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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 865 records · Page 48Linked to original sources

Monoclonal antibody to a structure expressed on a subpopulation of rat CD8 T cell subsets.

We have developed a monoclonal antibody, RTS-1, which can divide a rat CD8 (+) peripheral T cell population into two functionally distinct subsets. The cell-surface structure defined by this antibody is a glycoprotein with a molecular weight of 220 kDa found to be a high molecular isoform of rat CD45 antigen. CD4 (+) T cells were not stained by RTS-1 antibody. The cytotoxic T cell-enriched population did not express RTS-1 epitope on the cell surface. CD8 (+) spleen cells as well as RTS-1(+)CD8(+)T cells exhibited strong inhibition on mitogen-induced immunoglobulin G production by rat B cells. Furthermore, RTS-1 antibody, but not the control antibody, abolished CD8(+)T cell-mediated inhibition of immunoglobulin G production by rat B cells. These data suggest that RTS-1 antibody recognizes a unique determinant of rat CD45 antigen that is expressed on a fraction of CD8(+) cells.

Animals↗

Detection of bone-type alkaline phosphatase by monoclonal antibodies reacting with human osteosarcoma-associated antigen.

The antigen detected by monoclonal antibodies reacting with human osteosarcoma-associated antigen was shown to be a phosphatidyl-inositol (PI)-glycan-anchored protein, which can be released from the cell surface by PI-specific phospholipase C-treatment. The antigen detected by 2D3 and 2H10 antibodies exhibited alkaline phosphatase activity. Both antibodies strongly reacted with bone-type alkaline phosphatase. However, importantly, immunohistochemical analysis demonstrated that 2D3 and 2H10 did not react with alkaline phosphatase present in kidney or liver. In addition, neither placental nor intestinal alkaline phosphatase was recognized by 2D3 and 2H10 antibodies. These results indicated that two monoclonal antibodies, 2D3 and 2H10, are highly specific for bone-type alkaline phosphatase and can distinguish bone alkaline phosphatase from liver alkaline phosphatase in spite of the fact that liver and bone alkaline phosphatase are encoded by the same gene.

Alkaline Phosphatase↗

[Studies of dosing regimens and combination effects of aminoglycosides and beta-lactam in an experimental Pseudomonas aeruginosa infection in mice].

The optimal dosing regimens and combination effects of gentamicin (GM), or astromicin (ASTM) and piperacillin (PIPC) against P. aeruginosa in a mouse thigh infection model were studied. Therapeutic efficacy of the single regimen and duration of a postantibiotic effect (PAE) of GM and ASTM were dose dependent, but those of PIPC were dose independent. The optimal dosing of GM or ASTM with the same total daily dose was less frequent, but that of PIPC was frequent. Initial killing (the delta log bacteria changed at 2 hour after starting of the therapy) was the main significant pharmacokinetic and pharmacodynamic parameter determining efficacy for GM, whereas the time that serum levels exceeded the minimum inhibitory concentration (T greater than MIC) was the major parameter for PIPC. The optimal synergistic combinations of GM or ASTM plus PIPC in various dosing intervals with the same total daily dose were observed in the less frequent regimens of GM or ASTM and the frequent regimen of PIPC. The differences of therapeutic efficacy were observed in twice a day regimens of GM or ASTM plus PIPC in three dosing schedules (GM or ASTM before PIPC, with PIPC simultaneously, after PIPC). The effect of GM or ASTM after PIPC exposure was inferior to that of the other dosing regimens. These findings suggest that it may be possible to use the optimal regimens of aminoglycosides and beta-lactams against clinical P. aeruginosa infections in humans. Further careful, controlled clinical trials are needed.

Aminoglycosides↗

Expression of insulin-like growth factor-I during chicken development.

We have investigated the expression of insulin-like growth factor-I (IGF-I) during ontogeny in the chick. IGF-I mRNA was first detectable in whole embryos on day 6, while serum IGF-I could be measured on day 9, the earliest time point examined. Serum IGF-I values rose 10-fold from about 3 ng/ml on day 10 to a prehatch peak of 30-35 ng/ml during days 15-17, and then declined to about 10 ng/ml at the time of hatching. On days 17 and 20 of incubation, IGF-I mRNA was detected in eye, skeletal muscle, and brain, but could not be found in liver or heart until after hatching. During the posthatch period, serum IGF-I rose from 10 ng/ml in the first week to 35-40 ng/ml during weeks 3-6, and liver IGF-I mRNA increased nearly 5-fold from weeks 1-7. The increases observed during weeks 1-3 correlated with a posthatch rise in serum GH from 21 to 37 ng/ml, although GH levels declined over the subsequent 4 weeks without an appreciable change in serum IGF-I values. By contrast, before embryonic day 12 no GH could be detected in the circulation, while IGF-I was 19 ng/ml on day 11. These observations suggest that there is both GH-dependent and GH-independent regulation of IGF-I gene expression in the chick, as has been found in mammals, and support the idea that IGF-I plays a role in chicken embryonic development.

Animals↗

Erythrocyte carbonic anhydrase I concentration in patients receiving thyroxine.

We recently reported that the red blood cell (RBC) carbonic anhydrase I (CAI) concentration in patients with hyperthyroidism is reduced and reflects the patient's mean thyroid hormone level over the preceding months. In this study, RBC CAI concentrations were measured in patients with thyroid nodules who were receiving suppressive doses of thyroxine (group I) and compared with those obtained in patients with primary hypothyroidism receiving replacement doses of thyroxine (group 2). Of the 17 patients in group 1, 16 (94%) had elevated plasma free T4 levels, but all 17 had normal free T3 levels. Of the 17 patients in group 2, 16 (94%) had normal free T4 levels and all 17 had normal free T3 levels. Plasma TSH concentrations in group 1 were all below the lower limit of sensitivity of 0.04 mU/l. In group 2, 11 had normal and 6 had slightly elevated plasma TSH concentrations. The mean (+/- SD) RBC CAI concentration in group 1 (300 +/- 53 nmol/g Hb) was significantly lower than that in group 2 (340 +/- 57 nmol/g Hb). The RBC CAI concentration was significantly correlated with both the concentration of plasma free T4 and free T3. These observations indicate that in patients receiving suppressive doses of thyroxine a slight increase in the plasma free T4 concentration produces a slight but significant decrease in RBC CAI levels.

Adult↗

Lack of effect of oocytectomy on expansion of the porcine cumulus.

Oocyte-cumulus cell complexes (OCC) and complexes with an attached piece of membrana granulosa (C + P), isolated from prepubertal or cyclic gilts stimulated with pregnant mares' serum gonadotrophin, were cultured in media supplemented with follicle-stimulating hormone (FSH; 0.01-1.0 micrograms/ml) or forskolin (50-100 mumol/l) for 24 and 32 h. FSH and forskolin each induced dose-dependent cumulus and membrana granulosa expansion. After 2 h of culture, FSH (0.1 microgram/ml) or forskolin (100 mumol/l) increased the contents of intracellular adenosine 3',5'-phosphate (cAMP) in OCC from prepubertal gilts to almost 10 times that in unstimulated complexes. After 24 h of culture in media supplemented with FSH (0.1 microgram/ml) or forskolin (100 mumol/l), the oocytectomized OCC and C + P showed similar expansion to that of the control groups. The intracellular cAMP contents in intact and oocytectomized OCCs were similar in all groups except those treated with FSH, in which the intact OCCs had significantly higher contents than their oocytectomized counterparts (P less than 0.01). After hyaluronidase treatment, cumulus and membrana granulosa cells of intact and oocytectomized OCC and C + P were suspended, except for those of the innermost layers of the corona radiata. The results suggest that increases in cAMP contents and synthesis of an extracellular, hyaluronidase-sensitive mucus by pig OCC and C + P induced by FSH or forskolin are not dependent on the oocyte.

Animals↗

[Interdigestive migrating complex (IMC) and effect of cisapride in patients with non-ulcer dyspepsia (NUD)].

The 24-hr gastric and duodenal pressure measurement was performed in 5 patients with non-ulcer dyspepsia (NUD). The reduction of incidence of IMC and prolongation of the first appearance of IMC after evening meal were observed in NUD patients. The gastroprokinetic agent, cisapride 5 mg, 3 times a day for 7 days significantly increased the incidence of IMC and shortened the time before the first appearance of IMC after evening meal. This result indicates that in NUD patients impaired gastrointestinal motility is present in fasting phases and cisapride may be useful for correcting motility disorders.

Aged↗

Local image filing system in neurosurgery: validity of selective storage of radiographic images.

In an effort to achieve efficient image management in the practice of neurosurgery, a clinical data base system was designed and developed to process, store and retrieve neuroradiologic image information on hospitalized patients with the use of a local image filing system (EFPACS-500, Fuji Electric Co., Ltd). Storage and retrieval of radiographic images were studied to quantify existing procedures and to evaluate the validity of new technology. One of our hospitals (Southern Tohoku Research Institute for Neuroscience) has annually produced approximately 100,000 sheets of film radiographs, resulting in a great deal of serious problems, particularly lack of space for storage. In addition, the overall averaged ratio of selected key films to total files of radiographs was estimated to be 16.3% for hospitalized patients during the past 5 years. It is assumed that, by means of digital storage on this selective basis, radiographic storage problems can be solved with the use of the current data base system which efficiently handles image information involving patient care. In the practical view another substantial improvement in this work is the high functionality of the system, with which radiographic images coupled with a variety of clinical data on patients can be stored in a descriptive fashion.

Database Management Systems↗

[Efficacy of preoperative irradiation in midline oligodendrogliomas. Report of two cases].

Two midline oligodendrogliomas in young males were successfully totally removed after preoperative irradiation. A 33-year-old male with right lower extremity weakness had a large hypervascular mass occupying the left lateral ventricle. Even after 31 Gy whole-brain irradiation, massive bleeding occurred at surgery and resulted in only partial removal. The residual tumor markedly regressed with disappearance of abnormal vascularity after subsequent local boost irradiation. At the second operation, the tumor was totally removed. A 32-year-old male with progressive headache had a hypervascular mass with gross calcification in the right lateral ventricle. The tumor was partially resected due to its abundant vascularity and blood loss. After 60 Gy local irradiation, the tumor was moderately shrunk with a significant reduction in vascularity. At the second operation, the tumor was totally removed. Preoperative irradiation as an adjunct to surgery may increase the resectability of highly vascular tumors such as midline oligodendrogliomas.

Adult↗

[The coefficient of variation of RR intervals (CVRR) on electrocardiogram in patients with essential hypertension with reference to aging, hemodynamics and sympatho-adrenomedullary function].

To evaluate the significance of parasympathetic nerve activity in essential hypertension, we measured the coefficients of variation of RR intervals (CVRR) on electrocardiogram and examined the relationships between CVRR and aging, hemodynamics and sympatho-adrenomedullary function in normotensive subjects (NT) and in patients with essential hypertension (EHT). Mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline concentration (pNA), plasma adrenaline concentration (pAd) and CVRR resting in a supine position were simultaneously measured in 37 NT (33.8 +/- 2.0 years) and 47 mild-to-moderate EHT (51.3 +/- 1.5 years). In both NT and EHT, significantly negative correlations between CVRR and age (NT: r = -0.54, p less than 0.001, EHT: r = -0.41, p less than 0.005) were observed, however, CVRR correlated with neither MAP, HR nor pAd. CVRR tended to correlate negatively with pNA (r = -0.27, p less than 0.1) in NT, unlike in EHT. The mean value of CVRR in EHT (n = 10, age: 38.3 +/- 1.6 years, CVRR: 3.61 +/- 0.37%) was significantly (p less than 0.005) lower than in age-matched NT (n = 10, age: 38.3 +/- 2.5 years, CVRR: 5.76 +/- 0.45%). These results indicate that the parasympathetic tone suggested by CVRR may be related to aging and sympathetic nerve activity, and that parasympathetic function might be impaired in EHT.

Adolescent↗

[Immune response against BCG 65 kDa protein antigen in bladder cancer with BCG instillation therapy. Analyses carried out with the gene of this protein to develop a monoclonal antibody].

The BCG 65 kDa protein is part of the 60 kDa heat-shock protein (hsp) family. It is clear that hsp has a huge homology among mammalian and bacterial cells. In our study, we have observed the relevance of this protein in the anti-tumor response. Antibody production against the BCG 65 kDa protein was determined by solid phase ELISA using the sera of 51 bladder cancer patients who have undergone BCG instillation therapy. The BCG 65 kDa protein was made by E. coli transfected with pTB12 (plasmid DNA) which encodes this protein. It was clearly observed that the level of serum antibody titer to this protein was raised by the above instillation therapy. In order to investigate the role of this protein in anti-tumor response, we developed monoclonal antibodies against BCG 65 kDa protein. Four monoclonal antibodies were developed (B-20, B-97, B-108, B-167). We also estimated the epitope defined by each monoclonal antibody by using the truncated protein which was produced by E. coli transfected with the deletion mutants of pTB12. At this stage, we proceeded with observation of the cross epitope between mammalian cancer cells and BCG after using these monoclonal antibodies. There is no cross epitope defined by B-20, B-97 and B-167 in mammalian cells. However, the epitope defined by B-108 exists in normal tissue as well as in bladder cancer cells.

Administration, Intravesical↗

[Surgical treatment of pathological stage III and IV in non-small cell lung cancer with peripheral tumor of 3 cm or less in diameter].

Among 287 patients underwent pulmonary resection between Mar 1978 and Dec 1989, 49 were proved pathologically to have their primary tumor of 3 cm or less in the greatest dimension. Twelve of these 49 classified to stage III A by the modiastinal lymph node metastasis or stage IV by the pulmonary metastasis. The histologic type of tumor was adenocarcinoma in 10 and squamous cell carcinoma in 2. Mode of surgical treatment consisted of pneumonectomy in 2, lobectomy in 8, segmentectomy or wedge resection in 2, and complete mediastinal lymph node dissection was performed in all but 2. Survival rate in 1, 3, 5 year was 100%, 38.1% and 38.1% in 9 with stage III A disease, and 100%, 100% and 50% in 3 with stage IV disease, respectively, and significant difference was noted in comparison with control group with larger tumor in each stage (p less than 0.05). From these results, we concluded that patients with small primary tumor could expect longer survival after surgical treatment, even if mediastinal lymph node metastasis or pulmonary metastasis was present.

Adenocarcinoma↗

[Surgical results of small sized (less than 3 cm) advanced lung cancer].

We studied the surgical results in 31 patients with small sized but advanced lung cancer. Twenty-two patients had mediastinal lymph node metastasis, 6 had pulmonary metastasis, 3 had pleural dissemination. Histological type were adenocarcinoma in 21 patients, large cell carcinoma in 5 patients, small cell carcinoma in 4 patients. The 5-year survival rate in patients with mediastinal lymph node metastasis (pT1N2) was 24.1%. The 5-year survival rate in patients (pT1N2) for clinical N0, N1 was 34.6%, but no patient with clinical N2 disease survived more than 2 years after the operation. In the patients with pulmonary metastasis or pleural dissemination none survived more than 5 years after the operation.

Adenocarcinoma↗

Molecular cloning and sequence analysis of cDNA for the catalytic subunit 1 alpha of rat kidney type 1 protein phosphatase, and detection of the gene expression at high levels in hepatoma cells and regenerating livers as compared to rat livers.

A cDNA clone containing the full coding sequence of a type 1 protein phosphatase catalytic subunit 1 alpha has been isolated from a rat kidney lambda gt 10 library. The protein sequence deduced from the cDNA contains 330 amino acid residues with a molecular mass of 38 kDa. The cDNA clone from rat kidney was 89% identical at the nucleotide level in the coding region to type 1 protein phosphatase 1 alpha from rabbit skeletal muscle. However, the two protein sequences were completely identical. The type 1 alpha protein phosphatase from rat kidney shows 49% homology of amino acid sequence to the rat type 2A alpha protein phosphatase. Thus, the protein sequence of type 1 alpha protein phosphatase was completely conserved between rat and rabbit. The mRNA levels of type 1 protein phosphatase were determined in rat liver, AH13, a strain of rat hepatoma, and regenerating rat liver by Northern blot analysis using the cDNA fragment as a probe, under which conditions a single mRNA of 1.5 kb was detected. The mRNA levels of AH13 were remarkably increased when compared to those of normal ivers, whereas the mRNA levels of regenerating livers were slightly but significantly increased. These results demonstrate a marked increase in gene expression of type 1 protein phosphatase in hepatoma cells, suggesting an important role of the type 1 protein phosphatase in hepatocarcinogenesis.

Amino Acid Sequence↗

Rapid downregulation of transcription mediated by the cAMP response element of c-fos promoter does not require new protein synthesis.

Induction of the c-fos gene is well known to be transient, due to autorepression of its transcription. While the dyad symmetry element (DSE) in the c-fos promoter has been shown to mediate transient c-fos transcription in response to serum, it is yet unknown whether the cAMP response elements (CREs) in the promoter mediate transient transcription in response to cAMP. We observed that forskolin induced transient expression of the c-fos gene in the presence of a calcium ionophore A23187 in NIH3T3 fibroblasts. We investigated transcriptional abilities of one of the CREs (-60 CRE) as well as the DSE. Both of the elements mediated the synergistic effects of forskolin and A23187 on transcription. Transcription driven by the -60 CRE was downregulated at around 2 hrs. after stimulation of forskolin plus A23187 with similar kinetics to that by the DSE. The downregulation with the -60 CRE was less sensitive to an inhibitor of protein synthesis comparing with that by the DSE. These results suggest that function of the -60 CRE activated by forskolin plus A23187 is downregulated by activation of pre-existing factors.

3T3 Cells↗

[Shy-Drager syndrome: its autonomic function, alpha 2 receptor density and mechanism of postprandial hypotension].

The autonomic function, platelet alpha 2 receptor (alpha 2R) density, and mechanism of postprandial hypotension were examined in a 58-year-old man with Shy-Drager syndrome (SDS). His chief complaints were orthostatic syncope and impotence. His blood pressure was kept within normal limits in a supine position, but severe hypotension and fainting occurred when he assumed an upright posture. There were diminished sweating response to warm stress, abnormal pupil reactions to drugs, lack of blood pressure elevation at phase IV during the Valsalva maneuver, and a lack of pressor response to hyperventilation and cold stress. The plasma norepinephrine levels (pNE) were very low in a supine position at rest and in a head-up tilt position. Severe blood pressure fall (hypotension) associated with a lack of pNE elevation occurred during an oral glucose tolerance test (oGTT). Platelet alpha 2R density increased and the pressor response to infused norepinephrine (NE-R) was pronounced. The heart rate response to injected atropine was clearly attenuated. The coefficient of the R-R interval variation in the ECG (CVRR), which may reflect parasympathetic activity, was markedly low at rest. In addition, a decrease in a head-up tilt position and increase during oGTT also resolved. These results indicate that a dysfunction of the parasympathetic and sympathetic nervous systems and the up-regulation in the alpha 2R system that leads to an increase in alpha 2R density in SDS are involved in this disease and that the mechanism of postprandial hypotension in SDS may be different from that in normal elderly subjects.

Atropine↗

[A case of broncho-bronchiolitis obliterans associated with rheumatoid arthritis and Sjögren's syndrome].

A 45-year-old female patient with rheumatoid arthritis and Sjögren's syndrome was admitted because of progressive exertional dyspnea and palpitation. The chest X-ray film was normal except for slight overinflation. Pulmonary function tests indicated severe mixed-type impairment, and arterial blood gas analysis revealed hypoxemia. 99mTc-MAA lung perfusion scintigraphy and 81mKr lung ventilation scintigraphy showed multiple nonsegmental defects in both lungs. During six months of observation, the perfusion defect increased in size and intensity, although the chest radiography remained unchanged. The diagnosis of bronchobronchiolitis obliterans (BBO) was confirmed by open lung biopsy. Glucocorticoid therapy was ineffective, and she died of respiratory failure a month after discharge. It is noteworthy that perfusion scintigram demonstrated the progression of the disease much better than chest radiography, which showed no apparent change during the observation period.

Arthritis, Rheumatoid↗