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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 325 records · Page 18Linked to original sources
PubMed1999

Case report: mucinous cholangiocarcinoma featuring a multicystic appearance and periportal collar in imaging.

A case of mucinous cholangiocarcinoma (CC), a rare histological type of CC, featuring unusual images is reported. The patient was hospitalized because of acute development of jaundice and fever. Computed tomography demonstrated multiple cystic lesions in the liver and a band-like low density area parallel to the intrahepatic portal vein, a so-called 'periportal collar'. Endoscopic cholangiography revealed a stricture of the hepatic duct with slight upstream dilatation. Cytology of the bile juice and fine-needle aspiration of the cystic lesion in the liver disclosed mucinous carcinoma. The patient died of multiorgan failure 3 weeks after admission. The autopsied liver showed that multiple mucus lakes were lined with adenocarcinoma cells and signet ring cells were floating in the mucus lakes. The cancer cells had spread along the portal tract and invaded into the hepatic parenchyma.

Adenocarcinoma, Mucinous↗
PubMed1999

Aberrant pancreatic tissue accompanied by heterotopic gastric mucosa in the gall-bladder.

A 5 mm pancreatic heterotopia was incidentally identified in the gall-bladder with small cholesterol polyps following cholecystectomy in an asymptomatic 49-year-old female. Microscopically, inflammatory changes in the wall were minimal. The aberrant tissue consisted of acini and ducts but did not have islet formation. Heterotopic gastric mucosal tissue with a mixture of foveolar cells and pyloric glands was seen at the orifice of the pancreatic heterotopia. Islet peptide-immunoreactive endocrine cells were scattered among the pancreatic parenchyma, and the gastric-type gland contained cells positive for gastrin, somatostatin and glucagon. A noteworthy finding was the immunohistochemical detection of a single insulin-containing cell in the pyloric gland.

Choristoma↗
PubMed1999

Intraoperative radiotherapy for the abdominal lymphatic system in patients with esophageal carcinoma.

We applied intraoperative radiotherapy (IORT) to the esophageal carcinoma in an attempt to prevent abdominal lymph node recurrence, and retrospectively studied patterns of failure and controllability of abdominal lymph nodes in patients treated with or without IORT. Between July 1986 and October 1997, 81 patients with radically resected esophageal carcinoma, aged 42-76 years (mean 61), were divided into two groups, the IORT group (39 patients) and the non-IORT group (42 patients). All patients except two, who received transhiatal esophagectomy for superficial carcinoma, underwent subtotal esophagectomy with thoracic and abdominal with/without cervical lymphadenectomy. Fourteen patients underwent only surgical resection, and the remaining 67 patients received radiotherapy to the mediastinum post-operatively (40-50 Gy/20-25 Fr/4-5 W) in 37 and preoperatively (44 Gy/40 Fr/4 W) in 30 patients. Preoperative irradiation was performed as a neoadjuvant chemoradiotherapy consisting of two courses of cisplatin (each patient received 80-100 mg, mean 60 mg m(-2), day 1, bolus injection) and 5-fluorouracil (each patient received 500-1000 mg day(-1), mean 400 mg m(-2), days 1-4, continuous infusion). The target volume of IORT encompassed the upper abdominal lymph node area including lymph node groups of right/left cardia, left gastric artery, celiac artery and abdominal para-aorta. A single dose of high-energy electrons (9-12 MeV) of 20-23 Gy, prescribed to the 90% isodose curve, was delivered. Treatment for the abdominal lymphatic system was classified into four categories: surgery alone in 30 patients, surgery with chemotherapy in 12, surgery with IORT in 15, surgery with chemotherapy and IORT in 24. There were no complications related to IORT. Forty patients (49%) had recurring carcinoma: in the lymph nodes (36%), in distant organs (27%) and locally (6%). The incidence of lymph node metastasis was 29% in the neck, 32% in the mediastinum, and 27% in the abdomen. Abdominal lymph node recurrence in the IORT group was less frequent than in the non-IORT group (p=0.048). In particular, 24 patients treated with a combination of surgery, chemotherapy and IORT had no recurrence in the abdominal lymphatic system. The overall median survival was 46 months, the survival at 1, 3, and 5 years being 85%, 52%, and 44% respectively. However, there was no difference in survival between the IORT group and the non-IORT group. The IORT for the abdominal lymphatic system was feasible for reduction of the rate of abdominal lymphatic recurrence without survival benefit in this study. This retrospective finding should be confirmed by a prospective randomized study.

Adult↗
PubMed1999

Increased glomerular cytosolic phospholipase A2 activity of OLETF rats with early diabetes.

In view of the potential role of prostaglandins (PGs) in development of glomerular hyperfiltration leading to diabetic nephropathy, we studied the temporal relationship of the activity of cytosolic phospholipase A2 (cPLA2), a rate-limiting enzyme for eicosanoid biosynthesis, with hyperfiltration and the histological changes in glomeruli using OLETF rats, a model for non-insulin-dependent diabetes mellitus (NIDDM). Diabetes mellitus and associated histopathological changes, which developed spontaneously by 30-46 weeks after birth of OLETF rats, were accompanied by approximately 65% increase in glomerular cPLA2 activity that showed significant correlations with elevated plasma glucose levels and creatinine clearance. Moreover, mesangial cells cultured for 5 days with high glucose exhibited approximately 2-fold higher cPLA2 activity than those cultured with physiologic level of glucose. These data suggest that increased glomerular cPLA2 activity leads to production of PGs, which may promote the progression of early diabetic glomerular hyperfiltration and subsequent diabetic nephropathy.

Aging↗
PubMed1999

Effects of the new angiotensin II type 1 receptor antagonist KRH-594 on several types of experimental hypertension.

The antihypertensive effect of dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H- tetrazol-5-yl)biphenyl-4-yl]methyl-1,3,4-thiadiazoline-2- ylidene]aminocarbonyl]-1-cyclopentenecarboxylate (CAS 169328-25-0, KRH-594), a new angiotensin II type 1 (AT1) receptor antagonist, was studied in several experimental hypertensive models. The effects of KRH-594 on the circulating reninangiotensin system and on renal function were also investigated. Oral administration of KRH-594 (0.3 or 1 mg/kg) dose-dependently inhibited the angiotensin II-induced pressor response in common marmosets. KRH-594 (1, 3, or 10 mg/kg p.o.) dose-dependently exerted a long-lasting antihypertensive effect in spontaneously hypertensive rats (SHRs) and in 2-kidney 1-clip renal hypertensive rats (RHRs). Furthermore, repeated oral administration of KRH-594 (3 or 10 mg/kg/d) reduced blood pressure dose-dependently in SHRs, RHRs, and renal hypertensive dogs without tachycardia and with no evidence of a rebound phenomenon following drug withdrawal. On the other hand, in deoxycorticosterone acetate salt rats and normotensive rats, KRH-594 (10 or 30 mg/kg p.o.) did not have significant effects on systolic blood pressure. In SHRs, KRH-594 (3 or 10 mg/kg/d p.o. for 2 weeks) dose-dependently increased both plasma renin activity and the plasma angiotensin I concentration, but had no effect on the urinary excretion of sodium, potassium, and chloride or on creatinine clearance. These results suggest that KRH-594 should be effective in patients with essential or renal hypertension.

Administration, Oral↗
PubMed1999

Antianginal effects of ranolazine in various experimental models of angina.

The effects of ranolazine (CAS 95635-55-5, KEG-1295), a novel antianginal drug, on the ST-segment changes induced by coronary ligation, epinephrine, and vasopressin were examined following oral or intraduodenal administration. In anesthetized dogs, intraduodenal administration of KEG-1295 (10, 30, or 50 mg/kg) or atenolol (10 mg/kg) significantly attenuated the ST-T wave elevation induced by 2-min coronary ligation imposed during electrical heart pacing (200 beats/min). This antianginal effect of KEG-1295 persisted for 3 h without any changes in hemodynamic parameters, while that of atenolol was accompanied by more or less maintained decreases in diastolic blood pressure, heart rate, and the maximum first derivative of left ventricular pressure. In anesthetized rats, oral administration of KEG-1295 (10, 30, or 50 mg/kg) attenuated the ST-T wave elevation induced by epinephrine (0.3 microgram/kg i.v.) in a dose-dependent manner, although KEG-1295 (10 or 30 mg/kg p.o.) failed to attenuate the ST-segment depression induced by vasopressin (0.2 IU/kg i.v.). These findings suggest that, taken orally, KEG-1295 may exert potent protective effects against angina pectoris, except that caused by vasospasm. Further, KEG-1295 may be categorized as a new type of antianginal agent, without any primary hemodynamic effects.

Acetanilides↗
PubMed1999

Stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors by serum human chorionic gonadotropin of patients with hydatidiform mole.

We evaluated the stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors (CHO-hTSHR cell) by sera of five patients with hydatidiform mole before and after the evacuation of the mole, and compared the results with serum human chorionic gonadotropin (hCG) concentrations and serum free thyroid hormones in these patients. Significantly increased CHO-hTSHR cell stimulating activities were observed in sera from untreated patients, and the activity decreased promptly after the evacuation of the mole, concomitantly with the decrease in serum hCG and free thyroid hormones. CHO-hTSHR cell stimulating activity of sera of the untreated patients significantly correlated with serum hCG. Moreover, serum hCG stimulated CHO-hTSHR cells in a dose dependent manner similar to the dose-response curve of the stimulation by purified hCG. Sera of the patients and purified hCG did not stimulate nontransfected CHO-K1 cells. However, a significant correlation was not observed between serum-free thyroid hormones and serum hCG or between serum free thyroid hormones and CHO-hTSHR cell stimulating activities in untreated patients. These results indicate that serum hCG from patients with hydatidiform mole stimulates thyroid gland by interacting with TSH receptors, and suggest that the increase in thyroid hormones in patients may depend on both the increased serum hCG and the responsiveness of their thyroid glands to hCG.

Adult↗
PubMed1999

Characterization of heparin low-affinity phospholipase A1 present in brain and testicular tissue.

We identified a unique phospholipase A (PLA) with relatively low heparin affinity, which was distinguishable from the heparin-binding secretory PLA2s, in rat, mouse, and bovine brains and testes. The partially purified enzyme was Ca2+-independent at neutral pH but Ca2+-dependent at alkaline pH. It predominantly hydrolyzed phosphatidic acid (PA) in the presence of Triton X-100 and phosphatidylethanolamine (PE) in its absence. When rat brain-derived endogenous phospholipids were used as a substrate, the enzyme released saturated fatty acids in marked preference to unsaturated ones. Consistent with this observation, the enzyme hydrolyzed sn-1 ester bonds in the substrates about 2,000 times more efficiently than sn-2 ones, thereby acting like PLA1. The enzyme also exhibited weak but significant sn-1 lysophospholipase activity. On the basis of its limited tissue distribution, substrate head group specificity and immunochemical properties, this enzyme appears to be identical to the recently cloned PA-preferring PLA1.

Animals↗
PubMed1999

Roles of asp126 and asp156 in the enzyme function of sphingomyelinase from Bacillus cereus.

To elucidate the roles of conserved Asp residues of Bacillus cereus sphingomyelinase (SMase) in the kinetic and binding properties of the enzyme toward various substrates and Mg2+, the kinetic data on mutant SMases (D126G and D156G) were compared with those of wild type (WT) enzyme. The stereoselectivity of the enzyme in the hydrolysis of monodispersed short-chain sphingomyelin (SM) analogs and the binding of Mg2+ to the enzyme were not affected by the replacement of Asp126 or Asp156. The pH-dependence curves of kinetic parameters (1/Km and kcat) for D156G-catalyzed hydrolysis of micellar SM mixed with Triton X-100 (1:10) and of micellar 2-hexadecanoylamino-4-nitrophenylphosphocholine (HNP) were similar in shape to those for WT enzyme-catalyzed hydrolysis. On the other hand, the curves for D126G lacked the transition observed for D156G and WT enzymes. Comparison of the values and the shape of pH-dependence curves of kinetic parameters indicated that Asp126 of WT SMase enhances the enzyme's catalytic activity toward both substrates and its binding of HNP but not SM. The deprotonation of Asp126 enhances the substrate binding and slightly suppresses the catalytic activity toward both substrates. Asp156 of WT SMase acts to decrease the binding of both substrates and the catalytic activity to HNP but not SM. From the present study and the predicted three-dimensional structure of B. cereus SMase, Asp126 was thought to be located close to the active site, and its ionization was shown to affect the catalytic activity and substrate binding.

Aspartic Acid↗
PubMed1999

Human papillomavirus vaccines for cervical cancer.

Cervical cancer is one of the most common causes of cancer-related death in women. As a result of several recent advances in molecular biology, the association between human papillomavirus (HPV) infection and cervical cancer has been firmly established, and the oncogenic potential of certain HPV types has been clearly demonstrated. Several lines of evidence suggest the importance of the host's immune response, especially cellular immune response, in the pathogenesis of HPV-associated cervical lesions. These observations form a compelling rationale for the development of vaccine therapy to combat HPV infection. Both prophylactic and therapeutic HPV vaccine strategies are being developed. Prophylactic strategies currently under investigation focus on the induction of effective humoral immune responses against subsequent HPV infection. In this respect, impressive immunoprophylactic effects have been demonstrated in animals using papillomavirus-like particles (VLPs). VLPs are antigenic and protective, but are devoid of any viral DNA that may be carcinogenic to the host. For treatment of existing HPV infection, techniques to improve cellular immunity by enhancing viral antigen recognition are being studied. For this purpose, the oncogenic proteins E6 and E7 of HPV-16 and -18 are the focus of current clinical trials for cervical cancer patients. The development of successful HPV-specific vaccines may offer an attractive alternative to existing screening and treatment programs for cervical cancer.

Animals↗
PubMed1999

Computerized detection of malignant tumors on digital mammograms.

This paper presents a tumor detection system for fully digital mammography. The processing scheme adopted in the proposed system focuses on the solution of two problems. One is how to detect tumors as suspicious regions with a very weak contrast to their background and another is how to extract features which characterize malignant tumors. For the first problem, a unique adaptive filter called the iris filter is proposed. It is very effective in enhancing approximately rounded opacities no matter what their contrasts might be. Clues for differentiation between malignant tumors and other tumors are believed to be mostly in their border areas. This paper proposes typical parameters which reflect boundary characteristics. To confirm the system performance for unknown samples, large scale experiments using 1212 CR images were performed. The results showed that the sensitivity of the proposed system was 90.5% and the average number of false positives per image was found to be only 1.3. These results show the effectiveness of the proposed system.

Algorithms↗
PubMed1999

Clonal emergence in uremic parathyroid hyperplasia is not related to MEN1 gene abnormality.

It is difficult to differentiate between parathyroid neoplasia and hyperplasia. In an attempt to elucidate the clonality of uremic parathyroid hyperplasia and the molecular genetic abnormalities accounting for clonal emergence, we analyzed 20 cases of uremic parathyroid hyperplasia. Clonalities were determined using the X-chromosome-linked human androgen receptor (HUMARA) gene and the phosphoglycerate kinase (PGK) gene, and multiple endocrine neoplasia type 1 (MEN1) gene abnormality was analyzed by studying loss of heterozygosity (LOH) in 11q13 and somatic mutations in the MEN1 gene. As a positive control, a case of MEN1 with Zollinger-Ellison syndrome was analyzed simultaneously. Our analysis revealed that a majority (75%) of the uremic parathyroid hyperplasia tissues, including an autograft with recurrent hyperparathyroidism, was of monoclonal origin. Clonality did not correlate with serum carboxyl-terminal parathyroid hormone (C-PTH) level, calcium level, hemodialytic duration, gland weight or pathological features. Neither LOH in 11q13 nor somatic mutation in the MEN1 gene was detected. For the MEN1 case, a germline mutation (W198X) was detected in exon 3. We concluded that a majority of the uremic parathyroid hyperplasia cases was in fact monoclonal neoplasia. MEN1 gene abnormality played a minor role, if any, in the clonal emergence in uremic parathyroid hyperplasia.

Clone Cells↗
PubMed1999

Lack of synchrony among multiple nuclei induces partial DNA fragmentation in V79 cells polyploidized by demecolcine.

The nuclear morphology of polyploidized cells was examined in V79 Chinese hamster cells polyploidized by demecolcine or K-252a, inhibitors of spindle fibre formation and protein kinases, respectively. A variety of nuclear morphologies, including multinuclei, were observed in V79 cells polyploidized by demecolcine but not by K-252a, which produced mononuclear cells. A lack of synchrony in the nuclear cycle was observed among nuclei in multinuclear polyploidized cells. Partial DNA fragmentation, defined as DNA fragmentation of a nucleus in a multinuclear cell, was detected using the TUNEL method in V79 cells polyploidized by demecolcine but not by K-252a. Apoptosis occurred earlier in cell populations treated with demecolcine than in these treated with K-252a once the drugs were removed from the medium, suggesting that polyploidized cells with separate nuclei tend to apoptose earlier than those with mononuclei.

Animals↗
PubMed1999

In situ localization of S-phase-specific histone (H3) mRNA in Bowen's disease.

PCNA and Ki-67 immunohistochemistry has been used to assess cell proliferation in place of tritiated thymidine or BrdU labeling of S-phase cells. Recently, it has been possible to reliably demonstrate histone H3 mRNA by in situ hybridization in formalin-fixed and paraffin-embedded tissue sections. We have compared this new proliferation marker with Ki-67 and PCNA with regard to distribution of positive cells and labeling indices (LI%) for 22 cases of Bowen's disease. In normal skin, Ki-67-IHC positive cells and histone mRNA positive cells were observed in the basal and suprabasal layers of the epidermis. In Bowen's disease, positive cells with each marker were more frequent in upper neoplastic epidermis than in suprabasal layers, and the average LI%s were markedly elevated with all markers, the scores decreasing in the following order: PCNA-IHC, Ki-67-IHC and H3mRNA-ISH. However, the results of double staining demonstrated that S-phase cells do not necessarily show exactly the same distributions as with PCNA and Ki-67-IHC labeling. H3mRNA-ISH showed three different degrees of reaction with significantly different LI%s, whereas PCNA and Ki-67 LI% did not vary essentially in the same areas. These results strongly suggest that Bowen's disease, which is well known as a low-grade neoplastic state with malignant potential, also demonstrates clear intratumoral heterogeneity of S-phase cells using the H3mRNA-ISH method.

Adult↗
PubMed1999

Arginine vasopressin inhibits fluid secretion in guinea pig pancreatic duct cells.

The effects of arginine vasopressin (AVP) on pancreatic ductal secretion were studied in guinea pigs. In the isolated vascularly perfused pancreas, AVP reduced secretin-stimulated fluid secretion and increased the vascular resistance when the perfusion rate was held constant. In the isolated interlobular duct segments, AVP inhibited secretin-stimulated fluid secretion, indicating the direct inhibitory action of AVP on the duct cells. AVP affected neither the basal nor the secretin-induced cAMP productions, suggesting that AVP inhibits the fluid secretion at a point distal to the production of cAMP. AVP increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in the absence of extracellular Ca(2+). When [Ca(2+)](i) was elevated by the application of thapsigargin, AVP caused a rapid decrease in [Ca(2+)](i). AVP seems to activate both Ca(2+) release from intracellular stores and Ca(2+) efflux across the plasma membrane, but its relation to the inhibition of fluid secretion remains to be clarified. It is concluded that AVP directly inhibits secretin-stimulated ductal fluid secretion in the guinea pig pancreas.

Animals↗
PubMed1999

Topical CTLA4-Ig suppresses ongoing mucosal immune response in presensitized murine model of allergic rhinitis.

Allergic rhinitis is thought to be mediated by CD4+ T cells producing Th2-associated cytokines. Optimal Ag-specific T-cell activation requires the engagement of T-cell receptor with antigen (Ag) in the context of MHC, and the engagement of appropriate costimulatory molecules. One of the most well-characterized costimulatory pathways is the interaction of B7/CD28-CTLA4 molecules. Recent studies have suggested that the costimulatory pathway may influence the development of Th2 immune responses. The objective of this study was the examination of the role of B7/CD28-CTLA4 costimulatory pathway in the pathogenesis of ovalbumin (OVA)-induced immune response in presensitized murine model of allergic rhinitis. Systemically presensitized BALB/c mice significantly developed Ag-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine, nasal eosinophilia, serum levels of OVA- specific IgE and Th2-associated cytokines following repeated topical Ag challenges. Topical administration of CTLA4-Ig during nasal challenges inhibited Ag-induced nasal symptoms and histamine hyperresponsiveness. We also found a significant reduction in nasal lavage eosinophilia and serum levels of OVA-specific IgE. Furthermore, CTLA4-Ig treatment significantly decreased interleukin (IL)-4 content in nasal tissue, while there was no significant change in IL-5 or IFN-gamma levels. These results suggest that B7/CD28-CTLA4 costimulatory pathway mediates the development of ongoing Th2 immune responses and plays a major role in regulating allergic disease, such as allergic rhinitis.

Abatacept↗