Search PubMed⌕ Search

Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 595 records · Page 33Linked to original sources

Facilitatory effect of tonic voluntary contraction on responses to motor cortex stimulation.

To investigate the mechanisms underlying the facilitation of responses to motor cortical stimulation produced by tonic voluntary contraction, we studied the facilitatory effects in 7 normal volunteers during different levels of muscle contraction. Responses were similarly facilitated by voluntary contraction with 3 forms of stimulation: magnetic cortical, electrical cortical, and foramen magnum level stimulation. At a high level of contraction, however, only magnetic responses were markedly facilitated. We conclude that the facilitation of responses to cortical stimulation induced by tonic voluntary contraction occurs mainly at the spinal level, but that cortical excitability changes also contribute to the enlargement of magnetic responses in the case of a high level of contraction.

Adult↗

Prognostic significance of three novel biologic factors in a clinical trial of adjuvant therapy for node-negative breast cancer.

BACKGROUND: Five products of human breast carcinoma cells, including membrane-associated phospholipase A2 (M-PLA2), polymorphonuclear leukocyte elastase (PMN-E), tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and endothelin-1 (ET-1), have been implicated in the processes of tumor cell invasion and metastasis in human breast carcinoma. However, the prognostic significance of these factors has not been assessed previously in node-negative breast carcinoma, in which adjuvant treatment is dependent on risk stratification. METHODS: The five products of breast carcinoma cells were measured in 184 patients with node-negative breast carcinoma who were enrolled in the Kumamoto Adjuvant Chemo-Endocrine Therapy for Breast Cancer prospective randomized trial, and the predictive values of these factors for relapse-free and overall survival were evaluated. RESULTS: M-PLA2, PMN-E, and t-PA were found to be significant independent predictors of relapse-free and overall survival, whereas u-PA and ET-1 were not independently predictive. Further statistical analyses showed that the predictive powers of M-PLA2, PMN-E, and t-PA were additive. A combination of these three factors identified a group of patients (approximately 50% of those who manifested node-negative breast carcinoma) with a favorable prognosis, regardless of the administration of adjuvant therapy. CONCLUSIONS: This study identified three biologic factors that are valuable predictors of survival in node-negative breast carcinoma. A combination of these biologic factors may allow identification of low-risk patients who could be spared adjuvant therapy.

Breast Neoplasms↗

Double free-muscle transfer to restore prehension following complete brachial plexus avulsion.

Restoration of finger flexion and extension as well as elbow flexion and extension with a double free-muscle and multiple nerve transfers following complete avulsion of the brachial plexus (nerve roots C5 to T1) is reported. The procedure combines (1) free-muscle transfer with reinnervation by the spinal accessory nerve to achieve elbow flexion and finger extension, (2) free-muscle transfer with reinnervation by the fifth and sixth intercostal nerves to restore finger flexion, (3) third and fourth intercostal motor nerve transfer to the triceps brachi to extend and stabilize the elbow, (4) nerve transfer of the supraclavicular nerve or nerve transfer of the sensory rami of the intercostal nerves to the median nerve to restore hand sensibility, and (5) glenohumeral arthrodesis. Seven of 10 patients recovered elbow function and finger flexion and extension. Five patients reported use of their hand in activities of daily living.

Adolescent↗

Primary structure of N-acyl-D-glutamate amidohydrolase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6.

The gene coding the N-acyl-D-glutamate amidohydrolase of Alcaligenes xylosoxydans subsp. xylosoxydans A-6 (Alcaligenes A-6) was cloned and its complete DNA sequence was determined. The N-acyl-D-glutamate amidohydrolase structural gene consists of 1,464 nucleotides and encodes 488 amino acid residues. The molecular weight of the enzyme was calculated to be 51,490. This value is close to the apparent molecular weight of 59,000 determined for the purified enzyme from Alcaligenes A-6 by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE). The N-terminal amino acid sequence of the recombinant protein exactly matches the amino acid sequence derived from the DNA sequence and that determined from the Alcaligenes A-6 enzyme (NH2-MQEKLDLVIEGGWVIDGLGG). The deduced amino acid sequence of the cloned N-acyl-D-glutamate amidohydrolase showed high sequence homology with those of N-acyl-D-aspartate amidohydrolase (46%) and D-aminoacylase (47%) from Alcaligenes A-6. This fact strongly suggests that these three enzymes have evolved from a common ancestral gene.

Alcaligenes↗

Can the microsphere model by applied to cerebral blood flow measurement using N-isopropyl-p-[123I]iodoamphetamine with SPET regardless of washout from brain tissue?

The microsphere model and the continuous withdrawal of arterial blood have commonly been used in clinical studies when measuring regional cerebral blood flow (rCBF) by N-isopropyl-p-[123I]iodoamphetamine (IMP) single photon emission tomography. The method is considered to underestimate rCBF because of the washout of tracer from brain tissue; however, the extent of this underestimation is not known. To assess whether this underestimation can be determined quantitatively, we performed simulation analysis based on the microsphere model and the two-compartment model [influx, K1(rCBF); and outflux, k2(washout)] using the time-activity curves of 123I-IMP in arterial blood [Ca(t)] of 10 subjects. With the microsphere method, rCBF values fell as time post-injection increased. The extent of underestimation of rCBF was 4.7 +/- 0.28% (mean +/- S.D.) at 5 min, 10.2 +/- 0.42% at 10 min and 15.2 +/- 0.55% at 15 min. There was little variation in the extent of underestimation and it was not dependent on the Ca(t) of the subjects. We therefore considered the results to be generally applicable to various studies of the microsphere model. As 4.7% is considered to be negligible in clinical studies, we conclude that the microsphere model can be applied to obtain accurate measurement of rCBF up to 5 min regardless of washout.

Amphetamines↗

Corpus spongiosum penis pressure and perineal muscle activity during reflexive erections in the rat.

This experiment represents the first simultaneous analysis of corpus spongiosum of the penis (CSP) pressure and perineal muscle activity during reflex-induced penile erections in the awake rat and provides new data on the coordination of muscular and vascular events in erection physiology. Nine male Sprague-Dawley rats were implanted with pressure transducers under pentobarbital anesthesia (60 mg/kg) for use in a new technique of chronic erection recording involving simultaneous CSP pressure monitoring and electromyography (EMG) of the ischiocavernosus (IC) and bulbospongiosus (BS) muscles. The association of these physiological measurements with visually scored ex copula erectile events was investigated. Reflexive erectile events were systematically associated with an increase in baseline CSP pressure. Glans erections were associated with dramatic suprasystolic CSP pressure peaks concurrent with BS muscle bursts. Indeed, measures of CSP pressure and BS EMG activity were found to vary significantly with the intensity of glans erection. Flips of the penile body, however, involved small CSP pressure increases and IC bursts. These data demonstrate for the first time that both CSP pressures and perineal muscle activity vary significantly with the intensity of penile erection.

Animals↗

The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis.

Tryptase, a protease produced by all mast cells, was evaluated as a clinical marker of systemic mastocytosis. Two sandwich immunoassays were evaluated, one which used the mAb G5 for capture, the other which used B12 for capture. The B12 capture assay measured both recombinant alpha- and beta-tryptase, whereas the G5 capture assay measured primarily recombinant beta-tryptase. G5 binds with low affinity to both recombinant alpha-tryptase and tryptase in blood from normal and nonacute mastocytosis subjects, and binds with high affinity to recombinant beta-tryptase, tryptase in serum during anaphylaxis, and tryptase stored in mast cell secretory granules. B12 recognizes all of these forms of tryptase with high affinity. As reported previously, during systemic anaphylaxis in patients without known mastocytosis, the ratio of B12- to G5-measured tryptase was always < 5 and approached unity (Schwartz L.B., T.R. Bradford, C. Rouse, A.-M. Irani, G. Rasp, J.K. Van der Zwan and P.-W.G. Van der Linden, J. Clin. Immunol. 14:190-204). In this report, most mastocytosis patients with systemic disease have B12-measured tryptase levels that are elevated (> 20 ng/ml) and are at least 10-fold greater than the corresponding G5-measured tryptase level. Most of those subjects with B12-measured tryptase levels of < 20 ng/ml had only cutaneous manifestations. The B12 assay for alpha-tryptase and beta-tryptase, particularly when performed in conjunction with the G5 assay for beta-tryptase, provides a more precise measure of mast cell involvement than currently available assessments, a promising potential screening test for systemic mastocytosis and may provide an improved means to follow disease progression and response to therapy.

Acute Disease↗

Effect of acetylcholine on corticotropin-releasing factor gene expression in the hypothalamic paraventricular nucleus of conscious rats.

To examine the physiological role of cholinergic input in the regulation of CRF neurons in the paraventricular nucleus (PVN) of the hypothalamus, acetylcholine (ACh) was microinjected bilaterally into the dorsolateral border of the PVN of conscious rats. Changes in the levels of POMC messenger RNA (mRNA) in the anterior pituitary, CRF mRNA in hypothalamic tissue containing the PVN, and plasma ACTH were assessed. Plasma ACTH concentrations increased in a dose-dependent manner after ACh injection (1-100 pmol/side), reaching a peak 30 min after ACh injection and returning to baseline within 120 min. The POMC mRNA level in the anterior pituitary and the hypothalamic CRF mRNA level increased in a dose-dependent manner 120 min after ACh (0.1-10 pmol/side) injection. Intracerebroventricular pretreatment with atropine completely abolished the ACh-induced increase in plasma ACTH concentrations, whereas pretreatment with hexamethonium was without significant effect. The intracerebroventricular injection of ACh also increased plasma ACTH concentrations in a dose-dependent manner in conscious rats, but not in pentobarbital-anesthetized animals. Thus, cholinergic hypothalamic input stimulates CRF gene expression in the PVN and CRF secretion into the portal circulation under physiological conditions. The use of conscious animals is essential in elucidating the physiological roles of neurotransmitters and other modulators regulating CRF neurons.

Acetylcholine↗

Dietary high-linoleate safflower oil is not hypocholesterolemic in aged mice after a long-term feeding--comparison with lard, perilla oil and fish oil.

Aged mice (6 months of age) fed a conventional diet were shifted to diets containing 10% lard, high-linoleate safflower seed oil, high alpha-linolenate perilla seed oil or high-docosahexaenoate fish oil. A significant increase in whole body cholesterol (/g wt) was seen within 30 d after the shift (rapid response), followed by a gradual decrease in 60 to 120 d (slow response); similar changes occurred in all the dietary groups. Shortly after the shift, the serum cholesterol concentrations increased to higher levels in the lard and safflower oil groups than in the other groups, and the levels at 120 d were in the group order of safflower oil > lard > perilla oil > fish oil. Rapid and slow responses to dietary shifts were also seen in hepatic cholesterol levels (/g wt), which were higher in the lard group than in the other groups at 120 d. The arterial cholesterol contents of the fish oil group tended to be less than in the other groups at 120 d. Thus in aged mice after a relatively long-term feeding (> one tenth of the life-span), safflower oil was not hypocholesterolemic as compared with lard and other omega 3-rich oils. Long-term feeding of fish oil maintained serum cholesterol concentrations at lower levels than feeding with safflower oil or lard and without accumulating cholesterol in the aorta, liver or whole body; perilla oil was also hypocholesterolemic but to a lesser degree than fish oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Metal-characterization of N-acyl-D-glutamate amidohydrolase from Pseudomonas sp. strain 5f-1.

N-Acyl-D-glutamate amidohydrolase (D-AGase) from Pseudomonas sp. 5f-1 was a zinc-metalloenzyme which contained 2.06-2.61 g.atom of Zn per mole of enzyme. The zinc atom was required for the catalytic activity and stability of the enzyme. The N-terminal amino acid sequence of Pseudomonas sp. 5f-1 D-AGase showed 32% identity to that of Alcaligenes xylosoxydans subsp. xylosoxydans A-6.

Amidohydrolases↗

Cloning and sequencing of a gene encoding D-aminoacylase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6 and expression of the gene in Escherichia coli.

The gene encoding the D-aminoacylase of Alcaligenes xylosoxydans subsp. xylosoxydans A-6 (Alcaligenes A-6) was cloned and its complete nucleotide sequence was identified. The D-aminoacylase structural gene consists of 1452 nucleotides and encodes 484 amino acid residues. The molecular weight of D-aminoacylase was calculated to be 51,918. This value agreed well with the apparent molecular weight of 52,000 found for the purified enzyme from Alcaligenes A-6 by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). The N-terminal amino acid sequence (NH2-SQSDSQPFDLLRAG-) predicted by the nucleotide sequence exactly matched those of the purified D-aminoacylase both from Alcaligenes A-6 and from cloned Escherichia coli (E. coli), with the exception of the removal of the N-terminal methionine processed after translation. The purified recombinant enzyme showed almost the same enzymatic properties as the native enzyme from Alcaligenes A-6. Alcaligenes A-6 D-aminoacylase showed 25-29% homology with L-aminoacylases from Bacillus stearothermophilus, porcine and humans.

Alcaligenes↗

Characterization of the spatial-frequency spectrum in the perception of shape from texture.

The major cue to shape from texture is the compression of texture as a function of surface curvature [J. Exp. Psychol. 13, 242 (1987); Vision Res. 33, 827 (1993)]. A number of computational models have been proposed in which compression is measured by detection of changes in the spatial-frequency spectrum [Comput. Graphics Image Process. 5, (1976)]. We propose that the visual system uses a strategy of characterizing the frequency spectrum by a simple set of measures and of tracking the changes in this characterization rather than determining changes in the shape of the actual spectra. Our evidence is based on a number of psychophysical demonstrations that use stimuli with specifically tailored frequency spectra, constructed from white noise filtered in the frequency domain. Our evidence suggests that the visual system determines the average peak frequency of the spectrum and uses this measure as its characterization. Changes in fp are strongly correlated with the degree of surface curvature, and, over a range of stimuli, fp takes account of the variance in local estimates of the frequency spectrum. One computes fp by determining the peak frequency at each spatial location and then averaging these frequency values over a local spatial region. We show that fp is related to the second-order moment but is more biologically plausible and shows superior ability to function in the presence of noise. As a test of this model, we have constructed a neural network architecture for computing shape from texture. Our model is limited to orthographically projected, homogeneous textures without in-surface rotation. The early stages of the model consist of multiple simple-cell units tuned to different orientations and spatial frequencies. We show that these simple cells are inadequate for the determination of compression but that the outputs of complex-cell-like units after normalization generate estimates of surface slant and tilt. The network shows qualitative agreement with human perception of shape from texture over a wide range of real and artificial stimuli.

Form Perception↗

Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk.

The inhibitory activity of angiotensin I-converting enzyme in milk increased during fermentation with the Calpis sour milk starter containing Lactobacillus helveticus and Saccharomyces cerevisiae. Two kinds of peptides inhibitory to angiotensin I-converting enzyme were purified from the sour milk by using four-step HPLC. The amino acid sequences of these inhibitors were identified as Val-Pro-Pro and Ile-Pro-Pro. The concentrations of peptides providing 50% inhibition of angiotensin I-converting enzyme were 9 and 5 microM, respectively. Most of the inhibitory activity in sour milk was attributed to these two peptides.

Amino Acid Sequence↗

Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme.

This study reports the antihypertensive effect of orally administered doses of either Calpis sour milk or peptides (Val-Pro-Pro and Ile-Pro-Pro), which are inhibitors to angiotensin I-converting enzyme, isolated from the sour milk using strain SHR spontaneously hypertensive rats. Single oral administration of the sour milk (5 ml/kg of BW), corresponding inhibitory units of the peptides Val-Pro-Pro (.6 mg/kg of BW), or Ile-Pro-Pro (.3 mg/kg of BW) significantly decreased the systolic blood pressure from 6 to 8 h after administration. Blood pressure returned to the initial level at 24 h after administration. Antihypertensive activity of these two tripeptides was dose-dependent up to 5 mg/kg of BW. Conversely, the sour milk (25 ml/kg of BW) and mixed tripeptides (10 mg each of Val-Pro-Pro and Ile-Pro-Pro/kg of BW) did not change the systolic blood pressure of the normotensive strain WKY Wistar-Kyoto rats.

Amino Acid Sequence↗

Isolation, characterization and biological activities of novel triprenyl phenols as pancreatic cholesterol esterase inhibitors produced by Stachybotrys sp. F-1839.

Ten triprenyl phenol metabolites were isolated as inhibitors of pancreatic cholesterol esterase from cultures of Stachybotrys sp. F-1839 by solvent extraction and column chromatographies. Combination of spectroscopic analyses revealed that two of these compounds are K-76 (1) and stachybotrydial (2), and that the remaining eight are new congeners (designated F1839-A (3), -B (4), -C (5), -D (6), -E (7), -F (8), -I (9) and -J (10). These compounds inhibited pancreatic cholesterol esterase by 50% at 6 x 10(-5) to 1.1 x 10(-1) M. Inhibition of the enzyme by compound 2, the most potent one among these compounds, was time-dependent and irreversible. When administered to normal rats, 2, at a single oral dose of 100 mg/kg, reduced [14C]cholesterol absorption by 50-60%. In cholesterol-fed mice, dietary supplementation of 2 (0.1%) for 14 days resulted in a 20% reduction in serum total cholesterol level without causing significant change in the high density lipoprotein cholesterol level.

Animals↗

Soluble thrombomodulin purified from human urine exhibits a potent anticoagulant effect in vitro and in vivo.

We examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity > 5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (> 1 TMU /ml), APTT (> 5 TMU/ml), TT (> 5 TMU/ml) and PT (> 40 TMU/ ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Adult↗

[High-resolution CT findings of Pneumocystis carinii pneumonia].

High resolution CT (HRCT) was performed on 7 patients with pneumocystis carinii pneumonia (PCP). Six cases were proven bacteriologically by bronchoalveolar lavage; one case was proven by autopsy. Three patients were re-scanned after specific treatment and symptomatic relief. All the CT scans were abnormal, usually showing bilateral diffuse ground-glass opacity, through which the pulmonary vessels remained visible. Chest X-ray, on the other hand, showed a normal pattern in one patient. Other changes such as air space consolidation (in 4 cases) and thickening of peripheral pulmona vessels (in 2 cases) were also seen. Air space consolidation was found in three cases with mixed infection (cytomegalovirus pneumonia in 2 cases, aspergillosis in one case). No patient showed significant mediastinal or hilar lymph node enlargement, pleural effusion or cystic pulmonary change. HRCT findings such as ground-glass opacity and air space consolidation were shown to disappear in some cases of PCP after specific treatment. HRCT is useful to evaluate the sequential pulmonary changes after the specific therapy.

Adult↗