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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 163 records · Page 9Linked to original sources

[Idiopathic pulmonary fibrosis of the upper lobe: a case report].

A 26-year-old man was admitted to our hospital complaining of exertional dyspnea. Chest x-ray films disclosed reticulonodular shadows predominantly in the upper fields of both lungs, but no apical cap. Lung biopsy specimens obtained from the upper lobe by video-assisted thoracoscopy revealed subpleural elasto-fibrosis. Also, specimens obtained from the lower lobes disclosed micro-honeycombing due to peri-lobular fibrosis resembling usual interstitial pneumonia. Although pneumothorax occurred repeatedly, the lungs reinflated on each occasion without artificial intervention. Similar radiographic findings had been obtained on the patient's father, who died of idiopathic pulmonary fibrosis at the age of 56. Idiopathic pulmonary upper lobe fibrosis was conclusively diagnosed because the patient exhibited most of the features originally described by Amitani et al.

Adult↗

The efficacy of modular transitional implants placed simultaneously with implant fixtures.

After the placement of implants in areas in which several teeth have been lost, both the clinician and the patient face many difficulties, particularly during healing. If no prosthesis is provided, the patient's quality of life suffers. If a removable prosthesis is provided for optimum mastication and speech, many complicated adjustments of the denture may become necessary during healing, and the possibility of osseointegration failure increases. This case report describes simultaneous placement of implant fixtures and modular transitional implants, providing occlusal function immediately after placement. The use of modular transitional implants is very effective in maintaining good oral function for the patient.

Dental Implantation, Endosseous↗

[Clinical significance of allergen specific immunotherapy in adult house-dust-mite-sensitive bronchial asthma: impact on disease severity and medical cost].

The objective of this study was to evaluate the clinical significance of allergen-specific immunotherapy in house-dust-mite-sensitive adult bronchial asthma. Fifty patients treated with rush immunotherapy using house dust antigen were examined. The disease severity was compared between before and a year after the maintenance immunotherapy: reduction in the severity was observed in 27 patients (54.0%) following the treatment. The response rate was greater in the patients with step 3 (moderate, persistent) or step 4 (severe, persistent), disease period less than 10 years, or reversible airway obstruction. Patients who showed favorable clinical response also demonstrated the reduction in medical costs. These results suggest that allergen immunotherapy reduces the disease severity and medical cost in a certain population of adult atopic asthma.

Adolescent↗

Familial subepithelial corneal amyloidosis (gelatinous drop-like corneal dystrophy): exclusion of linkage to lactoferrin gene.

PURPOSE: Because corneal tissue with familial subepithelial corneal amyloidosis (FSCA; gelatinous drop-like dystrophy of the cornea) contains lactoferrin the possibility that the FSCA gene was the human lactoferrin (hLF) gene was investigated. Due to contradictory published information we also mapped the hLF gene. METHODS: We mapped the hLF gene using a genomic clone of the entire hLF gene as a probe by fluorescence in situ hybridization (FISH). Utilizing PCR primers that are specific to the hLF gene, we also mapped the hLF via radiation somatic cell hybrid analysis. Linkage of the FSCA gene to the hLF gene was evaluated by genetic linkage analysis using polymorphic markers within and in the vicinity of the hLF gene. RESULTS: The hLF gene mapped to the short arm of chromosome 3 at 3p21. Linkage analysis using polymorphic markers for hLF and haplotype analysis of the 3p21 loci indicates that the FSCA gene is not linked to the 3p21 locus. CONCLUSIONS: The gene for FSCA is not the hLF gene in these families.

Amyloidosis↗

Effects of thyroid hormone on the sorbitol pathway in streptozotocin-induced diabetic rats.

Sorbitol accumulation plays an important role in diabetic complications involving the kidney, nerves, retina, lens and cardiac muscle. To investigate the influence of thyroid hormone on the sorbitol pathway, we studied the effects of thyroid hormone on polyol metabolism in normal and diabetic rats. Rats were divided into three groups: controls, streptozotocin (STZ)-induced diabetic euthyroid rats (DM) and STZ-induced diabetic hyperthyroid (thyroxine-injected) rats (DM+HT). The sorbitol (Sor) concentrations in the kidney, liver and sciatic nerve (2.53+/-0.74, 0.97+/-0.16 and 24.0+/-5.1 nmol/mg protein, respectively) of the DM rats were significantly higher than those (1.48+/-0.31, 0.58+/-0.13 and 3. 1+/-0.6 nmol/mg protein) of the control rats. The Sor concentrations in the kidney and sciatic nerve of the DM+HT rats (1.26+/-0.29 and 9. 40+/-1.2 nmol/mg protein) were significantly lower than those in the DM rats. These values were reduced in the liver, unchanged in the kidney, and increased in the sciatic nerve from the hyperthyroid rats without diabetes. Thyroid hormone reduced the aldose reductase (AR) activities in the kidney, liver and sciatic nerve of the DM rats, and similarly reduced AR in the kidney and liver, but not in the sciatic nerve, of the non-diabetic rats. The sorbitol dehydrogenase (SDH) activities were decreased by thyroid hormone in the kidney and liver but not the sciatic nerve of DM rats. In the non-diabetic rats, this enzyme activity was decreased in liver, but not in kidney or sciatic nerve. A positive correlation between the Sor concentration and AR activity was observed in the kidney and liver but not in the sciatic nerve from control, DM and DM+HT rats. A negative correlation was observed between the Sor concentration and SDH activities in the same organs. These data suggest that thyroid hormone affects the sorbitol pathway, but the detailed mechanism whereby this hormone reduces the sorbitol content (especially in diabetic rats) remains to be clarified.

Aldehyde Reductase↗

Local expression of immunoregulatory IL-12p40 gene prolonged syngeneic islet graft survival in diabetic NOD mice.

Local production of immunosuppressive cytokines will be one of the most suitable therapeutic strategies against organ-specific autoimmune diabetes. To establish such a new therapy, we constructed recombinant adenoviral vectors with inserted mIL-12p40 (Ad.IL-12p40) and mIL-10 (Ad.IL-10). Sufficient amounts of IL-12p40 and IL-10 were secreted by relevant adenovirus-transfected nonobese diabetic (NOD) islets. Shortly after transfection, 400 NOD islets transfected with Ad.IL-12p40 or Ad.IL-10 were transplanted under the renal capsule of a newly diabetic NOD mouse. NOD mice with IL-12p40-producing islet grafts kept normoglycemia in all of 14 grafted mice for over 4 wk after transplantation. In contrast, NOD mice with IL-10-producing islet grafts became diabetic in all of six grafted mice within 2 wk af-ter transplantation. Reverse transcription-PCR analysis revealed that local production of IL-12p40 led to the decrease of interferon-gamma and the augmentation of transforming growth factor-beta at the graft site. These results suggest that IL-12 plays an important role in the destruction of islet cells at the inflamed site of autoimmunity. Such a local blockade of IL-12 would be a useful gene therapy for human autoimmune diabetes.

Adenoviridae↗

Isolation and characterization of a novel human lung-specific gene homologous to lysosomal membrane glycoproteins 1 and 2: significantly increased expression in cancers of various tissues.

We have isolated and characterized a novel human lung-specific gene and observed its increased expression in cancers arising from various tissues. The cDNA, designated TSC403, contained an open reading frame of 1248 nucleotides encoding 416 amino acids; the deduced amino acid sequence showed significant similarities to lysosomal membrane glycoproteins (lamps) 1 and 2. We localized the gene to chromosomal band 3q27, a genomic region that is often amplified in human cancers of several tissue types. We detected a high level of the TSC403 transcript in primary cancers of the esophagus, colon, fallopian tube, ovary, breast, and liver, although expression of this gene was barely detectable in corresponding normal tissues. These findings indicated that up-regulation of the TSC403 transcript may be related to the development and/or progression of cancer in humans.

Amino Acid Sequence↗

Infant temperament and child-rearing stress: birth order influences.

The relationship between an infant's temperamental difficulty and the mother's child-rearing stress was investigated in a sample of 128 children. Children's temperament was assessed by the Revised Infant Temperament Questionnaire (RITQ) at 6-7 months, and by the Toddler Temperament Scale (TTS) at 18 months. The mothers' child-rearing stress was assessed by a self-report questionnaire. At the children's age of 18 months, mothers of difficult children reported higher child-rearing stress than mothers of easy children. Although difference in the level of child-rearing stress reflecting birth order was not evident at either 6-7 months or 18 months, the proportion of child-rearing stress which could be explained by the children's temperament was highest for mothers of first-borns when their children were 18 months old.

Birth Order↗

Reduction of activity, but no decrease in concentration, of erythrocyte Cu,Zn-superoxide dismutase by hyperglycaemia in diabetic patients.

Cu,Zn-superoxide dismutase(SOD) activity in erythrocytes is affected by various diseases, including diabetes mellitus (DM). We investigated changes in the Cu,Zn-SOD activity compared to changes in the Cu,Zn-SOD concentration in erythrocytes obtained from patients with Type 2 (non-insulin-dependent) diabetes mellitus. Cu,Zn-SOD activity in erythrocytes was significantly lower in Type 2 DM patients than in healthy non-diabetic subjects. The activity correlated negatively with HbA1c, but not with other indicators of metabolic control, such as fasting blood glucose or plasma cholesterol or triglyceride. However, there was no statistically significant difference in erythrocyte concentration of Cu,Zn-SOD between diabetic and control samples. Concentration did not correlate with enzymatic activity or HbA1c. These findings indicate that the inactivation of Cu,Zn-SOD activity in erythrocytes of Type 2 DM patients by hyperglycaemia may be slow, because there is a negative correlation between the enzyme activities and HbA1c levels, but not fasting blood glucose levels. This is consistent with glycosylation of the active site of Cu,Zn-SOD, without any effect of hyperglycaemia on the concentration of Cu,Zn-SOD.

Adult↗

Administration of IL-4 prevents autoimmune diabetes but enhances pancreatic insulitis in NOD mice.

The present study demonstrated that the administration of recombinant interleukin-4 (rIL-4) prevented overt diabetes in nonobese diabetic (NOD) mice whose T cells produced relatively low amounts of IL-4. However, massive insulitis was observed in rIL-4-treated NOD mice. The flow cytometric analysis of islet-infiltrating T cells revealed that the number of CD45RBlowCD4+ T cells was significantly increased by in vivo administration of rIL-4. By measuring the cytokine production of splenic T cells after stimulation, it was shown that CD45RBlowCD4+ T cells predominantly produced IL-4 and IL-10 but produced less IL-2 and interferon-gamma (IFN-gamma). A semiquantitative reverse-transcriptase polymerase chain reaction assay revealed a higher expression of IL-4 and IL-10 mRNA and an apparent decrease in IFN-gamma mRNA in the islets of NOD mice which were administered rIL-4. These results suggested that autoreactive CD45RBlowCD4+ T helper 2 (Th2)-like cells which developed following rIL-4 administration were predominant in the infiltrate of the islets, and overt diabetes was prevented. On the other hand, when splenocytes from rIL-4-treated NOD mice were transferred to irradiated NOD recipients, along with splenocytes from diabetic NOD mice, all of the recipient mice became diabetic within 8 weeks after transfer. Considered together, a supplement of rIL-4 administered to NOD mice may protect against autoimmune diabetes by facilitating the development of Th2-like autoreactive T cells in the islets.

Animals↗

Surgical treatment of a solitary pancreatic metastasis from renal cell carcinoma: report of a case.

The pancreas is a rare site of metastasis from renal cell carcinoma (RCC). We present herein the case of a 47-year-old male in whom a solitary pancreatic metastasis was treated by a pylorus-preserving pancreatoduodenectomy (PpPD), 3 years after a radical nephrectomy for a RCC. The few reported cases of surgically treated pancreatic metastases from RCC are reviewed following the presentation of this case.

Carcinoma, Renal Cell↗

Drug susceptibility of PCA in WBB6F1-W/Wv mice.

Our previous study revealed that passive cutaneous anaphylaxis (PCA) can be produced in congenitally mast cell-deficient WBB6F1-W/Wv (abbreviated as W/Wv) mice on sensitization with undiluted or slightly diluted allogeneic and xenogeneic antisera but not on sensitization with allogeneic monoclonal immunoglobulin (Ig)E and IgG1 antibodies regardless of the antibody concentration [1]. In view of these findings, the present study was conducted to characterize PCA in this strain from its drug susceptibilities using mast cell-bearing WBB6F1-(+)/+ (abbreviated as +/+) and B6D2F1 mice as references. PCA in W/Wv mice mediated by a low dilution (1:4) of hyperimmune serum to bovine serum albumin of the B6D2F1 mouse origin was markedly suppressed by CV-6209, an antagonist of platelet-activating factor (PAF), but not by antihistamines such as cyproheptadine and oxatomide. In contrast, PCA in +/+ and B6D2F1 mice mediated by a high dilution (1:128) of the anti-serum (virtually by IgG1 antibody) was nearly completely suppressed by antihistamines but not by CV-6209. A remarkable difference between PCA in W/Wv and reference mice was also observed in the susceptibility to monoclonal anti-mouse granulocyte (Gr-1) antibody: PCA in W/Wv mice was potently suppressed by the 1- to 3-day pretreatment with this antibody but that in references was not at all. Putting these present results together with the previous finding that anti-granulocyte antibody greatly reduces circulatory Gr-1+ leukocytes, 1 to 3 days after the treatment [2], it is highly probable that PCA in W/Wv mice mediated by some antibody isotypes other than IgE and IgG1 is produced by PAF mainly released from Gr-1+ cells, while IgG1 antibody-mediated PCA in mast cell-bearing reference mice is evoked by histamine derived from mast cells. PCA homologous to that in W/Wv mice could also be produced in the reference mice on sensitization with undiluted or slightly diluted antiserum, when generalized blueing due to excess IgG1 antibody was removed by the oxatomide treatment before the antigen challenge.

Animals↗

Sustained induction of hepatocyte growth factor by sensitization with freeze-thawed hepatic tissue.

Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, and has therapeutic potential for fibrotic/cirrhotic liver. Therefore, the induction of HGF in vivo is considered to be useful in the treatment of liver dysfunction caused by cirrhosis, chronic hepatitis, or extensive surgical resection. In this study, we examined the sustained induction of HGF by inoculation of freeze-thawed hepatic tissue (FTHT). Serum from rats inoculated with FTHT increased [3H]thymidine incorporation i.e., increased DNA synthesis, in primary cultured rat hepatocytes. The DNA synthesis was significantly promoted by the addition of the FTHT-sensitized serum, while this DNA synthesis was inhibited by neutralizing anti-rat HGF antibody. The concentration of HGF in the FTHT-sensitized serum was increased by day 3 after the inoculation. The time of HGF induction was dependent on the inoculated volume of FTHT, but peaks of HGF concentration were found on day 5 with different volumes of FTHT. Injurins, inducers of HGF, were also induced in the FTHT-sensitized rats, with their peak levels on day 3. The FTHT inoculated tissue showed inflammatory cell infiltration, which was gradually absorbed, and had completely disappeared by day 14 after the inoculation. Although mild inflammatory cell infiltration was observed in non-freeze-thawed inoculated hepatic tissue (NFHT) a tight capsule formed around the NFHT, and was scarcely phagocytized on day 14. These results suggest that FTHT inoculation induces HGF sustainedly through the increased synthesis of injurins, and that freeze-thawed tissue, which is easily phagocytized, is important for the sustained induction of HGF.

Animals↗

Cell cycle regulation and differentiation in the human podocyte lineage.

Mature podocytes are regarded as growth-arrested cells with characteristic phenotypic features that underlie their function. To determine the relationship between cell cycle regulation and differentiation, the spatiotemporal expression of cyclin A, cyclin B1, cyclin D1, the cyclin-dependent kinase inhibitors (CKIs) p27 and p57, and markers of differentiating podocytes in developing human kidneys was investigated by immunohistochemistry. In S-shaped body stage, Ki-67, a cell proliferation marker that labels the G1/S/G2/M phase, was expressed in the majority (more than 80%) of presumptive podocytes, along with cyclin A (approximately 20% of the Ki-67-positive cells) and cyclin B1 (less than 5% of Ki-67-positive cells) expression. Among these cells), cyclin D1 and CKIs were markedly down-regulated. At the capillary-loop stage, by contrast, CKIs and cyclin D1 were intensely positive in podocytes, whereas no Ki-67, cyclin B1, or cyclin A expression was seen. Moreover, double-immunolabeling and serial-section analysis provided evidence that CKIs and markers specific for differentiating podocytes, namely PHM-5 (podocalyxin-like protein in humans), synaptopodin (a foot process-related protein), and C3b receptor, were co-expressed at the capillary-loop stage. Podocytes were the only cells within the glomeruli that expressed CKIs at immunohistochemically detectable levels. Furthermore, bcl-2 (an apoptosis inhibitory protein) showed a reciprocal expression pattern to that of CKI. These results suggest that 1) the cell cycle of podocytes is regulated by cyclin and CKIs, 2) CKIs may act to arrest the cell cycle in podocytes at the capillary-loop stage, and 3) the specific cell cycle system in podocytes may be closely correlated with their terminal differentiation in humans.

Biomarkers↗

Origin and phenotypic features of hyperplastic epithelial cells in collapsing glomerulopathy.

The characteristic pathological feature of collapsing glomerulopathy (CG) is marked cell hyperplasia and hypertrophy within the glomeruli. The present study investigated the phenotypic alteration of hyperplastic epithelial cells in CG to determine their origin. Renal biopsy specimens from two patients with CG were analyzed by immunohistochemical staining, using markers for podocytes (PHM-5), parietal epithelial cells (PECs; cytokeratin), and cell proliferation (Ki-67). In collapsed glomeruli, hyperplastic and hypertrophic epithelial cells were frequently connected to PECs and collapsed glomerular basement membranes (GBMs). These epithelial cells were more often Ki-67 positive and expressed cytokeratin, whereas PHM-5 was almost invariably negative. Serial section analysis showed that a small number of hyperplastic epithelial cells expressed both PHM-5 and cytokeratin, suggesting phenotypic conversion between podocytes and PECs. Moreover, cytokeratin-positive cells were associated with the sclerotic glomerular segments. Thus, we suggest that the majority of hyperplastic and hypertrophic epithelial cells in CG are of PEC origin. These epithelial features may participate in the development of characteristic tuft collapse and glomerulosclerosis in CG.

Biopsy↗

Inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on hepatic triglyceride accumulation with the progression of carbon tetrachloride-induced acute liver injury in rats.

The inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on hepatic triglyceride (TG) accumulation with the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). TJ-15 at a dose of 100, 250 or 500 mg/kg body weight (BW) was orally administered to male Wistar rats aged 7 weeks, 6 h after the intraperitoneal injection of CCl4 (1.0 ml/kg BW) at which time apparent liver injury and hepatic TG accumulation occurred. TJ-15 significantly prevented not only the progression of liver injury but also inhibited hepatic TG accumulation with the progression of the injury in a dose-dependent manner when these effects were examined 24 h after CCl4 injection. In CCl4-untreated rats with oral administration of TJ-15 at a dose of 100, 250 or 500 mg/kg BW, liver and serum TG concentrations decreased depending on the dose of the herbal medicine. These results indicate that in rats intoxicated once with CCl4, orally administered TJ-15 can inhibit hepatic TG accumulation with the progression of acute liver injury by its decreasing action on serum and liver TG levels, leading to a prevention of the progression of the liver injury.

Administration, Oral↗

Phacoemulsification, intraocular lens implantation, and trabeculotomy to treat pseudoexfoliation syndrome.

PURPOSES: To determine the long-term risk/benefit ratio of phacoemulsification and intraocular lens (IOL) implantation combined with trabeculotomy to manage eyes with pseudoexfoliation syndrome and co-existing cataract. SETTING: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine; Kurihara Eye Clinic; Departments of Ophthalmology, Tenri Hospital, Kumamoto University, and Matsue Red Hospital; Nagata Eye Clinic, Japan. METHODS: This multicenter retrospective study comprised 49 eyes of 36 patients with pseudoexfoliation syndrome and co-existing cataract who had the combined procedure for uncontrolled intraocular pressure (IOP) (> 21 mm Hg) even on antiglaucoma medication. RESULTS: After a mean follow-up of 20.0 months +/- 13.2 (SD), IOP in all 49 eyes was well controlled (< or = 21 mm Hg). Mean IOP at the final examination was 14.6 +/- 2.6 mm Hg on a mean of 0.9 +/- 0.8 glaucoma medications. Complications included an IOP spike in 11 eyes and fibrin exudation in 1 eye. CONCLUSION: Phacoemulsification and IOL implantation combined with trabeculotomy was an effective treatment for patients with pseudoexfoliation syndrome and cataract.

Aged↗