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Biomedical subjects

K Imai

Publications and source records attributed to K Imai.

At least 19 recordsLinked to original sources
PubMed1992

Molecular cloning of a novel protein-tyrosine phosphatase SH-PTP3 with sequence similarity to the src-homology region 2.

Protein-tyrosine phosphorylation and dephosphorylation are directly associated with cellular growth, signal transduction, and neoplastic transformation. Here we report the isolation of a complementary DNA (cDNA) clone encoding a novel protein-tyrosine phosphatase (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a approximately 68-kDa protein composed of 593 amino acids which contains two src-homology region 2's (SH2 domains) at the N terminus; this PTP is designated as SH-PTP3. Northern blot analysis revealed that SH-PTP3 mRNA was expressed throughout many tissues and the transcriptional size was consistent at about 6.0 kb. As with other SH2 domains in src-family kinases, the SH2 domains of SH-PTP3 may play a crucial role in interactions with tyrosine phosphorylated signaling proteins, including itself and protein tyrosine kinases (PTKs), to regulate targets' enzyme activity.

Amino Acid Sequence↗
PubMed1992

Cloning and characterization of a human cDNA encoding a novel putative cytoplasmic protein-tyrosine-phosphatase.

We have cloned and characterized a human cDNA encoding a new member of the family of cytosolic type protein-tyrosine-phosphatase (PTP), designated as PTPG1, from an adult colon tissue cDNA library by using the PCR product as probe. We obtained 5 cDNA clones, which cover the predicted open reading frame encoding a 88-kDa protein composed of 780 amino acids, and it had no apparent signal or transmembrane sequences, suggesting that it is a cytosolic protein. The N-terminal region had a PTP catalytic domain that is 30-40% identical to previously reported human PTPs. This revealed that the enzyme composes an additional family of human PTPs. PTPG1 was characterized by a long non-enzymatic domain located at the C-terminus, including PEST sequences which are characteristic for short half-life proteins in eukaryotes. Northern blot analysis of PTPG1 mRNA showed a 4.6-kb transcript that was detected in a wide variety of cell lines to suggest its extensive expression.

Amino Acid Sequence↗
PubMed1992

Molecular mechanism for ligand stabilization in the mollusc myoglobin possessing the distal Val residue.

Myoglobin extracted from the triturative stomach of Dolabella auricularia, a common mollusc found on the Japanese coast, possesses naturally occurring substitution at the distal E7 position (Val-E7) and its oxygen affinity is only slightly lower than those of the common mammalian myoglobins possessing the usual His-E7. 1H nuclear magnetic resonance studies of Dolabella met-cyano myoglobin have revealed that a guanidino NH proton of Arg-E10 is hydrogen-bonded to the Fe-bound CN-. The role of Arg-E10 as a hydrogen-bond donor for Fe-bound ligand in the present myoglobin appears to be responsible for its relatively high ligand affinity.

Animals↗
PubMed1992

Molecular cloning and chromosomal mapping of a human protein-tyrosine phosphatase LC-PTP.

We isolated cDNA clones encoding a protein-tyrosine phosphatase (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a approximately 40-kDa protein composed of 360 amino acids and has no apparent hydrophobic segments, suggesting that it is a nontransmembrane PTP, which was designated as LC-PTP (leukocyte PTP). Northern blot analysis revealed that the LC-PTP mRNA was preferentially expressed in a variety of hematopoietic cells and the transcriptional sizes were approximately 4.0 kilobases and approximately 2.9 kilobases. Fluorescent in situ hybridization revealed that the human LC-PTP gene is located on the chromosome region 1q32.1, which is known to be a site associated with chromosomal deletion in malignant lymphomas, where candidate tumor suppressor genes might be present.

Amino Acid Sequence↗
PubMed1992

Significance of a new stratification of alkaline phosphatase and extent of disease in patients with prostate carcinoma with bone metastasis.

Bone is the most frequent site of metastatic prostate cancer and the prognosis of patients with bone metastasis is poor. The authors have investigated a semiquantitative system to evaluate bone metastatic lesions in terms of cancer-specific survival. Based on the extension of disease (EOD) grade proposed by Soloway and associates, a new EOD grading system obtained from bone scintigraphy alone and EOD score obtained from bone scintigraphy and alkaline phosphatase was studied in 164 patients with prostate cancer with metastatic bone involvement. In terms of a cancer-specific survival and prostate cancer death, both the new EOD grade and the EOD score were apparently superior to eight other items studied (age, medical score, gait disturbance, histologic grade, erythrocyte sedimentation rate, prostatic acid phosphatase, and alkaline phosphatase). Multivariate analysis revealed that the EOD score was better than the new EOD grade. This improvement was due to the elimination of false-positive or nonactive metastatic bone lesions on bone scintigraphy through the alkaline phosphatase evaluation.

Aged↗
PubMed1992

Site-directed mutagenesis in hemoglobin: functional and structural role of inter- and intrasubunit hydrogen bonds as studied with 37 beta and 145 beta mutations.

In order to clarify the functional and structural role of intra- and intersubunit hydrogen bonds in human hemoglobin (Hb A), we prepared two artificial beta chain mutant hemoglobins by site-directed mutagenesis. The mutant Hb Phe-37 beta, in which Trp-37 beta is replaced by Phe to remove the intersubunit hydrogen bond between Asp-94 alpha and Trp-37 beta at the alpha 1-beta 2 interface in deoxy Hb A, showed a markedly increased oxygen affinity and almost completely diminished Bohr effect and cooperativity. However, 1H-NMR data indicated that the structure of deoxy Hb Phe-37 beta is rather similar to that of deoxy Hb A. The enhanced tetramer-to-dimer dissociation previously observed in Hb Hirose (Trp-37 beta----Ser) together with our observation of the effects of organic phosphate on the structure and function of Hb Phe-37 beta suggested that a large part of the abnormal properties of Hb Phe-37 beta observed for dilute solutions appears to result from partial dissociation into alpha beta dimers rather than direct destabilization of the T-quaternary structure in the deoxygenated state. Thus, the primary and direct role of the hydrogen bond between Asp-94 alpha and Trp-37 beta is to stabilize the tetrameric assembly, and thereby this hydrogen bond indirectly contributes to stabilization of the T-quaternary structure. The other mutant Hb Phe-145 beta has a Phe residue at the 145 beta site and lacks the intrasubunit hydrogen bond formed between Tyr-145 beta and the carbonyl group of Val-98 beta in deoxy Hb A.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Measurement of the zeta potential of human platelets by the use of laser-light scattering.

An instrument was developed to detect the shift in scattering of laser light that occurs when particles in suspension move in a chamber with an electrical load. The instrument measures the zeta potential of particles. We applied the instrument to study human blood cells. Platelet-rich plasma was used because of the stability of the suspension, without the sedimentation or autoaggregation that is often seen with red or white blood cells. The reproducibility of the measurements was satisfactory when there were enough platelets in the suspension. Platelets from healthy controls (n = 136) had a potential of -14.20 +/- 1.64 mV at the detection angle of 17.1 degrees. Platelets from patients with essential thrombocytosis (n = 16) or polycythemia vera (n = 8) had higher potentials than the healthy controls.

Blood Platelets↗
PubMed1992

Protein-tyrosine phosphatase expression in pre-B cell NALM-6.

Protein-tyrosine phosphatase (PTP)-related complementary DNAs from NALM-6 (pre-B cell line) were amplified by reverse transcriptase polymerase chain reaction using primers corresponding to the conserved catalytic domains of PTPs. Thirty-three polymerase chain reaction products, identified as PTP related complementary DNAs, were classified to RPTP-alpha, PTP1B, and 4 novel PTPs, which were designated as BPTP-1-4. Their expressions in NALM-6 and other cell lines were confirmed by Northern blot analysis. BPTP-1 and -2 exhibited extensive homology with the first and the second catalytic domains, respectively, of leukocyte common antigen related molecule (LAR) and human PTP delta. The transcriptional sizes of BPTP-1 and BPTP-2 are the same (7.2 kilobases) as that of LAR. The expression of BPTP-1 was abundant in lymphoid cell lines TALL-1 and NALM-6 but small in colon cell line BM314, which is in sharp contrast to the expression of LAR. These data suggest that the expression levels of BPTP-1 and LAR are altered in a cell specific manner, probably making them cell type associated PTPs.

Amino Acid Sequence↗
PubMed1992

Increased levels of circulating intercellular adhesion molecule 1 in Kawasaki disease.

OBJECTIVE: We investigated whether levels of intercellular adhesion molecule 1 (ICAM-1) antigen shed into the circulation increase during acute Kawasaki disease (KD). We also compared ICAM-1 levels in acute KD with those in anaphylactoid purpura (AP) and in measles. METHODS: Serum ICAM-1 levels were measured by a double-determinant immunoassay using 2 monoclonal antibodies in the FAST (Falcon assay screening test) system. Serum levels of tumor necrosis factor alpha (TNF alpha) were measured by a specific and sensitive sandwich enzyme immunoassay. RESULTS: Patients with KD, but not those with AP or measles, had increased levels of shed ICAM-1 antigen in serum samples obtained during acute stages. Moreover, during the acute stage, KD patients with coronary artery lesions (CAL) had still higher levels of shed ICAM-1 than did those without CAL. We found a positive correlation between serum levels of shed ICAM-1 and levels of TNF alpha during acute KD. CONCLUSION: Our findings suggest that the serum ICAM-1 level is an important immunologic parameter for determining the severity of vascular damage during acute KD.

Cell Adhesion Molecules↗
PubMed1992

Palliative radiotherapy of bone metastasis.

We analyzed the effects of radiotherapy on 226 sites of metastatic bone tumors from 1981 to 1984, and on 157 sites of bone metastases of prostate cancer from 1970 to 1988. The radiation effect on pain relief was recognized in about 90% of cases within the dose of 20Gy to 30Gy, and there were not many differences in these effects according to the original tumors or histological types. In prostate cancer, the sites which needed re-irradiation were not recognized within 6 months after irradiation, and only 12 out of 80 sites (15%) that could be observed after more than 6 months needed re-irradiation due to recurring pain. As more than 60% of the patients with prostate cancer who needed irradiation to control bone metastases died within a year, to get pain relief by irradiation immediately and safely was thought to be very useful from the viewpoint of useful life. One patient was irradiated on 16 sites and 2 of these 16 sites received 4 treatments of irradiation and the shortest interval was 10 months and the longest one was 18 months.

Bone Neoplasms↗
PubMed1992

Analysis of survival of prostate cancer patients in Japan and the U.S.A.

The prognosis of U.S.A. patients with prostate cancer based on reports from the American College of Surgeons and Roswell Park Cancer Institute was compared with that of Japanese in Nagasaki and Gunma. There was more than a 10% difference in survival rate between the two countries. Several clinical parameters were analyzed to determine the basis for this difference. In general, stage distribution, metastatic sites, bone pain and alkaline phosphatase in the USA patients with Stage D disease were more severe than in the Japanese patients. Moreover the prostate cancer death rate in the USA was higher than that in Japan. However, only the distribution of pathological grade in the USA was better than that in Japan. From these results, it is difficult to conclude that prostate cancer in the USA is more aggressive than in Japan. The possibility of selection bias in these studies is discussed.

Adenocarcinoma↗
PubMed1992

Preferred ambient temperature for old and young men in summer and winter.

To investigate the effects of age on thermal sensitivity, preferred ambient temperature (Tpref) was compared between old (71-76 years) and young (21-30 years) groups, each consisting of six male subjects in summer and winter. The air temperature (Ta) was set at either 20 degrees C or 40 degrees C at commencement. The subject was directed to adjust the Ta for 45 min by manipulating a remote control switch to the level at which he felt most comfortable. In the older group, the Tpref was significantly lower in trails starting at 20 degrees C than that starting at 40 degrees C in summer. The fluctuation of Tpref (temperature difference between maximum and minimum Ta during the last 10 min) was significantly wider in the older group in both summer and winter. Repetition of the same experiment on each subject showed a poorer reproducibility of Tpref in the older group than in the younger group in summer. Tympanic and esophageal temperatures of the older group kept falling throughout the trial starting at 20 degrees C in summer. These results suggest that thermal sensitivity is decreased with advancing age and that thermal perception in the elderly, especially to cold, is less sensitive in summer.

Acclimatization↗
PubMed1992

Phylogenetically different strains of a variant of coxsackievirus A 24 were repeatedly introduced but discontinued circulating in Japan.

Variations in the nucleotide sequence of 3 C proteinase of coxsackievirus A 24 variant (CA 24 v) were analyzed to define the route of transmission and spread of the virus which was introduced to Japan on three separate occasions, 1985-86, 1988, and 1989. The nucleotide sequences of isolates from the same year's outbreak in Japan were identical or closely related, while the isolates from different outbreaks were less closely related to one another than to those from other countries in the same year. All Japanese isolates from Okinawa and other prefectures in 1985 and 1986 were closely related to the Taiwan strains in those same years, indicating common-source outbreaks. Two 1988 isolates from Chiba Prefecture, Japan, were closely related to those from Singapore in 1987, China in 1988 and Hong Kong in 1988. All seven Japanese isolates from Chiba Prefecture in 1989 comprised a group together with the Taiwan and Singapore strains in 1988. The results indicate that CA 24 v was introduced into Japan on each occasion from the outside. Furthermore, in contrast to the explosive epidemics in Okinawa Prefecture in 1985 and 1986, the virus which was repeatedly introduced to other areas in Japan did not circulate endemically, and disappeared within a short time.

Base Sequence↗
PubMed1992

Predominant beta-adrenoceptor blocking effect of xamoterol averaged over the day in patients with mild to moderate heart failure: insight into the mechanism of its long-term clinical efficacy.

Xamoterol acts as a beta 1-adrenoceptor agonist at low sympathetic activity and as an antagonist at high activity. Although its long-term efficacy has been proven in patients with mild to moderate heart failure, it remains unclear which effect, agonism or antagonism, accounts for its long-term activity. To clarify the effect of xamoterol on cardiac sympathetic activity in daily life, 24-h R-R interval histograms were obtained during administration of xamoterol 100 mg b.d. for 1 week to 10 patients with mild to moderate heart failure. Eight normal subjects were also studied as controls. To examine the relation between the effect of xamoterol and sympathetic activity, plasma noradrenaline (NA) levels were measured under 5 graded conditions simulating daily living. Xamoterol administration significantly decreased the standard deviation of the R-R interval, both in patients with heart failure and in normal subjects. The mean R-R interval, however, was increased in patients with heart failure, relative to normal subjects. In both groups, the R-R interval histograms had two peaks, i.e. a short daytime peak and a long night-time peak. Xamoterol decreased the median of the night-time peak without changing the daytime peak in normal subjects. In contrast, it increased the median of the daytime peak without producing a significant change in the night-time peak in patients with heart failure. Levels of plasma NA were significantly higher in patients than in normal subjects under all conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1992

Adult T-cell leukemia/lymphoma (lymphoma type) with remarkable gastric lesions: a case report.

We report a case of a 53-year-old woman with adult T-cell leukemia/lymphoma (ATL) (lymphoma type) with multiple gastric lesions, admitted to our hospital because of systemic lymphadenopathy and epigastralgia. Gastroscopy showed a variety of gastric lesions including thickened folds, ulcerations and polypoid lesions. Biopsy specimens obtained from the stomach and lymph nodes revealed diffuse infiltration of pleomorphic mononuclear cells and the integration of HTLV-1 proviral DNA. We demonstrated through the investigation of 30 previously reported cases of ATL that this is a rare case of the lymphoma type of ATL presenting remarkable gastric lesions.

Blotting, Southern↗
PubMed1992

Circulating tumor-associated antigens detected by monoclonal antibodies against the polypeptide core of mucin--comparison of antigen MUSE11 with CA15-3.

The antigen MUSE11 detected by a monoclonal antibody (MAb) is an adenocarcinoma-associated antigen, while CA15-3 is a representative breast cancer-associated antigen detected by MAbs 115D8 and DF3. MAb MUSE11 showed higher binding activity to a synthetic peptide corresponding to the tandem repeat motif of the mucin core protein than that of MAb DF3, although MAb DF3 also had a significant binding activity indicating that MAbs MUSE11 and DF3 could recognize an identical polypeptide core. The reactivity of MAb DF3 to a breast cancer cell line MRK-neu-1 was completely abolished by neuraminidase treatment whereas that of MAb MUSE11 was partly conserved. The simultaneous measurement of the antigens MUSE11 and CA15-3 in sera from 35 cancer patients demonstrated that the incidence of abnormal serum level of CA15-3 was lower than that of antigen MUSE11. These data suggest that at least a part of the structural basis for the difference between the serum levels of antigen MUSE11 and CA15-3 could be carbohydrate side chains including sialic acids.

Antibodies, Monoclonal↗
PubMed1992

Using microparticle labeling and counting for attomole-level detection in heterogeneous immunoassay.

A new heterogeneous "sandwich" immunoassay utilizing microparticles as labels to realize high sensitivity is described. In this method, antibody fixed on the microparticles reacts with antigen previously trapped on a microplate surface, which makes the antigen molecules visible and countable with an inverted optical microscope. The method is highly sensitive because the reacted single microparticle, therefore single antigen molecule, can be detected. The sensitivity depends both on the reaction efficiency of the immunoreaction and on nonspecific adsorption of the microparticles on the microplate surface. Therefore, the protocol for preparing microparticle having antibody on the surface and a microplate having capture antibody was investigated to realize high sensitivity. Carboxylated microparticles of 0.76 microns in diameter were conjugated with affinity-purified antibody using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. It was determined that 1 g microparticles had 880 micrograms antibody (approximately 1100 antibody molecules per 1 microparticle). The immunoreaction efficiency reached 18% at 1 x 10(-13) mol/liter antigen concentration. The lower detection limit was 3.1 x 10(-14) mol/liter (1.6 amol) using human alpha-fetoprotein as a model antigen.

Adsorption↗