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Biomedical subjects

K Kato

Publications and source records attributed to K Kato.

At least 487 records · Page 27Linked to original sources

Successful bone marrow transplantation in a child with X-linked hyper-IgM syndrome.

We report a case of an 11-year-old boy who underwent successful bone marrow transplantation for X-linked hyper-IgM syndrome (XHIM). The donor was an HLA-matched brother. The patient was conditioned with busulfan, cyclophosphamide and anti-thymocyte globulin. He received 4.7 x 10(8) marrow cells per kg from the donor. Prophylaxis against graft-versus-host disease consisted of cyclosporine and short-term methotrexate. The clinical course after the bone marrow transplantation was uneventful, and 12 months after transplantation the patient was doing well with no need for therapy. We examined expression of the CD40 ligand (CD40L) on the patient's activated T lymphocytes and in vitro production of immunoglobulins by his lymphocytes. Although expression of CD40L was totally absent before the bone marrow transplant, subnormal expression appeared after the transplantation. In vitro production of IgG and IgA also was improved by the transplant. Based on our experience bone marrow transplantation appears to be a reasonable therapeutic option for patients with XHIM if HLA-matched family donors are available.

Bone Marrow Transplantation↗

Long-term liver function of recipients with hepatitis G virus infection after bone marrow transplantation.

To clarify the role of hepatitis G virus (HGV) infection in liver dysfunction following allogeneic BMT, we examined cryopreserved serum samples from 33 patients who had a history of blood transfusions before BMT and whose serum samples had been stored periodically, before BMT, on day 100, and thereafter for the presence of HGV-RNA and hepatitis C virus (HCV)-RNA by reverse transcription polymerase chain reaction. Nineteen patients (58%) out of 33 were positive for HGV-RNA before BMT and 10 for HCV-RNA. All patients positive for HCV-RNA were also positive for HGV-RNA. Patients were divided into three groups according to their viral status before BMT; namely, the G+C+ group (n = 10), the G+C- group (n = 9) and the G-C- group (n = 14). Two patients in the G-C- group became positive for HGV-RNA after BMT. One patient in the G+C- group suffered an acute exacerbation of hepatitis, with GPT levels reaching over 1000 IU/l, 2 and 3 years after BMT, showing quite a different clinical course from those in the G+C- group. Excluding these three patients, GPT levels of the patients in the G+C+ group were significantly higher after day 100 and remained higher than those of patients in the G+C- and G-C- groups for at least 4 years. There were no significant differences in post-transplant GPT levels between the G+C- group and the G-C- group at any time point. Of the seven patients followed-up for 5 to 10 years, three patients became HGV-RNA-negative, while four remained positive. In the absence of HCV co-infection, the behavior of GPT values post transplant in patients with HGV infection did not differ from those without HGV infection. With respect to the patient who was G+C- and showed high values of GPT 2 and 3 years post transplant, we suspect that his liver dysfunction might have been caused by some unknown virus or etiology.

Adolescent↗

Patent ductus venosus.

BACKGROUND: Patent ductus venosus is extremely rare with only 14 cases reported in the world literature. We present a case of patent ductus venosus. METHODS AND RESULTS: A 29-year-old male was admitted with melaena stool caused by gastric haemorrhagic ulcers. Laboratory data disclosed severe anaemia; however, liver function tests were normal. Serum ammonia was also within the normal range. Serological viral markers for hepatitis B or C were all negative. The abdominal ultrasonography and computed tomography indicated a 12 mm diameter shunt located in the left lobe of the liver, which connected the portal vein with the left hepatic vein. After treatment for gastric ulcers, percutaneous transhepatic portography was performed and an enormous shunt connecting the umbilical portion of the portal vein with the left hepatic vein was revealed. CONCLUSIONS: Histological findings of the liver biopsy showed that portal venules could not be observed in the portal areas and that no fibrosis or inflammatory cell infiltration were shown. Because of the anatomical position of the shunt, the case was diagnosed as patent ductus venosus.

Adult↗

A case of large cell calcifying Sertoli cell tumor in a child with a history of nasal myxoid tumor in infancy.

A case of an 8-year-old Japanese boy with a testicular large cell calcifying Sertoli cell tumor (LCCSCT) is presented. This report appears to be the first Japanese case of LCCSCT. The patient presented with left testicular swelling and gynecomastia. His family history was not contributory; however, his past history was remarkable for a benign myxoid tumor in the nasal cavity, which was removed at the age of 2 months. After removal of the testicular tumor, the gynecomastia disappeared gradually and no recurrence or metastasis developed during a 15 month follow-up period. Although the tumor was initially interpreted as a Leydig cell tumor, a review of the slides after the patient's past history of nasal myxoid tumor was revealed led us to the diagnosis of LCCSCT. An accurate diagnosis of LCCSCT is crucial because this tumor is occasionally associated with Carney complex, which can comprise various pathological conditions, including cardiac myxoma, that may be life-threatening. Myxoma of Carney complex has been described to occur in the heart, skin, oral cavity and breast in a wide age range, but there have been no reports referring to nasal myxoid tumor associated with Carney complex.

Calcinosis↗

Nasal chondromesenchymal hamartoma of infancy: the first Japanese case report.

The first Japanese case of nasal chondromesenchymal hamartoma, a rare infantile nasal neoplasm, is presented. A 4-month-old Japanese boy was referred to our Centre because of intranasal mass and oculomotor disturbance. Radiological images showed the intranasal tumor extending to the paranasal sinus, orbit, and anterior frontal fossa. Subtotal resection and radiation therapy to residual tumor were performed. There has been no recurrence of the tumor for 13 years. Histologically, the lesion demonstrated admixture of various mesenchymal elements, including cellular spindle cell stroma with occasional myxoid change, nodules of mature/immature cartilaginous tissue, focal osteoclast-like giant cells, and erythrocyte-filled spaces resembling aneurysmal bone cyst. The histology was consistent with the findings presented by McDermott et al. 1986. Immunohistochemically, the spindle cells were positive for vimentin and smooth muscle actin. Chondrocytes in the mature cartilaginous tissue were positive for S-100 and vimentin; chondrocytes in the immature cartilaginous tissue were positive for S-100, vimentin, and smooth muscle actin. Ultrastructurally, the spindle cells showed features of either fibroblast or myofibroblast.

Frontal Bone↗

CNS-specific prostacyclin ligands as neuronal survival-promoting factors in the brain.

Prostacyclin (PGI2) is a critical regulator of the cardiovascular system, via dilatation of vascular smooth muscle and inhibition of platelet aggregation (Moncada, S. 1982, Br. J. Pharmacol., 76, 3). Our previous studies demonstrated that a novel subtype of PGI2 receptor, which is clearly distinct from a peripheral subtype in terms of ligand specificity, is expressed in the rostral region of the brain, e.g. cerebral cortex, hippocampus, thalamus and striatum, and that (15R)-16-m-17,18,19,20-tetranorisocarbacyclin (15R-TIC) and 15-deoxy-16-m-17,18,19,20-tetranorisocarbacyclin (15-deoxy-TIC) specifically bind to the central nervous system (CNS)-specific PGI2 receptor. Here, we report that these CNS-specific PGI2 receptor ligands, including PGI2 itself, prevented the neuronal death. They prevented apoptotic cell death of hippocampal neurons induced by high (50%) oxygen atmosphere, xanthine + xanthine oxidase, and serum deprivation. IC50s for neuronal death were approximately 30 and 300 nM for 15-deoxy-TIC and 15R-TIC, respectively, which well correlated with the binding potency for the CNS-specific PGI2 receptor. 6-Keto-PGF1alpha (a stable metabolite of PGI2), peripheral nervous system-specific PGI2 ligands and other prostaglandins (PGs) than PGI2 did not show such neuroprotective effects. In vivo, 15R-TIC protected CA1 pyramidal neurons against ischaemic damage in gerbils. These results indicate that CNS-specific PGI2 ligands have neuronal survival-promoting activity both in vitro and in vivo, and may represent a new type of therapeutic drug for neurodegeneration.

Animals↗

A novel subtype of prostacyclin receptor in the central nervous system.

Recently, in the course of our search for the prostacyclin receptor in the brain, we found a novel subtype, designated as IP2, which was finely discriminated by use of the specific ligand (15R)-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin (15R-TIC) and specifically localized in the rostral part of the brain. In the present study, the tritiated compound 15R-[15-(3)H]TIC was synthesized and utilized for more specific research on IP2. The specificity of binding to rat brain regions was confirmed by use of several prostacyclin derivatives including 15S-TIC. Mapping of 15R- and 15S-[3H]TIC binding in adjacent pairs of frozen sections of rat brain demonstrated a quite similar pattern of distribution in almost all rostral brain regions, indicating that the regions may contain only the IP2 subtype. On the other hand, 15R-[3H]TIC binding was very faint as compared with 15S-[3H]TIC binding in the caudal medullary region. High densities of 15R-[3H]TIC binding sites were shown in the dorsal part of the lateral septal nucleus, thalamic nuclei, limbic structures, and some of the cortical regions. Scatchard plot analysis showed two components of high-affinity 15R-[3H]TIC binding in the rostral regions, one with a K(D) value at approximately 1 nM and the other with approximately 30 nM. These results strengthen our previous finding that a different subtype of prostacyclin receptor is expressed in the CNS, and the map with 15R-[3H]TIC obtained here could guide further studies on the molecular and functional properties of the IP2.

Animals↗

Responses of heat shock proteins hsp27, alphaB-crystallin, and hsp70 in rat brain after kainic acid-induced seizure activity.

We determined the changes in the levels of the mammalian small heat shock protein of 25-28 kDa (hsp27) and the hsp alphaB-crystallin in various regions of rat brain after kainic acid-induced seizure activity by means of specific immunoassays. The levels of hsp27 in the hippocampus and entorhinal cortex were markedly increased and reached a maximum (1.5-2 microg/mg of protein) 2-4 days after the seizure. The levels of hsp27 in these regions were considerably high even 10 days after the seizure. A marked increase in levels of mRNA for hsp27 was also observed in the hippocampus of rats 1-2 days after the seizure. A severalfold increase in the levels of alphaB-crystallin was observed in the hippocampus and entorhinal cortex of rats 2 days after the seizure. However, the maximum levels were <50 ng/mg of protein. The levels of protein sulfhydryl group and glutathione were significantly reduced in the hippocampus of rats at 24 h after the seizure, which might have enhanced the expressions of hsp27 and alphaB-crystallin. The expression of inducible mammalian hsp of 70 kDa (hsp70) was also enhanced in the hippocampus of rats after the seizure, as detected by western and northern blotting analyses. Immunohistochemically, an intensive staining of hsp27 was observed in both glial cells and neurons in the hippocampus, piriform cortex, and entorhinal cortex of rats with kainic acid-induced seizure. However, in the cerebellum, where the receptors for kainic acid are also rich, hsp27 was barely induced in the same rats. This might be due to high levels of the cerebellar calcium-binding proteins parvalbumin and 28-kDa calbindin-D, which might have a protective effect against the kainic acid-inducible damage.

Animals↗

High expression of the gamma5 isoform of G protein in neuroepithelial cells and its replacement of the gamma2 isoform during neuronal differentiation in the rat brain.

High concentrations of G proteins, which include multiple isoforms of each subunit, alpha, beta, and gamma, are expressed in the adult brain. In this study, we concentrated attention on changes of these isoforms during embryonic development in the rat brain. Concentrations of gamma2 as well as GoAalpha, GoBalpha, and beta2 were low in early embryogenesis and then increased, whereas expression of gamma5, in contrast, was initially high followed by a drop, with only very low levels observed throughout postnatal development. Among the other isoforms, Gi1alpha, G(s)alpha-short, G12alpha, G13alpha, beta4, gamma3, gamma7, and gamma12 were present in the embryonic brain at low levels, but their levels markedly increased after birth. In contrast, the levels of Gi2alpha, G(s)alpha-long, Gq/11alpha, and beta1 were essentially constant throughout. Immunohistochemical staining of the brain vesicles in the embryos showed gamma5 to be specifically expressed in the proliferative region of the ventricular zone, whereas gamma2 was mainly present in differentiated neuronal cells of the marginal zone. Furthermore, differentiation of P19 mouse embryonal carcinoma cells to neuronal cells with retinoic acid induced the expression of gamma2 and a decrease of gamma5, the major isoform in the undifferentiated state. These results suggest that neuronal differentiation is responsible for the on/off switch of the expression of gamma2 and gamma5 subunits.

Animals↗

Comparison of MR imaging with CT in depiction of tumour extension into the pterygopalatine fossa.

The computed tomography (CT) and magnetic resonance imaging (MRI) results of 30 consecutive patients with tumours in the skull base, and who had abnormalities of the pterygopalatine fossa (PPF) on CT or MRI, were retrospectively compared with respect to visualization of tumour infiltration into the PPF. CT did not depict the abnormalities in the PPF in five patients (17%), while unenhanced T1-weighted MR images depicted tumour infiltration in all patients. Obliteration of PPF fat was better visualized on CT than T2-weighted and proton density weighted MR images, as were bony abnormalities. On MRI, intracranial extension was seen in eight of 25 patients with extracranial tumour. MRI is a sensitive method of demonstrating both tumour infiltration of the PPF and perineural tumour spread.

Adolescent↗

Extracellular matrixes influence alpha-smooth muscle actin expression in cultured porcine lens epithelial cells.

PURPOSE: To determine whether extracellular matrix (ECM) influences the expression of alpha-smooth muscle actin (alpha-SMA), a marker for myofibroblasts, in cultured porcine lens epithelial cells (LECs). METHODS: Porcine LECs were cultured for 6 days in an F-12 nutrient mixture supplemented with 5% fetal bovine serum on wells that were coated with laminin, fibronectin, type I collagen, or type IV collagen. LECs cultured on uncoated wells served as a control. Alpha-SMA was detected immunocytochemically with a mouse monoclonal antibody, and the ratio of the number of alpha-SMA-positive cells to the total number of cells, the P/T ratio, was calculated. RESULTS: The P/T ratio of the LECs on the uncoated dishes was about 5%. LECs cultured on wells coated with laminin or type IV collagen significantly reduced the ratio, whereas fibronectin or type I collagen had no effect. CONCLUSIONS: The ECM influences alpha-SMA expression in cultured porcine LECs.

Actins↗

Immobilization of DNA by UV irradiation and its utilization as functional materials.

The water-insoluble DNA film was successfully prepared by UV irradiation. The DNA film was stable in water. It could effectively accumulated the DNA-binding intercalating materials, such as ethidium bromide, dibenzo-p-dioxin and benzo[a]pyrene, in their aqueous solutions. On the other hand, DNA was immobilized onto nonwoven cellulose fabrics, also by the UV irradiation. The DNA immobilized cloth was found to bind silver ions. The DNA-cloth containing silver ion showed antibacterial activity. The water-insoluble DNA prepared by UV irradiation has a potential ability to serve as biomaterials for medical, engineering and environmental objects.

Animals↗

Chemical synthesis and properties of (6-4) photoproduct and its analogs.

We report the preparation of a deoxyribooligonucleotide containing a new thymine (6-4) photoproduct analog. The (6-4) photoproduct is one of the major forms of DNA lesions, and leads to mutation in DNA. An antibody (64M5) that binds the (6-4) photoproduct has been described. To investigate the interaction of the photoproduct with the 64M5 antibody, we prepared a (6-4) photoproduct analog in which the two thymines were connected with a formacetal linkage. With UV-irradiation, the thymine dimer with the formacetal linkage reacted to the (6-4) photoproduct faster than the phosphodiesterified dimer, and the yields of the analog was higher than those of the natural thymine dimer. The 64M5 antibody exhibited sufficient binding to a tetranucleotide containing the (6-4) photoproduct analog with a formacetal linkage, although the association constant was slightly lower than that for the natural lesion. This (6-4) photoproduct analog may be useful for investigation of other proteins that recognize the (6-4) photoproduct.

Antibodies↗

Diverse glycosylation of MUC1 and MUC2: potential significance in tumor immunity.

Mucins are major epithelial luminal surface proteins and function as a physical and biological barrier protecting mucous epithelia. Diverse glycosylation of mucins potentially provides a basis for tissue-specific interaction with the milieu. When mucins are associated with malignant epithelial cells, they not only protect these cells from a host environment during metastatic dissemination but also generate immunogenic epitopes which are used by the host in the detection and immunological elimination of carcinoma cells potentially depending upon their status of glycosylation. Diverse mucin structures are generated by the combination of different core peptides, of which 10 have been reported so far, multiple types of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (pp-GalNAc-Ts), and the consequences of stepwise glycosylation events. For example, the mucin 1 (MUC1) associated with malignant cells was previously believed to exhibit unique features with a lower percentage of threonine and serine residues attached to N-acetylgalactosamine and/or without extension through core 2 structures. Some of MUC1-specific monoclonal antibodies and cytotoxic lymphocytes recognize the peptide sequences PDTR within the tandem repeat portion exposed by decreased degree of glycosylation. The specific arrangement of N-acetylgalactosamine residues is shown to be generated by a combination of pp-GalNAc-Ts with different specificities. The role of core 2 branching is somewhat confusing because well-known carcinoma-associated carbohydrate epitopes such as sialyl-Le(X), sialyl-Le(a), Le(Y), and others are often expressed when O-glycans are extended through core 2 branching. The other series of well-known carcinoma-associated carbohydrate structures are truncated O-glycans, conventionally called Tn and sialyl-Tn antigens. Interestingly, these are often found to be aligned on core polypeptides, resulting in three or more consecutive truncated O-glycans. MUC2 and other mucins, but not MUC1, have unique tandem repeats containing three or more consecutive serine or threonine residues, which potentially serve as a scaffold for trimeric Tn and sialyl-Tn epitopes. We recently found, using the MUC2 tandem repeat, that trimeric Tn is a high-affinity receptor for a calcium-type lectin expressed on the surface of histiocytic macrophages. The biosynthesis of trimeric Tn was strictly regulated by the acceptor specificity of pp-GalNAc-Ts. These results strongly suggest that variation in both glycan structures and distribution of glycans on the core polypeptides give mucins unique and diverse biological functions that play essential roles in carcinoma-host and other cellular interactions.

Amino Acid Sequence↗

Focused Assessment with Sonography for Trauma (FAST): results from an international consensus conference.

OBJECTIVE: To assemble an international panel of experts to develop consensus recommendations on selected important issues on the use of ultrasonography (US) in trauma care. SETTING: R Adams Cowley Shock Trauma Center, University of Maryland Medical System, Baltimore, Md. The conference was held on December 4, 1997. PARTICIPANTS: A committee of two co-directors and eight faculty members, in the disciplines of surgery and emergency medicine, representing four nations. Each faculty member had made significant contributions to the current understanding of US in trauma. RESULTS: Six broad topics felt to be controversial or to have wide variation in practice were discussed using the ad hoc process: (1) US nomenclature and technique; (2) US for organ-specific injury; (3) US scoring systems; (4) the meaning of positive and negative US studies; (5) US credentialing issues; and (6) future applications of US. Consensus recommendations were made when unanimous agreement was reached. Majority viewpoints and minority opinions are presented for unresolved issues. CONCLUSION: The consensus conference process fostered an international sharing of ideas. Continued communication is needed to advance the science and technology of US in trauma care.

Certification↗