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Biomedical subjects

M Higuchi

Publications and source records attributed to M Higuchi.

At least 289 records · Page 16Linked to original sources
PubMed1989

Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis.

Hemophilia A is an X-linked bleeding disorder caused by a deficiency or abnormality of factor VIII, affecting approximately 1 male in 10,000. A subgroup of the patients develops inhibitors against factor VIII during substitution therapy. Because a considerable percentage of all cases is thought to result from de novo mutations, it is likely that many different molecular lesions lead to hemophilia A. In order to understand the molecular basis of this disorder, we examined 160 patients with different clinical features using factor VIII gene probes. We could identify six different deletions and seven nonsense mutations within the factor VIII gene. Family analysis revealed that five of these mutations occurred de novo within two generations; two of them arose in the maternal grandfather and three in the mother. In one of these mothers we could identify a mitotic origin. Mapping of the deletions showed no deletion-prone region within the gene. Furthermore, we could not find any correlation between the particular gene defects and "inhibitor" phenotypes.

Base Sequence↗
PubMed1989

Fibrinogenolysis in thrombotic thrombocytopenic purpura.

Coagulo-fibrinolytic factors were studied in five patients suffering from thrombotic thrombocytopenic purpura (TTP). The change in coagulation factors in the acute stage was mild compared with that found in disseminated intravascular coagulation (DIC). We observed a slight increase of fibrin-fibrinogen degradation products (FDP) in the plasma of four patients during the acute stage of TTP, but the level of the D-dimer remained within normal variation and was extremely low compared with that in 27 samples from patients with DIC showing the same level of FDP. At the same time, both antigen levels of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in three of the four patients tested. Although a similar change was recognized in DIC patients' plasma, the elevation of PAI-1 in the acute stage of TTP was far higher than in overt DIC. The antigen levels of t-PA and PAI-1 were normal in remission, and a mild elevation of PAI-1 was detected in one of the three patients during the early stage of TTP relapse. Enzymography revealed the appearance of free t-PA and an increase of a substance with a 110 kD molecule, assumed to be a t-PA and PAI-1 complex, in TTP plasma in the acute stage, but the findings were normal for plasma from cases in remission and the early stage of relapse. Enzymography also showed a decrease of urokinase-type plasminogen activator (u-PA) only in the acute stage of TTP. These changes in the coagulo-fibrinolytic factors in the acute stage of TTP suggest that fibrinogenolysis might be induced by t-PA, released through vascular reaction at an uninvolved area of vascular lesions caused by platelet agglutinates, which would then release large amounts of PAI-1 inhibiting t-PA and u-PA activities at the occlusive lesion.

Adolescent↗
PubMed1989

Cardiovascular changes associated with decreased aerobic capacity and aging in long-distance runners.

Fifty-five male runners aged between 30 to 80 years were examined to determine the relative roles of various cardiovascular parameters which may account for the decrease in maximal oxygen uptake (VO2max) with aging. All subjects had similar body fat composition and trained for a similar mileage each week. The parameters tested were VO2max, maximal heart rate (HRmax), cardiac output (Q), and arteriovenous difference in oxygen concentration (Ca-Cv)O2 during graded, maximal treadmill running. Average body fat and training mileage were roughly 12% and 50 km.week-1, respectively. The average 10-km run-time slowed significantly by 6.0%.decade-1 [( 10-km run-time (min) = 0.323 x age (years) + 24.4] (n = 49, r = 0.692, p less than 0.001]. A strong correlation was found between age and VO2max [( VO2max (ml.kg-1.min-1) = -0.439 x age + 76.5] (n = 55, r = -0.768, p less than 0.001]. Thus, VO2max decreased by 6.9%.decade-1 along with reductions of HRmax (3.2%.decade-1, p less than 0.001) and Q (5.8%.decade-1, p less than 0.001), while no significant change with age was observed in estimated (Ca-Cv)O2. It was concluded that the decline of VO2max with aging in runners was mainly explained by the central factors (represented by the decline of HR and Q in this study), rather than by the peripheral factor (represented by (Ca-Cv)O2).

Adult↗
PubMed1989

Cytofluorometric study on lectin binding of isolated guinea pig keratinocytes.

Lectin binding was cytofluorometrically measured on fractionated keratinocytes of guinea pig. Free keratinocytes were obtained by treatment of EDTA and trypsin. After the treatment, they were separated into 3 fractions by centrifugation on a continuous colloidal silica (Percoll) density gradient. Cells in each fraction were stained by biotinyl lectins and avidin-FITC, and fluorescence intensity was measured by cytofluorometry. Results obtained indicate that little cell surface glycoconjugate is lost during the preparation of free keratinocytes.

Animals↗
PubMed1989

Direct characterization of factor VIII in plasma: detection of a mutation altering a thrombin cleavage site (arginine-372----histidine).

An immunoadsorbent method has been developed for the direct analysis of normal and variant plasma factor VIII. Using this method, the molecular defect responsible for mild hemophilia A has been identified for a patient whose plasma factor VIII activity is 0.05 unit/ml, even though the factor VIII antigen content is 3.25 units/ml. Although the variant factor VIII has an apparently normal molecular mass and chain composition, the 92-kDa heavy chain accumulates when the variant protein is incubated with thrombin and the 44-kDa heavy chain fragment cannot be detected. In contrast, thrombin cleavage of the 80-kDa light chain to the 72-kDa fragment is normal. As these data indicate a loss of factor VIII cleavage by thrombin at arginine-372, the genetic defect was determined by polymerase-chain-reaction amplification of exon 8 of the factor VIII gene and direct sequencing of the amplified product. A single-base substitution (guanine----adenine) was identified that produces an arginine to histidine substitution at amino acid residue 372. These data identify the molecular basis of an abnormal factor VIII, "factor VIII-Kumamoto," that lacks procoagulant function because of impaired thrombin activation.

Arginine↗
PubMed1989

In vivo binding of the winged bean basic lectin labeled with iodo[2-14C]acetic acid to the intestinal epithelial cells of the rat.

Winged bean basic lectin was labeled with iodo[2-14C]acetic acid. The radiolabeling affected neither the antigenicity nor the hemagglutinating activity of the lectin. A liquid test meal consisting of [14C]lectin and an unabsorbable marker, [3H]polyethylene glycol (PEG), was administered to rats in order to investigate behavior of the lectin in the gastrointestinal tract. At 1 h after administration, 54% of the administered [14C]lectin was still in the stomach, 1% had reached the cecum, and 1-6% was found in the intestinal mucosa, indicating that the lectin was binding to the mucosa. In another experiment, rats were fed a commercial nonpurified diet for 3 d after administration of the test meal. About 87% of the administered lectin as well as 83% of [3H]PEG was recovered from the feces during these 3d. Lectin bound to the epithelial cells of the intestinal mucosa was recovered by liberating it from the cells with D-galactose. The recovered lectin showed both hemagglutinating activity and the antigenicity identical with those of the original lectin. These results clearly indicated that the lectin remained intact in the gastrointestinal tract while a part of it was bound to the intestinal mucosa, the rest being excreted directly into feces.

Animals↗
PubMed1989

Relation of running distance to plasma HDL-cholesterol level in middle-aged male runners.

This study examined the relation of training distance to plasma high density lipoprotein cholesterol (HDLC) concentration in runners. Forty-eight male endurance runners, aged from 30 to 57 years, were classified into three groups according to training distance (Grade I: n = 12, 30 km/week; Grade II: n = 22, 60 km/week; Grade III: n = 14, 100 km/week in average running distance), with 12 non-lean and 12 lean subjects as age-matched untrained controls. There were no significant differences in plasma total cholesterol among the groups (194-208 mg/dl on average). HDLC level was significantly higher in the untrained, lean group than in the untrained, non-lean men (63 +/- 13 vs. 46 +/- 8 mg/dl, mean +/- SD). HDLC levels in all the runner groups were significantly higher than in untrained, lean subjects, and no differences were observed among Grade I, II and III runner groups (76 +/- 15, 76 +/- 13, 77 +/- 11 mg/dl, respectively). This study suggests that further increases in HDLC could not occur in response to further elevation of training distance in well-trained runners.

Adult↗
PubMed1989

Effect of human epidermal growth factor on lung surfactant production in fetal rabbit.

The effect of human epidermal growth factor (hEGF) on the maturation of fetal rabbit lung was studied. On the 25th day of gestation, 0.1 ml of saline solution containing 0.1 microgram of hEGF was injected intramuscularly through uterine wall into fetuses in one horn of the uterus (hEGF treated group) and the same amount of saline solution injected into fetuses in the other horn of the uterus (saline-control group). Sham operated group was also studied; saline was injected to fetuses in both horns. On the 27th day of gestation, fetuses were delivered by cesarean section. There were no significant differences in fatal body weight and fetal lung wet weight among three groups. Total phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) concentrations/g dry lung weight were high in order of hEGF treated group, saline injected group and sham operated group. There were no significant differences in PC concentrations among three groups. However, DSPC concentrations in both saline-control and hEGF treated group were significantly higher than that in sham operated group (p less than 0.01). The % composition of palmitic acid in PC molecule, which is the main component of saturated fatty acid of lung surfactant, was significantly higher in hEGF group than in sham operated group (p less than 0.05). Interestingly, there were no significant differences in DSPC level and the % composition of palmitic acid between saline-control and hEGF treated group. This phenomenon might be due to so called a "neighbor effect" that hEGF injected to fetuses in one side of the uterine horn influences the fetuses in the other side of the horn through placentas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Participation of the vasodilating property of nipradilol in improving ischemic derangement of myocardial energy metabolism.

The effects of equipotent doses in negative inotropic and chronotropic properties of nipradilol [10 micrograms/kg/min intravenously (i.v.)] and propranolol (20 micrograms/kg/min i.v.) on hemodynamics and transmural energy metabolites in ischemic hearts were examined in anesthetized dogs. After 5-min infusion of these agents, coronary perfusion pressure of 30 mm Hg was induced by acute coronary stenosis for 10 min. Coronary blood inflow and myocardial contractile force (MCF) in the control ischemic area decreased to about one-third and two-thirds of the respective starting levels. In the nipradilol group, similar changes were observed, but in the propranolol group the MCF tended to decrease further. Cardiac effort index decreased to about two-thirds in both groups. The left ventricular end-diastolic pressure (LVEDP) increased by 4.3 mm Hg with saline, by 8.8 mm Hg with propranolol, and by 1.3 mm Hg with nipradilol. ATP depletion in the ischemic myocardium (by 29 and 22% in inner and outer layers, respectively) was restored to normal level by either agent. A decrease in creatine phosphate and an accumulation of lactate were significantly alleviated by nipradilol (by 74 and 59----by 39 and 21%, and by 4.9 and 2.3----by 0.7 and 0.2 times, respectively), but not by propranolol. The results indicate that in addition to a decrease in myocardial oxygen consumption caused by the beta-adrenoceptor blocking effects of nipradilol, reductions in preload and afterload caused by the vasodilating property significantly contribute to nipradilol-induced improvement in the ischemic derangement of transmural energy metabolism.

Animals↗
PubMed1989

[A case of primary erythromelalgia (erythermalgia) treated with neural blockade].

A case of primary erythromelalgia which was treated successfully with lumbar sympathetic block and total spinal block (TSB) is reported. The patient was a 21-year-old woman with 18-year history of pain, burning, swelling, redness and warm sensation in both feet and lower part of the legs that caused the patient to soak her feet and legs frequently in ice cold water in order to obtain pain relief. The patient had been treated with a variety of medications including aspirin, indomethacin, methysergide maleate, and carbamazepine with no relief. Recently, the excessive exposure to cold water had caused extensive immersion foot (trench foot) with secondary infection (fusarium infection). Treatment with bilateral lumbar sympathetic block had markedly improved the symptom. Furthermore, treatment with TSB against causalgic state was performed 8 times for 4 months. During this period, the patient experienced the symptom which was much milder than those before treatment with TSB. Lumbar sympathetic block and TSB are useful methods for treatment of primary erythromelalgia.

Adult↗
PubMed1989

[Early diagnosis of the cervical incompetency by the ultrasonography].

To establish a reliable method for diagnosing cervical incompetency, we observed changes in the cervix by ultrasonography and tried to settle the criteria for early diagnosis. The ultrasonographic evaluation of the cervix was performed by real time B mode scanning (Aloka Echo camera SSD 650 with attached sector scanner using 3.5 MHZ transducers). The cervical length was defined as the distance from the lower edge of the fetal membranes to the edge of the portio vaginalis. In the case of normal pregnancy, the cervical length increased gradually from 14 to 24 weeks of gestation and then decreased gradually. In the case of patients who delivered before 33 weeks of gestation, the cervical length was less than -ISD. 78 of 79 cases in whom bulging of the membranes was not seen delivered at term, but 9 of 33 cases with bulging membranes delivered preterm (chi2, p less than 0.001). The criteria of cervical incompetency based on ultrasonographic findings are as follows: 1. Bulging of the fetal membranes into the endocervical canal 2. Shortening of the cervix a. the cervical length less than -ISD of the mean value b. the decrease in cervical length before 24 weeks of gestation

Cervix Uteri↗
PubMed1989

[Clinical significance of cross linked fibrin degradation products in thrombotic disorders].

We performed a clinical study by measuring the plasma levels of D-dimer, which is derived from the degradation of cross linked fibrin, in some thrombotic disorders using Dimertest EIA kit obtained from AGEN Corp. (Australia). The level of D-dimer in disseminated intravascular coagulation (DIC) were greater than that in thrombotic thrombocytopenic purpura (TTP). These levels of D-dimer in two thrombotic disorders showed a different pathogenesis between them. And also, the levels of D-dimer in some arteriosclerotic disorders, i.e.; aortic aneurysm , cerebral infarction and coronary insufficiency, and in venous thrombosis significantly increased compared with normal subjects. The level of D-dimer measured by Dimertest EIA kit was useful marker for detecting a thrombotic tendency in the low level of D-dimer, in which latex agglutination test for fibrin/fibrinogen degradation products (FDPL test) could not usually detect.

Adult↗
PubMed1989

Intestinal parasitic infections among schoolchildren in Chiang Mai, northern Thailand: an analysis of the present situation.

Stool examination from primary schoolchildren in Chiang Mai Province, north Thailand, was performed to determine the present state of parasitic infections in this area. Out of a total of 491 children, 239 proved positive (48.7%). The most common type of parasite was found to be soil-transmitted helminths such as hookworm (26.3%) or Strongyloides stercoralis (11.2%), while Ascaris lumbricoides was not so prevalent (1.2% being positive in one school out of three). These results are in contrast to earlier reports showing higher prevalence rates, leading the authors to hypothesize that improvements in sanitary conditions and eradication projects have been effective. Opisthorchiasis is another parasitic disease with a relatively high prevalence rate of 7.5%. This disease rate increases with age and it was found in two out of three schools (8.3-15.8%) and was the most common type of helminth infection. Ascariasis was not seen in these two schools, but strongyloidiasis was found to be the second most prevalent helminthiasis, having a higher infection rate than hookworm. Therefore, eradication efforts now need to be directed toward eliminating opisthorchiasis and strongyloidiasis in addition to continuing to eradicate ascariasis and hookworm infections. The most common protozoal infection with a high pathogenicity in this region was found to be giardiasis (7.7%).

Adolescent↗