anesthesia with volatile anesthetics appeared to be superior in actual outcome to ketamine anesthesia among the patients with high risk scores.

Anesthesia, General↗

[Efficacy of conventional CT in diagnosis of pulmonary emphysema: evaluation of low attenuation area by multiple observers].

The efficacy of conventional CT in the diagnosis of pulmonary emphysema (PE) was studied in 122 patients with miscellaneous diseases including 26 patients with PE. The density and the distribution of low attenuation area (LAA) were evaluated by six independent physicians. Analysis with kappa statistics showed a good inter-observer agreement in the detection of LAA. The grading of LAA correlated well with FEV1/FVC, DLCO/VA, and lung volumes, which indicated that PE could be detected by conventional CT by the evaluation of LAA. The agreement was poor, however, for the detection of low grade LAA and there were some false positives, and there was no specific pattern in the distribution of LAA in PE compared to other pulmonary diseases. We conclude that the evaluation of LAA by conventional CT is simple and effective in the screening of PE.

Aged↗