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Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 199 records · Page 11Linked to original sources

[Thermo-chemotherapy using low-dose CPT-11 in a patient with local recurrence of rectal cancer].

We report a case of pelvic recurrence of advanced rectal carcinoma, presenting a favorable response with a low dose (25 mg/m2) of CPT-11 (Irinotecan) combined with topical hyperthermia for relapse after treatment with 4 cycles of high-dose (100 mg/m2) CPT-11 chemotherapy alone. This combination therapy was safely carried out on an outpatient basis. The degrees of recovery of the left lower limb pain and edema, and of serum CEA reduction were comparable to those in high-dose chemotherapy alone. No significant adverse effects were encountered in the thermo-chemotherapy attempted. Since hyperthermic treatment enhances the cytotoxic effects of CPT-11 in vitro, topical hyperthermia with low-dose CPT-11 therapy may produce a response comparable to that in high-dose CPT-11 chemotherapy alone. However, an optimal dose and comparative study with other chemotherapeutic agents would be needed. This regimen may be advantageous in the maintenance of quality of life for the palliation of postoperative pelvic recurrence since this treatment can be performed on an outpatient basis.

Adenocarcinoma↗

[A case of true carcinosarcoma in bladder diverticulum].

We report a case of carcinosarcoma arising from a bladder diverticulum. A 71-year-old male was referred to our hospital for macroscopic hematuria. Two diverticula were identified in the left wall of the urinary bladder, one of which showed a broad-based tumor. The bladder tumor was resected using a transuretheral approach and the tumor was histologically diagnosed as leiomyosarcoma. The patient underwent partial resection of the bladder including the two diverticula and the tumor. Pathological examination revealed that the resected specimen was composed of three elements, transitional cell carcinoma (G3), squamous cell carcinoma, and leiomyosarcoma. Thus, the patient was diagnosed with carcinosarcoma. He died 5 months after surgery to remove the panperitonitis carcinomatosa. This case is the 38th reported case of bladder carcinosarcoma in Japan.

Aged↗

[Susceptibilities of Enterococcus faecium, PRSP and MRSA to RP59500 and their correlations with those to other drugs].

Investigations on emergence of vancomycin-resistant Enterococcus faecium (VREF) which has recently been attracting attention, especially in the Western countries, have been conducted in Japan. A total of 1,239 isolates of E. faecium were collected from 19 institutions during the period of April 1995 and June 1996, in the purpose of evaluating susceptibilities to variety of antimicrobial agents, including RP59500 and vancomycin (VCM), and detecting vancomycin-resistant genes (van genes). Susceptibilities of penicillin-resistant Streptococcus pneumoniae (PRSP) and methicillin-resistant Staphylococcus aureus (MRSA) were also studied. As a result, 2 isolates of E. faecium were found to be moderately resistant to VCM showing MIC of 8 micrograms/ml though the final identification in species level and the detection of van genes by PCR method have not been completed. On the other hand there detected no MRSA nor PRSP showing moderately resistant or resistant to VCM. It was concluded that RP59500 and VCM possessed favorable activity against clinically isolated E. faecium, PRSP and MRSA. Among other species of enterococci, moderately resistant strains to VCM showing MIC of 8 micrograms/ml were detected; 10 isolates of E. gallinarum, 4 of E. casseliflavus and 2 of E. flavescens. In those isolates, vanC1 and vanC2 were detected by PCR, and vanB was also detected in a isolates of E. gallinarum simultaneously.

Anti-Bacterial Agents↗

A novel splice acceptor site mutation which produces multiple splicing abnormalities resulting in protein S deficiency type I.

In an attempt to explore the molecular mechanisms for protein S deficiency, a patient with such a deficiency was examined at the DNA, RNA and protein levels. Nucleotide analyses revealed that the proband, the mother and the grandmother had a G-->C substitution in the invariant AG dinucleotide at the splicing acceptor site of intron A/exon 2. This patient was heterozygous for this substitution and the mutant allele was inherited from the proband's mother and grandmother. Reverse transcription-polymerase chain reaction analysis demonstrated several kinds of splicing abnormalities such as exon skipping and cryptic splicing, in addition to correct splicing. Semiquantitation of mRNA for the protein S gene revealed that the amount of the proband's mRNA was reduced to 60% of normal. Thus, this mutation impaired the normal processing of mRNA for the protein S gene, resulting in the subject's severe protein S deficiency.

Adolescent↗

Changes in muscle sympathetic nerve activity and effects of breathing maneuvers in humans during microgravity induced by parabolic flight.

The mechanism of cardiovascular deconditioning, such as an orthostatic intolerance after space flight, has not been well clarified. Several studies to investigate that mechanism have focused mainly on hemodynamic changes including heart rate, arterial blood pressure, cardiac output, etc., but no studies have yielded a direct insight into changes in the sympathetic nervous system. Among ground-based experiments, parabolic flight is the only maneuver to expose human subjects to actual microgravity although it lasts for only a short duration of approx. 20 sec. Using microneurography, the present study aimed to analyze the involvement of the sympathetic nervous system in regulating the acute effects of fluid shift induced by parabolic flight during the transitional changes from 1 G to hypergravity, hypergravity to microgravity, and microgravity to hypergravity by direct measurement of sympathetic outflow to the muscles. Some parts of the study were published elsewhere. We also investigated how the sympathetic outflow to muscle is modified during microgravity with elimination of the breathing effect by comparing the cardiovascular parameters under controlled and uncontrolled respiration.

Adult↗

Sustained elevation of plasma brain natriuretic peptide levels associated with progressive ventricular remodelling after acute myocardial infarction.

Previous studies have shown that levels of plasma brain natriuretic peptide (BNP) increase in an early phase of acute myocardial infarction. However, the relations between plasma BNP levels and left ventricular remodelling, which occurs long after acute myocardial infarction, are not fully understood. Venous plasma BNP levels were measured 2, 7, 14, 30, 90 and 180 days after the onset of acute myocardial infarction in 21 patients. Left ventricular end-diastolic volume index (EDVI, ml/m2) in acute (5 days) and chronic (6 months) phases were assessed by electron-beam computed tomography using Simpson's method. The remodelling group (n=9) was defined by an increase in EDVI >/=5 ml/m2 relative to the baseline value. Plasma BNP levels on days 2, 7, 14, 30 and 90 were significantly higher in the remodelling group than in the non-remodelling group (n=12, P<0.05). Sustained elevation of plasma BNP levels was noted from day 2 (61+/-12 pmol/l) to day 90 (55+/-12 pmol/l) and significantly decreased on day 180 (24+/-3 pmol/l) in the remodelling group. In contrast, plasma BNP levels significantly decreased from day 2 (25+/-4 pmol/l) to day 90 (9+/-1 pmol/l) and reached a steady level thereafter in the non-remodelling group. Plasma BNP levels on day 7 correlated positively with an increase in EDVI (r=0.70, P<0.001) from the acute to chronic phase. More importantly, the sustained elevation of plasma BNP (percentage decrease smaller than 25%) from day 30 to day 90 identified patients in the remodelling group with a sensitivity of 100% and a specificity of 83%. In conclusion, not only the high levels of plasma BNP in an acute phase, but also the sustained elevation of plasma BNP in a chronic phase, may be associated with progressive ventricular remodelling occurring long after acute myocardial infarction.

Adult↗

The release of tumor necrosis factor-alpha, interleukin-1, interleukin-6 and prostaglandin E2 in bovine Kupffer cells stimulated with bacterial lipopolysaccharide.

Kupffer cells, in response to gut-derived bacteria, viruses and endogenous endotoxins, are thought to be a major source of proinflammatory cytokines and other mediators. In the present study, we investigated the mode of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) production by bovine Kupffer cells in response to LPS in vitro. By semi-quantitative reverse transcription-polymerase chain reaction, both TNF-alpha and IL-1beta mRNAs were expressed between 3 and 12 h after stimulation with 1 microg/ml of LPS. The IL-1alpha transcript also increased at 3 h, and then disappeared at 6 h. Although IL-6 mRNA was slightly expressed without stimulation, it increased and reached a peak after 6 h, and then decreased to normal levels by 24 h. The secretion of TNF-alpha and IL-1 was detected after 3 h and increased until 12 and 24 h, respectively, as detected by bioassay. IL-6 was secreted at a low level without stimulation, peaked 6 h after stimulation and remained elevated until 24 h. The secretion of prostaglandin E2 continued to increase for 24 h. These results suggest that several inflammatory cytokines released from bovine Kupffer cells are regulated in different modes.

Animals↗

Thermally reversible xyloglucan gels as vehicles for rectal drug delivery.

The aim of this study was to investigate the potential application of thermoreversible gels formed by a xyloglucan polysaccharide derived from tamarind seed for rectal drug delivery. Xyloglucan that had been partially degraded by beta-galactosidase to eliminate 44% of galactose residues formed gels at concentrations of between 1 to 2% w/w at gelation temperatures decreasing over the range 27 to 22 degreesC with increasing concentration. The in vitro release of indomethacin and diltiazem from the enzyme-degraded xyloglucan gels followed root-time kinetics over a period of 5 h at 37 degreesC; the diffusion coefficients increasing with temperature increase between 10 and 37 degreesC. The in vitro release of indomethacin from the gels was significantly more sustained than from commercial suppositories. Measurement of plasma levels of indomethacin after rectal administration to rabbits of the gels and commercial suppositories containing an identical drug concentration indicated a broader absorption peak following administration of the gels, and a longer residence time. There was no significant difference in bioavailability of indomethacin when administered by these two vehicles. Morphological studies of rectal mucosa following a single administration of the gels showed no evidence of tissue damage. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for rectal delivery of drugs.

Administration, Rectal↗

Previous angina reduces in-hospital death in patients with acute myocardial infarction.

There is little information on how previous angina influences in-hospital deaths secondary to acute myocardial infarction (MI). This study evaluated the causes of in-hospital deaths in MI patients with and without previous angina. A total of 2,264 consecutive patients were admitted to our hospital due to acute MI. These patients were divided into 2 groups according to the presence or absence of prior MI. Both groups were further divided according to the presence or absence of previous angina. The causes of in-hospital deaths were classified into 4 categories: (1) cardiogenic shock or congestive heart failure, (2) cardiac rupture, (3) arrhythmia, and (4) other causes. In patients with a first MI, the in-hospital mortality rate was lower in patients with previous angina than those without (6.9% vs 11.4%, p <0.01). There was no significant difference between these patients with and without previous angina in in-hospital deaths due to cardiogenic shock or congestive heart failure, arrhythmia, or other causes. Death due to cardiac rupture was less frequent in patients with previous angina (1.4% vs 5.0%, p <0.01). In patients with prior MI, the in-hospital mortality rate was lower in patients with than without previous angina (17.7% vs 25.3%, p <0.05). In contrast to patients with their first MI, there was a trend toward a lower incidence of in-hospital death due to cardiogenic shock or congestive heart failure in patients with previous angina (12.8% vs 19.0%, p = 0.05). There were no significant differences in in-hospital deaths due to cardiac rupture, arrhythmia, and other causes between the 2 subgroups. In multivariate analysis, previous angina was an independent predictor of in-hospital death. Thus, in-hospital deaths after acute MI in patients with previous angina were less because of less cardiac rupture in patients with a first MI and less cardiogenic shock or congestive heart failure in patients with prior MI.

Aged↗

DNA Data Bank of Japan at work on genome sequence data.

We at the DNA Data Bank of Japan (DDBJ) (http://www.ddbj.nig.ac.jp) have recently begun receiving, processing and releasing EST and genome sequence data submitted by various Japanese genome projects. The data include those for human, Arabidopsis thaliana, rice, nematode, Synechocystis sp. and Escherichia coli. Since the quantity of data is very large, we organized teams to conduct preliminary discussions with project teams about data submission and handling for release to the public. We also developed a mass submission tool to cope with a large quantity of data. In addition, to provide genome data on WWW, we developed a genome information system using Java. This system (http://mol.genes.nig.ac.jp/ecoli/) can in theory be used for any genome sequence data. These activities will facilitate processing of large quantities of EST and genome data.

Animals↗

Clinical and epidemiologic studies of familial hemophagocytic lymphohistiocytosis in Japan. Japan LCH Study Group.

BACKGROUND AND PROCEDURE: The etiology of familial hemophagocytic lymphohistiocytosis (FHL), which is characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, remains unknown. We analyzed 43 FHL patients, all with affected siblings, in 18 families who were identified during the period 1986-1995 in Japan. RESULTS: The presence of consanguinity was evident in two families (11%). The majority of families lived in western Japan, where the frequency of consanguineous marriage is high. The incidence of FHL was significantly higher in the western island, Kyushu, than in other areas. The segregation ratio calculated for these families was 0.35 by the Weinberg proband method, showing the autosomal-recessive inheritance of the disease. Since the diagnosis of an FHL patient without affected siblings (sporadic case) is quite difficult, we calculated the possible number of sporadic cases; approximately 122 patients could be identified as sporadic FHL cases during the same period in Japan. Most of the clinical and laboratory findings were not distinguishable from those of other types of lymphohistiocytosis. However, atypical lymphoid cells with azurophilic granules in peripheral blood were observed in half of the patients at diagnosis, suggesting the clinical importance of this parameter for early diagnosis. Despite intensive therapy, the prognosis of FHL was extremely poor; but 4 of the 8 patients who have survived had received bone marrow transplantation (BMT), indicating the effectiveness of BMT for this disorder. CONCLUSIONS: The distribution of FHL in areas of highly frequent consanguineous marriage and the segregation analysis indicated a genetic factor in FHL. The identification of the genes for FHL is expected to contribute to a cure for this disorder, and might also enable FHL carrier detection and donor selection for BMT.

Adolescent↗

Correlation of residual stenosis immediately after coronary angioplasty with long-term prognosis.

This study evaluated the correlation of residual stenosis after percutaneous transluminal coronary angioplasty with the long-term prognosis. Among consecutive 1,230 patients who underwent coronary angioplasty in the National Cardiovascular Center in Osaka, Japan, 894 patients had de novo lesions. Of these, the 70 patients with acute myocardial infarctions and 105 with unstable angina who had emergency coronary angioplasties were excluded from the study. Among the remaining 719 patients, successful dilatation of the main target vessel was achieved in 592 patients, who then comprised the study group. They were divided into three groups according to their residual stenosis (RS) immediately after coronary angioplasty: group A, RS < 15% (n=208); group B, 15% < or = RS < or = 35% (n=286), and group C, 35% < RS < 50% (n=98). The duration of follow-up was 1,668, 1,660, and 1,680 days in group A, B, and C, respectively. The groups A, B, and C were not significantly different in terms of age, history of myocardial infarction, left ventricular ejection fraction, number of diseased vessels and target vessels, and risk factors such as hypertension, hyperlipidemia, and diabetes mellitus. Primary end point of follow-up was defined as death from any cause and the second end point was occurrence of cardiac events. Kaplan-Meier survival analysis showed significant differences among the three groups. Moreover, survival curves seem to be dependent on the degree of post-procedural residual stenosis. Multivariate analysis using a Cox proportional hazard regression model showed that age, ejection fraction, and residual stenosis were independent determinants of event-free, cardiac, and total survival. Residual stenosis immediately after coronary angioplasty is an independent contributor to long-term clinical prognosis in patients treated with successful balloon coronary angioplasty.

Analysis of Variance↗

Analysis of HIV by entropy evolution rate.

We analyze the variation of HIV after infection by means of an information measure, called the entropy evolution rate. In our analysis, we use a part of the external glycoprotein gp120 including the V3 region observed from six patients. Then we could make the following two aspects clear; (1) the relation between the change of the entropy evolution rate and the appearance of symptoms of disease, and (2) the relation between the change of the entropy evolution rate and that of the CD4 count of the patients.

Acquired Immunodeficiency Syndrome↗

Improvement by FUB 181, a novel histamine H3-receptor antagonist, of learning and memory in the elevated plus-maze test in mice.

Effects of FUB 181 [3-(4-chlorophenyl)propyl-3-(1H-imidazol-4-yl)propyl ether], a novel histamine H3-receptor antagonist, on a scopolamine-induced learning deficit in the elevated plus-maze test were studied in mice. FUB 181 alone (2.5 and 5 mg/kg, i.p.) ameliorated the scopolamine-induced learning deficit in mice. This effect was antagonized by BP 2.94 (10 mg/kg, i.p.), a prodrug of (R)-alpha-methylhistamine (histamine H3-receptor agonist), and by ketotifen (4 mg/kg, i.p.), a histamine H1-receptor antagonist, both penetrating the blood-brain barrier. However, the ameliorating effect of FUB 181 (2.5 mg/kg) was not antagonized by either terfenadine (10 mg/kg, i.p.), a histamine H1-receptor antagonist with poor penetration of the blood-brain barrier, or zolantidine (20 mg/kg, i.p.), a centrally effective histamine H2-receptor antagonist. In a biochemical study, FUB 181 had no significant effect on either acetylcholine or choline level in mice brain at the doses tested. These findings suggest that FUB 181 increases the release of histamine by blocking presynaptic histamine H3 autoreceptors, and that released histamine in turn activates postsynaptic H1 and H2 receptors, predominantly histamine H1 receptors, and in this fashion improves learning and memory in mice. Our findings also suggest that the histaminergic system may play an important role in learning and memory, and that FUB 181 may be a clinical candidate for the therapy of dementia.

Acetylcholine↗

Plasma brain natriuretic peptide is a biochemical marker for the prediction of progressive ventricular remodeling after acute myocardial infarction.

To investigate the relation between plasma brain natriuretic peptide (BNP) and progressive ventricular remodeling, we measured plasma BNP and atrial natriuretic peptide (ANP) in 30 patients with acute myocardial infarction on days 2, 7, 14, and 30 after the onset. Left ventricular end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and ejection fraction (EF) on admission and 1 month after the onset were assessed by left ventriculography. Changes in EDVI (deltaEDVI), ESVI (deltaESVI), and EF (deltaEF) were obtained by subtracting respective acute-phase values from corresponding chronic-phase values. Plasma ANP on days 2 and 7 showed only weak correlations with deltaEDVI (r = 0.48 and 0.54; both p < 0.01), whereas plasma BNP on day 7 more closely correlated with deltaEDVI (r = 0.77; p < 0.001). When study patients were divided into two groups according to plasma BNP on day 7, the group with BNP higher than 100 pg/ml showed greater increases in left ventricular volume and less improvement in EF compared with the other group with BNP lower than 100 pg/ml (deltaEDVI = 10.4 +/- 8 vs -3.4 +/- 9 ml/m2, deltaESVI = 6.2 +/- 7 vs -4.9 +/- 5 ml/m2, and deltaEF = 1.0% +/- 4% vs 4.9% +/- 5%; p < 0.05, respectively). Multiple regression analysis revealed that only plasma BNP on day 7, but not ANP, peak creatine phosphokinase level, left ventricular end-diastolic pressure, or acute-phase EF, correlated independently with deltaEDVI (p < 0.01). These results suggest that plasma BNP may be a simple and useful biochemical marker for the prediction of progressive ventricular remodeling within the first 30 days of acute myocardial infarction.

Adult↗