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Biomedical subjects

A Okada

Publications and source records attributed to A Okada.

At least 199 records · Page 11Linked to original sources
PubMed1997

Matrix metalloproteinases as stromal effectors of human carcinoma progression: therapeutic implications.

The matrix metalloproteinases (MMPs) are extracellular zinc-enzymes implicated in a number of physiological and pathological tissue remodeling processes, including cancer progression. For a long time they have been thought to be produced by malignant cells and to specifically contribute to tumor invasion, through their ability to degrade extracellular matrix components. However, studies performed over the last few years have demonstrated that extracellular proteinases implicated in the progression of human carcinomas, including most MMPs, are in fact predominantly expressed by stromal and not by cancer cells. Furthermore, membrane receptors, activators and/or binding sites for some of these proteinases are also predominantly found to be associated with stromal cells. These findings, together with the observation that MMPs can cleave some molecules implicated in controlling growth factor activities, suggest that the role of MMPs during cancer progression is not limited to facilitating malignant cell invasion alone but is also likely to participate in other aspects of the malignant phenotype. MMPs should in fact be regarded as pan-regulators of tissue neoformation characteristic of malignant tumors, which includes both epithelial cell expansion and stroma formation. In this context, synthetic MMP inhibitors which are presently designed should lead to the development of a new generation of anticancer agents with additional beneficial properties compared to the existing cytotoxic agents used in the treatment of human malignancies.

Extracellular Matrix↗
PubMed1997

Early time-dependent decompression for spinal cord injury: vascular mechanisms of recovery.

Although surgical decompression is often advocated for acute spinal cord injury, the timing and efficacy of early treatment have not been clinically proven. Our objectives were to determine the importance of early spinal cord decompression on recovery of evoked potential conduction under precision loading conditions and to determine if regional vascular mechanisms could be linked to electrophysiologic recovery. Twenty-one mature beagles were anesthetized and mechanically ventilated to maintain normal respiratory and acid-base balance. Somatosensory-evoked potentials from the upper and lower extremities were measured at regular intervals. The spinal cord at T-13 was loaded dorsally under precision loading conditions until evoked potential amplitudes had been reduced by 50%. At this functional endpoint, spinal cord displacement was maintained for either 30 (n = 7), 60 (n = 8), or 180 min (n = 6). Spinal cord decompression was followed by a 3-h monitoring period. Regional spinal cord blood flow was measured with fluorescent microspheres at baseline (following laminectomy) immediately after stopping dynamic cord compression, 5, 15, and 180 min after decompression. Within 5 min after stopping dynamic compression, evoked potential signals were absent in all dogs. We observed somatosensory-evoked potential recovery in 6 of 7 dogs in the 30-min compression group, 5 of 8 dogs in the 60-min compression group, and 0 of 6 dogs in the 180-min compression group. Recovery in the 30- and 60-min groups varied significantly from the 180-min group (p < 0.05). Regional spinal cord blood flow at baseline, 21.4+/-2.2 ml/100/g/min (combined group mean +/- SE) decreased to 4.1+/-0.7 ml/100 g/min after stopping dynamic compression. Reperfusion flows after decompression were inversely related to duration of compression. Of the 7 dogs in the 30 min compression group, 5 min after decompression the blood flow was 49.1+/-3.1 ml/100 g/min, which was greater than two times baseline. In the 180-min compression group early post-decompression blood flow, 19.8+/-6.2 ml/100 g/min, was not significantly different than baseline. Of the 8 dogs in the 60-min compression group, 5 who recovered evoked potential conduction revealed a lower spinal cord blood flow sampled immediately after stopping dynamic compression, 2.1+/-0.4 ml/100 g/min, compared to the 3 who did not recover where blood flow was 8.4+/-2.1 ml/100 g/min (p < 0.05). Reperfusion flows measured as the interval change in blood flow between the time dynamic compression was stopped to 5, 15, or 180 min after decompression, were significantly greater in those dogs that recovered evoked potential function (p < 0.05). Three hours after decompression, spinal cord blood flow in the 3 dogs in the 60-min compression group with no recovery, 11.1+/-2.1 ml/100 g/min, was significantly less than the spinal cord blood flow of the recovered group (n = 5), 20.5+/-2.2 ml/100 g/min. These data illustrate the importance of early time-dependent events following precision dynamic spinal cord loading and sustained compression conditions. Spinal cord decompression performed within 1 h of evoked potential loss resulted in significant electrophysiologic recovery after 3 h of monitoring. This study showed that the degree of early reperfusion hyperemia after decompression was inversely proportional to the duration of spinal cord compression and proportional to electrophysiologic recovery. Residual blood flow during the sustained compression period was significantly higher in those dogs that did not recover evoked potential function after decompression suggesting a reperfusion injury. These results indicate that, after precise dynamic spinal cord loading to a point of functional conduction deficit (50% decline in evoked potential amplitude), a critical time period exists where intervention in the form of early spinal cord decompression can lead to effective recovery of electrophysiologic function in the 1- to 3-h post-decompression p

Animals↗
PubMed1997

Induction of nitric oxide synthase in rat intestine by interleukin-1alpha may explain diarrhea associated with zinc deficiency.

Synthesis of inducible nitric oxide synthase (iNOS) in the intestine may result in local tissue damage. We investigated whether a challenge with interleukin-1alpha could give rise to intestinal iNOS expression and diarrhea in rats of differing zinc status. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) for 4 wk to induce zinc deficiency or a zinc-supplemented diet [50.8 mg zinc/kg; controls, including pair-fed (PF ) and ad libitum (AL) consumption groups], and then subcutaneously injected with interleukin-1alpha (2 x 10(7) units/kg body wt). Without the interleukin-1alpha challenge, ZD rats had significantly lower plasma zinc concentration than the other groups. Intestinal metallothionein-1 mRNA abundance was lower in ZD rats than in AL rats. iNOS was expressed in the intestine of ZD rats but not in the others. None of the rats experienced diarrhea during the feeding period. Interleukin-1alpha led to a reduction in plasma zinc concentration, enhancement in intestinal metallothionein-1 mRNA levels, and expression of the intestinal iNOS gene in all groups. However, the abundance of iNOS mRNA was significantly higher in ZD rats than in the other groups. The presence of iNOS protein was demonstrated by immunohistochemical staining in the intestine of ZD rats that had been treated with interleukin-1alpha 12 h earlier. In addition, diarrhea occurred in most of the ZD rats and some of the PF rats but not in AL rats after interleukin-1alpha treatment. We conclude that ZD rats respond to interleukin-1alpha challenge more severely than controls, reflected by a more marked and prolonged iNOS expression and a greater incidence of diarrhea.

Animals↗
PubMed1997

Identification of the nucleotides in the A-rich bulge of the Tetrahymena ribozyme responsible for an efficient self-splicing reaction.

P5abc is a large extension of the P5 element characteristic of subclasses IC1 and IC2 of group I introns. It has a conserved region termed the A-rich bulge, that is responsible for activation of the Tetrahymena self-splicing intron. By employing a modified color-colony assay system, we identified four adenosines in the bulge that are responsible for an efficient splicing reaction. On comparison with the X-ray crystal structure of the P4-5-6 domains of the Tetrahymena intron, three adenosines at positions 183, 184, and 186 were found to be identical to those significantly contributing to the formation of its tertiary structure. However, our results show that an adenosine at 187 is involved in the formation of a Watson-Crick base pair with U135, although it forms a Hoogsteen base pair in the crystal structure.

Animals↗
PubMed1997

Intragastric distribution of nonsteroidal anti-inflammatory drug-related ulcers in patients without collagen diseases.

During the long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs), approximately 3% of patients have gastric ulcers develop in each year. Although much is known about the endoscopic characteristics of NSAID-induced gastric ulcers in patients with rheumatoid arthritis (RA), it is not clear where in the stomach NSAIDs induce ulcers in patients without RA. We looked at that question. During the 1-year study period, 29 patients with gastric ulcer, who had been taking NSAIDs regularly for more than 4 weeks mainly for osteoarthritis, were identified. Seventy-five patients with gastric ulcers who had not taken NSAID also were found. The sites of gastric ulcers of these two groups were quite different. The NSAID-induced ulcers mainly were found in the gastric antrum, whereas the majority of NSAID-unrelated ulcers were in the gastric corpus. We conclude that NSAID-induced ulcers in non-RA patients mainly are formed in the gastric antrum.

Adult↗
PubMed1997

Effects of daily alcohol intake on the blood pressure differ depending on an individual's sensitivity to alcohol: oriental flushing as a sign to stop drinking for health reasons.

OBJECTIVE: To determine whether flushing of the facial skin in response to alcohol consumption (alcohol flushing) is a warning sign of hypertension. We also sought the relationship between alcohol flushing and other risk factors that may contribute to the development of hypertension. METHODS: We first investigated the relationship of the aldehyde dehydrogenase 2 (ALDH2) genotype to alcohol flushing for 53 normal volunteers. We evaluated the relationships among hypertension, alcohol consumption, and facial flushing for 1011 middle-aged Japanese men (aged 40-68 years; mean 51.6 +/- 5.5 years), on the basis of their responses to questionnaires and health records. RESULTS: The first examination of 53 normal volunteers showed that there were differences in the degree of alcohol flushing between the ALDH2 genotypes (P < 0.01). Hypertension was observed in 27.4% of the study population (277 of 1011), and was correlated positively to alcohol consumption (P < 0.01). The prevalence of hypertension differed significantly among these four groups: there was a 22.4% prevalence (70 of 312) among subjects with no flushing, a 33.8% prevalence (113 of 334) among those with slight flushing, a 27% prevalence (84 of 311) among those with visible flushing, and an 18.5% prevalence (10 of 54) among subjects who were almost completely intolerant to alcohol (P < 0.05). In particular, heavy drinkers who consumed > or = 1.5 Go (a traditional Japanese unit equivalent to 27 g ethanol) a day had a high prevalence of hypertension with slight and visible skin flushing [42% (63 of 150) and 40.7% (24 of 59), respectively]. That a family history of hypertension, greater age, heavy alcohol consumption, obesity, and symptoms of intoxication including flushing were correlated significantly to the prevalence of hypertension for all groups was demonstrated by multiple logistic regression analysis (P < 0.05). CONCLUSIONS: A repeated heavy alcohol intake could increase the risk of hypertension for Japanese subjects who exhibit skin flushing in response to alcohol consumption. Chronic alcohol intake by subjects with alcohol flushing might bring about a significant increase in blood acetaldehyde levels and cause an additional rise in the blood pressure.

Adult↗
PubMed1997

Spectral characteristics of ventricular response to atrial fibrillation.

To investigate the spectral characteristics of the fluctuation in ventricular response during atrial fibrillation (AF), R-R interval time series obtained from ambulatory electrocardiograms were analyzed in 45 patients with chronic AF and in 30 age-matched healthy subjects with normal sinus rhythm (SR). Although the 24-h R-R interval spectrum during SR showed a 1/f noise-like downsloping linear pattern when plotted as log power against log frequency, the spectrum during AF showed an angular shape with a breakpoint at a frequency of 0.005 +/- 0.002 Hz, by which the spectrum was separated into long-term and short-term components with different spectral characteristics. The short-term component showed a white noise-like flat spectrum with a spectral exponent (absolute value of the regression slope) of 0.05 +/- 0.08 and an intercept at 10(-2) Hz of 4.9 +/- 0.3 log(ms2/Hz). The long-term component had a 1/f noise-like spectrum with a spectral exponent of 1.26 +/- 0.40 and an intercept at 10(-4) Hz of 7.0 +/- 0.3 log(ms2/Hz), which did not differ significantly from those for the spectrum during SR in the same frequency range [spectral exponent, 1.36 +/- 0.06; intercept at 10(-4) Hz, 7.1 +/- 0.3 log(ms2/Hz)]. The R-R intervals during AF may be a sequence of uncorrelated values over the short term (within several minutes). Over the longer term, however, the R-R interval fluctuation shows the long-range negative correlation suggestive of underlying regulatory processes, and spectral characteristics indistinguishable from those for SR suggest that the long-term fluctuations during AF and SR may originate from similar dynamics of the cardiovascular regulatory systems.

Adult↗
PubMed1997

[Trial of a detachable Y-shaped tube with two valves for serial examinations of CT arterial portography and CT hepatic arteriography].

In five patients with hepatocellular carcinoma, CT arterial portography (CTAP) and CT hepatic arteriography (CTHA) were performed serially by using a newly developed detachable Y-shaped tube with two valves that could be attached to a conventional angiographic sheath. Two catheters could be inserted into the conventional angiographic sheath without blood backflow by using the Y-shaped tube. One catheter could be easily and safety placed on the common or proper hepatic artery, and the other on the superior mesenteric artery. This detachable Y-shaped tube with two valves could make it easy to perform serial CTAP and CTHA examinations.

Angiography↗
PubMed1997

[Home parenteral nutrition in the elderly].

The number of elderly patients receiving home parenteral nutrition (HPN) has been increasing. This could result from several factors such as advances in HPN therapy and the natural aging of long-term older patients on HPN. Our experience shows that elderly patients receiving HPN are likely to be highly dependent on family members to supervise their HPN therapy. Therefore, indepth education of family members is essential before HPN is initiated. The important points to manage the elderly HPN patients are as follows: 1) It takes a long time for the elderly to learn the technique. 2) They often make technical mistakes. 3) In many cases, patients are not living with their children. Therefore, it is often difficult for them to support the patient's HPN therapy. 4) Nurses play an important role in giving instructions on catheter care and HPN techniques to the patient or family members.

Aged↗
PubMed1997

[Management of anorectal malformations and Hirschsprung's disease].

Anorectal malformations include various type of anomalies resulting from abnormal development of hindgut, allantois and Müllerian duct. It is essential for the successful construction of new anorectum to know the correct anatomy of pelvic muscles. Peña and deVries proposed a new concept of pelvic muscles, the surgical entities "muscle complex". Based on new anatomical understanding, posterior sagittal anorectoplasty (PSARP) was described by Peña and deVries and has gained a wide acceptance in the world. This approach may lead us a better understanding of surgical anatomy and change our therapeutic concept. Hirschsprung's disease is known to be congenital disorder characterized by the absence of enteric nervous system. Recently, gene mutations associated with Hirschsprung's disease have been widely investigated and gene mutations of RET, glial cell line-derived neutrophic factor (GDNF), endothelin receptor B (EDNRB) and endothelin-3 (EDN3) have been identified in patients with Hirschsprung's disease. These results suggest a role of gene mutations in the migration and differentiations of neural crest-derived neuroblasts. One-stage endorectal pull-through procedure in the neonate and a primary laparoscopic pull-through procedure has been shown to be feasible.

Anus, Imperforate↗
PubMed1996

Respiratory sinus arrhythmia. A phenomenon improving pulmonary gas exchange and circulatory efficiency.

BACKGROUND: The primary mechanisms of respiratory sinus arrhythmia (RSA) are understood to be the modulation of cardiac vagal efferent activity by the central respiratory drive and the lung inflation reflex, and the degree of RSA increases with cardiac vagal activity. However, it is unclear whether RSA serves an active physiological role or merely reflects a passive cardiovascular response to respiratory input. We hypothesized that RSA benefits pulmonary gas exchange by matching perfusion to ventilation within each respiratory cycle. METHODS AND RESULTS: In seven anesthetized dogs, a model stimulating RSA was made. After elimination of endogenous autonomic activities, respiration-linked heartbeat fluctuations were generated by electrical stimulation of the right cervical vagus during negative pressure ventilation produced by phrenic nerve stimulation (diaphragm pacing). The vagal stimulation was performed in three conditions; phasic stimulation during expiration (artificial RSA) and during inspiration (inverse RSA) and constant stimulation (control) causing the same number of heartbeats per minute as the phasic stimulations. Although tidal volume, cardiac output, and arterial blood pressure were unchanged, artificial RSA decreased the ratio of physiological dead space to tidal volume (VD/VT) and the fraction of intrapulmonary shunt (Qap/Qt) by 10% and 51%, respectively, and increased O2 consumption by 4% compared with control. Conversely, reverse RSA increased VD/VT and Qap/Qt by 14% and 64%, respectively, and decreased O2 consumption by 14%. CONCLUSIONS: These results support our hypothesis that RSA benefits the pulmonary gas exchange and may improve the energy efficiency of pulmonary circulation by "saving heartbeats."

Animals↗
PubMed1996

Expression of inducible nitric oxide synthase mRNA in rat digestive tissues after endotoxin and its role in intestinal mucosal injury.

Nitric oxide (NO) production is increased in the intestine and may contribute to intestinal injury in sepsis. However, the tissue expression of inducible NO synthase (iNOS) mRNA throughout the digestive tract and its relation with the mucosal damage after endotoxin challenge remain unknown. We therefore measured tissue expression of mRNA encoding iNOS by Northern blot analysis and reverse transcription PCR. The iNOS mRNA was detectable at 1 h, peaked at 4 h, and remained faint at 24 h after endotoxin injection in esophagus, duodenum, jejunum, ileum, and colon, but not in the stomach. Pre-treatment with dexamethasone attenuated the rise of iNOS mRNA. Both dexamethasone and NOS inhibitor, L-NAME, ameliorated the endotoxin-induced increase in intestinal mucosal permeability. Our results indicate that there is tissue-specific expression of iNOS mRNA in the digestive tract. The manipulations that decrease NO production may have therapeutic potential in preserving intestinal mucosal integrity in sepsis.

Animals↗
PubMed1996

Inversely correlated expression of p16 and Rb protein in non-small cell lung cancers: an immunohistochemical study.

Cdk4-mediated phosphorylation of Rb protein is inhibited by p16, a product of a possible tumor suppressor gene. We examined the expression of p16 and Rb protein by means of immunohistochemistry in 61 non-small cell lung cancers and have demonstrated an inverse relationship between the expression of p16 and Rb protein: 28/30 specimens that did not stain for p16 stained for Rb and 21/31 p16-positive specimens did not stain for Rb. Only 1 of the p16-negative specimens had a mutation of exon 2 of the CDKN2 gene. Our results indirectly support the theory that p16 expression is negatively regulated by the functional Rb protein.

Base Sequence↗
PubMed1996

Synaptic relationships between axon terminals from the mediodorsal thalamic nucleus and layer III pyramidal cells in the prelimbic cortex of the rat.

A combined study of anterograde axonal degeneration and Golgi electron microscopic technique was designed to examine the distribution and density of axon terminals from the mediodorsal thalamic nucleus (MD) over layer III pyramidal cells in the prelimbic cortex of the rat. The reconstructive analysis of serial ultrathin sections of gold-toned apical and basal dendrites of layer III pyramidal cells showed that degenerating thalamocortical axon terminals from MD formed asymmetrical synaptic contacts predominantly with dendritic spines of the identified basal dendrites as well as apical dendrites. There was little difference in the numerical density of thalamocortical synapses from MD per unit length of both apical and basal dendrites.

Animals↗