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Biomedical subjects

N Yoshikawa

Publications and source records attributed to N Yoshikawa.

At least 145 records · Page 8Linked to original sources
PubMed1993

Studies of thyroid xenografts from Graves' disease in severe combined immunodeficient mice.

Thyroid tissues from normal (paranodular) subjects and patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT) were xenografted to severe combined immunodeficiency (SCID) mice, and the same tissues were engrafted into nude mice; in addition, peripheral blood mononuclear cells were engrafted to separate SCID mice (SCID-PB). Thyroglobulin (TG) and microsomal antibodies (Abs) became detectable with high titers by hemagglutination assays in SCID mice xenografted with thyroid tissues (SCID-TH) from GD and HT patients; moreover, TG Ab was detectable even in SCID-TH from TG Ab-negative GD and HT donors. On the other hand, only 2 of 10 SCID-PB had detectable Abs with low titers. TSH receptor (TSH-R) Ab was detectable in all sets of SCID-TH from GD. After peaking (3-7 weeks), their levels decreased despite the fact that immunoglobulin G levels increased. In addition, in 3 of 4 sets of SCID-PB from GD patients, TSH-R Ab was also detectable. SCID-TH from GD and HT patients showed transient hyperthyroxinemia, peaking at 2 weeks; these values were significantly higher [free T4, 6.48 +/- 0.90 and 5.50 +/- 0.77 pmol/L (mean +/- SE), respectively; P < 0.05] than SCID-TH from normal controls (2.5 +/- 0.24). Histologically, intrathyroidal infiltrating lymphocytes (ITL) survived in SCID mice, but not in nude mice after 8 weeks. The follicles of GD tissue in SCID mice were virtually destroyed with ITL, and their appearance was similar to that in HT. In conclusion, TSH-R Ab was clearly produced from ITL, and some peripheral blood mononuclear cells grafts could also produce TSH-R Ab. In spite of the presence of TSH-R Ab, SCID-TH from GD patients did not show persistent hyperthyroxinemia, presumably because destructive thyroiditis may be occurring in the grafted tissue, with decreasing levels of TSH-R Ab.

Animals↗
PubMed1993

Measurement of erythrocyte Na,K-ATPase activity in normal pregnant women.

To investigate the peripheral metabolic status during normal pregnancy, we measured the number of erythrocyte Na,K-ATPase units as well as the cation transport activity of the pump from 32 normal pregnant women and 12 normal controls. The number of pump units determined by maximal ouabain binding to erythrocyte in normal pregnancy was significantly higher than that in normal controls (mean +/- SEM: 0.52 +/- 0.03 vs. 0.39 +/- 0.04 pmol/10(9)RBC, P < 0.05). The total cation transport activity of the pump measured by 86Rb uptake also significantly increased during pregnancy (98.9 +/- 6.4 vs. 73.1 +/- 5.4 nmol/10(9) RBC, P < 0.01). However, the mean cation transport activity per pump unit, which was presumed to be an indicator of the peripheral metabolic status, was unchanged in any of three trimesters when compared with that in normal controls. Serum FT4 levels measured by two different methods were significantly lower in the third trimester than in the first trimester (P < 0.01). In conclusion, erythrocyte Na, K-ATPase activity per pump unit is normal in pregnant women, suggesting that the peripheral metabolic status in pregnancy seems to be normal. Increases in both the number and function of the pump may be influenced by factors other than thyroid function.

Adult↗
PubMed1993

Sensitization of T lymphocytes to thyroglobulin and thyroperoxidase in autoimmune thyroid diseases.

To investigate T-cell sensitization to thyroid autoantigens in autoimmune thyroid disease (AITD), purified soluble human thyroglobulin (Tg) and thyroid peroxidase (TPO) were used. Peripheral blood mononuclear cells (PBMC) as well as CD8-depleted, CD4-enriched PBMC ("selected" PBMC) from 9 patients with Graves' disease (GD), 13 Hashimoto's thyroiditis (HT) and 10 healthy subjects, were cultured for 6 days with or without varying concentrations (0.1, 1.0 and 5.0 micrograms/ml, respectively) of Tg or TPO and their responses were evaluated using the 3H-thymidine incorporation assay. Total PBMC as well as selected PBMC from GD and HT responded to both TPO and Tg, but normal PBMC did not. This induction was more marked in "selected" PBMC; on the other hand, CD8 depletion did not permit normal PBMC to respond to either antigen. However, reactivity of selected AITD PBMC to Tg differed from that of TPO. Two way analysis of variance showed that the proliferative response was significantly greater with Tg than with TPO, (again particularly notable with the "selected" PBMC) in both GD and HT. There was no difference between control and AITD preparations when an irrelevant (renal microsomal) antigen was employed. Taken together with our previous report that CD4 cells were induced by TPO even when cultured with CD8 cells, it is evident that suppressor CD8 cells do play a role in CD4 cells from proliferating against Tg and TPO; however their function alone or in combination with suppressor-inducer CD4 cells is partially disturbed, so that T cell sensitization to Tg and TPO can be identified in the AITD PBMC.

Adult↗
PubMed1993

Dactylfungins, novel antifungal antibiotics produced by Dactylaria parvispora.

Novel antifungal antibiotics, designated as dactylfungins A (1) and B (3), were isolated from the culture broth of Dactylaria parvispora D500. Dactylfungins A and B were found to be new substances containing an alpha-pyrone and a gamma-pyrone ring, respectively, which conjoined with a polyalcohol moiety and a long side chain, based on NMR spectral analyses. The antibiotics were active against Candida pseudotropicalis and other fungi, with an MIC value at less than 10 micrograms/ml.

Antifungal Agents↗
PubMed1993

Effect of famotidine on gastric mucosal lesions induced by gold thioglucose in rats.

Rats that were given an intraperitoneal injection of gold thioglucose (GTG, 0.3 mg/g) developed hemorrhagic lesions in the gastric mucosa 24 hours after the injection. The gastric juice volume and the generation of acid and pepsin were significantly increased 24 hours after the GTG injection (p < 0.01). Simultaneous administration of famotidine (3 mg/kg) with GTG significantly reduced gastric juice secretion and the generation of acid and pepsin (all p < 0.01), as well as suppressing the development of hemorrhagic lesions. These results indicate that there is a relationship between the hemorrhagic lesions induced by GTG and increased acid and pepsin generation. Rats treated with GTG seem to be a useful new animal model for the investigation of pepsin secretion.

Animals↗
PubMed1993

Glomerular anionic sites in minimal change nephrotic syndrome and focal segmental glomerulosclerosis.

In order to examine the changes in charge of the glomerular basement membrane (GBM) in nephrotic syndrome, anionic sites in the GBM were studied quantitatively. Renal biopsy specimens were obtained from 5 children with minimal change nephrotic syndrome (MCNS) and 5 with nephrotic syndrome and focal segmental glomerulosclerosis (FSGS). Biopsy specimens obtained from 5 patients without proteinuria were also examined as controls. Anionic sites were stained with polyethyleneimine (PEI) as a cationic probe and were examined by electron microscopy. The number of PEI-labeled anionic sites in the lamina rara externa of the GBM was counted in the glomerular capillary region and in the paramesangial region separately. The number of anionic sites per 1000-nm GBM was 20.9 +/- 0.6 in the capillary and 21.2 +/- 0.7 in the paramesangium in controls. They were significantly decreased in MCNS (16.5 +/- 0.7 in the capillary and 16.9 +/- 0.5 in the paramesangium, p < 0.001) and in FSGS (16.7 +/- 0.7 in the capillary and 17.0 +/- 0.6 in the paramesangium, p < 0.001). The decrease of anionic sites suggests a defect in the charge-selective barrier in the lamina rara externa of the GBM in MCNS and FSGS, and this defect both in the capillary and in the paramesangium may be responsible for the proteinuria in these two conditions.

Anions↗
PubMed1992

Cyclosporin reduces proteinuria in rats with aminonucleoside nephrosis.

The effect of cyclosporin (CS) was assessed in Sprague-Dawley rats with puromycin aminonucleoside (PA) nephrosis induced by a single intraperitoneal injection of PA. Three groups of rats were injected intraperitoneally with CS (10 mg/kg body weight) daily, beginning 1 day before PA administration, or 5 or 10 days after PA administration, for 10 days. CS significantly reduced proteinuria in rats with PA nephrosis in comparison with untreated nephrotic controls. After discontinuation of the CS treatment, proteinuria gradually increased, reaching values similar to those in control nephrotic rats. CS pretreatment did not prevent the induction of PA-induced nephrotic syndrome. Light microscopy and assessment of anionic sites in the glomerular basement membrane revealed no differences between normal rats, nephrotic controls, and CS-treated rats. These results show that CS can reduce proteinuria in PA nephrosis, but cannot ameliorate the glomerular changes.

Animals↗
PubMed1992

Clinical significance of serum 7S collagen in various liver diseases.

Serum type IV collagen fragment (7S collagen domain) was measured in 30 controls and 152 liver disease patients with a radioimmunoassay using a polyclonal antibody to human placenta 7S collagen. The serum concentrations of 7S collagen (mean +/- SD) were 4.2 +/- 0.9 ng/mL in controls, 5.1 +/- 2.0 ng/mL in acute hepatitis, 6.5 +/- 2.5 ng/mL in chronic inactive hepatitis, 9.5 +/- 3.8 ng/mL in chronic active hepatitis, 14.4 +/- 7.5 ng/mL in liver cirrhosis, and 14.4 +/- 6.9 ng/mL in hepatocellular carcinoma. In acute hepatitis, 7S collagen was slightly increased, whereas type III procollagen N-peptide and prolyl hydroxylase were markedly increased. In chronic liver disease, 7S collagen concentrations increased with the severity of the disease, and also reflected the degree of fibrosis. The serum 7S collagen concentrations were significantly correlated with those of type III procollagen N-peptide and prolyl hydroxylase in all subjects. These results suggest that serum 7S collagen concentration is a useful diagnostic aid for determining hepatic collagen metabolism in liver diseases.

Adult↗
PubMed1992

The nucleotide sequence of apple stem grooving capillovirus genome.

The complete nucleotide sequence of apple stem grooving virus (ASGV) genome has been determined. The genome is 6496 nucleotides in length excluding a 3'-terminal poly(A) tail and contains two overlapping open reading frames (ORFs). ORF1 begins at nucleotide position 37 and is terminated at position 6341, encoding a protein with a molecular weight of 241 kDa. ORF2, which is in a different reading frame within ORF1, begins at position 4788 and can encode a 36-kDa protein. The 241-kDa protein contains two consensus sequences associated with the RNA-dependent RNA polymerase and the NTP-binding helicase. Comparisons of amino acid sequences around these conserved motifs with other RNA viruses revealed that ASGV has extensive similarities with apple chlorotic leaf spot, tymo-, carla-, and potexviruses, and is a member of the sindbis-like supergroup. ASGV coat protein is found to be located in the C-terminal region of the 241-kDa polyprotein. The 36-kDa protein encoded by ORF2 contains the consensus sequence Gly-Asp-Ser-Gly found in the active site of several cellular and viral serine proteases.

Amino Acid Sequence↗
PubMed1992

Human chorionic gonadotropin induces c-myc mRNA expression via TSH receptor in FRTL-5 rat thyroid cells.

To elucidate the gene regulation of the thyroid-cell growth-promoting activity by human chorionic gonadotropin (hCG), we investigated the effect of hCG on c-myc proto-oncogene expression in cultured rat FRTL-5 cells by the Northern blot method. hCG induced c-myc mRNA expression, which peaked at 60-120 min. A dose-dependent increase in c-myc mRNA levels was also ascertained. In the presence of crude immunoglobulin G (IgG) from 2 patients with primary hypothyroidism who had blocking type TSH-receptor antibody, c-myc mRNA expressions induced by hCG were decreased to 82% and 62%, compared with that in the presence of normal IgG. The present results suggest that the expression of c-myc mRNA is a part of the molecular mechanism through which hCG regulates the proliferation of thyroid cells, and that hCG-induced c-myc mRNA expression is presumed to be mediated in part by TSH receptors.

Adenoma↗
PubMed1992

Evidence for translation of apple stem grooving capillovirus genomic RNA.

Apple stem grooving virus (ASGV) RNA was translated in a rabbit reticulocyte lysate system and shown to direct the synthesis of several polypeptides of Mr ranging from 200K to 43K. A polypeptide of 200K was a major product, but no polypeptide with electrophoretic mobility the same as that of the ASGV coat protein was synthesized. Immunoprecipitation experiments showed that a polypeptide of 200K was selectively precipitated by antiserum against purified ASGV. These results indicate that ASGV coat protein is translated as part of a 200K polyprotein.

Cell-Free System↗
PubMed1992

Infusion of peripheral blood mononuclear cell products from nephrotic children increases albuminuria in rats.

Supernatants of peripheral blood mononuclear cell culture from children with minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) were tested for their ability to increase glomerular basement membrane (GBM) permeability and for effects on anionic sites in the GBM. Supernatants from cultures of concanavalin A-stimulated peripheral blood mononuclear cells from patients with MCNS, those with FSGS and normal controls were infused into the renal arteries of normal rats. Infusion of the supernatants from patients with MCNS and FSGS caused a significant reduction of anionic sites in the GBM (p less than 0.001) and a significant increase in urinary albumin excretion (p less than 0.05), whereas infusion of supernatants in control cases did not reduce anionic sites nor increase urinary albumin excretion. These findings show that stimulation of peripheral blood mononuclear cells from MCNS and FSGS with concanavalin A results in liberation of soluble substances which reduce polyanions in the GBM and increases GBM permeability.

Albuminuria↗
PubMed1992

Prognostic indicators in childhood IgA nephropathy.

A number of clinical, laboratory and pathologic parameters were assessed for their prognostic significance in 200 children aged less than 15 years with IgA nephropathy, who had shown normal renal function at the time of initial biopsy and were followed for more than 2 years thereafter. After a mean follow-up period of 5.0 years from the initial biopsy, 93 patients had no demonstrable abnormality, 76 had minor urinary abnormalities, 21 had persistent heavy proteinuria and 10 had developed chronic renal impairment. A poor outcome was found to be correlated with heavy proteinuria at biopsy, diffuse mesangial proliferation, a high proportion of glomeruli showing sclerosis, crescents or capsular adhesions, the presence of moderate or severe tubulointerstitial changes, and the presence of subepithelial electron-dense deposits and lysis of the glomerular basement membrane by electron microscopy. The percentage of glomeruli displaying crescents, sclerosis and adhesions appeared to be the most reliable prognostic indicator. Nine of the 27 patients (33%) in whom greater than or equal to 30% of glomeruli showed crescents, sclerosis and adhesions developed chronic renal impairment, and only 14% of these patients had normal urine at follow-up. In contrast, only 1 of the 173 patients in whom less than 30% of glomeruli showed such lesions developed chronic renal impairment (p less than 0.001) and 51% of these patients showed complete remission at follow-up (p less than 0.001). These results demonstrate that an accurate prediction of the outcome based on the initial renal biopsy findings is possible early in the course of children with IgA nephropathy.

Adolescent↗
PubMed1992

3,3',5'-Triiodothyronine inhibits collagen-induced human platelet aggregation.

To clarify further the activity of rT3, we examined the effect of rT3 on collagen-induced platelet activation as reflected by aggregation, serotonin release, and protein phosphorylation. rT3, T4, T3, and triiodothyroacetic acid inhibited collagen-induced platelet aggregation and serotonin release from platelets in a dose-dependent manner. However, thyronine did not inhibit collagen-induced platelet aggregation. The concentration at which rT3 inhibited by 50% collagen-induced platelet aggregation was 30 +/- 4 (mean +/- SE) mumol/L. rT3, T4, and T3 did not differ significantly in their abilities to inhibit platelet aggregation. Moreover, rT3 inhibited collagen-induced phosphorylation of the 20-kilodalton protein (myosin light chain) in platelets. In contrast, rT3 did not inhibit 12-O-tetradecanoylphorbol 13-acetate (TPA)- or thrombin-induced platelet aggregation and inhibited only minimally TPA-induced 40-kilodalton protein phosphorylation. These results suggest that rT3 inhibits collagen-induced platelet activation by inhibiting the activity of myosin light chain kinase and that it may be interesting to investigate some kinds of activity of rT3.

Blood Platelets↗
PubMed1992

NADPH regeneration by glucose dehydrogenase from Gluconobacter scleroides for l-leucovorin synthesis.

A new process for (6S)-tetrahydrofolate production from dihydrofolate was designed that used dihydrofolate reductase and an NADPH regeneration system. Glucose dehydrogenase from Gluconobacter scleroides KY3613 was used for recycling of the cofactor. The reaction mixture contained 200 mM dihydrofolate, 220 mM glucose, 2 mM NADP, 14.4 U/ml dihydrofolate reductase, and 14.4 U/ml Glucose dehydrogenase, and the reaction was complete after incubation at pH 8.0, and 40 degrees C for 2.5 hr. With (6S)-tetrahydrofolate as the starting material, l-leucovorin was synthesized via a methenyl derivative. The purity of the l-leucovorin was 100%, and its diastereomeric purity was greater than 99.5% d.e. as the (6S)-form.

Folic Acid↗