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Biomedical subjects

H Kitamura

Publications and source records attributed to H Kitamura.

At least 127 records · Page 7Linked to original sources
PubMed2000

Morphology and functional roles of synoviocytes in the joint.

The joint capsule exhibits a unique cellular lining in the luminal surface of the synovial membrane. The synovial intimal cells, termed synoviocytes, are believed to be responsible for the production of synovial fluid components, for absorption from the joint cavity, and for blood/synovial fluid exchanges, but their detailed structure and function as well as pathological changes remain unclear. Two types of synoviocytes, macrophagic cells (type A cells) and fibroblast-like cells (type B cells) have been identified. Type A synoviocytes are non-fixed cells that can phagocytose actively cell debris and wastes in the joint cavity, and possess an antigen-presenting ability. These type A cells, derived from blood-borne mononuclear cells, can be considered resident macrophages (tissue macrophages) like hepatic Kupffer cells. Type B synoviocytes are characterized by the rich existence of rough endoplasmic reticulum, and dendritic processes which form a regular network in the luminal surface of the synovial membrane. Their complex three-dimensional architecture was first revealed by our recent scanning electron microscopy of macerated samples. The type B cells, which are proper synoviocytes, are involved in production of specialized matrix constituents including hyaluronan, collagens and fibronectin for the intimal interstitium and synovial fluid. The proliferative potentials of type B cells in loco are much higher than type A cells, although the transformation of subintimal fibroblasts into type B cells can not be excluded. In some mammals, type B cells show features suggesting endocrine and sensory functions, but these are not recognized in other species. The synoviocytes, which form a discontinuous cell layer, develop both fragmented basement membranes around the cells and junctional apparatus such as desmosomes and gap junctions. For an exact understanding of the mechanism of arthritis, we need to establish the morphological background of synoviocytes as well as their functions under normal conditions.

Animals↗
PubMed2000

[A case report of primary hemangiopericytoma of the chest wall].

A 35-year-male was found to have an abnormal shadow with an extrapleural sign located in the right lower lung field by a chest X-ray. Chest CT revealed a well demarcated tumor in the chest wall adjacent to the 4th rib. Chest MRI showed that the tumor contained punctate or linear low-intensity areas, which were considered to be small blood vessels. A diagnosis of hemangiopericytoma was established by percutaneous needle biopsy. Under the definite diagnosis, extended resection of the chest wall was performed to remove the tumor with a surgical margin of more than 5 cm, corresponding to surgery for other malignant soft-tissue neoplasmas. Hemangiopericytomas rarely arise in the chest wall, although they can be found in any region which contains pericytes. Preoperative definite diagnoses of hemangiopericytoma have rarely been reported. However, preoperative diagnosis is an important factor in deciding the operative procedure for hemangiopericytoma. It has been reported that hemangiopericytomas show local recurrences and distant metastases, although they are histologically benign. We consider that hemangiopericytomas in the chest wall should be treated with extensive resection corresponding to surgery for other malignant soft-tissue neoplasmas.

Adult↗
PubMed2000

Tertiapin potently and selectively blocks muscarinic K(+) channels in rabbit cardiac myocytes.

Tertiapin is a 21-residue peptide isolated from honey bee venoms. A recent study indicated that tertiapin is a potent blocker of certain types of inwardly rectifying K(+) (Kir) channels (). We examined the effect of tertiapin on ion channel currents in rabbit cardiac myocytes using the patch-clamp technique. In the whole-cell configuration, tertiapin fully inhibited acetylcholine (1 microM)-induced muscarinic K(+) (K(ACh)) channel currents in atrial myocytes with the half-maximum inhibitory concentration of approximately 8 nM through approximately 1:1 stoichiometry. The potency of tertiapin in inhibiting K(ACh) channels was not significantly different at -40 and -100 mV. Tertiapin also inhibited the K(ACh) channel preactivated by intracellular guanosine 5'-O-(3-thiotriphosphate), a nonhydrolyzable GTP analog. A constitutively active Kir channel, the I(K1) channel, was at least 100 times less sensitive to tertiapin. Another Kir channel in cardiac myocytes, the ATP-sensitive K(+) channel, was virtually insensitive to tertiapin (1 microM). The voltage-dependent K(+) and the L-type Ca(2+) channels were not affected by tertiapin (1 microM). At the single-channel level, tertiapin inhibited the K(ACh) channel from the outside of the membrane by reducing the NP(o) (N is the number of functional channels, and the P(o) is the open probability of each channel) without affecting the single-channel conductance or fast kinetics. Therefore, tertiapin potently and selectively blocks the K(ACh) channel in cardiac myocytes in a receptor- and voltage-independent manner. Tertiapin is a novel pharmacological tool to identify the functional role of the K(ACh) channel in the parasympathetic regulation of the heart beat.

ATP-Binding Cassette Transporters↗
PubMed2000

[Complement activation in heparin--plasma inhibitory effect of anticoagulants on serum complement activation, 2nd report].

Our previous study of the inhibitory effect of EDTA and citrate in plasma on complement activation revealed that complement is activated in usual citrate plasma but not in usual EDTA plasma. The present study is a similar one using other anticoagulants containing heparin. CH50 and activities of C4 and C2 were assayed in serum or plasma containing various concentrations of anticoagulant after incubation with latex particles bearing immunoglobulin(Ig-Latex). It was found that complement activation is inhibited by heparin in a dose-dependent manner and that 10 U/ml of heparin does not inhibit CH50 reduction and C2 inactivation but inhibit C4 inactivation partially, indicating that complement activation proceeds in plasma containing usual concentration of heparin. Similar results were obtained in cases of low molecular weight heparin(LMWH) and nafamostat mesilate(Futhan). Complement activation was not inhibited by gabexate mesilate(FOY) in the tested range of concentrations. Thus, it was revealed that complement activation is not inhibited by usual concentrations of heparin, LMWH, Futhan and FOY.

Adult↗
PubMed2000

Different pathological findings in each of four parathyroid glands in a long-standing hemodialysis patient.

A 51-year-old male patient with chronic renal failure, who had required dialysis for 22 years, presented with a cervical mass. Laboratory data were consistent with secondary hyperparathyroidism due to chronic renal failure. Cervical exploration was performed with excision of four parathyroid glands and autotransplantation of the normal gland into the forearm. The cervical tumor of the right inferior gland demonstrated parathyroid carcinoma histologically. Adenoma of the right superior gland and hyperplasia of the left superior gland were also recognized. The left inferior gland was normal. A few cases of parathyroid carcinoma in patients on maintenance hemodialysis have been previously reported. However, this is the first report in which all four parathyroid glands revealed different pathological findings: carcinoma, adenoma, hyperplasia and normal gland. Chronic stimulation of the parathyroid glands to release parathyroid hormone might have caused the variety of findings in the four parathyroid glands.

Adenoma↗
PubMed1999

Mesoporous Magnetic Materials Based on Rare Earth Oxides.

A novel family of mesoporous oxides of rare earth metals (Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) were synthesized with specific surface areas of 253-348 m(2) g(-1) and pore diameters of 2.5-3.0 nm (see Scheme). The mesoporous solids and their surfactant mesophase precursors are paramagnetic and exhibit a magnetic anomaly due to the mesostructured atomic arrangement.

Journal Article↗
PubMed1999

Extramedullary Plasmacytoma of the Breast with Serum IgD Monoclonal Protein: A Case Report and Review of the Literature.

A case of extramedullary plasmacytoma (EMP) of the breast in a 49-year-old woman is reported. Six cases of EMP of the breast have been previously reported inthe world literature, but this case is unusual in that it was associated with serum IgD lamda monoclonal protein detected by serum immuno-electrophoresis. The protein was identical to the immunoprotein found in proliferating cells of the breast. Bone marrow aspiration revealed normal plasma cells indicating that the breast tumor did not represent extramedullary involvement of multiple myeloma or myelomatosis. An associated tumor was found in the nasal cavity after local treatment (mastectomy) of the breast tumor, but the patient remained disease-free 12months after adjuvant chemotherapy using nidlan, natulan, alkelan, prednisone, cyclophosphamide and vincristine.

Journal Article↗
PubMed1999

The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells.

The natural killer T (NKT) cell ligand alpha-galactosylceramide (alpha-GalCer) exhibits profound antitumor activities in vivo that resemble interleukin (IL)-12-mediated antitumor activities. Because of these similarities between the activities of alpha-GalCer and IL-12, we investigated the involvement of IL-12 in the activation of NKT cells by alpha-GalCer. We first established, using purified subsets of various lymphocyte populations, that alpha-GalCer selectively activates NKT cells for production of interferon (IFN)-gamma. Production of IFN-gamma by NKT cells in response to alpha-GalCer required IL-12 produced by dendritic cells (DCs) and direct contact between NKT cells and DCs through CD40/CD40 ligand interactions. Moreover, alpha-GalCer strongly induced the expression of IL-12 receptor on NKT cells from wild-type but not CD1(-/-) or Valpha14(-/-) mice. This effect of alpha-GalCer required the production of IFN-gamma by NKT cells and production of IL-12 by DCs. Finally, we showed that treatment of mice with suboptimal doses of alpha-GalCer together with suboptimal doses of IL-12 resulted in strongly enhanced natural killing activity and IFN-gamma production. Collectively, these findings indicate an important role for DC-produced IL-12 in the activation of NKT cells by alpha-GalCer and suggest that NKT cells may be able to condition DCs for subsequent immune responses. Our results also suggest a novel approach for immunotherapy of cancer.

Adjuvants, Immunologic↗
PubMed1999

Ion exchange chromatography of aluminum using 3-carboxy-2-naphthylamine-N,N-diacetic acid as a fluorescent post-column chelating reagent.

Ion exchange chromatography of aluminum ion using 3-carboxy-2-naphthylamine-N,N-diacetic acid (CNDA) as a fluorescent post-column chelating reagent was studied. The solution containing ammonium chloride and hydrochloric acid was used for the eluent, and acetate buffer solution containing CNDA was used for the post column chelating reagent. The peak of aluminum was separated from that of calcium, magnesium and zinc, and the chromatogram was not affected by copper(II) and iron(III). The calibration curve gave linear plots with a range of 0.0027-0.54 ppm aluminum, the regression coefficient of correlation (r2) was 1.000, and the detection limit (S/N = 3) was 0.3 ppb, indicating that the method could determine aluminum with high sensitivity. It was demonstrated that CNDA is a useful metallofluorescent reagent for aluminum. This method has been successfully applied to the determination of aluminum in some tea drinks.

Aluminum↗
PubMed1999

The essential role of phorbol ester-sensitive protein kinase C isoforms in activation-induced cell death of Th1 cells.

Th1 and Th2 cells, which were induced from naive T cells of TCR-transgenic mice, showed differential sensitivity to activation-induced cell death (AICD) triggered by stimulation with anti-CD3 monoclonal antibody. The Th1 cells showed more rapid AICD than Th2 cells. This accelerated AICD of Th1 cells was strongly blocked by protein kinase C (PKC) inhibitors (H-7 or GF 109203X). Moreover, long-term treatment of Th1 cells with phorbol 12-myristate 13-acetate (PMA) caused the abrogation of anti-CD3-induced AICD in parallel with the disappearance of PMA-sensitive PKC isoforms such as PKC alpha, gamma, epsilon and theta. Therefore, it was clearly demonstrated that PMA-sensitive PKC isoforms are essential for AICD of Th1 cells. The different susceptibility to AICD between Th1 and Th2 cells was not due to their differential expression levels of PMA-sensitive PKC isoforms but appeared to be due to their differential requirement for PMA-sensitive isoforms in the up-regulation of Fas ligand which is involved in suicide killing of activated Th1 cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Mechanism of decrease in levels of hepatic P450 isozymes induced by intracerebral endotoxin: independence from sympathetic nervous and adrenocortical systems.

We previously reported that lipoplysaccharide (LPS) injected intracerebroventricularly (i.c.v.) at an ineffective dose (0.1 microgram/rat) decreased the drug metabolizing activities and related cytochrome P450 (CYP) isozymes in rat liver microsomes when injected intraperitoneally (i.p.). The dose study (doses < 0.1 microgram intracerebrally and > 0.1 microgram i.p.), which was carried out to examine how much more effective is i.c.v.-LPS than i.p.-LPS, showed that the pattern of alteration of expression of CYP isozymes induced by i.c.v.-LPS was different from that caused by i.p.-LPS at an effective dose (10 micrograms/rat). These results indicate that the decrease in hepatic CYP isozymes caused by i.c.v.-LPS could not be explained by the LPS leaked from the brain, suggesting that the decrease in hepatic CYP isozymes by i.c.v.-LPS may be caused by a central action of LPS. In this study, the possible involvement of sympathetic nervous and adrenocortical systems in the down-regulation of CYP isozymes by i.c.v.-LPS was investigated using surgical or chemical sympathetecomized or adrenalectomized rats. The norepinephrine (NE) content in the liver in rats with surgical hepatic sympathetectomy was reduced by 88% compared with that of sham-operated rats that received i.c.v.-saline and 85% compared with that of sham-operated rats that received i.c.v.-LPS, indicating that hepatic denervation was successful. The NE content in the liver in rats chemically sympathetectomized by two i.p. injections of 6-hydroxydopamine (40 mg/kg each time) 1 and 2 days before i.c.v. injection was reduced by 82% in i.c.v.-saline-treated and by 74% in i.c.v.-LPS-treated groups compared with that in rats pretreated with i.p.-saline. These results indicate that sympathetic NE terminals were effectively removed. Intracerebroventricular LPS decreased the total P450 content and the activities of CYP dependent drug metabolizing enzymes, ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD), imipramine N-demethylase (IMND) and erythromycin N-demethylase (ERND) after 24 h in both sympathetectomized rats and non-denervated rats. Adrenalectomy (ADX) reduced the level of corticosterone in serum by 81% compared to sham-operated rats, indicating that adrenalectomy was successful. ADX did not inhibit the decrease in the total P450 content and the metabolism of drugs induced by i.c.v.-LPS, but more profoundly emphasized the inhibitory effect of i.c.v.-LPS than the sham-operation. These results suggest that the sympathetic nervous systems both directly and indirectly innervating the liver do not participate in the primary mechanism of the decrease in the activities of CYP isozymes in rat liver microsomes induced by i.c.v.-LPS. Also, the adrenal glands, especially the adrenocortical system, play a suppressive role in the decrease in CYP isozymes caused by i.c.v.-LPS.

Adrenal Cortex↗
PubMed1999

Ontogeny of pulmonary neuroendocrine cells which express the alpha-subunit of guanine nucleotide-binding protein Go.

In order to ascertain that alpha-subunit of guanine nucleotide-binding protein Go (Go alpha)-positive cells in the lung epithelia are pulmonary neuroendocrine cells (PNECs), we carried out an immunohistochemical study in young adult and fetal lungs of rodents and in cultured fetal lung explants. Serial sections showed that Go alpha-positive cells were immunostained for calcitonin gene-related peptide and serotonin in young adult mouse, rat, and hamster lungs and that these cells are, therefore, PNECs. In the fetal lungs of hamster and mouse, Go alpha-positive PNECs appeared in the epithelium of the lobar bronchus by gestational day 13 in hamster and by day 15.5 in mouse, and they increased with a proximal-to-distal wave during the late fetal period. Explants of immature lung from the fetal hamster on gestational day 11 were cultured. After 2 days of culture, Go alpha-positive PNEC clusters appeared in the main and lobar bronchi and many PNEC clusters were seen after 4 days of culture. To determine the functional significance of Go in the development of the fetal lung, pertussis toxin, a Go inhibitor, was added to the medium, and changes in branching morphogenesis and PNEC development were studied. Although branching morphogenesis was not disturbed by pertussis toxin, the toxin treatment induced large PNEC clusters in the cultured lung explant. In summary, we showed that Go alpha is a neuroendocrine marker for PNECs and that Go alpha-positive cells appear along with development of PNECs in fetal hamster lung in vivo and in vitro. The functional significance of Go in the development of fetal lung is obscure, but signals mediated through this GTP-binding protein could be related to some functions of PNECs.

Animals↗
PubMed1999

The role of p53 in bleomycin-induced DNA damage in the lung. A comparative study with the small intestine.

To elucidate the role of p53 and apoptosis in the pathogenesis of lung injury, we examined histological changes, expressions of p53 and p21waf1/cip1 (p21), apoptosis, DNA double strand breaks, cell kinetics, and DNA synthesis in C57/BL6 mice (p53+/+) and mice deficient for p53 (p53-/-) at 2 hours to 7 days after a single intravenous administration of bleomycin. We also compared these parameters between the lung cells and small intestinal epithelial cells to explore potential differences in their response to DNA damage. Bleomycin induced p21 expression in a p53-dependent manner in p53+/+ mice but neither p53 nor p21 expression in p53-/- mice. In the lung of both groups of mice, focal inflammation followed by fibrosis was observed, but there was no evidence of apoptosis. Cells with DNA breaks and those undergoing DNA synthesis were unequivocally increased, but the cycling cell fraction remained unchanged, suggesting that the DNA synthesis detected in the lung reflected unscheduled DNA synthesis for repair of damaged DNA. DNA breaks and unscheduled DNA synthesis were prolonged in p53-/- mice compared to p53+/+ mice. By contrast, in the small intestine, marked cell cycle arrest and extensive apoptosis were evoked in the cycling crypt cells of both groups of mice, but these changes were milder and DNA breaks remained detectable for a longer time in p53-/- mice than in p53+/+ mice. Among the resting enterocytes in the villi, apoptosis was observed almost equally in both groups, but repair of DNA breaks was significantly delayed in the p53-/- mice. These observations imply that apoptosis is mediated largely by the p53-dependent pathway in the crypts but exclusively by the p53-independent pathway in the villi, that this pathway is particularly important in DNA repair in the villi, and that despite this difference in the significance of apoptosis, p53 plays an important role in DNA repair in both the crypts and villi. Our results suggest that the lung cells and small intestinal cells respond to the bleomycin treatment in different ways in terms of the induction of apoptosis and that p53 carries out an essential role in the early response to and repair of DNA damage by a non-apoptotic mechanism which appears to be crucial in the noncycling lung cells and enterocytes. Importantly, the p53-p21 pathway and apoptosis are unlikely to be essential for bleomycin-induced tissue injury in the lung.

Animals↗
PubMed1999

Basement membrane patterns, gelatinase A and tissue inhibitor of metalloproteinase-2 expressions, and stromal fibrosis during the development of peripheral lung adenocarcinoma.

To clarify the process and mechanisms of the development and progression of peripheral lung adenocarcinoma, we investigated the relationships among the patterns of basement membrane (BM), stromal fibrosis, and the expressions of gelatinase A and tissue inhibitor of metalloproteinases-2 (TIMP-2) in 33 lesions of atypical alveolar cell hyperplasia (AAH) and 48 lesions of lung adenocarcinoma, including 24 lesions of bronchioloalveolar carcinoma (BAC). We found that the architecture of alveolar BM was intact in all 33 AAH lesions and 11 nonsclerosing BAC lesions that formed no central scar, suggesting that these lesions are early-stage intraepithelial neoplasia. The preexistent BM of the lung was disrupted, and the BM components around the neoplastic glands were disrupted or absent in the area of the central scar of some sclerosing BAC lesions with collapse fibrosis alone (2 of 4) and in those of all of the adenocarcinoma lesions associated with desmoplastic stromal fibrosis (nine sclerosing BAC and 24 non-BAC tumors). These results suggested that, in lung adenocarcinomas, destruction of the BM was correlated with the formation of a central scar, particularly with desmoplasia. It is likely that adenocarcinomas with a central scar are advanced and invasive cancers potentially having metastatic activity. The expression of gelatinase A and TIMP-2 was associated with central scar formation as well as with destruction of the BM components. Both the neoplastic and stromal cells expressed gelatinase A and TIMP-2 and probably play a role in tumor cell invasion.

Adenocarcinoma↗
PubMed1999

Primary signet-ring cell carcinoma of the lung: histochemical and immunohistochemical characterization.

To establish criteria for differential diagnosis and to clarify the histogenesis of primary signet-ring cell carcinoma (SRCC) of the lung, five cases were studied by mucin-histochemical and immunohistochemical analyses and compared with SRCC of the gastrointestinal tract and mucus-producing adenocarcinoma of the lung. The proportion of signet-ring cell component varied from 10% to 90% in four cases, and the remaining tumor was a pure SRCC. Mucin-histochemistry showed a close similarity between lung SRCC and goblet cell-type or bronchial gland cell-type adenocarcinoma of the lung. Eighty percent of SRCCs showed positive immunoreactions for lactoferrin, a marker of bronchial gland cell differentiation, the results being consistent with the conclusions in previous studies that lung SRCC is closely related to bronchial gland cell-type adenocarcinoma. The incidence of K-ras mutation detected by the restriction fragment length polymorphism method was relatively high in lung SRCC (three of five) and goblet cell-type adenocarcinoma of the lung (four of four). Mucin-histochemistry indicated that lung SRCC has mucin production similar to that of the colon and colorectal-type SRCCs of the stomach but not to that of gastroduodenal-type SRCC of the stomach. Immunohistochemical staining for MUC-1 and MUC-2 glycoproteins showed a distinct difference; lung SRCC was positive for MUC-1 but negative for MUC-2, whereas colon SRCC and colorectal-type gastric SRCC were negative for MUC-1 but positive for MUC-2.Thus, by a combination of mucin-histochemistry and MUC-1 and MUC-2 immunohistochemistry, primary lung SRCC can be distinguished from metastatic lung SRCC originating in the gastrointestinal tract.

Adenocarcinoma↗
PubMed1999

Ovarian strumal carcinoid with severe constipation: immunohistochemical and mRNA analyses of peptide YY.

Functioning ovarian carcinoid tumors are well known to cause carcinoid syndrome. Recently, strumal and trabecular ovarian carcinoid tumors are reported to cause severe constipation possibly because of tumor-producing peptide YY (PYY). We studied a case of primary ovarian strumal carcinoid who had had severe constipation until the tumor was removed by surgical operation. Immunohistochemically, many tumor cells were strongly positive for PYY. By Northern blot and reverse transcription polymerase chain reaction analyses, PYY mRNA was expressed in a complete form as detected in normal human colon mucosa. From these findings, an ovarian strumal carcinoid is strongly suggested to express complete PYY mRNA and therefore complete PYY protein that results in severe constipation.

Blotting, Northern↗