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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 199 records · Page 11Linked to original sources

[Twelve cases of systemic lupus erythematosus in boys].

We compared clinical findings in 12 cases of systemic lupus erythematosus (SLE) in boys with those in 49 cases in girls. The age at which SLE developed in boys was consistent with that of infantile SLE and there was no age specificity. Momy cases in boys were diagnosed earlier as compared with cases in girls. Symptoms of infantile SLE, such as fever, arthalgia, butterfly rash, and urinary abnormalities, did not differ between boys and girls. However, a higher percentage of boys (58.3%) had central nervous system complications at onset than did girls (30.6%). Platelet counts tended to be higher in boys than in girls, a finding that suggests SLE tends to be more severe in boys than in girls. The incidence in the appiarance of LE cells, anti-Sm antibodies and immune complexes was higher in boys than in girls. Type IV or V renal pathologic changes (World Health Organization Histologic Classification) were present in 70% of boys. Our findings suggest that SLE in boys is more severe than that in girls and is more likely to be associated with central nervous system complications and severe renal complications.

Adolescent↗

[A case of renal oncocytoma associated with acquired cystic disease of the kidney].

We report a case of renal oncocytoma associated with acquired cystic disease of kidney (ACDK). A right renal mass was incidentally found on an annual ultrasonography of the kidneys in a 56-year-old female patient who had been on maintenance hemodialysis for 6 years. Computerized tomography (CT) showed a right hypervascular renal mass, suggesting a renal cell carcinoma associated with ACDK. Right radical nephrectomy was performed. The post-operative pathological diagnosis was renal oncocytoma. Renal oncocytoma in ACDK is very rare, and the pathological characteristics of oncocytoma are discussed.

Adenoma, Oxyphilic↗

Clonal selection of HIV type 1 variants associated with resistance to foscarnet in vitro: confirmation by molecular evolutionary analysis.

Foscarnet (trisodium phosphonoformate, PFA) is an effective inhibitor of retroviral reverse transcriptase (RT) and is known to block the replication of human immunodeficiency virus type 1 (HIV-1). In this article we analyzed the evolutionary process in generating HIV-1 strains related to drug resistance, using PFA as a selective pressure. PFA inhibited virus replication and protected the virus-induced cell killing, but it did not completely eliminate HIV-1 during the course of 7 weeks of treatment. The nucleotide sequence of the 859-bp DNA fragment spanning the core region of the HIV-1 pol gene was determined for 51 clones obtained from genomic DNA of the HIV-1-infected cells at different time points during PFA treatment. The nucleotide sequence analysis documented the presence of a minor HIV-1 variant prior to the PFA treatment. Molecular evolutionary techniques were utilized to analyze how the minor HIV-1 clones became predominant during this evolutionary process under the selective pressure of PFA. A phylogenetic tree analysis divided these 51 HIV-1 clones into 3 groups. One of the groups consisted of the clones associated with the resistance to PFA. The clones belonging to this group became predominant over time during the course of PFA treatment. Thus, the acquisition of PFA resistance by HIV-1 was considered to be due to clonal selection. Furthermore, among the various amino acid substitutions observed, the substitution of arginine at position 172 by lysine (Arg172Lys) clearly distinguished this group from the others. Since the consistent amino acid substitution observed here has not been identified in the HIV-1 strains resistant to other RT inhibitors, PFA in combination with other RT inhibitors is considered to be a feasible candidate for a convergent combined chemotherapy against HIV-1 in the treatment of patients with AIDS and related conditions.

Amino Acid Sequence↗

No changes in cerebrospinal fluid levels of nitrite, nitrate and cyclic GMP with aging. Short communication.

Nitric oxide (NO) is a free radical gas that plays a role in various signal transduction processes. NO has been proposed to have a function in the mechanism of synaptic plasticity, including long-term potentiation and memory formation in vivo. Because a failure in synaptic plasticity is considered to be involved in aging-associated brain dysfunction, NO production in the brain may be altered by aging. In the present study, we measured the levels of NO metabolites, nitrite and nitrate, and cyclic GMP in the cerebrospinal fluid (CSF) of human subjects without neurological or psychiatric disorders. There were no age-related changes in the CSF levels of either nitrite, nitrate or cyclic GMP. These results suggest that NO production in the brain may be maintained during the aging process.

Adult↗

Anti-granulocyte antibody suppression of active and passive anaphylactic shock in WBB6F1-W/Wv mice.

Our previous study revealed that anaphylactic shock can be produced in WBB6F1-W/Wv (abbreviated as W/Wv) mice. Because they are congenitally deficient in mast cells, we are certain that some other cell types are involved as mediator sources. In the present study, with the aim of examining the role of circulatory granulocytes, the effect of monoclonal antibody to a mouse granulocyte antigen, Gr-1, upon active and passive anaphylactic shock was tested in W/Wv mice using several mast cell-bearing strains as references. An intravenous injection of 40 micrograms of anti-granulocyte antibody one day before the antigen challenge produced a marked decrease in neutrophils and nearly complete abolition of lethal shock in W/Wv mice regardless of the sensitizing method. Both prevention of shock and reduction of neutrophils lasted for three days after the treatment with the antibody but not for six days. From these results, a reasonable conclusion would be that circulating Gr-1+ cells (predominantly composed of neutrophils) are the major mediator source. Reference experiments using mast cell-bearing strains revealed that the suppressive effect of anti-granulocyte antibody was also observed against active anaphylactic shock in C3H/HeN mice but not against active and passive anaphylactic shock in the other mice.

Anaphylaxis↗

CD8 cytotoxic T-cell clone rapidly transfers autoimmune diabetes in very young NOD and MHC class I-compatible scid mice.

A CD8 T-cell clone (YNK1.3) generated from acutely diabetic NOD mouse islets, showed proliferation and cytotoxicity when challenged with NOD and BALB/c islet cells and NOD-derived insulinoma cells. When 1-2 x 10(7) YNK1.3 cells were administered to 7-10-day-old NOD mice, the cells transferred overt diabetes very rapidly in each of the 16 recipients within 4 days of cell transfer. However, of 14 recipients receiving YNK 1.3 cells above 14 days of age none became diabetic. Fluorescent dye-labelled YNK1.3 cells extensively accumulated in the islets by 36 h after transfer in 7-day-old NOD recipients, while no significant insulitis was seen in 21-day-old recipients. Over half of NOD-scid recipients (5/9) rapidly became diabetic within 5 days after transfer of 1-2 x 10(7) YNK1.3 cells at 7 days of age, whereas only one of 12 recipients over 14 days of age became diabetic. Furthermore, YNK1.3 cells also transferred diabetes to H-2Kd-matched very young BALB/c-scid and CB17-scid mice, but not to C57BL/6-scid mice. Thus, optimally activated islet-specific CD8 T-cell clones are able to rapidly transfer diabetes to NOD and MHC class I compatible scid mice when a large enough number is administered at 7 days of age. Administration of monoclonal antibodies against adhesion molecules involved in the trafficking of lymphocytes from the circulation into the inflammatory tissues, could not prevent the cellular infiltration of YNK1.3 cells into the islets in 7-day-old NOD recipients. The results indicate that islet cells in the mouse around 7 days of age are generally susceptible to cytotoxic CD8 T cells, suggesting, therefore, that CD8 T cells may play an important role in the initiation of autoimmune diabetes in NOD mice.

Adoptive Transfer↗

Podocytes in metanephric organ culture express characteristic in vivo phenotypes.

Podocytes outgrown from isolated glomeruli in vitro have failed to express fully differentiated in vivo phenotypes. In an attempt to determine whether podocytes in metanephric culture accomplish terminal differentiation, as observed in vivo, we investigated expression of their characteristic phenotypic features in rat metanephric organ cultures using immunohistochemistry and electron microscopy. Rat metanephroi were harvested on embryonic day 12.5 and cultured on transmembrane filters for 9 days. Morphological examination revealed two maturation stages when the podocytes resembled those of the S-shaped body stage and maturational stages of glomeruli in vivo. Electron microscopy revealed that, firstly podocytes lost their intercellular contacts and, simultaneously, the tight junctions shifted into close proximity to cell bases, followed by foot process development. Immunohistochemistry demonstrated that the tight junction protein, ZO-1, and specific podocytic markers, pp44, 5-1-6, podocalyxin and vimentin were expressed in a cell maturity-dependent manner, as observed in newborn rat kidneys. Furthermore, glomerular basement membrane components, collagen type IV and laminin, were expressed in the glomerular center. Our findings that cell maturity-dependent expression of structural and functional phenotypes in podocytes in metanephric culture was the same as that observed in developing kidneys in vivo indicate that podocyte differentiation during glomerulogenesis may be operated by an intrinsic property, such as programmed cell fate. Furthermore, these highly differentiated podocytes in vitro may provide clues that will help to establish a podocyte culture system.

Animals↗

Merkel cell carcinoma with partial spontaneous regression: an immunohistochemical, ultrastructural, and TUNEL labeling study.

We report a case of Merkel cell carcinoma that partially regressed after biopsy. A 76-year-old woman presented with an 1 month history of a rapidly enlarging nodule on her left cheek. After biopsy, the nodule reduced to almost half the size and was excised 1 month later. The excised specimen showed a dense cluster of lymphocytes and fibrosis around the tumor nests. In addition, lymphocytes showed apposition with tumor cells. An immunohistologically dense, even infiltration of CD4+ and CD8+ cells was found around the tumor nests, and more CD8+ cells than CD4+ cells were seen in the tumor nests. By electron microscopy (EM), apoptosis of tumor cells and lymphocytes was observed. Many apoptotic cells were also detected by in situ nick end-labeling (TUNEL) of DNA-breaks, especially in the marginal area of tumor nests surrounded by dense lymphocytic infiltrates. It seems likely that T-cell immunity, which induces apoptosis of tumor cells, may have been involved in tumor regression.

Aged↗

Characteristics of juvenile dermatomyositis in Japan.

Questionnaires were sent to 1290 hospitals in Japan asking for data on patients with juvenile dermatomyositis (JDM) diagnosed between June 1984 and May 1994. Of the 204 patients identified by these questionnaires, 102 met the criteria for JDM. JDM is categorized into three subtypes: Banker-type JDM, Brunsting-type and fulminant-type; patients with the latter exhibit markedly elevated serum levels of creatinine phosphokinase (> 10,000 U/mL) and appear to be at risk of renal failure. Cutaneous manifestations were present in 98% of patients and preceded the appearance of other symptoms. This tendency is one of the reasons for the difficulty in some cases in diagnosing the onset of JDM. Better criteria for early treatment of JDM are needed. The results of the present study suggest that itching and calcinosis are factors that indicate a poor prognosis in patients with JDM. Muscle enzyme levels do not always reflect disease activity, suggesting that methods other than measurement of muscle enzymes, such as measurement of the levels of neoprerin and von Willebrand factor antigen, as well as magnetic resonance imaging should be used to be evaluate disease severity. Patients with Brunsting-type JDM who exhibit dysphagia and antinuclear antibody positivity and patients with Banker-type JDM should be treated aggressively. Pulse therapy should be selected as the initial therapy in patients with fulminant-type JDM.

Child↗

Outcomes of infants whose mothers are positive for human herpesvirus-6 DNA within the genital tract in early gestation.

It has been reported that HHV-6 (human herpesvirus-6) DNA has been identified within the female genital tract. However, the clinical significance of this finding has been unclear. The clinical outcome of the presence of HHV-6 DNA in the genital tract of pregnant women on their infants was evaluated in the present study. One hundred and ten pregnant women were enrolled. Vaginal swabs were collected between 4 and 8 weeks of gestation and the presence or absence of HHV-6 DNA was evaluated by nested polymerase chain reaction (nPCR). The swabs were cultured to isolate the virus. The women were divided into two groups: HHV-6 DNA-positive, and negative. The outcome variables of the infants of these two groups were statistically estimated at birth and at 1 month of age. Saliva and blood cells were collected from the infants at birth and at 1 month of age and were also evaluated by nPCR. HHV-6 DNA was detected in the vaginal swabs of 28 pregnant women (25.5%), but was not detected in any other samples, including saliva and blood cells from their infants. Virus could not be isolated from any vaginal samples. Any outcome variables were not significantly different between the two groups. The presence of HHV-6 DNA within the genital tract of pregnant women did not affect the health of their infants. It is suggested that HHV-6 transmission to infants through the genital tract of their mothers during pregnancy does not occur, or only very rarely.

Adult↗

Complications and reimplantation of penile implants.

BACKGROUND: Complications of penile prosthesis implants can be divided into surgical and mechanical failure. We investigated penile prosthesis implants to clarify the surgical and mechanical complications that have arisen in our clinical experience. METHODS: In the 11 years between 1984 and 1995, 83 penile prostheses were implanted in 74 patients ranging from 37 to 82 years of age. RESULTS: Of the 64 malleable and mechanical prostheses, 11 were extracted, including 4 removed because of surgical complications and 2 due to mechanical failure. Of the 19 inflatable prostheses, 6 were removed, including 1 extracted due to surgical complication and 5 extracted due to mechanical failure. Nine reimplantations for 8 patients were performed and all these cases had good results. As a result, 66 out of 74 patients could have coitus after prosthetic surgery. CONCLUSIONS: Penile prosthetic surgery is an established method of treating organic impotence, however, it should only be considered for selected and well-informed patients to avoid complications and revision surgery.

Adult↗

Preventive effect of oren-gedoku-to (huanglian-jie-du-tang) extract on progression of carbon tetrachloride-induced acute liver injury in rats.

The effect of oral administration of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). When TJ-15 at a dose of 500 mg/kg body weight (b.w.) was administered to male Wistar rats aged seven weeks 6 hours after i.p. injection of CCl4 (1.0 ml/kg b.w.), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found 24 hours after the injection judging from the activities of serum transaminases and other indices of liver cell damage. An increase in lipid peroxide level and decreases in reduced glutathione level and superoxide dismutase (SOD) activity occurred in the liver at 6 and 24 hours after CCl4 injection. Serum SOD activity increased 24 hours after CCl4 injection. Post-oral TJ-15 administration significantly ameliorated all these changes found at 24 hours after CCl4 injection. An increase in liver triglyceride level and a decrease in serum triglyceride level also occurred 6 and 24 hours after CCl4 injection. Post-oral TJ-15 administration prevented the increase in liver triglyceride level at 24 hours after CCl4 injection. Although the activity of liver tryptophan 2,3-dioxygenase (TDO), a marker of the inhibition of liver protein synthesis by CCl4, decreased 6 and 24 hours after injection of the toxicant, post-oral TJ-15 administration had no effect on this decrease in TDO activity at 24 hours after the injection. These results indicate that oral TJ-15 administration can prevent the progression of acute liver injury in CCl4-injected rats, and suggest that this prevention could be due to the action of TJ-15 to scavenge free radicals formed in the liver and to inhibit triglyceride accumulation in the liver.

Administration, Oral↗

Comparative study of oral and parenteral administration of sho-saiko-to (xiao-chaihu-tang) extract on D-galactosamine-induced liver injury in rats.

The preventive effect of Sho-saiko-to (Xiao-Chaihu-Tang) extract (TJ-9) on the progression of D-galactosamine (GaIN)-induced liver injury was examined in five week-old male Wistar rats with oral (p.o.) or intraperitoneal (i.p.) administration of the same dose of TJ-9. Rats treated once with GaIN (500 mg/kg body weight, i.p.) received TJ-9 at a dose of 1.0 g/kg body weight (p.o. or i.p.) 2 hours after GaIN treatment at which time an apparent liver injury occurred. Both p.o. and i.p. administration of TJ-9 showed similar significant prevention against the progression of liver injury 24 hours after GaIN injection. Although total protein and albumin concentrations in serum and protein concentration in the liver decreased with the progression of GaIN-induced liver injury, oral or i.p. administration of TJ-9 prevented these decreases in similar degree. However, decreases in serum and liver triglyceride concentration with the progression of liver injury were not attenuated after p.o. or i.p. administration of TJ-9. The activities of liver 5'-nucleotidase and glucose-6-phosphatase, marker enzymes of liver plasma and microsomal membranes, respectively, decreased during the progression of liver injury. A similar preventive effect on the decrease of both enzyme activities was found after p.o. or i.p. administration of TJ-9. These results indicate that the preventive effect on progression of GaIN-induced liver injury by oral or i.p. administration is approximately equal, and that the effect may be through improving the impaired liver protein synthesis and disrupted liver plasma and microsomal membranes in a similar degree.

5'-Nucleotidase↗

Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene that is highly homologous to genes encoding Xenopus importin, yeast SRP1 and human RCH1.

From a human fetal-brain cDNA library, we isolated and characterized a novel gene (KPNA3) encoding a protein highly homologous to certain nuclear transport proteins of Xenopus and human. The complete cDNA clone, designated karyopherin alpha 3, contained an open reading frame of 1,563 nucleotides encoding 521 amino acids. The predicted amino acid sequence showed 48%, 45% and 48% identity with Xenopus importin, yeast SRP1 and human RCH1, respectively. The similarities among these proteins suggest that karyopherin alpha 3 may be involved in the nuclear transport system. Eight repeats of the arm motif were well conserved among these proteins. The N-terminal region of the predicted karyopherin alpha 3 product was highly basic and the C-terminal region was strongly acidic. A 4.3-kb transcript was expressed in all adult human tissues examined by Northern blotting. The cDNA clone was assigned to chromosome band 13q14.3 by fluorescence in situ hybridization.

Amino Acid Sequence↗

Cloning and chromosome assignment to 1q32 of a human cDNA (RAB7L1) encoding a small GTP-binding protein, a member of the RAS superfamily.

A full-length cDNA homologous to RAB7, a member of the RAB-related GTP-binding protein subfamily, was isolated from a human placenta cDNA library. This cDNA, designated RAB7L1, has an open reading frame of 609 nucleotides encoding 203 amino acids. Northern analysis showed that the mRNA is ubiquitously expressed in human tissues, although signal intensities were different among the various organs examined. This gene was located on chromosome band 1q32 by fluorescence in situ hybridization.

Amino Acid Sequence↗