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Biomedical subjects

H Horiguchi

Publications and source records attributed to H Horiguchi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cadmium-induced acute hepatic injury is exacerbated in human interleukin-8 transgenic mice.

It is reported repeatedly that severe hepatocellular necrosis along with infiltration of neutrophils occurs after acute cadmium exposure. Neutrophils, which migrate by the gradient of chemoattractants such as interleukin-8, are believed to play an important role in inflammation at the damaged sites. To investigate whether neutrophils aggravate or repair the liver injury induced by cadmium, we checked the hepatotoxic effects of cadmium on human interleukin-8 transgenic mice (hIL-8Tg), which overexpressed IL-8 and displayed an inability of neutrophil migration resulting from both the lack of chemotactic gradient and the downregulation of l-selectin on the surface of neutrophils. A significantly lower survival rate was observed in hIL-8Tg compared with wild-type mice after subcutaneous administration of cadmium. Evident liver injury characterized by abrupt increases in plasma GOT and GPT levels was found in hIL-8Tg at 18 h after cadmium administration. Histological examinations, including H & E staining and esterase staining, revealed the infiltration of numerous neutrophils into the damaged liver tissues in wild-type mice, and the inhibition of the neutrophil migration into the liver as well as enhanced hepatocellular necrosis in hIL-8Tg. Peripheral white blood cell and polymorphonuclear cell counts increased and reached their peaks at 12 h after cadmium administration in wild-type mice, whereas the increase in blood leukocyte counts was delayed in hIL-8Tg. There was no significant difference in the amounts of cadmium accumulated in liver and kidneys between wild-type mice and hIL-8Tg. In conclusion, an acute cadmium hepatotoxic effect was exacerbated in hIL-8Tg resulting from inhibited neutrophil migration, suggesting that migrated neutrophils can prevent aggravation of liver injury by acute cadmium administration.

Alanine Transaminase↗
PubMed2000

Erythropoietin induction in Hep3B cells is not affected by inhibition of heme biosynthesis.

Erythropoietin (Epo) is one of the physiologically important genes whose transcription is up-regulated by hypoxia. Our laboratory previously proposed that the sensor of this event is a heme protein which turns over rapidly. We have investigated the effects of four inhibitors of heme synthesis (4,6-dioxoheptanoic acid (DHA), isoniazid (INH), N-methyl protoporphyrin IX (MPP), and deferoxamine mesylate (DSF)) on hypoxia-, cobalt-, and DSF-induced erythropoietin (Epo) mRNA expression, heme biosynthesis, and cell viability in Hep3B cells. DHA (0.1-1.0 mM) inhibited heme biosynthesis more than 85%, but did not suppress Epo mRNA expression. Epo mRNA expression was inhibited only at higher concentrations of DHA (2, 4 mM) which also inhibited cell viability. No suppression of Epo mRNA expression by INH was observed at doses known to inhibit heme biosynthesis. MPP did not suppress Epo mRNA expression although it showed an inhibitory effect on heme biosynthesis without any decreased cell viability. 130 microM DSF, a dose which inhibited heme biosynthesis without cell toxicity, suppressed hypoxia-induced Epo mRNA expression, but enhanced cobalt-induced Epo mRNA expression. These results show that although the oxygen sensor is probably a heme protein it does not turn over rapidly. Therefore, cobalt is unlikely to act by substituting for heme iron.

Cell Survival↗
PubMed2000

Renin-dependent cardiovascular functions and renin-independent blood-brain barrier functions revealed by renin-deficient mice.

Renin plays a key role in controlling blood pressure through its specific cleavage of angiotensinogen to generate angiotensin I (AI). Although possible existence of the other angiotensin forming enzymes has been discussed to date, its in vivo function remains to be elucidated. To address the contribution of renin, we generated renin knockout mice. Homozygous mutant mice show neither detectable levels of plasma renin activity nor plasma AI, lowered blood pressure 20-30 mm Hg less than normal, increased urine and drinking volume, and altered renal morphology as those observed in angiotensinogen-deficient mice. We recently found the decreased density in granular layer cells of hippocampus and the impaired blood-brain barrier function in angiotensinogen-deficient mice. Surprisingly, however, such brain phenotypes were not observed in renin-deficient mice. Our results demonstrate an indispensable role for renin in the circulating angiotensin generation and in the maintenance of blood pressure, but suggest a dispensable role for renin in the blood-brain barrier function.

Angiotensin I↗
PubMed2000

Hypersegmentation of inflammatory cells in Langerhans cell granulomatosis.

Langerhans cell granulomatosis (LCG) is characterized by a mixture of Langerhans cells and eosinophils in varying proportions. The characteristic morphology of Langerhans cells have already been described in many articles, but little attention has been paid to inflammatory cells. We examined six cases of Langerhans cell granulomatosis, which had originally been diagnosed as eosinophilic granuloma. Inflammatory cells present in LCG showed hypersegmentation. Twenty percent to 70% of eosinophils had three or more segmented nuclei, and 10-25% of neutrophils had five or more segmented nuclei. Such findings have never been described, and we believe hypersegmentation to be a feature of LCG. Furthermore, we emphasize that eosinophils in LCG mimic neutrophils in ethanol-fixed preparations, and thus may be a pitfall in making a diagnosis in cytology and intraoperative consultation.

Adult↗
PubMed2000

Gastrointestinal stromal tumor with skeinoid fibers of the ileum.

Gastrointestinal stromal tumor (GIST) is not uncommon among gastrointestinal nonepithelial tumors, but there are few reports describing the cytologic findings. We report a case of GIST with skeinoid fibers in scrape cytology preparation. The patient was a 53-year-old man with a tumor in the small intestine. Scrape preparations from the cut surface of the resected tumor revealed cellular material composed of spindle cells showing loose clusters or single cells. The nuclei were spindled, elongated or cigar-shaped, and relatively uniform. The cytoplasm was fragile and demonstrated a finely fibrillar material. Dense hyaline materials with irregular outline were observed within the loose clusters composed of the tumor cells. The hyaline materials were also observed in the background. Histologic preparation showed spindle cells arranged in a fascicular or storiform pattern. Most eosinophilic globules were distributed between the tumor cells. The globules were positive in periodic acid-Schiff reaction, and were stained blue with Masson's trichrome stain. Immunohistochemically, the tumor cells were strongly and diffusely positive for c-kit, focally and weakly positive for alpha-smooth muscle actin, and negative for CD34 and S-100 protein. We emphasize that skeinoid fibers are characteristic of GIST arising in the small intestine, and their presence predicts a good prognosis, even in malignant GIST.

Gastrointestinal Neoplasms↗
PubMed2000

Dilated rough endoplasmic reticulum corresponding to septate cytoplasmic vacuoles in papillary thyroid carcinoma.

Septate cytoplasmic vacuoles, which are one of the cytologic findings characteristic of papillary thyroid carcinoma, are small, uniform, and well-defined vacuoles, with defined strands of cytoplasm separating them. We report on a case with histologic and ultrastructural findings corresponding to septate cytoplasmic vacuoles, which have not been previously described. The patient was a 51-yr-old man with a mass in the left anterior of the neck, measuring 4.0 x 3.5 cm in diameter. Aspiration cytology smears revealed findings typical of papillary thyroid carcinoma, including papillary tissue fragments, intranuclear inclusions, nuclear grooves, powdery chromatin, and psammoma bodies. The tumor cells which were located at the periphery of small three-dimensional clusters, and others which showed a sheet-like arrangement, demonstrated uniform, small vacuoles in relatively abundant, dense cytoplasm. Histologically, a small number of papillary thyroid carcinoma cells with multiple vacuoles were observed, which were limited to the hobnail-shaped cells located at papillary configurations or floating tumor cells within the papillary lumen. Ultrastructurally, the hobnail-shaped tumor cells demonstrated various-sized dilated rough endoplasmic reticulum and rich heterochromatin. We emphasize that septate cytoplasmic vacuoles correspond to dilated rough endoplasmic vacuoles and are probably related to degenerative changes.

Carcinoma, Papillary↗
PubMed2000

Well-differentiated adenocarcinoma of the gallbladder mimicking minimal deviation adenocarcinoma of the cervix.

We report a case of well-differentiated adenocarcinoma of the gallbladder, histologically mimicking minimal deviation adenocarcinoma (MDA) of the cervix. A 71-year-old Japanese male underwent cholecystectomy because of the suggestion of gallbladder carcinoma. The resected gallbladder showed a localized thickening of the gallbladder wall with a polypoid lesion measuring 12x7 mm in diameter. Microscopically, the polypoid lesion proved to be a well-differentiated adenocarcinoma composed of columnar cells with a clear cytoplasm. In the thickened gallbladder wall, well-formed glands were extensively distributed; they were surrounded by a slightly desmoplastic reaction instead of lamina propria, or were directly in contact with smooth muscle cells. The diagnostic criteria for cervical MDA may be useful in distinguishing well-differentiated adenocarcinoma of the gallbladder from benign conditions, such as Rokitansky-Aschoff sinus and adenomyomatosis. It is remarkable that the tumor cells of the present case expressed gastric type mucin which is characteristic of mucinous type cervical MDA.

Adenocarcinoma↗
PubMed2000

Vasitis nodosa: immunohistochemical findings--case report.

We report the immunohistochemical features of vasitis nodosa and discuss the differential diagnosis. The patient was a 42-year-old Japanese man with bilateral small indurations of the vas deferens at the site of a previous vasectomy. Microscopically, small-sized ducts proliferated within the muscular wall of the vas deferens, and focally in the surrounding connective tissue. Immunohistochemically, most proliferating glandular cells were strongly positive for cytokeratins 7, 19, and 34betaE12, and vimentin. Epithelial membrane antigen and Leu-M1 reacted against the luminal surface of the cells. Focally, glandular cells were also positive for CA125. Cytokeratin 20, carcinoembryonic antigen, and prostate-specific antigen were negative. We discuss the immunohistochemical differentiation of vasitis nodosa from prostatic adenocarcinoma, adenocarcinoma of the rete testis, and adenomatoid tumor.

Adult↗
PubMed2000

Expression of hnRNP A2/B1 proteins in human cancer cell lines.

The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is recently reported informative as a marker of lung cancer for early detection. To examine whether the expression of the proteins is specific for lung cancer, immunological analyses were performed both in lung and non-lung cancer cell lines. In immunostaining and Western blotting, the expression of A2/B1 was observed not only in the lung cancer cells but also in non-lung cancer cells. The expression of hnRNP A2/B1 is not specific for lung cancer and quantitative determination of A2/B1 is required to elucidate their significance in carcinogenesis.

Heterogeneous-Nuclear Ribonucleoprotein Group A-B↗
PubMed2000

Ovarian fibrothecoma with massive edema.

We report a rare case of ovarian fibrothecoma with massive edema. The patient was a 59-year-old woman with a left ovarian mass measuring 11 x 10 x 7 cm. Magnetic resonance images revealed a solid mass showing unhomogeneous content with predominantly high signal intensity on T2-weighted image. Microscopically, the ovarian mass was composed of a cellular area and an edematous hypocellular area. The latter accounted for more than 75% of the tumor. In the cellular area, spindle-shaped or plump tumor cells were randomly distributed or arranged in a fascicular fashion. These cells contained abundant intracytoplasmic lipid. There was dense collagenous connective tissue in the stroma of the cellular areas. In contrast, in the edematous areas spindle or stellate cells were scattered. Alcian blue stain revealed only a small amount of stromal mucin even in the edematous areas. The microscopic findings were consistent with that of fibrothecoma with massive edema. The present case must be differentiated from massive edema of the ovary and sclerosing stromal tumor of the ovary. Immunohistochemistry was not helpful in distinguishing them. The age of the patient and careful histologic observation are important.

Diagnosis, Differential↗
PubMed1999

Male sterility in transgenic mice expressing activin betaA subunit gene in testis.

Activins and inhibins, which are endocrine regulators of anterior pituitary function, have also been reported to participate in the paracrine and autocrine regulation of reproductive function. To determine the in vivo effects of overexpressed activin/inhibin, we generated transgenic mice carrying the human activin/inhibin betaA subunit mini gene under the regulatory control of the mouse methallothionein promoter. In one of the transgenic line analyzed, the betaA subunit gene was preferentially expressed in the testis. Ectopic and allochronic expression of the betaA gene started at 3 weeks after birth and transgenic male mice became sterile in the ensuing several weeks. Histological analysis revealed testicular degeneration in these mice. The results from this transgenic line strongly support the in vivo activity of activin/inhibin in male reproductive functions.

Animals↗
PubMed1999

Induction of hydroxyapatite resorptive activity in bone marrow cell populations resistant to bafilomycin A1 by a factor with restricted expression to bone and brain, neurochondrin.

Bone, one of the favored sites for tumor metastasis, is a dynamic organ undergoing formation and resorption. We found bone metastasis with osteolytic lesion in the bone marrow of the femur by injecting BW5147 T-lymphoma cells into the tail vein of AKR mice. To understand this bone destruction, we constructed a cDNA library from BW5147 with a cloning vector that allowed in vitro synthesis of mRNAs, and then identified a particular cDNA clone by adding the conditioned medium from Xenopus oocytes following injection of the mRNA synthesized in vitro to primary bone marrow heterogeneous cell populations on hydroxyapatite thin films. By means of this method, we isolated a factor with 16% leucine residues, termed neurochondrin, that induces hydroxyapatite resorptive activity in bone marrow cells resistant to bafilomycin A1, an inhibitor of macrophage- and osteoclast-mediated resorption. Expression of the gene was localized to chondrocyte, osteoblast, and osteocyte in the bone and to the hippocampus and Purkinje cell layer of cerebellum in the brain. This may provide insights into the molecular mechanisms underlying bone resorption with potential implications for the activation of cells other than macrophages and osteoclasts in bone marrow cells.

Amino Acid Sequence↗
PubMed1999

Molecular characterization of the hnRNP A2/B1 proteins: tissue-specific expression and novel isoforms.

hnRNP A2/B1 proteins are among the most abundant pre-mRNA-binding proteins of vertebrates and structurally similar to hnRNP A1. We have produced two specific monoclonal antibodies against A2 and B1 and studied their molecular characteristics and in vivo expression in rat tissues. Immunoprecipitation demonstrated that the hnRNP A2/B1 complexes contain many snRNP (small nuclear ribonucleoprotein) proteins, consistent with their role in pre-mRNA splicing. RNA polymerase II inhibition causes nucleocytoplasmic shuttling of A2 and B1. In most tissues, they are localized in the nucleus; however, in the squamous epithelium of the skin and esophagus A2 is also distributed in the cytoplasm. The relative amounts of A2 and B1 are not constant among different tissues. In the adrenal, only A2 is extremely abundant in the medulla but not in the cortex. In the testis the expression of A2 and B1 are observed through spermatogenesis, and different from A1 which is stringently repressed in spermatocytes. We also found and cloned a novel testis-specific isoform of A2/B1, namely hnRNP B0. The difference of expression of A2, B1, and A1 provides new information on their in vivo roles. The diversity of A/B group hnRNP proteins may have important effects on the posttranscriptional regulation of cell-specific gene expression.

Amino Acid Sequence↗
PubMed1999

Lack of class II transactivator causes severe deficiency of HLA-DR expression in small cell lung cancer.

Small cell lung cancer (SCLC) is characteristically not associated with tumour-infiltrating lymphocytes. Since SCLC has been reported to show marked reduction of class I HLA, the reduced expression has been considered a means of escaping anti-cancer immunity. However, HLA-DR expressed in cancer cells is now known to contribute to anti-cancer immunity. To clarify the difference in HLA-DR expression between SCLC and non-small cell lung cancer (NSCLC), and the mechanism, the expression and the cis- and trans-acting factors involved were investigated. HLA-DR was not immunohistochemically detected in any SCLC and could not be induced by interferon gamma (IFN-gamma) in any SCLC cell line, whereas HLA-DR was expressed to varying degrees and was easily induced in NSCLC. SCLC cell lines lacked class II transactivator (CIITA) even after IFN-gamma induction, whereas NSCLC cell lines expressed CIITA. The other class II HLA-specific transcription factors were expressed and genomic DNA of HLA-DR, including the promoter, was conserved well both in SCLC and in NSCLC cell lines. CIITA transfection improved the expression of HLA-DR in SCLC. In conclusion, the lack of CIITA results in severe deficiency of HLA-DR expression in SCLC. Since CIITA has also been reported to induce class I HLA, CIITA transfection might make it possible to establish effective anti-cancer immunotherapy against SCLC through the up-regulation of class I and class II HLA.

Blotting, Northern↗
PubMed1999

Developmental stage-specific involvement of angiotensin in murine nephrogenesis.

Angiotensinogen-deleted mice (Agt-KO) show phenotypes of hypotension and renal atrophy. To investigate whether an alternative pathway other than angiotensin II (AII), i.e., processed angiotensin fragments, may play a biological role in nephrogenesis, we analyzed a congenic line of Agt-KO fetuses and neonates derived from two sources: one (Agt-KO/He) from mating with heterozygous angiotensinogen-deleted mice and the other (Agt-KO/Ho) from mating homozygous angiotensinogen-deleted mice. Although Agt-KO/He did not show a typical phenotype at birth, these mice showed papillary atrophy 2 weeks later and thereafter, a marked increase in renal size, i.e., pelvic dilatation. In contrast, Agt-KO/Ho showed renal abnormalities at birth and subsequently died. TUNEL staining and electron microscopy revealed that accelerated papillary apoptosis was present at birth in Agt-KO/Ho and caused abnormal papillary development; however, apoptosis was not detected in Agt-KO/He, suggesting that different mechanisms for the abnormal renal development exist in Agt-KO/He and Agt-KO/Ho. Two-week administration of an angiotensin fragment (3-8), angiotensin IV (AIV), to Agt-KO/He markedly attenuated the renal atrophy, decreasing the incidence from 81% to 14%. However, administration of AIV to fetal Agt-KO/Ho through the mother did not decrease the incidence. This is marked contrast to AII, which prevented renal atrophy in both fetal and neonatal periods. It is therefore suggested that AIV is involved in nephrogenesis in a developmental stage-specific manner.

Angiotensin II↗
PubMed1999

Double pituitary adenomas: six surgical cases.

While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

Acromegaly↗
PubMed1999

Loss of chromosome 10 in glioblastoma: relation to proliferation and angiogenesis.

Loss of chromosome 10 was assessed in 17 specimens of glioblastoma (GBM) by fluorescence in situ hybridization (FISH) technique using the centromere probe for chromosome 10. Cytospinned smear specimens were prepared from paraffin-embedded specimens. The percentage of nuclei containing a single fluorescent signal ranged from 19.2 to 88. 0% (mean, 49.3%). Thirteen tumors (76.5%) were designated as monosomy 10 because the proportion of single-signal nuclei exceeded the cut-off value (31.5%: mean of five control materials +3 standard deviations). The results confirmed the importance of the loss of chromosome 10 for the development of GBM, although no significant correlation was demonstrated between the loss of chromosome 10 and survival. In addition, proliferation potential and angiogenesis of GBM were immunohistochemically analyzed using antibodies against Ki-67 antigen (MIB-1), factor VIII-related antigen (FVIII R/Ag) and vascular endothelial growth factor (VEGF), respectively. The labeling indices of MIB-1 (1.5-57.8%) and the number of blood vessels immunoreactive for FVIII R/Ag (18-279/10 high-power fields) were not significantly related to the loss of chromosome 10. Vascular endothelial growth factor immunoreactivity in areas microvessels were counted was seen in 12 cases. However, neither the loss of chromosome 10 nor number of vessels was not correlated with VEGF expression. Other genetic abnormalities as well as loss of chromosome 10 may be involved in the cell proliferation and angiogenesis of GBM.

Adult↗