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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 793 records · Page 44Linked to original sources
PubMed1991

[Silent cerebral infarction in the patients with essential hypertension].

Evidence of old cerebral infarction of magnetic resonance imaging (MRI) is common in acute stroke patients without a prior history of stroke. This experience led us to investigate the incidence of silent cerebral infarction (SCI) in the patients with essential hypertension, as well-known major predisposing factor for stroke. The incidence, number, size and localization of SCI on MRI (MARK-J, 0.1 T) and the prevalence of risk factors for stroke were investigated both in 66 hypertensive patients (WHO stage I or II; 63 +/- 9 (mean +/- S.D.) years old) and in 42 age-matched normotensive patients (61 +/- 9 years old). Risk factors selected were as follows: diabetes mellitus, hypercholesterolemia, daily alcohol intake, cigarette smoking, obesity, cardiac disease (arrhythmia and ischemic heart disease), hyperuricemia and high hematocrit. In hypertensive patients, the relationships between the incidence of SCI and hypertensive damages in major organs were also investigated. SCI was found in 45 out of the 108 subjects studied and a total of 216 SCI lesions were detected. All of the SCI lesions were localized in the subcortical white matter or in the basal ganglia. All SCI lesions were smaller than 3 cm in diameter and 201 lesions (93%) were smaller than 1 cm. The incidence of SCI tended to be higher in hypertensive patients (47%) than that in normotensives (33%) and increased significantly with advancing age in hypertensives from 26.9% in the 50s to 86.7% in the 70s, while no significant increase was noted in normotensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Oxygen free radicals as pathogenic molecules in viral diseases.

Oxygen free radicals such as superoxide anion (O2-) were generated markedly in influenza virus-infected mouse lung, and these molecular species were identified as the potent pathogenic agents. This finding has many important implications for understanding viral pathogenesis: namely, the direct viral cytotoxicity (referred cytopathic effect) is only a fraction of several types of events induced by virus infection. The toxicity and reactivity of oxygen radicals, which are presumably generated in excessive amounts by the overreaction of the host's immune response against the organs or tissues in which viruses are replicating, may explain the mechanism of tissue injuries observed not only in influenza virus infection in mice, but also in other types of viral diseases in which immunological interactions are usually involved.

Animals↗
PubMed1991

An approach to optimal dialysis using urea kinetic modeling.

Urea kinetic modeling (UKM) was carried out to evaluate the water control in patients undergoing long-term hemodialysis. In 21 patients on chronic dialysis, the results of two different determinations of the total body water, i.e. by the deuterium oxide (D2O) method and by UKM, were compared. A correlation was observed with Y = 0.98X + 5.9 (P less than 0.01, r = 0.91) for males and Y = 0.97X + 6.2 (P less than 0.01, r = 0.90) for females, indicating that UKM is useful for determining the total body water. In addition, the 21 patients were classified into two groups based on their ECG findings, and UKM was performed in the two groups for comparison. The values of the total body water were 68.5 +/- 4.0% and 68.6 +/- 6.2% of body weight, respectively, with no significant difference between them. However, the CTR was 50.2 +/- 2.8% and 46.2 +/- 4.4%, respectively. Thus, not only X-ray examinations but also UKM should be carried out to determine the standard weight (SW-DW) in the presence of cardiac dysfunction. Instructions for water control were given when the total body water exceeded 73% during the UKM measurements over 5 years, which allowed an optimal total body water to be maintained thereafter. The possible influence of erythropoietin (EPO) was also examined by performing UKM in 8 cases receiving EPO and 7 cases without EPO. No noticeable difference was observed between the two groups. 17 patients using a polyacrylonitrile (PAN) membrane were further divided into those with and those without EPO to evaluate the possible influence of the PAN membrane-EPO combination. As a result, no significant difference was demonstrated, suggesting that UKM can be satisfactorily performed under such conditions. In 11 patients on chronic dialysis, the levels of alpha-human atrial natriuretic peptide (alpha-hANP) were measured pre- and post-dialysis to examine the relationship between the change in alpha-hANP and rate of weight loss (%). A significant correlation was observed with Y = 12.8X + 5.1 (P less than 0.05, r = 0.68). In conclusion, UKM was found to be useful for evaluating the water control and for assessing the optimal dialysis in patients receiving long-term hemodialysis.

Acrylic Resins↗
PubMed1991

[DNA typing of HLA].

Recent advance of molecular biology and genetic engineering has made a profound influence on clinical and laboratory medicine. In this article we will review present aspects of DNA typing of HLA-class II alleles. The HLA system is characterized by its highly genetic polymorphisms. HLA -class I (A, B, C) molecule consists of alpha 1, alpha 2, alpha 3, and beta 2-microglobulin domain, and HLA-class II (DR, DQ, DP) molecule consists of alpha 1, alpha 2, beta 1, and beta 2 domain. Differences of amino acid sequences determining polymorphisms of HLA-class II molecule are located mainly on the beta 1 domain, while alpha 1 chain of DQ molecule is also polymorphic. Polymerase chain reaction (PCR) has enabled us to make great progress in DNA typing of HLA, in place of RFLP (restriction fragment length polymorphisms) analysis. One of the most important and valuable advantages is to make us non-radioisotopic detection method available. There are several methods for the further analysis of products of PCR amplification; 1) dot-blot hybridization, 2) PCR-RFLP, 3) PCR-SSCP (single strand conformation polymorphism), 4) DGGE (denaturing gradient gel electrophoresis), 5) direct sequencing. As for dot-blot hybridization, there are also several methods for detecting hybridization; 1) radioactive detection with 32P - labelled probes, 2) colorimetric reaction and 3) chemiluminescent assay. Newly developed chemiluminescent assay yields as high sensitivity just as radioactive probes. HLA-D and -DP specificities have been typed cytologically by mixed lymphocyte culture (MLC) or primed lymphocyte test (PLT) method. Cytological typing will be replaced by PCR analysis in near future.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1991

Spreading of Serratia marcescens in experimental keratitis and growth suppression by chicken egg white ovomacroglobulin.

We studied the inhibitory effects of chicken egg white ovomacroglobulin, a broad-spectrum protease inhibitor, and a synthetic protease inhibitory peptide, Bz-GFR-O-mercaptoanilide, on the growth of two strains of Serratia marcescens in a synthetic medium. The growth of the virulent protease-producing strain, S. marcescens kums 3958 (kums 3958), was more rapid than that of the strain producing minimal protease, S. marcescens kums NA (kums NA), and kums 3958 was inhibited in a dose-dependent manner by ovomacroglobulin. The synthetic inhibitor also inhibited the growth of kums 3958 weakly. Dose-dependent enhancement of growth of kums NA was observed in the medium treated with the serratial 56 kilo Dalton protease. By immunohistochemical methods using an antibody to the bacteria, the spreading of kums 3958 was also studied in corneal tissue in experimental keratitis of the guinea pig. In vivo, kums 3958 grew locally, and then spread widely by destroying stromal tissue 7-8 hours after intrastromal injection of the organisms (3 x 10(4) colony-forming units). On the other hand, when kums 3958 mixed with ovomacroglobulin was injected into the cornea, the organisms remained locally in the corneal stroma which showed a lower grade of damage. These results indicate that proteases secreted from S. marcescens destroyed corneal stroma, yielding the organisms enough space for further spreading.

Anilides↗
PubMed1991

[5-Fluorouracil level and pyrimidine nucleoside phosphorylase activity in cancer patients after oral administration of doxifluridine (5'-DFUR)].

For the purpose to evaluate the distribution of 5'-DFUR in the cancerous tissues and non-cancerous tissues of 64 cancer patients (21 gastric, 25 colo-rectal and 18 breast cancers), pyrimidine nucleoside phosphorylase (PyNPase) activity and 5-FU level were determined by bioassay and GC-MS method. 5-FU levels in the plasma were also measured in all patients. Four hundred mg of 5'-DFUR was orally administrated three times a day for 3 to 7 days and just 3 hours before surgical operations. PyNPase activity and 5-FU level were significantly higher in the cancerous tissues than non-cancerous ones. 5-FU levels in the plasma were significantly lower than those in both cancerous and non-cancerous tissues. In conclusion, 5'-DFUR is expected to be an useful anticancer drug because of the selective accumulation of converted 5-FU in cancerous tissues.

Adenocarcinoma↗
PubMed1991

[Phase I clinical study of zinostatin stimalamer (YM 881) by intravenous injection].

A phase I clinical study by intravenous injection of zinostatin stimalamer (YM 881), a protein anti-cancer drug, was conducted in 50 patients with malignant tumors. The initial dose was 0.5 mg/m2 (n) in the single dose test, and 0.2 mg/m2/day in the repeated dose test for 5 successive days. Doses were increased up to 12n according to the modified Fibonacci's method in both the single and repeated dose tests. The dose limiting factor was thrombopenia in both the single and repeated dose tests. The maximum tolerated dose was 6.0 mg/m2 (12n) in the single dose test, and the subtoxic dose was 2.4 mg/m2/day in the five day repeated dose study. These results indicate that dose of 1.0 to 1.4 mg/m2/day (5 n to 7 n) are appropriate for the phase II repeated dose study.

Adult↗
PubMed1991

[Early phase II study of YM 881 (zinostatin stimalamer) by intravenous injection. Research group for intravenous YM 881].

An early phase II multicentered study of YM 881 (zinostatin stimalamer) was conducted in 36 patients to investigate response and the safety of the drug in malignant tumors. The response could be evaluated in 18 patients, one with brain tumor, 2 with lung cancer, one with breast cancer, one with liver cancer, one with pancreatic cancer, 6 with gastric cancer, and 6 with colon cancer. PR was found in the patient with brain tumor. Major subjective unwanted effects were gastrointestinal symptoms. Objective evidence of hematological changes (thrombocytopenia, decreased hematocrit, and lymphocytopenia) was also obtained.

Adult↗
PubMed1991

[Antitumor effects of a new antitumor agent, zinostatin stimalamer (YM881)--effects on experimental tumors in vitro and in vivo].

Zinostatin stimalamer (YM881) is an antitumor agent, chemically synthesized by coupling one molecule of neocarzinostatin (NCS), with 2 molecules of styrene maleic acid half-butylester copolymer. YM881 showed strong cytotoxicity to human (KB, ST4 and others) and mouse (P388, L1210) tumor cell lines and also drug-resistant tumor cell lines. The antitumor effects were observed in murine MM46, colon 26 and other tumor models. The antitumor activity was as effective as NCS or better than NCS at the effective dose ranges.

Animals↗
PubMed1991

[Action mechanisms of zinostatin stimalamer (YM881)].

The mechanism of action of zinostatin stimalamer (YM881) was studied. YM881 suppressed colony formation of HeLa cells dose-dependently, and showed cytocidal activity. The compound inhibited DNA synthesis, but neither RNA nor protein synthesis in L1210 cells, and caused cellular DNA strand breaks in HeLa cells and DNA cleavage of PM2 phage supercoiled DNA. YM881 was also shown to cause typical G2/M arrest on L1210 cell cycle, and inhibited DNA polymerase alpha of HeLa cells, but only at high concentrations. Present study showed that antitumor and cytotoxic mechanisms of YM881 were identical to neocarzinostatin (NCS) and due to the cellular DNA strand breaks caused by direct DNA-cleaving activity and the subsequent inhibition of DNA synthesis.

Animals↗
PubMed1991

[The merit of prescribed exercise using anaerobic threshold for myocardial infarction].

The merit of using anaerobic threshold (AT) for prescribed exercise was evaluated in 55 out-patients with old myocardial infarction (OMI) one to 3 months after the attacks. Comparisons of optimum exercise intensities using 2 methods; either heart rate at AT (ATHR) or heart rate by Karvonen's method (KHR), were conducted. Treadmill stress test was performed in all subjects. ATHR was determined by ramp protocol and KHR by Bruce's protocol. Items measured were AT, peak oxygen consumption (peak VO2), ATHR and KHR. The results were as follows: 1. Mean peak VO2 and AT in patients with OMI were 25.8 +/- 4.3 ml/min/kg and 16.5 +/- 2.1 ml/min/kg, respectively. Mean heart rates were 117.2 +/- 11.0 beats/min at AT and 121.9 +/- 13.0 beats/min by Karvonen's method, respectively. 2. A positive correlation (r = 0.85) was noted between AT and the peak VO2. 3. A positive correlation (r = 0.61) was also noted between the peak VO2 and ATHR. 4. Correlations of KHR with peak VO2 and with ATHR were insignificant. 5. There were 6 patients with ATHR > or = KHR and 15 with ATHR < KHR. There was no significant difference between their clinical backgrounds of 2 groups. It has been thought that with KHR, about 70% of the patients with OMI are overloaded due to excessive exercise intensity. We concluded that exercise training using AT is better and more useful in view of training efficiency and safety.

Anaerobic Threshold↗
PubMed1991

A new monoclonal antibody directed to sialyl alpha 2-3lactoneotetraosylceramide and its application for detection of human gastrointestinal neoplasms.

A new monoclonal antibody (NS24) directed to the N-acetylneuraminyl alpha 2-3Gal beta 1-4GlcNAc residue in type II sugar chain of N-acetylneuraminyllactoneotetraosylceramide [sialylparagloboside, IV3(NeuAc)nLc4Cer] was prepared by hybridoma technique. Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, IV3(NeuAc)nLc4Cer, and lipopolysaccharides from Salmonella minnesota R595 were used for immunization with IV3(NeuAc)nLc4Cer isolated from human erythrocytes. This method allowed the fusion of spleen cells of immunized mouse with myeloma cells only three days after immunization. NS24 reacted specifically to both naturally occurring and chemically synthesized IV3-(NeuAc)nLc4Cer, whereas it has no reactivity to structurally related gangliosides, such as IV6(NeuAc)nLc4Cer, N-glycolylneuraminyl alpha 2-3lactoneotetraosylceramide [IV3(NeuGc)-nLc4Cer], i-active ganglioside [VI3(NeuAc)nLc6Cer], I-active ganglioside [VIII3(NeuAc)-VI3(NeuAc)IV6kladoLc8Cer], GM4(NeuAc), GM3(NeuAc), GM3(NeuGc), GM1b(NeuAc), GD3-(NeuAc), other ganglio-series gangliosides, sulfatide, and paragloboside (nLc4Cer). Synthetic N-acetylneuraminyl alpha 2-3lactotetraosylceramide [IV3(NeuAc)Lc4Cer] and its asialo-derivative (Lc4Cer) carrying type I sugar chain also showed no reaction with NS24. One to 100 pmol of IV3(NeuAc)nLc4Cer was detected dose-dependently by a thin-layer chromatography/enzyme immunostaining procedure. Human gastric carcinomas showed positive reactions with NS24 immunochemically and histochemically. NS24 reacted preferentially with poorly differentiated adenocarcinomas rather than well differentiated ones.

Adenocarcinoma↗
PubMed1991

Construction of reshaped human antibodies with HIV-neutralizing activity.

Mouse monoclonal antibody (mAb) 0.5 beta binds to the envelope protein gp120 of human immunodeficiency virus (HIV) and neutralizes infection by HIV in vitro. Mouse mAb 0.5 beta, therefore, has potential as a therapeutic agent for the prevention and treatment of acquired immunodeficiency syndrome (AIDS). Since mouse mAbs are highly immunogenic in humans, efforts are being made to humanize mouse mAbs that are being considered for use in humans. This report describes the design, construction, and expression of reshaped human 0.5 beta antibodies. In these antibodies, the entire constant (C) regions were derived from human sequences. The variable (V) regions were derived from human framework regions (FRs) and mouse 0.5 beta complementarity determining regions (CDRs). One version of reshaped human 0.5 beta light (L) chain and six versions of reshaped human 0.5 beta heavy (H) chain were made and tested. Following transient expression in cos cells, all of the constructions were capable of producing humanlike antibody. Three of the H chain constructions (RHc, RHe, and RHf), when co-expressed with the L chain construction (RL), produced reshaped human antibody capable of binding to the epitope on gp120 recognized by mouse 0.5 beta mAb. The best version (RL + RHe) of reshaped human 0.5 beta antibody had both binding affinity and neutralizing activity that were within twofold that of the mouse or chimeric 0.5 beta antibody.

Amino Acid Sequence↗