Biomedical subjects

T Doi

Publications and source records attributed to T Doi.

At least 19 recordsLinked to original sources

PubMed1992

Comparison of coronary responses to intracoronary and intraaortic ergonovine and isosorbide dinitrate in patients with atypical chest pain.

Fifty patients with atypical chest pain were studied to compare coronary responses to intracoronary and intraaortic ergonovine. The diameters of the proximal, middle (1) and (2) (proximal segments of segments 2 and 3 [AHA classification], respectively), and distal segments of the right coronary artery were measured before and after intracoronary ergonovine (4 micrograms/minute over 4 minutes) and isosorbide dinitrate (ISDN) (2 mg) in 24 patients, and before and after intraaortic ergonovine (0.2 mg) and ISDN (5 mg) in 26. Mean vasoconstriction by intracoronary and intraaortic ergonovine were 13 +/- 1.5% and 9 +/- 0.8%, respectively (p < 0.02). Irrespective of the methods of administration, the responses to ergonovine were similar in the 4 segments. Mean vasodilation by intracoronary and intraaortic ISDN, which were used to quantify the degree of basal coronary tone, were 25 +/- 2.2% and 27 +/- 1.5%, respectively (p = not significant [NS]). There were significant negative linear correlations between the responses to ergonovine and ISDN in the middle (2) (r = -0.51; p < 0.05) and distal (r = -0.53; p < 0.01) segments in patients with intracoronary injection, and the proximal (r = -0.41; p < 0.05), middle (1) (r = -0.66; p < 0.01) and middle (2) (r = -0.69; p < 0.01) segments in patients with intraaortic injection. These observations indicate that low-dose administration of intracoronary ergonovine produces sufficient coronary vasoconstriction, similar to or slightly greater than that of intraaortic ergonovine in patients with atypical chest pain, but basal coronary tone may influence the vasoreactivity to ergonovine.

Aorta↗

PubMed1992

Role of the basic amino acid cluster and Glu-23 in pyrimidine dimer glycosylase activity of T4 endonuclease V.

T4 endonuclease V [endodeoxyribonuclease (pyrimidine dimer); deoxyribonuclease (pyrimidine dimer), EC 3.1.25.1] initiates repair of damaged DNA by hydrolysis of the N-glycosyl bond at the 5' side of a pyrimidine photodimer in double-stranded DNA. To study one of the active sites of T4 endonuclease V, systematic site-directed mutagenesis was performed on the synthetic T4 endonuclease V gene, in parallel with three-dimensional structure analysis by x-ray crystallography. The mutant proteins were evaluated for DNA glycosylase activity using an oligonucleotide duplex (14-mer) containing a single thymidine dimer as a substrate. Replacement of either Glu-23 with glutamine or asparatic acid or Arg-3 with glutamine completely abolished DNA glycosylase activity. Mutation of Arg-3 to lysine or of Arg-26 to glutamine or lysine in a basic amino acid cluster caused serious defects in DNA glycosylase activity, which are reflected in the increases in Km and decreases in kcat of DNA glycosylase activity. On the other hand, substitutions of lysine for Arg-22 or of glutamine for Arg-117 or Lys-121 resulted in increases in the Km value. The completely inactive mutant proteins, E23Q and R3Q, in which glutamine was substituted for Glu-23 and Arg-3, respectively, were further investigated by CD spectroscopy for their ability to bind the oligonucleotide substrate. It was found that the E23Q protein retained specific substrate-binding ability, whereas the R3Q protein did not. These results indicate that Glu-23 plays an important role in catalysis of the DNA glycosylase reaction, and that Arg-3 is a crucial residue for substrate binding. In addition, Arg-22, Arg-26, Arg-117, and Lys-121 in the basic amino acid cluster also participate in substrate binding. We conclude that the basic amino acid cluster in T4 endonuclease V is an essential structure for DNA glycosylase activity.

Amino Acid Sequence↗

PubMed1992

Participation of glutamic acid 23 of T4 endonuclease V in the beta-elimination reaction of an abasic site in a synthetic duplex DNA.

T4 endonuclease V catalyzes the hydrolysis of the glycosyl bond of a thymine dimer in a DNA duplex and the cleavage of the 3'-phosphate by beta-elimination. We have previously identified a catalytic site for the first reaction (pyrimidine dimer-glycosylase activity) by systematic mutagenesis (Doi et al. Proc. Natl. Acad. Sci. USA 1992 in press) and by x-ray crystallography (Morikawa et al. Science, 256: 523-526, 1992). The results showed that replacement of Glu23 with either glutamine or aspartic acid completely abolished the glycosylase activity. We describe the investigation of the second reaction (apurinic/apyrimidinic endonuclease activity), using twenty two mutants of T4 endonuclease V plus a DNA mini duplex containing an abasic site. Replacement of Glu23 by glutamine abolished the second reaction, but replacement with aspartic acid did not. The pH optima of the mutant (23 Asp) and the wild type were found to be 5.0 and 5.5, respectively. We conclude that the carboxylate anion in position 23 may act as a general base in the beta-elimination reaction of the endonuclease.

Amino Acid Sequence↗

PubMed1992

X-ray structure of T4 endonuclease V: an excision repair enzyme specific for a pyrimidine dimer.

The x-ray structure of T4 endonuclease V, an enzyme responsible for the first step of a pyrimidine-dimer-specific excision-repair pathway, was determined at a 1.6-angstrom resolution. The enzyme consists of a single compact domain classified into an all-alpha structure. This single domain has two distinct catalytic activities; it functions as a pyrimidine dimer glycosylase and as an apurinic-apyrimidinic endonuclease. The amino-terminal segment penetrates between two major helices and prevents their direct contact. The refined structure suggests the residues involved in the substrate binding and the catalysis of the glycosylation reaction.

Amino Acid Sequence↗

PubMed1992

Receptor-specific increase in extracellular matrix production in mouse mesangial cells by advanced glycosylation end products is mediated via platelet-derived growth factor.

Renal disease is one of the most common and severe complications of diabetes mellitus. The hallmark of the disease, glomerulosclerosis, is characterized by an accumulation of extracellular matrix in the mesangial areas, leading to progressive obliteration of the vascular spaces. The role of the metabolic derangements of diabetes mellitus in the development of these lesions is incompletely understood. One of the consequences of hyperglycemia is the formation of advanced glycosylation end products (AGEs), which result from a series of rearrangements secondary to nonenzymatic reaction of glucose with proteins. Specific receptors for proteins modified by AGEs, present in several cell types, were recently described in human and rat mesangial cells. Furthermore, exposure of mesangial cells to AGEs was followed by an increase in fibronectin production. In the present study we show evidence that mouse mesangial cells exhibit an increase in collagen type IV mRNA and peptide synthesis after exposure to AGEs. Antibodies to AGE receptors prevent this increase, indicating that the response is AGE-receptor-mediated. In addition, anti-platelet-derived growth factor abrogates the AGE response, suggesting that platelet-derived growth factor acts as an intermediate factor. Transcription assay reveals that the elevated mRNA levels are due to an increase in the transcription rate, rather than to an increase in the stability of the message. Finally, the mRNAs coding for laminin and heparan sulfate proteoglycan are also increased after exposure to AGE, whereas glyceraldehyde 3-phosphate dehydrogenase mRNA levels remain constant. The increase in extracellular matrix mRNAs seen in the current study suggests that AGE formation in vivo may be one of the metabolic events leading to the development of diabetic glomerulosclerosis.

Animals↗

PubMed1992

Hepatitis type C virus infection in patients with type B chronic liver disease.

Anti-c100-3 (Ortho) was determined in the sera of 152 patients with HBs antigen-positive chronic liver diseases to assess coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Eleven patients (7.2%) were positive for anti-c100-3. Anti-CP-9 (Okamoto) and HCV-RNA (RT-PCR) were also examined in these 11 patients. Anti-CP-9 was detected in 7 patients and HCV-RNA was detected in all 11 patients. Four of the 11 anti-c100-3-positive patients were positive for HBe antigen (HBeAg) and others were negative. In 8 of the 11 patients, HCV was suspected to be superinfected by blood transfusion. In HBeAg-positive patients, serum glutamic pyruvic transaminase (SGPT) was elevated in relation to active replication of HBV shown by DNA-polymerase activity. The histological findings showed chronic active hepatitis, with or without cirrhosis. On the other hand, in HBeAg-negative patients, SGPT fluctuated without evidence of active replication of HBV. Active inflammation in the liver was observed in 3 of 5 HBeAg-negative patients by liver biopsy. These findings suggest that HBV might play an important role in chronic active inflammation in HBeAg-positive patients coinfected with HCV, and that HCV might be responsible for continuous inflammation in HBeAg-negative patients coinfected with HCV.

Adult↗

PubMed1992

Acceleration of tail pinch-induced feeding in rats by analgesic effect of neurotropin.

Mechanisms of tail pinch-induced feeding and effects of neurotropin (NSP), an extract from the inflamed skin of rabbit inoculated with vaccinia virus, on behavioral responses were investigated in rats. Treatment of a 5-min tail pinch (tail pinch I) induced feeding response. An intensified 15-min tail pinch (tail pinch II) provoked emotional reactions besides feeding behavior. The rate of food intake (food intake/tail pinch duration) during tail pinch II was less than that at tail pinch I. Intraperitoneal administration of NSP (100 mg/kg/day) by itself produced no remarkable change in feeding or emotional behavior. However, NSP-treated rats increased eating size and prolonged eating duration during tail pinch I. Pretreatment of NSP increased feeding behavior more potently at tail pinch II than at tail pinch I and decreased the incidence of emotional reactions at tail pinch II. The results suggest that NSP, by its analgesic action, may modulate behavioral responses during tail pinch treatment through selective blockade of the nociceptive and feeding-inhibitory information, but not through the nonnociceptive and feeding-excitatory signals.

Analgesics↗

PubMed1992

Osteochondritis dissecans of the humeral head.

A rare case of osteochondritis dissecans (OCD) occurring in the humeral head is presented. As there are only six available records in the literature concerning OCD in the humeral head, clinical features, treatment, and etiology of OCD involvement of this anatomical part remains unclear. These points are discussed on the basis of the previous cases and ours. Osteochondritis dissecans of the humeral head commonly affects middle-aged and young males rather than females. The prevalent location of involvement is the anterosuperior aspect of the humeral head. We propose that repetitive microtrauma is one of the important causes of OCD in the humeral head. Moreover, we suggest that the most authentic treatment for OCD with a partial detached osteochondral fragment is removal of this fragment and drilling.

Arthroscopy↗

PubMed1992

Development of nitrate tolerance and usefulness of pulse therapy in a patient with vasospastic angina.

In a 58-year-old man with vasospastic angina, we investigated the relationship between the antianginal effects of isosorbide dinitrate (ISDN) and plasma ISDN concentration. Despite adequate plasma ISDN levels, sustained therapy using ISDN tapes and oral ISDN (transcutaneously 160 mg and orally 100 mg ISDN day-1) failed to exhibit antianginal effects. However, pulse therapy using sublingual short-acting ISDN prevented anginal episodes, although the plasma ISDN levels were less than those of sustained therapy. Nitrate tolerance of the antianginal effects was avoided by creating an abrupt plasma ISDN concentration gradient using sublingual ISDN.

Administration, Oral↗

PubMed1992

Nucleotide sequences of membrane-bound hydrogenase gene in Alcaligenes hydrogenophilus.

The nucleotide sequences of membrane-bound hydrogenase small (hupS) and large (hupL) subunit genes of hydrogen bacterium Alcaligenes hydrogenophilus were determined. The hupS and hupL genes encoded polypeptides of 363 and 619 amino acids, respectively. The hupS was located upstream of hupL with 35bp of intergenic region. The consensus ribosome-binding sequences were identified upstream of the start codons of hupS and hupL. Amino acid sequence of hupS is very similar to that of Rhodobacter capsulatus, Bradyrhizobium japonicum, and Azotobacter vinelandii at amino acid levels of 82%, 77%, and 81%, respectively. Similarly, amino acid sequence of HupL is similar to that of R. capsulatus, B. japonicum, and A. vinelandii at amino acid levels of 63%, 65%, and 68%, respectively. Northern hybridization analysis showed that hupS and hupL were co-transcribed, and addition of fructose to the culture medium remarkably decreased the amount of mRNA transcribed from hupS and hupL.

Alcaligenes↗

PubMed1992

[Seasonal variation of mean birth weight in Okinawa].

Seasonal variation of mean birth weight in Okinawa was examined by a traditional time-series analysis, which decomposed the variation in a series into trends, seasonal variations, other cyclic changes, and remaining irregular fluctuations, based on the data in Vital Statistics from January 1974 to December 1983. The seasonal index of mean birth weight showed a peak in winter to early spring and a bottom in summer with statistical significance. Previous reports have revealed that the gestational period is the most important factor associated with birth weight. Therefore, we carried out the time series analysis for the mean gestational period but could not observe seasonal periodicity in it. On the other hand, mean birth weight at 40 gestational weeks was significantly lower in summer. These results suggest that factors other than the gestational period, such as infectious diseases, nutritional conditions and so on, might play important role in seasonal variations of mean birth weight in Okinawa.

Birth Weight↗

PubMed1992

[Seasonal variation of mean birth weight and births in Nagano Prefecture].

Seasonal variation of mean birth weight in Nagano Prefecture was examined by a traditional time series analysis, which decomposes the variation in a series into trend, seasonal variation, other cyclic changes, and remaining irregular fluctuations, based on the data in Vital Statistics from January 1974 to December 1983. The seasonal index of mean birth weight showed a unimodal pattern with a peak in June for males, and a bimodal pattern with peaks in spring and autumn in females with statistical significance. Previous reports have revealed that gestational period is the most important factor associated with birth weight. Therefore, we carried out time series analysis for the mean gestational period and observed an apparent seasonal periodicity, which showed a unimodal pattern with a bottom in winter for both sexes and parities. According to the results of statistical testing of the degree of coincidence between two time series, the time series of mean birth weight and that of mean gestational periods showed statistically significant coincidences in their monthly variations for multiparae. On the other hand, mean birth weight at 40 gestational weeks, which reflects the intrauterine growth, did not show seasonality. These results suggest that seasonality in gestational periods might play an important role in creating seasonal variations of mean birth weight in Nagano Prefecture. The average daily number of births by month also showed apparent seasonalities both for primiparae and multiparae. Primiparae showed a bimodal pattern with peaks in February and August, while multiparae showed a unimodal pattern with a peak in May and a bottom in November. It has been said that the seasonality in marriage is one of important factors associated with seasonal variation in births.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Rate↗

PubMed1992

Ehlers-Danlos syndrome with soft-tissue contractures.

We report four patients with a form of Ehlers-Danlos syndrome associated with soft-tissue contractures from birth and skin hyperalgesia. In early infancy, these cases were thought to be forms of arthrogryposis multiplex congenita, Larsen's syndrome or Marfan's syndrome. The characteristic triad of signs of Ehlers-Danlos disease gradually appeared from four to six years of age, allowing us to establish the correct diagnosis. We discuss the differential diagnosis of these connective-tissue disorders and the problems of the orthopaedic treatment of the associated joint deformities. Ehlers-Danlos syndrome is a heterogeneous group of metabolic diseases of collagen and our cases constitute a group which is distinct from the conventional types.

Adult↗

PubMed1992

Hepatitis C virus antibody titration in patients with chronic hepatitis C, before and after interferon treatment.

We measured hepatitis C virus antibody titers in 13 patients with chronic hepatitis C to determine whether titration of hepatitis C virus antibody was useful or not, to predict and evaluate the efficacy of interferon (IFN) treatment. During administration of IFN, hepatitis C virus titers declined in all patients. Antibody titers performed before treatment as well as just at the end of treatment did not correlate with change of the alanine aminotransferase levels during administration of IFN. Antibody titers declined continuously after treatment in 5 patients with normal alanine amino-transferase levels for over 6 months after discontinuation of IFN. Antibody titers rose again in 6 patients whose alanine aminotransferase levels fluctuated after treatment. An exceptional pattern of change occurred in 2 patients whose antibody titers declined continuously although their alanine aminotransferase levels fluctuated after treatment. Repeated titration of hepatitis C virus antibody appears to be useful for evaluating the long-term efficacy of IFN treatment.

Adult↗

PubMed1992

[Physiological evaluation of clothing made of new material for protection against the solar heat load].

The purpose of this study was to evaluate the effects of clothing made of a new material that is, the polyester staple containing the ceramics and to reflect the solar heat load on physiological responses during rest, exercise (50% VO2max) and recovery on a cycle ergometer. Six young female subjects exposed their back to an artificial solar heat load of an intensity of 680 kcal/m2/h with an air temperature of 30 degrees C. The data were compared to those obtained by wearing clothing made of cotton material. The results were as follows. The cardiac output and oxygen consumption obtained at the end of recovery were increased by solar heat load when the subjects wore cotton material. However, these values showed no significant increase when the subjects wore solar heat reflecting clothing. Furthermore, the cardiac output at the end of submaximal work and recovery were higher for the cotton material compared to the heat reflecting clothing in the solar heat load. The increase of cardiac output for the cotton material may show the increase of skin blood flow for the body heat dissipation. Those results suggest that the solar heat reflecting clothing may decrease the physiological strain like a blood redistribution for the body heat dissipation during exercise in summer sunlight.

Adult↗

PubMed1992

Appropriate conditions for the plaque forming cell (PFC) assay in rats and effects of cyclophosphamide on PFC response.

The appropriate conditions for the plaque forming cell (PFC) assay using rat splenocytes were determined and effects of cyclophosphamide on PFC response were investigated using these conditions. The number of PFCs produced by immunization with a suspension of sheep red blood cells (SRBCs) was higher with i.v. injection than with i.p. injection. Subcutaneous injection of the suspension did not produce PFCs. The highest PFC response was observed when the number of PFCs was determined 4 days after i.v. immunization with 0.5 ml of a 1% SRBC suspension. Cyclophosphamide (3, 10, 30, 100 and 300 mg/kg, p.o.) dose-dependently decreased PFC response under the above-mentioned optimal conditions, and decreased PFC responses were noted even at the very low dose of 3 mg/kg: a dose at which a decrease in the number of PFCs has not been reported in studies using mice. From these results, the appropriate conditions for the PFC assay in rats are considered to be i.v. immunization with 0.5 ml of a 1% SRBC suspension and determination of the number of PFCs 4 days after immunization. Furthermore, it is considered that the PFC assay using rats might be more sensitive to immunosuppressive agents than that using mice.

Age Factors↗

PubMed1992

Four cases with intrafamilial clustering of hepatitis C virus infection.

Four hepatitis C patients with intrafamilial clustering of hepatitis C virus (HCV) infection are reported. Antibodies to C100-3 antigen, capsid protein of HCV and GOR epitope were tested to detect histories of HCV infection. Transmission of HCV from mother to children, from father to children, and from wife to husband was implicated. Of all family members studied, three were positive for all antibodies, one for only antibody to capsid protein, two for antibodies to capsid protein and GOR epitope but negative for antibody to C100-3 antigen and one vice versa.

Adult↗

PubMed1992

Relation between serum uric acid and angiographically defined coronary artery disease in postmenopausal women.

Serum uric acid (UA) levels were studied in 40 postmenopausal women and 57 men, almost matched for age and body mass index (BMI) and undergoing coronary angiography. For women, the mean value of UA increased as the number of coronary arteries with > or = 50% stenosis increased. Its value was significantly higher (p < 0.05) in a three-vessel disease group than that of a group without stenosis. No significant changes were seen in men. However, the increase in UA for postmenopausal women was statistically (p < 0.05) correlated with serum triglyceride levels. Possibly, UA is not an independent coronary risk factor. However, elevated UA levels may suggest the prevalence of severe coronary artery stenosis for postmenopausal women.

Aged↗