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Biomedical subjects

M Kitamura

Publications and source records attributed to M Kitamura.

At least 379 records · Page 21Linked to original sources
PubMed1993

[Functional evaluation of skeletal muscle ventricles for circulatory assist].

Skeletal muscle has a potential power for cardiac assist. Two approaches have been used to harvest this power: dynamic cardiomyoplasty, which involves the application of muscle directly to the heart to support cardiac contractile function; and the construction of skeletal muscle pouches or ventricles, which are used as separate pumps working either in parallel or in series with the heart. In this study, we evaluated the function of the skeletal muscle ventricles (SMVs) for circulatory assist. In six dogs (18.5 +/- 2.3 kg, mean +/- S.E.M.), SMVs were constructed from the right latissimus dorsi muscle, and placed in the right hemithorax. After a 3-week vascular delay period, the SMVs were preconditioned electrically by 2 Hz continuous stimulation for six weeks. Nine weeks later, SMVs were connected to a mock circulation device for functional evaluation. As right-sided pumps, at a preload of 10 mmHg, SMVs generated stroke work of 0.63 +/- 0.04 x 10(6) ergs with 25 Hz and 0.80 +/- 0.06 x 10(6) ergs with 85 Hz, which exceeded that of the native right ventricle. As left sided pumps, also at a preload of 10 mmHg, SMV stroke work was 0.49 +/- 0.13 x 10(6) with 25 Hz 0.90 +/- 0.09 x 10(6) ergs, which was roughly half that of the left ventricle. These results demonstrate that SMVs have the potential to function as left or right heart assist devices.

Animals↗
PubMed1993

A retinoid responsive cytokine gene, MK, is preferentially expressed in the proximal tubules of the kidney and human tumor cell lines.

The aim of this study was to survey the expression of an embryonic cytokine gene, MK, in the normal organs and neoplastic tissues of adults. Northern analysis showed that MK mRNA was exclusively expressed in the kidney among murine organs including thymus, lung, heart, spleen, liver, and kidney. In situ hybridization analysis revealed that MK expression was localized in the proximal tubules and metaplastic Bowman's epithelium, but not in other nephron segments such as glomeruli, loop of Henle, distal tubules, and collecting ducts. To investigate whether MK expression is a marker of tubular cell lineage, several cell lines originating from renal tubules were tested. No expression of MK was detected in PtK1 and LLC-PK1 cells derived from marsupial and porcine proximal tubules or in MDBK and MDCK cells from bovine and canine distal/collecting tubules. Unexpectedly, the MK gene was expressed in a human renal cell carcinoma line, VMRC-RCW, and the expression was up-regulated in the presence of retinoic acid. To elucidate the involvement of MK in the development of tumors, we further examined its expression in a variety of human neoplastic cell lines: YMB-1-C (breast cancer), EBC-1 (lung squamous cell carcinoma), RERF-LC-OK (lung adenocarcinoma), SBC-3 (lung small cell carcinoma), HSC-2 (mouth squamous cell carcinoma), NUGC-2 (gastric cancer), COLO201 (colon cancer), HepG2 (hepatoma), MIA PaCa-2 (pancreatic cancer), MCAS (ovarian cancer), HeLa (cervical cancer), BeWo (chorionic carcinoma), ITO-II (testicular tumor), T24 (urinary bladder tumor), and G-401 (Wilms' tumor). Strong signals were detected in COLO201, HepG2, ITO-II, T24, G-401, and weaker but distinct signals were detected in YMB-1-C, HSC-2, and MCAS cells. The MK gene was, therefore, widely expressed in neoplastic cells originating from genital organs, intestinal tract, liver, mammary gland, and urinary tract, and the expression was not restricted to adenocarcinomas, but was also observed in other types of tumor cells. These findings suggest that a retinoic acid responsive gene, MK, may play a role in the pathophysiology of renal proximal tubules and tumorigenesis in many types of neoplasms.

Animals↗
PubMed1993

[Study of metabolic dynamics under severe surgical stress--investigation by the method of respiratory gas analysis].

To elucidate quantitative analysis of the hypermetabolic status and classification of energy substrates kinetics, the metabolic dynamics after radical operation for thoracic esophageal cancer was investigated in 10 patients primarily by the method of respiratory gas analysis. 1) REE showed almost 30 kcal/kg/day and no significant change on each postoperative day. Energy intake in addition to surgical stress influenced the metabolic dynamics (specific dynamic action: SDA). So authors originally devised a postoperative metabolic index "PMI" in consideration for the effect of SDA. PMI is defined; PMI = (REE kcal/day-BEE kcal/day)/Energy Intake (non-protein kcal/day). according to PMI, it was clarified that the hypermetabolic status reached a maximum value on the first postoperative day, showed a steep decrease up to the 3rd postoperative day and afterwards slow recovery. PMI revealed a significant correlation (r = 0.792, p < 0.001) with daily urinary epinephrine excretion in the immediate postoperative period (up to the 3rd day). These results suggest PMI might be useful in the quantitative evaluation of the hypermetabolic status under surgical stress. 2) Energy substrates kinetics was clearly classified into six patterns according to three parameters such as energy balance, glucose balance, and predominant fat metabolism (fat oxidation or synthesis).

Catecholamines↗
PubMed1993

Phase 1 study of L-627, biapenem, a new parenteral carbapenem antibiotic.

The safety and pharmacokinetics of L-627, a new injectable carbapenem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 20, 40, 80, 150, 300 and 600 mg of L-627 were administered by i.v. infusions over 1 hour. Plasma concentration-time profiles were well described with a two-compartment open model. The half-life of elimination from plasma was 1.3 +/- 0.8 (mean +/- SD) hour, and the Cmax and AUC paralleled the doses given. The mean urinary recovery of unchanged L-627 within the first 12 hours was 63.1 +/- 2.7% of the dose. In the multiple-dose studies, 300 mg of L-627 (i.v. over 1 hour) was administered every 12 hours, 11 times in total and 600 mg of L-627 was administered every 12 hours, 9 times in total. No discernible accumulation of the drug in plasma was observed. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject in one of the multiple-dose regimens (300 mg b.i.d.) showed only a slight elevation of transaminase value, although the elevated value promptly recovered after completion of dosing. No abnormality was observed in the other multiple-dose regimen (600 mg b.i.d.). From these results, L-627 was concluded to be safe and well tolerated.

Adult↗
PubMed1993

[The significance of body weight measurement of esophageal cancer patients in intra- and postoperative fluid administration].

We tried to clarify the intra- and postoperative pathological state in resected thoracic esophageal cancer patients and analyze the particularity of fluid administration by measuring body weight at certain time serially. We studied 26 resected thoracic esophageal cancer patients between September, 1989 and January, 1991 who underwent an operation through right thoracotomy prior to laparotomy at the same time, and all cases were under general anesthesia combined with epidural anesthesia. We measured body weight preoperatively, just after operation, on the first, second and third postoperative days by means of LIFTER (Ted Hoyer & Co. Inc), and also calculated water balance and measured pressures and cardiac output by Swan-Ganz catheter in 19 cases. As a result, change in body weight was remarkable in resected thoracic esophageal cancer patients intra- and postoperatively. The peak of weight gain was noticed and they gained about 3 kilograms in weight on the 1st postoperative day, while in circulation hypovolemia was found on the data by means of Swan-Ganz catheter. There was a high correlation between rate of change in weight (kg/hr) and water balance (ml/kg/hr) (r = 0.91). We calculated insensible loss by the difference between water balance and body weight. It was about 1.73 intraoperatively, 0 postoperatively, 0.35-0.5 ml/kg/hr on from the 1st through the 3rd postoperative day. It is concluded that body weight measurement is a very easy, precise and useful bedside technique in the intra- and postoperative fluid administration of esophageal cancer patients, because it is very important not only to understand the circulation volume but also to know the interstitial fluid change.

Body Weight↗
PubMed1993

[Evaluation of the right ventricular function in postoperative esophageal cancer patients].

We evaluated the right ventricular function in pre- and post-operative esophageal cancer patients who had no complications after surgery by measurement of cardiopulmonary hemodynamics, right ventricular ejection fraction (RVEF) and right ventricular end-diastolic volume index (RVEDVI) using Swan-Ganz catheter and the thermodilution technique. The measurement of RVEF, RVEDVI and other cardiopulmonary hemodynamics were performed from the preoperative day to the 3rd postoperative day. The values of RVEF were stable about 40% from preoperative day to 3rd. RVEDVI was varied at 93.6 +/- 26.3 ml/m2 (preoperative day), 83.6 +/- 15.0 ml/m2 (after surgery), 70.2 +/- 10.6 mg/m2 (morning of the 1st POD), 95.6 +/- 19.4 ml/m2 (evening of the 1st POD), 103.2 +/- 17.9 m/lm2 (morning of the 2nd POD), 1108.3 +/- 14.2 ml/m2 (evening of the 2nd POD) and 112.4 +/- 31.0 ml/m2 (morning of the 3rd POD). The values of RVEDVI on the morning of the 1st POD were statistically lower than those at other times (p < 0.05). The values of RVEDVI were not correlated with mean pulmonary arterial pressure and pulmonary arteriolar resistance which were the afterload of the right ventricle. These data suggest that the right ventricular function of the patients who underwent esophagectomy with no complication does not change and that the changes of RVEDVI are influenced by the preload of the right ventricle.

Cardiac Output↗
PubMed1993

[A study on the integration of fetal behavior and the development of association between parameters evaluated].

To evaluate the development of the fetal behavioral state with reference to the association of the fetal parameters we selected, we simultaneously monitored fetal heart rate (FHR), fetal movement (FM), fetal eye movement (FEM) and fetal breathing movement (FBM). These various parameters were monitored with 2 ultrasonographic real time scanners and a doppler device to monitor fetal movement. We assessed the convergence and integration of these four parameters to evaluate the association rate (AR). FHR with a variation in excess of 3 min. was interpreted as the active phase (A), and reduced variation in excess of 3 min. as the inactive phase (I). When FM and FEM were observed in the 1 min. window of A, we labeled this A3, and when FBM was present in more than 10% of the 1 min. window, we labeled it A4. A3/A = AR-A3% and A4/A = AR-A4% was calculated. A similar calculation was done for I, without FM and FEM in the 1 min. window of I (I3) and when FBM was present less than 10% of 1 min. (I4), allow derivation AR-I3% and AR-I4%. A discrete separation of synchrony in A and asynchrony in I can be seen to develop as the fetus matures, and we feel that this may be a valuable tool in the evaluation of fetal central nervous system development in utero.

Central Nervous System↗
PubMed1992

Gene expression of metalloproteinase and its inhibitor in mesangial cells exposed to high glucose.

To clarify the roles of metalloproteinases and their inhibitor (TIMP) in diabetic glomerulopathy, we studied the effect of a high glucose concentration on the gene expression of metalloproteinase transin and TIMP as well as collagen type IV and laminin in cultured rat mesangial cells (MCs). In the high glucose group, collagen type IV, laminin, and TIMP mRNA levels were all elevated in a concentration-dependent manner, whereas transin expression was suppressed. Osmotic control of high glucose with mannitol selectively stimulated TIMP expression. We hypothesize that high glucose decreases matrix-degrading activity as well as increases matrix productivity in MCs.

Animals↗
PubMed1992

Molecular characterization of genetic mutations in human lactate dehydrogenase (LDH) B (H) variant.

We have previously detected a single base substitution of G by A at the Arg codon CGC in exon 4 of the mutant lactate dehydrogenase (LDH) gene, an unstable LDH-B variant (case 1). Here, we use the polymerase chain reaction (PCR) to amplify genomic DNA of two cases (the original case 1 and a new patient, case 2). We were able to confirm that case 1 is homozygous for the mutation, causing a replacement of the conserved Arg by His at residue 173. The resulting LDH-B variant subunit is unstable in vivo. Whereas the mutation in exon 4 was not observed in case 2, a different single base substitution of A by C was detected at the Ser codon AGT in exon 3. This mutation causes a replacement of the conserved Ser by Arg at residue 131. Genomic analysis of the family of case 2 by mismatched PCR showed that the missense mutation was consistent with their biochemical phenotypes. The replacement results in a conformational change of the residues near the Ser, probably because the side chain of Arg is much more bulky than that of Ser. The change may affect the arrangement of the cofactor binding site and result in the loss of enzyme activity. The experimental observations are consistent with computer graphics analyses.

Amino Acid Sequence↗
PubMed1992

Extracellular matrix contraction by cultured mesangial cells: modulation by transforming growth factor-beta and matrix components.

Cultured glomerular mesangial cells (MCs) have the ability to contract the surrounding collagen gel matrix (CGM). To investigate this phenomenon, we examined the effect of growth factors and extracellular matrix (ECM) components. Among some growth factors tested, transforming growth factor-beta (TGF-beta) and fetal calf serum (FCS) enhanced CGM contraction dose dependently. These factors acted through distinct mechanisms because: (1) when growth-arrested MCs were used, the effect of FCS was inhibited partially but that of TGF-beta was not; and (2) anti-TGF-beta had no influence on CGM contraction induced by FCS. Among the ECM components such as laminin, fibronectin, type IV collagen, and heparin-like proteoglycans (heparan sulfate and heparin), which were each mixed separately with CGM before gelling, heparin-like proteoglycans and type IV collagen inhibited contraction by MCs. The inhibitory effect of heparin was mediated by the interaction both with CGM and with MCs because: (1) when heparin was added to the culture medium, not into the gel, the inhibitory effect was diminished but still noted; and (2) using growth-arrested MCs, the inhibitory effect of heparin in the medium was reduced but still observed. This culture assay is useful for elucidating the tensional interaction between MCs and surrounding ECM.

Animals↗
PubMed1992

Cytokine gene expression in rejecting cardiac allografts.

Heart transplantation is now a viable therapeutic option for patients with certain end-stage cardiac diseases. However, episodes of rejection, opportunistic infection, and life-threatening side effects of generalized immunosuppression remain very real problems for these patients. A better understanding of the molecular mechanisms underlying rejection may provide the basis for the development of more specific, less toxic immunosuppressive therapies. While cytokines have long been implicated in the pathogenesis of rejection, the precise role of each cytokine in this process has yet to be defined. We report here the application of the polymerase chain reaction (PCR) to the detection of cytokine mRNA in biopsies obtained from heterotopic abdominal cardiac allografts in cynomolgus monkeys. With the exception of IL-6 and IL-8, cytokine transcripts were undetectable in samples obtained from the donor heart pretransplant. In contrast, IFN-gamma transcripts were detected in all transplants two days after surgery before evidence of rejection was demonstrable by histopathologic analysis. IL-1 beta, IL-2, and IL-6 transcripts were detected when minimal rejection was noted. At later times, IL-1 alpha, IL-1 beta, IL-2, IL-6, IL-8, TNF-beta, and IFN-gamma transcripts were detectable. Further characterization of the spectrum of cytokines expressed at various stages of rejection may lead to insights into the biology of transplant rejection and to the development of more specific and potent reagents to diagnose and/or treat rejection.

Animals↗
PubMed1992

Induction of endogenous retroviral gene product (SU) as an acute-phase protein by IL-6 in murine hepatocytes.

The effect of Lps locus and IL-6 on the production of SU (previously termed gp70), a mouse endogenous retroviral gene product, was studied. Back-cross studies using the progeny between (NZB x C3H/HeJ)F1 and C3H/HeJ mice indicate that the basal level of SU is not associated with the Lps locus on chromosome 4. Lipopolysaccharide (LPS) mitogen response-negative mice did not show the enhancement of serum SU production after LPS injection. Spleen cells from LPS-mitogen response-positive but not from negative mice showed increase of IL-6 synthesis in the presence of LPS. Since IL-6 may be involved in the production of serum SU, we tested the effect of IL-6 in a primary hepatocyte culture system. SU production was clearly enhanced in the presence of recombinant IL-6, indicating that IL-6 induced by LPS can enhance the expression of retroviral genome.

Acute-Phase Proteins↗
PubMed1992

Locoregional control for esophageal carcinoma treated with irradiation following surgery.

Locoregional failure was analyzed in a total of 34 esophageal carcinoma patients treated with postoperative prophylactic irradiation following curative surgery. All patients had squamous cell carcinoma and no prior treatment. Twelve patients had subsequent lymph node metastasis in the follow-up period. In the 12 patients with node metastasis, there were 5 instances of supraclavicular node metastasis, 7 instances of thoracic inlet node (uppermost part of mediastinum) metastasis, and 3 instances of mediastinal node metastasis. Three patients had 2 metastatic nodes and 9 patients had 1 metastatic node. Intervals between surgery and recurrence were a median of 12 months for mediastinal nodes, 19 months for thoracic inlet nodes, and 26 months for supraclavicular nodes. Ten (52.6%) of the 19 patients treated by using a 12-MeV electron beam had metastatic involvement at the supraclavicular and thoracic inlet nodes. On the other hand, 2 (13.3%) of the 15 patients had the above-described lymph node metastases when treated by using 15-MeV electron, 18-MeV electron, or 10-MV photon beams. The difference in the metastatic rate between these two groups was statistically significant at the level of p < 0.05 (chi-square test); this seems to be attributable mainly to the dose level at deep region. Doses of over 50 Gy to the thoracic inlet and supraclavicular nodes at deep location were necessary to reduce metastasis.

Adult↗
PubMed1992

[Clinical significance of measuring glycated fibrinogen in plasma in diabetes mellitus].

The clinical significance of measuring glycated fibrinogen (G Fbg) in plasma was studied using a simple, rapid method for determining plasma G Fbg developed by the authors. This method is based on modified fibrin clot formation for purification of plasma Fbg, and G Fbg was estimated by improved colorimetric fructosamine assay. The values of plasma G Fbg were expressed as glycated polylysine equivalents (mumol/l). In this clinical study, 106 examinees who underwent a screening test for diabetes mellitus (DM) because of glycosuria or hyperglycemia were investigated. According to the WHO diagnostic criteria, they were divided into 3 groups: non DM group (n = 35), impaired glucose tolerance (IGT) group (n = 31) and DM (non-treated) group (n = 40). In addition, healthy controls (n = 40) and treated diabetic patients (DM treated) were involved. Plasma G Fbg/Fbg, fasting plasma glucose (FPG), fructosamine and glycated hemoglobin (HbA1c) were also analyzed in subjects of the 5 groups. Non-treated DM patients showed high levels of plasma G Fbg, which were significantly higher than those of any other groups. G Fbg levels in IGT group were significantly higher than those in healthy controls or the non-DM group. Together with a significant positive correlation between G Fbg and FPG, these results indicate that the levels of plasma G Fbg depend on plasma glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗