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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 739 records · Page 41Linked to original sources
PubMed1993

Ultraviolet irradiation inhibits killer-target cell interaction.

The effects of ultraviolet (UV) irradiation on cell-mediated cytolysis were examined in order to clarify the inhibitory mechanisms of allosensitization by UV irradiation. UV-B-irradiated target cells (Sa; an Epstein-Barr virus-transformed B cell line) exhibited more resistance against alloreactive cytotoxic T lymphocytes (CTL) than mitomycin C (MMC)-treated target cells. In the conjugate formation assay, UV-B-irradiated target cells showed a considerably lower binding to alloreactive CTL than MMC-treated target cells. UV-B irradiation induced a reduction of HLA-class I, -DR, CD54 (ICAM-1) and CD58 (LFA-3) expression on target cells. However, it does not seem to contribute to the inhibition of cell adhesion induced by UV-B irradiation because a similar reduction of cell surface antigens was observed in MMC-treated target cells. Number of cells capped with anti-HLA-class I, -DR, CD54 or CD58 monoclonal antibody were markedly reduced by UV-B irradiation compared to that by MMC treatment. These findings suggest the possibility that the inhibition of cell adhesion between UV-B-irradiated Sa target cells and alloreactive CTL is due to the impaired mobility of cell surface antigens which will affect the early process of cell-mediated cytolysis.

Cell Communication↗
PubMed1993

Small bowel obstruction in children: review of 10 years experience.

Small bowel obstruction, excluding postoperative adhesive ileus, in patients > 1 month old treated between June 1982 and May 1992 at Gunma Children's Hospital Medical Center is reviewed. There were 32 patients, 22 boys and 10 girls, whose ages ranged from 1 month to 6 years (median 9 months). Intussusception was the most frequent cause of obstruction and was seen in 17 patients (53.1%). Causative lesions were identified in five patients, and were ileal duplication cysts in four and Meckel's diverticulum in one. Incarcerated inguinal hernia and mesenteric cysts resulted in bowel obstruction in six and three patients, respectively. Other causes included mesodiverticular band, ileal volvulus without malrotation, abnormal adhesion of omentum, abnormal band, vitelline duct remnant and trapping in a mesenteric defect. As for the age distribution, there was no significant correlation between the causes of obstruction and the age of patients. Ultrasonography was useful in differential diagnosis, and this modality should therefore be used in every patient with signs of small bowel obstruction.

Age Distribution↗
PubMed1993

Transposon mutagenesis by Tn4560 and applications with avermectin-producing Streptomyces avermitilis.

The Tn3-like Streptomyces transposon Tn4560 was used to mutagenize Streptomyces avermitilis, the producer of anthelmintic avermectins and the cell growth inhibitor oligomycin. Tn4560 transposed in this strain from a temperature-sensitive plasmid to the chromosome and from the chromosome to a plasmid with an apparent frequency of about 10(-4) to 10(-3) at both 30 and 39 degrees C. Auxotrophic and antibiotic nonproducing mutations were, however, obtained only with cultures that were kept at 37 or 39 degrees C. About 0.1% of the transposon inserts obtained at 39 degrees C caused auxotrophy or abolished antibiotic production. The sites of insertion into the S. avermitilis chromosome were mapped. Chromosomal DNA fragments containing Tn4560 insertions in antibiotic production genes were cloned onto a Streptomyces plasmid with temperature-sensitive replication and used to transport transposon mutations to other strains, using homologous recombination. This technique was used to construct an avermectin production strain that no longer makes the toxic oligomycin.

Anthelmintics↗
PubMed1993

Transgenic Fv-4 mice resistant to Friend virus.

Fv-4 is a mouse gene that confers resistance to infection with ecotropic retroviruses. A candidate Fv-4 gene was cloned previously and found to resemble the 3' half of a murine leukemia virus (MuLV). To study the effect of this gene in vivo, we generated two transgenic mouse strains carrying the Fv-4 env gene under control of its presumed natural promoter, a cellular sequence unrelated to retroviruses. Transgenic progeny expressed a 3-kb Fv-4 env RNA in all of the organs and tissues examined, as well as an Fv-4 envelope antigen on the surface of thymocytes and spleen cells, similar to mice carrying the natural Fv-4 gene. One of the two transgenic strains (designated Fv4-2) expressed three to nine times as much transgene RNA and protein as the other strain (Fv4-11). When challenged with a Friend virus complex containing up to 10(4) XC PFU of Friend MuLV, Fv4-2 mice were completely resistant to development of splenomegaly and had no detectable ecotropic virus in the spleen or blood, confirming that the cloned Fv-4 gene is responsible for resistance to ecotropic MuLV in vivo. In contrast, Fv4-11 mice were only partially resistant, developing viremia and splenomegaly at the highest inoculum dose but recovering from viremia several weeks after inoculation with 10-fold less virus. The phenotype of recovery from viremia in Fv4-11 mice was unexpected and suggests that low levels of expression of the Fv-4 gene enhance the effectiveness of the immune response.

Animals↗
PubMed1993

Lipocytes from fibrotic rat liver have an impaired feedback response to procollagen propeptides.

Procollagen propeptides have been previously shown to be taken up by cultured fibroblasts and to inhibit collagen production at translational and transcriptional levels. In hepatic fibrosis, Ito cells are thought to be major contributors to collagen overproduction. We wondered whether an impaired response to procollagen propeptides by Ito cells from fibrotic liver could be a mechanism involved in collagen overproduction in hepatic fibrosis. In the presence of type I procollagen carboxy-terminal propeptide (200 nM), collagen production by Ito cells from normal rats was significantly decreased to 62.0% of control, whereas collagen production by Ito cells from two models of hepatic fibrosis in the rat, bile duct ligation and carbon tetrachloride treatment, was not significantly changed (102.4 and 102.6% of controls, respectively). By measurement of type I procollagen mRNA levels, this difference in response to procollagen carboxy-terminal propeptide was determined to occur at a pretranslational level. The rates of uptake, transfer to the nuclear compartment, and degradation of procollagen propeptide were not significantly different in Ito cells from normal and fibrotic liver.

Animals↗
PubMed1993

Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product.

The c-kit proto-oncogene encodes a receptor tyrosine kinase. Binding of c-kit ligand, stem cell factor (SCF) to c-kit receptor (c-kitR) is known to activate c-kitR tyrosine kinase, thereby leading to autophosphorylation of c-kitR on tyrosine and to association of c-kitR with substrates such as phosphatidylinositol 3-kinase (PI3K). In a human mast cell leukemia cell line HMC-1, c-kitR was found to be constitutively phosphorylated on tyrosine, activated, and associated with PI3K without the addition of SCF. The expression of SCF mRNA transcript in HMC-1 cells was not detectable by means of PCR after reverse transcription (RT-PCR) analysis, suggesting that the constitutive activation of c-kitR was ligand independent. Sequencing of whole coding region 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 resulting in intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp. Amino acid sequences in the regions of the two mutations are completely conserved in all of mouse, rat, and human c-kit. In order to determine the causal role of these mutations in the constitutive activation, 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 a human embryonic kidney cell line, 293T cells. In the transfected cells, both c-kitR (Gly-559, Val-814) and c-kitR (Val-814) were abundantly phosphorylated on tyrosine and activated in immune complex kinase reaction in the absence of SCF, whereas tyrosine phosphorylation and activation of c-kitR (Gly-559) or wild-type c-kitR was modest or little, respectively. These results suggest that conversion of Asp-816 to Val in human c-kitR may be an activating mutation and responsible for the constitutive activation of c-kitR in HMC-1 cells.

Amino Acid Sequence↗
PubMed1993

TSH secretory responses to prolonged infusion of TRH in hypothyroid rats.

Continuous infusion of 0.1-10 micrograms/ml of TRH was performed through chronic i.v. cannulas in unrestrained, unanesthetized hypothyroid rats. Infusion of a constant concentration of TRH induced a peak in the plasma TSH concentration within 5-15 min which declined to the baseline within 1 h. The refractory period lasted 20-40 min after stopping the continuous TRH infusion. A second burst of TSH secretion was induced by increasing the TRH concentration during the refractory period while TRH was being continuously infused. These data indicate that in hypothyroid rats TSH secretion rapidly becomes refractory to continuous exposure to the same concentration of TRH but is stimulated by a higher TRH concentration. This suggests there is heterogeneity in TSH secretory units, which may consist of a constellation of thyrotrophs or of discrete intracellular secretory units, each with a threshold of specific response to TRH.

Animals↗
PubMed1993

Circulating levels and bone contents of bone gamma-carboxyglutamic acid-containing protein in rat models of non-insulin-dependent diabetes mellitus.

In order to investigate the pathophysiology of the diabetic osteopenia observed in non-insulin-dependent diabetes mellitus, the circulating levels and the bone contents of bone gamma-carboxyglutamic acid-containing protein (osteocalcin) were determined in rat models of non-insulin-dependent diabetes mellitus, neonatally streptozotocin-induced rats and in genetic Wistar fatty rats. In Wistar fatty rats the plasma level of osteocalcin was 8.1 +/- 0.8 nmol/l, significantly lower than the value of 17.3 +/- 0.9 nmol/l in their lean littermates (p < 0.001). Bone length, bone strength, and weight of powdered bone in Wistar fatty rats were significantly decreased compared to control rats (p < 0.001, p < 0.02 and p < 0.001, respectively). Bone content of osteocalcin per femur in Wistar fatty rats was also significantly decreased compared to controls (p < 0.001). In addition, plasma osteocalcin in neonatally streptozotocin-induced diabetic rats was 2.9 +/- 0.3 nmol/l, which was also significantly decreased compared to the value of 5.6 +/- 0.5 nmol/l in their controls (p < 0.001). Since it has been established that the plasma level of osteocalcin is well related to bone formation and turnover, the low plasma values in these animal models suggest that bone formation and turnover are decreased in non-insulin-dependent diabetes mellitus. Low bone formation and turnover are, therefore, postulated to be one of the pathophysiological characteristics of the skeletal tissue in non-insulin-dependent diabetes mellitus, and to be at least in part responsible for the occurrence of this complication.

Animals↗
PubMed1993

Prevalence of gastroesophageal varices supplied by intrahepatic portal branch.

The contribution of the intrahepatic portal branch to the gastroesophageal varices is rare. This anomalous pathway (a large left intrahepatic portal branch) was proved by portographic study and by imaging techniques in a 54-year-old man with cirrhosis. The overall prevalence of this type of collateral in the literature is only 1.9% in 908 patients with portal hypertension. In addition, all are via the left portal venous branch. It may be speculated that the mechanism of this variation is due to dilatation of the rest of the intrahepatic portal system via a small anastomosis due to portal hypertension.

Collateral Circulation↗
PubMed1993

Glucose sensitivity of ATP-sensitive K+ channels is impaired in beta-cells of the GK rat. A new genetic model of NIDDM.

In the Goto-Kakizaki rat, a new genetic model of NIDDM, insulin response to glucose is selectively impaired. To elucidate the mechanism of this abnormality, we studied the properties of ATP-sensitive K+ channels, the inhibition of which is a key step of insulin secretion induced by fuel substrates, using the patch-clamp technique. The glucose-sensitivity of KATP channels was considerably reduced in GK rats. However, the inhibitory effects of ATP on channel activity and unitary conductance were not significantly different between control and GK rats. Thus, it appears that the impaired insulinotropic action of glucose in beta-cells of GK rats is attributable to insufficient closure of the KATP channels, probably because of deficient ATP production by impaired glucose metabolism. KATP-channel activities in both control and diabetic beta-cells were found to be equally suppressed by glyceraldehyde and 2-ketoisocaproate. These results strongly suggest that the step responsible for the metabolic dysfunction of diabetic beta-cells is located within the glycolytic pathway before glyceraldehyde-3-phosphate or in the glycerol phosphate shuttle.

Adenosine Triphosphate↗
PubMed1993

Effects of topical capsaicin on autonomic nerves in experimentally-induced nasal hypersensitivity. An immunocytochemical study.

Effects of capsaicin on autonomic nerves in the nasal mucosa and olfactory bulb of toluene diisocyanate sensitized guinea pigs were studied using immunocytochemistry. In the nasal mucosa, substance P (SP)- and tyrosine hydroxylase (TH)-like immunoreactive (SPI and THI) fibers seemed to decrease after capsaicin application. Calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRPI) fibers did not show obvious alterations. In the olfactory bulb, SPI and CGRPI fibers were few and the effects of capsaicin on those fibers were difficult to evaluate. THI fibers seemed not to be affected by capsaicin. It is suggested that capsaicin affects not only sensory nerves but that it also impacts on THI sympathetic nerves in the nasal mucosa.

Administration, Intranasal↗
PubMed1993

Expression, function and activation of the proto-oncogene c-kit product in human leukemia cells.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is considered to play important roles in hematopoiesis. The proto-oncogene c-kit product is expressed on various types of human cell lines derived from leukemic cells of erythroid, megakaryocytic and mast-cell lineages. Also, the c-kit product is detectable in blast cells in most cases of acute myeloblastic leukemia (AML) and in some cases of chronic myelogenous leukemia (CML) in blastic crisis (BC). By contrast, little or no expression of c-kit is observed in human leukemia cell lines of lymphoid lineage and in blast cells in acute lymphoblastic leukemia (ALL). Tyrosine phosphorylation and activation of the c-kit product with the ligand for c-kit (stem cell factor: SCF) results in proliferation of some human leukemia cell lines, such as M07E, and blast cells in a substantial fraction of AML cases. In addition, SCF appears to have an activity in inducing differentiation of certain types of leukemic cells. In some cases, further, the c-kit product is found to be activated in leukemic cells even before the stimulation with SCF. These results suggest that c-kit may be involved in excessive proliferation and aberrant differentiation of human leukemia cells.

Cell Adhesion↗
PubMed1993

Changes in phenotype and proliferative potential of human acute myeloblastic leukemia cells in culture with stem cell factor.

The interaction of the proto-oncogene c-kit product with its ligand (stem cell factor or SCF) is considered to play crucial roles in hematopoiesis. In a series of human acute myeloblastic leukemia (AML) cells, the effects of recombinant human (rh) SCF on AML cells were examined in short-term and long-term cultures. c-kit expression was detected in 26 of 31 AML cases, and short-term treatment of AML cells with rhSCF led to proliferation in 13 of 18 AML cases that expressed the c-kit product. In seven of the 13 cases showing proliferative response to rhSCF, AML cells were exclusively composed of immature blast cells. We therefore used the seven AML cases for examining the effect of rhSCF on the differentiation and proliferation of AML cells in a long-term culture. Proliferation of AML cells was found to be maintained with rhSCF more than 2 weeks in five of seven cases and 4 weeks in two cases, whereas most of the AML cells died before 2 weeks in the absence of rhSCF. Further, in four of five AML cases, all of which expressed the CD34 antigen and showed a proliferative response to rhSCF in a long-term culture, rhSCF appeared to promote differentiation of blast cells toward lineages of various cell types, such as granulocytic and/or monocytic and mast-cell lineages. These results suggest that, at least in a fraction of AML cases, rhSCF can induce not only proliferation but also differentiation of AML cells, and also that phenotypic manifestation of AML cells may not mean definite cell commitment but can be changed by stimulation with rhSCF.

Antigens, CD↗
PubMed1993

Comparison of early glottic and supraglottic carcinoma treated with conventional fractionation of radiotherapy.

There were a few reports to compare the treatment results of glottic and supraglottic carcinoma. We investigated the difference of glottic and supraglottic carcinoma. From 1967 through 1985, 338 cases with early glottic (T1: 210, T2: 52) and supraglottic carcinoma (T1: 34, T2: 42) were treated with the conventional fractionation of radiation and evaluated the tumor response during radiation at the Department of Radiology, Osaka University Hospital. The ten-year actuarial survival rates of T1, T2 glottic and T1 and T2 supraglottic carcinoma were 63%, 64%, 58% and 46%, the corresponding ten-year cause-specific survival rates 92%, 89%, 88% and 78%, and the corresponding ten-year local control rates 76%, 67%, 69% and 59%, respectively. Tumor clearance rates of T1 and T2 glottic and T1 and T2 supraglottic carcinoma at 40 Gy were 68%, 40%, 35% and 24%, respectively. The local control rate of the tumor which disappeared at 40 Gy was 84%, that persisted at 40 Gy and disappeared at 60 Gy 69%, and that persisted at 60 Gy 33%. The local control rate and the tumor clearance rate of T1 glottic carcinoma were the highest among early laryngeal carcinoma, and those of T2 glottic carcinoma were the same as those of T1 supraglottic cases. The local control rate, the cause-specific survival rate, and the actuarial survival rate of T2 supraglottic were significantly lower than other cases.

Actuarial Analysis↗
PubMed1993

[An appraisal of intraoperative radiotherapy for pancreas cancer].

Intraoperative radiotherapy (IORT) which was originally used for unresectable cancer has been applied to the cases after pancreas resection. However, it has not been clarified which stages of patients will have the beneficial effect of IORT on their prognosis. In this study, IORT after pancreas resection was appraised on the basis of the patient prognosis. Seventy-two pancreatectomized patients including 6 cases of Stage I, 18 cases of Stage II, 25 cases of Stage III and 23 cases of Stage IV, which was determined by the general rules for cancer of the pancreas in Japan Pancreas Society were employed in this study. Four cases of Stage III and 15 cases of Stage IV were treated with IORT (25-30 Gy) after pancreatectomy. Ten of these patients underwent postoperative external beam radiotherapy (22-48 Gy). All but one case of Stage I were currently alive. The median survival time (MST) of Stage II were 908 days and 2 cases were alive over 5 year after operation. MST of Stage III without IORT was 310 pod and all died within 906 pod. In contrast, all four Stage III patients were currently alive without a sign of recurrence (3, 10, 15, 57 pom). All Stage IV cases without IORT died within 462 pod, while three cases with IORT were alive over this period. These data suggest IORT improves the prognosis of Stage III patients when combined with radical resection of the pancreas. But it is not the case with the more advanced cases, where systemic anticancer adjuvant therapy might be indicated.

Adult↗
PubMed1993

Prognostic factor of radiotherapy for squamous cell carcinoma of oropharynx without clinically positive nodes.

Local control rates of oropharynx carcinoma treated with radiation alone were reported as 40 to 71%. We investigate the factors which affect the local control rate for oropharynx carcinoma. From 1967 through 1982, 62 cases of squamous cell carcinoma of oropharynx without positive neck nodes were treated with external radiation at the Department of Radiology, Osaka University Hospital. Five-year actuarial survival rates of T1, T2, T3 and T4 cases were 53%, 63%, 47% and 0%, respectively. Five-year local control rates of T1, T2, T3 and T4 cases were 51%, 46%, 34% and 0%, respectively. In 52 cases treated with a total dose of 60 Gy or more, tumor response could be evaluated at the dose level of 40 and 60 Gy. The local control rates of tumors which disappeared and persisted at 40 Gy were 88% (7/8) and 39% (17/44), respectively (p < 0.05). Of 44 cases which persisted at 40 Gy, the local control rates of tumors which disappeared and persisted at 60 Gy were 48% (11/23) and 29% (6/21), respectively (p > 0.30). Evaluation of tumor response at 40 Gy was an important indicator of local control for N0 oropharynx carcinoma.

Adult↗
PubMed1993

High-dose-rate remote afterloading intestinal radiotherapy employing the template technique for recurrent cancer in the pelvic area.

Between December 1991 and August 1992, five patients with recurrent cancer in the pelvic area (four gynecological cancers and one rectal cancer) were treated at Osaka University Hospital with a remote afterloading interstitial implantation employing the template technique. External irradiation (40 to 50 Gy) was performed in four cases one to four weeks before brachytherapy. Interstitial high-dose-rate brachytherapy (24 to 40 Gy/four to eight fractions/two to four days) was performed twice a day. Three of the five patients achieved complete local tumor control. The remaining two patients obtained symptom relief. There were no complications serious enough to need surgical treatment. Moreover, this procedure is well tolerated and therefore an effective modality for elderly and frail patients.

Adenocarcinoma↗