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Biomedical subjects

T Horikoshi

Publications and source records attributed to T Horikoshi.

At least 55 records · Page 3Linked to original sources
PubMed1996

The expression of integrin alpha 2 beta 1 and attachment to type I collagen of melanoma cells are preferentially induced by tumour promoter, TPA (12-O-tetradecanoyl phorbol-13-acetate).

The adhesion of melanoma cells to the extracellular matrix (ECM) protein is likely to be essential in their invasive metastatic processes. Treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a potent protein kinase C (PKC) activator, preferentially induced the expression of alpha 2 beta 1 integrin, the receptor for collagen/laminin. The number of cells attached to type I collagen, but not laminin, was increased by treatment with TPA. Prior exposure to PKC inhibitors such as H-7 (20 mumol/l) and calphostin C (50 mumol/l) had no effect on TPA-induced alpha 2 beta 1 integrin expression and cell attachment to type I collagen, whereas prior exposure to the calmodulin antagonist W-7(50 mumol/l) inhibited these TPA-induced events. The augmented adhesion was also inhibited by anti-alpha 2 antibody. These data suggest that the increased attachment of melanoma cells to type I collagen appears to be mediated by the preferential augmentation of integrin alpha 2 beta 1, and the activation of calmodulin kinase, but not via the activation of PKC. Analysis of the expression of integrins and of cell attachment to ECMs is important in elucidating the mechanisms involved in the progression and metastasis of malignant melanoma.

Carcinogens↗
PubMed1996

A patient with plaque-stage mycosis fungoides has successfully been treated with long-term administration of IFN-gamma and has been in complete remission for more than 6 years.

We report the successful treatment of a patient with plaque-stage mycosis fungoides with long-term and intravenous administration of recombinant human interferon-gamma (IFN-gamma) and discuss the possible mechanisms of this therapy. A 55-year-old female patient had been resistant to existing treatments and had suffered repeated exacerbations over a 5-year period. Four weeks after initiation of 2 x 10(6) U/day of IFN-gamma, a > 10% decrease in the affected surface area was noted. Twenty-two weeks after the administration of 228 x 10(6) U of IFN-gamma, complete remission (CR) was obtained. The CR continued for 13 weeks, but this was followed by an exacerbation. The second CR was obtained after the IFN-gamma dosage was increased to 16 x 10(6) U/week. The dosage was then gradually reduced by 2-4 x 10(6) U every 2 or 3 months. She was treated with a total dose of 2814 x 10(6) of IFN-gamma. She has been followed up for more than 6 years, and there has been no recurrence of mycotic skin lesions nor any visceral involvement. During therapy, no serious side-effects were noted. Long-term administration of IFN-gamma is useful for the treatment of patients with intractable mycosis fungoides. A gradual decrease in the dose of IFN-gamma is important for maintaining remission.

Antineoplastic Agents↗
PubMed1996

[Comparative study on serological diagnosis of entamoebiasis histolytica].

The practicability of four diagnostic methods for entamoebiasis histolytica including micro-gel diffusion precipitin test (MGDP), indirect immunofluorescent antibody test (IFA), indirect hemagglutination test (IHA) and enzyme-linked immunosorbent assay (ELISA) was evaluated. The serological test methods were compared by using sera obtained from 30 entamoebiasis histolytica patients and 130 normal health individuals. The highest sensitivity was obtained with the method of ELISA, followed by IFA and IHA : the lowest was obtained with MGDP. On the contrary, the high specificity was obtained with IHA, IFA, MGDP : the lowest was obtained with ELISA. Intensity of the antibody titers in IHA was correlated well with that of IFA. In addition, we studied antibodies nonspecifically reactive to Entamoeba histolytica in sera from E. histolytica-negative individuals with high CRP patients with regard to the sensitivity and specificity. Among 101 sera examined, six showed false positive results of which five were the sera with extremely high CRP.

Animals↗
PubMed1996

Doses of solar ultraviolet radiation correlate with skin cancer rates in Japan.

We analyzed trends in the disease rate of skin cancers in the 1976-80 and 1986-90 intervals in the 27 university hospitals in Japan. We also measured doses of solar ultraviolet (UV) radiation at Sapporo, Kobe and Miyazaki to evaluate the relationship between the two in Japan. The rates of basal cell carcinoma (BCC) and actinic keratosis (AK) were higher in 1986-90 than in 1976-80, whereas the rate of squamous cell carcinoma (SCC) was lower in 1986-90 than in the earlier period. The rates of SCC, BCC and AK in the southern part of Japan were about five times higher than those in the north, and the average daily UV dose measured with a Robertson-Berger meter in 1995 was about 1.8 times higher in Miyazaki than in Kobe. That measured by MS-210D UV dosimeter in Sapporo was about 0.53 times lower than in Kobe. These results demonstrate that solar UV dose is higher in the southern part of Japan than that in the northern part, explaining the higher rate of non-melanoma skin cancer in southern part of Japan. A significant increase of AK and BCC may reflect the trend of UV increase in Japan.

Dose-Response Relationship, Radiation↗
PubMed1995

Up-regulation of ICAM-1 expression on human dermal fibroblasts by IFN-beta in the presence of TNF-alpha.

Unstimulated human fibroblasts show low or undetectable ICAM-1 expression. Interferon-beta (IFN-beta) at concentrations of 10, 100, and 1000 IU/ml in the presence of tumor necrosis factor-alpha (TNF-alpha) significantly increased the ICAM-1 expression of fibroblasts in a dose-dependent manner. Treatment with IFN-beta alone, however, did not up-regulate the ICAM-1 expression. Furthermore the attachment of peripheral blood mononuclear cells (PBMCs) to cytokine-treated fibroblasts was increased. This augmented attachment was partly inhibited by anti-ICAM-1 antibody. These results suggest that IFN-beta and TNF-alpha may cooperatively modulate the attachment of PBMCs in the dermis.

Cell Adhesion↗
PubMed1995

Expression of the p53 protein in malignant melanomas as a prognostic indicator.

It is currently widely accepted that the tumour suppressor gene p53 is critically involved in the proliferation and differentiation of tumour cells including melanoma cells. In the present study, we examined 60 cases of primary melanoma to compare the expression of p53 protein with conventional prognostic markers for melanoma such as clinical and histological parameters. No correlation was found between the p53 protein and clinical factors except for the presence of a metastatic node and development to clinical stage II. However, the expression of p53 protein was significantly associated with tumour thickness over 1.5 mm, levels IV and V of invasion, the presence of ulceration, and high mitotic rate for 5-year survival rate. Although many questions still remain to be answered, our results and those of others for various other malignant tumours, implicate p53 in malignant transformation of pigment cells. Indeed, it could be a new marker for an unfavourable prognosis of malignant melanoma, even though the gene mutation in this highly lethal tumour has yet to be established.

Adult↗
PubMed1995

Endoscopic ultrasonographic abnormalities and lower esophageal sphincter function in reflux esophagitis.

Endoscopic ultrasonography of the lower esophagus was performed in 25 patients with reflux esophagitis and 13 age-matched controls. Thickening of the esophageal wall and abnormalities of its architecture were detected. As these morphological changes became more extensive, the lower esophageal sphincter pressure and the decrease of sphincter pressure on relaxation were both progressively reduced. There was a significant correlation between morphological abnormalities and lower esophageal function. Our results suggest that inflammatory damage to the muscle layer of the lower esophagus may impair lower esophageal sphincter function further, especially in patients with advanced esophagitis.

Aged↗
PubMed1995

In vitro comparative study of the antitumor effects of human interferon-alpha, beta and gamma on the growth and invasive potential of human melanoma cells.

We have studied the effects of interferon (IFN)-alpha, beta, and gamma in vitro on the growth and invasive potential of human melanoma SK-MEL-118 cells. The antiproliferative effects of IFNs were assessed by a quantitative regrowth assay in which cells were treated with IFNs at concentrations of 10(2), 10(3) or 10(4) IU/ml for 3 days (until day 4) and then further incubated without IFNs for 7 days (until day 11). The growth inhibitory effect of each IFN on melanoma cells was dose- and time-dependent. Among these three types of IFNs, however, IFN-beta exerted the strongest inhibitory effect on cell growth. To assess the anti-invasive effect of each IFN on melanoma cells, we employed an in vitro assay system using matrigel-coated Transwell chambers. When cells were treated with 10(2), 10(3), or 10(4) IU/ml of the three types of IFNs for 24 hours, the amount of tritiated thymidine incorporated into melanoma cells were treated for 24 hours with 10(4) IU/ml of IFN-beta or gamma prior to the assay, the number of cells that invaded the filter decreased by 40%; this decrease was only 10% with the same amount of IFN-alpha. Simultaneous addition of IFNs during the invasion assay was not effective in any combination. Only when the cells were pretreated with IFNs, antiinvasive effects against melanoma cells were exerted. IFN-alpha was less inhibitory than IFN-beta or gamma on proliferation and not at all inhibitory on invasion. Considering both the antiproliferative and antiinvasive effects of IFNs, our results suggest that IFN-beta has the strongest antitumoral effect on human melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1995

Type II citrullinemia associated with neutropenia.

A 37-year-old Japanese man was admitted with delirium and hyperammonemia. He was diagnosed as having type II citrullinemia because of an elevated citrulline level on amino acid analysis and very low hepatic argininosuccinate synthetase activity. He also showed a low neutrophil count and a low serum level of granulocyte colony-stimulating factor. Reduced production of this cytokine and/or impairment of its feedback regulation by the neutrophil count may have played a role in the neutropenia of this patient.

Adult↗
PubMed1995

Observation of vasospasm after subarachnoid hemorrhage by magnetic resonance angiography--a preliminary study.

Serial evaluation of cerebral vasospasm following subarachnoid hemorrhage was attempted in 11 patients using magnetic resonance (MR) angiography. MR angiography demonstrated vasospasm with angiographic confirmation in three patients as a segmental narrowing or loss of flow signal, usually accompanied by decreased distal flow signal. MR angiography also showed decreased flow signal suggestive of vasospasm in another patient with clinical evidence of vasospasm but no angiographic confirmation was possible because of poor condition. MR angiography showed no vasospasm in five patients without clinical evidence of vasospasm, except in one patient with disappearance of the unilateral anterior cerebral artery signal, shown to be involvement of the clipped artery. MR angiography is a potential method for detection of vasospasm with further improvement of the technique.

Acute Disease↗
PubMed1995

Retinoblastoma gene mutation in primary human renal cell carcinoma.

We searched for possible mutations in the E2F-binding region of retinoblastoma gene in primary human renal cell carcinomas, using polymerase chain reaction and single-strand conformational polymorphism analysis of RNA. Retinoblastoma gene mutation was detected in 1 of 21 cases (5%). DNA sequencing of the polymerase chain reaction product verified that this case had a 6-base deletion at the beginning of exon 8. Our findings suggest that mutation of the retinoblastoma gene is involved in only a subgroup of sporadic human renal cell carcinomas.

Base Sequence↗
PubMed1995

[A case of cutaneous malignant melanoma metastatic to the choroid].

A case of metastasis of cutaneous malignant melanoma to the choroid was reported. The patient, a 61-year-old man, had undergone an amputation of his right first finger 3 years ago due to cutaneous malignant melanoma. Ophthalmoscopic examination revealed a whitish yellow elevated choroidal lesion and serous retinal detachment in the left eye. Fluorescein angiography demonstrated multiple pinpoint leaks in the early phase and progressive pooling of dye into the subretinal space in the late phase. In magnetic resonance imaging, the tumor showed a hyperintense image in both T1 and T2-weighted images. Autopsy was performed and histopathological examination of the eye showed that the tumor cells were polygonal in shape, and had round or oval nuclei, but the cytoplasms had little melanin pigment. Immunohistochemistry for S-100 and HMB-45 antibody showed positive staining in choroidal tumor and other metastatic lesions, indicating that they were metastatic tumors from cutaneous malignant melanoma (amelanotic melanoma cells).

Choroid Neoplasms↗
PubMed1994

Effect of 5-fluoro- and 5-bromouracil substitution on the translation of human thymidylate synthase mRNA.

The synthesis of thymidylate synthase (TS) from 5-fluorouracil (FUra)- and 5-bromouracil (BrUra)-substituted mRNAs was examined to investigate the effect of incorporation of uracil (Ura) analogs on translation. Human TS cDNA was transcribed in the presence of Ura-, FUra-, or BrUTP to obtain 100% substituted mRNA. The mRNAs were translated in a rabbit reticulocyte lysate system. The TS protein that was formed from each of the templates reacted identically with TS antibody in Western blots. Time courses of TS formation revealed a characteristic peak which occurred at 45 min for the Ura- and FUra-RNAs and at 2 h for the BrUra-RNA. Substitution of Ura with FUra did not alter the rate of translation, while substitution of BrU for Ura decreased the rate of translation. Substitution of Ura with FUra or BrUra enhanced the stability of the mRNAs in the rabbit reticulocyte lysate by 3- and 10-fold, respectively. Incorporation of BrUra influenced the binding and catalysis on the ribosome, resulting in a 3.5-fold greater rate of activation (Kact) and 6-fold lower Vmax than the equivalent values for the Ura- and FUra-substituted mRNAs. Nondenaturing gel electrophoresis revealed that different conformations exist among the mRNAs. These data show that translation can be influenced by the incorporation of fraudulent bases into mRNA and those bases that stabilize RNA secondary structure will have the greatest inhibitory effect on translation.

Base Sequence↗
PubMed1994

Evaluation of melanin-related metabolites as markers of melanoma progression.

BACKGROUND: Urinary excretion of 5-S-cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. Melanomas produce not only 5-S-CD but also 5,6-dihydroxyindole-2-carboxylic acid (5,6DHI2C) as major intermediates in melanin formation. 5,6DHI2C is then metabolized to the two O-methyl derivatives, 5H6MI2C and 6H5MI2C. The aim of this study was to determine which marker in serum and urine most sensitively reflected the progression of melanoma. METHODS: Serum and 24-hour urine samples were collected and assayed serially by high-performance liquid chromatography every 1 to 4 months in 28 patients with primary or recurrent melanomas, for up to 48 months. RESULTS: Serum concentration and urinary excretion of 5-S-CD and 6H5MI2C in patients with melanoma without metastases were close to those obtained from normal subjects. Metastases developed in 9 of the 28 patients. In seven of these nine patients, serum or urinary 5-S-CD values were elevated before or at the time of clinical detection of visceral metastases. However, serum 5-S-CD was elevated significantly earlier and reflected melanoma progression better than the physical examination and/or laboratory tests, such as scintigraphy and echography. Serum 6H5MI2C values exceeded the normal range shortly before death in three patients, and urinary 6H5MI2C did not increase at any stage in most patients, therefore these metabolites did not reflect progression of disease. CONCLUSIONS: Among the four markers, serum 5-S-CD appears to be the best biochemical marker for the detection of progression of melanotic melanoma, a value of more than 10 nmol/l suggesting the presence of metastasis.

Adult↗
PubMed1994

Detection of intracranial aneurysms by three-dimensional time-of-flight magnetic resonance angiography.

The purpose of this study was to investigate the reliability of magnetic resonance angiography (MRA) for detection of intracranial aneurysms. Ninety-six consecutive patients who underwent both MRA using the three-dimensional time-of-flight technique (3D TOF) with the rephase/dephase subtraction method and conventional angiography were reviewed. MRA showed 22 aneurysms in 19 patients, and conventional angiography 28 aneurysms in 23 patients. The sensitivity of MRA was thus 79% for aneurysms in 83% of patients. MRA showed no aneurysm in 67 of 73 patients without aneurysms; its specificity was therefore 92%. The 6 false positive interpretations were suspected internal carotid artery aneurysms.

Adolescent↗