Biomedical subjects

M Adachi

Publications and source records attributed to M Adachi.

At least 451 records · Page 25Linked to original sources

PubMed1993

Cytotoxic cell function and phenotypic analysis of peripheral blood mononuclear cells in cancer patients treated with low-dose interleukin-2 and mitomycin C.

We previously found that the ability of peripheral blood mononuclear cells (PBM) of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C administration. On the basis of the clinical findings, we designed a treatment regimen comprised of 12 mg/m2 mitomycin C i.v. on day 1 and 700 U/m2 recombinant interleukin-2 (IL-2) i.v. every 12 h from day 4 through day 8. Of 25 patients with advanced carcinoma, 9 had a partial response and 3 had a minor response. Cytotoxic cell function, including natural killer activity, lymphokine-activated killer (LAK) activity, and the ability to generate LAK cells, and lymphocyte subsets in PBM was measured 1 day before and after either the first or second course of this therapy. The relationship between these parameters and the clinical antitumor response to this treatment was examined. Although the cytotoxic activities were significantly augmented after either the first or second treatment course, no positive correlation was observed between the changes in these cytotoxic activities and the clinical response to this therapy, when patients who either showed a partial response or whose disease remission was partial or minor were defined as responders. Further, phenotypic analysis showed a significant increase in CD2+, CD3+, CD4+ and CD4+Leu8- cells after the first course, and CD25+ cells after either the first or second course of this treatment. The percentages of CD2+ and CD25+ cells were significantly elevated only in responders but not in nonresponders, suggesting the increase in these subsets was related to clinical response.

Aged↗

PubMed1993

Malignant potential in flat elevations.

Ninety-nine colonoscopically removed flat elevations were examined. They were divided into two groups: Group 1--flat elevations 1 to 5 mm in diameter (55 cases)--and Group 2--flat elevations 6 to 10 mm in diameter (44 cases). Group 2 had a higher percentage of adenomas (86.4 percent) than Group 1 (67.3 percent). In adenoma cases (flat adenomas), Group 2 tended to show a higher degree of dysplasia. The rates of mild and moderate dysplasia were 83.8 percent and 16.2 percent in Group 1 vs. 1.70 percent and 13.2 percent in Group 2, respectively. Group 2 contained six cases (15.8 percent) of intramucosal carcinoma (severe dysplasia), while there were no cancer cases in Group 1. Both malignancy rate and degree of dysplasia were size dependent; the larger the lesion the more severe the dysplasia. Our study also revealed that small flat elevations tend to contain higher numbers of nonneoplastic lesions than do larger lesions. Increased detection of nonneoplastic lesions seems to have contributed to an overall decline in the malignancy rate of flat elevations in recent reports.

Adenoma↗

PubMed1993

Elevated Le(y) antigen expression on T-lymphocytes in schizophrenic patients.

Le(y) is a carbohydrate determinant of membrane glycoconjugates and is expressed in some tumor and embryonic cells. On T lymphocytes, it is known that human immunodeficiency virus (HIV)-infected human lymphocyte T-cell lines express elevated Le(y) antigen and AIDS patients show the highest Le(y) expression in T lymphocytes at lower CD4/CD8 ratio. Later, a comparative elevation of Le(y) expression on T-cell subsets has been noticed to be mainly present in patients with viral diseases, such as acute and chronic hepatitis, implying an association of the highest Le(y) expression with viral infection. We found that Le(y) antigen was most expressed in both CD4+ and CD8+ subsets of peripheral T lymphocytes in hospitalized schizophrenic patients. On the other hand, atypical lymphocytes with stimulated morphology are known to appear in the blood circulation of schizophrenic patients. Similar atypical lymphocytes have also been described in viral and autoimmune diseases. Two possibilities have been discussed: viral association in the pathology in some schizophrenic patients; and immunological abnormalities including environmental effects under hospitalization on immune status, since normal controls (staff in psychiatric hospitals) showed higher Le(y) expression than normal controls under non-psychiatric circumstances.

Adult↗

PubMed1993

Estimation of anterior infarct size with body surface QRST integral maps in the presence of abnormal ventricular activation sequence in dogs.

The possibility of estimating infarct size with body surface QRST integral (IQRST) maps was investigated in dogs. IQRST maps were constructed from 87-lead body surface ECGs, which were recorded 1 week after the production of anterior myocardial infarction during artificial pacing that simulated normal conduction, left bundle branch block, and Wolff-Parkinson-White syndrome in 11 dogs. Small differences were observed between the IQRST maps of the normal conduction and left bundle branch block models (r = 0.93, root mean square difference = 8.71 mVmsec) and between the normal conduction and Wolff-Parkinson-White models (r = 0.96, root mean square difference = 6.03 mVmsec). Summation of the QRST integral values over the body surface leads (QRST index) inversely correlated with infarct size in all three conductions models: r = 0.91 (p < 0.001) in the normal conduction model; r = -0.81 (p < 0.001) in the left bundle branch block model; and r = -0.86 (p < 0.001) in the Wolff-Parkinson-White model. These results show that IQRST maps permit noninvasive estimation of infarct size, even in the presence of abnormal activation sequences.

Animals↗

PubMed1993

Comparative study of QRST values from body surface potential mapping, 12-lead ECGs, VCGs in detecting inferior myocardial infarction, and evaluating the severity of left ventricular wall motion abnormalities in simulated left bundle branch block.

The authors compared the ability of QRST time-integral values (QRST values) from body surface potential maps (BSPM), 12-lead electrocardiograms (ECGs), and Frank lead vectorcardiograms (VCGs) in diagnosing a prior inferior myocardial infarction (MI) in simulated left bundle branch block (LBBB). The study included 32 patients whose digitized ECGs were recorded simultaneously for BSPM, ECGs, and VCGs during normal sinus rhythm and during right ventricular pacing simulating LBBB (18 with and 14 without an inferior MI). QRST values were calculated in each lead point of ECGs. Data on 608 normal subjects were used as controls; mean +/- 2 SD was regarded as the normal range. The following parameters were derived: sigma DM, sigma DE, sigma DV, the sum of the differences between the normal mean QRST value, and the QRST value of a given patient in leads where the QRST value was less than the normal range ("-2 SD area") in BSPM, ECGs, and VCGs (Y lead). The correlation coefficients for sigma DM, sigma DE, and sigma DV between the two activation sequences were highly significant. Sensitivity and specificity were as follows: 89% and 93% for sigma DM > 100 mV.ms, 89% and 93% for sigma DE > 50 mV.ms, and 56% and 100% for sigma DV > 10 mV.ms, respectively. Although sigma DM, sigma DE, and sigma DV were significantly (P < .01) correlated with the asynergy index calculated from left ventriculograms, sigma DM showed the best correlation. QRST values from BSPM, ECGs, and VCGs provide information that is useful in detecting an inferior MI and in estimating the severity of left ventricular wall motion abnormalities in the setting of LBBB. Of the three parameters, BSPM showed the best correlation with the severity of left ventricular wall motion abnormalities.

Aged↗

PubMed1993

Correlation between various parameters derived from body surface maps and ejection fraction in patients with anterior myocardial infarction.

To determine the best map parameter to predict cardiac function, various map parameters were correlated with the left ventricular ejection fraction (EF) in patients with a previous (between 3 months and 1 year) anterior myocardial infarction, but without overt congestive heart failure or ventricular dyssynergy. From 300 consecutive patients with a previous myocardial infarction, 82 patients with only an anterior infarction and who underwent cardiac catheterization and body surface mapping were selected for this study. The maps from 100 healthy subjects were used as normal controls. Body surface maps using 87 unipolar electrodes were recorded and various parameters were derived from the Q map, the QRS departure maps, the QRS isointegral (IQRS) map, and the QRST isointegral (IQRST) maps. They were compared with the angiographically determined EF. The EF was correlated with nQ (r = -0.72), four parameters derived from the QRS departure map (r ranged from -0.73 to -0.79), two parameters derived from the IQRS map (r = -0.90 and -0.86), and two parameters derived from the IQRST map (r = -0.84 and -0.85). Some parameters derived from body surface maps were found to have a very high correlation with the EF in patients who had a previous anterior myocardial infarction.

Electrocardiography↗

PubMed1993

Anti-allergic activity of roxithromycin: inhibition of interleukin-5 production from mouse T lymphocytes.

This study was designed to evaluate the effects of roxithromycin (RXM), a newly synthesized macrolide antibiotic on allergic responses in mice. RXM was orally administered into BALB/c mice once a day for 42 days in a single dose of 5 mg/kg body weight. Spleen cells (Sp C) collected from mice on day 7, 14, 28 and 42 post-RXM administration showed higher blastic activity of lymphocytes than those from control. The activity peaked on the 7th day, then gradually decreased, and returned to the control level by the 42nd day. Production of cytokines, IL-2 and IL-5, by Sp C in response to concanavalin A stimulation was also examined in the course of RXM administration. The capacity of Sp C to produce IL-2 was enhanced by oral administration of RXM for 28 days. However, a long-term (for 42 days) administration inhibited it. On the other hand, the capacity of of Sp C to produce IL-5 was strongly inhibited by oral administration of RXM; the titer of IL-5 was similar to that obtained in cultures of Sp C from control mice. These results strongly suggest that oral administration of RXM inhibits the function of Th2-type helper T lymphocytes and that a long-term administration of RXM may be beneficial in asthma and allergy.

Animals↗

PubMed1993

Inhibitory action of azelastine on cytokine production from human peripheral blood leukocytes in vitro.

Effects of azelastine (AZ) on human peripheral blood leukocytes (PBL) in culture were examined. Addition of 10.0 micrograms/ml of AZ resulted in a marked inhibition of PBL blastic activity, but lower concentrations (1.0 and 0.5 microgram/ml) had no demonstrable suppressive effects on the activation. Interleukin (IL)-2, IL-3 and IL-4 production from PBL in response to Concanavalin A stimulation was also strongly suppressed when the cells were cultured in the presence of AZ. This suppression was observed even when lower concentrations (1.0 and 0.5 microgram/ml) of AZ were added to cell cultures.

Adult↗

PubMed1993

Detection of a circulating antibody against a peptide epitope on a mucin core protein, MUC1, in ulcerative colitis.

This study aims at clarifying whether the humoral immune response to the tandem repeat domain of MUC1 can be induced or not in vivo. The expression of MUC1 mRNA in the colon was revealed by Northern blot analysis, and cDNA cloning of an extracellular tandemly repeated domain of MUC1 was then performed to prepare the recombinant MUC1 protein. A cDNA clone coding for ten repeat domains was ligated into an expression vector in prokaryotes, resulting in a recombinant protein which could react with the MAb MUSE11 against an adenocarcinoma-associated antigen whose epitope has been shown to be localized in the tandem repeat domain on MUC1. The reactivity of sera from patients with ulcerative colitis with the recombinant protein was evaluated by SDS-PAGE and Western blot analysis to detect the antibodies against this tandem repeat domain. Five out of 19 serum samples tested positive, and these reactions were totally inhibited by MAb MUSE11, suggesting that the epitope recognized by these antibodies in sera is almost identical to that recognized by MAb MUSE11. The data represent the first demonstration of antibody production against a peptide epitope of the tandem repeat domain of MUC1.

Adolescent↗

PubMed1993

Induction of an eosinophil chemotactic factor production from T lymphocytes by a B cell lymphoma line.

Production of an eosinophil chemotactic factor (ECF) from human mononuclear leukocytes (MNL) was induced by coculture with an irradiated B cell lymphoma line, BALL-1. BALL-1 induced ECF production from OKT4-positive T lymphocytes without evident IL-2 production. Treatment of MNL with anti-IL-2 antibody failed to suppress the BALL-1-induced ECF production, whereas the treatment strongly inhibited IL-2-induced ECF production. Control supernatants of BALL-1 cells alone did not induce ECF production. BALL-1 fixed with periodate-lysine-paraformaldehyde, but not acetone or ethanol, induced evident ECF production. The isoelectric point of BALL-1-induced ECF (m.w. 10-30 kD) was around pI 7, whereas that of the IL-2-induced ECF was around pI 5. A combination of monoclonal antibodies against IL-3, IL-5, and GM-CSF suppressed the activity of the IL-2-induced ECF but not that of the BALL-1-induced ECF. BALL-1-induced ECF suppressed a respiratory burst from an eosinophilic cell line (YY-1) induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine, whereas the IL-2-induced ECF did not, suggesting that the biological function of these two ECF is different, at least in the effect on respiratory burst of eosinophils. From the present results we propose that one reason for infiltration of eosinophils into the stroma of tumors is that some tumor cells can stimulate OKT4-positive T lymphocytes to produce an ECF, and that eosinophils attracted by this ECF exhibit biological functions which are different from those of eosinophils attracted by other ECF.

Antibodies, Monoclonal↗

PubMed1993

The ability of QRST isointegral maps to detect myocardial infarction in the presence of simulated left bundle branch block.

The clinical value of QRST isointegral maps (I-maps) for the detection of myocardial infarction (MI) in the presence of left bundle branch block (LBBB) was investigated. We recorded I-maps during sinus rhythm and right ventricular (RV) pacing, which simulated LBBB, in 62 patients with MI (42 patients had at least one akinetic segment and the remaining 20 patients had only hypokinesis or normal contraction) and 26 patients without MI. An abnormal decrease in the QRST value of the I-map was assessed by the difference map (D-map), which indicated a '-2SD area', where the QRST integral value was less than the lower limit of the normal range (mean -2SD) calculated from 608 normal individuals. The I-maps recorded during the two activation sequences were similar to each other in patients with and without MI (r = 0.87 and 0.92, respectively). The '-2SD area' was located over the left anterior chest in patients with an anterior MI and over the lower torso in patients with an inferior MI during each activation sequence. We were able to diagnose MI during simulated LBBB with a sensitivity of 84%, a specificity of 81% and a diagnostic accuracy of 83% when we used the criterion that MI is present if the sum of QRST integral values below the normal range (sigma DM) exceeds 100 mV.ms. We were able to diagnose an akinesis with a sensitivity of 81%, a specificity of 85% and a diagnostic accuracy of 83% when we used the criterion that akinesis is present if sigma DM exceeds 500 mV.ms during simulated LBBB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Le(y) antigen expression is correlated with apoptosis (programmed cell death).

Apoptosis (programmed cell death) is a basic physiological process which determines specific patterns of tissue size and shape, and balance of cell number, during morphogenesis, and seems to play an integral role in oncogenic progression. Since dramatic changes of cellular glycosylation pattern are well known to be closely correlated with differentiation, development and oncogenesis, it is likely that similar specific changes are associated with apoptosis. However, this possibility has not been systematically investigated. We therefore carried out histological studies of many tumours and normal tissues for which a high incidence of apoptosis is believed to occur. Sections were stained with monoclonal antibodies (MoAbs) directed to carbohydrate antigens Le(y) and Le(x), proliferating cellular nuclear antigen (PCNA) and Fas (previously claimed to be an apoptosis-inducing antigen). Antibody staining patterns were compared with morphological cell characteristics as revealed by haematoxylin/eosin staining, and DNA fragmentation patterns (a marker of apoptosis) as revealed by 3'-OH nick-end labelling technique. We found that expression of Le(y) (defined by MoAb BM1) is closely correlated with the process of apoptosis, but not with cell proliferation or necrosis. Within Le(y)-positive areas of tissue sections, typical apoptotic morphological changes and DNA fragmentation (as revealed by positive nick-end labelling) were frequently observed in certain loci, although not all Le(y)-positive cells showed such signs of apoptosis. Le(y)-positive areas showed consistent negative staining by MoAb directed to PCNA and negative or weak staining by MoAb directed to Fas antigen, regardless of tissue source. No such trends were observed for Le(x) glycosylation. We conclude that Le(y) expression is a useful phenotypic marker predictive of apoptosis, i.e. some (although not all) Le(y)-positive cells subsequently become apoptotic.

Antibodies, Monoclonal↗

PubMed1993

The structure of recombinant human carboxy-terminal-truncated macrophage colony-stimulating factor derived from mammalian cells.

The structure of recombinant human carboxy-terminal-truncated macrophage colony-stimulating factor expressed in CHO cells was investigated. The bioactive protein ([-32-153]M-CSF), expressed from a nucleotide sequence that encoded a signal peptide of 32 amino acids and N-terminal amino acids numbers 1-153, was heterogeneous in terms of molecular mass, as analyzed by SDS-PAGE, because of the presence of N-linked sugar moieties. The primary structure of the polypeptide was determined by sequence analysis and amino acid analysis of the fragments obtained from lysylendopeptidase digests of reduced and alkylated M-CSF, and from pepsin digests of the intact molecule. A sugar chain was located only at Asn-122 of the two putative sites of N-glycosylation that were present per subunit. The homodimeric structure appeared to have seven disulfide bonds, formed by inter- or intra-molecular linkages, since there were no free thiol groups in the molecule. The assignment of disulfide bonds by sequence analysis using peptide fragments indicated the combinations of Cys7-Cys90, Cys48-Cys139, and Cys102-Cys146. Gel-filtration analysis of Ser31[-32-153]M-CSF, in which the remaining Cys31 was replaced by Ser and which was expressed in COS cells, suggested that the mutein existed as a monomer. Our study shows that the disulfide-bond pairings of [-32-153]M-CSF that is expressed and post-translationally modified in mammalian cells are identical to those of Escherichia coli-derived [3-153]M-CSF with only one intermolecular disulfide bond, namely, Cys31-Cys31.

Alkylation↗

PubMed1993

Functional domains of human endothelin receptor.

The ligand binding site to the ETA receptor was investigated by substitution of each 5-amino acid sequence located in the second extracellular (B) region of the ETA receptor with the cognate sequences of the beta 2-adrenergic receptor. A 5-amino acid sequence (140-KLLAG-144) in the B-loop region was implicated as the most important element required for ligand binding. In addition, both the third and the fourth extracellular regions (C- and D-loops), including the flanking transmembrane regions, were found to play an important role in ligand selection. As for the biological significance of the intracellular regions of the ETA receptor, we have found that the C-terminal 8-amino acid residues located in close proximity to the seventh transmembrane region and the C-terminal 16-amino acid residues in the third intracellular loop are important for the binding of ET-1. Therefore, the intracellular third loop and C-terminal domains seem to contribute to the three-dimensional structure of the ligand binding site located in the extracellular domains. The same lines of experiment showed that the ETA receptor requires > 13 amino acid residues at the proximal cytoplasmic tail and 10 amino acid residues in the C-terminal region of the third intracellular loop to induce an ET-1-dependent increase in [Ca2+]i. Both regions are possibly involved in the interaction with G-protein.

Amino Acid Sequence↗

PubMed1993

Intralymphocytic free calcium and magnesium in stroke-prone spontaneously hypertensive rats and effects of blood pressure and various antihypertensive agents.

1. Free Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were measured in peripheral lymphocytes from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) at the age of 5, 7 and 17 weeks, from various antihypertensive agents-treated SHRSP, and from secondary hypertensive WKY. 2. At the age of 5 weeks, no difference was observed in systolic blood pressure (SBP), or lymphocyte [Ca2+]i and [Mg2+]i between SHRSP and WKY. At the age of 7 or 17 weeks, SBP and [Ca2+]i of SHRSP were significantly higher than in WKY, and at the age of 17 weeks, [Mg2+]i of SHRSP was significantly lower than in WKY. Further, [Ca2+]i or [Mg2+]i was positively or negatively correlated to SBP, and [Mg2+]i was negatively correlated to [Ca2+]i. 3. SBP of SHRSP fell significantly after antihypertensive treatment with calcium antagonist, angiotensin-converting enzyme (ACE) inhibitor or hydralazine for 40 days. [Ca2+]i was significantly lower in calcium antagonist and hydralazine groups, and tended to be low in ACE inhibitor group. These four groups showed no difference in [Mg2+]i. 4. After 40-day administration of NG-nitro-L-arginine (L-NNA), WKY developed severe hypertension, but there were no significant differences in lymphocyte [Ca2+]i and [Mg2+]i between the L-NNA treated and non-treated groups. 5. These results suggested that increased lymphocyte [Ca2+]i and decreased [Mg2+]i observed in SHRSP are not only secondary to hypertension but possibly related to a basic genetic abnormality of divalent cation handling.

Animals↗

PubMed1993

Immunohistological differentiation of benign thyroid follicular cell tumors from malignant ones: usefulness of anti-peroxidase and JT-95 antibodies.

An immunohistological investigation using anti-thyroid peroxidase (PO) and JT-95 (JT) antibodies was conducted on surgical specimens of papillary carcinoma (n = 12), follicular carcinoma (n = 8), follicular adenoma with prominent papillary structure (n = 12), follicular adenoma (n = 8) and adenomatous goiter (n = 8). In benign lesions, follicle-forming and papillae-forming epithelia showed positive staining with anti-PO antibody. In 26 of 28 benign lesions, PO-positive areas covered 50% or more of the cut surface area of the lesions. However in carcinomas, PO-positive areas were non-existent (13/20) or only focal (7/20) and the papillae did not stain. The incidence of JT-positive cases was higher in papillary carcinomas (12/12) than in other lesions (13/36). JT-positive areas were much wider than PO-positive areas in papillary carcinomas, whereas in benign lesions, PO-positive areas were wider than or at least roughly equal to, JT-positive areas. Follicular carcinomas did not stain or stained only focally with these antibodies. In conclusion, these two antibodies seem useful in differentiating benign from malignant follicular cell tumors.

Adenocarcinoma, Follicular↗

PubMed1993

Effect of transurethral resection of prostate on plasma hormone levels in benign prostatic hyperplasia.

Circulating levels of pituitary and adrenal hormones were measured in patients with benign prostatic hyperplasia before and after transurethral resection of the prostate (TURP). TURP caused a significant increase in plasma LH levels 2 weeks and 3 weeks after surgery. The plasma prolactin level decreased significantly 3 weeks after prostatectomy but plasma concentrations of FSH and ACTH were unchanged. TURP did not alter circulating levels of aldosterone, cortisol, DHEA-S and testosterone. These data suggest that the human prostate has a role in regulating the pituitary secretion of LH and prolactin.

Adrenal Cortex Hormones↗

PubMed1993

Effects of right ventricular pacing on QRST isointegral maps in patients with and without myocardial infarction: body surface distribution of significant changes in QRST area compared to supraventricular complex.

To assess the effects of right ventricular (RV) pacing on body surface QRST distributions, we recorded QRST isointegral maps (I-maps) during sinus rhythm and RV pacing in 25 patients with anterior myocardial infarction (MI), 19 with inferior MI, and 14 without MI. The QRST values at each lead point recorded during sinus rhythm and RV pacing with an 87-lead system were analyzed with a paired t-test in each patient. An abnormal decrease in the QRST value of the I-map was assessed by the difference map, which indicated a "-2SD area," where the QRST integral value was less than the normal range (mean - 2SD) calculated from 608 normal individuals. The I-maps were similar during the two activation sequences in patients with and without MI. However, during RV pacing, QRST values significantly decreased over the upper right anterior chest and increased over the lower left anterior chest and back. The sigma DMs (sum of QRST integral values below the normal range) for both activation sequences were strongly correlated in patients with anterior MI and with inferior MI (r = 0.91 and r = 0.92, respectively; P < 0.001). Although small but significant changes in QRST values were detected, the distribution of the "-2SD area" and the sigma DM were similar during both activation sequences in patients with prior MI. Thus, these findings demonstrate that an altered activation sequence produces small but significant changes in QRST values but that I-maps still provide information that is useful for the diagnosis of MI during RV pacing.

Adult↗