Biomedical subjects

M Adachi

Publications and source records attributed to M Adachi.

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

Identification of a domain of ETA receptor required for ligand binding.

Various chimeric ETA and ETB receptors were produced in CHO cells for the elucidation of a specific domain which influences the affinity of the receptor toward BQ-123, a selective ETA antagonist. Replacement of the first extracellular loop domain (B-loop) of the ETA receptor with the corresponding domain of the ETB receptor, reduced the inhibition by BQ-123 drastically, while the replacements of other extracellular domains of ETA did not. By contrast, the introduction of the B-loop of ETA in place of the corresponding domain of the ETB receptor endowed the ETB-based chimeric receptor with a sensitivity to BQ-123. These observations suggest that the B-loop domain of the ETA receptor is involved in ligand binding.

Amino Acid Sequence↗

PubMed1992

Effects of simulated left bundle branch block on QRST time-integral values of 12-lead electrocardiograms in patients with and without prior anterior wall myocardial infarction.

The effects of right ventricular pacing, which simulated left bundle branch block (BBB), on QRST time-integral values of 12-lead electrocardiograms (ECGs) were examined, and the clinical usefulness of QRST values for estimating the severity of left ventricular wall motion abnormalities due to a prior anterior wall myocardial infarction (MI) in the setting of left BBB were evaluated. Digitized ECGs were recorded during normal sinus rhythm and simulated left BBB in 38 patients (24 with and 14 without prior anterior wall MI). QRST values were calculated in each lead point of 12-lead ECGs. Data from 608 normal subjects were used as control values; the mean +/- 2 SD of these values was regarded as the normal range. The parameter sigma DE was defined as the sum of the differences between the normal mean QRST value and the QRST values of a given patient in leads where the QRST value was less than the normal range. The correlation coefficient of sigma DE for the 2 activation sequences was highly significant. Although small but significant changes were seen in QRST values in leads I, II, III, aVR, aVF and V1 during simulated left BBB, left precordial leads showed no significant changes in QRST values. A criterion of sigma DE > 40 mV.ms for detecting an anterior wall MI showed a sensitivity of 88%, a specificity of 93%, and a diagnostic accuracy of 89%. The sigma DE was significantly (p < 0.001) correlated with the asynergy index calculated from left ventriculograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Bundle-Branch Block↗

PubMed1992

Bone marrow transplantation as a strategy for treatment of non-insulin-dependent diabetes mellitus in KK-Ay mice.

The effects of allogeneic bone marrow transplantation (BMT) on non-insulin-dependent diabetes mellitus (NIDDM) were examined using KK-Ay mice. KK-Ay mice reconstituted with KK-Ay bone marrow cells showed glycosuria, hyperinsulinemia, and hyperlipidemia. However, KK-Ay mice (H-2b) that had been lethally irradiated (9.0 Gy) and then reconstituted with T cell-depleted bone marrow cells from normal BALB/c mice (H-2d) showed negative urine sugar with decreases in serum insulin and lipid levels 4 mo after BMT. Morphological recovery of islets and glomeruli was also noted after allogeneic BMT. These findings suggest that BMT can be used to treat not only a certain type of NIDDM but also its complications such as hyperlipidemia and diabetic nephropathy.

Animals↗

PubMed1992

Truncation of N-terminal extracellular or C-terminal intracellular domains of human ETA receptor abrogated the binding activity to ET-1.

We have investigated the function of N-terminal and C-terminal domains of the human ETA receptor by expressing truncated mutants in COS-7 cells. Three kinds of ETA receptors truncated in the N-terminal extracellular or C-terminal intracellular domains were produced. Deletion of the entire extracellular N-terminal or intracellular C-terminal domain completely inactivated the ET-1 binding activity. However, the deletion of one half of the N-terminal extracellular domain of the ETA receptor, missing one of two N-linked glycosylation sites, maintained complete binding activity. Specific monoclonal antibodies detected all the truncated ETA receptors in the cell membrane fraction of transfected COS-7 cells. The size of the ETA receptor was heterogeneous due to differential glycosylation and distributed in 48K, 45K and 42K dalton bands in Western blot analysis. These results demonstrated that a part of the N-terminal domain in close proximity to the first transmembrane region is required for the ligand binding activity of the ETA receptor, and the C-terminal domain is perhaps necessary as an anchor for maintenance of the binding site.

Amino Acid Sequence↗

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

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

[Non-tumor enhancement at the surgical margin on CT after the removal of brain tumors].

Marginal enhancement is occasionally seen at the surgical margin on CT after the total removal of brain tumors. This enhancement disappears in due time, and therefore we call it non-tumor enhancement. It is often difficult, however, to differentiate non-tumor enhancement from tumor recurrence. In this study, we attempted to determine the characteristics of non-tumor enhancement. The subjects of the study consisted of 15 patients with astrocytoma and one with metastatic tumor in whom sequential CT scans had been performed after total removal of the tumor. Based on the observation of these sequential CT scans, the characteristics of non-tumor enhancement were presumed to be as follows: 1) In four cases, enhancement at the surgical margin persisted more than four months after surgery and then disappeared. Therefore, these cases were considered non-tumor enhancement. Prolonged duration of enhancement such as that in these cases is not necessarily due to recurrence. 2) Marginal enhancement within 3 mm in thickness and with a well-demarcated border like that of a falx is likely to be non-tumor enhancement.

Adolescent↗

PubMed1992

Deficiency of P62, a putative collagen receptor, in platelets from a patient with defective collagen-induced platelet aggregation.

Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen-induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2 in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2-loaded platelets. In contrast, thrombin caused TXB2 formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The IgG from the ITP-patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPIa/IIa and thrombospondin were normally present. These results indicate that impaired collagen-induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation.

Adenosine Triphosphate↗

PubMed1992

Dilatation of the temporal horn in subarachnoid haemorrhage.

CT studies of 50 patients with spontaneous subarachnoid haemorrhage (SAH) and 100 randomly selected patients were reviewed with regard to the size of the frontal and temporal horns of the lateral ventricles. The temporal horn was classified into four grades, based on the size of its posterior portion at the level of the midbrain. The horn was clearly visible in 66% of patients with SAH, but in only 2% of controls. In the SAH group, the temporal horn tended to dilate sooner than the frontal horn after haemorrhage and could be seen clearly in a larger proportion of patients. Thus, assessment of the size of the temporal horn appears to be a simple and sensitive method for assessing ventricular dilatation. In addition, dilatation of the temporal horn may prove to be an important indirect sign suggesting SAH in patients in whom no high density clot is seen on CT.

Adult↗

PubMed1992

Monoclonal antibody GOM-2 binds to blood group B-Le(y) active glycolipid antigens on human gastric cancer cells, KATO-III.

The antigen structure of a mouse monoclonal antibody, GOM-2, established by immunization with KATO-III human gastric cancer cells, was examined. GOM-2 reactive glycolipids were prepared from KATO-III cells and treated with endoglycoceramidase. Structural studies of ten GOM-2 reactive oligosaccharides by a combination of glycosidase digestions, methylation, and affinity chromatography on an Ulex europeus agglutinin I (UEA-I) column revealed that nine of them had a Y-related B-active difucosylated determinant (B-Le(y)) and one had a B-active determinant. Affinity chromatography of the purified and modified oligosaccharides on an immobilized GOM-2 column demonstrated that GOM-2 has a novel binding specificity: it binds tightly to the biantennary structure carrying the B-Le(y) determinant at the termini or the branched structure carrying the B-Le(y) structure at two nonreducing termini.

Antibodies, Monoclonal↗

PubMed1992

Immunohistochemical analysis of lymphocyte subsets infiltrating gastric carcinoma after mitomycin C administration.

The intensity of lymphoid cell infiltration and distribution of lymphocyte subsets in tumors were investigated immunohistochemically on tumor tissues obtained from 11 patients with gastric carcinoma, who had been treated with mitomycin C (MMC), 12 mg/m2, i.v. 5 days before operation. The results were compared with those obtained from 24 untreated patients as controls. In the tumor tissues from pretreated patients, the intensity of lymphoid infiltration was not significantly different from that of untreated patients. However, high-grade infiltration of CD4+ cells was observed in 55% of pretreated patients, whereas only 8% of control patients exhibited the high-grade infiltration (P < 0.02). Since the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells was more frequently estimated to be more than 1 in patients pretreated with MMC, as compared to untreated controls (P < 0.02). Further, CD25+ cells in pretreated tumor tissues were more predominant than those in control tumor tissues (P < 0.05). These results suggest that MMC administration induces these alterations in lymphocyte subsets in tumor tissue in patients with gastric carcinoma.

Aged↗

PubMed1992

Electrical stimulation of pelvic floor musculature by percutaneous implantable electrodes: a case report.

A forty-year-old man with reflex urinary incontinence due to spinal cord injury was treated with electrical stimulation of the pelvic floor musculature. In this case we employed percutaneous implantable electrodes and an external pulse regulator. After 4 weeks of stimulation incontinence was improved and urodynamically maximum cystometric capacity increased from 220 ml to 350 ml. Our method is easy and not invasive. This technique can be an alternative for the electrical stimulation for urinary incontinence.

Adult↗

PubMed1992

Effects of non-collagenous proteins on the formation of apatite in calcium beta-glycerophosphate solutions.

The effects of the non-collagenous proteins; osteonectin, bone Gla protein and dentine phosphoprotein, on the formation of apatite were studied in calcium beta-glycerophosphate solutions containing catalytic amounts of alkaline phosphatase under physiological conditions. In the system used, calcium phosphate precipitates de novo at levels of supersaturation precisely determined through the enzymatic hydrolysis of beta-glycerophosphate. At 1.7 mM of calcium beta-glycerophosphate, calcium phosphate precipitated when inorganic phosphate accumulated to about 1.4 mM. In the presence of the proteins, however, a greater accumulation of inorganic phosphate was needed for calcium phosphate to precipitate, suggesting that a higher degree of supersaturation, though still a slight undersaturation with respect to dicalcium phosphate dihydrate, is required for calcium phosphate to precipitate in the presence of the proteins. At the same protein (micrograms/ml) concentration, dentine phosphoprotein was approximately four times as effective as bone Gla protein, which was about twice as effective as osteonectin in delaying precipitation. The proteins also retarded subsequent crystal growth, with apatite formed in the presence of the more inhibitory proteins having the smallest crystals, especially in width.

Alkaline Phosphatase↗

PubMed1992

Relationship of QRST isointegral maps during simulated left bundle branch block to impairment of left ventricular function due to myocardial infarction.

The clinical usefulness of QRST isointegral maps for assessing left ventricular (LV) dysfunction due to myocardial infarction (MI) in patients with MI in the setting of simulated left bundle branch block (LBBB) was investigated. Isointegral maps were recorded during sinus rhythm and right ventricular pacing, which simulated LBBB, in 62 patients with MI and 26 patients without MI. An abnormal decrease in the QRST value in the isointegral map was assessed by the difference map that indicated a "-2 SD area" where the QRST integral value was less than the normal range (mean - 2 SD) calculated from 608 normal individuals. The isointegral maps during the two activation sequences were similar in patients with and without MI (r = 0.87 and 0.92, respectively). The sum of QRST integral values less than the normal range (sigma DM) during simulated LBBB correlated significantly with the asynergy index, derived from left ventriculographic data (r = 0.81, p < 0.01). LV dysfunction (asynergy index > or = 2) was diagnosed in simulated LBBB with a sensitivity of 81%, specificity of 77%, and diagnostic accuracy of 80% when the criterion that LV dysfunction is present if the number of lead points in the -2 SD area exceeds 4, and a sensitivity of 71%, specificity of 81%, and diagnostic accuracy of 74% if sigma DM exceeds 200 mVms was used. The findings demonstrate that isointegral maps may be useful in assessing LV dysfunction due to MI in patients with MI and LBBB in addition to detecting the presence and site of MI in these patients.

Adult↗

PubMed1992

Small differences among body surface and epicardial QRST integral maps recorded during normal activation and experimentally simulated left bundle branch block or preexcitation in canine hearts.

QRST integral maps were constructed from 87-lead body surface electrocardiograms (ECGs) and from 45-lead epicardial electrograms during artificial pacing, which simulated left bundle branch block (LBBB) and Wolff-Parkinson-White syndrome in 12 dogs. Although the ECGs and electrograms differed in configuration for each conduction model, the body surface and the epicardial QRST integral maps showed only small differences. Correlation coefficients (r) and root mean square differences (rms) were calculated to assess quantitatively the similarities in the QRST integral maps among the different conduction models. Mean r values between the normal conduction and the left bundle branch block models were 0.95 in the body surface maps and 0.89 in the epicardial maps. Mean r values between the normal conduction and the Wolff-Parkinson-White ECG models were 0.97 in the body surface maps and 0.91 in the epicardial maps, and rms values were small enough. The small differences were also verified by the difference maps and by paired t tests. QRST integral maps on the epicardium and on the body surface were largely independent of altered activation sequences in both the left bundle branch block and the Wolff-Parkinson-White ECG models.

Animals↗

PubMed1992

Inhibition of human T-lymphocyte activation by macrolide antibiotic, roxithromycin.

Effects of macrolide antibiotic, roxithromycin (RXM) on human lymphocytes in culture were studied. The drug showed a dose-dependent inhibition of 3H-thymidine and 35S-methionine uptake responding to T cell mitogens and purified protein derivative of tuberculin (PPD). Activation by PPD, as assessed by 3H-thymidine uptake, was more sensitive to inhibition than the response to T cell mitogens. The drug produced a loss of blasts when added soon after transformation commenced. Immunosuppressive effects of RXM were further characterized by using four different types of metabolized RXM, RU 28111, RU 39001, RU 44981 and RU 45179. The most potent inhibitor of lymphocyte transformation was RU 45179, followed by RU 44981, RU 39001 and RU 28111 have little activity.

Cells, Cultured↗