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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 451 records · Page 25Linked to original sources

The role of the spleen, platelets, and plasma hepatocyte growth factor activity on hepatic regeneration in rats.

BACKGROUND: Hepatocyte growth factor (HGF) is a humoral factor that may act as a trigger for hepatic regeneration. In this study, changes in the plasma HGF activity on hepatic regeneration in a splenectomized condition were measured for the first time, while the role of the spleen and platelets on hepatic regeneration were also carefully evaluated. STUDY DESIGN: Seventy-five male Wistar rats were classified into three groups: group A consisted of rats who underwent a sham operation and a partial hepatectomy; group B consisted of those who underwent a splenectomy and partial hepatectomy; and group C consisted of those who underwent a splenectomy, partial hepatectomy, and were administered an antiplatelet agent. RESULTS: At 24 hours after partial hepatectomy, the weights of the livers of the rats in groups B and C were significantly greater than those of group A, while the labeling index of group C was significantly higher than that of group A and also tended to be higher than that of group B. Regarding the number of platelets, the transient increase in group A occurred earlier than that of either group B or C. The plasma HGF activities also showed a transient increase and the maximum levels were reached at 24 hours in group A, six hours in group B, and 12 hours in group C. CONCLUSIONS: It is suggested that the spleen plays an inhibitory role in hepatic regeneration. In the early stage of hepatic regeneration, platelets possibly control HGF induction, while in the following stage, a possible feedback mechanism is also postulated to exist.

Animals↗

Detection of specific genetic alterations in cancer cells.

The genetic changes found in human neoplasms suggest that hematopoietic tumors develop mainly from inappropriate expression (usually overexpression) of a growth promoting gene (oncogene). In contrast, the progression to malignancy of carcinomas occurs mainly through loss of tumor suppressor genes. Gene therapy might be used to turn off an activated oncogene, eg, by antisense treatment, whereas gene therapy to overcome tumor suppressor gene loss necessarily would focus on gene replacement in the tumor cell or pharmacologically substituting for lost gene function. On the other hand, the protein products of mutations that activate oncogenes or that inactivate tumor suppressor genes are both potential tumor antigens. Increasingly, characterization of the molecular changes that contribute to the malignant phenotype provides information impacting on tumor diagnosis and patient prognosis.

Base Sequence↗

Loss of ganciclovir sensitivity by exclusion of thymidine kinase gene from transplanted proinsulin-producing fibroblasts as a gene therapy model for diabetes.

To establish a practical method of somatic gene therapy, we aimed to develop a regulatory system at the cellular level using a suicide vector. We introduced the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene into the human proinsulin-producing Ltk-cells and examined whether ganciclovir (GCV) administration could control proinsulin production in vivo. The cells transfected with the HSV-tk gene showed more than 100-fold increase in sensitivity to GCV compared with the parent cells. Analysis of blood glucose in diabetic nude mice with transplanted cells showed that proinsulin production by these cells was strongly suppressed by GCV treatment in vivo as reflected by the reversal to hyperglycemia. However, in the in vivo experiment, the plasmid containing the HSV-tk gene was spontaneously lost from the transplanted cells in one of six cases resulting in the resistance to GCV as reflected by the persistent hypoglycemia and increased tumor size. This system of HSV-tk and administration of GCV may be applicable to gene therapy as a suicide vector, but the system of stable expression of the HSV-tk gene must be established.

Animals↗

Interleukin-8 activity correlates with histological severity in Helicobacter pylori-associated antral gastritis.

OBJECTIVES: To examine the background histology, interleukin-8 (IL-8) secretion, and expression of IL-8 mRNA and protein, using the gastric antral mucosa infected with Helicobacter pylori. METHODS: The antral biopsies were obtained from an area of endoscopically intact mucosa in 147 patients whose endoscopic diagnoses were normal (n = 41), duodenal ulcer (n = 58), gastric ulcer (n = 21), or gastritis (n = 27). Levels of IL-8 secreted in the organ cultures of mucosal biopsies were measured by an ELISA assay, and the expression of IL-8 mRNA and protein was analyzed in fresh biopsy tissues with RT-PCR and immunofluorescent microscopy, respectively. RESULTS: Significantly greater levels of IL-8 were secreted in patients with H. pylori infection, and its elevation was more prominent in duodenal ulcer patients than in those with gastric ulcer or endoscopically defined gastritis. There was an association among H. pylori density, IL-8 activity, and histological severity of activity and inflammation of gastritis in the Sydney system. Consistent with enhanced IL-8 activity in the organ cultures, IL-8 mRNA was detected in 16 of 23 fresh biopsy tissues studied in H. pylori-positive patients. In contrast, IL-8 transcript was detected in only one of 12 H. pylori-negative cases. Immunofluorescent microscopy showed localization of IL-8 protein in the gastric epithelial cells and lamina propria cells, primarily CD68+ macrophages in specimens with H. pylori infection. CONCLUSIONS: This study indicates that a strong correlation exists between mucosal IL-8 activity and histological severity in H. pylori-associated antral gastritis. Further studies will be necessary to determine the mechanisms involved in elevated mucosal IL-8 activity in H. pylori infection.

Adult↗

Laparoscopic splenectomy for idiopathic thrombocytopenic purpura: comparison of laparoscopic surgery and conventional open surgery.

In chronic idiopathic thrombocytopenic purpura (ITP), the two main therapeutic choices are steroid treatment or splenectomy. The adult form of ITP is described as a disease found primarily in young adults, with a female predominance. Treatment with steroids effects a complete response in less than 30% of patients, whereas splenectomy is successful in more than 60% of patients who undergo it. The minimal access afforded by laparoscopic splenectomy is considered highly desirable for these patients. The purpose of this study was to compare the clinical benefits of a laparoscopic splenectomy with those of conventional open surgery for patients with ITP. From 1968 to 1993, splenectomy was performed on 51 patients: 10 operations done laparoscopically and 41 performed conventionally. Complications, postoperative pain, recovery, and hospital charges were then compared. Laparoscopic splenectomy involved minimal incisions, and a significantly lower frequency of analgesia was required for postoperative abdominal pain (1.3 vs. 3.3); hospital stay was shorter (8.2 vs. 20.1 days) (p < 0.005). Operative time was significantly longer for the laparoscopic surgery (249.2 vs. 99.8 min) (p < 0.0001), but blood loss was less (176.0 vs. 511.7 g) (p < 0.01). No intraoperative or postoperative major complications occurred with the laparoscopic procedures, compared with 46.3% with conventional surgery. Finally, the total hospital costs were lower with laparoscopic splenectomy, especially for postoperative care (p < 0.05). A laparoscopic splenectomy may well be considered the surgical treatment of choice for patients requiring a splenectomy in view of both quality of life and economy.

Adult↗

TCV-116 inhibits renal interstitial and glomerular injury in glomerulosclerotic rats.

TCV-116 and enalapril were given in two stages: (early phase) for 6 to 10 weeks to 5/6 nephrectomized (NX) rats two weeks after nephrectomy, 12-week-old Wistar fatty (WF) rats and 7-week-old spontaneously hypercholesterolemic (SHC) rats; and (late phase) for 6 to 16 weeks to 5/6 NX rats 11 weeks after nephrectomy, 27-week-old WF rats and 10-week-old SHC rats. Urinary albumin, blood pressure (BP), glomerular filtration rate (GFR) and renal histology were examined. In the early phase, both agents inhibited proteinuria and tended to inhibit glomerulosclerosis. TCV-116 also inhibited interstitial inflammation. The antiproteinuric effects did not necessarily correlate with the BP-lowering effects. In the late phase, both agents showed equal antiproteinuric and antihypertensive effects. In 5/6NX and WF rats, TCV-116 inhibited tubulointerstitial inflammation/fibrosis, glomerulosclerosis and renal dysfunction, but enalapril had little effect on these parameters. In the SHC rats, TCV-116 inhibited renal tubulointerstitial inflammation and glomerulosclerosis, but enalapril inhibited only glomerulosclerosis. After drug administration, there was a positive correlation between proteinuria and BP, and a negative correlation between the severity of tissue damage and GFR, but not BP. These findings suggest that initial BP-independent tubulointerstitial inflammation may enhance glomerulosclerosis in the late phase, and TCV-116 might prevent the development of glomerulosclerosis through inhibition of angiotensin II-mediated tubulointerstitial damage in these models.

Angiotensin-Converting Enzyme Inhibitors↗

A highly repetitive sequence isolated from genomic DNA of the medaka (Oryzias latipes).

A highly repetitive interspersed DNA sequence (MRE) was isolated from the genome of medaka, Oryzias latipes, and characterized. Three distinct sequences of MRE were cloned and compared. The conserved sequences of MRE were approximately 220 bp in length. On average, one copy of MRE was present in every 153 kb, and the number of copies of MRE in the genome was calculated to be approximately 9800. MRE constituted approximately 0.14% of the genome. MRE-related sequences were not detected in carp (Cyprinus carpio) red-spot masu trout (Oncorhynchus masou macrostomus), masu salmon (Oncorhynchus masou masou), rainbow trout (Oncorhynchus mykiss), eel (Anguilla japonica), Arctic lamprey (Lampetera japonica), or yellowtail (Seriola quinqueradiata). MRE was randomly distributed in the medaka genome, indicating a high incidence of polymorphism in the five medaka inbred lines.

Animals↗

[Prediction and the results of postoperative performance status in patients with giant bulla--prospective study of 47 patients].

The discriminant function (Z) for predicting postoperative performance status in patients with giant bulla was addressed in our previous paper. In the present study, patients with dyspnea were classified into Group 1 or Group 2 based on preoperative function, Group 1 showing continuous improvement in dyspnea and Group 2 unchanged or worsened condition after bullectomy. Of the 47 patients in this study, 28 had dyspnea of grade 2 or more, 19 revealing no symptoms prebullectomy. The group predictions for the 28 patients were compared with the postoperative status in dyspnea for over four years following surgery. The predicted grouping in 26 of the 28 (93%) agreed with the postoperative status but in two it did not: one was familial bullous emphysema the other had repeated episodes of pneumonia, both of which were predicted for Group 1. All 19 patients without preoperative dyspnea were studied their symptoms and lung functions before and after bullectomy. After surgery, none showed dyspnea and significant changes of functions. As to preoperative pulmonary function, patients with FEV1.0% of more than 60% and delta N2 of less than 2% were improved, the prediction agreeing with the actual results. Fourteen patients with FEV1.0% of less than 55% showed high delta N2. When delta N2 exceeded 3.5%, deterioration of dyspnea was observed following surgery. Bullectomy is indicated in patients with low pulmonary function, by preoperative FEV1.0% and delta N2.

Adult↗

[Thoracoscopic enucleation for sclerosing hemangioma of the lung--a case report].

A 30-year-old female with sclerosing hemangioma of the lung (SHL) was managed by thoracoscopic enucleation. Under the left lateral decubitus position, four small skin incisions were made. The tumor, approximately 2.5 cm in diameter, was just under the pleura at the right S5, and was clearly demarcated without adhesions to mediastinal pleura. Because the tumor located near the hilum, a partial resection by intrathoracic Endo-GIA could not be performed. So the tumor was enucleated bluntly with an electrode knife being tugged by a tractive thread. After it was diagnosed as SHL by intraoperative imprint cytology, the stump was closed with running suture of 3-0 nylon. The patient was discharged on the 10th postoperative day without complication. No recurrence was found during a follow-up period of six months after the operation. Immunohistochemical findings suggested that the tumor cells were derived from type II pneumocytes. Thoracoscopic surgery appears to be a good indication for SHL which commonly occurs in young or middle-aged women and which is difficult to be diagnosed preoperatively. Thoracoscopic enucleation is considered to be a one of the safe methods especially for SHL which can not be resected by Endo-GIA.

Adult↗

Radioimmunoprecipitation assay for glutamic acid decarboxylase antibodies evaluated clinically with sera from patients with insulin-dependent diabetes mellitus.

We evaluated a new, commercially developed radioimmunoprecipitation assay for measuring glutamic acid decarboxylase (GAD) antibodies by using recombinant human GAD65. The intra- and interassay CVs were 8.0% (n = 20) and 8.6% (n = 15), respectively. We found GAD antibodies in 74% (23 of 31; 95% confidence interval 55-88%), 70% (14 of 20; 46-88%), and 65% (28 of 43; 49-79%) of patients at, respectively, < or = 1 year, 1-2 years, and 2-4 years after the onset of insulin-dependent diabetes mellitus (IDDM) and in 30% (30 of 99; 21-40%) of patients with long-term diabetes (4-22 years). We also detected GAD antibodies in 8% (9 of 106; 4-16%) of patients with non-insulin-dependent diabetes mellitus (NIDDM). The frequency of GAD antibodies in the NIDDM group was markedly higher in the insulin-deficient patients [67% (6 of 9; 30-93%)], who initially were nonketotic and non-insulin-dependent for > or = 6 months but later became insulin dependent, than in the non-insulin-deficient patients [3% (3 of 97; 1-9%)]. This new commercial assay is easy to use and provides a specific and sensitive method for evaluating GAD antibodies in IDDM.

Adolescent↗

Human T lymphotropic virus type I (HTLV-I)-specific T helper cell responses from HTLV-I seronegative patients with chronic myelopathy and MS in Japan.

Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to Adult T cell leukemia (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although most HAM/TSP patients have high anti-HTLV-I antibody titers in their sera, HTLV-I infected but seronegative patients with neurological diseases have been reported. To clarify whether seronegative, HTLV-I related neurological disease may exist, we have developed a method that measures the production of interleukin-2 (IL-2) from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I infected persons. This method is sensitive enough to detect exposure to HTLV-I before seroconversion or even before detection by PCR. We examined 12 patients with chronic progressive myelopathy and eight patients with multiple sclerosis (MS) in central Japan, where the prevalence rate of HTLV-I is between one and four percent among asymptomatic blood donors, using the IL-2 production assay. None of them were positive by the assay, suggesting seronegative HTLV-I myelopathy is very rare among patients with chronic progressive myelopathy and MS in Japan.

Adult↗

Loss of heterozygosity at the familial RCC t(3;8) locus in most clear cell renal carcinomas.

Previously, we had observed that more than 80% of clear cell renal carcinomas (RCCs) exhibited loss of heterozygosity (LOH) between the microsatellite markers D3S1285 (in 3p14.1) and D3S1295 (in 3p21.1), a region which includes the protein tyrosine phosphatase gamma locus (PTPRG locus, PTP gamma gene) and the 3p14.2 break of the familial RCC-associated translocation, t(3;8)(p14.2;q24), which has been hypothesized to affect expression of an RCC suppressor gene or oncogene. Using seven microsatellite markers and four markers derived from a PTPRG YAC contig, we have further delineated the 3p14.2 region of LOH in RCCs. Eighty-nine % of clear cell RCCs (31 of 35) showed a common region of loss between the D3S1481 and D3S1312 loci which flank the 3p14.2 t(3;8) translocation breakpoint and the PTP gamma gene. The PTP gamma gene occupies approximately 780 kilobase pairs between markers D3S1480 and D3S1312, with its currently defined 5' end greater than 200 kilobase pairs centromeric to the 3p14.2 translocation break. Although most of the RCCs with LOH between D3S1481 and D3S1312 loci have lost at least a portion of one PTP gamma allele, we have tested all known exons of the remaining PTP gamma gene in a number of the kidney tumors and have not observed mutations. Thus, there may be another gene in the vicinity of the 3p14.2 break that is important not only in the familial RCCs in the t(3;8) family but in the majority of clear cell RCCs.

Adenocarcinoma, Clear Cell↗