Search PubMed⌕ Search

Biomedical subjects

K Hata

Publications and source records attributed to K Hata.

At least 145 records · Page 8Linked to original sources

Problems on the diagnosis of sudden infant death syndrome.

Various autopsy cases of sudden unexpected death (SUD) in infancy were examined at the Tokyo Medical Examiner's Office between 1985 and 1994. More than half of the SUD were diagnosed as sudden infant death syndrome (SIDS), but a number of other causes, such as mechanical asphyxia, were also diagnosed. SIDS is diagnosed by autopsy, but there are no clear diagnostic criteria differentiating SIDS from other causes of SUD. SUD is diagnosed as SIDS when other causes are excluded, but it is difficult to distinguish between SIDS and mechanical asphyxia. There was not a large difference in autopsy findings, or in death scene or statistical data, between SIDS and non-SIDS cases. In their estimation of the diagnostic ratio of SIDS to other causes of death, medical examiners might be divided into three groups: 'SIDS tolerationist' examiners think that SUD should be positively diagnosed as SIDS, insofar as another cause of death is not proved clearly. A second group of examiners might be regarded as 'SIDS exclusionist': these consider microscopic findings or peculiar death scenes as important contributing factors leading to death. The third group represents a middle stance somewhere between these two. We thought that (forensic) pathologists as well as medical examiners in Japan might have differing stances on SIDS diagnosis. The statistical analysis of SIDS in certain research areas may be affected by the diagnostic 'preference' of pathologists belonging to a certain institute.

Asphyxia↗

Disparate effects of preconditioning and MLA on 5'-NT and adenosine levels during coronary occlusion.

Ischemic preconditioning has been proposed to protect the heart against infarction by increasing 5'-nucleotidase (5'-NT) activities and augmenting adenosine levels during sustained coronary artery occlusion. To test this theory, anesthetized dogs received four 5-min episodes of preconditioning ischemia, pretreatment with the pharmacological "preconditioning mimetic" monophosphoryl lipid A (MLA, 35 micrograms/kg i.v.) or no intervention before coronary artery ligation. At 20 min into occlusion (the crucial time at which myocyte death begins in this model), myocardial samples were obtained for measurement (by high-performance liquid chromatography) of ectosolic and cytosolic 5'-NT activity and adenosine levels. Preconditioning and MLA pretreatment limit infarct size in the canine model by 75 and 50%, respectively. However, only MLA augmented 5'-NT activity [i.e., cytosolic 5'-NT in the ischemic subendocardium was 26 +/- 1, 39 +/- 7, and 26 +/- 6 nmol. mg protein-1. min-1 in preconditioned, MLA, and control groups (P < 0.05), respectively]. Moreover, adenosine levels (in nmol/mg protein) were increased with MLA treatment (2.30 +/- 0.44) but attenuated in preconditioned dogs (1.11 +/- 0.23; P < 0.05) versus controls (1.87 +/- 0.29). Thus 5'-NT and adenosine levels need not be increased beyond control values during sustained occlusion to elicit cardioprotection.

5'-Nucleotidase↗

Sulfidoleukotriene release test (CAST) in hypersensitivity to nonsteroidal anti-inflammatory drugs.

There is a great need to develop a method for making an accurate and reliable in vitro diagnosis of adverse hypersensitivity reactions to drugs. We measured the amount of sulfidoleukotriene (sLT) released from the peripheral blood leukocytes obtained from 25 patients who developed hypersensitivity reactions following the administration of nonsteroidal anti-inflammatory drugs (NSAIDs); 12 patients demonstrated reactions to Voltaren, 8 patients to Bufferin, and 5 patients to Sedes G. The stimulation index, the ratio of the amounts of sLT (pg/ml) incubated with and without drugs, was considerably higher in the patients than in the controls, which consisted of 5 nonallergic healthy subjects. The sensitivity of the CAST (cellular antigen stimulation test) was evaluated to range from 62.5 to 80%, while the specificity was 70-100%. The CAST may thus be useful as a novel in vitro test system in order to screen for possible hypersensitive reactions to NSAIDs with both reliability and safety.

Adult↗

Plasma catecholamines and Doppler-derived cardiac time intervals in vaginally and cesarean delivered neonates.

OBJECTIVE: Our purpose was to compare Doppler-derived cardiac time intervals and cord plasma levels of catecholamines in vaginally and cesarean delivered neonates. METHODS: Doppler echocardiographic assessments of fetal and neonatal cardiac time intervals were made to determine differences in circulatory changes in 8 neonates delivered vaginally and 12 delivered by elective cesarean section. Aortic and pulmonary acceleration time (AT), ejection time (ET), and the AT/ET ratio in systole were assessed at various time points from antenatal to 72 h after delivery. Umbilical artery blood gas and acid-base values, and cord blood concentrations of epinephrine and norepinephrine were also measured. RESULTS: Umbilical artery blood pH in the cesarean section group was significantly lower than that in the vaginal delivery group (p < 0.05). Base deficit in umbilical artery blood and cord blood norepinephrine in cesarean delivered neonates were significantly higher than those in vaginally delivered neonates, respectively (p < 0.05). There were no significant changes in aortic cardiac time intervals between the 2 groups at any of the various time points. However, pulmonary AT and the AT/ET ratio were significantly lower in the normal vaginal delivery group than those in the cesarean section group 6 h after delivery (p < 0.05). CONCLUSIONS: The lower AT and AT/ET ratio of the pulmonary artery in vaginally delivered neonates may reflect an increase in pulmonary vascular resistance, indicating transient pulmonary hypertension. The findings were the reverse of what might be expected from an elevated pulmonary vascular resistance and transient pulmonary hypertension in cesarean delivered neonates.

Adult↗

Doppler ultrasound in a patient with ovarian Brenner tumor of low malignant potential: comparison with Gray-scale ultrasound, magnetic resonance imaging and tumor marker suggesting malignancy.

We present a postmenopausal patient with giant lower abdominal tumor. Gray-scale ultrasound and magnetic resonance imaging showed typical abnormal morphology suggesting malignancy. The serum CA 125 level was 69 U/ml, and that of CA 19-9 was 2,097 ng/ml. Transvaginal color and pulsed Doppler sonography of the tumor vasculature demonstrated low peak systolic velocity (6.7 cm/s) with low pulsatility (resistance index: 0.49). Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histological diagnosis was ovarian Brenner tumor of low malignant potential. Transvaginal Doppler findings seemed to give specific information for the diagnosis in this case.

Aged↗

Interleukin-4, interleukin-10, and soluble tumor necrosis factor receptors in cord blood.

OBJECTIVE: We assessed cord blood for levels of interleukin-4 (IL-4), interleukin-10 (IL-10), and p55 (sTNFR-I) and p75 (sTNFR-II) soluble tumor necrosis factor receptors. STUDY DESIGN: Umbilical cord IL-4, IL-10, tumor necrosis factor alpha (TNF alpha), sTNFR-I, and sTNFR-II were measured in 21 normal appropriately grown newborns delivered vaginally (normal pregnancy), and 3 abnormal pregnancies (1 preterm delivery, 1 premature rupture of membranes with chorioamnionitis, and 1 abruptio placentae with fetal and neonatal distress). Umbilical cord arterial blood pH and PO2 were also measured. RESULTS: The TNF alpha, sTNFR-I, and sTNFR-II were detectable in all cord blood samples in normal pregnancies. IL-4 was detected in 10 of 21 samples (47.6%), and IL-10 was undetectable in normal pregnancies. IL-10 could be detected in the cases with chorioamnionitis and abruptio placentae. Soluble tumor necrosis factor receptors in the case with preterm delivery and the case with abruptio placentae were elevated compared with the levels in control samples. CONCLUSION: Both the p55 and p75 soluble tumor necrosis factor receptors are physiologic constituents of term cord blood. An immunosuppressive role of IL-10 and a protective role of soluble tumor necrosis factor receptors are suggested in abnormal pregnancies. However, in view of the small number of abnormal pregnancies, these observations must be considered preliminary.

Abruptio Placentae↗

Antenatal diagnosis of aberrant umbilical vessels.

OBJECTIVE: To evaluate the antenatal screening of aberrant umbilical vessels and assess the association of fetal abnormality with these entities. STUDY DESIGN: 444 pregnant women were studied with routine obstetric ultrasound and Doppler color flow imaging in late second trimester or early third trimester. Fetal growth and anomaly, and the number of umbilical cord vessels were screened. RESULTS: Out of 444 subjects, 3 cases with discordant umbilical artery, 2 with four vessels in the umbilical cord, and 1 with single umbilical artery were detected (1.4%). Fetal anomaly was noted in 2 of 6 cases with aberrant umbilical vessels (33.3%). CONCLUSION: These results suggest that antenatal screening of umbilical cord vessels is necessary for detection of fetal anomalies.

Congenital Abnormalities↗

Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover.

Patients with poorly controlled noninsulin dependent diabetes mellitus (NIDDM) are shown to have higher bone mass. However, the influence of changes in glycemic control on bone turnover is not known. To clarify whether metabolic improvement of poorly controlled NIDDM affects bone turnover, markers for glucose, mineral, and bone metabolism were assessed before and after glycemic control for 3 weeks in 78 poorly controlled NIDDM patients with initial hemoglobin A1c over 8%. Metabolic improvement caused a reduction in urinary calcium (Ca) and phosphate (Pi) and serum 1,25(OH)2D levels, and an increase in serum Pi without changes in serum Ca or parathyroid hormone levels. Bone resorption markers, urinary deoxypyridinoline (Dpd) and type I collagen carboxy-terminal telopeptide (CTx), as well as a bone formation marker, serum bone type alkaline phosphatase (BALP), were reduced. However, another bone formation marker, serum osteocalcin (OC), was low before treatment and was elevated after treatment. The decrease in Dpd, CTx and BALP, but not the increase in OC, correlated with each other and with the improvement in glycemic indices. In conclusion, metabolic improvement of poorly controlled NIDDM decreases bone turnover within a short period. Thus, glycemic control may protect NIDDM patients from bone loss. It is possible that serum OC is affected by hyperglycemia per se, and may not correctly reflect bone turnover.

Adult↗

Urinary excretion of aquaporin-2 water channel protein in human and rat.

Previous studies by the authors demonstrated that the response of urinary aquaporin-2 (AQP2) excretion to dDAVP (deamino-8-D-arginine vasopressin) infusion is an index of vasopressin action on the kidney (N Engl J Med 332: 1540-1545, 1995). In the study presented here, the characteristics of urinary excretion of AQP2 were examined further. An RIA suitable for AQP2 in the urine was established. Relatively high concentrations of detergent and bovine serum albumin in the RIA buffer allowed analysis of urine samples with a wide range of concentrations and increased the sensitivity of the assay. AQP2 in the urine existed as a high molecular weight form of approximately 190 kD by HPLC analysis. The mean urinary AQP2 concentration corrected for creatinine in spot urine samples of healthy subjects who voided in the morning was 1081 +/- 699 fmol/mg creatinine (mean +/- SD, n = 208). The amount of daily excretion of AQP2 in the urine was the same in men and women. Urinary AQP2 content was not affected by age of the subjects and showed a positive correlation with urine osmolality. Finally, the fraction of AQP2 excreted in the urine compared with whole kidney content was determined in the rat. Approximately 3% of AQP2 in the kidney was excreted daily, and this fraction did not change when rats were dehydrated for 3 d. These data demonstrate the necessity of establishing well-designed protocols to use urinary AQP2 as a marker of AVP action.

Adult↗

2,3-Butanedione monoxime suppresses excitation-contraction coupling in the canine blood-perfused left ventricle.

The negative inotropism of 2,3-butanedione monoxime (BDM) < or = 5 mmol/l has been attributed primarily to directly suppressed crossbridge force development without much suppressed intracellular Ca2+ handling. However, there is evidence that BDM simultaneously or even primarily suppresses myocardial excitation-contraction (E-C) coupling. We therefore studied the mechanoenergetic effects of intracoronary BDM in the left ventricle (LV) of 11 canine excised cross-circulated hearts. We fully utilized the VO2-PVA-Emax framework that we have developed, where VO2 is myocardial O2 consumption, PVA is the systolic pressure-volume area as a measure of the total mechanical energy, and Emax is a contractility index. We gradually depressed Emax from 5.9 to 3.4 mmHg/(ml/100 g) on average by increasing intracoronary BDM to 2.6 +/- 2.1 mmol/l, and then gradually restored Emax to the pre-BDM level by increasing intracoronary CaCl2. We compared the O2 cost of Emax between BDM and Ca2+. We found that BDM and Ca2+ had a similar O2 cost of Emax. BDM did not affect the concentrations of blood-borne catecholamines. We therefore conclude that the negative inotropism of BDM is primarily due to suppressed E-C coupling in canine blood-perfused hearts.

Analysis of Variance↗

Effects of oophorectomy and hormone replacement therapy on ophthalmic artery blood flow velocity waveforms.

Our objective was to compare ophthalmic artery flow velocity waveforms in unilateral oophorectomized patients not on hormone replacement therapy with findings in bilateral oophorectomized patients on hormone replacement therapy. Ten patients who underwent hysterectomy and unilateral oophorectomy and 10 women treated by hysterectomy and bilateral oophorectomy were studied using color and pulsed Doppler ultrasonography 1 day before and on days 7 and 28 after surgery. Serum estradiol levels were measured serially. Bilateral oophorectomy patients were given hormone replacement therapy (conjugated estrogen, 0.625 mg/day, and medroxyprogesterone acetate, 2.5 mg/day) orally starting on day 8 after surgery. The pulsatility index values of the ophthalmic artery in unilateral oophorectomy patients were 1.93 +/- 0.41, 2.10 +/- 0.26, and 1.68 +/- 0.27 for 1 day before and on days 7 and 28 after surgery, respectively. The pulsatility index values of the ophthalmic artery in bilateral oophorectomy patients were 1.99 +/- 0.39, 2.17 +/- 0.47, and 1.75 +/- 0.32 for 1 day before and on days 7 and 28 after surgery, respectively. No significant differences were found between pulsatility index values in the unilateral and bilateral oophorectomy patients in each time period. The pulsatility index values on day 28 decreased significantly compared with the findings on day 7 in both groups (P < 0.05). The serum estradiol levels were significantly reduced from 1 day before to day 7 day after surgery and were significantly elevated by day 28 after surgery (P < 0.05) in both groups of patients. No significant differences were found between the serum estradiol levels in the unilateral and bilateral oophorectomy patients in each time period. Vascular tone in the ophthalmic artery seems to change according to serum estradiol levels, a finding that may help explain some of the beneficial effects of hormone replacement therapy for bilateral oophorectomized patients.

Adult↗

[Intraocular neovascularization].

To investigate the mechanism of intraocular neovascularization, we studied how vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are expressed in the ocular tissues under hypoxic conditions. Prior to proliferation of vascular endothelial cells resulting in neovascularization, the retinal tissues such as pericytes, retinal glial cells, ganglion cells, and ciliary epithelium react directly to hypoxia expressing VEGF and/or IL-8 and stimulate endothelial cell proliferation in a paracrine manner. We demonstrated that transcription factor activator protein-1 (AP-1) is activated for expression of VEGF messenger ribonuculeic acid (mRNA) and in a similar way nuclear factor kappa B (NF-kappa B) is activated for expression of IL-8 mRNA. However, hypoxia-induced expression of VEGF and/ or IL-8 is only one aspect of the complicated processes in intraocular neovascularization. We hope that further detailed analysis of the mechanism will make it possible to inhibit and treat clinically intraocular neovascularization in the near future.

Adult↗

Mechanoenergetic effect of pimobendan in failing dog hearts.

The effect of cardiotonic drugs with a calcium-sensitizing effect (Ca2+ sensitizers) on cardiac mechanoenergetics in the failing heart is not fully understood. Accordingly, we measured left ventricular (LV) contractility (Emax) and the relation between myocardial oxygen consumption (VO2) and pressure-volume area (PVA; a measure of LV total mechanical energy) before and during enhancement of contractility by infusion of dobutamine (DOB) or pimobendan (PIMO) in six cross-circulated hearts isolated from pacing-induced heart failure (FL) dogs, and compared the results with those reported in normal hearts (NL, n = 12). Although the baseline Emax was much lower in FL dogs than in NL dogs (P < 0.01), DOB and PIMO comparably enhanced Emax in the FL dogs. The O2 cost of contractility, defined as the increase in unloaded VO2 at zero PVA divided by the increase in Emax, obtained during an enhancement of contractility with DOB, was significantly higher in FL dogs than in NL dogs, suggesting that a larger amount of O2 is consumed during Ca2+ cycling with DOB in FL dogs. In contrast, the O2 cost of contractility with PIMO was similar between FL and NL dogs. Furthermore, the VO2 per minute was significantly higher with DOB (P < 0.05) than with PIMO partly because of an excessive positive chronotropic effect of DOB. We concluded that (1) PIMO exerts a positive inotropic effect comparable to that of DOB in both NL and FL dogs; (2) the O2 cost of contractility with DOB is higher in FL dogs than in NL dogs; and (3) PIMO has a relative O2-saving effect compared with DOB in FL dogs.

Animals↗

Assembly and activation of the phagocyte NADPH oxidase. Specific interaction of the N-terminal Src homology 3 domain of p47phox with p22phox is required for activation of the NADPH oxidase.

The phagocyte NADPH oxidase is activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. The activation involves assembly of membrane-integrated cytochrome b558 comprising gp91(phox) and p22(phox), two specialized cytosolic proteins (p47(phox) and p67(phox)), each containing two Src homology 3 (SH3) domains, and the small G protein Rac. In the present study, we show that the N-terminal SH3 domain of p47(phox) binds to the C-terminal cytoplasmic tail of p22(phox) with high affinity (KD = 0.34 microM). The binding is specific to this domain among several SH3 domains including the C-terminal one of p47(phox) and the two of p67(phox) and requires the Pro156-containing proline-rich sequence but not other putative SH3 domain-binding sites of p22(phox). Replacement of Trp193 by Arg in the N-terminal SH3 domain completely abrogates the association with p22(phox). A mutant p47(phox) with this substitution is incapable of supporting superoxide production under cell-free activation conditions. These findings provide direct evidence that the interaction between the N-terminal SH3 domain of p47(phox) and the proline-rich region of p22(phox) is essential for activation of the NADPH oxidase.

Cytochrome b Group↗

Negative chronotropic effect of beta-blockade therapy reduces myocardial oxygen expenditure for nonmechanical work.

BACKGROUND: The negative chronotropic effect of beta-blocking agents is likely to provide hemodynamic and energetic advantages. However, the negative chronotropic effect on cardiac energetics observed on the initiation of beta-blockade therapy has not been fully elucidated. METHODS AND RESULTS: In 18 patients with heart failure, left ventricular pressure and volume, external work (EW), myocardial oxygen consumption per beat (total Vo2), mechanical efficiency (EW/total Vo2), and Vo2 for nonmechanical work (total Vo2-2.EW) were measured with the use of conductance catheter and Webster catheter at the following three states: under control conditions and after beta-blockade (0.15 +/- 0.07 mg/kg propranolol IV) with and without atrial pacing to keep the heart rate at control levels. Heart rate decreased after atrial pacing was stopped. EW decreased during beta-blockade with pacing and returned to the control level after pacing was stopped. Total Vo2 did not change during beta-blockade with or without pacing, whereas Vo2 for nonmechanical work increased with pacing and returned to the control level after pacing was stopped. As a result, mechanical efficiency decreased during beta-blockade with pacing and returned to the control level after pacing was stopped. CONCLUSIONS: The negative chronotropic effect of a beta-blocking agent may offset the mechanoenergetical deterioration resulting from its negative inotropic effect through a reduction in oxygen expenditure for nonmechanical work. These findings suggest that the negative chronotropic effect is an important aspect of beta-blockade therapy.

Adrenergic beta-Antagonists↗

Clinical significance of simultaneous determinations of alpha-fetoprotein and des-gamma-carboxy prothrombin in monitoring recurrence in patients with hepatocellular carcinoma.

BACKGROUND: Measurements of serum alpha-fetoprotein (AFP) concentration and plasma concentration of des-gamma-carboxy prothrombin (DCP) have been widely used for the early diagnosis of hepatocellular carcinoma (HCC). The two markers generally run parallel to each other. However, in our study, they sometimes fluctuated independently in response to tumor regression or recurrence. METHODS: A longitudinal series of concentrations of serum AFP and plasma DCP were determined simultaneously for 245 patients with HCC from the time of diagnosis to tumor recurrence after treatment. RESULTS: Positive reactions for AFP were noted in 168 patients (69%) and for DCP in 126 patients (51%). One hundred and ten of 245 patients with HCC (45%) were positive for both AFP and DCP. In 35 patients (14%), these 2 tumor markers fluctuated independently in response to tumor regression and recurrence. These patients were categorized into four groups as follows: Group 1 had elevated AFP only at diagnosis; it then decreased after treatment, but DCP was elevated at the time of tumor recurrence without AFP elevation (3 patients); Group 2 had elevated DCP at diagnosis and elevated AFP at tumor recurrence (4 patients); Group 3 had elevated AFP and DCP at diagnosis, but only AFP (8 patients) or DCP (7 patients) was elevated at tumor recurrence; Group 4 had only elevated AFP (2 patients) or DCP (11 patients) at diagnosis, but both AFP and DCP were elevated at tumor recurrence. CONCLUSIONS: The results of this study indicate that simultaneous determinations of AFP and DCP are useful for monitoring recurrence in patients with HCC after treatment, and that the decrease to normal levels of a single marker does not always indicate the absence of tumor recurrence.

Adolescent↗

The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium.

Through the specific binding of a negative calcium-responsive element to its binding protein in response to extracellular Ca (Ca2+e), negative calcium-responsive element-bearing genes, such as the human parathyroid hormone gene, are negatively regulated by Ca2+e. The Ku antigen mediated negative gene regulation by Ca2+e by interacting with a redox factor protein, REF1. Although sequence-nonspecific DNA binding activity of the Ku antigen has been well characterized, the mechanism of its sequence-specific DNA binding remained obscure. Here, we report that the specific binding of the Ku antigen to another protein, REF1, leads to DNA-protein complex formation with a novel sequence specificity and thereby regulates gene expression.

Amino Acid Sequence↗