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Biomedical subjects

J Shindo

Publications and source records attributed to J Shindo.

At least 19 recordsLinked to original sources

Granulocyte-macrophage colony-stimulating factor prevents the progression of atherosclerosis via changes in the cellular and extracellular composition of atherosclerotic lesions in watanabe heritable hyperlipidemic rabbits.

BACKGROUND: A cytokine network is involved in atherogenesis. This study was conducted to investigate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the development and composition of atherosclerotic lesions in Watanabe heritable hyperlipidemic (WHHL) rabbits. METHODS AND RESULTS: GM-CSF (10 microg. kg-1. d-1) was administered to 4-month-old WHHL rabbits (n=9) 5 days a week for 7.5 months, whereas an equal dose of human serum albumin was administered to controls (n=9). The cholesterol levels were not changed significantly by the treatment. Age-matched 4-month-old rabbits (n=7) had atheromatous plaques over 30.7+/-5.7% of the inner surface area of the aortic arch. After treatment, the percentages of surface atheromatous plaques to total aortic arch area were 45.0+/-12.6% in the GM-CSF group and 74.3+/-11.0% in controls (P<0.0001). Histological examination demonstrated that GM-CSF reduced the ratio of intima to media (P<0.01) and cross-sectional areas of atherosclerotic lesions (P<0.0001). Quantitative analysis indicated a marked decrease in the areas of smooth muscle cells (P=0.0001), collagen (P=0.0001), and extracellular lipid deposits (P<0.05) of atheromatous plaques in GM-CSF-treated rabbits compared with controls. The terminal deoxynucleotidyltransferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method and immunohistochemistry were performed to examine the relationship between decreased atherosclerotic lesions and apoptosis. The percentage of TUNEL-positive cells increased in the GM-CSF group (GM-CSF, 24.1+/-4.4% versus control, 11.6+/-3.2%; P<0.0001). GM-CSF enhanced the apoptosis of smooth muscle cells in the shoulder region and the fibrous cap (P<0.0001), suggesting one of the mechanisms for the antiatherogenic effect. CONCLUSIONS: GM-CSF altered the composition of atherosclerotic lesions and reduced the atherosclerosis in WHHL rabbits.

Animals

[Anesthesia for tracheobronchial stent insertion].

We experienced nine cases of general anesthesia for tracheobronchial stent insertion. As far as possible, we anesthetized the patients under spontaneous respiration with inhalation anesthesia, depending on the types of the tracheobronchial stent (Dumon stent or expandable metallic stent), or respiratory status of the patient. Having experienced a case requiring PCPS (percutaneous cardiopulmonary support) to recover from severe ventilatory insufficiency due to tracheal perforation, we, in advance, inserted 18- or 20-gage cannulas into the femoral artery and vein for PCPS standby, and could manage general anesthesia safely for tracheobronchial stent insertion.

Adult

Kidney-alone transplantation in diabetic patients with end-stage renal disease.

From January 1989 to December 1995, 5 diabetic patients with end-stage renal disease (1 woman, 4 men) underwent kidney-alone transplantation. The mean age of the recipients at the time of transplantation was 37.4 years (range, 32 to 43). Craft function and glucose tolerance was evaluated for 5 to 72 months after surgery. Postoperative complications were seen in 2 patients; nonspecific subcutaneous infections and an asymptomatic partial allograft infarction. All renal allografts were functioning 1 year after transplantation, with a mean serum creatinine level of 1.10 mg/dL (range, 0.8 to 1.8 mg/dL), and a mean urinary protein level of 17.8 mg/dL (range, 5 to 27 mg/dL). The postoperative daily dose of insulin was higher than the preoperative dose, while the level of glycated hemoglobin (HbA1C) increased after surgery and peaked 6 months after transplantation; 1 year after transplantation it had reverted to the preoperative level. As long as the diabetic complications of the renal allograft recipients are not severe, the short-term survival and the renal function of diabetic patients with end-stage renal disease improves after kidney-alone transplantation, which is still the standard method of treatment in Japan.

Adult

Effects of eye position on saccades evoked by stimulation of the monkey superior colliculus.

Effects of different initial eye positions on saccades evoked by electrical stimulation of the superior colliculus (SC) were investigated in alert monkeys with the head restrained. The dependence of saccade vector on initial eye position was studied quantitatively by multiple regression analysis. Following stimulation at 240 of 367 sites in the SC, saccade vector was influenced by initial eye position. The magnitude of eye position effects on horizontal saccade component was similar to that for vertical component. These effects were mostly found with stimulation in the caudal SC. Results suggest that eye position signals may control excitability of neurones in the SC.

Animals

Effects of granulocyte-macrophage colony-stimulating factor on the levels of VLDL and LDL receptor mRNAs in vivo.

We investigated the mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) lowers plasma cholesterol levels. Recombinant human GM-CSF (rhGM-CSF) was administered to normal and Watanabe heritable hyperlipidemic (WHHL) rabbits. Treatment with rhGM-CSF reduced the levels of cholesterol and triglyceride in these animals. In vitro colony assay for hematopoietic progenitors indicated that rhGM-CSF was capable of supporting granulocyte-macrophage colony formation in rabbits, suggesting that rhGM-CSF stimulates macrophage function even in rabbits. Northern blot analysis of rabbit very-low density lipoprotein (VLDL) receptor showed that rhGM-CSF elevated the levels of VLDL receptor mRNA 2.6- and 1.8-fold in muscles of normal WHHL rabbits, respectively, 1.5 hours after a single injection. Increases of 1.5- and 1.4-fold were observed in muscles of these rabbits after 5 days of administration. No changes were found in the LDL receptor mRNA levels in liver, spleen or bone marrow. These findings show that the lowering of lipids by GM-CSF may be mediated through the up-regulation of the VLDL receptor mRNA and the enhancement of macrophage function.

Animals

Expression of very low density lipoprotein receptor mRNA in rabbit atherosclerotic lesions.

The expression of very low density lipoprotein (VLDL) receptor mRNA in atherosclerotic lesions in rabbits was investigated. To examine the expression of the VLDL receptor in the vascular wall, poly(A)+ RNA was isolated from whole aortas of cholesterol-fed New Zealand White (NZW), Watanabe heritable hyperlipidemic (WHHL), and normal NZW rabbits, and then Northern blot analysis was performed. The VLDL receptor mRNA was detected in aortas from both NZW rabbits fed 0.5% cholesterol for 16 weeks and 12-month-old WHHL rabbits, whereas no expression was seen in normal NZW rabbit aortas. To further determine the localization of the VLDL receptor mRNA, in situ hybridization using digoxigenin-labeled riboprobes and immunohistochemistry using monoclonal antibodies against each cell component were performed. Early atherosclerotic lesions, termed fatty streaks, in the NZW rabbits fed 0.5% cholesterol for 4 weeks demonstrated strong expression of the VLDL receptor mRNA by macrophages. The VLDL receptor mRNA was also expressed in more advanced atherosclerotic lesions from both atherogenic animal models. The predominant origin of the VLDL receptor mRNA-positive cells was macrophages, and some intimal smooth muscle cells appeared to express a weak but significant signal in these advanced lesions. Our findings suggest that the VLDL receptor expression may play a role in the development of atherosclerosis.

Animals

Lidocaine action and conformational changes in cytoskeletal protein network in human red blood cells.

The mechanism of action of lidocaine, which is commonly used clinically as a local anesthetic, was studied in human red blood cells. The influx of [14C]lidocaine through the cell membrane induced reversible transformation of human red blood cells from discocytes to stomatocytes. This change in shape depended on the lidocaine concentration and required both ATP and carbonic anhydrase. The lidocaine-induced shape change occurred as a result of spectrin aggregation, which altered the intracellular environment of the human red blood cells, mediated by carbonic anhydrase and activation of vacuolar type H(+)-ATPase (V-ATPase). Lidocaine controlled the influx of 22Na into the human red blood cells in a concentration-dependent manner. When incubated in media containing 6-chloro-9-[(4-diethylamino)-1-methyl-butyl]amino-2-methoxyacridine (mepacrine), an inhibitor of Na+ channels, human red blood cells changed shape from discocytes to stomatocytes and the intracellular pH decreased. This phenomenon was very similar to the shape change induced by lidocaine. These results suggest that the mode of action of lidocaine is related to a conformational change in the cytoskeletal protein network.

Adenosine Triphosphate

Effects of roxithromycin on proliferation of peripheral blood mononuclear cells and production of lipopolysaccharide-induced cytokines.

Roxithromycin (RXM), a new macrolide antibiotic, has a 14-member macrocycline ring structure which is similar to that of erythromycin. We investigated the effects of RXM on the proliferation of peripheral blood mononuclear cells (PBMCs) and the production of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) by PBMCs stimulated with lipopolysaccharide (LPS). At concentrations greater than 25.0 micrograms/ml, RXM suppressed the proliferation of PBMCs stimulated with phytohemagglutinin, probably due to cytotoxicity. When the PBMCs were incubated with RXM for 7 d, the number of adherent cells (monocyte/macrophages) increased. Incubation with RXM at a concentration of 25.0 micrograms/ml induced the greatest increase (p < 0.05). IL-1 beta and TNF-alpha were present 3 h after LPS-stimulation, and IL-1 beta production reached a peak at 12 h and TNF-alpha production at between 6 and 12 h, and then their production declined. RXM (25 micrograms/ml) suppressed the production of IL-1 beta and TNF-alpha slightly during the entire course of the incubation. This suppression was dose-dependent. Anti-human granulocyte-macrophage colony-stimulating factor and anti-human macrophage colony stimulating factor antibodies had no effect on the RXM-induced proliferation of adherent cells. Suppression of the production of IL-1 beta and TNF-alpha by RXM suggested that this drug might have anti-inflammatory and immunosuppressive effects.

Anti-Bacterial Agents

[Home days ratio in patients treated with long-term oxygen therapy].

The home days ratio (days at home/observation period) is an important index for evaluating the efficacy of therapy for chronic disease. To compute the home days ratio in patients treated with long-term oxygen therapy, we retrospectively studied the records of 72 consecutive patients with chronic respiratory failure who received long-term oxygen therapy from the Department of Pulmonary Medicine, Ogaki Municipal Hospital. These patients were representative of those treated with long-term oxygen therapy in terms of age, cause of hypoxemia, blood gas values, and pulmonary function. The home days ratio gradually decreased; it was 92.7 +/- 15.2% during the first year, 87.5 +/- 24.0% during the second year, and 78.5 +/- 39.7% during the third year. The home days ratios in survivors (n = 39) were greater than in non-survivors (n = 33). For the first year: 96.7 +/- 7.5% vs. 85.8 +/- 21.9%, p = 0.034; for the second year: 99.0 +/- 2.6% vs. 71.4 +/- 31.0%, p = 0.004; for the third year: 96.0 +/- 9.0% vs. 48.4 +/- 53.1%, p = 0.081, for survivors and non-survivors, respectively. These data suggest that non-survivors can be distinguished from survivors soon after the start of oxygen therapy.

Aged

Potent cholesterol-lowering effect by human granulocyte-macrophage colony-stimulating factor in rabbits. Possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor.

The mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) lowers plasma cholesterol levels is not well understood. We tested recombinant human GM-CSF (rhGM-CSF) on plasma cholesterol and triglycerides in rabbits and attempted to determine the mechanisms of the cholesterol-lowering effect. rhGM-CSF (20 micrograms.kg-1.d-1) was administered to normal and cholesterol-fed rabbits for 2 weeks and to Watanabe heritable hyperlipidemic (WHHL) rabbits for 1 week. The administration of rhGM-CSF markedly lowered cholesterol and triglycerides, an effect that persisted in normal and cholesterol-fed rabbits even after termination of treatment. The cholesterol-lowering effect of rhGM-CSF was also observed in WHHL rabbits. rhGM-CSF was capable of stimulating granulocyte-macrophage colony formation in vitro in rabbits with an effect comparable to that in humans. Northern blot analysis with rabbit very-low-density-lipoprotein (VLDL) receptor cDNA revealed that rhGM-CSF increased the levels of VLDL receptor mRNA in muscle of rabbits after only 1.5 hours of treatment compared with control (2.6-fold), with the 1.5-fold increase following a 5-day administration. No changes in the levels of LDL receptor mRNA in liver, spleen, and bone marrow were observed in the treated rabbits. These findings suggest that the cholesterol-lowering effect of rhGM-CSF may be mediated by enhancement of macrophage functions in lipid metabolism and the increase in mRNA for VLDL receptor in rabbits.

Animals

[Clinical study of patients with nocturnal asthmatic attacks admitted to an emergency room].

Over the periods of a year, we studied the patients who were admitted to the emergency room at our hospital at night with asthmatic attacks. From July 1991 to June 1992, 10,932 patients were admitted to the internal department of our emergency room, 707 (6.5%) of them because of asthmatic attacks. These 707 consisted of 364 patients (51.5%) with mild attacks, 242 (34.2%) with moderate attacks and 101 (14.3%) with severe attacks according to Mitsui's score. Most patients admitted before 23:00 and after 5:00, but more patients with severe attacks were admitted around midnight. A large part of the patients with moderate or severe attacks had chronic hypoxemia, and more than half of the patients' serum theophylline concentration was under the therapeutic rate. More than half patients were treated within 5 minutes. But within those who were not, 6 patients with mild attacks on admission needed hospitalization later. For prevention of life threatening attack, we should regard it as an important problem to follow up the patients who don't come to the hospital in the daytime in spite of frequent visits to the emergency room at night.

Asthma

[Relationship between limitation of daily life and prognosis in patients with sequelae of tuberculosis treated with long-term oxygen therapy].

The sequelae of tuberculosis (TBC) sometimes causes severe restrictive lung disorders. In Japan, lung tuberculosis was pandemic up to the 1950s, with TBC being a major underlying disease of chronic respiratory failure and cor pulmonale. Until the end of 1991, we encountered 95 cases of Home Oxygen Therapy (HOT) in Ogaki area, 30 of which were patients with TBC. To clarify factors affecting the prognosis of these patients, we examined background factors, directing special attention to daily activities. In this study, 10 inactive patients (Group A) whose daily activity was limited to indoors and 10 control patients (Group B) whose age, vital capacity and arterial PO2 were equal to inactive patients, from the 30 TBC cases were used. A comparison was made of the prognoses. Among the patients, activity was closely related to dyspnea grade and arterial PCO2. Group A patients showed more marked dyspnea and lower arterial PCO2 than those of group B patients. Percentage home stay and cumulative survival rates of Group A patients (percentage home stay, 59.2 +/- 38.7% and 3 year survival, 26.3%) were significantly less than those of Group B patients (91.0 +/- 16.4% and 87.5%, p < 0.05, respectively). Among chronic pulmonary emphysema patients treated with HOT, no significant relation between activity and prognosis could be found, when factors of age, arterial PO2 and forced expiratory volume in 1 sec were excluded. There would thus appear to be a close relation between activity and prognosis in TBC patients specific for underlying disease.

Activities of Daily Living

[Type III procollagen N-terminal peptide (P-III-P, prolyl hydroxylase (PH), and laminin P1 levels in serum and BALF of radiotherapy patients].

The etiology of pulmonary fibrosis remains unclear, and at present there are no definite biochemical markers of its activity. We measured serum and BALF levels of type III procollagen N-terminal peptide (P-III-P), prolyl hydroxylase (PH), and laminin P1 in patients who had undergone radiotherapy for malignant neoplasms, and investigated their value as biochemical markers in a model of pulmonary fibrosis. The following results were obtained: 1) Patients with abnormal liver function had significantly higher serum P-III-P levels and showed a tendency to have higher serum PH levels. If P-III-P or PH are to be used as markers of pulmonary fibrosis, the effect of liver function must be taken into consideration; however, no significant difference was detected with respect to laminin P1 levels. 2) Serum P-III-P levels were significantly elevated by radiotherapy. 3) Laminin P1 levels rose in a similar manner to P-III-P levels after radiotherapy, but no significant change was detected. 4) In most cases, the levels of all markers in BALF were below the threshold of detection, nevertheless all three markers were elevated in a patient who developed diffuse radiation pneumonitis during radiotherapy. Increases in the lymphocyte count were found in BALF of this patient. 5) BALF hyaluronic acid levels were negative in the 3 cases assayed. 6) A significant correlation between P-III-P and laminin P1 in serum was shown, but no significant correlations could be found between the other combinations of markers in serum. Thus it appears that serum P-III-P and laminin P1 are valid biochemical markers of pulmonary fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid

[Percent home stay, an index for the clinical evaluation of home oxygen therapy].

To evaluate the usefulness of % home stay as an index for evaluation of the clinical effects of long term home oxygen therapy (HOT), we retrospectively examined 70 consecutive cases with chronic respiratory failure treated by HOT in the Ogaki area. The clinical data, underlying diseases, and survival rate of the cases were similar to recent official statistics in Japan; thus, we considered these cases to be a representative population. For evaluation, we tentatively used a % home stay of 70% as the standard level, which was determined by the 25th percentile line. To examine the usefulness of this standard, we classified the study population into 2 groups (the group with % home stay of greater than 70% (Group A, n = 54), and the group with % home stay of less than 70% (Group B, n = 16)), and compared the outcomes, survival rates, life situations, and background factors between these groups. As a result, there were significant differences in outcome (at home 34%, hospitalized 11%, and dead 22% in group A, and 6%, 44%, and 50%, respectively in group B, p less than 0.05), survival rate (p less than 0.05 by logrank test), and life situation between these groups. Thus, a % home stay of 70% is thought to be a useful standard for clinical evaluation, because it reflects both the prognosis and quality of life of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living

Technetium-99m pertechnetate and gallium-67 imaging in salivary gland disease.

Thirty-two patients with salivary gland tumors or sialadenitis were studied with Tc-99m pertechnetate and Ga-67 imaging and, in some instances, sialography. The diagnostic algorithm presented allows the correct categorization of the salivary gland pathology in the vast majority of patients. The patients were studied serially with Tc-99m pertechnetate, Ga-67 and in certain situations sialography (or CT-sialography). Use of the algorithm can distinguish benign salivary tumors from malignant tumors and malignant tumors from inflammatory disease. The limitations and pitfalls of interpretation are discussed.

Adult