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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 883 records · Page 49Linked to original sources

Intestinal absorption of ursodeoxycholic acid in children and adolescents with inflammatory bowel disease.

BACKGROUND: Ursodeoxycholic acid absorption in the proximal intestine may be impaired in patients with inflammatory bowel disease. METHODS: We examined the intestinal absorption of ursodeoxycholic acid by the oral ursodeoxycholic acid tolerance test in 19 children and adolescents with inflammatory bowel disease at various stages, including 8 patients with unoperated Crohn's disease, 3 patients with ileal-resected Crohn's disease, 8 with ulcerative colitis, and 8 healthy control subjects. RESULTS: Ursodeoxycholic acid malabsorption was present in all patients with unoperated Crohn's disease in the first diagnosed active stage, in 3 of 5 patients in a relapsing active stage, and in 2 of 8 patients in remission. Ursodeoxycholic acid absorption was significantly lower in patients in the first diagnosed active stage than in the healthy controls (p < 0.01) or in patients in remission (p < 0.01). There was no significant difference between healthy controls and the patients in a relapsing active stage or in remission. Ursodeoxycholic acid absorption was abnormal during the first postoperative month in patients with ileal-resected Crohn's disease, but normalized over time. Malabsorption of ursodeoxycholic acid was not observed in any patients with ulcerative colitis. CONCLUSIONS: These findings suggest that absorption of ursodeoxycholic acid in the proximal intestine is impaired in patients with Crohn's disease and that the oral ursodeoxycholic acid tolerance test is a convenient and useful means of evaluating the absorption of bile acid in the proximal intestine in pediatric patients with ileal or ileocolic Crohn's disease.

Adolescent↗

In vitro effect of contrast agents during immunoradiometric assay for tumour-associated antigens.

The aim of this study was to investigate if contrast agents interfere with the performance of an immunoradiometric assay (IRMA) in vitro for serum tumour-associated antigen. Each of five carcinoembryonic antigen (CEA)-positive sera, CA-130-positive sera and tissue polypeptide antigen (TPA)-positive sera was mixed with six contrast agents: Ioversol 350, Iopamidol 370, Iomeprol 300, Iomeprol 400, Iohexol 300 and Gadopenteic acid in 50:50, 50:20, 50:5.0, 50:1.0, 50:0.5 and 50:0.1 microl proportions. Following IRMA, the interference of binding rates in each mixture was calculated, and the serum concentrations of CEA, CA-130 and TPA were estimated and compared with the originals. All contrast agents used were able to inhibit the binding rate with IRMA and the inhibition rates were in proportion to the amount of contrast agent. The detection of serum concentrations of CEA, CA-130 and TPA was significantly inhibited in the mixtures with more than 5.0 microl of contrast agent in all cases. Apart from Iomeprol 400, there was no significant inhibition of detection at the lowest concentrations of contrast agents. Iomeprol 400 was the strongest inhibitor and Gadopenteic acid the weakest inhibitor for each IRMA of the contrast agents employed. In conclusion, our results demonstrate that contrast agents may reduce the immunoreaction of antibody and antigen and lead to in vitro inhibition during immunoassays. It would be unwise to perform any plasma/serum immunoassay on a sample collected within 24 h of the administration of contrast agent considering the pharmacokinetics.

Aged↗

99Tcm-labelled chimeric human/mouse anti-granulocyte antibody bone marrow scintigraphy: a preliminary clinical study.

Bone marrow scintigraphy using 99Tcm-labelled chimeric anti-granulocyte antibody (anti-NCA-95) was performed in 17 patients with haematological disorders and skeletal metastases. Chimeric anti-NCA-95 antibody (chNCA95 Ab, 0.2 mg) labelled with 444 MBq 99Tcm was administered to obtain bone marrow images 4 h post-injection. One week later, an 111In-chloride bone marrow scan was performed on nine patients with haematological disorders. Lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B) uptake ratios were calculated for each scan. In six patients with suspected skeletal metastases, 99Tcm-HMDP bone scans were performed. No patient had any adverse reaction or any immune reaction over 20 weeks. In the patients with haematological disorders, the L/B and I/B ratios of the 99Tcm-chNCA95 Ab scan were 3.41 +/- 0.90 and 1.23 +/- 0.31, whereas those of the 111In-chloride scan were 1.58 +/- 0.32 and 1.00 +/- 0.32, respectively. In assessing findings of irregular central bone marrow uptake and peripheral expansion of the bone marrow, the 99Tcm-chNCA95 Ab scan was much better than the 111In-chloride scan. In the six patients with suspected skeletal bone metastases, three true-positive and two true-negative results were observed. This preliminary study has revealed that 99Tcm-chNCA95 Ab scanning is safe and useful in the diagnosis of haematological disorders and skeletal metastases.

Adult↗

A method for estimating the integral of the input function for the quantification of cerebral blood flow with 123I-IMP using one-point arterial blood sampling.

We have developed a new method to replace the conventional method of quantitatively measuring cerebral blood flow (CBF), in which octanol-extracted radioactivity counts are measured in continuous arterial blood samples. With the new method, the whole-brain time-activity curves early after the intravenous injection of N-isopropyl-p-[123I]iodoamphetamine were first obtained by the least-squares curve-fitting method. The equation thus obtained was differentiated and the radioactivity counts were corrected by the 5-min octanol-extracted radioactivity counts of the arterial blood sample obtained at a single time point. In the present study, the value obtained by integrating the equation from 0 to 5 min, which was obtained by curve-fitting, was compared with the octanol-extracted radioactivity counts obtained by 5-min continuous arterial blood sampling in 160 patients with cerebrovascular disorders. The results showed good agreement between the values obtained by the two procedures (y = 1.049x - 1522.4; r = 0.987). Using the CBF obtained by the 5-min continuous arterial blood sampling as the standard, the errors using the present integral values of the input function were 7.1 +/- 4.9%. Measurements of the integral of the input function by the present one-point arterial blood sampling method has the potential for use in the routine measurement of CBF, because it is less invasive and more convenient than the conventional method, and it is unaffected by cardiopulmonary disease or smoking.

Arteries↗

Growth hormone and insulin-like growth factor I augment bactericidal capacity of human polymorphonuclear neutrophils.

Effects of growth hormone (GH) and insulin-like growth factor (IGF)-I on bactericidal capacity of human polymorphonuclear neutrophils (PMNs) were investigated. Venous blood was collected from healthy volunteers. In Experiment 1, PMNs were isolated, incubated with GH or IGF-I, and cocultured with Escherichia coli. E. coli-killing capacity, viability, and CD11b and CD16 expressions of PMNs were then assessed. Both GH and IGF-I enhanced E. coli killing by PMNs. GH preserved PMN viability during E. coli killing, whereas IGF-I enhanced PMN CD11b expression before coculture with E. coli. In Experiment 2, whole blood was washed and incubated with GH or IGF-I. PMNs in washed whole blood were then analyzed for phorbol myristate acetate (PMA)-stimulated CD11b, CD35, and CD16 expressions and production of reactive oxygen intermediates (ROI), as well as phagocytosis with/without anti-CD11b antibody. IGF-I enhanced PMN expressions of CD11b and CD35, but not CD16, stimulated with PMA. Both hormones enhanced phagocytosis, which was abrogated by anti-CD11b antibody, and intracellular ROI production by PMNs. These results indicate that both GH and IGF-I augment human PMN bactericidal capacity, via increased phagocytosis and intracellular ROI production. Preservation of PMN viability by GH and enhanced complement receptor expression by IGF-I may also be associated with augmented PMN bactericidal capacity. Although PMN activation has potentially harmful aspects, these results encourage additional studies to confirm the clinical relevance of exogenous GH or IGF-I for the prevention or management of septic complications in perioperative or critically ill patients especially with low circulating GH and/or IGF-I levels.

Cell Survival↗

Molecular characterization of low-molecular-weight component protein, Flp, in Actinobacillus actinomycetemcomitans fimbriae.

Fimbriae preparation from Actinobacillus actinomycetemcomitans was found to contain an abundant low-molecular-weight protein (termed Flp) with an apparent molecular mass of approximately 6.5 kDa, in addition to a small amount of 54-kDa protein. Immunogold electron microscopy localized the Flp protein at the bacterial fimbriae but not at the cell surface. The DNA fragment including the flp gene was cloned from A. actinomycetemcomitans 304-a and its nucleotide sequence was determined. An open reading frame of the flp gene was composed of 225 bp encoding a protein of 75 amino acids. Comparison of the translated amino acid sequence with the sequence of native Flp determined by Edman degradation indicated that the N-terminal part of 26 amino acids is leader peptide. The N-terminal sequence of mature Flp exhibited some similarity to type-IV pilin. Furthermore, the processing site of premature Flp is also similar to that of type-IV prepilin, and a gene encoding a protein homologous to type-IV prepilin-like protein leader peptidase was found downstream of the flp gene. These findings indicate that Flp is the major component protein of A. actinomycetemcomitans fimbriae.

Aggregatibacter actinomycetemcomitans↗

Polymorphism of TAPASIN and its linkage disequilibria with HLA class II genes in the Japanese population.

Tapasin plays an important role in HLA class I assembly. The gene has been mapped on the human MHC region. We identified two alleles of TAPASIN in the Japanese population and analyzed the association of the alleles with HLA-DPB1, -DQB1 and -DRB1 alleles. The allele frequencies of TAPASIN*01 and *02 were estimated to be 0.37 and 0.63, respectively, in the Japanese population. TAPASIN showed strong linkage disequilibrium with the HLA-DPB1 locus. Several frequent four-locus haplotypes were identified, including DRB1*0901-DQB1*0303-DPB1*0501-TAPASIN*02, DRB1*0901-DQB1*0303-DPB1*0201-TAPASIN*02 and DRB1*1302-DQB1*0604-DPB1*0401-TAPASIN*02.

Antiporters↗

Basaloid-squamous cell carcinoma of the oral mucosa: report of two cases and study of the proliferative activity.

Two cases of basaloid-squamous cell carcinoma (BSC) of the oral mucosa are described. The first case occurred at the floor of the mouth in a 58-year-old man, and the second case occurred at the mandibular gingiva in a 79-year-old woman. The laboratory data of the first case showed a positive response to hepatitis C virus antibody. In the first case, the tumor mass measured 4 x 4 cm in size, and was located at the lingual side of the median mandible beside the sublingual gland. In the second case, the tumor mass measured 25 x 15 mm in size, and was located in the alveolar mucosa of the right mandible. Histologically, both tumors showed a neoplastic epithelium arranged in a solid pattern with evidence of peripheral palisading, central necrosis, and some squamous differentiation. The proliferative activities of the BSC were compared with conventional squamous cell carcinomas (SCC) in the oral floor and gingiva, respectively, by employing a sensitive argyrophilic nuclear organizer region (AgNOR) staining method. The number of AgNOR per nucleus of the BSC was higher than that of any other SCC cases. The results support the opinion that BSC of the oral mucosa has a worse prognosis than conventional SCC.

Aged↗

Synchronous testicular seminoma and adrenocortical carcinoma: a case report.

We report a rare case of synchronous testicular seminoma and adrenocortical carcinoma. A 57-year-old man had a left testicular seminoma (clinical stage IIIB) with metastases to the lung and paraaortic lymph node. A complete response was obtained after 3 courses of chemotherapy with single-agent carboplatin. However, a left adrenal tumor was detected 1 2 months later and demonstrated a tumor volume doubling time of 2.1 months. Chemotherapy with bleomycin, etoposide and cisplatin failed to stop the tumor growth. A laparoscopic adrenalectomy was performed and pathology revealed an adrenocortical carcinoma. The patient has been free of recurrence for 42 months postoperatively.

Adrenal Cortex Neoplasms↗

[A clinical study of pulmonary cryptococcosis. The Study Group of Respiratory Mycosis in Kyoto].

During the 7 years from 1990, thirty-two patients (20 in male and 12 in female, mean age; 53 years old) were diagnosed as having pulmonary cryptococcosis. To clarify the essential points for early diagnosis of pulmonary cryptococcosis, we reviewed the clinical records and chest images. Three patients had a past history of pulmonary tuberculosis and eleven patients had underlying disorders such as malignancy, chronic pulmonary diseases and so on, but no HIV infection, which would affect this disease. Eighteen patients did not have any past history nor complications. The symptoms such as cough, sputum, chest pain and fever were generally of low-grade, 14 patients had no symptom at diagnosis. Except of some patients with severe infections and severe underlying disorders, laboratory findings such as inflamatory and nutritious markers were almost within near the normal range. On plain chest X-ray films the distribution of lesions was almost in proprtion to the volume of the lobes. The multifocal nudular and/or infitrative shadows wer observed in about 2/3 cases and single lesion in about 1/3. The width of lesions were minimal except of one case with interstitial pneumonia and two cases with multifocal segmental pneumonia. The cavity lesions were observed in 7 cases and hilar lymphadenopathy in 3 cases. On CT images, the lesions were almost located in the outer zone, the lesions which were adjacent to the pleura were observed in 15 cases. Cavitary lesions were almost smooth in edge and ubiquitous, the walls were also thick. The peripheral air-bronchogram in the nodular/infitrative shadows were observed in three cases. Pulmonary cryptococcosis is air-borne and almost a chronic infection except in AIDS patients, so careful planning for examination is essential with considerations of the characteristics of clinical and imaging features of this infection.

Adult↗

Expression of synaptotagmin VIII in rat kidney.

The synaptotagmins are a family of integral membrane proteins proposed to function as regulators of both exocytosis and endocytosis. Here, we have used immunochemical techniques and RT-PCR to assess sites of renal expression of synaptotagmin VIII. A polyclonal antibody was raised to a synthetic peptide corresponding to the carboxy-terminal 21 amino acids of mouse synaptotagmin VIII. On immunoblots of membrane fractions from renal cortex and medulla (and in several other tissues), the antibody labeled a 52-kDa band (absent with preimmune IgG). Immunofluorescence localization was carried out in tissue sections from rat kidney. The synaptotagmin VIII antibody labeled early proximal tubules, thin ascending limbs, thick ascending limbs, connecting tubules, and collecting ducts. In collecting ducts, both type A and B intercalated cells exhibited basolateral labeling, whereas principal cells were labeled chiefly in the apical and subapical portion of the cells. Thick ascending limbs were labeled in both the basolateral and apical regions. RT-PCR experiments using total RNA extracted from cortex and medulla or microdissected inner medullary collecting ducts gave a single band of appropriate size. Sequencing of the PCR product confirmed that the amplified target is synaptotagmin VIII. We conclude that synaptotagmin VIII is broadly expressed among renal tubule epithelia, raising the possibility that it is involved in regulation of transport and/or cell remodeling at several sites in the nephron and collecting duct.

Amino Acid Sequence↗

SNAP-23 in rat kidney: colocalization with aquaporin-2 in collecting duct vesicles.

Vesicle targeting proteins ("SNAREs") have been proposed to direct vasopressin-induced trafficking of aquaporin-2 water channels in kidney collecting ducts. A newly identified SNARE protein, SNAP-23, is proposed to mediate vesicle targeting to the plasma membrane in diverse tissues. The current studies were done to determine whether SNAP-23 is expressed in collecting ducts with an intracellular distribution compatible with a role in aquaporin-2 trafficking. RT-PCR demonstrated SNAP-23 mRNA in microdissected collecting ducts and other tubular segments including the proximal tubule and thick ascending limb. Immunoblotting using a polyclonal antibody raised against a COOH-terminal peptide revealed a solitary band at an apparent molecular mass of 30 kDa in renal medullary membrane fractions and inner medullary collecting duct suspensions. Differential centrifugation revealed that SNAP-23 is present in membrane fractions including the low-density fraction enriched in intracellular vesicles. Immunocytochemistry revealed SNAP-23 labeling at both the apex and the cytoplasm of collecting duct principal cells. Immunoblotting of intracellular vesicles immunoisolated using an aquaporin-2 antibody revealed the presence of both SNAP-23 and synaptobrevin-2 (VAMP-2) in aquaporin-2-bearing vesicles. We conclude that SNAP-23 is strongly expressed in collecting duct principal cells, consistent with a role in vasopressin-regulated trafficking of aquaporin-2. However, localization of SNAP-23 in both intracytoplasmic vesicles and plasma membranes suggests a function different from that originally proposed for SNAP-25 in synaptic vesicle targeting.

Animals↗

Effects of low phosphate intake on bone and mineral metabolism in rats: evaluation by biochemical markers and pyridinium cross-link formation in bone.

We have investigated the changes in biochemical markers and in pyridinium cross-links in bone in hypophosphatemic rats. Six-week-old female Wistar rats were divided into two groups (normal diet and a phosphate-deficient diet) and fed for 8 weeks. A low phosphate intake caused a significant difference in the concentrations of osteocalcin and alkaline phosphatase with advancing rachitis as well as an increase in bone resorption marker concentrations in urine. Femur biochemical analysis revealed a significant (p < 0.005) increase in deoxypyridinoline per mole collagen in the phosphate-deficient group which suggested that urinary excretions of pyridinium cross-links might reflect not only bone resorption but also increased pyridinium cross-links in bone matrix collagen. Our results demonstrate that a low phosphate intake causes an increase of pyridinium cross-link formation as well as a discrepancy between the circulation levels of alkaline phosphatase and osteocalcin with advancing rachitis. These alterations induced by low phosphate intake should be considered when interpreting the values of biochemical markers.

Alkaline Phosphatase↗

The relationship between pentosidine and hemodialysis-related connective tissue disorders.

Dialysis-related amyloidosis (DRA), such as destructive spondyloarthropathy (DSA) and carpal tunnel syndrome (CTS), occurs in the connective tissues of patients on long-term hemodialysis (HD). Recently, it was suggested that advanced glycation end products (AGEs) and beta2-microglobulin (beta2m) modified with AGEs are related to DRA. The aim of this study is to elucidate whether serum levels of pentosidine, which is an AGE, relate to the occurrence of DRA in patients with long-term HD. 127 end-stage renal failure patients, with DSA or CTS and undergoing HD, were examined. Serum pentosidine was measured by the HPLC method with column switching. Beta2m and intact parathyroid hormone (i-PTH) were measured. Pentosidine levels were significantly elevated in the DSA, CTS, and DRA groups (patients in the DRA group had either DSA and/or CTS). There were no significant differences in the beta2m and i-PTH levels between any group. The duration of HD did not correlate with either pentosidine or beta2m levels, but did with i-PTH. Receiver-operating characteristic (ROC) analysis was performed to examine the discriminatory ability of pentosidine, beta2m, and i-PTH for DRA. The area under the ROC curve was the greatest for pentosidine. Serum beta2m levels were not related with the occurrence of DRA. The fact that serum pentosidine was higher in DRA than in non-DRA indicates that it has potential as an indicator of the occurrence of DRA in long-term HD patients.

Adult↗

The advanced glycation endproduct, pentosidine, in the carpal ligament in patients with carpal tunnel syndrome undergoing hemodialysis: comparison with idiopathic carpal tunnel syndrome.

BACKGROUND/AIMS: Carpal tunnel syndrome (CTS) is a major complication that occurs in the musculoskeletal system in patients on long-term hemodialysis (HD). Pentosidine is an advanced glycation endproduct (AGE) and there is evidence that shows AGEs contribute to the pathogenesis of the complications in patients undergoing HD. The aim of this study is to investigate whether pentosidine accumulates in the carpal ligament in patients undergoing HD with CTS in comparison with idiopathic CTS. METHODS: Carpal ligaments and skin were obtained during surgery from 28 patients with CTS undergoing HD and 13 patients with idiopathic CTS (ID CTS). Pentosidine was measured by HPLC after hydrolysis of the samples, and amyloid deposits in the samples of HD CTS were examined histologically. RESULTS: Pentosidine levels in ligament and skin were significantly higher in HD CTS than ID CTS. On the other hand, there was no difference in pyridinoline which is a physical cross-link between HD and ID CTS. Amyloid deposits were observed in 14 ligament samples, whereas there was none in 14 other samples. There was no significant difference in pentosidine and pyridinoline in ligament, pentosidine in skin, duration of HD and serum beta2-microglobulin between the amyloid+ group and the amyloid- group. CONCLUSION: A greater concentration of pentosidine in the carpal ligament in HD patients compared with idiopathic patients suggests that an accumulation of AGEs contributes to one of the pathologies of occurrence of CTS in patients undergoing HD.

Aged↗

Effects of a neutrophil elastase inhibitor (ONO-5046) on acute pulmonary injury induced by tumor necrosis factor alpha (TNFalpha) and activated neutrophils in isolated perfused rabbit lungs.

The aim of this study was to examine the effect of ONO-5046, a neutrophil elastase (NE) inhibitor, on a model of acute lung injury induced by tumor necrosis factor alpha (TNFalpha) and phorbol myristate acetate (PMA)-activated neutrophils in isolated perfused rabbit lungs. 120 min after TNFalpha (4,000 JRU/ml) was injected into the pulmonary artery (PA), 5 x 10(7) PMA-stimulated neutrophils were infused into the PA together with 1251-rabbit serum albumin (RSA). In the ONO-5046-treated group (ONO), ONO-5046 (20 mg/kg/h) was continuously infused during the experimental period from 30 min prior to neutrophil administration. Saline, the ONO-5046 vehicle, was infused instead of ONO-5046 in the positive control group (ALD) and nonactivated neutrophils were infused without TNFalpha in the negative control group (Cont). PA pressure was monitored over a 240 min period, and bronchoalveolar lavage (BAL) was performed at the end of the experiment. Lung tissues were examined immunohistochemically for the expression of thrombomodulin (TM). The levels of TM in the perfusate were also measured by ELISA and the radioactivities in the BAL fluid, lung tissue and perfusate were determined to calculate the permeability index (PI) as an indicator of alveolar septal or vascular endothelial damage. The rabbit lungs infused with ONO-5046 showed slower and less increases in PA pressure compared with ALD group. The PI was significantly higher in ALD group (PI[BAL] = 0.028 +/- 0.014, PI[LUNG] = 0.04 +/- 0.003) than Cont (PI[BAL] = 0.002 +/- 0.001, PI[LUNG] = 0.015 +/- 0.003) and ONO group (PI[BAL] = 0.004 +/- 0.003, PI[LUNG] = 0.028 +/- 0.003 (p < 0.05). ALD group had higher TM levels in the perfusate and showed decreased expression of TM on the vascular endothelium compared to Cont and ONO group, suggesting that there was shedding of TM on endothelium and ONO-5046 attenuated a shedding of TM. In conclusion, ONO-5046 attenuated acute lung injury by inhibiting the alveolar epithelial and vascular endothelial injury triggered by activated neutrophils. NE appears to play an important role in the neutrophil-induced increase of pulmonary epithelial and microvascular permeability observed in acute lung injury.

Animals↗