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Biomedical subjects

M Kanazawa

Publications and source records attributed to M Kanazawa.

At least 109 records · Page 6Linked to original sources

Localization of laminin subunits in the central nervous system in Fukuyama congenital muscular dystrophy: an immunohistochemical investigation.

We have undertaken an immunohistochemical study of laminin subunits in the central nervous system (CNS) of fetuses and patients with Fukuyama congenital muscular dystrophy (FCMD) and of controls including five fetuses. Immunoreaction product deposits with antibodies to laminin alpha 1, alpha 2, beta 1 and gamma 1, and beta-dystroglycan were detected on the surface and vessels of the CNS of controls. No staining with anti-alpha-sarcoglycan antibody was detected in the CNS. Neurons and glia did not react with any of the antibodies used. In utero expression of laminin subunits and beta-dystroglycan seemed to be lower in the cerebrum than in the spinal cord. Moreover, immunostaining for laminin alpha 2 and beta 1 tended to be weak on the fetal spinal cord surface. Expression of laminin subunits and dystrophin-associated proteins in the CNS may be modulated during development, as in the skeletal muscle. The distribution of immunoreaction product deposits was basically the same in FCMD and controls, although laminin alpha 2 and beta-dystroglycan expression appeared to be decreased in the CNS of the FCMD cases. Defects of the pial-glial barrier of the fetal brain surface have been considered the main cause of micropolygyria in FCMD, and these observations suggest that the co-localization and secondary loss of these proteins in association with the unknown product(s) of the FCMD gene might be involved in the CNS lesions of this disorder.

Adult↗

Alterations of insulin and glucagon secretion from the perfused pancreas before, at the onset and after the development of diabetes in male Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an obese non-insulin dependent diabetes mellitus (NIDDM) model of an inbred strain. In this study, basal (2.8 mM glucose) insulin and glucagon and their responses to glucose (16.7 mM) were examined at the age of 9 weeks (n = 3) before the onset of diabetes, at 23 weeks (n = 6) at the onset of diabetes, and at 48 weeks (n = 5) after the development of diabetes by pancreatic perfusion. In Long-Evans Tokushima Otsuka (LETO, control) rats, insulin responses to glucose showed a biphasic pattern at all three ages, while in OLETF rats, basal insulin concentrations were significantly increased compared to those in controls at the age of 9 and 48 weeks. Insulin responses to glucose showed no difference from controls at 9 and 23 weeks, however, at 48 weeks the response was significantly decreased. In controls, high basal glucagon concentrations showed significant decrease in response to glucose at all ages. In OLETF rats, basal glucagon concentrations showed significant decrease compared to those in control rats at 23 and 48 weeks. Glucagon response to glucose significantly decreased at 9 and 23 weeks, but at 48 weeks there was no change in concentration in response to glucose. Pancreatic insulin content was lower at 48 weeks in OLETF rats than in LETO rats, although no differences were observed at other ages. There were no significant differences in pancreatic glucagon content between the two groups at any age. Morphologically, in OLETF rats the number of pancreatic B cells were decreased and A cells migrated into the center of islets at 48 weeks. The results suggested that one of the causes of diabetes in OLETF rats is impaired insulin response to glucose.

Animals↗

HSDJ, a human homolog of DnaJ, is farnesylated and is involved in protein import into mitochondria.

The role of HSDJ, a human homolog of bacterial DnaJ and yeast YDJ1p/MAS5, in mitochondrial protein import was examined. Recombinant HSDJ was purified and an antibody was prepared. HSDJ mRNA was heat-induced in cultured cells. In pulse-labeling and chase experiments using COS-7 cells, the endogenous HSDJ homolog was prenylated. Transiently expressed HSDJ was also prenylated, whereas its mutant C394S in which cysteine of the "CaaX box" was mutated to serine, was not. HSDJ, but not C394S, synthesized in rabbit reticulocyte lysate was farnesylated. The HSDJ antibody inhibited import of ornithine transcarbamylase precursor (pOTC) into isolated mitochondria when added prior to pOTC synthesis, but not when added prior to import assay. In transient expression of pOTC in COS-7 cells, pOTC was synthesized and processed to the mature form with an apparent half-life of 2-3 min. Coexpression of HSDJ or C394S resulted in slight retardation of the pOTC processing. These results indicate that HSDJ is involved in an early step(s) of protein import into mitochondria.

Animals↗

Circadian blood pressure rhythm in patients with higher and lower spinal cord injury: simultaneous evaluation of autonomic nervous activity and physical activity.

OBJECTIVE: To examine the relationships among the circadian rhythms of blood pressure, autonomic nervous function, and physical activity of patients with varying levels of spinal cord injury. DESIGN AND METHODS: We studied 19 patients with spinal cord injury [10 tetraplegic patients with cervical cord injury (C4-C7), and nine paraplegic patients with thoracic cord injury (Th6-Th12)] compared with 16 control subjects. A new multibiomedical recorder was used to measure blood pressure (every 30 min), cardiac vagal activity (hourly frequency of R-R50), and physical activity (integrated acceleration/min) for 24 h under hospital conditions. Systemic sympathetic nervous activity and sympathoadrenal functioning were assessed by examination of hormone levels in the blood. RESULTS: Daytime and night-time values were compared; the variations in systolic and diastolic blood pressures and heart rate were slight in members of the tetraplegia group, but almost normal differences were observed in members of the paraplegia group. The circadian profile of cardiac vagal activity was normal for both patient groups, suggesting that an alteration in the sympathetic nervous rhythm had occurred in the tetraplegic patients. The plasma norepinephrine level was lower in members of the tetraplegia group than it was in members of the control group (P< 0.001), but was normal in members of the paraplegia group. The plasma level of epinephrine was lower in members of the tetraplegia (P< 0.05) and the paraplegia (P < 0.1) groups than it was in members of the control group. Daytime physical activity of members of both groups of patients was lower than that of subjects in the control group (P< 0.001 for both). CONCLUSION: The central sympathoexcitatory pathway to the upper thoracic cord plays a critical role in the maintenance of normal circadian blood pressure rhythm in humans. Motor nerve functioning and sympathoadrenal secretion are not essential to this regulation.

Adolescent↗

Basaloid-squamous cell carcinoma of the floor of the mouth: characterization of a cell line.

Since it was first described in 1986, basaloid-squamous cell carcinoma (BSC) has been considered a distinct variant of squamous cell carcinoma that occurs in a variety of anatomic sites, including the head and neck region. We report the characterization of the first cell line established from a basaloid-squamous cell carcinoma of the floor of the mouth. The cell line exhibited a highly invasive capacity, indicating that BSC has very aggressive behavior. This cell line may be a useful model for elucidation of the biological characteristics of BSC.

Actins↗

Downmodulation of IL-8 receptors, type A and type B, on human lung neutrophils in vivo.

We examined the expression of interleukin (IL)-8 receptors (Rs), type A (IL-8-RA) and type B (IL-8-RB), on peripheral blood and bronchoalveolar lavage (BAL) fluid neutrophils; we also examined IL-8 and other chemoattractants in the epithelial lining fluid (ELF) of patients with chronic lower respiratory tract infection (CLI) to elucidate the in vivo regulation of IL-8Rs. Neutrophils were stained with monoclonal antibodies specific for IL-8-RA and IL-8-RB. We detected higher levels of IL-8 (81.6 +/- 25.4 ng/ml, mean +/- SE), leukotriene (LT) B4, and IL-1 beta in the ELF of the CLI patients than in their serum (P < 0.05). The expression of IL-8Rs on BAL neutrophils was significantly lower than that on peripheral blood neutrophils (P < 0.01 for both). In vitro analysis showed that low-level IL-8 (50 ng/ml) alone did not affect IL-8R expression but that it was downregulated by high-level IL-8 (500 ng/ml) alone and by low-level IL-8 in combination with LTB4 or IL-1 beta. Staurosporine reduced the downmodulation by low-level IL-8 plus LTB4 or IL-1 beta but not by high-level IL-8 alone. We speculate that pulmonary IL-8-RA and IL-8-RB may have been downmodulated by the combined effect of local chemoattractants through, in part, a protein kinase C-dependent mechanism.

Adult↗

Fatal diffuse alveolar damage from bird fanciers' lung.

A 68-year-old man, who had continuing exposure to budgerigars, developed fatal acute respiratory failure following years of slowly progressive pulmonary deterioration. His lung function was characterized first by mild airflow obstruction and later by progressive loss of lung volume. Computed tomography showed progressive development of pulmonary fibrosis and honeycombing. His serum disclosed precipitins to pigeon antigen. During his final illness his chest radiograph showed widespread patchy consolidation. At autopsy, his lungs revealed left lower lobe bronchopneumonia, fibrosis and honeycombing at the bases and widespread evidence of diffuse alveolar damage with organized exudate in some alveoli. To our knowledge, this is the second reported fatality due to acute alveolar injury in bird fanciers' lung.

Acute Disease↗

New successful treatment with disinfectant for atopic dermatitis.

For the treatment of atopic dermatitis, a variety of therapies are used including folk medicine. At present, there is no single treatment which is effective to cure the symptoms of atopic dermatitis completely in all patients. We are drawing attention to the high isolation rate of Staphylococcus aureus when starting disinfectant treatment combined with topical steroid therapies for the purpose of killing S. aureus. As a result, we examined many patients in whom almost a complete remission was obtained even after short periods of therapy, though it had been difficult to obtain improvement by conventional treatments. In many patients, IgE values and reagin antibody titer decrease dramatically soon after starting treatment. As a disinfectant, 10% povidone-iodine solution was used. We investigated also the effect of iodine contained in the povidone-iodine solution on the thyroid gland.

Administration, Topical↗

[Thoracoscopic unilateral fold plication method in lung volume reduction surgery for diffuse pulmonary emphysema].

We have devised a 'Fold Plication Method', which helps ensure safe and simple lung volume reduction surgery (LVRS) for pulmonary emphysema and prevent air leakage from pulmonary stumps, which is most crucial problem, in addition to postoperative interstitial pneumonia that is occasionally caused by the use of the bovine pericardium. We performed LVRS on seven patients with the disease, using this method and the thoracoscopic surgery, which is based on the 'Two Windows Method' we had previously developed. The operation was performed without observable bleeding within approximately one hour for all patients, who then recovered favorably.

Aged↗

[Gastroesophageal reflux and airway disease].

Gastroesophageal reflux may cause a variety of airway diseases such as asthma, aspiration pneumonia, chronic bronchitis, posterior laryngitis, and ulceration or polyp formation on the vocal cords. Among these asthma seems most common and important clinically. Reflux not only may trigger and aggravate an episode of airway obstruction but also may contribute to nocturnal symptoms. Both clinical and experimental observations suggest that the pathogenetic mechanism may be a vagal reflux following stimulation of lower esophageal receptors and/or microaspiration of gastric acid into the trachea. Diagnosis is usually based on clinical history of asthma and symptoms of gastroesophageal reflux, but in some cases, diagnostic tests such as 24-hour esophageal pH monitoring may be necessary. General measures to avoid reflux and an H2-receptor antagonist together with supportive gastric medications may be the standard treatment. If symptoms persist, proton pump inhibitor may be helpful. Antireflux surgery may provide long-term improvements. Although surgical treatment is indicated only in patients with intractable esophagitis at present, it may be used more commonly through a laparoscopic approach in the near future.

Asthma↗

[A case of interstitial pneumonia induced by intravesical administration of bacillus Calmette-Guerin (BCG)].

A 61-year-old man with superficial bladder cancer, which was detected after he complained of hematuria, was treated three times with intravesical BCG administration. Since liver dysfunction was detected thereafter, he was admitted to our hospital. Three days after admission, he complained of dyspnea on exertion associated with severe hypoxemia, as well as abnormal findings on chest X-ray, i.e. extensive bilateral lung densities. We performed bronchoscopic examination and obtained bronchoalveolar lavage fluid (BALF) and lung biopsy specimens (TBLB). In the BALF, a marked increase in the total cell number, particularly lymphocytes with a high CD4/CD8 ratio was noted. TBLB specimens revealed the lesions to be numerous non-caseating granulomas. We failed to obtain definite evidence of BCG in the sputum, urine, blood, and BALF. Instead, we found that a lymphocyte stimulation test for BCG (DLST) was strongly positive. Based on these findings, severe interstitial pneumonia probably induced by hypersensitivity against BCG, was diagnosed. Anti-tuberculous agents, and steroid-pulse therapy followed by oral administration of relatively low dose of steroid ameliorated the abnormal conditions, including chest X-ray film findings and hypoxemia. The population of lymphocytes and CD4/CD8 ratio in the BALF were reduced as well. Serious interstitial pneumonia was induced by the intravesical administration of BCG, which resulted in transitional changes in the BALF cell component.

Administration, Intravesical↗

Cell-associated IL-8 in human blood monocytes: analysis by flow cytometry.

Several cell-associated cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor, exist on the cell surface and are biologically active. Although extracellular IL-8, a potent chemotactic factor for primarily neutrophils, has been studied extensively, cell-associated IL-8 has barely been studied. In this study, we analyzed the intracellular and cell-surface IL-8 in human blood monocytes in vitro by using flow cytometry and predicted the biological activity of the cell-associated IL-8 in vivo. After fixation with paraformaldehyde, mononuclear cells were divided into two subgroups. One subgroup was left untreated to study cell-associated antigens, and the other subgroup was permeabilized with saponin to detect intracellular antigens. In lipopolysaccharide (LPS)-stimulated monocytes, IL-8 was detected solely intracellularly, whereas both the intracellular and cell-surface IL-1 beta was detectable. In a time-course study, the intracellular IL-8 increased in response to LPS stimulation, but the cell-surface IL-8 was undetectable throughout the course. In an LPS-stimulated monocytic cell line, both ELISA and flow cytometry detected the quantitative change of the intracellular IL-8. The dissimilar localization between IL-8 and IL-1 beta within cells was confirmed by the immunohistochemical analysis. In summary, LPS stimulation induced a time-dependent increase in intracellular but not cell-surface IL-8 in monocytes. Thus, it is unlikely that the cell-associated IL-8 is functioning physiologically. The semiquantitative flow cytometric procedure may be useful for simultaneous examination for cell-surface and intracellular cytokines.

Antibodies, Monoclonal↗

Establishment of high- and low-invasion clones derived for a human tongue squamous-cell carcinoma cell line SAS.

Distant-organ metastasis and regional lymph node metastasis are still the major cause of mortality of oral-cavity squamous-cell cancer (SCC). However, only a few studies have been undertaken to elucidate the mechanism of invasion and metastasis of oral SCC. In this study, we attempted to establish human oral SCC clones with different invasiveness, defined by endothelial cell monolayer assay, which can be used for the study of invasion and metastasis of oral SCC. We established five clones from the human oral SCC cell line SAS by a limiting-dilution method. Two distinct clones, SAS-L1 with very low invasive potential and SAS-H1 with very high invasive potential, were picked out by rat lung endothelial cell monolayer assay. The number of SAS-H1 that penetrated the rat lung endothelial cell monolayer was six fold higher than the number of SAS-L1. There were no differences of metalloproteinase production and cell adhesiveness to Matrigel of SAS-L1 and SAS-H1. However, SAS-H1 exhibited a higher migration ability than SAS-L1. This pair of clones would be a useful experimental model to help in the study of the invasiveness of human oral SCC.

Basement Membrane↗