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Biomedical subjects

R Abe

Publications and source records attributed to R Abe.

At least 181 records · Page 10Linked to original sources

Potential roles of the B7 and CD28 receptor families in autoimmunity and immune evasion.

Recognition of self major histocompatability complex (MHC)-presented antigen (MHC:Ag) by the T cell antigen receptor (TCR) is by itself not sufficient to induce T cell proliferation. Rather, to be fully activated T cells require both a TCR-generated signal and a "costimulatory" signal. This important costimulatory signal is not completely understood. Recent evidence suggests that this costimulatory signal is generated by the interaction of the T cell CD28 receptor with the B7 counterreceptor found on antigen-presenting cells. Regulation of costimulation may well prove to be more complex than was previously imagined based on the discovery that CD28 and B7 are each members of larger gene families. The present review highlights recent advances in the understanding of the CD28 and B7 receptor families with an emphasis on controversies in the field. Certain forms of immunopathology that might result from the aberrant regulation of CD28 and/or B7 expression are also discussed.

Animals↗

Molecular cloning and nucleotide sequence of the 90k serine protease gene, hspK, from Bacillus subtilis (natto) No. 16.

We previously reported purification and characterization of a 90k serine protease with pI 3.9 from Bacillus subtilis (natto) No. 16 [Kato et al. 1992 Biosci Biotechnol Biochem 56:1166]. The enzyme showed different and unique substrate specificity towards the oxidized B-chain of insulin from those of well-known bacterial serine proteases from Bacillus subtilisins. The structural gene, hspK, for the 90k serine protease was cloned and sequenced. The cloned DNA fragment contained a single open reading frame of 4302 bp coding a protein of 1433 amino acid residues. The deduced amino acid sequence of the 90k-protease indicated the presence of a typical signal sequence of the first 30 amino acids region and that there was a pro-sequence of 164 amino acid residues after the signal sequence. The mature region of the 90k-protease started from position 195 of amino acid residue, and the following peptide consisted of 1239 amino acid residues with a molecular weight of 133k. It might be a precursor protein of the 90k-protease, and the C-terminal region of 43k might be degraded to a mature protein from the precursor protein. The catalytic triad was thought to consist of Asp33, His81, and Ser259 from comparison of the amino acid sequence of the 90k-protease with those of the other bacterial serine proteases. The high-molecular-weight serine protease, the 90k-protease, may be an ancient form of bacterial serine proteases.

Amino Acid Sequence↗

Prognostic factors associated with differentiated thyroid cancer.

A multivariate analysis was conducted on the survival data of 180 patients who underwent curative resection for differentiated thyroid cancer between 1966 and 1987, and the 10- and 20-year survival rates were found to be 80.6% and 73.1%, respectively. A survival analysis was also performed, testing the following factors: the patient's age at the time of diagnosis, tumor size, extraglandular extension, nodal status, distant metastases, operative procedure, sex, and histology. A univariate analysis found the initial six factors to be significant prognostic variables, but the latter two to be of no significance. On the other hand, the multivariate analysis showed that distant metastases, age, and tumor size were the most significant prognosticators. Thus, the age of the patient should be taken into consideration during the follow-up of treatment for differentiated thyroid cancer.

Adenocarcinoma, Follicular↗

Evaluation of aspiration biopsy cytology and combined preoperative tests in the diagnosis of breast cancer.

This study was conducted to investigate the usefulness of aspiration biopsy cytology (ABC) and other combined tests for the preoperative diagnosis of breast cancer. In an analysis of 599 aspirates of breast tumors, "suspicious" cases were included among the positive, while "borderline" cases were considered to be negative. The sensitivity of ABC was 87.3%, the specificity was 92.3%, and the predictive value of a positive diagnosis was 92.8%. A total of 207 cases of breast cancer were evaluated to determine the diagnostic significance of breast cancer, particularly for tumors less than 2.0cm by means of quadruple test including physical examination, mammography (MMG), ultrasonography (US), and ABC. The combined tests of MMG or US, and ABC resulted in a sensitivity of 96.2% and 94.9%, respectively, and were considered to complement each other in the diagnosis of small breast cancer. Surgical biopsy is thus not always necessary in malignant cases that are conclusively diagnosed by the combined quadruple test.

Biopsy, Needle↗

Venous invasion as a prognostic factor in colorectal cancer.

Venous invasion as a prognostic factor was evaluated in 124 patients with colorectal cancer. By classifying the patients as having either negative to mild invasion or moderate to marked invasion, a significant correlation was found between the degree of venous invasion and clinicopathological variables such as lymphatic invasion, lymph node metastasis, liver metastasis, and DNA ploidy. Significantly more favorable survival was seen in those with a lower degree of vascular invasion; however, of the six prognosticators analyzed by Cox's proportional hazard model, the only significant factors were depth of invasion and DNA ploidy. Although venous invasion showed no significance, it is still considered a valuable prognostic indicator that is easy and economical to perform.

Adenocarcinoma↗

Nitric oxide modulates pancreatic edema formation in rat caerulein-induced pancreatitis.

This study was designed to investigate the role of nitric oxide (NO) in the formation of pancreatic edema in caerulein-induced pancreatitis in rats. Pancreatitis was produced by two intraperitoneal injections of caerulein, and plasma amylase concentration, pancreatic edema index (pancreatic wet weight/body weight), and Evans blue extravasation (as a measure of vascular permeability) were evaluated 5 h after the first injection. Four doses (1, 2.5, 5, and 10 mg/kg) of NG-nitro-L-arginine (L-NNA), an NO synthase inhibitor, were subcutaneously administered at -0.5, 0.5, 1.5, 2.5, and 3.5 h after the first injection of caerulein. L-NNA significantly lowered the edema index, the wet/dry weight ratio of the pancreas, and Evans blue extravasation in the rats with pancreatitis. The maximal effect was obtained by L-NNA at a dose of 2.5 mg/kg; this inhibited the increase in pancreatic edema formation from the control value by 60%-70%. Intraperitoneal injections (20 mg/kg, five times) of L-arginine, a substrate for NO production, partly reversed the L-NNA-induced inhibition of pancreatic edema formation, but D-arginine, an enantiomer of L-arginine, did not show any effect. Plasma amylase concentrations were not significantly affected by any dose of L-NNA, nor were they affected by L- or D-arginine. These findings strongly suggest that endogenous NO plays an important role in the formation of pancreatic edema in caerulein-induced pancreatitis in rats, probably by increasing vascular permeability and protein extravasation.

Acute Disease↗

The role of endogenous glucocorticoids in rat experimental models of acute pancreatitis.

BACKGROUND & AIMS: Cytokines activate the hypothalamic-pituitary-adrenal axis and suppress inflammation by stimulating glucocorticoid secretion. The state of adrenocortical function during acute pancreatitis and its role in this disease were determined. METHODS: Cerulein-induced pancreatitis or closed duodenal loop pancreatitis was produced in rats that had undergone adrenalectomy or sham adrenalectomy, and the serum corticosterone and interleukin 8 levels and the intensity of the pancreatitis were examined. RESULTS: Serum corticosterone levels were significantly higher than basal levels in both models of experimental pancreatitis. In both models, adrenalectomy increased serum amylase and pancreatic edema and produced more severe inflammation. Adrenalectomy significantly increased mortality in animals with closed duodenal loop pancreatitis. Exogenous hydrocortisone administered to adrenalectomized animals suppressed the elevation of serum interleukin 8 levels and decreased both the severity of pancreatitis and mortality. CONCLUSIONS: These results suggest that the adrenocortical function is stimulated during acute pancreatitis and that the secretion of endogenous glucocorticoids may play an important role in mitigating the progress of this disease, probably by inhibiting cytokine production.

Acute Disease↗

Lymph node metastases in gastric cancer invading the submucosal layer.

We investigated the incidence of lymph node metastasis in 80 patients with early gastric cancer invading the submucosal layer and the relation of metastasis to other clinicopathological variables. All patients underwent curative gastric resection with lymphadenectomy. Lymph node metastasis was detected histologically in 15 patients. The incidence of nodal involvement showed significant increase paralleling the depth of cancer invasion. There was no relation between nodal involvement and histological differentiation. No patients died of gastric cancer during the follow-up. We conclude that gastrectomy with R2 lymphadenectomy is an appropriate operative method for early gastric cancer in which precise diagnosis of cancer invasion cannot be confirmed preoperatively.

Adult↗

p53 mutations and overexpressions in Japanese breast cancer.

Mutations in the p53 gene were analysed in 50 cases with breast cancer by PCR-SSCP and direct DNA sequencing. Mutations were found in 10 of 50 cases (20%) including a case with Tis, and loss of the normal allele was found in five of these cases. Eight of the 10 mutations occurred within highly conserved domains, but no mutational hot spots were found. GC to AT transitions were the most frequent mutations (six of 10 cases), while mutations at CpG dinucleotides were found in three cases (30%). AT to TA transversions were the second most frequent mutation (20%). The level of expression of p53 protein was assessed by Western blot analysis in 62 cases. Overexpression of p53 protein was detected in 21 of 62 cases (34%) including a case with Tis. There was a strong correlation between missense mutations in the p53 gene and overexpression of p53 protein. Overexpression of p53 protein was closely associated with increasing tumour size and ER-negative status among the various factors investigated, suggesting that p53 overexpression may reflect the lack of differentiation in breast cancer.

Base Sequence↗

Surgical treatments for oesophageal cancer concomitant with gastric adenoma with severe epithelial atypia.

The various surgical treatments for oesophageal cancer concomitant with gastric adenoma with severe epithelial atypia (SEA) are discussed by presenting three such cases. As gastric adenoma with SEA had been considered to be a precancerous condition but not normally an indication for gastrectomy, we devised an operative strategy of laparotomy and thoracotomy. For Case 1, with early oesophageal cancer and gastric adenoma with SEA in the body of stomach, a laparotomy and local resection of the gastric lesion were carried out prior to thoracotomy in order to determine the safest reconstructive method after measuring the length of the well-nourished gastric tube. In Case 2, with advanced oesophageal cancer, a thoracotomy was first performed to assess the curability of surgery for the oesophageal cancer and a gastric adenoma was removed. In contrast, for Case 3 with advanced oesophageal cancer, and in whom post-operative survival was deemed to be short, a gastric adenoma was not resected. The most appropriate operative methods should thus be decided after careful consideration of the stage of the oesophageal cancer and characteristics of the gastric adenoma.

Adenoma↗

Comparison of false negative rates among breast cancer screening modalities with or without mammography: Miyagi trial.

False negative rates were compared in two screening modalities, physical examination with or without mammography, in an intervention study for women aged over 50 in Miyagi Prefecture. Thirty-five breast cancers were detected in 12,515 subjects who participated in the trial consisting of physical examination and mammography, whereas 44 breast cancers were detected in 50,105 subjects who received physical examination alone, so that the detection rates were 0.28% and 0.09%, respectively. Among 50,061 subjects who received physical examination alone, 8 women were diagnosed as having breast cancer within 12 months after the screening, while only one of 12,480 screenees receiving the combined modality was so diagnosed, implying false negative rates of 15.4% and 2.8%, respectively. When the screening sensitivity in the combined system was analyzed according to each single modality, the false negative rate provided by physical examination with mammography turned out to be 2.8%, significantly lower than that (33.3%) by the physical examination alone. Minimal breast cancers represented 25.7% of all screen-detected cancers in the combined modality, compared with 9.1% in the modality without mammography. The trial thus indicates that physical examination combined with mammography may be an appropriate modality for breast cancer screening in women aged over 50 on the basis of screening sensitivity.

Aged↗

Distinct roles for B7-1 (CD-80) and B7-2 (CD-86) in the initiation of experimental allergic encephalomyelitis.

The activation and differentiation of T cells require both antigen/MHC recognition and costimulatory signals. The present studies examined the role of B7-1 (CD80) and B7-2 (CD86) costimulation in the prototypic autoimmune disorder, experimental allergic encephalomyelitis (EAE). In adoptively transferred EAE, in vitro activation of myelin basic protein (MBP)-specific lymph node cells was inhibited by the combination of anti-CD80 plus anti-CD86, but not individually. However, in actively induced disease, one injection of anti-CD80 significantly reduced disease, while anti-CD86 exacerbated disease. Interestingly, one injection of CTLA-4Ig suppressed disease, while multiple injections resulted in enhanced disease. Thus, the costimulation provided by B7-1 molecules appears to be important for the development of encephalitogenic T cells. The enhanced disease caused by multiple injections of CTLA-4Ig or a single injection of anti-CD86 suggests an inhibitory function for CD86 interaction with its counterreceptors CD28 and CTLA-4 in EAE. Alternatively, these results are consistent with an essential timing requirement for the coordinated interaction of B7 and CD28 family receptors, and that disruption of this critical timing can have opposing results on the outcome of an immune response.

Animals↗

Development of an apparatus to measure plasma colloid osmotic pressure mounted on the extracorporeal hemodialysis circuit.

We newly developed an apparatus to measure colloid osmotic pressure (COP) of blood plasma continuously by hemodialysis (HD) or extracorporeal ultrafiltration method (ECUM) without any invasive procedure or blood sampling. The COP value measured by this apparatus highly correlated with the COP value calculated from the concentration of total protein of blood plasma (TP) sampled simultaneously (y = 21.182 + 0.96256x, r2 = 0.911). Measurement of the COP with this apparatus seems to be reliable.

Adult↗

Very-low-dose streptozotocin induces diabetes in insulin promoter-mB7-1 transgenic mice.

Transgenic mice that express mouse B7-1 (mB7-1, recently designated CD80) on their pancreatic beta-cells maintain normal islet architecture, have normal pancreatic insulin content, and only rarely spontaneously develop insulitis and diabetes. Nevertheless, these mice display an extreme sensitivity to streptozotocin (STZ)-induced diabetes. Female mice were administered two STZ doses intraperitoneally, 20 and 40 mg/kg body wt, each for five consecutive days. Nontransgenic but otherwise syngeneic mice responded to the STZ with a moderate diminution in pancreatic insulin content but not with persistent glycosuria. In striking contrast, STZ administered to transgenic mice resulted in a severe diminution of pancreatic insulin content and in diabetes. Notably, the lower STZ dose resulted in diabetes only after a prolonged (26- to 100-day) latency. STZ-induced diabetes appears to be T-cell dependent, since treatment with T-cell-depleting (and in particular CD8+ subset-depleting) antibodies ameliorated the response. Anti-mB7-1 monoclonal antibody administration also prevented STZ-induced diabetes. Thus, unmasked mB7-1 is a required component in the pathway resulting in beta-cell killing. Immunohistological analysis revealed that early after STZ administration, both mB7-1 transgenic and nontransgenic mice developed insulitis. While this insulitis resolved in the nontransgenic mice, the islet-infiltrating CD4+ and CD8+ T-cells in the transgenic mice were associated with complete beta-cell destruction. These data suggest that STZ-induced diabetes in mB7-1 transgenic mice is an immune-mediated process with distinct potential advantages over existing insulin-dependent diabetes models.

Animals↗

[The criteria for the prediction of paroxysmal atrial fibrillation by time domain analysis of the P wave-triggered signal-averaged electrocardiogram].

In order to determine the criteria for definition of atrial late potentials in patients with paroxysmal atrial fibrillation (Paf), the P wave-triggered signal-averaged electrocardiogram (SAE) was recorded in 88 patients with Paf (Paf group) and in 216 normal subjects (Normal group). Three SAE variables, duration of the filtered P wave (FPD), root-mean-square voltage of the last 20 msec (V20) and duration of under 5 microV (D5) of the vector magnitude were measured. FPD and D5 were significantly longer in the Paf than in the Normal group (FPD; 137 +/- 13 vs. 115 +/- 7 msec, D5; 27 +/- 12 vs. 16 +/- 5 msec, p < 0.001, respectively). V20 was also significantly lower in the Paf than in the Normal group (2.5 +/- 1.1 vs. 3.9 +/- 1.1 microV, p < 0.001). The sensitivity and specificity for the prediction of Paf was computed (for all dichotomy points) and compared with various criteria for atrial late potentials based on the three SAE variables. Analysis showed that 1) FPD was a better predictor of Paf than the other two variables, 2) the criteria of [FPD > 125 msec and V20 = 3.0 microV or less] as defining "atrial late potentials" gave a sensitivity of 68%, a specificity of 99% and a predictive accuracy of 90%. These findings suggest that the SAE is useful to predict Paf. Additionally, prospective studies are needed with a larger number of patients to compare the different criteria of "atrial late potentials" by time domain analysis of the SAE.

Adolescent↗

[Evaluation of nuclear morphometric risk grade as a prognostic factor of early breast cancer].

The prognostic significance of nuclear areas was studied in 241 patients with primary stage I or II breast cancer. The mean follow-up period was 56.4 months. The nuclear areas of 100 breast cancer cells in HE stained specimen in each patient were measured by means of an image analyzing system, and the mean nuclear area (MNA) and standard deviation of nuclear area (SDNA) were calculated. MNA and SDNA were significantly larger in patients with recurrence than without it. Patients were divided into 2 groups according to the Nuclear Morphometric Risk Grade (NMRG), which was defined as follows: high risk: MNA > or = 80 microns 2 and SDNA > or = 28 microns 2; low risk: MNA < 80 microns 2 or SDNA < 28 microns 2. High risk patients revealed significantly poor disease free and overall survival than low risk patients (p < 0.0001, p < 0.0001). Furthermore, NMRG was a significant prognostic factor in node-negative patients. Cox multivariate analysis showed that nodal status and NMRG were independent predictors of tumor recurrence (n:p = 0.001; NMRG:p = 0.27) and survival (n:p < 0.001; in the NMRG:p = 0.0007). NMRG was a strong prognostic factor in patients in the early stage and it might support the decision for or against adjuvant therapy.

Breast Neoplasms↗

[Clinical effects of carmofur (Mifurol) on advanced and recurrent breast cancer in a cooperative study. Research association for re-evaluation of direct effects of Mifurol on breast cancer].

The direct effect and safety of carmofur (Mifurol) in cases of advanced and recurrent breast cancer were evaluated as a cooperative study at twenty-two facilities nationwide. Carmofur 12 mg/kg/day within the maximum daily dose of 600 mg was administered orally for eight weeks or longer. Of 42 patients registered for the study, 38 met the eligibility criterial (qualified patients), of whom 31 completed all tests for evaluation (completely qualified patients). The response rates were 18.4% with the qualified patients (PR, 7; Long NC, 3; NC, 11; PD, 12; NE, 5; ie, 7/38), and 22.6% with the completely qualified patients (PR, 7; Long NC, 2; NC, 10; PD, 12; ie, 7/31). The interval before the onset of PR after administration of carmofur was started was a minimum 29 days, a maximum 190 days and a median 82 days. Side effects were observed in eighteen patients (42.9%). Frequent micturition, loss of appetite, dizziness or feverish feeling were major symptoms, but none were serious.

Administration, Oral↗