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Biomedical subjects

S Muro

Publications and source records attributed to S Muro.

49 records · Page 3Linked to original sources
PubMed1997

Molecular cloning of a novel mouse aspartic protease-like protein that is expressed abundantly in the kidney.

By use of the signal sequence trap method, we isolated a cDNA encoding a novel aspartic protease-like protein from the mouse kidney, and termed it 'kidney-derived aspartic protease-like protein (KAP).' The protein, a 419-amino-acid polypeptide with a 16-amino-acid signal sequence, had 47% identity with mouse cathepsin D, and its overall structure was closely related to known aspartic proteases. Northern blot analysis revealed that KAP mRNA is expressed at the highest level in the kidney, at a moderate level in the lung, and at low levels in the spleen and adipose tissue. In situ hybridization analysis demonstrated that the mRNA is expressed abundantly in the proximal straight tubule and slightly, but significantly, in the proximal convoluted tubule in the kidney. This intra-renal distribution differs distinctly from those of previously reported proteases such as cathepsins B, D, and H.

Amino Acid Sequence↗
PubMed1997

The effect of the level of ventilatory assist on the level of respiratory drive in decerebrate cats.

The present study was undertaken to investigate whether, independent of changes in PaCO2, ventilatory assist influences not only the pattern but also the level of the respiratory drive. The experiments were performed on decerebrate and paralyzed cats ventilated by a phrenic-driven servo respirator at three different FICO2 levels (0, 0.30, 0.05). The level of ventilatory assist was altered within the range where PaCO2 did not exceed 80 Torr. A higher FICO2 accompanied a higher level of ventilatory assist. The relationship between the minute phrenic activity and log10 PaCO2 at a given FICO2 was linear. No significant difference was found in the regression lines at different levels of FICO2. We conclude that ventilatory assist has little effect on the respiratory drive at a constant level of chemical feedback during hypercapnia.

Animals↗
PubMed1997

Ventilatory responses and subjective sensations during arm exercise and hypercapnia in patients with lower-cervical and upper-thoracic spinal cord injuries.

We measured the ventilatory responses and subjective sensations during arm exercise in patients with lower cervical and upper thoracic spinal cord injuries in order to evaluate the effects of chest wall deafferentation on these responses. Visual analog scales with verbal descriptors were used to quantify respiratory sensations of different affectional qualities. Patients as well as normal subjects reported stronger respiratory sensations upon CO2 rebreathing as compared to during arm exercise with an equivalent minute ventilation (p<0.05). There were no qualitative nor quantitative differences in the respiratory sensations during CO2 rebreathing between the patients and normal subjects. However, patients with spinal cord injuries showed a higher minute ventilation and a lower end-tidal PCO2 during incremental arm exercises (p<0.01), and thus tended to hyperventilate. We conclude that chest wall afferent denervation does not contribute significantly to the perception of breathlessness in patients with spinal cord injuries.

Adult↗
PubMed1996

Gene expression of the human prostaglandin E receptor EP4 subtype: differential regulation in monocytoid and lymphoid lineage cells by phorbol ester.

We isolated a cDNA clone encoding the human prostaglandin (PG) E receptor EP4 subtype and examined the gene expression in human blood cells. Northern blot analysis revealed that the EP4 gene is expressed at a high level in peripheral blood mononuclear cells, and at lower levels in cultured human blood cell lines, THP-1 and U937 (monocytoid cell lines), MOLT-4 and Jurkat (T-cell lines), and Raji (B-cell line). To examine regulation of the EP4 gene expression in the immune system, we studied the effects of phorbol 12-myristate 13-acetate (PMA) on these cell lines. Gene expression was upregulated in THP-1, U937, and Raji cells by PMA, and was downregulated in MOLT-4 and Jurkat cells. In THP-1 cells the effects of PMA were further analyzed, and the upregulation of the EP4 gene was shown to be followed by an increase in PGE2 binding sites and in PGE2-induced cAMP accumulation. In the striking contrast, other PGE receptor subtypes (EP1, EP2 and EP3) and other prostanoid receptors (IP and DP) were shown not to be upregulated by PMA. Therefore, this is the first demonstration of a highly specific upregulation of the EP4 subtype in THP-1 cells treated with PMA, suggesting the importance of the EP4 subtype in the immune system. In the present study we also clarified that EP4 gene expression is regulated differently among human monocytoid and lymphoid lineage cells, thus leading to the better understanding of the regulatory mechanisms for the human EP4 gene expression in the immune system.

Burkitt Lymphoma↗
PubMed1996

Relationship between dyspnea in daily life and psycho-physiologic state in patients with chronic obstructive pulmonary disease during long-term domiciliary oxygen therapy.

We examined the relationships among dyspnea ratings in daily life, the physiologic state, and anxiety and depression of fifty-two patients with chronic obstructive disease (COPD) during long-term domiciliary oxygen therapy (LTOT). Clinical ratings of dyspnea were assessed by the visual-analog scale (VAS) during eight types of basic behavior in indoor daily life. Analysis of the physiologic state included forced expiratory volume in 1 second (FEV1.0), and arterial blood gas (PaO2, PaCO2) at rest while breathing room air. The hospital anxiety and depression (HAD) scale, which consists of 14 questions, was used to assess the degree of anxiety (HAD-A) and depression (HAD-D). The mean age of the patients was 69.5 +/- 10.8 year (SD), and the duration of LTOT was 944 +/- 739 days. The mean values were 0.77 +/- 0.45 L for FEV1.0, 57.7 +/- 7.4 Torr for PaO2, and 47.4 +/- 8.1 Torr for PaCO2. FEV1.0 was correlated with PaCO2(r = -0.548, p < 0.0001), but it was not correlated with PaO2. High correlation was noted between HAD-A and HAD-D (r = 0.693, P < 0.0001), whereas correlation was not noted between HAD and the physiologic state. VAS was significantly correlated with FEV1.0 (r = 0.320, p < 0.05), as well as with HAD-A (r = 0.358, p < 0.01) and HAD-D (r = 0.444, p < 0.01). Dyspnea ratings were found to be influenced by anxiety and the depression state, and also by the degree of flow limitation in patients with COPD during LTOT. In contrast, the physiologic state scarcely influenced the anxiety and depression state. Thus, psychotherapy may play an important role in the reduction of dyspnea sensation, which is an important determinant of quality of life.

Activities of Daily Living↗
PubMed1995

Gene expression of prostacyclin receptor in the hypertrophied heart of spontaneously hypertensive rats.

1. Prostacyclin elicits potent vasodilation and inhibition of platelet aggregation through binding to its membrane receptor. The impairment of prostacyclin receptor activity is implicated in various human cardiovascular diseases. We recently succeeded in molecular cloning of cDNA for the mouse, rat, and human prostacyclin receptors. 2. In the present study, we examined the mRNA expression of the prostacyclin receptor in various rat tissues, and further investigated its gene expression in the hypertrophied cardiac ventricles of stroke-prone spontaneously hypertensive rats (SHRSP). 3. In rat tissues, a single RNA band of approximately 3.7 kb was detected by northern blotting analysis using rat prostacyclin receptor cDNA as a probe. In adult Wistar rats, abundant mRNA expression was observed in the aorta, lung and spleen. Substantial amounts of transcript were expressed in the heart, pancreas, thymus and stomach. In contrast, no mRNA expression was detected in the brain. 4. We further examined the mRNA expression of the prostacyclin receptor in the ventricles of 21 week old SHRSP. The ventricles of SHRSP showed remarkable hypertrophy, compared with those of age-matched Wistar-Kyoto (WKY) rats. The expression of prostacyclin receptor mRNA in the hypertrophied ventricles of SHRSP was almost equivalent to that in the ventricles of WKY. 5. The present study revealed the gene expression of the prostacyclin receptor in various rat tissues, and further demonstrated the receptor mRNA expression in hypertensive cardiac hypertrophy. The present study will give a clue to investigate the clinical implication of prostacyclin and its receptor.

Animals↗
PubMed1994

Effect of IL-1 receptor antagonist and antiserum to TNF-alpha on LPS-induced plasma ACTH and corticosterone rise in rats.

Using an antiserum against tumor necrosis factor (TNF)-alpha and an interleukin (IL-1) receptor antagonist, we studied putative roles of these cytokines in mediating the endotoxin-induced elevation of plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in freely moving rats. Intravenous administration of Escherichia coli lipopolysaccharide (LPS) increased plasma ACTH and corticosterone levels in a dose-dependent manner. The plasma corticosterone reached to its highest level among a series of experiments after the administration of even the smallest dose (0.03 microgram/kg) tested. Plasma ACTH and corticosterone levels in these rats were completely inhibited by the intravenous administration of anti-murine TNF-alpha-rabbit antiserum (anti-TNFAS) after the administration of LPS but not by the intravenous administration of IL-1 receptor antagonist (IL-1RA). On the other hand, both recombinant human IL-1RA and anti-TNFAS significantly inhibited plasma ACTH increase stimulated with 10 micrograms/kg LPS. These findings indicate that 1) when the plasma corticosterone increase induced by intravenous LPS remains below its maximum, the effect is exclusively mediated by TNF-alpha, and 2) when a larger amount of LPS is administered, both IL-1 beta and TNF-alpha participate at least in part in the hypothalamic-pituitary-adrenal axis activation.

Adrenocorticotropic Hormone↗
PubMed1993

Bacterial lipopolysaccharide-induced expression of interleukin-6 messenger ribonucleic acid in the rat hypothalamus, pituitary, adrenal gland, and spleen.

Whereas the stimulatory effect of interleukin-6 (IL-6) on the hypothalamic-pituitary-adrenal (HPA) axis is well established, its mode of action in this axis has yet to be fully elucidated. To further study the role of IL-6 in the HPA axis, we compared the expression of IL-6 messenger RNA (mRNA) in the rat hypothalamus, pituitary, and adrenal gland with that in the spleen after ip or intracerebroventricular (icv) administration of bacterial lipopolysaccharide (LPS). After either ip or icv administration, LPS induced the expression of IL-6 mRNA, which consists of 1.2 kilobases (kb) and 2.4 kb subclasses, in all these tissues of the HPA axis as well as in the spleen. Although we used 100 times less amount of LPS for the icv administration than that used for ip LPS, plasma ACTH levels in both the conditions rapidly reached comparable levels. This icv dose induced IL-6 mRNA expression in the hypothalamus faster than ip dose but also stimulated IL-6 mRNA expression in the hypothalamus, pituitary, and adrenal gland more effectively and smoothly than the ip LPS dose did. Northern blot analysis revealed that in the hypothalamus, pituitary, and adrenals, the predominant subclass of IL-6 mRNA was not 1.2 kb but 2.4 kb. In contrast, this subclass was the minor component in the spleen induced under the same circumstances. These findings indicate that IL-6-synthesizing cells in the HPA axis differ in character from those in the spleen, and that LPS applied in vivo may modulate IL-6 expression in these cells directly and/or indirectly through secondarily activated functions in the neuronal or endocrine systems.

Animals↗
PubMed1993

[An autopsy case of acute lymphocytic leukemia associated with secondary pulmonary alveolar proteinosis and systemic aspergillosis].

A 49-year-old woman with acute lymphocytic leukemia (ALL) who had been intermittently treated with chemotherapy during a 3-year period developed cough and expectoration of increasing severity. Chest X-ray film revealed miliary shadows and bilateral hilar enlargement. Milky fluid was obtained by bronchoalveolar lavage. The intensity of these shadows showed temporary decrease, but thereafter progressively increased until the time of the patient's death. Autopsy findings were consistent with pulmonary alveolar proteinosis and systemic aspergillosis. Secondary alveolar proteinosis is rare, and in most reported cases is associated with hematological malignancy. To our knowledge, only 45 cases in which it was associated with hematological disorders have been reported. The examination of a patient with any hematological disorder, however, should include differential diagnosis of chest X-ray abnormalities to exclude secondary alveolar proteinosis, which can be lethal if left untreated.

Aspergillosis↗
PubMed1992

Roles of interleukin-1 alpha and -1 beta in endotoxin-induced suppression of plasma gonadotropin levels in rats.

Using specific antagonists to rat interleukin (IL)-1 alpha and IL-1 beta, the roles of these IL-1s in endotoxin-induced suppression of plasma gonadotropin levels in freely-moving rats were studied. In orchiectomized rats, recombinant rat IL-1 alpha and IL-1 beta administered into the lateral ventricles almost equipotently suppressed plasma LH levels. Twenty five micrograms of bacterial endotoxin or lipopolysaccharide (LPS) administered similarly showed a comparable effect as that of 1 microgram IL-1 alpha or IL-1 beta, and completely lowered plasma LH levels by 60 min after the injection. To examine the roles of endogenous IL-1 alpha and IL-1 beta, anti-rat IL-1 alpha antiserum (anti-IL-1 alpha) and a recombinant human IL-1 receptor antagonist (IL-1ra) were used as specific blockers for IL-1 alpha and IL-1 beta, respectively. Anti-IL-1 alpha (10 microliters) or IL-1ra (10 micrograms) administered intracerebroventricularly (icv) with 25 micrograms LPS, significantly attenuated the LPS-induced effect on plasma LH levels during the first 60 min after LPS infusion, but not during the second 60 min. LPS at a dose of 5 micrograms induced smaller but still significant changes in plasma LH levels compared with 25 micrograms LPS or 1 microgram IL-1 beta. IL-1ra (10 micrograms) completely blocked LH suppression induced by 1 microgram IL-1 beta, but did not completely reverse the changes of LH induced by 5 micrograms LPS. IL-1ra injected iv also significantly attenuated the early suppressive effect of iv administered LPS, but not its late effect on plasma LH levels. However, iv administered IL-1ra had no influence on the effects of icv administered LPS. These data indicate that at least a part of plasma LH suppression caused by icv administered LPS is mediated via IL-1 alpha and IL-1 beta synthesized within the brain, while factor(s) other than IL-1 also participate in the LPS-induced change, particularly during the later period. A similar mechanism may also work peripherally in the case of iv administered LPS-induced plasma LH suppression.

Animals↗
PubMedDate not supplied

Optimized scanning conditions of high resolution CT in the follow-up of pulmonary emphysema.

PURPOSE: To address the optimal scanning condition of high resolution computerized tomography from the perspective of minimizing exposed dose. METHOD: The influence of the electric current, the slice number, and the slice thickness on precise percent ratio of the low attenuation area to whole lung field (LAA%) of chronic obstructive pulmonary disease patients was examined. The standard conditions were 250 mA, 3 slices, 2 mm slice thickness, and a varied parameter. RESULTS: In cases showing an LAA% less than 30, LAA% obtained by < or =150 mA were significantly larger than those by 250 mA. The mean LAA% with 3 and 10 slices were well correlated and the correlation with lung function was similar. The correlation of LAA% with lung function was approximately the same between the 2 and 5 mm slice thicknesses. CONCLUSION: The electrical current must be > or =200 mA, and 3 slices and 2 mm slice thickness are appropriate.

Electricity↗