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Biomedical subjects

M Kawaguchi

Publications and source records attributed to M Kawaguchi.

At least 91 records · Page 5Linked to original sources

Immunohistochemical analysis of apoptosis-related proteins in human embryonic and fetal pancreatic tissues.

BACKGROUND: The growth of both cancer cells and fetal tissue is rapid; however, cancer cells de-differentiate and proliferate in a disorderly manner, whereas fetal tissues differentiate and proliferate in an orderly manner. Thus, there may be both common and different factors that are involved in the process of the uncontrolled cell growth of pancreatic cancers and the development of the fetal pancreas. The common part of the mechanisms should be in the regulation of the cell cycle, resulting in rapid proliferation via such mechanisms as growth stimulation and avoidance of apoptosis. Therefore, in the current study we investigated the expression of apoptosis-related proteins in fetal pancreatic tissues. METHODS: Sixteen human embryonic and fetal pancreatic tissues obtained between 6 and 32 wk of gestation were used. We immunohistochemically examined the protein expression of Bcl-2, Bcl-XL, Mcl-1, and Bax. Further, the expression of insulin, glucagon, and proliferting cell nuclear antigen (PCNA), and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining were examined. RESULTS: In embryonic and fetal pancreatic tissues, Bcl-2 was not detected in any type of pancreatic cell (acinar, ductal, or islet). Bcl-XL was expressed in all types of pancreatic cells throughout the gestation. Mcl-1 was expressed in all types of pancreatic components, and strongly expressed in the margin of the islets. Bax, a pro-apoptotic protein, was expressed in all components. PCNA was strongly expressed in the embryonic and fetal pancreas, especially in early stages of gestation; however, TUNEL staining was negative in all samples. At least one antiapoptotic protein was expressed in all types of pancreatic cells. CONCLUSION: The results of the current study indicate that active proliferation and avoidance of apoptosis take place in embryonic and fetal pancreatic tissues, which may be controlled by particular combinations of apoptosis-related proteins. Among these proteins, Bcl-XL and Mcl-1 may play an important role in the proliferation and differentiation of the embryonic and fetal pancreas.

Apoptosis↗

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 14). Comparison of the effects of 2- and 4-weeks intravenous administration of etoposide.

In order to examine whether effects on male reproductive organs following 2-weeks administration of Etoposide (ET) are detectable, ET was administered intravenously once a week to rats for 2 and 4 weeks at 5 and 10 mg/kg/week. No deaths and no drug-related changes in body weight or in gross pathology were observed. However, decreased testis and/or thymus weights were noted. And histopathological examination revealed decrease and/or loss of spermatogonia and spermatocytes in the testes. It was evident that the target cells of the test article in the male reproductive organs are spermatogonia. Atrophy of the medulla and increase of immature lymphocytes in the cortex of the thymus and increase of fatty cells and increase of immature hematopoietic cells in the bone marrow were also apparent. The histological changes in the testis, thymus and bone marrow suggest that ET inhibits cellular mitosis which reflects its mechanism of action as an anticancer agent. It is concluded that effects of ET on male reproductive organs can be detected by histopathological examination of the testes after 2-weeks repeated administration.

Animals↗

A diabetic patient with scrotal subcutaneous abscess.

A 51-year-old type 2 diabetic patient with a scrotal subcutaneous abscess is reported. He was diagnosed as having diabetes mellitus five years earlier. He had left scrotal swelling and pain with granulocytosis, elevated C-reactive protein and hyperglycemia. He was successfully treated with incision and drainage (Streptococcus agalactiae was identified in the pus), debridement, antibiotics, immunoglobulin and insulin. This case resembled Fournier's gangrene, an infective necrotizing fasciitis of the perineal, genital or perianal regions. Diabetes mellitus is a basic disorder often associated with Fournier's gangrene. Scrotal subcutaneous abscess should be prevented from progressing to Fournier's gangrene with early and appropriate treatment.

Abscess↗

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. II. Physico-chemical properties and structure elucidation.

The structures of new antifungal antibiotics, PF1163A and B, were elucidated by spectroscopic analyses of the degradation products and by X-ray crystallography of the de-2-hydroxyethyl derivative of PF1163B. Both antibiotics consist of a 13-membered macrocyclic structure containing a derivative of N-methyl tyrosine and a hydroxy fatty acid. PF1163A differs from PF 1163B by having an additional hydroxyl group on the side chain.

Antifungal Agents↗

Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells.

Betacellulin (BTC) was identified in mouse pancreatic beta cell tumors as a member of the epidermal growth factor (EGF) family, and was found to bind and activate the EGF receptor. BTC is also expressed in some human malignancies and may have an important role in tumor growth progression. We examined whether BTC and EGF have a growth stimulatory effect on human pancreatic cancer cell lines both in vitro and in vivo. We also investigated the BTC expression and autonomous induction of BTC in pancreatic cancer cells. in vitro, both BTC and EGF had almost the same proliferative effect on Panc-1, MIA PaCa-2 and AsPC-1. in vivo, in a Panc-1 inoculated athymic mice model, BTC-treated tumors grew approximately five times larger than in control. Immunocytochemistry showed that BTC expression occurred in three pancreatic cancer cell lines, with MIA PaCa-2 showing the strongest intensity. Semi-quantitative RT-PCR of MIA Paca-2 showed that mRNA levels of BTC gradually increased after treatment with 1 nM BTC. Immunocytochemistry also demonstrated that the intensity of BTC-like immunoreactivity was increased when treated with 1 nM BTC but was reduced after treatment with 100 nM of AG1478, an EGF receptor tyrosine kinase inhibitor. BTC has thus a significant growth stimulatory effect on pancreatic cancer cells and might function as an autocrine and paracrine growth factor. BTC expression in pancreatic cancer cells is, at least in part, controlled by an auto-induction mechanism.

Animals↗

[Intraoperative motor evoked potential monitoring: a review of 115 cases].

We reviewed our experiences of intraoperative motor evoked potentials (MEPs) monitoring for 115 operations on the spine or spinal cord. We observed compound muscle action potentials from bilateral anterior tibial muscles by electrical transcranial stimulation of the motor cortex under general anesthesia induced and maintained with intravenous anesthetics (ketamine, propofol, or droperidol), fentanyl, and 50% nitrous oxide. Partial neuromuscular blockade was obtained with continuous infusion of vecuronium. MEPs were recorded bilaterally in 91 cases (79%) and laterally in 18 cases (16%). Postoperative deterioration of motor function was observed in 2 cases and amplitude of MEPs decreased more than 50% of control values in both cases. Intraoperative monitoring of MEPs might be a reliable indicator of spinal cord motor function.

Adult↗

[The effect of preoperative factors on intraoperative oxyhemoglobin dissociation curve].

The position of oxyhemoglobin dissociation curve (ODC) expressed with P50, has a large influence on the oxygen supply. It has been reported that during hypoxia with increased oxygen demand, P50 can increase with a reduction in oxygen affinity. In this study, we investigated the effect of preoperative factors on intraoperative P50 and the relation between the P50 values of the mixed venous blood and those of internal jugular bulb venous blood in seventy patients for cardiac surgery. Preoperative reduction in percentage vital capacity (%VC) and reduced hemoglobin concentration were associated significantly with an increase in intraoperative P50 value. The P50 act (P50 value with only temperature adjusted to 37 degrees C) of the internal jugular bulb venous blood was significantly higher than that of mixed venous blood. These results suggest that intraoperative tolerance to hypoxia and the increase in oxygen demand might be reduced in patients with preoperative abnormality of %VC and the hemoglobin concentration. And this tolerance might be limited in brain.

Aged↗

[Risk factors and effect of reperfusion therapy on left ventricular free wall rupture following acute myocardial infarction].

Reperfusion therapy is one of the most effective treatments for acute myocardial infarction, but the effect on left ventricular free wall rupture remains to be determined. This study tried to clarify the risk factors and effect of reperfusion therapy on the risk of free wall rupture following acute myocardial infarction. 2,671 consecutive patients with acute myocardial infarction admitted to our hospital were examined. Incidence of free wall rupture showed no degenerative change(0 to 5.8%; mean 2.1%). The 1,269 consecutive patients from 1985 to 1995 were examined closely to evaluate risk factors and the effect of reperfusion therapy on the risk of free wall rupture. Fourteen patients who underwent emergent coronary artery bypass surgery were excluded. Free wall rupture was found in 25 patients (2.0%). Multivariate analysis confirmed that high age(> or = 70 years) and first acute myocardial infarction were independent risk factors of free wall rupture (odds ratio 3.62, p = 0.003; odds ratio 7.69, p = 0.046, respectively). The incidence of free wall rupture in the conservative therapy group(n = 799) was 2.1%, successful reperfusion group(n = 373) was 0.5%, and unsuccessful reperfusion group(n = 83) was 7.2% with significant statistical differences(p < 0.01). There was no statistical difference between the direct percutaneous transluminal coronary angioplasty group(n = 84, 3.6%) and the thrombolysis group(n = 372, 1.3%). Successful reperfusion was the only independent factor in the reperfusion therapy group that reduced the incidence of free wall rupture(odds ratio = 0.07, p = 0.001). We conclude that reperfusion of the infarct-related artery and more intensive management of unsuccessful reperfusion is important to prevent free wall rupture following acute myocardial infarction.

Age Factors↗

[The correlation between the exacerbation of bronchial asthma and picornavirus (human rhino virus) infection in throat gargles by RT-PCR].

Viral infection is one of important factors to cause the exacerbation of bronchial asthma. We have investigated 167 adults of asthmatics to clarify the correlation between viral infection and exacerbation of asthma. Patients were classified to four group by the symptoms of common cold and asthma attack. Furthermore, we have examined Picornavirus and Human rhino virus RNA from throat gargles of patients using RT-PCR (reverse transcription--polymerase chain reaction) method. Forty of 65 (61.5%) asthmatics with common cold revealed asthma attack and common cold was significantly associated with acute exacerbation of asthma (p < 0.01). We identified Picornavirus RNA, which include 113 of Human rhino virus serotypes and enterovirus, from the samples of 16 of 52 (30.8%) patients who had acute exacerbation. It was significantly higher than the detection rate of viral RNA from patient without asthma attack. Furthermore, we analyzed Human rhino virus RNA from the same samples by RT-PCR and 93.7% of Picornavirus were identified as Human rhino virus. Taken together, these findings suggest that common cold is significantly associated with the exacerbation of bronchial asthma. Human rhino virus infection might be one of important virus in this procedure.

Adult↗

Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases.

Two women with endometrial carcinoma who wished to preserve their childbearing ability received conservative treatment by medroxyprogesterone acetate (MPA, 600 mg/day for 22 weeks and 29 weeks, respectively). Following regression of endometrial lesions, their infertility was treated by inducing ovulation. Intact pregnancy was diagnosed 13 months and 11 months after completion of the MPA treatment, respectively. One patient had a twin pregnancy and delivered two infants at 35 weeks of gestational age. The other patient delivered a full-term baby. They had no evidence of recurrence 60 months and 31 months after the conservative treatment, respectively. We believe this conservative treatment with progestin may be safely performed for young patients with endometrial cancer who wish to preserve their fertility.

Adenocarcinoma↗

[Monitoring of motor evoked potentials during insertion of iliosacral screws for reconstruction of pelvic fracture in two patients].

Monitoring of myogenic motor evoked potentials (MEPs) induced by transcranial electrical stimulation has become a promising tool for intraoperative monitoring. We described 2 patients who had developed significant decrease in MEP during the insertion of iliosacral screws for reconstruction of pelvic fractures. In both patients, MEPs were successfully obtained prior to the insertion under general anesthesia and partial neuromuscular blockade (propofol, ketamine, fentanyl, and nitrous oxide in oxygen: vecuronium), but reduced in association with the insertion. In one patient, they were restored by the re-insertion of screw and no new neurological deficits were observed postoperatively. However, in another patient, the decrease was not normalized and he suffered from paresis of the lower extremities after the surgery. We consider that intraoperative changes in MEPs could precisely predict postoperative motor function.

Aged↗

[Chemo/endocrine therapy for breast cancer patients].

Standard adjuvant chemo/endocrine therapy for breast cancer patient is based upon St. Gallen's consensus 1998. Recent development in the field of adjuvant chemo/endocrine therapy is an usage of LH-RH analogue with tamoxifen for premenopausal hormone receptor positive women, and also an emerging role of taxans. Orally given 5-FU derivatives may work in adjuvant settings. The third generation aromatase inhibitors have established their role in second line hormone therapy for the advanced or recurrent breast cancer patients. High dose chemotherapy should not be used in outside clinical trials.

Anastrozole↗

Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression.

To examine the expression of the stromal cell-derived factor 1 (SDF-1)/CXCR4 receptor ligand system in pancreatic cancer cells and endothelial cells, we performed immunohistochemical analysis for 52 pancreatic cancer tissue samples with anti-CXCR4 antibody and reverse transcription-PCR analysis for CXCR4 and SDF-1 in five pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, HPAC, and PANC-1), an endothelial cell line (HUVEC), and eight pancreatic cancer tissues. We then performed cell migration assay on AsPC-1 cells, HUVECs, and CFPAC-1 cells in the presence of SDF-1 or MRC-9 fibroblast cells. Immunoreactive CXCR4 was found mainly in pancreatic cancer cells and endothelial cells of relatively large vessels around a tumorous lesion. The immunopositive ratio in the pancreatic cancer was 71.2%. There was no statistically significant correlation with clinicopathological features. SDF-1 mRNA expressions were detected in all pancreatic cancer tissues but not in pancreatic cancer cell lines and HUVECs; meanwhile, CXCR4 mRNA was detected in all pancreatic cancer tissues, cancer cell lines, and HUVECs. The results indicate that the paracrine mechanism is involved in the SDF-1/CXCR4 receptor ligand system in pancreatic cancer. In vitro studies demonstrated that SDF-1 significantly increased the migration ability of AsPC-1 and HUVECs, and these effects were inhibited by CXCR4 antagonist T22, and that the coculture system with MRC-9 also increased the migration ability of CFPAC-1 cells, and this effect was significantly inhibited by T22. Our results suggested that the SDF-1/CXCR4 receptor ligand system may have a possible role in the pancreatic cancer progression through tumor cell migration and angiogenesis.

Adult↗

[Two cases of ischemic changes indicated in the amplitude of motor evoked potentials during thoracoabdominal aortic aneurysm repair].

Monitoring of motor-evoked potentials (MEPs) is employed to examine functional integrity of descending motor pathway during thoracic aortic surgery. We experienced two cases of intraoperative changes in MEPs during thoracic aortic replacement. In one case, MEPs recovered after the intercostal artery reattachment, and in another case after the release of aortic clamping. No postoperative paraplegia was found in both cases. We conclude that monitoring of MEPs is useful not only because we can detect symptoms of the spinal cord injury from ischemia immediately but also because they give us a clue to decide operative procedures.

Aged↗

Effect of pregnancy on insulin metabolism in spontaneously hypertensive rats.

Several lines of evidence suggest that insulin resistance and/or hyperinsulinemia may play an important role in the pathogenesis of hypertension. We studied the effect of pregnancy on insulin metabolism in spontaneously hypertensive rats (SHRs) and in Wistar-Kyoto rats (WKYs) as a control. Pregnancy markedly reduced blood pressure in both strains of rats, but insulin resistance as determined by the hyperinsulinemic glucose clamp (10 mU/kg/min) increased in SHRs and was unchanged in WKYs. The plasma insulin response to an intravenous glucose challenge in SHRs was low and did not change with pregnancy. Therefore, it is suggested that the regulation of blood pressure in these animals is linked to an unknown factor rather than to insulin resistance and hyperinsulinemia. Fetuses from SHRs had a lower body weight and plasma glucose level and higher plasma insulin and pancreatic insulin levels than those from WKYs. Thus, fetal hyperinsulinemia in the SHR may be linked to the development of hypertension in adulthood.

Animals↗

Effect of dentin primers containing N-methylolacrylamide or N-methylolmethacrylamide on dentin pretreatment.

The effect of experimental dentin primers containing N-methylolacrylamide (MEAA) or N-methylolmethacrylamide (MEMA) on the bonding of three commercial light-cured resin composite systems [Restorative Z 100 (Scotchbond), Palfique Estelite (Macbond) and Photo Clearfil A (Clearfil Photobond)] to etched dentin was investigated. Water solutions of 35% hydroxyethyl methacrylate (HEMA). 50% MEAA or 30% MEMA were used as dentin primers. The dentin etched with 10% phosphoric acid solution was pretreated with dentin primers for 30 s. The resin composite systems were applied in a Teflon tube positioned onto pretreated dentin surfaces. After water immersion for 1 day, the shear bond strengths were measured. The thicknesses of hybrid layers at dentin-resin interfaces treated with 6 mol/l HCl and 1% NaOCl were measured by scanning electron microscopy. The dentin primer pretreatment increased the bond strengths of all resin composite systems. For Macbond and Clearfil Photobond, the bond strengths (14.2-26.5 MPa) with MEAA and MEMA were higher than those (10.5 and 17.8 MPa) with HEMA. All hybrid layer thicknesses were 1-1.5 microns after HCl immersion. The hybrid layers after NaOCl immersion become narrower. The main fracture pattern of specimens exhibiting high bond strengths (more than 14.2 MPa) was dentin cohesive fracture after bond test. For Macbond and Clearfil Photobond, the layers of specimens pretreated with MEAA and MEMA were clearly thicker than those pretreated with HEMA after NaOCl immersion. MEAA and MEMA solutions were more effective in improving the bond strength of Macbond and Clearfil Photobond to etched dentin than was HEMA. Macbond and Clearfil Photobond created good hybrid dentin layers which could resist NaOCl-attack when MEAA and MEMA solutions were used as dentin primers.

Acrylamides↗