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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 433 records · Page 24Linked to original sources

A simple method for screening assessment of skin and eye irritation.

A stepwise, simple screening test for skin and eye irritations, suitable for industrial chemicals or pesticides which are not required to be examined for their exact potential irritancy levels, was developed. The efficacy of the test was evaluated using 15 chemicals including typical irritants (acetic acid, ammonia, chloroacetic acid, dioxane, ethanolamine, formaldehyde, formic acid, hydrogen peroxide, phenol, phosphoric acid, propionic acid, sodium hydroxide, sodium hypochlorite, sulfuric acid, and trichloroacetic acid). Chemicals were chosen so as to represent irritants which act by different mechanisms (i.e., strongly acidic, alkaline, reactive to protein, oxidizing etc.). The method consisted of physicochemical tests and animal tests using rats, mice or guinea pigs, namely, a skin irritation test, an intradermal reaction test and an eye irritation test in a sequential manner such that further tests are not required if a positive result is obtained in earlier steps. Results obtained between two laboratories using this method were very similar. Comparison of our results with the data obtained by the conventional method using rabbits showed fairly good coincidence. The method was shown to be useful in assessing skin and eye irritation of chemicals and causes minimal suffering to animals.

Animals

A congenital variant of thrombotic thrombocytopenic purpura in two siblings.

We describe two siblings affected by chronic relapsing thrombotic thrombocytopenic purpura from infancy. The elder brother, a 12-year-old boy had 50 such episodes characterized by acute onset of fever, headache, drowsiness, vomiting, dark urine, thrombocytopenia and anemia. The younger sister, a 6-year-old girl, had 8 episodes with the same clinical manifestations. Petechiae and ecchymoses on the extremities were present throughout their lives. Furthermore, anemia with evidence of red blood cell fragmentation and thrombocytopenia were present chronically. Periodical transfusion of frozen fresh plasma prevented recurrent episodes. These cases suggest that there is a congenital variant of thrombotic thrombocytopenic purpura.

Child

Scanning electron microscopy of the organelles of rat incisor odontoblasts--in particular the tubulo-vesicular elements.

The fine structure of rat odontoblasts (OBs) showing the developmental sequence of cellular maturation along the long axis of the incisor was studied. The cytomorphological changes and relationships of the intracellular components, particularly the membranous component, were investigated mainly by scanning electron microscopy (SEM) using the AODO (A: aldehyde prefixation; O: osmium tetroxide postfixation; D: dimethyl sulfoxide (DMSO) freeze-fracture; O: osmium tetroxide maceration) method and transmission electron microscopy (TEM) using the conventional methods. The following results were obtained: 1) The elongated young OBs were highly polarized and characterized by well-developed concentric cisternal granular (rough) endoplasmic reticulum (rER) layers and Golgi complex. SEM showed the rER was continuous to the agranular (smooth) ER (sER). 2) Transformation of the concentric rER to a tubular network was closely related to the maturation and secretory activity of the OBs. 3) Many branched and elongated tubular mitochondria were observed in the supranuclear region of young OBs. On the other hand, many round-to-ovoid mitochondria were observed particularly in the distal clear area of old OBs. 4) SEM also revealed tubulo-vesicular elements, which are believed to be structures relating to secretory and absorptive functions, composed of secretory granules and small tubules, having connections with the cell membrane in both young and old OBs. Furthermore, the small tubules were continuous with the larger sER tubules in the distal clear area and cell process of the OBs. 5) Using TEM, long lysosomes, various cytosomes and multivesicular bodies (MVBs) were usually observed in the peripheral region and in the distal cytoplasm and major processes of the OBs. The present SEM and TEM studies indicated the MVBs were closely associated with sER tubules of the tubulo-vesicular elements. 6) Both TEM and SEM showed cytosegresomes containing laminated ER and other organelles particularly in the distal clear area of old OBs. 7) SEM also showed some thin lateral branchings of the OBs running along the fine matricial fibrils, as well as matrix-vesicle-like structures deeply invaginated at the basal portion of the cell processes and distributed in the predentine. The present morphological study demonstrated a three-dimensional configuration of the structures relating to secretory and absorptive functions of young and old OBs.

Animals

FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity.

A novel antitumor bicyclic depsipeptide, FR901228, was isolated from a broth culture of Chromobacterium violaceum No. 968 as colorless prisms and the molecular formula was determined as C24H36N4O6S2. This antibiotic reverted the transformed morphology of a Ha-ras transformant to normal, and exhibited prominent antitumor activities against murine and human tumor cell lines both in vitro and in vivo.

3T3 Cells

[Usefulness of twenty-four-hour home monitoring of oxygen saturation in patients with chronic obstructive pulmonary disease].

The clinical usefulness of 24 hr home monitoring of oxygen saturation (SaO2) with pulse oximeter was studied in 48 outpatients with COPD. In addition, doppler echocardiography for measurement of acceleration time (AcT), which inversely correlates with mean pulmonary arterial pressure, a 6-minute walk test, and an exercise study on a bicycle ergometer were performed in 26, 17, and 14 patients, respectively. Nadir SaO2 and the total time during which SaO2 was below 90% were calculated to estimate diurnal and nocturnal oxygen desaturation (diurnal nadir SaO2, diurnal TSaO2 < 90%, nocturnal nadir SaO2, and nocturnal TSaO2 < 90%). Relations between the indices of desaturation measured during home monitoring and dyspnea grade (Fletcher-Hugh-Jones), awake PaO2, AcT, Hb, Ht, and oxygen desaturation during the exercise tests were also studied. Diurnal nadir SaO2 was lowest and diurnal TSaO2 < 90% was longest in the group with dyspnea grade IV. In the other groups, various degrees of oxygen desaturation were observed, even within groups. Diurnal nadir SaO2 and nocturnal nadir SaO2 correlated with awake PaO2, but not with diurnal TSoO2 < 90%. Diurnal nadir SaO2 was similar to nadir SaO2 during the exercise tests. AcT, hemoglobin, and hematocrit correlated with diurnal oxygen desaturation but not with nocturnal oxygen desaturation. From the above findings, we conclude that pulmonary hypertension may be associated with diurnal oxygen desaturation, and that home monitoring of SaO2 is useful for the detection of oxygen desaturation not predicted from dyspnea grade and PaO2 while awake.

Aged

[Nearly total aortic replacement for DeBakey type-I aortic dissection in a patient with Marfan's syndrome].

A successful nearly total aortic replacement for DeBakey type-I aortic dissection in a patient with Marfan's syndrome is reported. A 36-year-old woman developed a DeBakey type-I aortic dissection in October 1987. We replaced the ascending aorta and resuspended the aortic valve urgently, when she had not been diagnosed with Marfan's syndrome. In August 1989, we replaced the distal portion of the descending aorta and the infra-renal abdominal aorta because of dilatation in the diameter of these regions. In September 1990, she had sudden severe chest pain. Computed tomography and Doppler ultrasonography revealed that a new aortic dissection developed in the aortic arch and the descending aorta (three-channeled dissection) and that the new false lumen compressed the true and the old false lumens obstructing the blood flow to the abdominal aorta. She was immediately placed an axilo-femoral bypass, and in January 1991 she underwent the arch and descending aorta replacement using permanent bypass to the supra-aortic branches and partial extracorporeal circulation (first reported by Larmi et al). Postoperative course was satisfactory, and she has been well at 3 years after the operation. Because progressive dilatation of an untreated dissecting aorta is common in patients with Marfan's syndrome, aggressive replacement of the diseased aorta is indicated in these patients.

Adult

Protection against natural killer cells by interferon-gamma treatment of K562 cells cannot be explained by augmented major histocompatibility complex class I expression.

Prior study has revealed that the expression of certain major histocompatibility complex (MHC) class I molecules on the membranes of normal or transformed cells can prevent natural killer (NK)-cell-mediated killing. This has been explained by either (1) the target interference model, or (2) the effector inhibition model. In both cases, MHC class I molecules are concerned but the precise mechanisms are still unclear. The erythroleukaemia K562 cell is known as a NK-sensitive target. This sensitivity has been explained mostly as being due to lack of MHC class I antigens on the K562 membrane. However, several recent studies have indicated that the expression of MHC class I antigens on the cell does not solely explain the protection against NK cells. To elucidate the mechanism of NK-cell-mediated killing, we investigated the killing profiles of the K562 cells by NK cells. Previous studies indicated that the NK-sensitive K562 cells can express some MHC class I antigens on their surface, and become protective against NK-cell killing after treatment with human interferon-gamma (hIFN-gamma). In the present study, we show that this resistance is not rendered by MHC class I expression, because addition of anti-MHC class I monoclonal antibodies (mAb) in the killing assay of hIFN-gamma-treated K562 cells, which express MHC class I antigens as the target, did not restore the sensitivity to NK cells. Moreover, we show that spontaneously occurring K562 clones which could not express MHC class I antigens even after hIFN-gamma treatment, could be protected after treatment with the cytokine. Taken together, these results strongly suggest that the susceptibility of K562 cells to NK cell killing is due to some elements distinct from those related to MHC class I antigens.

Antibodies, Monoclonal

Anti-Ro/SS-A antibody-positive interstitial pneumonitis in a non-lupus patient.

We describe a 42-year-old anti-Ro/SS-A antibody positive non-lupus patient who developed interstitial pneumonitis in combination with several common clinical features with previously reported lupus pneumonitis patients whose anti-Ro/SS-A antibodies were positive, while whose antinuclear antibodies were negative. We consider that these patients may belong to a same new clinical entity. A variety of characteristic manifestations related to anti-Ro/SS-A antibodies has been reported in patients with systemic lupus erythematosus (SLE) and other connective tissue diseases [1] [2], and an association between these antibodies with pulmonary parenchymal involvement has been reported by Hedgpeth and Boulware in patients with SLE [3] [4]. We report here a 42-year-old non-lupus male patient with pulmonary fibrosis who presented with anti-Ro/SS-A antibodies.

Adult

Modulation of protein kinase C in aorta of spontaneously hypertensive rats with enalapril treatment.

We measured protein kinase C (PKC) activity, levels of PKC alpha enzyme and PKC alpha mRNA in aortic media of spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto rats (WKY) and enalapril treated SHR (enal-SHR) to examine whether hypotensive treatment of enalapril modulates PKC in aortic media of SHR. The cytosolic PKC activity in crude samples of aortic media of SHR was higher than in those of WKY or enal-SHR (p < 0.01) and was closely associated with blood pressure (r = 0.84, p < 0.001). The membrane PKC activity was detected in samples of SHR, but virtually no activity was detected in samples of WKY or enal-SHR. The cytosolic PKC activity in DEAE column purified samples of SHR was also higher than in those of WKY or enal-SHR (p < 0.01). The PKC alpha enzyme levels (74-kDa and 77-kDa protein) detected by immunoblot were higher in SHR than in WKY or enal-SHR (p < 0.01). The mRNA levels of PKC alpha were higher in SHR than in WKY (p < 0.01) and were much decreased in enal-SHR (p < 0.01). Thus, PKC activity, PKC alpha and its mRNA levels were higher in aortic media of SHR than those in WKY and these increased levels were reversed with enalapril treatment. Considering the pivotal roles of PKC in the mechanism of cellular proliferation and the pathogenesis of hypertension, these results provide clues in understanding the pathogenesis of hypertension, mechanisms of vascular hypertrophy in hypertension and the beneficial effects of angiotensin converting enzyme inhibitor in the treatment of hypertension.

Animals

Attenuation of hypoxic ventilatory response after recovery from chronic hypoxaemia in a case of pulmonary A-V fistula.

We studied respiratory chemosensitivity in a patient with pulmonary arterio-venous (AV) fistulae before and after surgical removal of the lesions. The patient had had moderate hypoxaemia with hyperventilation before the operation. When first studied, 21 days following surgery, both hypoxic and hypercapnic ventilatory responses were found to be lower than they were preoperatively. During the next 1-2 months, hypoxic ventilatory response continued to fall significantly to a steady value, whereas hypercapnic response showed no further fall. There has been no previous report of such a phenomenon in humans after recovery from chronic hypoxaemia.

Adult

Enhancement of hypertension and renal injury by salt-loading during chronic nitric oxide inhibition. Effects of TCV-116, a novel angiotensin II receptor antagonist.

Endothelium-derived nitric oxide (EDNO) and angiotensin II play a role in the regulation of vascular tone and sodium handling. The objective of this study was to determine the role played by angiotensin II in mediating the arterial pressure and renal response to increments in sodium intake during chronic EDNO inhibition. Six groups of Wistar rats were studied; they were fed either a normal sodium diet (groups I, II, and III) or a high sodium diet (groups IV, V and VI). Rats in groups II, III, V and VI were placed on oral L-N-nitroarginine-methyl ester (L-NAME) for 4 weeks. In groups III and VI, the angiotensin II receptor antagonist, TCV-116, was administered. A significant increase in blood pressure was observed in group V compared with group II at the end of the experimental period. TCV-116 attenuated the L-NAME-induced hypertension in both group III and group VI. Urinary protein excretion and the glomerular sclerotic injury score in group V were greater than in group II. TCV-116 attenuated the proteinuria and glomerular injury induced by chronic EDNO inhibition in the groups with normal (group III) and high sodium intake (group IV). Systemic hypertension and glomerular injury were enhanced by salt loading during EDNO inhibition, and the angiotensin II receptor antagonist, TCV-116, attenuated this salt-induced increase in blood pressure and renal injury, suggesting that EDNO may counteract the renal effects of angiotensin II.

Angiotensin Receptor Antagonists

[Nuclear DNA ploidy pattern and proliferating cell nuclear antigen labeling index in gastric cancer with mucosal involvement].

The DNA ploidy pattern and the expression of proliferating cell nuclear antigen (PCNA) were investigated in 72 gastric carcinoma patients to determine the possible correlation between proliferation kinetics and biological behavior. The diploid pattern was more often observed in cases with mucosal invasion (m cancer) than other cases (sm or advanced cancer). The PCNA labelling index in cases with mucosal invasion was significantly lower than in other cases. The sm cancer was more often observed in patients with high PCNA labelling index (> or = 30%) and aneuploid pattern, while m cancer was more common in patients with low PCNA labelling (< 20%) index and diploid pattern. As a result of this study, we conclude that proliferating kinetics of m cancer may differ from that for sm or advanced cancer. Furthermore, DNA ploidy pattern and PCNA labelling index may be useful as a parameter of depth of invasion.

Adult

[A trial use of prostaglandin E1 for prevention of hepatic veno-occlusive disease after allogeneic bone marrow transplantation].

We performed retrospective analysis of hepatic veno-occlusive disease (VOD) in 57 cases with leukemia after allogeneic bone marrow transplantation (BMT). Prostaglandin E1 (PGE1) was used to prevent VOD in 8 cases at a dose of 0.3 micrograms/kg/hr from day -8 to day 30. No VOD was noted in the PGE1 group, while the incidence of VOD was 8/49 (16.3%) in the non PGE1 group. In twelve patients with pretransplant liver dysfunction, VOD was noted in 0/3 in the PGE1 group and 4/9 (44.4%) in the non PGE1 group, respectively. However, prophylactic effects of PGE1 on VOD is not significant in this study, so further studies are needed to determine the efficacy of PGE1. One of 8 patients with PGE1 prophylaxis had edema and erythema on extremities, however, severe toxicity was not experienced.

Adolescent

A rare case of typical carcinoid of the lung coincident with thymoma.

The present report describes a 42-year-old woman with a coin lesion of the upper lobe of the right lung, preoperatively diagnosed as a small cell lung carcinoma of unusually slow growth. The preoperative workup revealed a mass in the mediastinum, diagnosed as a thymoma. Accordingly, a right upper lobectomy and mediastinal lymph node dissection, followed by a radical thymectomy, were performed. The resected pulmonary specimen was histologically diagnosed as a typical carcinoid and the mediastinal mass as a mixed type thymoma with microscopic invasion. The postoperative course was uneventful. The patient is doing well with no sign of recurrence one year after her operation. To our knowledge, the coincidence of a bronchopulmonary carcinoid and thymoma is believed to be the first such case reported in the literature.

Adult

Evaluation of leukocyte-depleted terminal blood cardioplegic solution in patients undergoing elective and emergency coronary artery bypass grafting.

Leukocyte depletion at reperfusion may have a role in myocardial protection when combined with terminal cardioplegia. We applied this method in a selected group of 68 patients with coronary artery bypass grafting either for elective surgical procedures (n = 38) or emergency surgical procedures with the use of a preoperative intraaortic balloon pump (n = 30) because of developing acute myocardial infarction. Basic cold potassium crystalloid cardioplegic solution was used. During delivery of leukocyte-depleted terminal cardioplegic solution, warm arterial blood delivered from cardiopulmonary bypass was passed through a leukocyte removal filter, mixed with potassium crystalloid cardioplegic solution, and administered to the aortic root for the first 10 minutes of reperfusion. Patients were randomized into three groups for reperfusion: whole blood, terminal cardioplegic solution, and leukocyte-depleted terminal cardioplegic solution reperfusion groups. In elective coronary artery bypass grafting, no significant difference was found in the clinical data. However, in emergency coronary artery bypass grafting, the leukocyte-depleted terminal cardioplegic solution group (n = 10) showed significantly lower peak creatine kinase MB levels (leukocyte-depleted terminal cardioplegic solution versus terminal cardioplegic solution versus whole blood: 27 +/- 11, 56 +/- 13, 74 +/- 18, respectively; p < 0.05) and maximum dopamine doses required at the weaning of cardiopulmonary bypass (6.3 +/- 1.1 versus 11.2 +/- 3.3 versus 9.2 +/- 2.2; p < 0.05) than did the terminal cardioplegic solution (n = 10) and whole blood groups (n = 10). Moreover, the leukocyte-depleted terminal cardioplegic solution group showed significantly lower difference of malondialdehyde between arterial and coronary sinus blood (0.15 +/- 0.09 versus 0.36 +/- 0.06 versus 0.06 +/- 0.12 nmol/ml, p < 0.05) than did the terminal cardioplegic solution or whole blood groups. These results showed that leukocyte-depleted terminal blood cardioplegic solution may have a role in attenuating reperfusion injury in patients with critical conditions such as preoperative myocardial ischemic injury.

Adult

Methods in pathology. An improved method for DNA diagnosis of leprosy using formaldehyde-fixed, paraffin-embedded skin biopsies.

To improve the sensitivity of the previously reported polymerase chain reaction (PCR) for the detection of Mycobacterium (M.) leprae in the formaldehyde-fixed, paraffin-embedded tissues, we adapted the PCR designed to amplify an internal 372 bp fragment of a M. leprae-specific repetitive sequence to 39 skin biopsies taken from patients with leprosy of the lepromatous type and tuberculoid type. Crude DNA samples were prepared from tissue sections that were deparaffinized and subjected to proteinase-K digestion without any further treatment for DNA purification. Overcoming a false-negative reaction by an elongation of the period for enzymatic digestion and an appropriate dilution of the samples, an amplification of the target sequence was obtained as a single band with all 39 skin biopsies tested. The fragments specifically amplified by the PCR were subjected to direct sequencing and were confirmed to be identical with an internal 372 bp of M. leprae-specific repetitive sequence. Although in nine of 24 nonleprosy control samples, a false-positive amplification was observed as from one to several bands, they were distinguishable from the specific one by the electrophoretic pattern. This PCR makes up for the classic histological methods used in the diagnosis of leprosy.

Base Sequence

Characteristics of the two newly established cell lines of human pulmonary adenocarcinoma and their sensitivity to anticancer agents.

Two adenocarcinoma cell lines were established from metastatic lymph node of lung cancer patients. The cell lines were named NUTLC-1 and NUTLC-3. They were found to have the following biological characterization and sensitivity to anticancer agents by comparison with clinical effect of the drugs on each donor patient: 1) By chromosomal analysis, the tumor cells of two cell lines were human-origin cells. Number of chromosomes of these cell lines ranged from 67 to 77 in NUTLC-1 cells and from 61 to 66 in NUTLC-3 cells, with the modal numbers of 73 and 64, respectively. 2) The tumor cells of the two cell lines were heterotransplanted subcutaneously into nude mice, but, no natural distant metastasis was observed 2 months after transplantation. 3) Sensitivity to anticancer agents on NUTLC-1 and NUTLC-3 cells differed individually according to methylthiazol tetrazorium (bromide) (MTT) colorimetric assay. NUTLC-1 cells were sensitive to Mitomycin C (MMC) and Adriamycin (ADM), and insensitive to Cisplatinum (CDDP), 5-Fluorouracil (5-FU) and Etoposide (VP-16). Antitumor effect of CDDP and 5-FU on recurrent tumor of donor patient was not observed clinically. NUTLC-3 cells were sensitive to CDDP, MMC and ADM, and insensitive to 5-FU and VP-16. Sensitivity to CDDP and MMC on NUTLC-3 cells also correlated to clinical effect of the drugs on the donor patient. From these results, it appears that these new cell lines are useful materials for studies on lung cancer.

Adenocarcinoma

Heat shock induces synthesis of plastid-associated hsp70 in etiolated and greening pumpkin seedlings.

Heat shock proteins of hsp70 family with molecular weight of 76 and 73 kDa were detected both in etiolated as well as in greening pumpkin seedlings using immunoblotting technique. Both proteins exhibited heat shock inducibility and their apparent amount depended on the plant organ examined as well as on the greening time. Sucrose density gradient centrifugation revealed that the 76 kDa band should be attributed to chloroplasts and the 73 kDa band to mitochondrial fraction. The 76 kDa band dominated in cotyledons and was hardly detectable in root preparation whereas the 73 kDa band was prevailing in hook samples but was also clearly detectable both in cotyledons and in roots.

Centrifugation, Density Gradient