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Biomedical subjects

T Hirose

Publications and source records attributed to T Hirose.

At least 199 records · Page 11Linked to original sources

Immunohistochemical localization of lysosomal cathepsin D in schwannomas.

The immunohistochemical localization of cathepsin D (CD) was demonstrated for the first time in 54 schwannomas (32 intra- and 22 extracranial; 47 benign and 7 malignant) and 5 normal nerve fibers. Granular or vesicular CD-reactive structures were observed in all normal Schwann cells. All tumors contained CD-reactive tumor cells, although the population of CD-reactive tumor cells, the density, intracellular localization, and morphology of CD-reactive structures, and the intensity of CD immunoreactivity varied from case to case, portion to portion, and cell to cell, differing variously from those in normal Schwann cells. The variations were greater in malignant than in benign schwannomas. In mildly degenerate tumor cells, CD immunoreactivity was increased, possibly in response to the increased intracellular degenerate proteins, suggesting that the mechanism of induction of lysosomal proteases preserved in normal cells is not affected by the process of neoplastic transformation. In lesions of severe degeneration or necrosis, CD immunoreactivity was lost in most tumor cells but was strong in macrophages invading the lesions and perivascular regions. CD immunoreactivity was observed at various intensities in tumor cells in the Antoni type A area but not in most tumor cells in the Antoni type B area, suggesting that Antoni type B lesions show degenerative changes. The presence of CD-reactive tumor cells in all tumors examined and strong CD immunoreactivity observed at the invasion front of tumors in some cases of benign or malignant schwannoma suggests the possible role of CD in tumor invasion in some cases.

Adult↗

Epithelioid angiosarcoma of bone.

Angiosarcoma of bone is a rare, high-grade sarcoma of vascular origin. This article describes an epithelioid angiosarcoma in the humerus of a 48-year-old man. A multilocular osteolytic lesion with undefined margins and destroyed cortical and medullary bone, associated with a large soft tissue mass was demonstrated radiologically in the proximal metaphysis of the right humerus. The tumor, resected by amputation, was composed mostly of proliferating malignant cells with an epithelioid morphology. It had a predominantly sheet-like growth pattern, and an occasional pseudoglandular or alveolar arrangement, mimicking an adenocarcinoma. The dilated anastomotic vascular spaces lined by epithelioid endothelial cells and the intracytoplasmic lumina/vacuoles that sometimes contained erythrocytes suggested focal endothelial differentiation. On immunohistochemical investigation, many neoplastic cells expressed cytokeratin and endothelial markers: factor-VIII related antigen, CD31, and UEA-I. The ultrastructure of the tumor was consistent with that of an angiosarcoma. Our patient died of disease shortly after the diagnosis, implying an aggressive clinical course. Awareness of the existence of skeletal epithelioid angiosarcoma, combined with the identification of intracytoplasmic lumina, or at least small vasoformative foci, and immunohistochemical positivity for endothelial markers provide the best guide for distinguishing this tumor from metastatic carcinomas.

Biomarkers, Tumor↗

Oxygen dependency of epidermal growth factor receptor binding and DNA synthesis of rat hepatocytes.

BACKGROUND/AIMS: Changes in oxygen availability modulate replicative responses in several cell types, but the effects on hepatocyte replication remain unclear. We have studied the effects of transient nonlethal hypoxia on epidermal growth factor receptor binding and epidermal growth factor-induced DNA synthesis of rat hepatocytes. METHODS: Lactate dehydrogenase activity in culture supernatant, intracellular adenosine triphosphate content, 125I-epidermal growth factor specific binding, epidermal growth factor receptor protein expression, and 3H-thymidine incorporation were compared between hepatocytes cultured in hypoxia and normoxia. RESULTS: Hypoxia up to 3 h caused no significant increase in lactate dehydrogenase activity in the culture supernatant, while intracellular adenosine triphosphate content decreased time-dependently and was restored to normoxic levels by reoxygenation (nonlethal hypoxia). Concomitantly, 125I-epidermal growth factor specific binding to hepatocytes decreased time-dependently (to 54.1% of normoxia) and was restored to control levels by reoxygenation, although 125I-insulin specific binding was not affected. The decrease in 125I-epidermal growth factor specific binding was explained by the decrease in the number of available epidermal growth factor receptors (21.37+/-3.08 to 12.16+/-1.42 fmol/10(5) cells), while the dissociation constant of the receptor was not affected. The change in the number of available receptors was not considered to be due to receptor degradation-resynthesis, since immunodetection of the epidermal growth factor receptor revealed that the receptor protein expression did not change during hypoxia and reoxygenation, and since neither actinomycin D nor cycloheximide affected the recovery of 125I-epidermal growth factor binding by reoxygenation. Inhibition of epidermal growth factor-induced DNA synthesis after hypoxia (to 75.4% of normoxia by 3 h hypoxia) paralleled the decrease in 125I-epidermal growth factor binding. CONCLUSIONS: Transient hypoxia, which caused no increase in lactate dehydrogenase leakage but affected intracellular adenosine triphosphate levels, did, however, modulate the number of available epidermal growth factor receptors without affecting the receptor protein expression, and inhibit the epidermal growth factor-induced DNA synthesis of hepatocytes. This suggests that even transient nonlethal hypoxia affects the epidermal growth factor-induced DNA synthesis of rat hepatocytes through reversible changes in the epidermal growth factor receptor molecule, which depends on oxygen availability.

Adenosine Triphosphate↗

A phase I study of irinotecan and infusional cisplatin with recombinant human granulocyte colony-stimulating factor support in the treatment of advanced non-small cell lung cancer.

We conducted a phase I study to examine whether support with recombinant human granulocyte colony-stimulating factor (rG-CSF) would permit dose intensification of irinotecan (CPT-11) in combination with cisplatin (20 mg/m2 x 5 days) in non-small cell lung cancer (NSCLC) patients. CPT-11 was administered by bolus infusion at a starting dose of 100 mg/m2 on day 1, followed by serial increments at 20 mg/m2, given every 4 weeks. The major toxic effects were granulocytopenia and diarrhoea. The response rate was 55% (11/20). The optimum dose for phase II studies appears to be 20 mg/m2/day (5-day continuous infusion) for cisplatin and 160 mg/m2 (day 1) for CPT-11 with rG-CSF support in NSCLC.

Aged↗

Characterization of mechanisms of interleukin-6 gene repression by estrogen receptor.

Estrogens are the most effective agents available for preventing osteoporosis, and their principal role in bone metabolism is the inhibition of interleukin-6 (IL-6) production in osteoblasts and bone marrow stromal cells. We examined the mechanism of inhibitory effect of estrogens on the 190 bp proximal promoter of the IL-6 gene. Promoter activity induced by transfection of both NF-kappaB p65 subunit and NF-IL6 was decreased by 45% by estradiol (E2)-estrogen receptor (ER) complexes. The inhibitory effect of E2 was also observed on a mutant IL-6 promoter in which the NF-IL6 binding site was disrupted. E2 repressed the wild-type promoter activity induced by NF-kappaB p65 subunit alone, but had no effect on that induced by NF-IL6 alone. These findings suggested that estrogens inhibit IL-6 production by interfering with the function of NF-kappaB rather than that of NF-IL6. The ER mutant, HE19, which does not contain the A/B domain, repressed the induction by NF-kappaB to the same extent as wild-type ER HE0, whereas the effect of C-terminal deletion mutant, HE21, was only marginal. The antiestrogen, 4-hydroxytamoxifen (OHT), had no effect on IL-6 promoter activity, suggesting that E2-induced conformational change of the hormone binding domain plays an important role in protein-protein interaction between ER and NF-kappaB. E2 had no effect on the nuclear translocation of NF-kappaB, and electrophoretic mobility shift assay showed that the presence of E2-ER complexes did not affect the ability of NF-kappaB to bind to specific DNA sequences.

Animals↗

cDNA cloning and tissue specific expression of a gene for sucrose transporter from rice (Oryza sativa L.).

We describe the cloning and expression analysis of a sucrose transporter cDNA from a monocot (the rice plant, Oryza sativa L.). The cDNA clone (OsSUT1) encoded an open reading frame of 1,611 bp (537 amino acids) and showed 76.8 to 79.7% similarity at the amino acid level to other sucrose transporters of dicot species. The predicted membrane topology of OsSUT1 protein is made up of 12 transmembrane helices which is consistent with most of the mono- and disaccharide transporters previously identified. When OsSUT1 cDNA was introduced into yeast and expressed, the cells rapidly accumulated sucrose demonstrating that OsSUT1 does, in fact, encode a sucrose transporter. From genomic Southern hybridization OsSUT1 appeared to be a single copy gene. OsSUT1 was expressed in source organs such as leaf blade, leaf sheath and germinating seed whereas little or no expression was observed in some sink organs such as the panicles before heading and the roots. Transcript was observed at high levels in panicles after heading, particularly in the portion containing endosperm and embryo. In addition, expression of OsSUT1 was high in etiolated seedlings and decreased during light-induced greening.

Amino Acid Sequence↗

Pleuropulmonary blastoma: fluorescence in situ hybridization analysis indicating trisomy 2.

We report a case of pleuropulmonary blastoma occurring in the right upper lobe and pleura of a 29-month-old boy. Histologically, the tumor was composed of undifferentiated mesenchymal cells with occasional rhabdomyoblastic and chondroid differentiation. Immunohistochemical analysis showed vimentin immunoreactivity in most of the tumor cells, myoglobin, desmin, and actin in the rhabdoid cells, and S-100 protein in the chondroid cells. Fluorescence in situ hybridization (FISH) analysis showed trisomy 2 and normal chromosomal copy numbers for chromosomes 7, 12, 17, 18, and X in the majority of the tumor cell nuclei. The identification of trisomy 2 in the current pleuropulmonary blastoma confirms a previous cytogenetic finding of chromosome 2 abnormality with cultured metaphase cells of a similar case, indicating that the acquisition of an additional chromosome 2 copy in pleuropulmonary blastoma is a nonrandom chromosomal alteration and that pleuropulmonary blastoma is cytogenetically distinct from pulmonary blastoma in which chromosome 2 is bisomic. It is also suggested that pleuropulmonary blastoma may have an intimate tumorigenetic relationship with embryonal rhabdomyosarcoma.

Actins↗

Utility of low-dose helical CT as a second step after plain chest radiography for mass screening for lung cancer.

We evaluated the usefulness of low-dose helical computed tomography (CT) as a routine second step in patients screened for lung cancer with plain chest radiography (PCR). Of 5,437 people who underwent mass screening for lung cancer by PCR, further work-up was required for 230 because of abnormal findings. Of 221 subjects who had CT as a second step, abnormal shadows were detected in 110 and no abnormal shadows were seen in 111. Screening CT (helical scan; beam collination, 10 mm; pitch of 2:20 mm/s; and tube current, 50 mA) detected 17 lung cancers, 87 benign lesions, and 6 extrapulmonary lesions, with an average diameter of 10 mm (range, 2-35 mm). All lung cancers were peripheral (12 stage I, 4 stage IIIA, and 1 stage IV). In 40% of screened subjects, 37 with benign lesions and 7 with lung cancer (6 stage I), lesions were delineated only by screening CT. In conclusion, low-dose helical CT was found to be useful as a second step in patients who have been screened for lung cancer by PCR and can delineate the early stage of lung cancer.

Adenocarcinoma↗

Season of birth of schizophrenics in a recent Japanese sample.

An excess of schizophrenic births in winter or early spring is a well replicated finding in studies on Western populations. However, there are few studies on Asian populations, and their results are not consistent. We examined the seasonality of schizophrenic births in Japanese subjects (n = 1024) born between 1955 and 1960. Our results showed a significant inverse relationship between temperature and number of schizophrenic births, which is in line with the findings in Western populations. In our data, observed reduction of schizophrenic births in summer was more marked than excess births in winter. We suggest the possibility that birth in summer may have some advantage in brain growth early in life, which results in reducing the risk of developing schizophrenia.

Adult↗

Functional outcome and late complications in patients with continent urinary reservoirs.

BACKGROUND: We reviewed the functional outcome and late complication of continent urinary reservoirs (CUR) constructed with a cecocolonic segment, including the Indiana pouch, in 37 patients treated in our clinic. METHODS: The CUR procedure was performed on 37 patients, creating partially detubularized (PD) reservoirs in 9 patients, totally detubularized (TD) reservoirs in 16 patients and reservoirs with an ileal patch (IP) in 12 patients. Continence was achieved by the nipple valve in 10 patients and by ileal plication in 27 patients. The mean follow-up period was 46 months (range, 15 to 87 months). The function of the reservoir was evaluated by measurement of the intrareservoir pressure. RESULTS: Patients with the TD reservoir had less frequent appearance of involuntary, phasic elevation of the intrareservoir pressure (30.8%) than those with the PD reservoir (62.5%). In contrast, this phasic elevation was found in only 1 patient with an IP reservoir. The IP reservoir had the largest capacity accompanied by the lowest maximum intrareservoir pressure. Total incontinence was observed in 2 patients with ileal plication due to disruption of the plicated sutures on the terminal ileum. Frequent difficulty in catheterizing the reservoir was found in 2 patients, and reservoir-ureter reflux was found in 3 renal units. The serum chloride level was significantly elevated after surgery, however, in most patients the levels remained within normal limits. CONCLUSION: Our experience of the outcome and late complications of reservoirs indicates that the cecocolonic reservoir with an ileal patch and stapled ileal plication, i.e., the Indiana pouch, is a better choice for continent urinary diversion for patients who need a cystectomy.

Adult↗

Five years' experience with the Grating disc. A simplified method of evaluating vision in young children.

The Grating Disc (GD) is a simplified visual test designed for children 18 months to 4 approximately 5 years. Two hundred pediatric patients (103 males, 97 females; aged 5 months to > 6 years) participated in this study to determined how the GD visual acuity (VA) correlates with the Preferential Looking (PL) VA. Forty-six percent of the patients had varying degrees of retinopathy of prematurity. The PL acuity was determined using the up-and-down staircase procedure. To measure GD acuity, six GDs with vertical gratings equivalent to acuities of 20/1920 to 20/60 were used. The examiner presented one GD simultaneously with the homogeneous disc from 57 cm. The VA was determined by the finest GD that the child could differentiate from the homogeneous disc. The overall correlation between the PL and the GD acuities was very high (R2 = 0.861). One hundred twenty-eight patients (64.0%) had an acuity agreement within 0.5 octave and 178 (89.0%) patients were within 1.0 octave. When the PL acuity was > or = 20/100, the GD and PL acuities showed good agreement. When the PL acuity was poorer, the GD acuity was poorer than the PL acuity. Although the GD acuity tended to be lower than the PL acuity in severely visually impaired patients, the GD acuity agreed with the PL in most visual assessments of young children. GD testing could be a useful alternative when sophisticated assessment systems such as the PL are unavailable.

Adolescent↗

A monoclonal antibody affects chromophore apoprotein interactions of phytochrome A.

A monoclonal antibody designated Mep-1 was raised against phytochrome A from pea (Pisum sativum L.). The binding of this antibody (class IgG1) to partially degraded phytochrome (114 kDa) caused a considerable increase in the far-red peak at the red-light-induced stationary state. The effect reached a plateau value when the antibody and phytochrome were present in approximately equimolar amounts. The dark transformation of the far-red-light-absorbing form to the red-light-absorbing form of the 114 kDa phytochrome was inhibited by the addition of the antibody. However, binding of the antibody to the undegraded 121 kDa phytochrome had no effects on the spectrum of the red-light-induced steady state. The site at which the antibody bound to phytochrome was determined to be between amino acid residues 256 and 383 of pea phytochrome A. This is the first report of a monoclonal antibody that enhances the far-red absorption of phytochrome in the red-light-induced photostationary state.

Animals↗

Computed tomography and magnetic resonance findings in two dogs and a cat with intracranial lesions.

Two dogs and a cat with intracranial lesions were evaluated by both computed tomography (CT) and magnetic resonance (MR) imaging. In a dog with vestibular syndrome, better quality images of the medulla oblongata surrounded by thick bones were obtained by MR than by CT, on which the appearance of artifacts impeded the clear image of the area. In a dog with multiple brain metastases of lymphoma, contrast CT delineated lesions more clearly than MR, which was performed one week after CT. During that week dexamethasone which might affect the clarity of MR images of the lesion was administered to reduce brain edema. In a cat with meningeal syndrome of lymphocytic leukemia, only contrast MR imaging identified the width and site of the lesion. These results indicate that it is necessary to select either one of these imaging methods according to the type and site of lesions that are suspected in a particular case.

Animals↗

Cloning of the human orphan receptor germ cell nuclear factor/retinoid receptor-related testis-associated receptor and its differential regulation during embryonal carcinoma cell differentiation.

We have cloned a cDNA encoding the full-length coding region of the human homologue of the germ cell nuclear factor (GCNF)/retinoid receptor-related testis-associated receptor (RTR), from a human testis cDNA library. The amino acid sequence of human GCNF/RTR is highly homologous to that of the mouse GCNF/RTR. The largest difference between the two homologues is a 15 amino acid deletion in the human GCNF/RTR at amino acid 47. The GCNF/RTR gene was localized on human chromosome 9. Northern blot analysis using poly(A)+ RNA from different human tissues showed that GCNF/RTR mRNA is most abundantly expressed in the testis. GCNF/RTR was also highly expressed in embryonic stem cells and embryonal carcinoma cells but repressed in its differentiated derivatives. Induction of differentiation of mouse embryonal carcinoma F9 cells and human embryonal carcinoma NTERA-2 clone D1 (NT2/D1) cells by all-trans retinoic acid was accompanied by a down-regulation of GCNF/RTR. Our observations suggest that GCNF/RTR plays a role in the control of gene expression in early embryogenesis and during spermatogenesis.

Amino Acid Sequence↗

A patient with acromegaly who showed remarkable improvement of hyperglycemia after treatment with octreotide.

A case with diabetes mellitus associated with growth hormone (GH)-producing pituitary adenoma is described. A 56-year-old woman who had been treated for diabetes mellitus for 3 years, was admitted for the treatment of hyperglycemia. She showed a few acromegalic features and her plasma GH level was 146 +/- 16 ng/ml. After improvement of plasma glucose level by insulin injection, octreotide therapy (100 micrograms/8 hours) was started. Seven days after the initiation of octreotide therapy, the fasting plasma glucose level was almost normalized without insulin injection. After the octreotide treatment, urinary C-peptide excretion was significantly decreased and the plasma GH level became within normal range. In this case, octreotide appears to have improved the insulin sensitivity by reducing the plasma GH level.

Acromegaly↗

Thiazolidinediones downregulate stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes.

Thiazolidinediones (TZDs) are known to have potent increases of insulin sensitivity. Because peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a receptor for TZDs, is mainly expressed in adipocytes, we tried to search the TZD-targeted genes in mouse 3T3-L1 adipocytes. By the mRNA differential display method, one band repressed by troglitazone was obtained, which corresponded to the partial sequences of the stearoyl-CoA desaturase 1 (SCD1) gene. Troglitazone dramatically decreased SCD1 mRNA levels in 3T3-L1 adipocytes in a dose-dependent manner. Pioglitazone also repressed the SCD1 mRNA expression, whereas WY-14,643 had no apparent effect. Both troglitazone and pioglitazone raised the composition (weight percentage) of myristic acid (C14:0), palmitic acid (C16:0), and stearic acid (C18:0), but lowered the composition of the delta9-cis desaturated fatty acids such as myristoleic acid (C14:1, delta9), palmitoleic acid (C16:1, delta9), oleic acid (C18:1, delta9), and linoleic acid (C18:2, delta9,12). These results indicate that TZDs repress SCD1 activity in 3T3-L1 adipocytes via downregulating SCD1 enzyme gene expression.

3T3 Cells↗