Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 613 records · Page 34Linked to original sources

PubMed1995

Three groups of afferent pulpal feline nerve fibres show different electrophysiological response properties.

Responses were recorded, after the application of four types of stimuli (slow or rapid elevation of temperature, hydrostatic negative pressure through thin dentine, and bradykinin directly applied to exposed pulp), from functional single fibres innervating the cat lower canine tooth pulp, dissected from the inferior alveolar nerve. A total of 278 single pulpal fibres were isolated. A fibres (n = 220) were divided into two groups: one (FA; fast A fibre, n = 160) consisting of those whose conduction velocities (CVs) were more than 2 m/s both inside and outside the tooth pulp, and the other (SA delta; slow A delta fibre, n = 60) consisting of those whose intrapulpal CVs were less than 2 m/s and extrapulpal CVs greater than 2 m/s. Fifty eight C fibres (C) were also found. None of FA, 40% of SA delta and 52% of C responded to continuous heat. None of C, 47% of FA and 45% of SA delta responded to rapid elevation of temperature. None of C, 20% of FA and 20% of SA delta responded to hydrostatic pressure. None of FA, 83% of SA delta and all of C responded to bradykinin. It was found that 21 of 60 SA delta responded to both types of stimuli that reportedly activate only A (rapid heat and hydrostatic negative pressure) or C (continuous slow heat and bradykinin) nerve fibres and that 29 SA delta responded to slow heating and/or bradykinin, similar to C fibres.

Animals↗

PubMed1995

TMP-153, a novel ACAT inhibitor, inhibits cholesterol absorption and lowers plasma cholesterol in rats and hamsters.

Effects of TMP-153, N-[4-(2-chlorophenyl)-6,7-dimethyl-3-quinolyl]-N'-(2,4-difluorophe nyl)urea, on intestinal and hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activities, cholesterol absorption and plasma cholesterol level in rats and hamsters were studied. TMP-153 has IC50 values of around 5-10 nM for the hepatic and intestinal ACAT from various animals. The most potent inhibition was observed in the intestinal ACAT from Golden hamsters (IC50 = 2.3 nM). The inhibition mode of TMP-153 was non-competitive for rat intestinal ACAT. TMP-153 inhibited cholesterol esterification both in human colonic adenocarcinoma cells, LS180, and in human hepatoma cells, HepG2 (IC50 = 150 nM and 330 nM, respectively). [14C]cholesterol and cold cholesterol absorption from the small intestine was markedly inhibited by oral administration of TMP-153 (1 mg/kg) without affecting lymph flow and triglyceride absorption. When the compound was given as a dietary admixture, plasma cholesterol was reduced in rats fed a cholesterol diet (ED50 = 0.25 mg/kg/day), but not in those fed a stock diet. On the other hand, TMP-153 showed more prominent hypocholesterolemic effect in Golden hamsters fed the stock diet (ED50 = 0.81 mg/kg/day) than in those fed the cholesterol diet (ED50 = 8.01 mg/kg/day). In hamsters fed the stock diet, TMP-153 markedly decreased the hepatic unesterified cholesterol in addition to esterified cholesterol content, but did not affect bile flow and the biliary secretion of bile acid and lipids. Different mechanisms for plasma cholesterol lowering by TMP-153 between rats and hamsters was discussed.

Adenocarcinoma↗

PubMed1995

TMP-153, a novel ACAT inhibitor, lowers plasma cholesterol through its hepatic action in golden hamsters.

The mechanism of the hypocholesterolemic action of N-[4-(2-chlorophenyl)-6,7-dimethyl-3-quinolyl]-N'-(2, 4-difluorophenyl) urea (TMP-153), a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was studies in Golden hamsters. TMP-153 (0.5-1.5 mg/kg) dose-dependently reduced plasma total- and low density lipoprotein (LDL)-cholesterol without affecting high density lipoprotein (HDL)-cholesterol. TMP-153 markedly reduced the cholesterol influx into the plasma upon intravenous injection of Triton WR-1339. The compound also decreased cholesterol absorption calculated from dietary intake, biliary secretion and the absorption co-efficient. Hepatic cholesterol secretion was calculated by substracting the cholesterol absorption from the cholesterol influx. In hamsters, the liver accounted for 92% of the cholesterol influx with the remaining 8% coming from the intestine, and both were markedly decreased by TMP-153. Thus, it is likely that TMP-153 lowers plasma cholesterol through its hepatic action. In the liver, the compound significantly reduced the unesterified cholesterol content in addition to markedly reducing the content of esterified cholesterol. In accordance with this reduction, the half-life time of [125I]-LDL was significantly shortened by the compound, suggesting an increase in LDL receptors. However, the hepatic cholesterogenesis from [14C]acetate was decreased by TMP-153 treatment. This effect seems to be secondary, since the compound did not inhibit cholesterogenesis from [14C]acetate in HepG2 cells. From the data described above, the contribution of hepatic secretion and intestinal absorption of cholesterol to the plasma cholesterol level in Golden hamsters are discussed.

Animals↗

PubMed1995

Bcl-2 oncoprotein expression and apoptosis in neuroblastoma.

Bcl-2 protooncogene, originally discovered at the chromosomal breakpoint of the t(14;18) in follicular lymphoma, is known to regulate the process of programmed cell death or apoptosis. The inhibition of apoptosis is thought to be one of the mechanisms involved in the development of tumors. To investigate the possible association of bcl-2 protooncogene with the tumorigenesis of neuroblastomas, the authors examined bcl-2 expression by immunohistochemistry in 49 neuroblastomas and 7 ganglioneuromas. The distribution of apoptotic cells was also examined by the TUNEL method (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Bcl-2 oncoprotein was detected in the cytoplasm in 40 of 49 neuroblastomas (81.6%). There was no correlation between bcl-2 oncoprotein expression and the clinical features of neuroblastoma. The incidence of bcl-2-positive tumors in ganglioneuroma was significantly lower than that in neuroblastoma (28.6%) (P < .01). TUNEL stained the nuclei of tumor cells in 11 of 34 (32.4%) neuroblastomas. TUNEL-positive cells tended to be located around calcifications in neuroblastomas in patients less than 1 year old. Examination of serial sections showed that apoptotic cells were distributed in the area where bcl-2 oncoprotein was not expressed. What we have observed indicates that apoptosis of neuroblastoma cells may be regulated by bcl-2 expression. Our observations suggest that the survival of neuroblastoma cells might be promoted by bcl-2 expression and that bcl-2 might be associated with the tumorigenesis of neuroblastomas.

Adrenal Gland Neoplasms↗

PubMed1995

Retrospective analysis of biological factors in a recurrent IV-S neuroblastoma with intermediate-grade malignancy.

A clinical stage of IV-S neuroblastoma is known to include heterogeneous tumors. The authors report a case of IV-S neuroblastoma that relapsed after regression 4 years and 10 months after diagnosis. Multiagent chemotherapy was necessary to control the disease, and the patient has been doing well with no evidence of disease for more than 5 years. Although Shimada's classification showed favorable characteristics, N-myc protein was positive and DNA ploidy was diploidy in the tumor at diagnosis. Discrepancy in DNA ploidy was observed and aneuploidy was shown in tumor specimens at recurrence. Experience in this case showed the following important clinical features: (1) IV-S neuroblastoma of intermediate-grade malignancy does exist, and patients with such a disease may be cured by aggressive treatment; (2) Identifying IV-S patients with an unfavorable clinical course is possible by examining biological prognostic factors.

Adrenal Gland Neoplasms↗

PubMed1995

A novel assay for illegitimate recombination in Escherichia coli: stimulation of lambda bio transducing phage formation by ultra-violet light and its independence from RecA function.

We developed a novel assay system for illegitimate recombination, in which the frequency of the formation of lambda Spi- phages formed during prophage induction was measured with an E. coli P2 lysogen as the indicator bacteria. Since almost all of the lambda Spi- phages thus detected contain attR, they have essentially the same structures as lambda bio transducing phages, indicating that this assay system enables us to detect specialized transducing phages that produce heterogenote transductants, thus ignoring the occurrences of docL and docR particles which carry only one cohesive end. The following results on the formation of specialized transducing phages have been obtained by this assay system to date. (1) Irradiation with UV light greatly enhanced the formation of lambda Spi- phages. (2) Treatments with other DNA-damaging agents also enhanced the formation of lambda Spi- phages. (3) Illegitimate recombination during prophage induction does not require the RecA function, indicating that enhancement of lambda Spi- phage formation is not controlled by the SOS regulatory system. (4) Preliminary results suggested that DNA gyrase is involved in the formation of lambda Spi- phage during pro-phage induction. Since the above results were consistent with most of the previous observations on the illegitimate recombination in other systems, the Spi- assay system can provide important clues to the mechanism of illegitimate recombination.

Attachment Sites, Microbiological↗

PubMed1995

Intermediate lymphocytic lymphoma with both t(14;19)(q32.3;q13.1) and t(3;22)(q27;q11.2).

Chromosome translocations involving various chromosomes sites, including the sites of immunoglobulin loci (14q32,2p12,22q11) represent recurrent aberration in non-Hodgkin lymphoma (NHL). We report a novel case of intermediate lymphocytic lymphoma (ILL) with both t(14;19)(q32.3;q13.1) and t(3;22)(q27;q11.2). The t(14;19)(q32.3;q13.1) and t(3;22) (q27;q11.2) may represent reciprocal recombinations between immunoglobulin (Ig) H chain gene (14q32.3) and bcl-3(19q13.1) and between Ig lambda chain gene (22q11.2) and bcl-6 (3q27), respectively.

Aged↗

PubMed1995

An alpha-glucosidase inhibitor, AO-128, retards carbohydrate absorption in rats and humans.

The present study was designed to determine the possible significance of a therapeutic dose (0.2 mg) of AO-128 on carbohydrate absorption by measuring the breath hydrogen concentration, which is an index of the amount of unabsorbed carbohydrate in the large intestine. Post-prandial hyperglycemia is common among diabetic patients. AO-128, a potent alpha-glucosidase inhibitor, suppressed post-prandial hyperglycemia and hyperinsulinemia in healthy volunteers at a dose of 0.2 mg with each meal. These volunteers increased the breath hydrogen concentration in response to ingestion of non-absorbable lactulose, but decreased only slightly its concentration from the basal level after sucrose ingestion, indicating complete absorption. When AO-128 (0.2 mg) was given with sucrose, hydrogen production increased only slightly compared with placebo, suggesting that the inhibitory effect of AO-128 on sucrose absorption was minimal. Only 5 g of the 100 g of sucrose was not absorbed and this 5% reduction is too small to explain the observed inhibitory effect on the post-prandial rise in plasma glucose. Sucrose loading in rats (about 443 mg) sharply increased blood glucose and was accompanied by the rapid disappearance of sucrose from the upper small intestine. AO-128 (0.03 or 0.1 mg/kg) lessened the elevation of blood glucose after sucrose ingestion. The lower dose (0.03 mg/kg) retarded small intestinal absorption, but did not induce an influx of sucrose into the cecum and large intestine, while the higher dose (0.1 mg/kg) caused an increased influx of sucrose into the large bowel. These results indicated that AO-128 retards the absorption of carbohydrate and reduces post-prandial hyperglycemia.

Adolescent↗

PubMed1995

A female heterozygous patient with Fabry's disease with renal accumulation of trihexosylceramide detected with a monoclonal antibody.

We describe a female patient with heterozygous Fabry's disease. The patient had persistent proteinuria and microhematuria but lacked any other diagnostic signs such as corneal and cutaneous involvement. Kidney tissue obtained at biopsy showed the segmentally distributed enlarged glomerular epithelia. These cells were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid structures under electronmicroscopic observation. Accumulation of trihexosylceramide (CTH) in these foamy epithelial cells was confirmed with immunohistochemical staining with the use of anti-CTH monoclonal antibody. Alpha-galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg protein/hr, n = 20). All of these findings were compatible with the diagnosis of heterozygous Fabry's disease. We recommend that kidney tissue biopsy specimens suggesting Fabry's disease be immunostained with anti-CTH antibody.

Antibodies, Monoclonal↗

PubMed1995

Disappearance of giant negative T waves in patients with the Japanese form of apical hypertrophy.

OBJECTIVES: The present study investigated the long-term changes in the electrocardiographic (ECG) hallmarks of the Japanese form of apical hypertrophy. BACKGROUND: Giant negative T waves and tall R waves in the left precordial leads are the ECG hallmarks of the Japanese form of apical hypertrophy. However, the long-term course is largely unknown. METHODS: Twenty-nine patients with apical hypertrophy (26 men, 3 women, mean age +/- SD 50.4 +/- 8.2 years) who showed left precordial giant negative T waves (< or = -10 mm) and tall R waves (> or = 26 mm) and spade configuration in the left ventriculogram were followed up for 10.9 +/- 3.7 years. RESULTS: The intermediate follow-up ECGs (5 to 9 years) showed disappearance of giant negative T waves in 31% and of tall R waves in lead V5 in 6%. At the long-term follow-up study (> or = 10 years), loss of giant negative T waves increased to 71%, with average T wave negativity in lead V4 or V5 decreasing from -16.5 +/- 5.1 to -6.9 +/- 4.2 mm. These T wave changes were associated with decreases in R wave amplitude in lead V5 from 40.7 +/- 9.6 to 26.1 +/- 13.8 mm, with loss of tall R waves in lead V5 in 38% of patients and development of abnormal Q waves in two patients. CONCLUSIONS: During the long-term follow-up of the Japanese form of apical hypertrophy, giant negative T waves disappeared in association with decreases in R wave amplitude in lead V5, indicating that these ECG hallmarks are clinical features that evolve progressively during the natural course of the disease.

Adult↗

PubMed1995

Cerebral mass lesions associated with adult T-cell leukemia/lymphoma.

Three patients with adult T-cell leukemia/lymphoma (ATLL) accompanied by cerebral mass lesions in their courses are reported. The findings of cerebrospinal fluid and their history suggested that those three cerebral involvements were the mass lesions derived from ATLL. Two of the three patients had acute type and the other one had chronic type ATLL. During the same period in which these three patients were observed, we experienced 17 other patients with ATLL. Although this group included 12 lymphoma type and five acute type ATLL, involvement of the central nervous system (CNS) was not observed in these 17 patients. The incidence of CNS involvement was 3/20 (15%). The prognoses of the three patients after the occurrence of CNS involvement was 1, 4, and 8 months, respectively. In these three patients, cerebral lesions became the cause of death for two patients although they continued to be in complete remission hematologically. Cerebral lesions, once occurring, are very hard to cure and spoil the quality of life for sufferers. From these points, prophylactic therapy against central nervous system involvement seems necessary not only for acute leukemias, but also for ATLL patients.

Adult↗

PubMed1995

Immunohistochemical demonstration of TGF-beta-receptor type II in human pituitary adenomas.

To investigate whether the signalling pathway of transforming growth factor-beta (TGF-beta) is active in human pituitary tumors, an antibody against TGF-beta-receptor type II (TGF beta-R-II) was prepared to demonstrate immunohistochemically TGF beta-R-II expression in 48 cases of human pituitary adenoma. Positive immunoreactivity for TGF beta-R-II was found in 26 adenomas: 1 of 2 somatotroph cell adenomas, 1 of 9 mammotroph cell adenomas, 0 of 3 mixed somatotroph and mammotroph cell adenomas, 5 of 9 corticotroph cell adenomas, 3 of 3 gonadotroph cell adenomas, 12 of 15 plurihormonal adenomas, and 4 of 7 null cell adenomas. Expression of TGF beta-R-II varied between histological types of adenomas and increased with decreasing grades of differentiation. It is concluded that TGF-beta-mediated signals may be passed via TGF beta-R-II in pituitary tumors.

Adenoma↗

PubMed1995

Immunohistochemical demonstration of tenascin in human pituitary glands and adenomas.

The expression of tenascin in 8 cases of normal fetal and adult human pituitary glands and in 51 cases of human pituitary adenomas was investigated immunohistochemically with the use of polyclonal antibodies against human tenascin. The immunohistochemical study demonstrated that tenascin is expressed in both fetal and adult normal epithelial cells of the anterior lobe of pituitary glands and in tumor cells of pituitary adenomas, which suggests that tenascin is synthesized by normal pituitary cells as well as by pituitary adenoma cells. Plurihormonal pituitary adenomas, especially those producing 4 or 5 different hormones, tended to show the highest incidence of positive immunoreactivity for tenascin, suggesting that tenascin may be involved in the aggressive behaviour of plurihormonal adenomas.

Adenoma↗

PubMed1995

Importance of clinical examination and diagnosis. A case of dens invaginatus.

A case report is presented that shows a radiolucent lesion between the maxillary left lateral incisor and canine tooth, both of which were vital. The cause of the lesion was initially unclear. The patient was to be treated surgically, however, precise examination made it clear that the cause of the radiolucent lesion was due to the exposure of a second canal because of attrition of the lateral incisor crown. The final diagnosis of the tooth was dens invaginatus. This case highlights the importance of careful examination and correct diagnosis.

Child↗

PubMed1995

Molecular analysis of lambda bio transducing phage produced by oxolinic acid-induced illegitimate recombination in vivo.

To study the mechanism of DNA gyrase-mediated illegitimate recombination in Escherichia coli, we examined the formation of lambda Spi- phage during prophage induction. The frequency of Spi- phage was two to three orders of magnitude higher in the presence of oxolinic acid, an inhibitor of DNA gyrase A subunit, than in the absence of the drug, while it was very low in nalAr bacteria with the drug. RecA function is not required for the formation of these phages, indicating that this enhancement is not caused by the expression of SOS-controlled genes. Analyses of att region and recombination junctions of Spi- phages revealed that they have essentially the same structures as lambda bio transducing phages but are classified into two groups with respect to recombination sites. In the majority class of the transducing phages, there were not more than 3-bp homologies between the parental E. coli bio and lambda recombination sites. In the minority class of the transducing phages, on the other hand, 9-10-bp homologies were found between the parental recombination sites. These results suggested that oxolinic acid-induced illegitimate recombination takes place by two variants of a DNA gyrase-dependent mechanism.

Bacteriophage lambda↗

PubMed1995

Transient expression of a brain/embryonic-type myosin heavy chain isoform (MIIB2) in regenerating rat liver.

The expressions of non-muscle-type (MIIA) and brain/embryonic-type (MIIB2) myosin heavy-chain isoforms in regenerating rat liver were examined. In regenerating liver after partial hepatectomy, the level of MIIA was nearly constant, while that of MIIB2 increased transiently. The level of MIIB2 was very low in normal livers, and increased gradually and then declined with a peak at the 4th day, when the regeneration was almost completed. The level of proliferating cell nuclear antigen was highest at the 2nd day. Serine dehydratase activity in the liver decreased on partial hepatectomy, began to increase at the 5th day, and reached 71% of the control at the 7th day. These results suggest that MIIB2 plays a role in reconstruction or differentiation of the regenerating tissues rather than in proliferation of hepatocytes.

Animals↗

PubMed1995

T-cell receptor gene structures of HLA-A26-restricted cytotoxic T lymphocyte lines against human autologous pancreatic adenocarcinoma.

We isolated two cytotoxic T lymphocyte (CTL) lines, which were independently obtained by mixed lymphocyte-tumor cell culture from tumor-infiltrating lymphocytes of a patient with pancreatic adenocarcinoma. Both lines behaved identically in all the functional aspects tested and appeared to be HLA-A26-restricted. We analyzed their T cell receptor (TCR) gene structures, including V-(D)-J junctional sequences, which are unique to each T-cell clonotype and contribute to TCR diversity. Each line consisted of a clonal T-cell expressing V alpha 18 and V beta 7. The alpha chain gene was composed of V alpha 18/J alpha F/C alpha and the beta-chain gene, of V beta 7.1/D beta/J beta 1.4/C beta 2. The sequences were all in-frame and therefore should yield functional transcripts. The junctional sequences were identical between the two lines. These data suggested that the two CTL clones having the same CDR3 had descended from a common precursor lymphocyte. The clonal expansion of CTL lines with the identical CDR3 implies that they are directed against the same tumor antigen, which seemed to be immunologically dominant in the specific interaction between the CTL and the autologous pancreatic adenocarcinoma.

Adenocarcinoma↗

PubMed1995

Induction of DNA recombination by activated 3-amino-1-methyl-5H-pyrido[4,3-b]indole.

To investigate the genotoxic properties of a food-derived carcinogen, 3-amino-1-methyl-5H-pyrido-[4,3-b]indole (Trp-P-2), we have tested whether Trp-P-2 and its metabolically transformed products can induce DNA recombinations. Trp-P-2 is a strong mutagen and its activated form, the N-hydroxylated derivative, Trp-P-2(NHOH), is known to form DNA adducts and cause DNA chain cleavage. Using a system in which phage lambda undergoes recombination inside host Escherichia coli, we have found that Trp-P-2(NHOH), but not Trp-P-2 itself, can induce recombination. A nitroso derivative of Trp-P-2, Trp-P-2(NO), which can be reduced intracellularly to form Trp-P-2(NHOH), also induced recombination. Active oxygens are implicated in this recombinogenic action, since Trp-P-2(NHOH) is known to undergo spontaneous oxidative degradation, generating active oxygen radicals which can cause DNA chain cleavages. 4-Hydroxyaminoquinoline N-oxide and phenyl-hydroxylamine also showed recombinogenic actions in this assay system; hence, it is suspected that aromatic amine-type carcinogens have this property in common.

Bacteriophage lambda↗