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Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 217 records · Page 12Linked to original sources

Pharmacological studies on a new antihypertensive agent, S-2150, a benzothiazepine derivative: 2. Hypotensive effects in normotensive and hypertensive rats.

S-2150 is a new 1,5-benzothiazepine derivative possessing both calcium channel-blocking and alpha 1-adrenoceptor-blocking effects. In isolated rat thoracic aorta precontracted with KCl (18 mM), the 50% inhibitory concentration (IC50) value was 190 nM for S-2150, which was similar to that of diltiazem. In aorta precontracted with phenylephrine (0.3 microM), IC50 values of S-2150 and diltiazem were 29 nM and > 10 microM, respectively. The relative contribution of calcium channel-blocking and alpha 1-adrenoceptor-blocking activities to hypotension was determined by using anesthetized rats before and after masking of the alpha 1-receptors with prazosin. The hypotensive effect of S-2150 [0.3 and 1 mg/kg intravenously (i.v.)] was attenuated by 40% after prazosin treatment, whereas that of diltiazem was not. In conscious spontaneously hypertensive rats (SHRs), renal hypertensive rats, and normotensive rats, S-2150 [10, 30, and 60 mg/kg orally (p.o.)] caused dose-dependent hypotensive effects. The effect of S-2150 was 4-7 times more potent than that of diltiazem. There were no changes in the hypotensive effects with consecutive administration of S-2150 during 6-8 weeks in SHRs and stroke-prone SHRs (SHRSPs). In SHRSPs, S-2150 reduced the mortality by stroke and small arterial hyperplasia in abdominal organs and also ameliorated renal excretory function. These results suggest that S-2150 may be a useful antihypertensive agent possessing both calcium-antagonistic and alpha 1-adrenoceptor-blocking effects.

Adrenergic alpha-1 Receptor Antagonists↗

Distribution of transforming growth factor-beta and its receptors in gastric carcinoma tissue.

The distribution of the three mammalian isoforms of transforming growth factor (TGF)-beta (TGF-beta 1, -beta 2, and -beta 3) as well as their signaling receptors, TGF-beta type I and type II receptors (T beta R-I and T beta R-II, respectively), in gastric carcinoma tissue was examined by immunohistochemistry using specific antibodies. Tissue specimens were obtained from 25 cases of gastric carcinoma, which were classified into two groups according to Lauren's classification, i.e. 15 cases of diffuse carcinoma and 10 cases of intestinal carcinoma. In normal gastric mucosa apart from carcinoma nests, all of TGF-beta 1, -beta 2, -beta 3, T beta R-I and T beta R-II were clearly demonstrated in fundic glands. In sharp contrast, none of them was detectable in surface mucous cells. In carcinoma cells, strong staining for TGF-beta 1, -beta 2 and -beta 3 was obtained only in diffuse-type carcinoma. In particular, carcinoma cells scattered as single cells or small nests had a tendency to show strong staining for TGF-betas. The receptors tended to be distributed concomitantly with the ligands, and diffuse-type carcinoma showed stronger receptor staining than intestinal-type carcinoma. In cancer stroma, TGF-betas and receptors were detected in both diffuse and intestinal types, but the area with positive staining was wider and more dispersed in diffuse-type carcinoma than in intestinal carcinoma. These results suggest that TGF-beta may contribute in part to the variety of histogenesis and mode of progression of gastric carcinoma.

Adenocarcinoma↗

Reflection of structural abnormality in the axoneme of respiratory cilia in the clinical features of immotile cilia syndrome.

In immotile cilia syndrome (ICS), respiratory symptoms show a wide range of severity. Various types of axonemal abnormalities related to ICS are known, but it is unclear whether the symptom severity is related to the type of abnormality. We sent a questionnaire concerning respiratory symptoms to ICS patients. Another type of the questionnaire regarding the clinical features and axonemal abnormality of ICS was sent to the physicians in charge. Analysis of the results showed that in the 48 patients responding, those lacking outer dynein arms (LO) in cilia were more likely to be associated with situs inversus (SI) than those lacking inner dynein arms (LI). Sputum symptoms were more serious in those associated with SI than those unassociated with SI, as was the case in those associated with LO compared to those with LI. Based on these results, it may be concluded that the type of dynein arm defect in cilia is related to the clinical features in ICS.

Adolescent↗

Estimation of the prevalence of non-insulin dependent diabetes mellitus in a rural area of Japan.

The objective of this paper is to describe a method of estimating the prevalence of non-insulin dependent diabetes mellitus (NIDDM) in a community. We first counted subjects with previously diagnosed NIDDM and those newly diagnosed by use of the 75-gram oral glucose tolerance test (OGTT). We then used the OGTT data to predict the prevalence of NIDDM at different levels of fasting plasma glucose (FPG) among the subjects who did not undergo the OGTT. Data were derived from 3,614 residents aged 20 years and older in a rural area where population-based screening for NIDDM was performed using FPG or post-prandial plasma glucose (PG). Of the 318 participants who underwent an OGTT in 1992, 35 (11.0%) were judged to have NIDDM by the 2-hour PG criterion. We applied the above-described method to the 1,179 subjects who had anFPG but failed to undergo the OGTT. The estimated prevalence of NIDDM, which included the previously diagnosed group, the newly diagnosed group and the expected group, was calculated. The estimated prevalence of diabetes in this population aged 20 years and older turned out to be 6.1% (95% CI: 5.3-6.9). As a validation study, the same method was applied to 220 subjects who did not undergo the OGTT in 1992 but did so in 1994. The actual prevalence of NIDDM among these subjects was compared to the prevalence expected from the 1992 data by our method. The actual value was within the 95% confidence interval of the expected value.

Adult↗

Enhanced expression of platelet-derived growth factor-beta receptor by high glucose. Involvement of platelet-derived growth factor in diabetic angiopathy.

Coronary heart disease is a major complication of diabetic subjects, and platelet-derived growth factor (PDGF) has been implicated in the development of atherosclerosis. We investigated the effects of high glucose on expression of PDGF-beta receptor. In a binding assay with 125I-labeled PDGF-BB homodimer, high concentrations of glucose increased high-affinity binding of PDGF-BB on human monocyte-derived macrophages and rabbit aortic medial smooth muscle cells. Northern blot analysis confirmed the enhanced effect of glucose on expression of PDGF-beta receptor mRNA in human monocyte-derived macrophages. The protein kinase C inhibitor, staurosporin, completely suppressed an increase in PDGF-BB binding by high glucose, and high glucose significantly activated protein kinase C. These results indicated that PDGF-beta receptor expression was enhanced by high glucose through the activation of protein kinase C. Furthermore, we observed similar effects of high glucose on both PDGF-beta receptor expression and protein kinase C activation in rat mesangial cells and human capillary endothelial cells. Our results suggest that stimulation of the PDGF system is significantly involved in the development not only of diabetic atherosclerosis but also of microangiopathy.

Alkaloids↗

Dose-dependent effect of niceritrol on plasma lipoprotein-a.

Lipoprotein-a, Lp(a), is a variant form of low density lipoprotein (LDL) that contains apolipoprotein-a, whose structure has 75-85% homology with plasminogen. Elevated plasma levels of Lp(a) are considered to be one of the independent risk factors for cardiovascular disease. We studied the effects of niceritrol, a nicotinic acid derivative, on plasma Lp(a) levels in 72 patients with hypercholesterolaemia. The dose of niceritrol was increased every 4 weeks, from 750 to 1500 and then to 2250 mg day-1. The final dose was adjusted to obtain a plasma cholesterol level less than 5.69 mmol l-1. Niceritrol led to significant decreases in plasma levels of median Lp(a), from 16.1 mg dl-1 (interquartile intervals, 8.7 to 32.8) to 11.1 mg dl-1 (interquartile intervals, 6.6 to 21), the mean reduction rate being 17.6%. In the group with pretreatment Lp(a) levels of over 20 mg dl-1, Lp(a) decreased by 10.0, 22.0 and 31.8% at the doses of 750, 1500, and 2250 mg day-1, respectively. In the group with levels less than 20 mg dl-1, only the dose of 2250 mg day-1 was effective in the reduction of Lp(a). The results suggest that the reduction of Lp(a) was dependent on the dose of niceritrol and on the pretreatment level of Lp(a). In conclusion, niceritrol is effective, in a dose-dependent manner, for reducing Lp(a) levels.

Aged↗

[A clinical and pathological study of radical prostatectomy for prostate cancer].

BACKGROUND: Thirty-one patients with prostate cancer underwent radical prostatectomy and simultaneous pelvic lymphadenectomy at Matsumoto National Hospital between 1988 and 1994. Prognostic factors are discussed from their clincopathological findings. METHODS: The patients ranged from 54 to 80-year-old, with an average age of 69.9 years. The median follow-up period was 44 months. The diagnosis was confirmed by needle biopsy or transurethral resection of the prostate. All the patients received short-term endocrine therapy preoperatively, and only noncuratively resected patients underwent adjuvant therapy postoperatively. At initial diagnosis, the tumor grades were well, moderately, and poorly differentiated adenocarcinoma in 9, 12, and 10 patients, respectively. The clinical stage was defined as A2, B, C, D1, and D2 in 12, 4, 6, 3, and 6 patients, respectively. RESULTS: A difference of tumor grade was found between the initial diagnosis and the final diagnosis based on the resected prostate in 8 patients (26%), with 7 of them (88%) showing an increase in grade in the final diagnosis. Also revealed was that 11 of the 25 patients (44%) in stage A2, B, C, or D1 had been understaged preoperatively. The five-year actuarial survival rates were 100%, 92%, and 51% for patients with well, moderately, and poorly differentiated adenocarcinoma, respectively, with a significant difference noted between well and poorly differentiated adenocarcinoma (p = 0.03). Recurrence only developed in patients with pathological stage D tumors. However, the presence or absence of lymph node metastasis did not affect the crude 5-year survival rate. Several stage D patients were successfully treated by radical prostatectomy and adjuvant therapy, achieving long survival. CONCLUSION: These results indicate that patients in clinical stage C have tumors which exhibit differing biological behavior. These patients should be analyzed and classified more precisely so that the most appropriate therapy can be chosen.

Adenocarcinoma↗

[Acute effect of use of the Flutter on expectoration of sputum in patients with chronic respiratory diseases].

The acute effects of use of the Flutter on expectoration of sputum were studied in patients with chronic respiratory diseases who had problems expectorating sputum. The Flutter is a handy, simple, physiotherapy device that is easy to use. Seventeen patients were enrolled in the study. For three consecutive days, the patients were asked to use the Flutter for 15 min when they had the hardest time expectorating sputum. They were also asked to measure the volume of the expectorant obtained during those 15 min and the following 30 min. Expectoration, coughing, and breathlessness were graded with visual analogue scales designed by us. Peak expiratory flow rate was also measured. For the control condition, the patients were asked to remove the stainless steel ball from the device and then to use the device as stated above on the three consecutive days immediately before or after the experimental days. Scores of "difficulty in expectoration" and "chest discomfort" were lower on the second and third experimental days than on the control days (mean+/-SE of difficulty in expectoration on the second day: 3.8+/-0.6 vs 4.4+/-0.6, p<0.05: on the third day: 3.0+/-0.5 vs 4.2+/- 0.6, p<0.02; chest discomfort on the second day: 2.9+/-0.6 vs 3.5/+-0.7, p<0.04; on the third day: 2.3+/-0.6 vs 2.9+/-0.6, p<0.01). No significant differences were noted in cough intensity, cough frequency, breathlessness, or peak expiratory flow. Sputum volume was larger on the second and third experimental days than on the control days (second day: 13.9+/-3.6 vs 11.3+/-3.1 ml, p<0.04; third day: 13.2+/-2.8 vs 9.9+/-2.1 ml, p<0.01). We conclude that use of the Flutter can increase the expectoration of sputum and can relieve related symptoms.

Adult↗

[Pleural fibroma with a cavity-like air space].

A 45-year-old man was admitted to the hospital because of an increase in the size of an abnormal shadow on chest X-ray films over the preceding 5 years. A chest X-ray film on admission revealed a round air space in a mass-like shadow in the right upper lung field. Results of physical examination, sputum cytologic examination, and Ziehl-Neelsen staining were negative. Histopathological examination of a percutaneous lung biopsy specimen revealed a benign fibrous tumor of the pleura. Thoracotomy revealed a pedunculated tumor arising from the visceral pleura at the apical segment of the right upper lobe. A wedge resection was done. Histological examination revealed that the tumor consisted of regularly-shaped spindle cells with densely collagenous tissue. Normal lung tissue was found to be invaginated into the tumor tissue. These findings are consistent with the radiologic findings.

Fibroma↗

[Massive hemoptysis caused by disruption of a bronchial aneurysm diagnosed by microscopic examination of the resected lung].

A 29-year-old woman in the 6th month of pregnancy was admitted to our hospital because of repeated hemoptysis after an acute respiratory infection. Fiberoptic bronchoscopy revealed a polypoid lesion at the orifice of the right B3 bronchus and bleeding around the lesion. Bronchial arteriography showed no abnormalities. Transcatheter embolization was unsuccessful. Therefore, a right upper lobectomy was done. Microscopical examination showed a mass of coagulated blood on the mucosal surface of the wall of the B3 bronchus, and a bronchial artery running toward the mucosal surface was seen underneath. The mass was thought to be the polypoid lesion seen during bronchoscopy. Serial sections showed a bronchial aneurysm 1 mm in diameter that had ruptured into the bronchial lumen. Several bronchial arteries were located in the propria mucosa in other bronchial segments, as observed in the B3 bronchus, but no other focus of bleeding was identified. Some cases of hemoptysis of unknown cause may result from similar histological alterations.

Adult↗

[Clinical analysis of 169 patients with prostate cancer].

At Matsumoto National Hospital, 169 patients with prostate cancer were diagnosed between April 1986 and May 1994. The prostate cancer incidence was the highest in the latter half of the seventies, with an average age of 74.3 years. The clinical stage was defined as A1, A2, B, C, and D2 in 24 (14.2%), 38 (22.5%), 39 (23.1%), 23 (13.6%) and 45 (26.6%) patients, respectively. The clinical stage was not correlated with the patient's age. Incidental carcinoma was discovered in 5.8% of the patients who underwent prostatectomy for benign prostatic hypertrophy (BPH). At initial diagnosis, the tumor was well, moderately, and poorly differentiated adenocarcinoma in 71 (42.0%), 64 (37.9%), and 34 (20.1%) patients, respectively. The median follow-up period was 38.7 months. The over all five-year crude survival rate was 54.8%, while the cause-specific five-year survival rate was 80.0%. The five-year crude survival rate was 58.4, 82.0, 55.2, 42.5 and 37.4%, for patients with cancer at stage A1, A2, B, C, and D. The survival rate was higher for patients with cancer at clinical stage A and shorter for those with cancer at clinical stage D than in other stages. Prognosis was also worse in patients with moderately or poorly differentiated adenocarcinoma than in those with well-differentiated adenocarcinoma. The clinical stage and the pathological grade are important as prognostic factors, although the high incidence of death from other diseases shows that the patients' age should be considered to choose the modality of therapy. These findings indicate that intensive treatment of the patients in clinical stage A2, B and C prostate cancer in combination with screening for the men between 50 and 75 years old for early cancer detection is required.

Adenocarcinoma↗

[Effect of on-demand inhalation of dry oxygen on nasal mucociliary clearance].

AIM: To determine whether nasal mucociliary clearance is affected by dry oxygen delivered on demand. METHODS: Saccharin nasal transit time was measured as an index of nasal mucociliary clearance. One group of patients was given dry oxygen via a nasal cannula and a demand delivery system, and another group was given dry oxygen by continuous inhalation. In each group, continuous inhalation of humidified oxygen served as the control. Saccharin transit time was measured before and after 8 hours of oxygen inhalation. SUBJECTS: The subjects were 25 patients with chronic respiratory failure who were receiving home oxygen therapy via nasal cannula. All the subjects were clinically stable (age 72.1, mean +/- SE), %VC 46.6 +/- 3.0. FEV/FVC% 9.0 +/- 1.5, PaO2 55.7 +/- 2.0 Torr. PaCO2 53.9 +/- 1.9 Torr). RESULTS: Saccharin transit time after inhalation of dry oxygen on demand did not differ from that after continuous inhalation of humidified oxygen (15.6 +/- 1.5 vs 14.9 +/- 1.4 min). Saccharin transit time after continuous inhalation of dry oxygen was significantly lower than that after continuous inhalation of humidified oxygen (26.6 +/- 5.4 vs 16.7 +/- 2.6 min. p > 0.05). CONCLUSION: We conclude that using the demand oxygen delivery system with a nasal cannula for 8 hours had no adverse effects on nasal mucociliary clearance.

Aged↗

Manifestations of cancer cachexia induced by colon 26 adenocarcinoma are not fully ascribable to interleukin-6.

In order to further clarify the role of interleukin 6 (IL-6) in the pathogenesis of cachexia, recombinant human IL-6 (hIL-6) was administered s.c. by osmotic pump for 9 days at a dose of 1 or 10 micrograms/day into CDF1 mice inoculated with a non-cachexia-inducing subclone of colon 26 adenocarcinoma (clone 5), or with a cachexia-inducing subclone (clone 20) of this malignancy. The serum level of IL-6 in non-cachectic mice with clone-5 tumors was 35% lower than in cachectic mice bearing clone 20 of colon 26 adenocarcinoma on the 19th day after tumor inoculation. IL-6 administration induced anemia, thrombocytosis and visceral organ hypertrophy not only in mice with clone-5 tumors but also in control mice with no tumor burden. Lipolysis and proteolysis became conspicuous when a large dose (10 micrograms/day) of IL-6 was infused into mice with clone-5 tumors. However, IL-6 supplementation did not induce loss of body weight, a decline in food intake or lymphocytopenia, which were characteristically observed in cachectic mice with clone-20 tumors. In conclusion, IL-6 appears to be a permissive factor for the development of cachexia but, while it can induce some of the symptoms typical of cachexia, it cannot in itself induce the full cachectic syndrome.

Adenocarcinoma↗

Kinetic studies on the interaction of nonlabeled antagonists with the angiotensin II receptor.

Angiotensin AT1 receptor antagonists are divided into two types, surmountable and insurmountable, based on the way they inhibit angiotensin II-induced vasoconstriction. To elucidate what causes the difference, we studied how antagonists associate with and dissociate from AT1 receptor sites in rat liver membranes. Three antagonists, 6-propyl-7-oxo-4[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-4,7- dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid (SRL1080227), 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylic acid (CV-11974) and 2-butyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-3H-imidazo- [4,5-b]pyridine (FK739), showed competitive antagonism when they were added simultaneously with [125I]angiotensin II, but CV11974 and SRL1080227 showed apparently noncompetitive antagonism when membranes were preincubated with each antagonist. The longer the preincubation time with CV11974 or SRL1080227 was, the more effectively the antagonist inhibited [125I]angiotensin II binding, while the inhibition by FK739 did not change with the preincubation time. To estimate their dissociation rate from the receptor binding site, we studied [125I]angiotensin II binding to membranes which had been preincubated with each antagonist and washed twice. Membranes pretreated with FK739 completely recovered the ability to bind [125I]angiotensin II with a period of 60 min, while membranes preincubated with CV11974 did not read this level of recovery. [125I]angiotensin II binding to membranes preincubated with SRL1080227 increased gradually, but did not reach the control level during the experiment. The kinetic properties of SRL1080227, CV11974 and FK739 were consistent with their characteristic modes in inhibiting angiotensin II-induced contraction of isolated rabbit aorta and decreasing blood pressure of spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists↗