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Biomedical subjects

K Eguchi

Publications and source records attributed to K Eguchi.

At least 397 records · Page 22Linked to original sources

Urinary and plasma epidermal growth factor levels are decreased in neonates with intrauterine growth retardation and in their mothers.

Epidermal growth factor (EGF) concentrations in urine and plasma samples collected from pregnant women and neonates were measured by RIA. The EGF concentration of the first voided urine was higher in appropriate-for-date (AFD) neonates (33.9 +/- 23.0 ng/mg creatinine) than in those with intrauterine growth retardation (IUGR; 23.5 +/- 7.7 ng/mg creatinine, p less than 0.05) and heavy-for-date (19.8 +/- 5.2 ng/mg creatinine, p less than 0.05) neonates. The urinary EGF concentration of pregnant women showed no marked changes throughout pregnancy. Urinary EGF concentrations of women with AFD fetuses (45.9 +/- 31.2 ng/mg creatinine) did not differ significantly from those of women with diabetes (39.9 +/- 26.8 ng/mg creatinine) or women with multiple fetuses (44.6 +/- 30.6 ng/mg creatinine). However, women with IUGR fetuses showed lower urinary EGF concentrations (13.8 +/- 7.4 ng/mg creatinine, p less than 0.05) than women with AFD fetuses. Maternal and fetal platelet-poor plasma EGF concentrations at delivery were lower in the IUGR group (mother: 2.62 +/- 0.38 ng/ml, fetus: 2.16 +/- 0.07 ng/ml, respectively, p less than 0.05 and p less than 0.005) than in the AFD group (mother: 3.34 +/- 0.64 ng/ml, fetus: 3.24 +/- 0.93 ng/ml). In the IUGR group, the EGF concentration in fetal blood was always lower than that in maternal blood (p less than 0.05), although the AFD groups showed no such difference. These data suggest that EGF levels are closely related to fetal growth.

Birth Weight↗

Developmental changes of glutamate dehydrogenase activity in rat liver mitochondria and its enhancement by branched-chain amino acids.

The developmental changes of glutamate dehydrogenase activity in the fetal and neonatal rat liver were investigated, as well as the effects of branched-chain amino acids on this enzyme. Hepatic glutamate dehydrogenase activity showed a marked increase at the end of the fetal period and peaked on the 5th day of neonate at approximately 3 times higher than the adult level. Glutamate dehydrogenase was activated by leucine, isoleucine, and valine in this order when they were added to isolated intact liver mitochondria in vitro. The enhancement of enzyme activity was more marked in fetal rats than in adults. In contrast, when branched-chain amino acids were added after disrupting the mitochondrial membrane by sonication, only leucine slightly activated glutamate dehydrogenase, while isoleucine and valine slightly inhibited its activity. Our findings suggest that glutamate may be actively synthesized in the developing rat liver mitochondria and then transaminated to other nonessential amino acids for protein synthesis, and that increased intramitochondrial branched-chain amino acid concentrations may enhance glutamate dehydrogenase activity. This anabolic metabolism will contribute to the fetal growth and development.

Amino Acids, Branched-Chain↗

Development changes of polyamine biosynthesis in rat liver.

To investigate the role of polyamine metabolism in fetal development, we determined the hepatic polyamine content and the activity of enzymes related to polyamine metabolism in fetal, newborn and adult rats. In the fetuses, spermidine was detected at the highest level, followed by spermine and then putrescine. Putrescine and spermidine levels were higher in the fetuses than in adult rats, while the spermine level was significantly lower in the fetuses. The activities of the enzymes investigated were also higher in the fetuses than in adult rats. These findings indicate that polyamine synthesis was enhanced in the fetal liver, and that degradation of spermidine via spermidine N1-acetyltransferase contributes to the increase in putrescine levels. Thus, our study suggests that an increase in putrescine is important for fetal growth and that putrescine per se has a significant role in fetal cellular proliferation.

Acetyltransferases↗

Changes in plasma human atrial natriuretic peptide (hANP) level in normal pregnancy and pregnancy induced hypertension.

We determined plasma human atrial natriuretic peptide (hANP) levels in normal pregnancy and pregnancy induced hypertension (PIH). The plasma hANP levels slightly decreased in the first trimester of normal pregnancy and tended to recover as pregnancy advanced, although these changes were slight. However, the plasma hANP level in puerperium was higher than that in the third trimester of normal pregnancy. The plasma hANP level in mild PIH was not significantly higher than that in the third trimester of normal pregnancy. In contrast, the plasma hANP level in three cases of severe PIH was approximately 200% higher than those in the normal third trimester and mild PIH.

Atrial Natriuretic Factor↗

Remarkable increase in CD26-positive T cells in patients with human T lymphotropic virus type I (HTLV-I) associated myelopathy.

We used two-color flow cytometric analysis to investigate CD26+ (Ta1+) cells in peripheral blood T lymphocytes from patients with human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM). The percentage of CD26+ cells among CD3+ cells was markedly increased in patients with HAM, compared with anti-HTLV-I seropositive carriers (p < 0.001) and seronegative controls (p < 0.01). Within the subpopulation of T cells, a significantly high percentage of CD26+ cells was detected in both CD4+ and CD8+ cell populations. Furthermore, analysis of HLA-DR+ T cells revealed similar results. In contrast CD4+CD45RA+ cells were significantly decreased in comparison with controls. These results suggest that immunologically activated or memory T cells found in peripheral blood may be etiologically relevant to HAM.

Adult↗

Cytokines and immune regulation in thyroid autoimmunity.

We studied the role of cytokines and immune regulation in thyroid tissue from patients with Graves' disease. Immunohistochemistry showed that the thyroid glands are characterized by an aberrant expression of HLA class II antigens on thyrocytes, generation of new blood vessels and infiltration of mononuclear cells. We demonstrated that CD4+ memory cells were more frequent in thyroid glands from Graves' patients than were CD4+ naive cells. The intrathyroidal T cells demonstrated an enhanced expression of the adhesion molecules LFA-1, CD2, VLA-4 and VLA-5, and vascular endothelial cells of capillaries and thyrocytes in thyroid glands reacted with anti-ICAM-1 monoclonal antibody. The adhesion molecules and HLA antigens on both vascular endothelial cells and thyrocytes were regulated by inflammatory cytokines. These results suggest that circulating lymphocytes migrate into thyroid tissues and that memory T cells are retained in the thyroid tissues by cellular interactions with thyrocytes or with extracellular matrix.

Animals↗

[A study of falls experienced by institutionalized elderly].

This study was conducted to determine what factors are related to falls, conditions contributing to falls and the associated injuries. Subjects who had lived in 3 institutions for the elderly in the western region of Shizuoka Prefecture were chosen. Subjects (n = 181) had an average age of 76.4 +/- 7.8 years, and all were interviewed regardless of their history of falls. For those who had experienced falls further interviews were conducted. The following results were obtained: 1) There were 64 subjects (35.4% of the subjects) who had experienced falls, some having experienced multiple falls (for a total count of 89 falls). 2) The frequency of falls of differed by sex or age was significantly. The frequency of females was significantly higher than that of males. The frequency for those in their 70's was lower than in other age groups. 3) At the time of experiencing falls the majority of subjects had hypertension, eye symptoms, insomnia, paralysis, functional restrictions, were going up or down stairs, working, and had difficulty reading characters in newspapers, had experiences of stumbling or need of medical attention within for the past 2 years. Results of this study showed that, while the use of tranquilizers or hypnotics were not statistically significant, they were closely connected to and increase in falls among the aged. 4) In the causes of falls, intrinsic factors figured in 34 (34.0%) cases, and the extrinsic factors in 66 (66.0%). 5) Both falls and fall-caused external injuries were higher among females than males. Furthermore, female subjects mainly suffered contusions and fractures while male subjects mainly suffered abrasions.

Accidental Falls↗

Fibroblast growth factors released by wounded endothelial cells stimulate proliferation of synovial cells.

We demonstrated that vascular endothelial cells mechanically wounded by scraping from the substratum were able to release growth promoting factors for synovial cells as well as for endothelial cells. The wounded endothelial cell conditioned medium stimulated the proliferation of synovial cells derived from different human donors dose dependently and induced transit of growth arrested synovial cells (predominant in the G0 and G1 phases), through the S phase and into the G2 and M phases. When the wounded endothelial cell conditioned medium was applied to heparin-sepharose columns, mitogenic activity was eluted with 2.0 M NaCl. The mitogenic activity in wounded endothelial cell conditioned medium, which was heat sensitive, was inhibited by protamine sulfate and a specific mouse monoclonal antibody against basic fibroblast growth factor (bFGF). Our results are evidence that the wounded endothelial cell conditioned medium contained growth promoting factors for synovial cells, including bFGF. We also showed the presence of bFGF in the endothelial cells of the small blood vessels and stromal synovial fibroblast-like cells in patients with rheumatoid arthritis (RA). Our results suggest that the endothelial cells in the luxuriant capillaries in the synovial tissues from patients with RA may have a critical role in the stimulation of neighboring synovial cell proliferation, resulting in pronounced synovial hyperplasia.

Antibodies, Monoclonal↗

[Coronet status of digital radiography in chest medicine].

It has been ten years since Computed Radiography (CR) was introduced to evaluate its efficacy on the diagnosis of chest diseases in Japan. Over 600 CR systems are in their daily clinical use. CR images improve the quality of chest X-ray diagnosis with its enhancement parameters, that is, the digital image's contrast and edge enhancement. In daily clinical work, however, some abnormalities on the images, such as infiltrative shadows and fine miliary shadows, have shown CR imaging to have no superiority in visualization compared to conventional X-ray films. The quality of CR images greatly depends on the reconstruction algorithm. The diagnostic system of CR images using CRT monitor and workstations will be warranted in order to make the CR system the optimal and most useful modality in chest medicine. The CR system is potentially applicable in Picture Archiving and Communication System (PACS).

Humans↗

Polyarteritis nodosa with aortic dissection: necrotizing vasculitis of the vasa vasorum.

A 59-year-old woman was admitted to our hospital with acute onset of chest pain. She had experienced high fever, weight loss, polyarthralgia, myalgia, polyneuropathy and hallucinations for 3 years before admission. The diagnosis of polyarteritis nodosa with hepatitis B surface antigenemia was made by muscle biopsy and serological examinations, and administration of prednisolone induced remission of all the manifestations. After developing the acute attack of severe chest pain, she died suddenly. At autopsy, a DeBakey type 1 aortic dissection was found and the immediate cause of death was found to be cardiac tamponade secondary to rupture of the aortic dissection. Microscopically, necrotizing inflammatory lesions were present in the medium sized vascular arteries throughout her body. Furthermore, necrotizing vasculitis was also found in the vasa vasorum of the adventitia and media of the thoracic aorta. The dissecting lesion was seen in the outer layer of the media. Our results suggest that spontaneous dissection of the aorta may be attributed to necrotizing vasculitis of the vasa vasorum.

Aortic Dissection↗

[Clinical characteristics and prognosis of secondary amyloidosis in patients with rheumatoid arthritis--renal involvement and therapy].

Secondary amyloidosis is an important complication that may have a strong influence on the prognosis of patients with rheumatoid arthritis (RA). We studied 21 RA patients with secondary amyloidosis. The two major initial signs were gastrointestinal symptoms and renal involvement. When 15 of the 21 patients were diagnosed as having secondary amyloidosis, they displayed renal involvement including proteinuria, hematuria and hypercreatininemia. The 15 patients with amyloidosis were either subjected to dialysis or died within 35 months on the average. The causes of death in 13 patients were cardiac failure, gastrointestinal bleeding and infection, which were strongly implicated with renal failure. Dialysis was applied to seven patients. Three of them were maintained with chronic dialysis. We discussed the induction-time and the method of dialysis in patients with amyloidosis secondary to RA.

Adolescent↗

[A comprehensive fact finding study of home care elderly for planning of the community based rehabilitation system in Koga City, Ibaraki Prefecture].

An interview survey was held with the purpose of grasping the problems faced by the home care elderly living in Koga city in Ibaraki prefecture. The subjects of the study were 100 cases who had been registered as elderly requiring home care in the municipality. The main results were as follows: (1) The most frequent underlying disorders that were considered as causes of disabilities in the home care elderly were cerebrovascular diseases, senile dementia and external injuries. In 67 percent of the subjects, one of these three disorders had caused the disabilities. (2) Disabilities in self care activities and in mobility were closely related to each other and the order of the difficulty in performing these activities was similar in many cases. A large number of the subjects sustaining severe disabilities expressed discontent with their daily life. (3) Forty two percent of the subjects were so-called bedridden elderly who got out of bed for less than 3 hours a day. The Barthel index score was 60 or less in all of the bedridden subjects. (4) For most of the bedridden elderly, bed rest was not required and probably exacerbated the disuse syndrome. In order to ameliorate their condition, adequate rehabilitation programs and assistance in their daily activities need to be offered. (5) Seventy eight percent of the care givers complained about the burden of care. Those who had no assistant care giver complained more frequently. Many of the care givers complaining about their burden had their own health problems. (6) The utilization of social welfare services were not always without any problems. The number of the experts who can deal with the psychosocial aspects in the elderly should be increased in order to improve the situation.

Aged↗

[Tryptophan and its metabolite concentrations in human plasma during the perinatal period].

The concentration of tryptophan (free and protein bound) and its metabolites in the plasma of the maternal vein and in the umbilical vein, umbilical artery and neonatal vein were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in the umbilical vein and artery were significantly higher than those in the maternal vein. Especially the 3-OHAA level in umbilical blood was approximately 50 times as high as that in maternal blood. The concentration of total tryptophan in the plasma of the neonatal vein showed a marked decrease at one day after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in the plasma of the neonatal vein. In the blood, ratios of free to total tryptophan and kynurenine were kept at a constant level throughout the perinatal period. In conclusion, the present study suggests that tryptophan metabolism may play an important role in fetal development.

Chromatography, High Pressure Liquid↗

Bucillamine inhibits T cell adhesion to human endothelial cells.

We investigated the ability of bucillamine [N-(2-mercapto-2-methyl-propionyl)-L-cysteine] to prevent T cell adhesion to endothelial cells (EC) isolated from human umbilical vein. When EC were pretreated with bucillamine, T cell binding to the EC was suppressed in a dose dependent fashion. The T cells could bind preferentially to recombinant interferon-gamma (rIFN-gamma) treated EC compared with untreated EC. Bucillamine could also suppress T cell binding to rIFN-gamma treated EC as well as untreated EC. Addition of copper sulfate to bucillamine decreased significantly the percent T cell adhesion to the EC compared with bucillamine alone. The magnitude of inhibition by bucillamine and copper sulfate was similar in EC treated with rIFN-gamma as well as in untreated EC. H2O2 also inhibited the T cell binding to both untreated and rIFN-gamma treated EC. The inhibitory effects of bucillamine with or without copper sulfate on T cell binding to EC were abolished completely by catalase but not by superoxide dismutase. Our results suggest that hydrogen peroxide generated by bucillamine, with or without copper sulfate, inhibits T cell binding to EC. We believe, therefore, that bucillamine may suppress inflammation, such as that in rheumatoid synovitis, by reducing the emigration of chronic inflammatory cells from capillaries into tissue.

Anti-Inflammatory Agents, Non-Steroidal↗

Feasibility study on quality-of-life questionnaires for patients with advanced lung cancer.

In order to evaluate quality-of-life (QOL) questionnaires, we studied the reliability and validity of the self-rating forms: A, comprising 16 questions; B, comprising 39 questions (Table II and III), in a special study supported by the Ministry of Health and Welfare. Sixty-four patients with inoperable lung cancer and 50 patients with chronic, non-malignant disease were entered into the study. Form A was translated and modified to Japanese culture from Schipper's Functional Living Index-Cancer, and Form B was of our own design. The internal consistency of the forms was examined by Cronbach's alpha coefficient. Both forms except for aspects of physical and social concern on form B, had alpha values greater than 0.65. A concurrent validity with performance status was shown over all aspects of concern (Pearson's correlation, r greater than 0.27, P less than 0.05) except for social (forms A and B) and psychological (form B). Analysis of variance of the QOL scores revealed significantly lower scores for the cancer patients than for the non-malignant-disease patients, except for the social aspect of concern (P less than 0.001). Factor analysis, using the principal component method, identified four major factors to account for 60 and 42% of the total variance on forms A and B, respectively. The factors were: patient's mood, anxiety over disease and treatment, relationships with other people, physical capability. In conclusion, this has been the first feasible study to show that QOL forms from the West could be used in Japan with some modifications. We are at present studying successive changes in QOL for advanced lung cancer patients in clinical trials.

Adult↗

Phase I study and pharmacological analysis of cis-diammine(glycolato)platinum (254-S; NSC 375101D) administered by 5-day continuous intravenous infusion.

A phase I study of cis-diammine(glycolato)platinum (254-S; NSC 375101D) was conducted in 15 patients with refractory or relapsing malignancy by 5-day continuous i.v. infusion. Three to 5 patients per dose were given 50, 75, 87.5, or 100 mg/m2/120 h (10-20 mg/m2 daily for 5 days). Toxicity evaluation and pharmacokinetic analysis were performed in 15 and 14 patients, respectively. Thrombocytopenia and neutropenia were the dose-limiting toxicities at the maximum tolerated dose of 87.5 mg/m2/120 h (17.5 mg/m2/day); however, nonhematological toxicities including renal toxicity, nausea and vomiting, and peripheral neuropathy were mild and well tolerated. The nadir of platelets and neutrophils was observed 4 and 5 weeks, respectively, after the initiation of drug infusion. Plasma and urine samples were obtained during and after infusion for quantification by atomic absorption spectrophotometry of total and free platinum levels derived from 254-S. The maximum level of total platinum was obtained after 120 h of infusion, whereas the steady state concentration of free platinum in the patients given 75 mg/m2 or more was over 0.1 microgram/ml. Free platinum levels declined monophasically, with half-lives of 0.65-2.56 h/100 mg/m2 dose. The mean area under the concentration versus time curve (AUC) in the patients treated with 75 mg/m2 was 1069 micrograms/ml, which was similar to that obtained in the patients receiving 100 mg/m2 of 254-S by i.v. drip infusion over 30 min. There was a direct correlation between the dose administered and the AUC of platinum (R = 0.757, P = 0.002) or the steady state plasma concentration of free platinum (R = 0.763, P = 0.002). The percentage of platinum excreted in urine 144 h after the initiation of infusion ranged from 73.1 to 100% for each dose level. No significant relationship was established between creatinine clearance in patients before treatment and the AUC or steady state concentration of free platinum. The plasma platinum AUC showed a linear correlation with the percentage of change in leukocytes [formula: see text] (R = 0.736, P = 0.003). In conclusion, the recommended phase II dose for a continuous infusion of 254-S is 75.5 mg/m2/120 h every 6 hours.

Adult↗

Effects of lobenzarit disodium on human endothelial cells. Lobenzarit disodium inhibits proliferative response, HLA-DR antigen expression, and T cell adherence toward endothelial cells.

The therapeutic action of lobenzarit disodium (CCA) on the function of endothelial cells (EC) isolated from human umbilical cord veins was investigated. CCA suppressed 3H-thymidine incorporation into EC in a dose-dependent manner. Significant inhibition was detected at a concentration of 50 micrograms/ml. The expression of HLA-DR antigen on the surface of EC was increased when EC were cultured with recombinant interferon-gamma (rIFN gamma). Treatment of EC with either IFN gamma or interleukin-1 enhanced the adhesion of T cells to EC. The kinetics of HLA-DR antigen expression by EC cultured with IFN gamma was different from the kinetics of T cell-EC adhesion, however. Neither anti-HLA-DR nor anti-HLA-ABC monoclonal antibody inhibited T cell binding to EC monolayers. CCA suppressed the expression of HLA-DR antigen by EC cultured with rIFN gamma. In an EC monolayer adhesion assay, CCA also inhibited T cell adhesion to EC in the presence of either IFN gamma or interleukin-1. Significant inhibition was observed at a CCA concentration of 10 micrograms/ml, a level that is easily attainable in serum. These results suggest that CCA may suppress rheumatoid synovitis by reducing the angiogenesis and emigration of chronic inflammatory cells from the blood into the synovium.

Cell Adhesion↗

Prediction of the antitumor activity of new platinum analogs based on their ex vivo pharmacodynamics as determined by bioassay.

We report the predictive model for the clinical response of new platinum analogs against lung cancer by a bioassay using human lung-cancer cell lines including small-cell (SCLC) and non-small-cell lung cancer (NSCLC). Exponentially growing cells of six different SCLC and six NSCLC lines were exposed to different concentrations of the three platinum compounds, cisplatin, carboplatin, and 254-S in a double-agar colony-forming cell assay. The concentrations inhibiting 50% of colony formation (IC50 value) for cisplatin, carboplatin and 254-S in SCLC cell lines were significantly lower than those in NSCLC cell lines. A total of 15 patients entered the pharmacological study. In all, 80 mg/m2 cisplatin, 450 mg/m2 carboplatin, and 100 mg/m2 254-S were each given to five patients by intravenous drip infusion. Bioassay as well as chemical assay was achieved by clonogenic techniques using NCI-H-69 (SCLC cell line) and PC-9 (NSCLC cell line) as target cells. Biological comparison of antitumor activity was performed on the basis of the antitumor activity of patients' plasma using the antitumor index (ATI), which was defined as the area under the percentage of colony suppression versus time curve obtained by bioassay and calculated by the trapezoidal rule. When NCI-H-69 and PC-9 were used as target cells for bioassay, colony-inhibitory activity was revealed by the ATIs. The ATIs obtained by bioassay showed better correlation than the AUCs obtained by chemical assay with the clinical response for cisplatin and carboplatin against SCLC and NSCLC, according to the following equation: [Reported Response (%)] = 11.5668 + 0.0014 x [ATI] (r = 0.97). The response rates for 254-S against SCLC and NSCLC were predicted by this formula to be 40%-65% and 14%-16%, respectively. 254-S is prospectively suspected of having the same, if not more, activity then carboplatin against SCLC and of having almost the same activity as cisplatin against NSCLC.

Antineoplastic Agents↗