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Biomedical subjects

K Imai

Publications and source records attributed to K Imai.

At least 721 records · Page 40Linked to original sources

Internal image-bearing anti-idiotypic monoclonal antibodies.

Five anti-idiotypic (Id) monoclonal antibodies (MAbs) (Ab2) were prepared from a BALB/c mouse immunized with anti-carcinoembryonic antigen (CEA) MAb MA208 (Ab1) in a syngeneic system. These anti-Id MAbs appear to recognize unique idiotopes at the combining site of MAb MA208, because they were specifically reactive with MAb MA208 and showed inhibitory activity against the binding of MAb MA208 to CEA. These MAbs were divided into three groups according to the analysis of anti-anti-Id antibodies (Ab3) induced with each anti-Id MAb. Anti-anti-Id MAb M7-625 antiserum (Ab3) reacted with purified CEA in a binding assay and in Western blot analysis, and competed with Ab1 binding to CEA. Furthermore, the binding of anti-Id MAb M7-625 to MAb MA208 was inhibited with CEA, indicating that Ab2 mimics the structure of the epitope in CEA which was recognized with Ab1. These serologic findings suggest that anti-Id MAb M7-625 carries the internal image of the antigen. According to the amino acid sequences of complementarity determining region (CDR) 1, 2 and 3 of the MAb M7-625 variable region, homology of amino acid sequences exists between CDR2 in the H chain (5 amino acids of 10) and domain III of CEA (545-554). Seven anti-Id MAbs were then generated using anti-CEA synthetic peptide MAb P1-356 to analyze further the epitope structure of CEA. These anti-Id MAbs were divided into four groups. Serological analyses as described above suggested that among them, anti-Id MAb M315 had an internal image. We therefore prepared anti-anti-Id MAbs using anti-Id MAb M315. Among them, anti-anti-Id MAb 11B2 reacted directly with CEA and competed with MAb P1-356 in the competition assay. In addition, MAb 11B2 stained both cultured CEA-producing cells and colonic cancer tissues, suggesting that MAb 11B2 is Ab1 like Ab3. These MAbs (Ab1-3) will be of use for the structural analysis of the internal image.

Amino Acid Sequence↗

Preventive effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer in a double-blind trial. The BLP Study Group.

A double-blind trial was conducted in 138 patients with superficial transitional cell carcinoma of the bladder following transurethral resection to evaluate the prophylaxis of recurrence by an oral Lactobacillus casei preparation (BLP). Patients were stratified into the following 3 subgroups: (A) with primary multiple tumors; (B) with recurrent single tumors, and (C) with recurrent multiple tumors. In each group, patients were randomly allocated to receive BLP or placebo. BLP showed a better prophylactic effect in subgroups A and B than placebo, whereas no significant difference was observed in subgroup C. Cox multivariate analysis showed that the outcome with BLP was significantly better than with placebo (p = 0.01). Slight and tolerable adverse reactions occurred in 3 patients receiving BLP and in 3 of the placebo-treated patients. Oral administration of BLP was thus safe and effective for preventing recurrence of superficial bladder cancer.

Administration, Oral↗

Determination of D-amino acids in serum from patients with renal dysfunction.

D-Ala and D-Ser were detected in the sera of both normal subjects and patients with renal dysfunction, and their concentrations were higher in the patients than in the normal subjects. A positive correlation between the concentration of D-Ala or D-Ser and that of creatinine (r = 0.733, p < 0.001 or r = 0.634, p < 0.001) or blood urea nitrogen (BUN) (r = 0.449, p < 0.05 or r = 0.629, p < 0.001) was observed in sera from 20 patients with renal dysfunction. The fraction (%D) of D-Ala in the total Ala in serum ([D/(D+L)] x 100) correlated well with the concentration of creatinine (r = 0.811, p < 0.001), suggesting that it is a candidate as a marker for renal proximal tubular dysfunction. The correlations of %D of Ser with creatinine and BUN levels were 0.796 (p < 0.001) and 0.919 (p < 0.001), respectively, indicating that %D of Ser may reflect protein turnover or catabolism in certain tissues as well as renal proximal tubular dysfunction.

Amino Acids↗

High-performance liquid chromatography of fullerence (C60) in plasma using ultraviolet and mass spectrometric detection.

Fullerence (C60) was determined by high-performance liquid chromatography using both ultraviolet and mass spectrometric detection. The detection limit for each method was 0.05 and 2.0 ng (signal-to-noise ratio (S/N = 2)) per injection, respectively. Rat plasma spiked with C60 (10 micrograms/ml) was extracted using solid phase extraction with a recovery of 62.1% and the coefficient of variation (c.v., n = 5) between intra-day assays was 4.0%. The calibration curve for peak area and plasma C60 concentration with ultraviolet detection showed good linearity (r = 0.996) over the range 0.5-60 micrograms/ml. This newly developed method was applied to rat plasma samples after intravenous administration of C60 solubilized with polyvinylpyrrolidone.

Animals↗

Involvement of pituitary hormone in the sex-related regulation of hepatic epoxide hydrolase activity in mice.

The involvement of the pituitary gland in the expression of sex-related differences in the activities of epoxide hydrolase (EH) in liver was examined in hypophysectomized and neonatally monosodium L-glutamate (MSG)-treated male and female mice. In hypophysectomized mice, the hepatic microsomal EH activity of males and females increased considerably above those of the respective sham-operated controls, and the female activity exceeded that of the sham-operated males. The hypophysectomy caused a decrease in soluble EH activity in males, while the operation led to an elevation of the activity in females. Neonatal treatment with MSG resulted in marked increases of microsomal EH activity in males and females at adulthood and the activity was about 2 times that of the male control mice. Treatment of hypophysectomized males and females with growth hormone (GH) resulted in a significant decrease in microsomal EH activity below those of the corresponding hypophysectomized controls, while the hormone treatment had no effect on the soluble enzyme activities. These results suggest that murine hepatic microsomal EH activity is principally under the suppressive control of the pituitary and GH is a causal hormone involved in the expression of sexual dimorphism in the enzyme activity.

Animals↗

Resistance of hepatic lysosomes, mitochondria and microsomes of protoporphyrin-administered rats to peroxidative damage.

Antioxidative inhibition by protoporphyrin (PP) of peroxidative damage in lysosomes, mitochondria and microsomes of rat liver was investigated at 24 h after an intravenous administration of PP. Using a lysosome-containing (3500 x g) fraction, the release of lysosomal marker enzymes, acid phosphatase and aryl sulfatase, from lysosome which had been stimulated by L-ascorbic acid (AsA), was decreased dose-dependently, as was the inhibition of lipid peroxidation by PP in the fraction. Swelling of mitochondria induced by Fe2+ and AsA was also inhibited in the PP-injected rat. In microsomes, lipid peroxidation stimulated by AsA caused a decrease in activity of a microsomal marker enzyme, glucose 6-phosphatase, and in P450 content. The extent of the decrease by AsA, both in activity and content, was diminished in PP-administered rat liver microsomes. These results indicate that PP protects those subcellular fractions from deterioration by lipid peroxidation.

Animals↗

Diagnosis of occlusion site in the left anterior descending coronary artery in patients with anterior myocardial infarction--comparison of thallium-201 myocardial scintigraphy and 12-lead electrocardiography.

To evaluate whether the site of occlusion/stenosis in the left anterior descending coronary artery (LAD) could be diagnosed by noninvasive techniques, thallium-201 myocardial scintigraphy (TMS), 12-lead electrocardiography (ECG), and coronary arteriography were performed in 33 patients with anterior acute myocardial infarction (AMI). The subjects were divided into two groups according to the location of stenosis: ie, either proximal to the first diagonal branch (PRO, n = 18), or beyond the first diagonal branch (NON-PRO, n = 15). The location of the anterior interventricular groove was defined as 0 degrees. The extent of persistent perfusion defect was greater in the PRO group than in the NON-PRO group (0.43 +/- 0.12 vs 0.31 +/- 0.14, p < 0.01). The left margin of the defect in the basal short-axis layer was at 75 +/- 30 degrees in the PRO group and at -19 +/- 43 degrees in the NON-PRO group (p < 0.001). A defect with a left margin at > 30 degrees in the basal layer was found in 94% (17/18) of the patients in the PRO group and in 6% (1/15) of the patients in the NON-PRO group (p < 0.001). An abnormal Q wave in leads a VL/I was found in 78% (14/18) of the patients in the PRO group and in 20% (3/15) of the patients in the NON-PRO group (p < 0.001). The sensitivity, specificity and total predictive accuracy of detection of proximal lesions of the LAD were 94%, 93% and 94% by TMS, and 78%, 80% and 79% by ECG, respectively. A significant difference in accuracy existed between TMS and ECG (p < 0.05). These data suggest that it is possible to diagnose the site of occlusion/stenosis of the LAD as either proximal or non-proximal in patients with anterior AMI by TMS and ECG.

Coronary Angiography↗

Quantitative assessment of daily physical activity levels in patients with chronic heart failure by measuring energy expenditure--effects of converting enzyme inhibitor therapy.

Although a major goal in the treatment of chronic heart failure is to improve daily physical activity levels, this has not been assessed quantitatively. An increased daily activity level may be reflected by an increase in daily energy expenditure. In the present study, measurements of energy expenditure with a commercially available ambulatory calorimeter were first validated using cardio-pulmonary exercise tests in 5 normal volunteers. The energy expenditure measured by the calorimeter correlated well with that estimated from oxygen uptake (r = 0.89). Subsequently, the daily energy expenditure was serially measured with the calorimeter during long-term administration of the converting enzyme inhibitor ramipril for 24 weeks in 8 patients with chronic heart failure. Changes in echocardiographic parameters and exercise capacity were also studied. Peak oxygen uptake and anaerobic threshold assessed with symptom-limited maximal bicycle exercise were significantly increased 12 weeks or more after the initiation of treatment (P < 0.01 and P < 0.01, respectively). Left ventricular fractional shortening substantially, but not significantly, increased during this period (P < 0.1). These results strongly suggest that an overall improvement in heart failure was achieved after long-term ramipril therapy. The energy expenditure during daily activities was also significantly increased after ramipril therapy for 24 weeks (P < 0.01). Thus, the daily energy expenditure increased with improvement of heart failure, probably reflecting an increase in daily activity levels. We conclude that calorimetric measurement of daily energy expenditure is a novel and simple technique for quantitative evaluation of the effect of therapy on daily physical activity levels in patients with chronic heart failure.

Activities of Daily Living↗

Desensitization and selective down-regulation of rat cardiac beta 1-adrenoceptors by prolonged in vivo infusion of T-0509, a beta 1-adrenoceptor full agonist.

We studied the effects of prolonged infusion of a selective beta 1-adrenoceptor (beta 1AR) full agonist, T-0509 [(-)-(R)-1-(3,4-dihydroxyphenyl)-2-[(3,4- dimethoxyphenethyl)amino]ethanol hydrochloride], with regard to its inotropic effect in vivo and cardiac beta AR density. The results were compared with those for isoproterenol. Continuous infusion of isoproterenol at doses of 2.5-40 micrograms/kg/hr, s.c. for 6 days shifted the dose-response curves of isoproterenol (i.v.) for LVdP/dtmax to the right and increased the ED50 values up to fourfold. Isoproterenol infusion at 40 micrograms/kg/hr reduced the density of both beta 1- and beta 2ARs by 36% and 43% respectively, in left ventricular membranes. Following 6-day infusion of T-0509 at doses sufficient to induce a positive inotropic effect (5-40 micrograms/kg/hr), the ED50 value of T-0509 (i.v.) for LVdP/dtmax was also increased up to fourfold. In contrast to isoproterenol, infusion of T-0509 caused selective down-regulation of beta 1ARs by 30% without changing the number of beta 2ARs. These results indicate that long-term application of a selective beta 1AR full agonist causes desensitization to its inotropy in vivo, with subtype-selective down-regulation of beta 1ARs in cardiac ventricles.

Adrenergic beta-Agonists↗

Effects of age at first-pairing on the reproductive performance of Mongolian gerbils (Meriones unguiculatus).

Effects of age at first-pairing on the reproductive performance of the gerbil were studied throughout the reproductive life. Six groups of 7-30 female gerbils were paired monogamously with males at different ages. Out of 101 pairs in 6 groups, 79 (78.2%) produced 1 or more litters. The mean litter size at birth and mean weaning rate of 846 litters were 4.4 (totally 3,733 pups) and 67.4% (2,517 pups), respectively. Reproduction was compared in the 6 age groups. The littering rate (No. of females with litters/No. of female paired) was significantly lower in two groups in which mature females were paired with age-matched males (Group 4) or the oldest females with younger, sexually mature males (Group 6). The interval from pairing to the first litter was shortest in two groups in which mature females were paired with one month older, sexually mature males (Groups 3 and 5). Although the oldest pairs (Group 6) produced about 7 litters, the pairs from the other 5 groups produced about 10 or more litters throughout their reproductive life. The weaning rate was significantly higher in Group 6 (the oldest pairs) than in the younger groups. The effects of parity on reproduction were estimated from the data for the 61 pairs which produced more than 8 litters in the 6 groups. The number of pups at birth and the weaning rate were decreased in last 20-30% of the total parity in all 6 groups, although the age at the last litter in all groups was significantly different. The data suggest that any decline in reproduction may be due to not age but parity in the Mongolian gerbil.

Aging↗

Collagenous colitis.

Collagenous colitis is characterized clinically by chronic watery diarrhea and pathologically by colonic mucosal subepithelial collagen deposition. We report a 72-year-old woman who had collagenous colitis associated with chronic watery diarrhea. She received a non-steroidal anti-inflammatory agent (sulindac) because of rheumatoid arthritis. Histological examination of biopsy showed a thick subepithelial collagen layer with lymphocytes, plasma cells, and infiltration of a few eosinocytes in the lamina propria. These findings led to the diagnosis of collagenous colitis. After treatment with salazosulfapyridine, her bowel movement became normalized and mucosal subepithelial collagen deposition disappeared.

Aged↗

Polymyositis associated with thymoma and the subsequent development of pure red cell aplasia.

A 53-year-old woman with polymyositis associated with thymoma subsequently developed pure red cell aplasia (PRCA). She was hospitalized because of fever and muscle weakness, and diagnosed as having polymyositis by muscle biopsy. Remarkable clinical improvement followed administration of prednisolone. Progressive anemia became evident, however, while prednisolone was being tapered. Erythroid aplasia and the presence of thymoma confirmed the diagnosis of PRCA. Further examinations revealed that cytotoxic T cells may play an important role in the pathogenesis of this case.

Cytotoxicity, Immunologic↗

[A case of ANCA negative Wegener's granulomatosis with pulmonary giant bulla showing high level of soluble ICAM-1].

This paper reports a rare case of the limited form of Wegener's granulomatosis (WG) with pulmonary giant bulla, which was pathologically identified only in the lung and showed a high level of soluble intercellular adhesion molecule-1 (ICAM-1) but not anti-neutrophil cytoplasmic antibody (ANCA). A 46 year-old male was admitted for the further examination of right anterior chest pain and dyspnea. Chest X-ray and CT examination showed giant bulla accompanied with the invasive lesions in upper lobe of right lung. Partial lobectomy was done. Granulomatous and necrotizing vasculitis characteristics of WG were confirmed by the histopathology of resected tissues. Immunological analysis on admission showed a high level of soluble ICAM-1 and ANCA negative, but that of soluble ICAM-1 was reduced after surgical operation and remained within normal range during an administration of prednisolone and cyclophosphamide. These results suggest that soluble ICAM-1 may be one of the useful parameters for a diagnosis of WG and for an estimation of its treatments, especially in the cases of ANCA negative WG.

Antibodies, Antineutrophil Cytoplasmic↗

[Case report: rheumatoid arthritis complicated by chronic myelogenous leukemia treated with interferon].

A fifty-six-year old man complained of arthralgia and swelling of both feet, morning stiffness in both hands and finger joints in March 1987, and was treated with non-steroidal anti-inflammatory agents at another hospital. He has been treated for chronic myelogenous leukemia (CML) since May 1990. He was admitted to our hospital in March 1991 because of worsening of his multiple arthralgias, and a diagnosis of rheumatoid arthritis (RA) (Stage I, Class 2) was made on the basis of gait disturbance, arthralgia persisting for more than 6 weeks, the presence of subcutaneous nodules and X-ray findings. CML was confirmed by peripheral blood and bone marrow findings and the presence of the Philadelphia chromosome and bcr gene rearrangement. High fever and dyspnea developed suddenly 3 days after administration of interferon in May 1991. In addition to pneumonia, a leucostasis was suspected and he was treated with high dose steroids and antibiotics. After improvement, the steroids were tapered and he was discharged from hospital in July 1991.

Antineoplastic Agents↗

Endocrine environment of benign prostatic hyperplasia: prostate size and volume are correlated with serum estrogen concentration.

Estrogen plays an important role in the development of benign prostatic hyperplasia (BPH), as has been shown in both experimental and clinical studies. T determine the endocrine environment of BPH, serum total testosterone (Total-T), free testosterone (Free-T), and estradiol (E2) conceptions were measured, and the relationship between these levels and prostate size and volume was analyzed. Blood samples were collected from subjects who attended the mass screening for prostate disease performed by our institute. No significant correlations were found between Total-T levels, Free-T levels, and prostate size, as determined by digital rectal examination. However, E2 levels and the ratios for E2 levels and the ratios for E2/Total-T and E2/Free-T were significantly correlated with prostate size. To confirm these relationships, prostate volume was calculated from transrectal ultrasonographic images. E2 levels and these two ratios were, indeed, highly correlated with prostate volume. These results suggest that an estrogen-dominant environment plays an important role in the development of BPH.

Adult↗

[An analysis of familial prostate cancer].

BACKGROUND: Clinical and pathological features of familial prostate cancer patients were examined. METHODS: We compared 7 pairs (14 patients) of familial prostate cancer patients (Group F) with those of 1741 prostate cancer patients diagnosed in around Gunma Prefecture between 1987 and 1993 (Group G). Relative survival rates were compared because the average age was different in two groups. RESULTS: In Group F and Group G, age at diagnosis ranged from 54 to 86 and 47 to 97 years old, and the averages were 68.1 +/- 8.5 (S.D.) and 74.2 +/- 8.3, respectively. The average age tended to be younger in Group F. The ratio of early stage cancer tended to be higher and that of poorly differentiated cancer tended to be lower in Group F. The 3- and 5-year relative survival rate was 82.4% and 57.6% in Group F, and 84.3% and 73.9% in Group G, respectively. The 5-year survival rate tended to be lower in Group F, but almost no difference was observed between two groups on the whole. In Group F, of 6 patients whose causes of death were clear, 4 (66.7%) died of prostate cancer, while in Group G, of 398 patients whose causes of death were elaar, 224 (56.3%) died of prostate cancer. Family history of other cancer sites was positive in 3 of 6 families in Group F. CONCLUSIONS: Familial prostate cancer patients tended to be young, in early stage and low ratio of poorly differentiated cancer.

Aged↗

Establishment and characterization of a novel cell line, TK-6, derived from T cell blast crisis of chronic myelogenous leukemia, with the secretion of parathyroid hormone-related protein.

We established a novel T cell line, designated TK-6, from a patient with T cell lineage blast crisis of chronic myelogenous leukemia (CML) complicated by hypercalcemia. A surface marker study showed T cell phenotype, cluster designation (CD)4, CD5 and CD7. Light and electron microscopic examination revealed myeloperoxidase (MPO)-negative, however, ultrastructural examination under certain specific conditions demonstrated that some cells were MPO-positive. The TK-6 cell karyotype carried a t(9;22)(q34;q11) and additional chromosome aberrations, including a deletion of the long arm of chromosome 6 and the abnormality of chromosome 7. Southern blot analysis showed rearrangement of the T cell receptor beta-chain (TCR beta) gene and the major breakpoint cluster region (bcr) gene. Northern blot analysis detected the expression of the parathyroid hormone-related protein (PTHrP) gene, however, the proviral genome of human T cell leukemia virus type I (HTLV-I) was negative. This cell line will provide a valuable resource for the analysis of the relationship between T cell lineage crisis and myeloid differentiation and for the analysis of humoral hypercalcemia of malignancy (HHM) or leukemia.

Adult↗