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Biomedical subjects

Y Fujiwara

Publications and source records attributed to Y Fujiwara.

At least 325 records · Page 18Linked to original sources

Clinical significance of measurements of urinary and serum thrombomodulins in patients with non-insulin-dependent diabetes mellitus.

UNLABELLED: The aim of our study was to elucidate whether serum thrombomodulin (S-TM) and urinary thrombomodulin (U-TM) levels would reflect the pathogenesis of diabetic complications. Studies were conducted in 188 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 132 age-matched healthy subjects. TM was measured by a newly developed enzyme immunoassay. Both S-TM and U-TM levels in NIDDM were much higher than those in healthy controls. S-TM values in NIDDM correlated significantly with age (P < 0.05), HbA1c (P < 0.05), serum 1.5 anhydroglucetol (AG) (P < 0.05) and urinary albumin concentration (UAC) (P < 0.01), respectively. On the other hand, fasting plasma glucose (FPG) (P < 0.001), HbA1c (P < 0 .01), serum fructosamine (P < 0.05) and serum 1.5 AG (P < 0.05) were closely correlated with U-TM values in NIDDM. Patients with clinical nephropathy showed obviously higher S-TM levels (P < 0.05) than patients with latent nephropathy. Furthermore, S-TM values in patients with diabetic proliferative retinopathy increased significantly compared with those in patients without diabetic retinopathy (P < 0.05). When all diabetic patients with normoalbuminuria were studied, no significant changes of S-TM were observed between the no diabetic retinopathy group and the proliferative diabetic retinopathy group. CONCLUSIONS: The present data suggest that an increase in U-TM reflects the grade of glucose metabolism, whereas an increase in S-TM appears to reveal the advance of diabetic microangiopathy, including nephropathy.

Adult↗

Locations of local anesthetic dibucaine in model membranes and the interaction between dibucaine and a Na+ channel inactivation gate peptide as studied by 2H- and 1H-NMR spectroscopies.

To study the molecular mechanisms of local anesthesia, locations of local anesthetic dibucaine in model membranes and the interactions of dibucaine with a Na+ channel inactivation gate peptide have been studied by 2H- and 1H-NMR spectroscopies. The 2H-NMR spectra of dibucaine-d9 and dibucaine-d1, which are deuterated at the butoxy group and at the 3 position in its quinoline ring, respectively, have been observed in multilamellar dispersions of the lipid mixture composed of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine. 2H-NMR spectra of deuterated palmitic acids incorporated, as a probe, into the lipid mixture containing cholesterol have also been observed. An order parameter, SCD, for each carbon segment was calculated from the observed quadrupole splittings. Combining these results, we concluded that first, the butoxy group of dibucaine is penetrating between the acyl chains of lipids in the model membranes, and second, the quinoline ring of dibucaine is located at the polar region of lipids but not at the hydrophobic acyl chain moiety. These results mean that dibucaine is situated in a favorable position that permits it to interact with a cluster of hydrophobic amino acids (Ile-Phe-Met) within the intracellular linker between domains III and IV of Na+ channel protein, which functions as an inactivation gate. To confirm whether the dibucaine molecule at the surface region of lipids can really interact with the hydrophobic amino acids, we synthesized a model peptide that includes the hydrophobic amino acids (Ac-GGQDIFMTEEQK-OH, MP-1), the amino acid sequence of which corresponds to the linker part of rat brain type IIA Na+ channel, and the one in which Phe has been substituted by Gln (MP-2), and measured 1H-NMR spectra in both phosphate buffer and phosphatidylserine liposomes. It was found that the quinoline ring of dibucaine can interact with the aromatic ring of Phe by stacking of the rings; moreover, the interaction can be reinforced by the presence of lipids. In conclusion, we wish to propose that local anesthesia originates from the pi-stacking interaction between aromatic rings of an anesthetic molecule located at the polar headgroup region of the so-called boundary lipids and of the Phe in the intracellular linker between domains III and IV of the Na+ channel protein, prolonging the inactivated state and consequently making it impossible to proceed to the resting state.

Amino Acid Sequence↗

Hemorrhagic ovarian cyst in childhood: a case report.

A 12-year-old girl with massive hemoperitoneum caused by a ruptured hemorrhagic ovarian cyst (HOC) is described. Although HOC is not common in early adolescence, it should be included in the differential diagnosis of any adnexal mass or lower abdominal pain in a girl.

Abdominal Pain↗

Novel marine di-Z-carotenoids: cucumariaxanthins A, B, and C from the sea cucumber Cucumaria japonica.

The novel marine carotenoids, cucumariaxanthins A (1), B (2), and C (3), were isolated from the northern sea cucumber Cucumaria japonica. Their structures and absolute stereochemistries were determined to be (5S,6S,5'S,6'S)-(9Z,9'Z)-5,6,5',6'-tetrahydro-beta,beta- carotene-4,4'-dione for 1; (5S,6S,4'S,5'S,6'S)-(9Z,9'Z)-4'-hydroxy-5,6,5',6'-tetrahydro-beta, beta- caroten-4-one for 2; and (4S,5S,6S,4'S,5'S,6'S)-(9Z,9'Z)-5,6,5',6'-tetrahydro-beta,beta-car otene-4,4'- diol for 3 by extensive spectroscopic analysis and by the modified Mosher's method. Cucumariaxanthin C showed an inhibitory effect on Epstein-Barr virus activation in a short-term in vitro assay.

Animals↗

Prognosis of recurrent hepatocellular carcinoma: a 10-year surgical experience in Japan.

BACKGROUND & AIMS: Little has been addressed on the characteristics and prognostic factors of recurrent hepatocellular carcinoma after undergoing a hepatic resection for primary hepatocellular carcinoma. The aim of this study was to clarify the aforementioned matters of recurrent hepatocellular carcinoma. METHODS: One hundred fifty-nine patients with recurrent hepatocellular carcinoma were studied retrospectively. Twenty-four clinicopathologic variables, including the period until recurrence (less than or more than 1 year), types of recurrence (intrahepatic nodular type, intrahepatic multiple type, and extrahepatic type), and types of treatment after recurrence (no treatment, lipiodolization, ethanol injection, or hepatectomy) were univariately and multivariately analyzed. RESULTS: The following three variables were finally selected as independent and prognostic indicators after recurrence: (1) period until recurrence, (2) type of recurrence, and (3) types of treatment after recurrence. CONCLUSIONS: The prognostic factors in patients with recurrent hepatocellular carcinoma were as follows: (1) period until recurrence, (2) types of recurrence, and (3) types of treatments received after recurrence. The establishment of a follow-up system, including an examination for extrahepatic recurrence, and the development of an effective method of adjuvant chemotherapy are required to obtain better treatment results.

Aged↗

Diagnosis of borderline adenomas of the stomach by endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: The correct histological diagnosis of gastric borderline adenomas is often difficult, especially in excluding malignancy, since the usual diagnostic methods, such as radiography and histological examination of forceps biopsy specimens, are of limited accuracy. The aim of this study was to retrospectively analyze the value of endoscopic mucosal resection in establishing the correct diagnosis of borderline adenomas. RESULTS: Fourteen borderline adenomas were finally diagnosed as containing early gastric cancer type IIa (well-differentiated tubular adenocarcinoma) after endoscopic mucosal resection, of the remaining 36 tubular adenomas, six represented mild dysplasia, 24 moderate dysplasia, and six severe dysplasia. Most parts of the 14 adenomas containing early gastric cancers had regions of structural atypia, and cellular atypia was moderate in all. Seven of 14 cancers were completely resected, all patients being tumor-free after a follow-up of 33-61 months. CONCLUSIONS: These results suggest that diagnosing borderline adenoma on the basis of radiographic and endoscopic-bioptic findings is generally unreliable, because biopsy specimens may not be representative of the entire lesion. Borderline adenomas of the stomach should be completely resected by endoscopic mucosal resection to obtain a final diagnosis and - depending on the size and type of the lesion - possibly also definitive treatment.

Adenoma↗

Biosynthetic transport of a major lysosome-associated membrane glycoprotein 2, lamp-2: a significant fraction of newly synthesized lamp-2 is delivered to lysosomes by way of early endosomes.

Lysosomal membranes contain two highly glycosylated proteins, designated as lamp-1 and lamp-2, as major components. Lamp-1 and lamp-2 are similar to each other in the protein structure. Here, we investigated the biosynthetic transport of lamp-2 through the endocytic vacuoles in cultured rat hepatocytes in comparison with that of lamp-1, which has previously been studied [Akasaki et al. (1995) Exp. Cell Res. 220, 464-473]. Newly synthesized lamp-2 (NS-lamp-2) was transported to the trans-Golgi from rough endoplasmic reticulum with a half time (t1/2) of 32 min, more slowly than NS-lamp-1 (t1/2 = 13 min). After leaving the trans-Golgi, NS-lamp-2 is transferred to at least three compartments; the cell surface (t1/2 = 47 min), cell peripheral early endosomes (t1/2 = 38 min) and perinuclear late endosomes (t1/2 = 48 min). NS-lamp-2 transported to any compartment is delivered finally to lysosomes (t1/2 = 90 min). A significant fraction of NS-lamp-2 (45% of the total) was transported from the trans-Golgi to early endosomes, and then delivered to dense lysosomes via perinuclear late endosomes, whereas a major portion of NS-lamp-1 follows an intracellular route to late endosomes without passing through the cell periphery. NS-lamp-2 leaves the cell peripheral region more rapidly than NS-lamp-1. The kinetic and quantitative data for biosynthetic transport of NS-lamp-2 to early endosomes and the cell surface indicate that NS-lamp-2 may be transported first to early endosomes, from which a small portion of it (approximately 3.5% of the total) moves to the plasma membrane via a recycling system. In contrast, a small fraction of NS-lamp-1 is transported to the plasma membrane directly from the trans-Golgi, since NS-lamp-1 is delivered to the plasma membrane and early endosomes with almost the same half times.

Animals↗

Sleep-related breathing disorders in patients with multiple system atrophy and vocal fold palsy.

We performed sleep studies in eight patients with multiple system atrophy (MSA) and three patients with peripheral bilateral vocal fold palsy (PBVFP) and investigated stenosis of the upper airway tract during sleep in MSA patients with vocal fold palsy. Among the eight MSA patients in this study, five had definite glottic snoring and two others were suspected of having glottic snoring. Of the PBVFP patients, two had glottic snoring. Three of 11 patients died, and two of the three deaths occurred during sleep. Glottic snoring indicated a high degree of negative esophageal pressure. High negative esophageal pressure demonstrates severe narrowing of the upper airway tract. Therefore, glottic snoring should be considered a risk factor for sudden death in sleep. Repeated laryngoscopic examination is useful in evaluating the progressive process of vocal fold palsy while awake, but this examination performed only while awake is not enough to evaluate narrowing of the upper airway during sleep. Sleep studies that include the measurement of esophageal pressure can be very useful in evaluating the severity of narrowing in the upper airway tract. It is suspected that sudden nocturnal death in MSA patients is caused not only by abnormal respiration resulting from impairment of the respiratory center, but also by glottic obstruction caused by sputum or by edema of the vocal folds. We recommend treatment of respiratory disorders when loud laryngeal snoring occurs in patients with MSA, even if they do not complain of dyspnea while awake.

Adult↗

No alteration in DNA topoisomerase I gene related to CPT-11 resistance in human lung cancer.

Mutations and reduced expression of DNA topoisomerase I (topo I) gene have been shown to be important in the acquisition of resistance to camptothecin and its analogues in vitro, but their significance has not been verified in vivo. We investigated possible topo I gene mutations and topo I mRNA expression levels in 127 samples obtained from 56 patients with lung tumors, including patients who had developed clinical resistance to topo I inhibitors. No mutations were detected in any of the samples examined and expression levels did not differ significantly between clinically resistant cases and others. However, the topo I mRNA expression level was significantly higher in small cell lung carcinomas than in non-small cell lung carcinomas (P < 0.05). These results suggest that topo I mRNA levels may affect CPT-11 sensitivity in human lung cancer. However, topo I gene mutations and reduced topo I mRNA expression may not be the main mechanism of clinically acquired resistance to camptothecin analogues in vivo.

Adult↗

The value of sleep nasendoscopy in the evaluation of patients with suspected sleep-related breathing disorders.

Fifty patients with sleep-related breathing disorders were tested with nocturnal polysomnography and with nasendoscopic diurnal polysomnography after diazepam administration, and various indices of breathing disorders were examined, and the results obtained in the two sleep studies compared. There were no significant differences between the two sleep studies in either the type of apnoea or the indices of breathing disorder except for the longest duration of apnoea. There was a significant difference in the duration of REM sleep between the two sleep studies, but no significant difference in the duration of each stage of non-REM sleep. We speculate that nasendoscopic diurnal polysomnography with diazepam can be used as a substitute for nocturnal polysomnography in the clinical study of non-REM sleep stage but it is not sufficient in evaluating REM sleep stage, in patients with sleep-related breathing disorders without pathological obesity or abnormal respiratory function.

Diazepam↗

Effect of chronic ipsapirone treatment on the density of 5-HT1A receptors and 5-HT1A receptor mRNA in discrete regions of the rat brain.

There is increasing evidence that the 5-hydroxytryptamine (HT)1A partial agonist ipsapirone is an effective anxiolytic/antidepressant agent, although its mechanism of action is not clear. In this study, we investigated the effects of chronic ipsapirone treatment (5 or 10 mg/kg; twice daily, 3 weeks) on 5-HT1A receptor density 8-hydroxy-2-(di-n-propyl amino) tetralin (8O H-DPAT) binding and the level of its mRNA (in situ hybridization) in various regions of the rat (male Wistar 250 g) brain. Receptor density was reduced in the frontal cortex, but did not change significantly in the hippocampus and dorsal raphe nucleus. The level of receptor mRNA was unchanged in each of these brain regions. The present results suggest that the clinical anxiolytic effects of ipsapirone may be mediated partly by postsynaptic action on serotonergic transmission in the frontal cortex, but not in the hippocampus or dorsal raphe nuclei.

Animals↗

Evaluation of the therapy for streptococcal pharyngitis using Abbott Test Pack strep A.

A total of 953 children (511 boys and 442 girls) with streptococcal pharyngitis diagnosed with Abbott Test Pack Strep A (ATPSA) or throat cultures were analyzed. ATPSA specimens were repeatedly obtained until ATPSA turned negative during or after the treatment. The percentage of positive ATPSA specimens reached the lowest value (9.2%) on the fourth day of the course of the treatment, which indicates the acquisition from an infected individual is probably uncommon after the initial treatment. Bacteriological treatment failure (positive ATPSA after 14 days of treatment) occurred in 4.1% of the children. Out of 953 subjects studied, 216 (22.7%) had recurrent infections. More than 30% of the recurrent infections occurred within 2 months after initial infection. ATPSA is useful for establishing a rapid diagnosis and confirming the bacteriological success of the treatment.

Adolescent↗

Acute anterior uveitis in a child with HLA-B60 after Salmonella enteritis associated with the transient appearance of auto-antibody.

A Japanese girl with HLA-B60, but not B27, who developed acute anterior uveitis after Salmonella enteritis is described. There was no evidence of arthritis or urethritis during this episode. This is the first report that acute anterior uveitis after Salmonella enteritis was associated with the transient appearance of auto-antibody in the serum at an early period.

Antibodies, Antinuclear↗

Isolation and characterization of the cDNA encoding BKLF/TEF-2, a major CACCC-box-binding protein in erythroid cells and selected other cells.

CACCC boxes are among the critical sequences present in regulatory elements of genes expressed in erythroid cells, as well as in selected other cell types. While an erythroid cell-specific CACCC-box-binding protein, EKLF, has been shown to be required in vivo for proper expression of the adult beta-globin gene, it is dispensable for the regulation of several other globin and nonglobin erythroid cell-expressed genes. In the work described here, we searched for additional CACCC-box transcription factors that might be active in murine erythroid cells. We identified a major gel shift activity (termed BKLF), present in yolk sac and fetal liver erythroid cells, that could be distinguished from EKLF by specific antisera. Through relaxed-stringency hybridization, we obtained the cDNA encoding BKLF, a highly basic, novel zinc finger protein that is related to EKLF and other Krüppel-like members in its DNA-binding domain but unrelated elsewhere. BKLF, which is widely but not ubiquitously expressed in cell lines, is highly expressed in the midbrain region of embryonic mice and appears to correspond to the gel shift activity TEF-2, a transcriptional activator implicated in regulation of the simian virus 40 enhancer and other CACCC-box-containing regulatory elements. Because BKLF binds with high affinity and preferentially over Sp1 to many CACCC sequences of erythroid cell expressed genes, it is likely to participate in the control of many genes whose expression appears independent of the action of EKLF.

Amino Acid Sequence↗

Isolation of 45 exon-like fragments from 8p22-->p21.3, a region that is commonly deleted in hepatocellular, colorectal, and non-small cell lung carcinomas.

The loss of heterozygosity that is frequently observed at chromosome 8p22-->p21.3 in hepatocellular carcinomas (HCC), colorectal cancers (CRC), prostate cancers (PRC). and non-small cell lung cancers (NSCLC), suggests the presence there of one or more tumor suppressor genes associated with development and/or progression of these types of carcinomas. We have constructed a cosmid contig map of the target region by means of Southern hybridization and have isolated 45 exon-like fragments by exon amplification, using cosmid clones derived from three yeast artificial chromosomes (YACs). The map and the exon-like fragments reported here will be useful resources for isolation of the putative tumor suppressor gene(s) as well as other novel genes located in the 8p22-->p21.3 region.

Amino Acid Sequence↗

Detection of p53 gene mutations in cytopathology and biopsy specimens from patients with lung cancer.

In order to ascertain the feasibility of detecting p53 gene mutations in patients with lung cancer in a nonsurgical diagnostic setting before starting treatment, we screened for p53 gene mutations in tumor specimens obtained using diagnostic methods such as fiberoptic bronchoscopy, thoracentesis, and percutaneous needle aspiration. We examined 206 specimens from 66 patients diagnosed with primary lung cancer at Hiroshima University Hospital between October 1991 and July 1993 using the polymerase chain reaction/denaturing gradient gel electrophoresis technique. p53 gene mutations were found in 64 of 159 (40%) cytologically positive specimens, but in none of 47 cytologically negative specimens. The PCR-based assay did not increase the sensitivity of the cytopathologic examination in detecting malignant cells. The type and location of the p53 gene mutation was the same in cytologically positive specimens obtained by different methods, but from the same patient. Of the 66 patients, p53 gene mutations were found in 27 (41%) at the time of the first nonsurgical diagnostic examination: 7 of 12 (58%) with small cell carcinoma, 9 of 20 (45%) with squamous cell carcinoma, and 11 of 34 (32%) with adenocarcinoma of the lung. The incidence of p53 gene mutation for each histologic subtype was comparable to previously published data examining surgically and/or autopsy-obtained specimens. These results indicate that detection of p53 gene mutations in a nonsurgical, diagnostic setting is feasible. This technique will make it possible to assess the significance of p53 gene mutations in relation to survival and response to therapy before starting treatment, in future prospective studies.

Adenocarcinoma↗

Synthesis of human C-type natriuretic peptide 22 using chlorotrityl resin and tetrafluoroboric acid deprotection.

Human C-type natriuretic peptide 22 (hCNP22), the third member of the natriuretic peptide family, was efficiently synthesized by Fmoc-based peptide chain construction on a 2-chlorotrityl (Clt) resin, followed by deprotection using tetrafluoroboric acid (HBF4). The use of Clt resin was effective in suppressing racemization at the C-terminal cysteine residue caused by the base treatment for Fmoc-cleavage. The disulfide bond of hCNP22 was constructed using the silyl chloride-sulfoxide method to avoid oxidation at the Met residue. Using amino acid- and dipeptide-resin derivatives, the effects of bases, protecting groups and resin supports on the racemization at the C-terminal Cys residue were examined in detail.

Amino Acid Sequence↗