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Biomedical subjects

M Nagai

Publications and source records attributed to M Nagai.

At least 343 records · Page 19Linked to original sources

[The prevalence of diabetes mellitus and impaired glucose tolerance studied by 75 gram oral glucose tolerance test in a rural island population].

A mass health examination was performed to assess the glucose tolerance of inhabitants of the island of Ojika, in the Goto islands, Nagasaki prefecture Japan. There were 554 males and 820 females older than 34 years who participated in the mass health examination, a response rates of 42 percent and 52 percent for males and females respectively. Serum glucose levels after overnight fasting and at 2 hours after a 75 gram oral glucose tolerance were used with WHO criteria to classify individuals. Among these subjects, the prevalence of diabetes mellitus increased with age, with a prevalence of diabetes mellitus of around 10 percent in the older subjects. The prevalence for males was higher than that for females. Prevalences of impaired glucose tolerance were roughly in the 15-25 percent range and did not show clear differences among different age groups and sexes. From a questionnaire survey of all island inhabitants, it was considered that the degree of bias of the results was small, if any. The true prevalence for all the inhabitants may be a little larger than the observed prevalence of these subjects.

Adult↗

[Analysis of factors influencing the recent decline in birth rate in Tokyo].

This study was undertaken in an attempt to find factors which affected the recent declining birth rate in Tokyo. Vital statistics of the female population, age 20-39, for the period of 1970 through 1985 for Tokyo were compared to national averages. Indices examined were birth rate, percentage of married women, birth rate for married women, and birth rate for married women by live birth order. Results thus obtained were as follows: 1. Birth rates for females aged 20-24 and 25-29 were largely dependent on percentages of married women rather than birth rates for married women both in Tokyo and in the nation as a whole, while the birth rates for females aged 30-34 and 35-39 were more dependent on birth rates for married women. 2. Percentages of married women aged 20-24 and 25-29 decreased during the observation period both in Tokyo and in the nation as a whole. 3. Birth rates for married women aged 30-34 and 35-39 dropped in the first 5 or 10 years of observation in both groups as a result of the reduction in high order live births. Thereafter, the decline changed to an upturn trend. 4. Yearly changes of birth rate, percentage of married women, birth rate for married women, birth rate for married women by live birth order, and birth rate of first child for married women appeared to have the same timing both in Tokyo and in Japan as a whole in each age category.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hypothermia enhances contractile responses of the guinea pig taenia caeci to acetylcholine, 5-hydroxytryptamine, caffeine and calcium.

Isometric contraction of isolated guinea-pig taenia caeci was induced with acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) at 37 and 30 degrees C to investigate the effect of hypothermia on the response of smooth muscle to neurotransmitters. Lowering the temperature increased the amplitude of contraction in response to 10(-6) M ACh. Contraction in response to 10(-6) M 5-HT was also greater at 30 degrees C. 5-HT-contraction was not inhibited by atropine, but was inhibited by ketanserin. Calcium-contraction was also induced in an isosmotic high potassium solution. The amplitude of the contraction elicited by 5 x 10(-3) M Ca was significantly greater at 30 degrees C, and was inhibited by verapamil. The amplitude of the contractile response to 5 x 10(-3) M caffeine was also greater at 30 degrees C than at 37 degrees C. The finding that both calcium- and caffeine-contraction were enhanced at low temperature raises the possibility that intracellular calcium participate in cold-induced enhancement of contraction.

Acetylcholine↗

The role of serotonergic system in body temperature regulation.

Results indicate that vascular responses to temperature stimulation are predominantly impaired in animals with 5-HT deprivation. A hypothesis is therefore raised that the 5-HT system participates in body temperature regulation in such a way as to link the regulatory output with vasomotor pathways. The 5-HT system in the spinal cord has been shown to inhibit the afferent transmission of temperature signals. Therefore, depletion of 5-HT does not prevent sensory transmission, at least at the spinal cord level.

5,7-Dihydroxytryptamine↗

An evaluation of serum microelement concentrations in lung cancer and matched non-cancer patients to determine the risk of developing lung cancer: a preliminary study.

In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer.

Adenocarcinoma↗

Selective up-regulation of type II inosine 5'-monophosphate dehydrogenase messenger RNA expression in human leukemias.

The discovery of isozymes (types I and II) of IMP dehydrogenase (IMPDH; EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, has attracted attention as a possible novel approach to cancer diagnosis and selective tumor cell chemotherapy. To elucidate differences in expression and regulation of the two IMPDH isozymes, we examined the steady-state levels of these mRNAs in various types of leukemic cells from patients. Northern blot analysis revealed that type II IMPDH was more active transcriptionally (1.5- to 5.1-fold) in all the leukemic cells examined than in normal lymphocytes, whereas type I expression was similar. The increased expression of type II mRNA in leukemic cells was closely linked with the increase in total IMPDH activity (r = 0.92). When leukemic cells from a patient with chronic granulocytic leukemia in blast crisis were separated into blast-rich and mature leukocyte-rich fractions, the expression of type II mRNA correlated positively with the population of immature leukemic cells, whereas type I expression was unchanged. Treatment of leukemic blasts with 12-O-tetradecanoyl-phorbol-13-acetate for 5 days resulted in a 90% decrease in the expression of type II mRNA with macrophage-like differentiation, while the expression of type I mRNA was relatively stable. These observations suggest that expression of type II IMPDH is stringently linked with immature characteristics of leukemic cells; thus, it should be a selective target for antileukemic chemotherapy.

Cell Differentiation↗

Unusual CO bonding geometry in abnormal subunits of hemoglobin M Boston and hemoglobin M Saskatoon.

To clarify the role of the proximal histidine (F8-His), distal His (E7-His), and E11 valine (E11-Val) in ligand binding of hemoglobin (Hb), we have investigated the resonance Raman (RR) spectra of the carbon monoxide adduct of Hbs M (COHb M) in which one of these residues was genetically replaced by another amino acid in either the alpha or beta subunit. In the fully reduced state, all Hbs M gave v3 at approximately 1472 cm-1 and vFe-His at 214-218 cm-1, indicating that they have a pentacoordinate heme and the heme iron is bound to either E7-His or F8-His. The porphyrin skeletal vibrations of the COHb M were essentially unaltered by replacements of E7- or F8-His with tyrosine (Tyr) and of E11-Val by glutamic acid (Glu). The vCO, vFe-CO, and delta Fe-C-O frequencies of COHb M Iwate (alpha F8-His----Tyr), COHb M Hyde Park (beta F8-His----Tyr), and COHb M Milwaukee (beta E11-Val----Glu) were nearly identical with those of COHb A. In contrast, the RR spectra of COHb M Boston (alpha E7-His----Tyr) and COHb M Saskatoon (beta E7-His----Tyr) gave two new Raman bands derived from the abnormal subunits, vFe-CO at 490 cm-1 and vCO at 1972 cm-1, in addition to those from the normal subunits at 505 cm-1 (vFe-CO) and 1952 cm-1 (vCO). The CO adduct of the abnormal subunits exhibited apparently no photodissociation upon illumination of CW laser with a stationary cell under which the normal subunit exhibited complete photodissociation.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

Expression of human IMP dehydrogenase types I and II in Escherichia coli and distribution in human normal lymphocytes and leukemic cell lines.

Two distinct cDNAs encoding proteins with 84% sequence identity have been isolated for human IMP dehydrogenase (EC 1.1.1.205) (Natsumeda, Y., Ohno, S., Kawasaki, H., Konno, Y., Weber, G., and Suzuki, K. (1990) J. Biol. Chem. 265, 5292-5295), an important target in antileukemic chemotherapy. We constructed expression plasmids containing these cDNAs in full length with pUC plasmids and produced lacZ'-IMP dehydrogenase fusion proteins in Escherichia coli. Both synthesized proteins exhibited IMP dehydrogenase activity and were partially separated from endogenous E. coli IMP dehydrogenase. By injecting the fusion proteins into mice we generated a polyclonal antibody specific to type I IMP dehydrogenase and an antibody which reacted with both types. Immunoblot analysis revealed that the total amounts of types I and II enzymes increased in human leukemic cell lines K562 and HL-60 in agreement with the increase in IMP dehydrogenase activity to 7.8- and 9.4-fold, respectively, above that of normal lymphocytes. The extent of expression of type I IMP dehydrogenase was similar in these cells, however, indicating that the increase in IMP dehydrogenase amount in leukemic cells was due to specific up-regulation of type II enzyme. Northern blot analysis also showed specific and predominant expression of type II in the leukemic cells. Thus, de novo GTP biosynthesis may be controlled differently in normal and neoplastic cells by different IMP dehydrogenase molecular species.

Cell Line↗

Inclusion complex of 8-anilinonaphthalene-1-sulfonate with beta-cyclodextrin.

The interaction of 8-anilinonaphthalene-1-sulfonate with beta-cyclodextrin was investigated in 0.1 M phosphate buffer at pH 7.4 by fluorescence spectrophotometry. Utilizing the fact that the fluorescence intensity of 8-anilinonaphthalene-1-sulfonate increases in the presence of beta-cyclodextrin, the thermodynamic parameters for the inclusion complex formation were determined as follows: delta G degrees = -2.52 kcal/mol at 25 degrees C, delta H degree = -1.92 kcal/mol, and delta S degree = 2.1 eu. The driving forces for the inclusion complex formation were considered to be van der Waals-London dispersion force and hydrophobic interaction. Also, from the measurements of 1H NMR spectra and from studying the Corey-Pauling-Koltun (CPK) model, the structure of the inclusion complex was discussed.

Anilino Naphthalenesulfonates↗

Protective effect of ACE- and kininase-inhibitor on the onset of cardiomyopathy.

Attempts at treating idiopathic cardiomyopathy have been made both clinically and experimentally using the cardiomyopathic Syrian hamster. In recent years, the angiotensin converting enzyme (ACE) inhibitor has attracted considerable attention as an agent to treat heart failure. We administered the ACE inhibitor captopril to the cardiomyopathic hamster. In this study, 15 mg/kg body weight of captopril was administered to the cardiomyopathic hamster J2N at 5 weeks of age for 10 weeks; age matched J2N hamsters were used as non-treated control animals. At the end of captopril administration, blood was collected from the ventral aorta. Serum malondialdehyde (MDA), serum CPK, aldolase and LDH were determined, and myosin isoenzyme patterns of the extirpated myocardium were compared. Additionally, ECGs were compared and the fibrotic ratio of both ventricles determined. Serum MDA, CPK, and aldolase increased significantly in the cardiomyopathic hamster, whereas these indices were significantly inhibited in the hamster treated with captopril. The pathological ECG findings and the ventricular V3 predominant myosin isoenzyme patterns of the J2N were also much improved in the captopril group. However, the improvement in these parameters by enalapril administration was less than that seen with captopril. These results suggested that the effect of captopril is not only due to decrease of the angiotensin II level, but also due to increase in tissue kinin and vasodilatory prostaglandin which play an important role in the beneficial effect of captopril.

Angiotensin II↗

Regulation of de novo and salvage pathways in chemotherapy.

An overview was presented of our approach of inhibition of de novo and salvage pathways in pyrimidine and purine metabolism. 1. Combination of acivicin, an inhibitor of de novo biosynthesis, and dipyridamole, a transport inhibitor, provided synergistic cytotoxicity in hepatoma and colon carcinoma cells. 2. AZT, a competitive inhibitor of the salvage enzyme, thymidine kinase, and 5-FU or MTX provided synergistic cytotoxicity in hepatoma 3924A. In human colon carcinoma HT-29 cells AZT and methotrexate yielded synergistic cytotoxicity and thymidine and hypoxanthine together provided protection from the action of these drugs. 3. These observations are significant because in rat hepatoma 3924A and in human cell lines HT-29, HL-60 and K562 thymidine kinase activity was 16- to 67-fold higher than that of dTMP synthase. Therefore, inhibition of dTMP synthase activity alone may provide poor responses because the salvage pathways can circumvent this block. 4. In leukemic patients treated with tiazofurin, an inhibitor of IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis, and with allopurinol, which inhibits GPRT activity through raising plasma hypoxanthine levels, synergistic therapeutic results were obtained. The responses in sensitive patients entailed a decrease in IMP dehydrogenase activity and GTP concentration in leukemic cells and down-regulation of the ras and myc oncogenes. The down-regulation of the ras oncogene by tiazofurin through the decrease of GTP concentration has now been shown in K562, HL-60 and hepatoma cells and in patients with chronic granulocytic leukemia in blast crisis. Tiazofurin may be useful in studies on selective depression of the expression of the ras oncogene. 5. In 27 consecutive patients 50% responded positively to tiazofurin treatment. From this group, 10 out of 12 patients (83%) with chronic granulocytic leukemia in blast crisis responded to tiazofurin treatment.

Antimetabolites, Antineoplastic↗

A characteristic change in infant mortality rate decrease in Japan.

Changes in infant mortality rate (IM) in Japan were observed over a 41-year period, since the end of the Second World War (1947-1987). Both neonatal mortality rate (NM) and infant mortality rate excluding neonatal deaths (IEN) were measured. It was observed that IM had considerably decreased during the observation period. A decrease of IEN contributed greatly to this fall till the 1960s and less so since the 1970s. The slope of the decrease of NM became steeper after entering the 1980s compared with that of IEN, and this contributed to the decrease of IM in this period. In order to analyse this phenomenon, detailed observations were made of the causes of death. On studying three of the major causes of infant deaths in Japan (congenital anomalies, birth trauma and perinatal asphyxia, and injuries and poisoning) it was found that there was only a small annual difference in the number of deaths due to congenital anomalies compared with the much greater difference seen with the other two causes; therefore, improvement of mortality rate by congenital anomalies seemed difficult because the efficacy of improvement of medical treatment and care are already approaching their limits. For a further reduction of IM in the future, improvement of perinatal care and prevention of injuries are considered to be essential.

Cause of Death↗

Myringoplasty in children.

Our 11 years of experience of myringoplasty in 87 children aged 3 to 14 years were retrospectively studied. The children were followed up over a period of 3 years. Children in the 3-to-12-year-old age group had a success rate of 57.7%. Graft-take rate was 100% in children operated on at the age of 13 and 14 years. Revision surgery was needed in 33 ears, and ultimate success was achieved in 88.9%. Within the same period, 38 ears were conservatively treated and 20 perforations of them were spontaneously closed. The state of the opposite ear and the perforation size were not a decisive factor in the results of myringoplasty. Children between 7 and 10 years old with small mastoid pneumatization had a statistically lower graft-take rate. We concluded that myringoplasty is warranted for children 13 years of age and older or children aged 7 to 12 years with large mastoid pneumatization.

Adolescent↗

A case-control study of stomach cancer and its genesis in relation to alcohol consumption, smoking, and familial cancer history.

A case-control study of stomach cancer and its genesis has been conducted in relation to alcohol consumption, cigarette smoking, and familial cancer history. Two hundred and ninety-four cancer cases, discovered by mass screening and histologically verified after endoscopic examination, have been compared with 588 randomly selected controls, who received the same early detection program and were verified as being free of the disease. No statistically significant association was observed between the development of stomach cancer and alcohol consumption or familial cancer history. However, the development of stomach cancer was found to have a positive correlation with smoking (relative risk for those who smoke less than 19 cigarettes/day, 3.56: 95% confidence interval, 2.39 to 5.31; relative risk for those who smoke more than 20 cigarettes/day, 2.58: 95% confidence interval, 1.60 to 4.17). The results of this study suggest that cigarette smoking appears to have a more harmful effect on the development of stomach cancer than either alcohol consumption or a familial history of cancer. The high relative risk of smoking revealed by this study implies that further research on the effects of smoking in the development of stomach cancer would be desirable.

Aged↗

[A case report of siblings with hemolytic uremic syndrome from whose stool E. coli O157:H7 was isolated].

We experienced siblings of hemolytic uremic syndrome which occurred following diarrhea and bloody stool. They were immediately treated with dipyridamole and aspirin, and recovered from hemolytic uremic syndrome in about two weeks. E. coli O157:H7 (verotoxin producing E. coli) which is recently thought to be related to the pathogenesis of hemolytic uremic syndrome was isolated in their stool cultures on admission. As far as we know, this is the first case in Japan from which stool E. coli O157:H7 was detected. Moreover, we reported clinical effectiveness of genomic investigation utilizing polymerase chain reaction method for verotoxin coding region in a rapid diagnosis of this bacterial infection.

Child, Preschool↗

[Saponins of anemarrhenae rhizoma].

Three steroidal saponins 3, 4 and 5a were newly isolated from Anemarrhenae Rhizoma. Compounds 3 and 4 were identical with desgalactotigonin and F-gitonin, respectively. Compound 5a was established as (25S)-26-O-beta-D-glucopyranosyl-22-hydroxy-5 beta-furostane-3 beta,26-diol 3-O-beta-D-glucopyranosyl-(1----2)-O-beta-D-galactopyranoside on the basis of chemical and spectroscopic evidence.

Drugs, Chinese Herbal↗