Search PubMed⌕ Search

Biomedical subjects

K Arai

Publications and source records attributed to K Arai.

At least 415 records · Page 23Linked to original sources

No evidence for oncogenic mutations in the adrenocorticotropin receptor gene in human adrenocortical neoplasms.

The mechanism(s) of tumorigenesis for the majority of adrenocortical neoplasms remain unknown. G-Protein-coupled receptors were recently proposed as candidate protooncogenes. That activating mutations of this class of receptors might be important for tumor induction or progression of endocrine neoplasms was strengthened by the recent identification of such mutations in hyperfunctioning thyroid adenomas. To examine whether the ACTH receptor (ACTH-R) gene could be an oncogene in human adrenocortical tumors, we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH-R gene in 25 adrenocortical tumors (17 adenomas and 8 carcinomas) and 2 adrenocortical cancer cell lines. We found no missense point mutations or even silent polymorphisms in any of the tumors and cell lines studied. We conclude that activating mutations of the ACTH-R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis.

Adolescent↗

A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome.

Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, usually without mineralocorticoid deficiency. Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 families with triple A syndrome. The proband with IGD was a homozygote for an A-->G substitution, changing tyrosine 254 to cysteine in the third extracellular loop of the receptor protein, probably interfering with ligand binding. Both of her parents were heterozygotes for this mutation, which was not detected in 100 normal alleles. No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome.

Adenine↗

Production and immunohistochemical characterization of specific antibody to oviductal fluid of miniature 'Shiba' goat.

Monoclonal antibodies were produced against the oviductal secretory substances in 'Shiba' goats and their nature was characterized. In the ampullary region, very strong immunoreactivity with one clone (EE-1) was localized within the cytoplasm of non-ciliated cells ("secretory cells"), whereas very little or no immunoreactivity was observed in the isthmus region. This reactivity pattern was observed in both estrous and luteal phases. Immunohistochemical analysis showed the antigen to be either absent or minimally present in other organs including the alimentary canal, liver, pancreas, lung, kidney, uterus, thyroid gland, heart, spleen and spinal cord, and in oviducts of other species such as hamster, sheep and cow. The immunoglobulin isotype of EE-1 was determined as IgM with a kappa light chain. The positive reactions were eliminated by treating deparaffinized sections with periodic acid or testicular hyaluronidase. Results obtained in this study suggest that ampullary secretory cells in 'Shiba' goat oviduct contain a species- and tissue-specific antigen containing hyaluronic acid or hyaluronidase-sensitive carbohydrates.

Animals↗

1,5-Anhydro-D-glucitol evaluates daily glycemic excursions in well-controlled NIDDM.

OBJECTIVE: To evaluate the usefulness of plasma 1,5-anhydro-D-glucitol (1,5-AG) as a possible marker for daily glycemic excursion, we measured plasma 1,5-AG, HbA1c, fasting plasma glucose (FPG) level, and daily excursion of glycemia, from which the M-value (after Schlichtkrull) was calculated as an index of daily glycemic excursion. RESEARCH DESIGN AND METHODS: The subjects were 76 patients with well-controlled non-insulin-dependent diabetes mellitus (NIDDM) treated with diet therapy only (diet, n = 17), oral hypoglycemic agents (OHA, n = 28), conventional insulin therapy (CIT, n = 16), or multiple insulin injection therapy (MIT, n = 15). RESULTS: HbA1c values were similar among all the groups (diet, 6.9 +/- 0.6; OHA, 7.2 +/- 0.5; CIT, 7.1 +/- 0.6; MIT, 7.2 +/- 0.5%). The MIT group showed a significantly higher 1,5-AG concentration (11.5 +/- 5.3 micrograms/ml), a significantly lower M-value (9.2 +/- 5.2), and little risk of hypoglycemia ( < 4 mmol/l) and hyperglycemia ( > 10 mmol/l) (1.3 +/- 1.1 times/24 h) compared with the CIT group (6.9 +/- 3.3 micrograms/ml, 15.7 +/- 8.9, 2.2 +/- 1.6 times/24 h, respectively). Insulin doses (22.4 +/- 4.5 vs. 22.0 +/- 8.9 U/day), FPG (6.6 +/- 2.2 vs. 7.4 +/- 2.4 mmol/l), and HbA1c concentrations were not significantly different between the CIT and MIT groups. M-values significantly correlated with 1,5-AG concentrations (r = 0.414, P < 0.05), but not with HbA1c concentrations. CONCLUSIONS: The findings suggest that the plasma 1,5-AG concentration can be a useful index of the daily excursion of blood glucose, especially in patients with well-controlled NIDDM.

Biomarkers↗

Adhesion molecules on intermediate TCR cells. I. Unique expression of adhesion molecules, CD44+ L-selectin-, on intermediate TCR cells in the liver and the modulation of their adhesion by hyaluronic acid.

In addition to thymus-derived T cells, it was demonstrated recently that extrathymically differentiated T cells exist in the liver and other immune organs of mice. Since such extrathymic T cells have T-cell receptors (TCR) of intermediate intensity (i.e. intermediate TCR cells) and constitutively express IL-2 receptor beta-chain (IL-2R beta) similar to natural killer (NK) cells, they are easily distinguished from thymus-derived T cells with a TCR-bright+ IL-2R beta- phenotype (i.e. bright TCR cells). In the present study, the expression of adhesion molecules CD44 and L-selectin was compared between these T-cell subsets. Intermediate TCR cells in the liver and other organs were found to be CD44+ L-selectin- and, inversely, bright TCR cells were CD44- L-selectin+. CD3- IL-2R beta+ NK cells were also estimated to be CD44+ L-selectin-. Hyaluronic acid, which is known to adhere to a CD44 ligand, bound to intermediate TCR cells, but not to bright TCR cells. Among many extracellular matrices, hyaluronic acid induced a prominent decrease in the numbers and proportions of intermediate TCR cells and NK cells in the liver from 6 to 24 hr after in vivo administration. The half-life span of injected hyaluronic acid was approximately 7 hr in the plasma. These results suggest that the CD44 molecule, which is uniquely expressed on intermediate TCR cells and NK cells, is eventually associated with their adhesion to the sinusoidal walls in the liver.

Animals↗

The virological and histological states of anti-hepatitis C virus-positive subjects with normal liver biochemical values.

We investigated anti-hepatitis C virus (HCV) titers, HCV RNA levels in liver and serum, genetic variability in the hypervariable region of the genome, the form of the virus in the circulation, and liver histology in 21 anti-HCV-positive subjects with sustained normal liver biochemical values. Titer of anti-HCV was determined by second generation anti-HCV-passive hemagglutination assay, and HCV RNA levels were semiquantitated by reverse transcriptase polymerase chain reaction (PCR). In 19 (90%) of the 21 subjects who had a higher titer of anti-HCV (> or = 2(14)), HCV RNA was detected in both serum and liver, and histological examination showed minimal or mild chronic hepatitis in all. In the remaining 2 patients who had a lower titer of anti-HCV, HCV RNA was not detected in serum and liver, and liver histology was normal. Anti-HCV titers and HCV RNA levels in serum and liver in the 19 HCV RNA-positive subjects were compared with those levels in the 41 patients with biopsy-proven chronic hepatitis C and elevated serum aminotransferase levels as a control group. There were no significant differences in viral levels in serum and liver between the two groups. To further investigate virological differences between the two groups with regard to degree of genetic variability and the form in the circulation, we performed the PCR-single strand conformation polymorphism (PCR-SSCP) of the hypervariable region 1 and the immunoprecipitation analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Changes in CT-scan findings of liver metastases from gastric carcinoma treated by hepatic arterial infusion chemotherapy, especially after chemo-embolization and induced hypertensive chemotherapy].

The purpose of this study was to clarify the effectiveness of hepatic arterial infusion chemotherapy (HAIC) from not only the reduction rate but also the characteristic findings in CT-scan. Subjects were nine responders of HAIC for liver metastases from gastric carcinoma (chemo-embolization, 4 cases; induced hypertensive chemotherapy, 5 cases). Low density (LD), enhancement and indentation of the metastatic lesions were the characteristic findings. As the result, LD was more frequent in chemo-embolization cases (100%) than in induced hypertensive chemotherapy cases (60%). LD change, which was appeared in four cases before partial response, was one of the findings indicating the effectiveness. On the other hand, autopsy revealed severe LD to be necrosis or abscess of metastatic lesion. Therefore, we should pay attention to avoid complications such as rupture, and discontinue HAIC when severe LD appears.

Aged↗

[Evaluation of intraoperative peritoneal cytology and intraperitoneal chemotherapy using CDDP combined with MMC for gastric carcinomatous peritonitis].

A cytological examination in the lavaged peritoneal fluid during operation was performed in 462 patients with gastric cancer. The incidence of positive cytology was 36% in serosal invasion cases. The prognosis of positive cytology cases without peritoneal dissemination was slightly better than the P (+) cases. The incidence of the positive cytology was 48% in patients with serosal invasion more than 16 cm2. The prognosis of patients with serosal invasion below 32 cm2 was significantly better than in the patients with above 32 cm2. Intraperitoneal repeated administration of MMC 10 mg/body and CDDP 40-50 mg/body was continued one a month via the drug delivery system. Negative change of cytology was observed in 7 out of 14 patients, and the prognosis of these patients was better than that of the unchanged cytology group. Side effects such as severe gastrointestinal symptoms and bone marrow toxicities were not observed. Further studies should be done to confirm the efficacy of the intraperitoneal chemotherapy in terms of the prolongation of life.

Adult↗

[Intraperitoneal distribution of drug after gastric surgery].

To evaluate intraperitoneal distribution of drug after surgery, a radiographic study using peritoneography was performed. Five cases with positive intraoperative cytology of gastric carcinoma were studied. The tip of the subcutaneous injection catheter was located in the Douglas's fossa intraoperatively. As control group, 7 cases of inguinal hernia who underwent radical resection for gastrointestinal carcinoma and 2 cases who failed intraperitoneal chemotherapy through injection port, underwent peritoneography. The distribution of contrast medium in the peritoneal cavity was compared between groups. (Conclusion) The distribution of drug after gastric surgery was observed in all of the peritoneal cavity below the transverse colon. Distribution was not observed in the region where lymphadenectomy or bursectomy was done. The peritoneum has an important role in the distribution of drugs in the peritoneal cavity.

Cisplatin↗

[A case of intrahepatic infusion chemotherapy with angiotensin II human for liver metastasis from early gastric cancer].

A 71-year-old woman underwent subtotal distal gastrectomy for II a+ II c type early cancer of the gastric antrum. Histological type was poorly differentiated adenocarcinoma with medullary proliferation, and the lesion invaded the submucosal layer. Two years and 6 months after the operation, multiple liver tumors were found on the CT scan. A surgical resection of the liver tumor was performed. Microscopically, the liver tumors were compatible with gastric cancer. The remnant liver metastases were treated by intrahepatic infusion chemotherapy with Angiotensin II human (Delivert) using a subcutaneous implanted pump. The liver metastases disappeared on the CT scan after 3 courses of chemotherapy, but bone metastasis occurred after 2 months. This mode of chemotherapy was therefore considered a useful treatment for liver metastasis in gastric cancer. We concluded that not only intrahepatic infusion chemotherapy with Angiotensin II human but also another systemic chemotherapy was necessary to treat patients with liver metastasis in gastric cancer.

Adenocarcinoma↗

[Measurement and clinical significance of serum concentrations of pyridinium cross-links in patients with renal osteodystrophy].

Serum concentration of the pyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), which are markers of bone resorption, was measured by high-performance liquid chromatography in 56 patients on maintenance hemodialysis. The following analyses were conducted: 1) correlation with known markers of bone metabolism, 2) correlation with findings on bone changes on plain X-ray film, 3) elimination rates by hemodialysis, and 4) increment per day in pyridinoline after hemodialysis (delta Pyr/day). There was a very close correlation found between serum Pyr and Dpyr (r = 0.861). Both serum Pyr and Dpyr showed correlations with known markers of bone metabolism: C-PTH (r = 0.806 and r = 0.747, respectively), M-PTH (r = 0.766 and r = 0.749), osteocalcin (r = 0.717 and r = 0.693), Alp-3 (r = 0.523 and r = 0.441) and tartrateresistant acid phosphatase (r = 0.549 and r = 0.548). In addition, a correlation between the duration of hemodialysis and serum Pyr and Dpyr was observed (r = 0.426 and r = 0.318, respectively). When comparing the mean values of serum Pyr or Dpyr in three groups of patients divided according to bone changes seen on plain X-ray film, there were statistically significant differences between the group without bone changes and the remaining two groups with some bone changes (p < 0.05). A mean of 45.3% of serum Pyr was removed by hemodialysis. The serum Pyr level returned almost to the original concentration by the following hemodialysis. delta Pyr/day showed a close correlation with C-PTH (r = 0.656).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Hemodynamic effects of amrinone on patients with moderate and severe cardiac dysfunction after open heart surgery].

Hemodynamic effects of amrinone and the changes in pulmonary shunt were studied in patients for open heart surgery. Eighteen patients were allocated into two groups (group L, H) on the first day of surgery. Group L consisted of 10 patients who received moderate-dose catecholamine (DOA + DOB < 12 micrograms.kg-1.min-1) and group H consisted of 8 patients who needed high-dose catecholamine (DOA + DOB > or = 12 micrograms.kg-1.min-1) to maintain normal hemodynamics. After baseline measurement, amrinone infusion was started and the dose was increased by every 2 hours (5, 10, 20 micrograms.kg-1.min-1). At dose of 20 micrograms.kg-1.min-1, cardiac index increased significantly in group L but not in group H. SVRI and PVRI decreased by dose related fashion in both groups. Systemic arterial pressure was unaltered in group L while it decreased significantly in group H. PaO2 decreased and pulmonary shunt increased in both groups. These results suggest that inotropic response of amrinone depends on the basal level of myocardial contractility although vasodilative property and the effect on the pulmonary shunt are almost similar in both groups.

Adult↗

[The development of a tissue calcium-detecting apparatus].

Calcium phosphate is deposited in tissues with progression of aging and arteriosclerosis, causing impairments of organ functions. Localization and quantification of tissue calcium phosphate are important for elucidation of the cause of this calcium phosphate deposition. Tissue calcium phosphate has been detected by Von Kossa-Nishiyama staining using the heavy metal substitution technique. By this method, however, the reaction was weak because of the use of sunbeam as the light source, and consistent detection was difficult. Especially, fine calcium phosphate granules that appear in early stages of the pathological changes could not be detected. Therefore, we evaluated a method for preparation of tissue specimens, light source, filter, and staining conditions, and developed a more reliable method for detection and assay of tissue calcium phosphate. The human aortic tissue was fixed with formalin, embedded with paraffin, and cut to a thickness of 4 microns using a glass knife. Solax-XCA100B, an artificial sunbeam lamp with a spectrum nearly identical with that of the sun, was used as the light source. A B filter, which selectively filters out the wavelengths 290nm or less and 800-1,000nm, was used. The appearance of abnormal granules due to excessive reaction could be prevented by eliminating ultraviolet rays with wavelengths of 290nm or less, and burning of the tissue and the appearance of silver particles could be prevented by excluding infrared rays with wavelengths of 800nm or above. Distilled water was continuously dripped into the reaction solution to prevent an increase in the concentration due to evaporation. The reaction showed appreciable progression until after 40 minutes and stopped completely after 80 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗

[Local spread of carcinoma of the esophagus by perineural invasion].

For clarification of the clinico-pathological features of carcinoma of the esophagus by perineural invasion (pni), 107 resected specimens were histologically examined. A correlation between pni and other findings, including clinical results, was sought. Pni was found in 31 patients (29.0%). It was found in no cases without adventitial cancerous invasion, at 26.3% in a1, 36.5% in a2 and 66.7% in a3. Pni would thus appear to be closely correlated with the depth of invasion. It also showed correlation with lymph-canal invasion but not with venous invasion or lymph node metastasis. Pni positivity was the same regardless of patient's age and sex, as well as tumor size, location and histological differentiation. In patients who had undergone preoperative radiotherapy, lymph-canal and venous invasion were noted to have markedly decreased but not pni. Curative resection was carried out in 57.9% of the pni negative patients and in 32.3% of the pni positive. Local recurrence was observed in 30.0% of pni positive and only 4.5% of negative cases. The cumulative survival rate was not significantly less in positive compared to negative patients.

Adult↗