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Biomedical subjects

H Kishi

Publications and source records attributed to H Kishi.

At least 109 records · Page 6Linked to original sources
PubMed1997

Direct extracranial-intracranial bypass for children with moyamoya disease.

To improve cerebral hypoperfusion in the ischemic type of Moyamoya disease, we have applied superficial temporal artery-middle cerebral artery (STA-MCA) double anastomoses in combination with encephalo-myo-synangiosis (EMS) for 19 hemispheres of 10 children (age from 5 to 11 years at surgery). Two branches of the STA were anastomosed to the two cortical arteries which were selected in the watershed area of the cerebral hemisphere estimated as a hypoperfusion area on the preoperative angiograms. Before surgery transient ischemic attacks (TIAs) developed from every month to every 6 months in association with hyperventilation or sobbing. No perioperative completed stroke or wound complications was observed, although single TIA developed in four patients within 1 month after surgery. Postoperative angiogram demonstrated that, not only the preoperative watershed area, but also the most of the middle cerebral artery territory was oppacified via the 2 branches of the STA in all 19 hemispheres. In a mean follow-up period of 4 years, no ischemic episode was induced by hyperventilation, and there was no mental or neurological deterioration. STA-MCA double anastomoses, to the cerebral watershed area, in combination with EMS are safe and effective even for younger children with Moyamoya disease.

Anastomosis, Surgical↗
PubMed1996

Induction of recombination activating gene expression in a human lymphoid progenitor cell line: requirement of two separate signals from stromal cells and cytokines.

The activation and expression of recombination activating genes (RAGs) plays critical roles in V(D)J gene recombination machinery and lymphocyte development. We showed that RAG gene expression was induced in freshly isolated human bone marrow cells and a human lymphoid progenitor cell line, FL8.2.4.4, by coculture on a monolayer of a murine bone marrow-derived stromal cell line, PA6, in the presence of a mixture of recombinant cytokines. The RAG transcripts were detected 12 hours after initiation of culture, and the increased level was sustained at 24 hours. Among recombinant cytokines, interleukin-3 (IL-3), IL-6, and IL-7, but not IL-2, IL-4, stem cell factor (SCF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) could induce RAG-1 activation in FL8.2.4.4 cells, and a significant synergistic effect between IL-3, IL-6, and IL-7 was observed. Using a double chamber culture technique, it was shown that a cognate interaction between FL8.2.4.4 cells and PA6 stromal cells was a prerequisite for RAG-1 activation. Furthermore, RAG-1 transcripts were induced in FL8.2.4.4 cells when they were cocultured on paraformaldehyde-fixed PA6 stromal cells in the presence of cytokines. These results suggest that two separate signals are both required for induction of RAG-1 activation in lymphoid progenitors; one from the cell surface molecule(s) on stromal cells, and the other from the recombinant cytokine(s). Finally, we showed that expression of RAG mRNA in FL8.2.4.4 cells was concomitant with induction of recombinase activity. This system may provide useful means for further understanding the mechanisms controlling RAG activation and lymphocyte development in the human system.

Bone Marrow Cells↗
PubMed1996

Chromatin structure and transcriptional regulation of human RAG-1 gene.

The recombination activating genes (RAGs) play a critical role in V(D)J recombination machinery and lymphocyte development. Their expression is strictly regulated during lymphocyte ontogeny, with expression being rapidly lost as the lymphoid precursors differentiate into their progeny. To elucidate molecular mechanisms of regulation of human RAG-1 gene expression, we examined a chromatin structure of a approximately 24-kb DNA segment adjacent to a human RAG-1 promoter region in various cell lines by analyzing DNase I hypersensitive (DNase I HS) sites. In a RAG-1-expressing human pre-B-cell line, at least four DNase I HS sites (HS1, HS2, HS3, and HS4) were identified. Among these HS sites, one HS site (HS1) was ubiquitously detected in all cell lines examined, but the other three HS sites (HS2, HS3, and HS4) were associated only with RAG-1-expressing lymphoid cell lines. Using transient expression assays, we showed that the 5' upstream region of the major transcription start site showed low but significant promoter activity and that a DNA segment within HS3 located in the promoter region was indispensable to its basal promoter activity. Importantly, this promoter region was shown to be active in both RAG-1-expressing and RAG-1-nonexpressing cell lines. These results suggest that alteration of chromatin structure in the promoter region, in addition to other control elements outside of the promoter region, is one of the mechanisms regulating tissue- and stage-specific expression of human RAG-1 gene.

B-Lymphocytes↗
PubMed1996

Molecular cloning and characterization of a novel stromal cell-derived cDNA encoding a protein that facilitates gene activation of recombination activating gene (RAG)-1 in human lymphoid progenitors.

The activation and expression of recombination activation genes (RAGs) in lymphoid progenitors are regulated by signals from surface molecules of stromal cells and/or cytokines. Using a mRNA differential display method, we isolated a novel stromal cell-derived cDNA clone, C2.3, whose transcripts were intensively expressed in RAG-1-inducible stromal cell line, but rarely expressed in RAG-1-non inducible mutant cell line (PA6). The cDNA sequence had no homology to the known genes. The sequence revealed an open reading frame that encodes a 221 amino acid protein with 4 potential transmembrane domains, suggesting a possible role of C2.3 product as a membrane receptor. Introduction of C2.3 cDNA into PA6 mutant line restored the ability to activate RAG-1 gene in lymphoid progenitors, indicating that a C2.3 product may be involved in the induction of RAG-1 gene activation.

Amino Acid Sequence↗
PubMed1996

Morphological study of thymus stromal cells (TEL-2 cell) which play a role in the elimination of double positive immature thymocytes by phagocytosis.

BACKGROUND: The process of the selective elimination of immature double positive thymocytes, during culture with TEL-2 cells (an epithelial cell line from the thymus stroma), is initiated by the contact between thymocytes and TEL-2 cells (Nakashima et al. 1990 Eur. J. Immunol., 20: 47-53; Hirata et al. 1991 Anat. Rec., 230: 524-530). METHODS: Our approach was to follow the process of thymocyte internalization as a sequelae of this interaction with scanning electron microscopy (SEM), transmission electron microscopy (TEM), and electron microscopic cytochemistry for the hydrolytic enzyme acid phosphatase (Ac Pase). RESULTS: With SEM, numerous thymocytes lay underneath the TEL-2 cells. An enhanced activity of the TEL-2 cell membrane, consisting of several thin thread-like projections either with or without an expanded termination, was involved with contacting the thymocytes. With TEM, close appositions were noted either at adjacent segments of the cellular membrane or between thick plump local protrusions of the plasma membrane. Blunt pseudopodia and deep invaginations on indented portions of the TEL-2 surface engulfed one or more thymocytes. With Ac Pase histochemistry: 1) the incorporation of thymocytes into a phagosome was indicated by the Ac Pase negative thymocytes enclosed in a membrane beneath the protuberance of a TEL-2 cell surface without fusion to the TEL-2 lysosomes; 2) most of these thymocytes were morphologically intact, whereas the rest were already damaged, having changes similar to apoptosis; and 3) a few Ac Pase positive dense bodies of the TEL-2 cell, mostly with the morphology of secondary lysosomes, fused with the thymocyte-enclosing membrane after which the digestion of several thymocytes proceeded. CONCLUSIONS: With the prominent activity of the plasma membrane involving the initial attachment and subsequent phagocytosis, a murine thymic epithelial cell line TEL-2 plays a demonstrating role in the mechanism of the elimination of double positive thymocytes.

Acid Phosphatase↗
PubMed1996

Preliminary results of concurrent methotrexate, cisplatin and radiation treatment for locally advanced urothelial cancers.

Ten patients with invasive bladder cancer and one with locally advanced renal pelvic cancer were treated with concurrent methotrexate, cisplatin and radiotherapy. Methotrexate 30 mg/m2 was administered intravenously on the day of the initiation of radiotherapy and cisplatin 70 mg/m2 on the second day. The number of chemotherapy cycles delivered was 1 in 7 patients and 2 in 4. The median dose of radiation was 50 Gy. Of 11 patients, 7 (64%) achieved a partial response and 4 had no change in disease. The median duration of response was 16 months for patients with a partial response. Six patients with a partial response (55%) are alive for a median of 22.5 months and 2 of 4 with no change are alive for 4 and 15 months, respectively. Leukopenia less than 3000 cell/mm3 was observed in 4 (36%) and thrombocytopenia less than 100,000 cells/mm3 in 3 (27%). Local control could be achieved safely with concurrent methotrexate, cisplatin and radiation therapy in patients with locally advanced urothelial cancer who were unsuitable for surgery.

Aged↗
PubMed1996

Very poor prognosis in cases with extravasation of the contrast medium during angiography.

BACKGROUND: The rebleeding of a ruptured intracranial aneurysm in the acute stage has been thought to indicate a very poor prognosis. In our experience, the outcome of patients with extravasation of the contrast medium is worse than that of patients with rerupture under circumstances other than angiography. We demonstrated the poorer outcome of the patients with extravasation, compared to that of the patients developing rerupture under circumstances other than angiography, and examined the factors that contributed to the poorer outcome of the patients with extravasation. METHODS: Among the 641 cases of ruptured intracranial aneurysm, we have handled over the past 10 years, 36 (5.6%) patients have rebled before surgery was performed. Thirteen patients rebled during angiography (Group I), and the remaining 23 patients rebled in other circumstances (Group II). We compared the outcome of both groups. RESULTS: The rebleeding occurred within 6 hours of the initial rupture in 29 (80%) patients. The outcome of Group I was significantly poorer than that of Group II (p < 0.05). In Group I, SD was achieved in only 1 patient and the remaining 12 patients died, while in Group II, 8 patients were in GR or MD, 2 were in SD, and the remaining 13 patients died. CONCLUSION: Because rebleeding during angiography most often occurs in the acute stage and because the outcome of patients with extravasation is very poor, we recommend that the performance of angiography be delayed at least between 3 and 6 hours after the initial rupture.

Adult↗
PubMed1996

Isolation and characterization of a TATA-less promoter for the human RAG-1 gene.

Human recombination activating gene-1 (RAG-1) genomic DNA clones containing the first exon coding for the 5' untranslated region and the second exon coding for the remaining 5' untranslated region, coding region, and 3' untranslated region were cloned. Primer extension analysis and RNase protection analysis demonstrated the multiple RAG-1 transcription start sites, clustered in a 31 nucleotide (nt) region. Sequence analysis showed that the RAG-1 promoter lacked a TATA box as well as an initiator sequence. Transient expression assays using a luciferase reporter gene with truncated promoter fragments and substitution mutants, showed that the 5' promoter region containing the CCAAT box between -110 and -86, is indispensable for its basal promoter activity in RAG-1 expressing Nalm 6 cell line. Comparative transient expression assays in various cell lines revealed that the 854 nt upstream promoter region was active, not only in RAG-1 expressing cell lines but also in RAG-1 non-expressing cell lines. These data indicate that the 854 nt upstream region of RAG-1 gene confer basal promoter activity, and that the tissue- and stage-specific expression of RAG-1 is controlled by elements present outside of the promoter region and/or differential chromatin structure(s) of the individual cells.

Base Sequence↗
PubMed1996

Expression of metastasis suppressor gene product, nm23 protein, is not inversely correlated with the tumour progression in human malignant melanomas.

An inverse correlation between the nm23 RNA level and tumour progression of melanocytes has been reported. To elucidate whether the expression of nm23 gene product in malignant melanoma is also inversely correlated with metastatic potential, conventional prognostic parameters or the tumour suppressor protein p53, immunohisto-chemical studies using a monoclonal antibody against nm23-H1 protein were performed on 138 benign and malignant melanocytic tumours. The expression of nm23 protein was compared with that of p53 protein and conventional clinicopathological prognostic factors. The nm23 protein level in benign melanocytes and metastatic melanoma cells was also studied by Western blot analysis. No significant difference regarding the protein was observed between naevi and melanomas, either at histological or protein levels. The expression correlated with local recurrence within 1 year after surgery, level of invasion and tumour thickness, but no parallels were observed between the nm23 and p53 proteins, suggesting that gene is regulated by independent mechanisms, although located on the same chromosome. There was no inverse correlation between the nm23 protein and melanoma metastasis which suggested that the nm23 protein does not appear to be lost during melanoma metastasis.

Adult↗
PubMed1996

Induction of superovulation by immunoneutralization of endogenous inhibin through the increase in the secretion of follicle-stimulating hormone in the cyclic golden hamster.

The present study was conducted to study the effect of immunoneutralization against endogenous inhibin on FSH, LH, oestradiol-17 beta and progesterone secretion and to investigate the effect of removal of endogenous inhibin on subsequent follicular development in the hamster. After treatment with anti-inhibin serum (inhibin-AS) at 1100 h on day 2 of the oestrous cycle (day 1 = day of ovulation), a marked increase in plasma levels of FSH and a slight increase in plasma levels of LH were noted and pituitary contents of FSH, but not LH, were also increased. In the group treated with inhibin-AS, superovulation occurred on day 1 of the following cycle. Plasma levels of oestradiol-17 beta markedly increased with the increase in the number of ovulations induced by human chorionic gonadotrophin (hCG) as compared with those in control animals. In the second cycle, plasma concentrations and pituitary contents of FSH in the animals given 200 microliters inhibin-AS still showed high values as compared with those in the animals treated with control serum, although superovulation did not occur on day 1 of the third cycle. Plasma concentrations and pituitary contents of LH in the hamster given 200 microliters inhibin-AS tended to decrease as compared with those in control animals during the second cycle. Plasma concentrations of oestradiol-17 beta in the animals treated with 200 microliters inhibin-AS changed in a similar way to controls. A marked increase in plasma concentrations of progesterone was noted on days 1 and 2 of the second cycle in the group receiving inhibin-AS. The twice daily injection of 1 IU hCG during the second cycle to the animals given 200 microliters inhibin-AS induced superovulation on day 1 of the third cycle. These results indicate that circulating inhibin may be an important indicator of the number of developing follicles and may maintain the species-specific number of developing follicles through suppression of FSH secretion in the cyclic hamster. They also suggest that high levels of inhibin slightly suppress plasma levels of LH, indicating that plasma LH may also regulate follicular development in the cyclic hamster.

Animals↗
PubMed1996

Stimulation of retinal pigment epithelial cell growth by neuropeptides in vitro.

PURPOSE: The proliferation of many cell types are regulated by cytokines and neuropeptides by autocrine and paracrine mechanisms. Retinal pigment epithelial (RPE) cells are also regulated by cytokines. But RPE cells are very close to the neural retina which has some neuropeptides. The present study was to investigate the effects of neuropeptides on the growth of RPE cells. METHODS: RPE cells were obtained from the eyes of 11 day old chick embryos and cultured in Dulbecco's modified Eagle's culture medium containing 10% fetal calf serum. The growth of RPE cells was evaluated by [3H]-thymidine uptake. RESULTS: Substance P, beta-endorphin and calcitonin gene-related peptide markedly stimulated the growth of RPE cells. The effects of methionine-enkephalin, somatostatin and vasoactive intestinal peptide were intermediate. The strongest effects of substance P, beta-endorphin and calcitonin gene-related peptide were observed at 10(-6) to 10(-7) M. The stimulation of RPE cells with beta-endorphin was inhibited by naloxone, suggesting that the stimulation with beta-endorphin is mediated by an opioid receptor. beta-endorphin and substance P induced RPE cell growth stimulating activity. Leucine-enkephalin and neuropeptide Y did not affect the growth of RPE cells. CONCLUSIONS: These results suggest that neuropeptides play an important role in the regulation of RPE cell growth.

Animals↗
PubMed1996

[A case of rheumatoid factor-positive pachymeningitis].

We report a case of rheumatoid pachymeningitis involving the posterior fossa. A 71-year-old woman presented with headache, vertigo and dizziness. MRI demonstrated hypertrophic masses in the meninges of the left cerebellar tentorium, cerebellopontine angle and the fourth ventricle. Six months of treatment with betamethasone, prednisolone and azathioprine improved the patient's neurological status. Because an inappropriate immune process and systemic immune disease may cause idiopathic pachymeningitis, the performance of immunological studies for idiopathic cases is mandatory.

Aged↗
PubMed1995

Antigen-receptor induced clonal expansion and deletion of lymphocytes are impaired in mice lacking HS1 protein, a substrate of the antigen-receptor-coupled tyrosine kinases.

HS1, an intracellular protein expressed specifically in hematopoietic cells, is rapidly tyrosine phosphorylated after cross-linking of antigen receptors on B and T lymphocytes, implicating involvement of this molecule in the signal transduction pathways from the antigen receptors as a substrate of membrane-associated tyrosine kinase(s). The development of lymphoid cells in HS1-deficient mice, generated through gene targeting, appeared normal. However, antibody production to T-independent antigen and proliferative responses of splenic B and T cells after cross-linking of the antigen receptors were impaired in these mutant mice. Furthermore, B cells in the peritoneal cavity of the mutant mice were resistant to multivalent cross-linking of the antigen receptor, which causes apoptosis of such cells in normal mice. Crossing the HS1-deficient mice with the mice harboring transgenes encoding alpha and beta chains of T-cell antigen receptor against a male H-Y antigen resulted in a progeny that demonstrated a significantly impaired ability of thymic negative selection. These results indicate that HS1 is a novel molecule involved in the antigen-receptor-derived signaling pathways and plays important roles not only in clonal expansion, but also in clonal deletion of B and T cells.

Adaptor Proteins, Signal Transducing↗
PubMed1995

A novel cell surface antigen, immature thymocyte antigen-1, is involved in the differentiation of murine thymocytes.

A mAb, 1-23, which recognizes a novel cell surface Ag on immature murine thymocytes (designated as IMT-1 for immature thymocyte antigen-1) was prepared. IMT-1 was found to be expressed on 40 to 50% of CD4-8- double negative (DN), 5 to 10% of CD4-8+, and 5 to 20% of CD4+8+ double positive (DP) thymocytes in adult mice, but not expressed on CD4+8- thymocytes or peripheral T lymphocytes. It was not expressed on either nonlymphoid cell lines or thymic stromal cells. In subsets of DN thymocytes, IMT-1 was detected on 40 to 50% of the heat-stable Ag+, 15% of CD44+25+, 70% of CD44-25+, and 70% of CD44-25- populations, whereas it was not detected on heat-stable Ag- and CD44+25- populations. IMT-1+ thymocytes expressed low levels of or no CD3 molecules. In fetal thymuses, IMT-1 was expressed on a minor population of thymocytes at day 14.5 and 15.5 of gestation. However, at day 16.5 of gestation, a majority of DN as well as DP thymocytes became IMT-1-positive. Addition of the 1-23 Ab to the fetal thymus organ culture relatively increased CD8+ SP thymocytes. These results show that IMT-1 is expressed during the late DN stage as well as the early DP stage of thymocyte maturation and suggest the possible involvement of IMT-1 in thymocyte differentiation.

Animals↗
PubMed1995

Reciprocal IL-1 beta gene expression in medial and lateral hypothalamic areas in SART-stressed mice.

Specific alteration of rhythm of temperature (SART) stress has been found to induce thymic atrophy via activation of the hypothalamus-pituitary-adrenal (HPA) axis. We demonstrate here that SART stress induces increment of IL-1 beta mRNA levels in the medial hypothalamic area (MHA) and decrement of IL-1 beta mRNA levels in the lateral hypothalamic area (LHA). The altered levels of IL-1 beta expression in these loci return to those of non-stressed mice upon cessation of the stress. These data imply that the reciprocal wave of SART stress-induced IL-1 beta gene expression in MHA and LHA may contribute to activation of the HPA axis and the resulting immunological dysfunction.

Animals↗
PubMed1995

Immunohistochemical localisation of stem cell factor (SCF) with comparison of its receptor c-Kit proto-oncogene product (c-KIT) in melanocytic tumours.

In order to characterise the distribution and role of stem cell factor (SCF), a recently-reported growth factor for normal melanocytes, we carried out an immunohistochemical study on benign and malignant melanocytic tumours with a comparison with the presence of its receptor c-Kit proto-oncogene product (c-KIT). In normal skin, SCF was mainly observed in endothelial cells of blood vessels but not frequently in basal melanocytes, whereas c-KIT was predominantly localised in tissue mast cells. In benign neoplastic melanocytes (common melanocytic naevi), localisation of SCF and c-KIT was complementary: SCF was mostly found in dermal naevus cells while c-KIT was revealed in epidermal naevus cells, although the expression of the latter antigen was not frequent. Malignant melanoma cells showed less frequent expression of these antigens than those in benign lesions. Of five cultured melanoma cell lines, SCF was observed in only one, and c-KIT was not found in any melanoma cells. No quantitative or qualitative alterations assessed by Western blot analysis were induced in the presence of phenotypic modifiers (sodium butyrate and HMBA). Present data suggest that loss of SCF expression in neoplastic melanocytes is commonly associated with malignant transformation of pigment cells rather than loss of its receptor c-KIT.

Humans↗
PubMed1995

Angiographic extravasation of contrast medium in acute "spontaneous" subdural hematoma.

Acute spontaneous subdural hematoma is very rare. We have encountered four such cases and verified the arterial origin of the bleeding at operation. None of the patients had a history of head trauma, and each had developed sudden onset of headache and other neurologic deficits, which simulate other cerebrovascular diseases. CT directly revealed subdural hematoma but gave no indication as to the source of the bleeding. Cerebral angiography was performed in all cases, with three of them showing localized extravasation of the contrast material into the subdural space. The extravasation was noted usually in the late arterial phase. This is a useful finding for diagnosing this disease and localizing the bleeding point. It is expected that with more routine use of cerebral angiography in cases of acute spontaneous subdural hematoma, extravasation of the contrast medium will be seen more frequently.

Acute Disease↗