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Biomedical subjects

M Kodama

Publications and source records attributed to M Kodama.

At least 73 records · Page 4Linked to original sources
PubMed2000

Localization of biologically uncommon D-beta-aspartate-containing alphaA-crystallin in human eye lens.

PURPOSE: Previous studies demonstrated that the Asp-151 residue of alphaA-crystallin from human eye lens is stereoinverted to the biologically uncommon D-isomer and isomerized to the beta-aspartyl residue (isoaspartate) with age. To detect the locality of the D-beta-Asp-containing peptide in aged human lens, we prepared a highly specific antibody against peptide Gly-Leu-D-beta-Asp-Ala-Thr which corresponds to positions 149-153 of human alphaA-crystallin using peptide Gly-Leu-D-beta-Asp-Ala-Thr-Gly-Leu-D-beta-Asp-Ala-Thr-Gly-Leu-D-beta- Asp-Ala-Thr (designated peptide 3R) as an immunogen. METHODS: Peptide 3R was synthesized with F-moc (9-fluorenylmethoxycarbonyl) solid phase chemistry and then the peptide was immunized in rabbits to generate antibody against peptide 3R. The antibody in rabbit serum was purified by affinity chromatography using peptide 3R and bovine alphaA-crystallin as ligands. The specificity and titer of antibody were checked by ELISA assay. We synthesized four kinds of peptide T18 (IQTGLDATHAER; corresponding to the amino acid sequences 146-157 in human alphaA-crystallin) in which Asp-151 residues were normal L-alpha-Asp, abnormal D-alpha-Asp, L-beta-Asp, and D-beta-Asp, respectively. The specificity of antibody was confirmed by ELISA using these peptides and utilized in immunohistochemistry. RESULTS: The antibody we prepared crossreacted specifically to D-beta-Asp-151-containing alphaA-crystallin. Immunohistochemical staining of human lens with the antibody demonstrated that D-beta-Asp-151-containing alphaA-crystallin was predominantly localized in the core of aged human lens. CONCLUSIONS: The peptide 3R antibody clearly recognized the presence of racemized and isomerized Asp-151 in both protein solution and lens tissue obtained from aged human lens.

Aged↗
PubMed2000

Expression of coxsackievirus and adenovirus receptor in hearts of rats with experimental autoimmune myocarditis.

The expression of coxsackievirus and adenovirus receptor (CAR) was dominant in the brains and hearts of mice until the newborn phase. There is no detailed information concerning the relation between the expression of CAR and development of hearts. It is also uncertain whether CAR is able to be induced in adult hearts after cardiac injury. We demonstrated that CAR was abundant in the hearts of newborn rats but was barely detectable in the hearts of adult rats. The expression of CAR in rat hearts with experimental autoimmune myocarditis, which was induced by immunization of purified cardiac myosin, was serially investigated. Active myocarditis was observed from day 15 after immunization. By immunohistochemistry, cardiomyocytes were strongly stained for CAR antibody from days 24 to 42. CAR mRNA was also detected from days 18 to 30 by using reverse transcription-polymerase chain reaction. In the next experiment, the induction of CAR on isolated cardiomyocytes was investigated. CAR was barely detectable in cultured cardiomyocytes by Western blot analysis after isolation. This molecule gradually appeared along with the creation of clusters and beating of cardiomyocytes. Furthermore, the induction of CAR in cultured cardiomyocytes increased after supplement with conditioned medium of rat splenocytes activated by concanavalin A. In conclusion, rat CAR is expressed strongly in the hearts of newborn rats and is suppressed in those of adult rats. The expression of CAR is enhanced during the active phase of experimental autoimmune myocarditis and is induced by inflammatory mediators. CAR may play a role in cell-to-cell contact and adhesion of cardiomyocytes.

Aging↗
PubMed2000

Antiplatelet drugs attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes.

The intima-media thickness of the carotid artery has been established as a surrogate of definite atherosclerosis in subjects with high risk of vascular events. This study was done to evaluate the effectiveness of long-term antiplatelet therapy in attenuating progression of the intima-media thickness of the carotid artery of subjects with type 2 diabetes. Subjects who had an intima-media thickness over the threshold of the normal subjects but showed no symptoms of vascular events were randomly divided into groups given antiplatelet drugs [ticlopidine (n = 34) or a small dose of aspirin (n = 40)] or no drugs (n = 74). For the follow-up period (3.0+/-0.06 years), the subjects not given antiplatelet drugs showed a significantly higher progression of intima-media thickness (0.067+/-0.009 mm/year) than those given ticlopidine (0.034+/-0.013 mm/year) or aspirin (0.033+/-0.010 mm/year). Stepwise multivariant regression analysis showed that long-term administration of ticlopidine or aspirin significantly reduced the progression of intima-media thickness of diabetic subjects by 0.041 mm/year or 0.032 mm/ year, respectively. These data indicated that despite differences of their pharmacological mechanisms, antiplatelet drugs could attenuate the progression of intima-media thickness of the carotid artery wall of asymptomatic type 2 diabetics who had early-stage carotid atherosclerosis.

Aged↗
PubMed2000

Protease inhibitor reduces loss of tensile strength in rat anastomosis with peritonitis.

BACKGROUND: The tensile strength in intestinal anastomoses decreases postoperatively in association with degradation of the extracellular matrix, and these changes would be expected to be more intense in the presence of peritonitis. MATERIALS AND METHODS: In this study, we investigated extracellular matrix degradation and tensile strength in a rat model of intestinal anastomosis with peritonitis. In the chemical peritonitis model, peritonitis was induced 24 h earlier with intraperitoneal HCl. A serine protease inhibitor, nafamostat mesilate (NM), was given intraperitoneally to some animals every 12 h from immediately after the operation for 3 days. Immunostaining was performed by the standard streptavidin-biotin-peroxidase method after fibronectin (Fn) and factor XIII antigen retrieval on paraformaldehyde-fixed, paraffin-embedded tissue sections. RESULTS: In comparison with controls, administration of NM reduced the loss of tensile strength on Day 3 in a dose-dependent manner, and high-dose NM (20/mg/kg) significantly prevented the loss of tensile strength on Day 3 (P < 0. 05). In the control group, degradation of the collagen layer in the anastomosis was associated with disappearance of Fn and factor XIII staining on Day 3. The administration of NM attenuated these changes with intense immunostaining for Fn and factor XIII seen particularly between collagen fibers on both sides of the anastomosis on Day 3. In the chemical peritonitis model, administration of NM also significantly prevented the loss of tensile strength on Day 3 without disappearance of collagen fibers. CONCLUSION: These findings suggest that NM may be clinically useful for preventing intestinal leakage, particularly when anastomoses are performed under protease-activating conditions, such as intestinal edema and inflammation.

Anastomosis, Surgical↗
PubMed2000

Cellular distribution and clinical value of urokinase-type plasminogen activator, its receptor, and plasminogen activator inhibitor-2 in esophageal squamous cell carcinoma.

To assess the participation of the plasminogen activation system in the invasiveness of esophageal squamous cell carcinoma, we performed immunohistochemistry and in situ hybridization to study the distribution of a urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR), and plasminogen activator inhibitor-2 (PAI-2). u-PA and PAI-2 were expressed heterogeneously in cancer cells, and restricted expression was found in stromal cells, especially fibroblasts, that were located in the immediate proximity of the cancerous cells. u-PAR was found only in cancer cells located at the periphery of tumors. Compared with patients with u-PA-negative cancer cells, patients with u-PA-positive cancer cells more frequently showed a neoplastic invasion beyond the muscularis propria and lymph node metastases. They also showed a significantly shorter 5-year overall survival. Patients with PAI-2-positive fibroblasts showed significantly lower levels of local invasiveness, represented by a neoplastic invasion beyond the muscularis propria, than those who were PAI-2 negative. Our results suggest that the expression of u-PA in esophageal squamous cell carcinoma is predictive of poor survival, whereas the expression of PAI-2 in the fibroblasts surrounding them is protective. An analysis of u-PA and PAI-2 expression in cancer cells and their surrounding fibroblasts may be useful for predicting the prognosis of patients with esophageal squamous cell carcinoma.

Adult↗
PubMed2000

The in vitro differentiating capacity of nonparenchymal epithelial cells derived from adult porcine livers.

Specific nonparenchymal epithelial cell (NPEC) clusters derived from normal adult porcine livers demonstrate a characteristic developmental pattern in the presence of other types of nonparenchymal cells in vitro. This pattern includes scattering, colonial growth, and an emergence of duct-like structures (DLSs) in the colonies. It has been confirmed that 96% of the scattered cell clusters in these cultures develop into colonies containing DLSs. In this study, we examine the differentiation of NPEC clusters using the scattered formation as a marker of the DLS-emerged colonies. We report that the NPECs expressed albumin, alpha-fetoprotein, transferrin, cytokeratin (CK) 18, CK7, and c-met, but not alpha-1-antitrypsin (AAT), at the scattering stage. In addition, at the same stage, NPECs expressed oval-cell-related markers such as OV6, but not biliary epithelial cell (BEC) markers such as gamma-glutamyltransferase, CK19, and CK14. At the DLS emerging stage, hepatocyte markers, including AAT, were detectable in the cells either at the periphery of colonies or in the cells surrounded by the DLSs. On the other hand, the cells constituting DLSs expressed BEC markers, suggesting a bile duct nature of the DLSs. Furthermore, the cells in the colonies possessed an ultrastructural appearance of differentiated hepatocytes and BECs. These results suggest that certain NPECs are bipotent, and that, in culture, they mimic hepatoblast development in vivo.

Animals↗
PubMed2000

Frequent occurrence of paralytic shellfish poisoning toxins as dominant toxins in marine puffer from tropical water.

Considerably high toxicity was detected in marine puffers collected from Masinloc Bay, Philippines. The toxicity was detected in the liver, intestine, muscle and skin. Noteworthy, the specimens, the muscle of which showed high toxicity, appeared in high frequency, indicating that puffers from this area is not safe for human consumption. These puffer specimens contained paralytic shellfish poisoning (PSP) toxins, often as major toxin components, the profile of which was similar to that of freshwater puffers reported from tropical areas. These results indicate that PSP toxins are common in tropical puffers both from marine and freshwater.

Animals↗
PubMed2000

Low dose carvedilol inhibits progression of heart failure in rats with dilated cardiomyopathy.

The cardioprotective properties of carvedilol (a vasodilating beta-adrenoceptor blocking agent) were studied in a rat model of dilated cardiomyopathy induced by autoimmune myocarditis. Twenty-eight days after immunization, surviving Lewis rats (32/43=74%) were divided into three groups to be given 2 mg kg(-1) day(-1) (Group-C2, n=10) or 20 mg kg(-1) day(-1) (Group-C20, n=10) of carvedilol, or vehicle (0.5% methylcellulose, Group-V, n=12). After oral administration for 2 months, body weight, heart weight (HW), heart rate (HR), rat alpha-atrial natriuretic peptide (r-ANP) in blood, central venous pressure (CVP), mean blood pressure (mean BP), peak left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP), +/-dP dt(-1) and area of myocardial fibrosis were measured. Values were compared with those for normal Lewis rats (Group-N, n=10). Two out of 12 (17%) rats in Group-V died from day 28 to day 42 after immunization. No rat died in Groups-C2, -C20 and -N. Although the CVP, mean BP, LVP and +/-dP dt(-1) did not differ among the three groups, the HW, HR and r-ANP in Group-C2 (1.14+/-0.03, 339+/-16 and 135+/-31) and Group-C20 (1.23+/-0.04, 305+/-8 and 156+/-24) were significantly lower than those in Group-V (1.36+/-0.04 g, 389+/-9 beats min(-1) and 375+/-31 pg ml(-1), respectively). The LVEDP in Group-C2 was significantly lower than that in Group-V (7.4+/-1.4 and 12.2+/-1.2 mmHg, respectively, P<0. 05). The area of myocardial fibrosis in Group-C2 was smaller than that in Group-V (12+/-1 and 31+/-2%, P<0.01). These results indicate that a low dose of carvedilol has beneficial effects on dilated cardiomyopathy.

Animals↗
PubMed2000

Effect of argatroban on trinitrobenzene sulfonic acid-induced colitis.

BACKGROUND: Recent studies have suggested that heparin is effective for treatment of inflammatory bowel disease (IBD) and its various effects (in addition to the anticoagulant effect). We evaluated the effects of argatroban as an antithrombin drug on trinitrobenzene sulfonic acid (TNB)-induced colitis, an established model of IBD. METHODS: Rats were randomly assigned to four groups in which mini-osmotic pumps containing saline (TNB-S), argatroban (TNB-A), or 100 U/kg heparin (TNB-H) were intraperitoneally implanted. Three days after the pumps were implanted, TNB was infused via the anus, and colitis was induced. After 5 days, prothrombin time (PT), activated partial prothrombin time (APTT), antithrombin III (AT-III), platelet, fibrinogen, colonic wet weight, macroscopic damage score, histological score, mucosal myeloperoxidase activity and mucosal leukotrien B4 (LTB4) levels were compared among the four groups. RESULTS: The APTT was prolonged in the heparin treatment group but only slightly prolonged in the argatroban treatment group. The platelet count and the fibrinogen level were higher in the TNB-S group than in the healthy control group and the AT-III level was slightly lower in the TNB-S group than in the healthy control group and lower still in the TNB-H group. CONCLUSIONS: The colonic wet weight was similar among the four groups while the macroscopic damage score, histological score, mucosal myeloperoxidase activity and the mucosal LTB4 level were significantly decreased in the TNB-A and TNB-H groups. Argatroban, as well as heparin may be effective for treatment of TNB-induced colitis.

Analysis of Variance↗
PubMed2000

Continuous recordings of skin conductance change during sleep.

Using a new compact and stable device, skin conductance change (SCC) was measured in five female undergraduates during sleep. The SCC trends and waveforms were almost identical to those of simultaneously recorded skin potential activity (SPA). A gradual increase in sympathetic sweating during sleep was also observed using SCC. However, the confounding effects of a burst of positive skin potential responses usually seen in SPA were absent using SCC.

Adult↗
PubMed2000

Influence of 5-hydroxytryptamine and the effect of a new serotonin receptor antagonist (sarpogrelate) on detrusor smooth muscle of streptozotocin-induced diabetes mellitus in the rat.

BACKGROUND: We evaluated the changes in the response of detrusor muscle to 5-hydroxytryptamine (5-HT; serotonin) and its receptor mechanisms in pathologic bladder of diabetes mellitus rats. METHODS: Eight-week-old male Wistar rats were given an intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in order to induce diabetes mellitus (4 weeks' duration). The bladder strips (10 x 2 mm) were subjected to a tension of 1.0 g in organ baths for the measurements of isotonic contractile responses to 5-HT or relaxation responses to 5-HT antagonists. RESULTS: Bladder strips from STZ-diabetic rats responded to 5-HT with greater contractions than did those of control rats, given vehicle alone. However, bladder strip weights gradually increased in the STZ-diabetic rats as compared with control rats and when the contractile response to 5-HT was expressed as a percentage of the response to 10(-1) mol/L KCl there was no statistically significant difference between the groups. In both control and diabetic rats, the 5-HT3 selective antagonist did not markedly inhibit the contractile response to 5-HT. In contrast, the 5-HT2A selective antagonist inhibited the contractile response to 5-HT in a dose-dependent manner. CONCLUSIONS: These results suggest that the increased contractile response to 5-HT in diabetic rats' bladder is related to smooth muscle hypertrophy and/or hyperplasia and indicate that this effect is mediated by activation of 5-HT2A receptors.

Animals↗
PubMed2000

Cytoreductive surgery with liver-involved renal cell carcinoma.

The purpose of this study was to demonstrate the benefits of cytoreductive surgery for renal cell carcinomas that also involve the liver. Between 1994 and 1997, four patients with renal cell carcinoma with liver involvement were surgically treated with nephrectomy and hepatectomy. Two of them underwent a simultaneous hepatectomy and nephrectomy (group 1), and the remaining two patients underwent a hepatectomy after a nephrectomy and had a diagnosis of postoperative recurrence (group 2). Two patients, one from each group, died of multiple bone metastasis and lung metastasis 30 months and 12 months after the hepatectomy; the second patient from group 1 died 40 months after the first operation due to gastrointestinal hemorrhaging. The second patient from group 2 displayed no evidence of recurrence 18 months after the second surgical procedure. The survival rates for these patients were 66% and 33% at 1 and 3 years, respectively. Autopsy studies revealed that one patient from group 2 had a local recurrence in the liver while the other two patients from group 1 did not. Our results suggested that a progressive approach may therefore be useful for patients demonstrating renal cell carcinoma where there is liver involvement.

Carcinoma, Renal Cell↗
PubMed2000

Gastric mucosal damage caused by monochloramine in the rat and protective effect of taurine: endoscopic observation through gastric fistula.

BACKGROUND AND STUDY AIMS: The mechanism of Helicobacter pylori-induced gastric mucosal injury is unknown, but H. pylori infection is conducive to accumulation in the stomach of monochloramine, a cytotoxic substance. The present study involved morphological investigation of the damaging effects of monochloramine on rat gastric mucosa, using endoscopic observations through a gastric fistula. The study also examined the protective effect of taurine against monochloramine-induced gastric mucosal lesions in rats. MATERIALS AND METHODS: The effects of monochloramine in rats were studied by administering the substance via a gastrostomy, which was then used to conduct a series of endoscopic observations. Local blood flow was measured using a laser Doppler method. Histological examination was carried out after 24 hours. Various monochloramine concentrations were used, and some animals were pretreated with taurine, a monochloramine scavenger, via the gastrostomy. RESULTS: Endoscopically, monochloramine was found to produce hemorrhagic mucosal erosions, mainly in the gastric body, in a time-dependent and concentration-dependent manner. Blood flow was decreased in advance of mucosal erosion. Taurine prevented mucosal injury by 30 mM monochloramine, the highest concentration tested. CONCLUSIONS: Although only the first 24 hours of mucosal injury were observed in the present study, the most likely mechanisms by which monochloramine caused injury to the gastric mucosa appeared to be both oxidative damage and a reduction in blood flow, impairing the mucosal defense mechanism.

Analysis of Variance↗
PubMed2000

Deletion of NKX2.1 gene encoding thyroid transcription factor-1 in two siblings with hypothyroidism and respiratory failure.

Thyroid transcription factor-1 encoded by the NKX2.1 gene is a candidate regulator of thyroid and lung morphogenesis and function in humans. We report 2 female siblings with congenital thyroid dysfunction and recurrent acute respiratory distress carrying a heterozygous deletion of chromosome 14q12-13.3, resulting in haploinsufficiency for the NKX2.1 gene. This observation further supports a physiologic role for thyroid transcription factor-1 in early human thyroid and pulmonary function.

Chromosomes, Human, Pair 14↗
PubMed2000

Temporal changes in expression of neuronal nitric oxide synthase mRNA in the rat hippocampus associated with kainate-induced seizures.

We studied the temporal changes in expression of neuronal nitric oxide (NO) synthase (nNOS) mRNA in the hippocampus of rats treated with kainic acid by use of in situ hybridization technique. Intraperitoneal injection of 10 mg kg-1 kainic acid decreased expression of nNOS mRNAs in the dentate gyrus and CA3 region of the hippocampus at 3 h and 8 h and increased it in the dentate gyrus and CA1 at one week after treatment. Although our previous study indicated that administration of kainic acid increased NO generation in the rat hippocampus, present results suggest that the injection of kainic acid results in differential regulation of nNOS mRNA and NO formation in the rat hippocampus.

Animals↗