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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 703 records · Page 39Linked to original sources

Mapping of the human gene for inducible heme oxygenase to chromosome 22q12.

Heme oxygenase is an essential enzyme in heme catabolism that cleaves heme to form biliverdin, releasing carbon monoxide and iron. There are two isozymes of heme oxygenase: heme oxygenase 1 (HO-1) and heme oxygenase 2, each of which is encoded by a separate gene. It is noteworthy that HO-1 is inducible by various environmental factors, while heme oxygenase 2 is not. Here we have localized the human HO-1 gene to chromosome 22 by polymerase chain reaction (PCR) analysis of human-hamster somatic cell hybrids. The precise region of the HO-1 locus was then determined by fluorescence in situ hybridization, revealing that the human HO-1 gene is localized to 22q12.

Animals↗

[13-week oral toxicity study of lactitol (NS-4) in dogs followed by 4-week recovery test].

UNLABELLED: 13-week repeated dose toxicity studies were conducted on lactitol, a hepatic encephalopathy drug. In the experiment I, male and female dogs were orally treated with lactitol at doses of 0, 1.0, 2.5 and 6.25 g/kg/day for 13 weeks, followed by 4 weeks recovery period. In the experiment II, male and female dogs were orally treated with lactitol at doses of 0, 0.25, 0.50 and 1.0 g/kg/day for 13 weeks in order to require the no-toxic dose. RESULTS: 1. Soft stool and diarrhea were observed at the 0.50 g/kg group and above, and vomiting was observed at the 1.0 g/kg group and above. Increased water consumption was observed at the 6.25 g/kg group. No deaths occurred at all groups. 2. In urinalysis, increased urine volume was observed at the 6.25 g/kg group. 3. Blood chemistry showed decreased BUN at the 6.25 g/kg group. 4. There were no drug-related changes in body weight, food consumption, ophthalmological examination, electrocardiography, hematology and pathology. 5. At the end of the recovery period, all these changes observed at the end of the administration period were disappeared. Based on these results, it was considered that the no-toxic dose of lactitol is 0.25 g/kg/day.

Administration, Oral↗

Activating mutations of the c-kit proto-oncogene in a human mast cell leukemia cell line.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play a crucial role in mast cell growth and differentiation. In a human mast cell leukemia cell line (HMC-1), KitR was found to be constitutively phosphorylated on tyrosine, activated and associated with phosphatidylinositol 3-kinase (P13K) in the absence of autocrine production of SCF. Sequencing of c-kit cDNA revealed that c-kit genes of HMC-1 cells were composed of a normal, wild-type allele and a mutant allele with two point mutations in codon 560 and codon 816, resulting in intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp, respectively. Murine c-kit mutants encoding Gly-559 and/or Val-814, corresponding to human Gly-560 and/or Val-816, were constructed by site-directed mutagenesis and expressed in cells of a human embryonic kidney cell line (293T). In the transfected cells, KitR (Gly-559 + Val-814) and KitR (Val-814) were strikingly phosphorylated on tyrosine and activated in the absence of SCF, whereas tyrosine phosphorylation and activation of KitR (Gly-559) or wild-type KitR was modest or little, respectively. These results suggest that constitutive activation of KitR in HMC-1 results from the activating mutations of c-kit gene, and raise the possibility that the activating mutations, particularly at codon 814 of murine c-kit or at codon 816 of human c-kit, may participate in oncogenesis of mast cells.

Humans↗

Soluble form of P-selectin in patients with acute myocardial infarction.

BACKGROUND: P-selectin, an integral membrane glycoprotein of platelets and endothelial cells, is rapidly redistributed to the cell surface after cellular activation. The soluble form of P-selectin has been shown to be present in people with normal circulation. The purpose of the present study was therefore to examine the soluble form of P-selectin in patients with acute myocardial infarction (AMI). METHODS: Whole blood was obtained from nine patients with AMI and from 10 volunteers who made up the control group. Plasma concentrations of the soluble form of P-selectin were examined with a monoclonal antibody-based enzyme immunoassay. RESULTS: Plasma P-selectin levels in control volunteers were 178 +/- 44 ng/ml. In patients with AMI, plasma P-selectin levels on days 1, 2 and 3 were 743 +/- 374, 627 +/- 267, and 588 +/- 223 ng/ml, respectively (P < 0.001)--significantly higher than the levels in the control volunteers. CONCLUSION: Plasma concentrations of the soluble form of P-selectin were markedly higher in patients with AMI, suggesting the activation of platelets, or endothelial cells, or both. Thus, quantitative measurements of plasma P-selectin concentrations may help to assess the pathophysiology of inflammatory reactions in patients with AMI.

Adult↗

[Usefulness of 99mTc-PMT SPECT and 18F-FDG PET in diagnosing orbital metastasis of hepatocellular carcinoma].

We reported a case in which 99mTc-PMT scintigraphy was useful in diagnosing orbital metastasis of HCC. The case involved a 70 y.o. male, who had undergone nine transcatheter arterial embolizations over two years because of HCC and who had a past history of gastric cancer. The patient had complained of headache and visual disturbance for two months. Cranial CT and MRI studies showed a large homogeneous mass with remarkable bone destruction in the right lateral orbital wall. Because AFP was elevated, orbital metastasis of HCC was suspected, and 99mTc-PMT scanning was performed. On the planar and SPECT images, very high uptake was found in the right orbital tumor. The FDG-PET study showed remarkable hypermetabolism in the medial portion of tumor and follow-up MRI revealed that the tumor had expanded and invaded to the medial side of the orbit. 99mTc-PMT scanning was critical in diagnosing this case of orbital metastasis, and FDG-PET imaging was useful in determining the most active portion of the tumor.

Aged↗

[A rare case of high cervical spinal cord dural arteriovenous fistula presenting with intracranial subarachnoid hemorrhage].

It is now recognized that spinal dural arteriovenous fistula causes myelopathy, resulting from congestive venous hypertension of the spinal cord. We have recently encountered a rare case of high cervical spinal cord dural arteriovenous fistula which caused intracranial subarachnoid hemorrhage. The patient was a 62-year-old female, who had exhibited an abrupt onset of severe headache and loss of consciousness. Plain head CT scan revealed intracranial subarachnoid hemorrhage. No abnormal vascular lesions were found on the first cerebral angiography. The second angiographical examination demonstrated a spinal arteriovenous malformation at the high cervical region. A dural arteriovenous fistula around the right C2 nerve root was found by surgical intervention. The fistula was recognized between rt. C2 radicular artery and dural sheath of rt. C2 nerve root, draining to the epidural plexus and intradural local medullary vein. No serpentine coronal venous plexus on the dorsal aspect of the cervical cord was seen as it is in a usual dural type of spinal arteriovenous fistula. The bleeding point was an intradural varix of the medullary vein just where it penetrated the nerve root area. Feeder ligation of the C2 radicular artery and coating of the varix complex were performed. The postoperative course was uneventful. The patient was discharged from our institute with no neurological deficits.

Arteriovenous Fistula↗

Tissue-specific suppressor T cells involved in self-tolerance are activated extrathymically by self-antigens.

Autoimmune prostatitis developed spontaneously in (C57BL/6N x A/J)F1 (B6A) mice, when thymectomy (Tx) was conducted on day 3 after birth (Tx-3). The lesion could be prevented by a single injection of CD4+ spleen cells (4 x 10(6)) from normal males, but not from normal females or newborn orchidectomized (Orx-0) mice. However, when spleen cells were obtained from Orx-0 mice that had received a dihydrotestosterone (DHT) pellet when adult to develop a mature prostate, prostatitis could be prevented, suggesting that immune tolerance to prostate antigen(s) is maintained by a CD4+ tissue-specific suppressor T cell (Ts) population(s), which is activated by a specific autoantigen(s) in the mature prostate. The result that even CD4+ cells from Orx-0 mice that were thymectomized as adults and treated thereafter with DHT were effective for prevention of prostatitis suggests that activation of this Ts population takes place in the peripheral lymphoid organs, and that it maintains peripheral tolerance to autoantigen in the prostate of these mice and probably also in normal mice.

Animals↗

[A case of lipoid pneumonia showing a pulmonary nodule mimicking lung cancer].

A 49-year-old man was admitted to our hospital because of hemosputum, left chest pain and an abnormal shadow on chest X-ray. Computed tomography of the chest revealed a tumor-like shadow with a low density area in the left lower lung field. Ga scintigraphy revealed strong Ga uptake in the left lower lung. Fiberoptic bronchoscopy showed obstruction of subsegmental bronchi of it. B9+10. Neither transbronchial biopsy nor sputum cytology showed any malignant cells. Transcutaneous lung biopsy showed infiltration of foamy macrophages in alveolar spaces and lymphocytes and plasma cells in alveolar septa. Since there was a possibility of complicating lung cancer, and because of refractory hemosputum, the patient underwent left lower lobectomy. The cut surface of the resected left lobe showed the features of golden pneumonia with cavitation. The histological features of the resected specimen were those of lipoid pneumonia, and no cancer cells were detected.

Diagnosis, Differential↗

Germinoma originating in the basal ganglia and thalamus: MR and CT evaluation.

PURPOSE: To describe MR and CT features of germinoma originating in the basal ganglia and thalamus and to discuss the roles of each modality for its diagnosis. METHODS: MR and CT studies of six cases of germinomas, five of which were histologically proved, were retrospectively reviewed. T1-weighted, T2-weighted, and contrast-enhanced T1-weighted conventional spin-echo images, and unenhanced and contrast-enhanced CT images were evaluated. RESULTS: Typically, the tumor consisted of an irregular solid area with contrast enhancement and various-size cysts. Cystic components were found in five cases and calcification in four. Intratumoral hemorrhage was noted in one. Ipsilateral cerebral hemiatrophy and brain stem hemiatrophy were noted in three cases each. MR was superior to CT in evaluating precise tumor extension, cystic components, and intratumoral hemorrhage, although in one case, extension of the tumor was better defined on CT in its early stage. Calcification was difficult to identify by MR alone. The solid components of the tumors generally showed slightly high density on CT, which seemed to be characteristic compared with nonspecific intensity pattern on MR. CONCLUSION: The combination of CT and MR findings allows early detection and appropriate diagnosis of the mass in the basal ganglia and/or thalamus.

Adolescent↗

High-dose rate and low-dose rate intracavitary therapy for carcinoma of the uterine cervix. Final results of Osaka University Hospital.

BACKGROUND: High-dose rate (HDR) intracavitary radiation therapy for carcinoma of the uterine cervix has gradually found wider acceptance. In 1983, the authors first presented the results of prospective randomized comparative study of HDR versus low-dose rate (LDR) therapy. In the current study, the final results of this study with a longer follow-up are presented. METHODS: From January 1975 through August 1983, 430 previously untreated patients with carcinoma of the uterine cervix in Stages I-III were treated with either HDR 60Co therapy or LDR 137Cs therapy at our department. HDR was administered to a total of 259 patients: 32 patients in Stage I, 80 in Stage II, and 147 in Stage III. LDR was administered to a total of 171 patients: 28 patients in Stage I, 61 in Stage II, and 82 in Stage III. RESULTS: The 5-year cause-specific survival rates of Stage I-III patients treated with HDR were 85%, 73%, and 53%, respectively. The corresponding figures for LDR were 93%, 78%, and 47%, respectively. There was no significant difference between these survival rates. Moderate-to-severe complications developed in 10% of the patients treated with HDR and 4% of those with LDR. This difference in the incidence of complications was statistically significant (P = 0.023). CONCLUSIONS: Treatment results in terms of cause-specific survival were equivalent for HDR and LDR treatment. However, the incidence of complications was higher for the HDR group, although within acceptable levels, than for the LDR group.

Actuarial Analysis↗

Quartz crystal microbalance for the detection of microgram quantities of human serum albumin: relationship between the frequency change and the mass of protein adsorbed.

We have developed a piezoelectric immunosensor for the detection of microalbumin. Human serum albumin (HSA) in the range 0.1-100 micrograms mL-1 could be detected using a flow cell; the immunosensor is sensitive enough to monitor levels of albuminuria. The immunosensor did not respond to bovine serum albumin, only to HSA, implying that the specificity for HSA was high. We investigated the relationship between the frequency change (delta F) and adsorption per unit area of piezoelectrically active quartz crystal (delta M). delta M was estimated with radioisotope-labeled anti-HSA or HSA. When anti-HSA was adsorbed onto the surface of the crystal or HSA was bound to anti-HSA supported by the crystal, values of magnitude of delta F/delta M were larger than the value predicted from theory (Sauerbrey's equation). Furthermore, magnitude of delta F/delta M for HSA was larger than that for anti-HSA.

Adsorption↗

Enzyme release assay of human NK cell activity using beta-galactosidase-expressing K562 target cell line.

In the present report, we established a K562 cell line useful for an enzyme release assay of human natural killer (NK) activity. Human myelogenous leukemia cell line, K562, was transfected with a plasmid carrying Escherichia coli beta-galactosidase (beta-gal) gene. A colony that permanently expresses the enzyme activity was isolated, and designated K562/Zneo. Incubation of K562/Zneo cells (1 x 10(4)) with nonadherent human peripheral blood lymphocytes (PBL) resulted in the release of beta-gal activity depending on the incubation time and the number of effector cells. Released beta-gal activity was assayed sensitively by using 4-methylumbelliferyl-beta-D-galactoside, a fluorescent substrate. The cytolytic activity of PBL was augmented significantly when the cells were preincubated with interleukin-2 for 20 h. This enzyme release assay showed a comparable sensitivity to that of 51Cr release assay. Thus, K562/Zneo cell line is thought to be useful for the nonradioactive assay of human NK and lymphokine-activated killer activities.

Cytotoxicity, Immunologic↗

The regulation of gene expression by insulin is differentially impaired in the liver of the genetically obese-hyperglycemic Wistar fatty rat.

The regulation by insulin and carbohydrates of the gene expression of three key enzymes involved in glucose metabolism was studied in the liver of the Wistar fatty rat, a model of obese non-insulin-dependent diabetes mellitus. A high glucose or fructose diet, or insulin administration caused a similar magnitude of increase in the level of L-type pyruvate kinase mRNA in the liver of Wistar fatty rats and their lean littermates. However, the induction of glucokinase mRNA and repression of phosphoenolpyruvate carboxykinase mRNA by dietary glucose or insulin were impaired in the fatty rats, whereas fructose caused a similar decrease in phosphoenolpyruvate carboxykinase mRNA in both types of rats. These results indicate that the regulation of gene expression of glucokinase and phosphoenolpyruvate carboxykinase, but not of L-type pyruvate kinase, by insulin is impaired in the liver of the Wistar fatty rat.

Animals↗

Prognostic factors in telecobalt therapy for early supraglottic carcinoma.

BACKGROUND: The local control rates of T1 and T2 supraglottic carcinoma treated with radiation alone were reported as 71% to 92% and 59% to 83%, respectively. The factors that affect the local control rate for early supraglottic carcinoma were investigated. METHODS: From 1967 through 1985, 100 cases with early supraglottic carcinoma (T1N0, 51; T2N0, 49) were treated with telecobalt therapy at the Department of Radiology, Osaka University Hospital. RESULTS: The 5-year actuarial survival rates of cases with T1 and T2 were 69% and 74%, respectively. The 5-year local control rates of cases with T1 and T2 were 77% and 62%, respectively. The local control rate for the epilarynx (94%) was significantly better than that for the lower supraglottis (66%; P < 0.05). For the lower supraglottis, the local control rates of 24 tumors that disappeared at 40 Gy and 58 tumors that persisted at 40 Gy were 88% and 55%, respectively (P < 0.05). CONCLUSIONS: The tumor site was an important prognostic factor in radiation therapy for the supraglottis, as was the tumor response at 40 Gy for the lower supraglottis.

Cobalt Radioisotopes↗

Analysis of T-cell receptor V region gene usage of cytotoxic T-lymphocytes and tumor-infiltrating lymphocytes derived from human autologous gastric signet ring cell carcinomas.

To determine the T-cell receptor (TCR) V alpha/V beta gene usage of the human autologous gastric tumor-specific cytotoxic T-lymphocytes (CTLs), we first established two pairs of tumor cell lines, HST2 and SSTW, from the malignant peritoneal effusions of signet ring cell carcinomas and their peripheral blood lymphocyte-derived tumor-specific CD8-positive CTL lines, TcHST2 and TcSSTW. TCR V alpha/V beta gene usage from these CTL was examined using the reversely transcribed-polymerase chain reaction method, demonstrating that the V alpha 7, V alpha 12, and V beta 20 transcripts were commonly detected. The fact that repeated antigenic stimulation by mixed lymphocyte-autologous tumor cell cultures brought about the specific cytolysis and the restricted TCR usage of TCR V alpha 7, V alpha 12, and V beta 20 strongly suggests that these TCR V region products participated in T-cell-cancer interaction. This restricted TCR V gene usage in the gastric signet ring cell carcinomas led us to examine further the frequency of TCR V alpha/V beta usage in 11 cases of in vivo tumor-infiltrating lymphocytes with this particular type of tumor. The data showed that V alpha 7, V alpha 12, V beta 6, and V beta 20 were also predominantly expressed among these tumor-infiltrating lymphocytes in vivo. However, it seemed that T-cells with these TCR V region products are not specific for the gastric signet ring cell carcinomas, since they also frequently infiltrate into noncancerous lesions, such as peptic ulcers. These data may suggest that T-cells with certain TCR V alpha/V beta products could preferentially infiltrate into the stomach tissue, while some of these T-cells may be cytotoxic to the neoplastic autologous tumor cells.

Adenocarcinoma, Mucinous↗

UV irradiation can induce in vitro clonal anergy in alloreactive cytotoxic T lymphocytes.

The alloreactive cytotoxic T lymphocytes (CTL) were generated by coculturing peripheral blood mononuclear cells (PBMC) with allogeneic Sa cells (an Epstein-Barr virus [EBV]-transformed B-cell line). The CTL did not proliferate in response to UV-B-irradiated Sa cells unless exogenous interleukin-2 (IL-2) was present, although they could kill the UV-B-irradiated Sa cells. The results indicate that UV-B-irradiated Sa cells do not provide sufficient signals for the proliferation of the CTL while they can be recognized by CTL and induce high-affinity IL-2 receptor (IL-2R) expression on them. The alloreactive CTL could be rendered anergic by previous exposure to UV-B-irradiated Sa cells. The alloreactive CTL previously stimulated with UV-B-irradiated Sa cells failed to proliferate in response to nontreated Sa cells. Proliferation of the anergic CTL could not be restored by Sa cells and exogenous IL-2 but by the combination of phorbol 12-myristate 13-acetate (PMA) and calcium ionophore (A23187). The anergic CTL showed a considerably low cytotoxic activity against Sa target cells. The expression of TCR on the anergic CTL was downregulated while expression of high-affinity IL-2R was upregulated. Their CD28 and CD8 expression were unchanged. In addition, the proliferative response and cytotoxicity of the anergic CTL to Sa cells could be restored after the cells had been rested for 7 days to allow reexpression of TCR. These results suggest that downregulation of T-cell receptor (TCR) and impairment in the post-IL-2/IL-2R signaling pathway are relevant to the clonal anergy induced in the alloreactive CTL by stimulation of UV-B-irradiated Sa cells.

Antigens, CD↗