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Biomedical subjects

H Yamada

Publications and source records attributed to H Yamada.

At least 181 records · Page 10Linked to original sources

Massive intravenous immunoglobulin treatment in women with four or more recurrent spontaneous abortions of unexplained etiology: down-regulation of NK cell activity and subsets.

PROBLEM: The aims of this study were to investigate the efficacy of massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology, and to investigate changes in peripheral natural killer (NK) cell activity and subsets. METHOD OF STUDY: MIVIg treatment was performed in 18 pregnancies from 15 women with 4 or more consecutive RSA of unexplained etiology. NK cell activity and subsets were assessed in 8 of the pregnancies. RESULTS: 14 pregnancies resulted in live births and 4 resulted in abortions with chromosome abnormality. The pre-infusion NK cell activity (mean + SD. 40.9 + 17.0%) at 4.4 +/- 0.5 weeks of gestation (GW) decreased to 15.0 +/- 7.90% at post-infusion status (5.4 +/- 0.5 GW). Pre-infusion percentages of CD56+ CD16- cells (3.5 +/- 2.1%) and CD56+ CD16- cells (16.8 +/- 8.8%) decreased to 3.0 +/- 2.2% and 11.1 +/- 6.9%, respectively, after MIVIg treatment. CONCLUSIONS: MIVIg treatment was effective in all 14 pregnancies from RSA women of unexplained etiology, excluding 4 abortions with chromosome abnormality. Peripheral NK cell activity and subsets were suppressed by MIVIg treatment.

Abortion, Habitual↗

Anti-phosphatidylserine/prothrombin antibodies are not frequently found in patients with unexplained recurrent miscarriages.

OBJECTIVE: To determine whether the presence of anti-phosphatidylserine/ prothrombin antibodies (anti-PS/PT) can be a major factor in otherwise unexplained recurrent miscarriages. PATIENTS AND METHODS: Eighty-one consecutive patients with history of 2 or more recurrent miscarriages were studied. Patients with history of overt thrombotic events were not included. Patients were examined for plausible causes of miscarriages, and titer of IgG, IgM and IgA anti-PS/PT were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirty-five patients had one or more plausible causes of recurrent miscarriages, including 12 positive for well-established anti-phospholipid antibodies, such as anti-beta2-glycoprotein I. None of the patients included in this study was found to be positive for anti-PS/PT. CONCLUSION: Detection of anti-PS/PT in addition to other anti-phospholipid antibodies does not seem to aid in the evaluation of patients with unexplained recurrent miscarriages.

Abortion, Habitual↗

IgG1 anti-P2 as a marker of response to interferon in patients with chronic hepatitis C.

To study the relations of antibody production to long-term outcomes after interferon (IFN) treatment in patients with chronic hepatitis C (CH-C), we used ELISA to measure the levels of antibodies against HCV core protein and peptides. Samples from 21 complete responders and 36 non-responders were collected before IFN therapy, soon after the end of IFN therapy and 6 months later. Using a set of 19 synthesized HCV core peptide antigens, we found that anti-P2 (11-25a.a.) was the most prevalent of all IgG antibodies (93%: 39/42). Among complete responders, IgG1 anti-P2 levels had fallen by the end of IFN therapy (from 79.8 +/- 60.4-46.1 +/- 44.2: P < 0.01), and were lower still 6 months after the end of IFN therapy (31.0 +/- 35.2: P < 0.001); this change was the greatest of all antibodies studied. Among the non-responders, there was no change within the follow-up period. Soon after the end of IFN therapy, IgG1 anti-P2 levels were more than 30% lower than the initial value in more than two-thirds of the complete responders, but in only one-third of the non-responders (14/20 vs. 8/25: P < 0.05). Six months after the end of IFN therapy, IgG1 anti-P2 levels were more than 30% lower than the initial value in more than 85% of the complete responders, but in only 12% of the non-responders (17/20 vs. 3/25: P < 0.001). In conclusion, the changes in levels of IgG1 anti-P2 paralleled the activity of chronic hepatitis C after IFN therapy, and IgG1 anti-P2 levels may be markers of the efficacy of IFN therapy.

Adult↗

Persistent infection with Listeria monocytogenes in the kidney induces anti-inflammatory invariant fetal-type gammadelta T cells.

After intraperitoneal inoculation with Listeria monocytogenes, gammadelta T cells appear in the peritoneal cavity preceding the appearance of alphabeta T cells. Such gammadelta T cells predominantly express T-cell receptor (TCR)Vgamma1/Vdelta6, develop through an extrathymic pathway, and contribute to host defence against the bacteria. We have observed a gradual increase in gammadelta T cells in kidneys of mice after intrarenal inoculation with L. monocytogenes, which resulted in an unusually long-lasting local infection. In this study, we examined the characteristics and the roles of the gammadelta T cells induced in this model. It was found that these gammadelta T cells predominantly expressed TCRVgamma6/Vdelta1 with canonical junctional sequences identical to those expressed on fetal thymocytes. Although depletion of such gammadelta T cells in vivo did not affect the number of bacteria, it resulted in histologically exacerbated inflammation in the kidneys. These results indicate that a persistent infection with L. monocytogenes in kidneys induces a different kind of gammadelta T cell from that induced after intraperitoneal infection. The former expresses invariant fetal-type Vgamma6/Vdelta1+TCR and plays a regulatory role in resolution of inflammation.

Animals↗

Evidence of the extrathymic development of tyrosinase-related protein-2-recognizing CD8+ T cells with low avidity.

The majority of the human tumour-associated antigens characterized to date are derived from non-mutated self-proteins. However, nothing is known about the development of autoreactive and tumour-associated antigen-recognizing T cells. Tyrosinase-related protein (TRP)-2 is a non-mutated melanocyte differentiation antigen and TRP-2-recognizing CD8+ T cells are known to show responses to melanoma both in humans and mice. In addition, TRP-2-reactive T cells with low avidity have been suggested to be readily induced from the spleen cells of naïve mice. On the other hand, recent reports suggest that self antigen-reactive CD8+ T cells can be positively selected in the periphery. In this study, we tested the possibility that TRP-2-reactive CD8+ T cells in naïve mice could develop via the extrathymic pathway. As a consequence, TRP-2-reactive CD8+ T cell precursors in naïve C57BL/6 mice were suggested to express both interleukin-2 (IL-2) receptor beta chain (IL-2Rbeta) and CD44 molecules, in a manner similar to that of extrathymically developed T cells. Furthermore, IL-2Rbeta+ CD44+ CD8+ T cells were detected in the adult thymectomized and bone marrow-reconstituted mice, and functional TRP-2-reactive T cells were generated from their spleen cells. Overall, these results suggest that low avidity CD8+ T cells recognizing TRP-2 can be developed extrathymically.

Animals↗

A novel heat stress-responsive gene in the marine diatom Chaetoceros compressum encoding two types of transcripts, a trypsin-like protease and its related protein, by alternative RNA splicing.

We investigated the change of mRNA expression patterns in the laboratory-grown diatom Chaetoceros compressum under heat-stress conditions by mRNA arbitrarily primed (RAP) RT-PCR. Cells grown at 20 degrees C were subjected to heat treatment at 30 degrees C for 15 min and subsequently maintained at 20 degrees C for 8 h. Four genes including HI-5 were detected as heat stress-responsive genes by fingerprint analysis of RAP RT-PCR. Cloning for full-length cDNA sequences of HI-5 transcripts and related genomic DNA analysis revealed that two types of mRNA, HI-5a and HI-5b, were transcribed from the single HI-5 gene. While the HI-5a protein contained a catalytic domain characteristic to trypsin-like proteases, the HI-5b protein lacked this domain due to an insertion in the associated mRNA of 112 nucleotides; this insertion sequence contained a stop codon near the central region. Quantitative RT-PCR was performed to investigate the changes in expression levels of the two types of mRNA following heat treatment. The HI-5b transcripts were constitutively expressed in both unstressed and heat-stressed cells. In contrast, the number of HI-5a transcripts markedly increased in cells immediately after heat stress, reaching levels 19-fold higher at 8 h after heat stress than that in unstressed cells. These results suggest that RNA splicing plays a key role in heat stress-dependent expression of the HI-5a and HI-5b transcripts from the single HI-5 gene in the diatom.

Alternative Splicing↗

Ganglioside as an endogenous growth suppressor for glomerular mesangial cells.

BACKGROUND: Glomerular mesangial cells potentially secrete many growth-modulating substances that could regulate mesangial cell proliferation. To date, however, the properties of such factors have not been fully evaluated. METHODS: For that purpose, conditioned medium (CM) from mesangial cells was used for cross-feeding experiments. Cell proliferation was evaluated by 3H-thymidine incorporation assay and direct cell counting. The growth-regulatory molecule was further characterized using biochemical techniques. RESULTS: Cross-feeding this CM to mesangial cells in vitro, despite stimulation with platelet-derived growth factor (PDGF), effectively suppressed the cells' synthesis of DNA in a dose-dependent manner. The inhibitory substance derived from mesangial cells was less than 3 kD in molecular mass, was heat stable, and was insensitive to proteinase K. After neuraminidase digestion, this inhibitory activity was lost. These data indicated that the inhibiting substance bore the typical features of gangliosides, which are multifunctional glycolipids that reside in cell membrane. Gangliosides were abundant in the CM from mesangial cells, as detected by metabolic radiolabeling and thin-layer chromatography (TLC). This result suggested that mesangial cells constitutively shed gangliosides. The growth suppressive activity in the CM was blunted when mesangial cells were pretreated with the ganglioside synthesis inhibitor d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl (d-threo-PDMP; 20 micromol/L) in accordance with the decreased ganglioside content in cells. Finally, gangliosides isolated from CM of mesangial cells suppressed PDGF-induced DNA synthesis of mesangial cells. CONCLUSIONS: These results suggest that mesangial cells constitutively shed gangliosides that then suppress the division of these cells in an autocrine-like manner.

Animals↗

Histologic analysis of the tibial bone tunnel after anterior cruciate ligament reconstruction using solvent-dried and gamma-irradiated fascia lata allograft.

Anterior cruciate ligament (ACL) reconstruction using free tendon graft requires biologic fixation in the bone tunnel. This report describes the intratunnel histology retrieved from a 47-year-old woman who underwent high tibial osteotomy 17 months after ACL reconstruction using a hybrid graft (a solvent-dried and gamma-irradiated fascia lata allograft as a core wrapped with iliotibial autograft). The patient underwent revision because of pain resulting from osteoarthrotic change, and the graft appeared to be taut and healthy on second-look arthroscopy. The sample was taken from the site of the metaphyseal osteotomy site. Histologic examination of the samples was performed with a light microscope (H&E and Masson trichrome stain). Biologic fixation of the graft to the bone was evident from observation of collagen fiber continuities, resembling Sharpey fibers. Integration of the autograft and allograft seemed to have occurred; the junction between the allograft and the autograft could not be determined. However, there was a difference in ligamentization depending on location. In the peripheral region of the graft (the autograft region), the collagen fibers showed a distinct crimped pattern; the fibroblasts were arranged regularly along the major axis of the collagen fiber bundle. In the central part of the graft (the allograft region), remodeling seemed to be delayed. There were acellular, bubbly or myxoid degeneration areas in which the fiber bundles were less oriented and there was increased vascularity.

Anterior Cruciate Ligament↗

Effects of high molecular weight hyaluronan on the distribution and movement of proteoglycan around chondrocytes cultured in alginate beads.

OBJECTIVE: To evaluate the effects of high molecular weight hyaluronan (HA) on the distribution and movement of proteoglycan (PG) formed around rabbit chondrocytes cultured in alginate beads. DESIGN: Rooster comb-derived HA (MW 8x10(5) Da) was co-polymerized in alginate gel to study the direct effects of extrinsic HA on chondrocytes. PG metabolism of rabbit chondrocytes cultured in alginate beads was examined by measuring the incorporation of [(35)S]sulfate into glycosaminoglycan in two distinct regions, the cells with their cell-associated matrix (CM) and the further-removed matrix (FRM). Immunohistochemical analysis was performed using monoclonal antibodies against chondroitin sulfate and keratan sulfate. Autoradiography using degenerated cartilage tissue from the rabbit osteoarthritis (OA) model was performed to discover the effect of HA on the distribution of newly-synthesized PG in the cartilage tissue. RESULTS: The incorporation of [(35)S]sulfate into newly-synthesized PG in the cells with CM decreased with the addition of 0.125-1.0 mg/ml HA, while the incorporation in the FRM increased. These effects of HA on the distribution of newly-synthesized PG were the same either in chondrocytes with CM or chondrocytes without CM. Immunohistochemical analysis showed that staining of PG in the CM was decreased and staining in the FRM was increased in the HA treated group compared to the control group. Autoradiography using degenerated cartilage tissue from the rabbit OA model indicated that [(35)S]-labeled macromolecules showed a more diffuse distribution in the HA treated group compared with the control group. CONCLUSION: These results indicate that extrinsic HA could affect the movement of newly-synthesized PG from the CM to the FRM in both alginate beads and cartilage tissue.

Adjuvants, Immunologic↗

Recurrent pregnancy loss: etiology of thrombophilia.

Congenital and acquired thrombophilia are associated with an increased risk of pregnancy-associated venous thrombosis and fetal loss. Two hundred eighty-nine patients with a history of recurrent spontaneous abortion were subjected to screening examinations for the etiology of these abortions. Endocrine abnormality (28.0%), uterine abnormality (10.4%), autoimmune diseases (1.4%), antiphospholipid antibody syndrome (4.5%), and balanced type chromosome translocation (4.2%) were found as underlying causes of recurrent abortions, and the remaining 55.0% of the 289 patients were classified as having an unexplained etiology. Congenital thrombophilia such as protein C (PC) deficiency, protein S (PS) deficiency, antithrombin deficiency, and factor V Leiden mutation was not frequently detected; only one patient had PS deficiency. A reduced factor XII activity was found at a frequency of 4.2%. The frequency of methylene tetrahydrofolate reductase gene C677T mutation in recurrent aborters (0.38) was the same as that found in a fertile control group. Although the prevalence of anti-beta2-glycoprotein I antibody (abeta2-GPI) syndrome was very low (1.7%), patients with a high titer of immunoglobulin G (IgG) class abeta2-GPI, despite anticoagulation therapy, experienced severe fetomaternal complications in subsequent pregnancies. The rate (13.8%) of positive tests for serum IgA class abeta2-GPI in patients with unexplained etiology was higher than that in the controls (0%) (P < .05). We conclude that congenital thrombophilia is rare in Japanese patients who had experienced consecutive spontaneous abortions.

Abortion, Habitual↗

Multivariate analysis of genetic and acquired factors; T235 variant of the angiotensinogen gene is a potent independent risk factor for preeclampsia.

Preeclampsia is known to be a multifactorial disease. Recently, the angiotensinogen gene has been shown to be a candidate gene that could be related to preeclampsia, and acquired factors such as lifestyle during pregnancy have also been considered to be risk factors. The aim of this study was to investigate the interrelations among the angiotensinogen gene and various acquired risk factors in preeclampsia. Fifty-eight primiparous patients with pre-eclampsia were compared with 164 normal primiparous controls. A variant of the angiotensinogen gene (M235T) was analyzed along with the acquired factors obtained from both medical records and a questionnaire consisting of 98 questions. Univariate analysis disclosed 11 factors that were significantly associated with preeclampsia (P < .05). Multivariate analysis revealed four significant independent factors: "prepregnancy high body mass (body mass index > or = 24)," "T235 homozygotes of the angiotensinogen gene," "mentally stressful condition during pregnancy," and "salty dishes preferred during pregnancy." The odds ratios of the four factors were 6.2, 2.5, 3.0 and 2.6, respectively, in a multiple logistic model. Our results support the concept that T235 of the angiotensinogen gene is a potent, independent risk factor for preeclampsia, as well as other lifestyle-related risk factors.

Adult↗

Acidic polysaccharides from rhizomes of Atractylodes lancea as protective principle in Candida-lnfected mice.

Prophylactic effects upon imunnosuppressed mice lethally infected by Candida albicans were examined in fractions prepared from a constituent herb of Juzen-taiho-to (TJ-48, Si-Quan-Da-Bu-Tang), rhizomes of Atractylodes lancea DC. The oral administration of water extract obtained from a residue after MeOH extraction of rhizomes significantly prolonged the survival period of the infected mice at a dose of 140 mg/kg/day compared with control mice, while the MeOH extract did not. In the crude polysaccharide fraction (F-2) obtained by EtOH precipitation of the water extract, a significant life-prolonging effect was observed by the administration of 70 mg/kg/day. F-2 was further fractionated, and the resulting strongly acidic polysaccharide fraction, F-2-2, had a protective effect at a dose of 17.5 mg/kg/day. This fraction mainly consisted of acidic pectic polysaccharides containing about 80% galacturonic acid. The protective activity of F-2-2 was lost by periodate oxidation, but not by protease digestion, suggesting that the polysaccharide component of F-2-2 plays a major role in the protective activity against Candida-infected mice.

Animals↗

Pyoderma gangrenosum associated with biphenotypic acute leukemia.

Pyoderma gangrenosum is a neutrophilic dermatosis that may be associated with myeloid malignancies. Less information is available about the association of pyoderma gangrenosum with lymphoid malignancies. We present, to our knowledge, the first case of pyoderma gangrenosum associated with biphenotypic acute leukemia wherein the malignant cells show a phenotype specific for myelogenic and lymphocytic leukemia. Histopathologic examination revealed rather nonspecific features without involvement of leukemic cells in the skin lesions. Treatment with systemic steroids was followed by characteristically rapid healing of the skin lesion.

Female↗

Age-related changes in cortical and trabecular bone mineral status. A quantitative CT study in lumbar vertebrae.

PURPOSE: To investigate the age and sex dependence of the bone mineral status of human lumbar vertebrae with special regard to differences between cortical and trabecular bone. MATERIAL AND METHODS: The study group comprised 125 normal Japanese healthy volunteers (54 males and 71 females), and was subdivided into adult male and female groups (subjects younger than 40 years), intermediate male and female groups (ages ranging between 41 and 64 years) and old male and female groups (subjects older than 65 years). The cortical bone mineral status was estimated using a single-energy quantitative CT (SE-QCT) technique, whereas trabecular bone mineral density (BMD) was estimated using a dual-energy (DE-QCT) technique. RESULTS: A considerable gender difference in the age-related cortical bone status was found. There was a significant reduction of the mean values of the cortical volume and BMD in the old female group compared with those obtained in the old male group. CONCLUSION: The results suggest that in men, cortical and trabecular bone volume decrease very little with age. In women, cortical volume and BMD and trabecular BMD decrease with age while trabecular bone volume does not. The study showed that all variables had higher values in men than in women and that the difference increased with age.

Adult↗

Muscle repair after a transsection injury with development of a gap: an experimental study in rats.

Lacerated muscle needs fusion with muscle fibres to regain good function, but it often lose its elasticity and the repair seems poor. We think that the scar healing is caused by the development of a gap. In this study in 20 rats we made silicone tube models to keep a constant distance between the muscle ends, and examined the repair inside the silicone tube. In the short gap (1 mm), aligned collagen fibres and muscle fibres bridged both ends. However, when the gap was long (4 mm) they could not bridge both ends and collagen fibres covered the cut ends of muscle. Muscle contains a large fibrous component and will regenerate simultaneously after transsection injury. This result suggests that fibrous repair influences the muscle repair and muscle regeneration will be disturbed as the gap widens.

Animals↗