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Biomedical subjects

T Doi

Publications and source records attributed to T Doi.

At least 307 records · Page 17Linked to original sources

[Studies on development of evaluation method for wood-based floors. Part 1. Evaluating the attenuational capacity of human locomotor system due to the acceleration at several parts of the human body].

Experiments were conducted to compare the impact on several parts of the body caused by the striking of the heel during human gait. In these experiments, five kinds of wood flooring that have differing levels of light weight-impact sound insulating efficiency were used. The obtained results were as follows: 1) The generated acceleration of calcaneus varied with the difference of flooring. According to the regression analysis, the open polygonal relationship between bound back coefficient of floor and acceleration of calcaneus was determined. 2) The impact force given to the calcaneus propagated from the heel to the forehead after most of the force being absorbed at the ankle and the knee. We found direct correlation between the subjective feeling of floor pliabilty and the force to the leg. Therefore, it was suggested that the measurement of the force to the ankle and the knee was important in evaluating the efficiency of floors.

Acceleration↗

Tubotympanoplasty.

Prognostic value of the Eustachian tube function test remains controversial. To prevent ear drum adhesion or the recurrence of cholesteatoma it is important to select cases with severe organic obstruction of the Eustachian tube and to use surgical procedures to restore function. We summarize here the indications and the surgical procedure for organic obstruction of the Eustachian tube, especially in the region of the tympanic orifice. Adequate preoperative evaluation of Eustachian tube function and pertinent surgical procedures will pave the way for a better prognosis for patients subjected to ear surgery.

Adult↗

A possible masking effect of tinnitus. Evaluation of CNV audiometry.

To determine whether tinnitus has a masking effect similar to that of general external sounds, the hearing threshold shift when the tinnitus was changed by intravenous administration of lidocaine was measured by contingent negative variation (CNV) audiometry. In a preliminary study, the reliability of CNV audiometry was evaluated in 12 patients with tinnitus. The reproducibility of CNV audiometry was confirmed, based on repeated measurements of CNV audiometry at the tinnitus frequency. The threshold difference between CNV audiometry and pure tone audiometry was -0.76 +/- 1.35 dB, and a high statistical correlation between the threshold of CNV audiometry and pure tone audiometry was evident. The CNV threshold shift at tinnitus frequency after lidocaine injection was measured in 89 ears. In the tinnitus-decreased group, the CNV threshold decreased (4-6 dB) in 22% of cases; however, in the tinnitus-unchanged group, the CNV threshold was little changed. These findings suggest that tinnitus may have a masking effect as is the case with external sounds.

Audiometry, Evoked Response↗

Active opening function of the human eustachian tube: comparison between sonotubometry and pressure equilibration test.

Sonotubometry and pressure equilibration test are representative test methods to evaluate the active opening capacity of the Eustachian tube. We applied these tests to 72 ears with otitis media with effusion and 21 ears with chronic otitis media. In 73 ears, both tests showed identical results (11 ears with good active function and 62 ears with poor function). Twenty ears showed good active opening by sonotubometry despite inability to relieve applied negative pressure by swallowing. This inconsistency is believed to result from a too short duration of the tubal opening, by which sound is transmitted through the Eustachian tube, without pressure change in the middle ear cavity. We propose that sonotubometry is a suitable method of detecting impairment of the tubal active opening function, but that a good result by sonotubometry does not always indicate a satisfactory pressure equilibration capacity of the Eustachian tube.

Adult↗

Otitis media with effusion and eustachian tube dysfunction in adults and children.

Eustachian tube (ET) function was studied in 162 ears with otitis media with effusion (OME) and chronic otitis media (COM), using tubo-tympanoaerodynamic graphy, patency and pressure equilibration test in the inflation-deflation test. Severe impairment of active opening function was found in both OME children and adults compared with that of COM patients. This impairment in active opening was thought to result from functional obstruction of the ET in 71.8% of OME children and 51.8% of OME adults. However, 45.6% of OME adults had an organic obstruction while such was present only in 28.2% of OME children. We deduce from this study that impaired active opening function of the ET in both OME children and adults is the result of functional obstruction rather than organic obstruction, but organic obstruction is considered to be related to the pathogenesis of OME in adults.

Adolescent↗

Helminths of the Tsushima leopard cat (Felis bengalensis euptilura).

Three Tsushima leopard cats (Felis bengalensis euptilura) in Japan were collected as road kills. Three species of trematodes (Pharyngostomum cordatum, Paragonimus sp. and Dicrocoeliidae gn. sp.), one species of cestode (Spirometra erinacei) and nine species of nematodes (Arthrostoma hunanensis, Uncinaria felidis, Uncinaria sp., Ancylostoma tubaeforme, Molineus springsmithi, Toxocara cati, Capillaria aerophila, Capillaria felis-cati, and Capillaria sp.) were found. Among these helminths, Arthrostoma hunanensis, Uncinaria spp., and Molineus springsmithi have not been reported previously in Japanese domestic cats.

Animals↗

[Circulating immune complexes and anti-mite specific IgG antibody in status asthmatics--effects of methylprednisolone and analysis of an anti-complementary factor].

Serial changes of circulating immune complexes and anti-mite specific IgG antibody in the peripheral blood were measured eight times in six status asthmatics treated with high doses of methylprednisolone (MPS). Circulating immune complexes decreased to normal levels three hours after MPS administration. By contrast, anti-mite specific IgG antibody increased to beyond the normal range 14 days after MPS administration. Serum levels of IgE and allergen specific IgG4 antibody did not show any significant changes. In vitro experiments, circulating immune complexes in the sampled sera were decreased by an absorption test with anti-mite specific IgG antibody, and increased by reaction with an adequate volume of mite allergen. These facts indicate that circulating immune complexes are an anti-complementary factor working on the complement system, as previously reported, and that mite allergen and anti-mite IgG antibody relate to their conformation in status asthmatics. Clinically, MPS might possess an inhibitory effects on the formation of immune complexes and/or accelerate complement-dependent solubilization of antigen-antibody complexes, so that anti-mite specific IgG antibody increased markedly in the peripheral blood.

Adult↗

Seasonality of mean birth weight and mean gestational period in Japan.

Seasonal variations of mean birth weight from January 1974 to December 1983 and of mean gestational period from January 1979 to December 1983 in Japan are analyzed by time-series analysis. This analysis decomposes the variation in a series into trend, seasonal variation, other cyclic changes, and a remaining irregular fluctuation. The results of the present analysis support the existence of a seasonal rhythm of mean birth weight and mean gestational period in Japan with statistical significance (p < 0.001). Seasonal patterns of mean birth weight show two peaks in May and October-November and two troughs in June-September and December. Mean gestational periods shows two peaks in October and February-March and a deep trough in winter and a much smaller one in June-September. Two time series demonstrated a coincidence in monthly variations with statistical significance. These results indicate that a part of seasonality in birth weight could be explained by the seasonal variations in mean gestational period.

Age Factors↗

[Left ventricular function during hypoxia--II: Effects of intramyocardial pH].

We investigated the effects of intramyocardial acidosis on cardiac function during hypoxia in mongrel dogs (n = 50). Intramyocardial pH in subendocardium of left ventricle was measured continuously using a pH electrode. During hypoxia (PaO2 = 20 mmHg) caused by inhalation of low oxygen fraction, intramyocardial pH decreased significantly following initial enhancement. Intramyocardial pH correlated significantly with arterial pH, base excess, lactic acid (LA) levels, coronary venous PcO2, and coronary venous-arterial PcO2 difference. There were significant correlations between intramyocardial pH with maximum rate of rise of left ventricular pressure (LV dp/dt max), left ventricular end-diastolic pressure (LVEDP), LVEDP/LVP and the time constant of exponential isovolumic left ventricular pressure fall. High arterial LA levels tended to cease myocardial LA uptake and production, turning LA balance into zero. LV dp/dt max was low in such a condition. Myocardial LA production decreased intramyocardial pH, but LV dp/dt max was maintained at high levels of LA production. These observations suggest that myocardial LA production maintains left ventricular function with the increase of ATP by acceleration of anaerobic glycolysis. In conclusion, during hypoxia, intramyocardial acidosis was caused by the increase of arterial LA level, myocardial anaerobic glycolysis and ATP breakdown, and it worsened left ventricular contractile function and relaxation. Arterial LA levels can play a major part in intramyocardial acidosis, but the increase in myocardial LA production might be beneficial to left ventricular contractile function.

Animals↗

Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone. Studies in transgenic mice.

BACKGROUND: Mice transgenic for bovine growth hormone (bGH) gene have increased body weight and severe glomerulosclerosis leading to death in uremia. EXPERIMENTAL DESIGN: The aim of this study was to determine if body growth and glomerulosclerosis were mediated by different bGH regions. Amino acid substitutions in the bGH alpha-helix III were generated, and lines of transgenic mice that expressed these products were developed. Female transgenic mice carrying the native bGH gene (bGH mice), a mutated bGH gene that encodes a destabilized alpha-helix III (bGH-L121P, E126G; bGH-m11 mice), or a mutated bGH gene that encodes a perfect amphiphilic alpha-helix III (bGH-E117L, G119R, A122D; bGH-m8 mice) were examined at 2-3 months and 6-9 months of age. Body, kidney, and heart weights were measured. Urinary glucose, albumin, creatinine, and serum glucose were measured in all mice. Serum levels of insulin-like growth factor I (IGF-I) were measured in the 2-3 month group. Whole blood hemoglobin A1 was measured in some mice of the 6-9 month group. Kidney sections were examined by light and immunofluorescence microscopy. Glomerular volume was measured and related to body weight by allometry. RESULTS: The bGH-m11 mice developed glomerulosclerosis indistinguishable from that seen in bGH transgenic mice, even though they had normal body size. Glomerular growth exceeded body growth by allometry in both bGH and bGH-m11 strains. bGH-m8 mice had glomeruli of appropriate size and normal histologic appearance; however, they were dwarfs. IGF-I was increased in bGH mice; they also had an increased albumin/creatinine ratio at 6-9 months. None of the mice were hyperglycemic. CONCLUSIONS: These data indicated that development of glomerulosclerosis and body growth promotion were mediated by different regions of the growth hormone molecule. The glomerular response to bGH was unique and consisted of increased size and glomerulosclerosis.

Animals↗

Natural course of chronic hepatitis C.

We studied 333 chronic hepatitis C patients to evaluate the natural course of this disease. Among 57 patients undergoing serial biopsies, 20 had chronic persistent hepatitis (CPH) at the first biopsy, and 10 of them progressed to chronic active hepatitis (CAH) or liver cirrhosis (LC) after 11 yr. Sixteen patients had CAH 2A, and this progressed to CAH 2B or LC in 10 cases over 9 yr. Among the 21 patients with CAH 2B, progression to LC was noted in 15 after 7 yr. Among the 100 patients observed for over 5 yr, the normalization of liver function for at least 3 yr was seen in only four patients. In two of these four patients, serum HCV-RNA was tested serially. Despite the sustained normalization of alanine aminotransferase levels, HCV-RNA continued to be detectable in one patient. We conclude that many patients with chronic hepatitis C eventually show progression of their disease after a long and symptomless course.

Adolescent↗

[A case of pulmonary tuberculosis complicated with drug toxicosis--value of shosaikoto and hochuekito as anti-allergic agents].

A clinical course of pulmonary tuberculosis was reported about adverse reaction of anti-tuberculous chemotherapy. A fifty-eight-year-old male patient was complicated with agranulocytosis induced by RFP, hepatic dysfunction and systemic eruption induced by INH, and high fever induced by SM. Adjuvant therapy with Shosaikoto and Hocheukito suppressed INH induced hepato-dermatological toxicosis moderately and suppressed SM induced high fever completely. By these anti-allergic therapy, combined chemotherapy with SM, EB, PAS and PZA became possible during more than six months, and chemotherapeutic effect was marked. This case report suggested possibility and significance of those Kampo agents against serious allergic reaction complicated with the chemotherapy for pulmonary tuberculosis.

Antibiotics, Antitubercular↗

A new method using computed tomographic scan to measure the rectus femoris-patellar tendon Q-angle comparison with conventional method.

The Q-angle should be the angle generated by a line connecting the anteroinferior iliac spine (AIIS), the bottom of the groove of the femoral condyle, and the tibial tubercle. The Q-angle was measured by computed tomography (CT) in 43 lower limbs with recurrent patellar dislocation and 26 normal controls. The mean Q-angle was 20 degrees in the dislocated group and 13 degrees in controls, a significant difference. No significant difference was found in the Q-angle between the dislocated and control groups using the conventional method. Lower limb rotation had little effect on accuracy of the method.

Adolescent↗

[Left ventricular function during hypoxia. 1: Effect of blood glucose level].

We investigated the effects of blood glucose levels and myocardial glucose uptake on cardiac function during hypoxia in mongrel dogs (N = 50). During hypoxia (PaO2 = 20 mmHg) caused by inhalation of low concentration of oxygen for 2 hours, left ventricular (LV) function including LV pressure, maximum rate of rise of LV pressure, and cardiac index decreased significantly following initial enhancement. There were significant correlations between these hemodynamic parameters and blood glucose levels. The blood glucose levels correlated significantly with myocardial glucose uptake and blood lactic acid levels (r = 0.660: P = 0.000, r = 0.380: P = 0.000, respectively). Eight of nine dogs which died within 90 minutes during hypoxia showed low blood glucose levels and high lactic acid levels. During hypoxia, myocardial glucose uptake increased to more than five times of control value. On the other hand myocardial lactic acid uptake decreased and turned to production. At the same degree of blood lactic acid levels, LV function was maintained better with high blood glucose levels than with low levels. With low blood glucose levels, myocardial lactic acid uptake and production tended to cease. The pronounced change in LV function during hypoxia could be partially explained by decreased production of ATP due to decrease in myocardial glucose uptake and high lactic acid levels. It seems that high blood glucose levels are preferable to maintain cardiac performance under such a condition.

Animals↗

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↗

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↗

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↗

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↗