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Biomedical subjects

K Okubo

Publications and source records attributed to K Okubo.

At least 55 records · Page 3Linked to original sources
PubMed2001

Characteristics of the human ocular surface epithelium.

An appreciation of the biological characteristics of the human ocular surface epithelium affords us a great insight into the physiology of the human ocular surface in health and disease. Here, we review five important aspects of the human ocular surface epithelium. First, we recognize the discovery of corneal epithelial stem cells, and note how the palisades of Vogt have been suggested as a clinical marker of their presence. Second, we introduce the concept of the gene expression profile of the ocular surface epithelium as arrived at using a new strategy for the systematic analysis of active genes. We also provide a summary of several genes abundantly or uniquely expressed in the human corneal epithelium, namely clusterin, keratin 3, keratin 12, aldehyde dehydrogenase 3 (ALDH3), troponin-I fast-twitch isoform, ssig-h3, cathepsin L2 (cathepsin V), uroplakin Ib, and Ca(2+)-activated chloride channel. Genes related to limbal and conjunctival epithelia are also described. Third, we touch upon the genetic abnormalities thought to be involved with epithelial dysfunction in Meesmann's dystrophy, gelatinous drop-like corneal dystrophy, and the ssig-h3-mutated corneal dystrophies. Fourth, we provide an update regarding the current state of knowledge of the role of cytokines, growth factors and apoptosis in relation to ocular surface homeostasis and tissue reconstruction; the main factors being epidermal growth factor (EGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), transforming growth factor-ss (TGF-ss), and some inflammatory cytokines. Fifth, corneal epithelial barrier function and dysfunction as measured by fluorophotometry is remarked upon, with an explanation of the FL-500 fluorophotometer and its ability to detect corneal epithelial dysfunction at a subclinical level. The research described in this review has undoubtedly generated a complete understanding of corneal epithelial pathophysiology-an understanding that, directly or indirectly, has helped advance the development of new therapeutic modalities for ocular surface reconstruction.

Apoptosis↗
PubMed2001

Cerebral metabolism and regional cerebral blood flow during moderate systemic cooling in newborn piglets.

BACKGROUND: Clinical trials of hypothermic therapy in asphyxiated infants have started recently. However, clinical studies have been delayed by the difficulty in selecting infants with a bad neurological prognosis and by the concern regarding adverse effects of hypothermia. The purpose of this study is to examine the effects of systemic cooling on cerebral metabolism (CMR) and the regional cerebral blood flow (rCBF) in newborn piglets. METHODS: The rCBF in the seven parts of the brain were measured with colored microspheres. The blood samples for the measurement of cerebral oxygen consumption (CMRO2) and cerebral glucose consumption (CMRglc) was collected from the umbilical artery and the superior sagittal sinus. RESULTS: Reductions of cerebral cortex temperature to 32 degrees C decreased blood flow in all brain regions. In particular, blood flow in the brainstem decreased more significantly than in any other region. The total cerebral blood flow (CBF), CMRO2 and CMRglc, respectively, decreased to 32.3+/-3.9 mL/100 g per min, 2.8+/-1.0 mLO2/100 g per min and 22+/-12 mmol/100 g per min at 32 degrees C (41, 53 and 46% of the initial value). The CBF decreased in parallel with CMRO2 and CMRglc down to 35 degrees C, but CBF decreased to a greater extent than CMRO2 and CMRglc at below 35 degrees C. CONCLUSIONS: The indication of hypothermic therapy and the degree of cooling have to be performed very carefully. Systemic cooling is especially dangerous for the total asphyxiated infants who might have damage to the brainstem because the blood flow in the brainstem has significantly decreased during hypothermia.

Animals↗
PubMed2001

Acute normovolemic hemodilution for radical prostatectomy: can it replace preoperative autologous blood transfusion?

BACKGROUND: Although preoperative autologous blood donation (PAD) is accepted as a standard of care for radical prostatectomy, it is costly, time-consuming and has risks associated with blood storage. Acute normovolemic hemodilution (ANH) is reported to be less expensive and to preserve blood components more effectively than PAD. In the present study, the efficacy and safety of these two autologous blood-collection techniques were compared. METHODS: The study included 16 consecutive patients scheduled for radical prostatectomy. The first eight patients underwent conventional preoperative autologous blood donation of 400 mL 1 week before the operation (PAD group) and the second eight patients underwent acute normovolemic hemodilution followed by immediate operation (ANH group). All blood collected was transfused in the perioperative period. Preoperative and postoperative hematocrit levels in these two groups were compared. RESULTS: There were no differences in preoperative hematocrit, time of operation or operative blood loss between the two groups. In the ANH group, 1080 +/- 160 mL of blood were collected. The postoperative hematocrit level did not differ significantly between the groups. No patient in either group received allogeneic blood transfusion or experienced an adverse event directly related to blood transfusion. CONCLUSION: The two blood-conservation strategies resulted in similar postoperative hematologic outcomes. Given its advantages, which include lower cost, lower risk and higher convenience, ANH is one of the procedures that may replace conventional PAD for use in radical prostatectomy.

Aged↗
PubMed2001

Intrarenal bacillus Calmette-Guérin therapy for carcinoma in situ of the upper urinary tract: long-term follow-up and natural course in cases of failure.

OBJECTIVE: To assess the long-term efficacy of intrarenal bacillus Calmette-Guérin (BCG) therapy for the treatment of cytologically diagnosed upper tract carcinoma in situ (CIS) and report the time course in cases of failure. PATIENTS AND METHODS: Fourteen renal units in 11 patients cytologically diagnosed as having upper urinary tract (UUT) CIS were treated with intrarenal BCG instillation. The BCG solution was administered by retrograde ureteric catheterization weekly for 6 weeks. RESULTS: Seven units were radiologically and cytologically free of disease at a median follow-up of 60 months. Two units which showed an initial response had recurrence with ipsilateral UUT CIS. The remaining five units did not respond to BCG. Of seven units with an initial negative response or recurrent UUT CIS, nephroureterectomy was undertaken in one because of coincidental renal cell carcinoma. In four of the remaining six units, invasive pelvic tumour developed at a mean follow-up of 20.5 months after the final instillation. Computed tomography showed wall thickening of the renal pelvis in two and mass-forming tumour in the renal parenchyma mimicking renal cell carcinoma in two. In three of these four cases, retrograde pyelography did not show typical findings of renal pelvic tumour, e.g. filling defect, infundibular obstruction or stenosis. CONCLUSIONS: Intrarenal BCG is effective in the treatment of UUT CIS in a long-term follow-up. In cases with a poor response or ipsilateral recurrence of CIS, there is a high risk of developing invasive tumour. Close follow-up using computed tomography is recommended because of the atypical radiographic findings of such tumours.

Adjuvants, Immunologic↗
PubMed2001

Diverse transcriptional initiation revealed by fine, large-scale mapping of mRNA start sites.

Determination of the mRNA start site is the first step in identifying the promoter region, which is of key importance for transcriptional regulation of gene expression. The 'oligo-capping' method enabled us to introduce a sequence tag to the first base of an mRNA by replacing the cap structure of the mRNA. Using cDNA libraries made from oligo-capped mRNAs, we could identify the transcriptional start site of an individual mRNA just by sequencing the 5'-end of the cDNA. The fine mapping of transcriptional start sites was performed for 5880 mRNAs in 276 human genes. Contrary to our expectations, the majority of the genes showed a diverse distribution of transcriptional start sites. They were distributed over 61.7 bp with a standard deviation of 19.5. Our finding may reflect the dynamic nature of transcriptional initiation events of human genes in vivo.

Base Sequence↗
PubMed2001

Divergent renal vasodilator action of L- and T-type calcium antagonists in vivo.

OBJECTIVE: To assess the in-vivo action on the renal microvasculature of the calcium antagonists nifedipine (L-type blocker), efonidipine (L/T-type blocker), and mibefradil (predominant T-type blocker). DESIGN: An intravital needle-type charge-coupled device (CCD) camera videomicroscope was introduced to visualize the renal microcirculation directly in vivo. METHODS: In anesthetized mongrel dogs, nifedipine (0.01-1 mg/kg per min), efonidipine (0.033-0.33 mg/kg per min), or mibefradil (0.01-1 mg/kg per min) was infused intravenously after the insertion of a CCD probe into the kidney. Renal microvascular responses to calcium antagonists were directly evaluated, with concomitant observation of renal clearance. RESULTS: Each calcium antagonist caused modest vasodepressor action without affecting heart rate. Nifedipine (1 mg/kg per min, n = 9) increased renal plasma flow (RPF) (14 +/- 4%, P < 0.05) and glomerular filtration rate (GFR) (19 +/- 5%, P < 0.05), and tended to increase the filtration fraction (5 +/- 2% increment, P = 0.07). Efonidipine (0.33 mg/kg per min, n = 9), however, had no effect on filtration fraction, with 14 +/- 6% increments in RPF (P < 0.05) and 14 +/- 7% increments in GFR (P = 0.08). Rather, mibefradil (1 mg/kg per min, n = 9) elicited 6 +/- 2% decreases in filtration fraction (P < 0.05), with slight increments in RPF (6 +/- 3%) and no changes in GFR. In direct in-vivo microvasculature observations, nifedipine caused predominant (22 +/- 2%) dilatation of afferent arterioles (from 15.5 +/- 0.4 to 18.9 +/- 0.4 microm, n = 5), compared with that of efferent arterioles (10 +/- 2%; from 11.0 +/- 0.4 to 12.1 +/- 0.3 microm). In contrast, efonidipine caused a similar magnitude of vasodilatation (16 +/- 4%) compared with 18 +/- 2%; n = 6), and mibefradil caused greater dilatation of efferent arterioles (20 +/- 4%, n = 7) than that of afferent arterioles (13 +/- 4%). CONCLUSIONS: There exists marked heterogeneity in action of nifedipine, efonidipine and mibefradil on the renal microvascular in canine kidneys in vivo. Furthermore, our current observations suggest an important contribution of T-type calcium channel activity to efferent arteriolar tone in vivo.

Animals↗
PubMed2001

Laparoscopic partial nephrectomy with a microwave tissue coagulator for small renal tumor.

PURPOSE: Laparoscopic partial nephrectomy is a challenging procedure due to the risk of excessive bleeding. We evaluated the usefulness of a microwave tissue coagulator during laparoscopic partial nephrectomy for small renal tumor. MATERIALS AND METHODS: From January to July 2000, 6 patients with small renal tumors, from 11 to 25 mm. in diameter, underwent laparoscopic partial nephrectomy with a microwave tissue coagulator without renal pedicle clamping. There were 4 patients who underwent the transperitoneal and 2 who underwent the retroperitoneal approaches. RESULTS: Mean operating time was 186 minutes (range 131 to 239), and blood loss was minimal. Complications were mild and tolerable, and there was no significant deterioration of renal function. CONCLUSIONS: Laparoscopic partial nephrectomy with a microwave tissue coagulator is a useful and less invasive method for treatment of select small renal tumors. Long-term followup of patients is warranted to determine the potential for cancer control with this method.

Adult↗
PubMed2001

Identification and characterization of the potential promoter regions of 1031 kinds of human genes.

To understand the mechanism of transcriptional regulation, it is essential to identify and characterize the promoter, which is located proximal to the mRNA start site. To identify the promoters from the large volumes of genomic sequences, we used mRNA start sites determined by a large-scale sequencing of the cDNA libraries constructed by the "oligo-capping" method. We aligned the mRNA start sites with the genomic sequences and retrieved adjacent sequences as potential promoter regions (PPRs) for 1031 genes. The PPR sequences were searched to determine the frequencies of major promoter elements. Among 1031 PPRs, 329 (32%) contained TATA boxes, 872 (85%) contained initiators, 999 (97%) contained GC box, and 663 (64%) contained CAAT box. Furthermore, 493 (48%) PPRs were located in CpG islands. This frequency of CpG islands was reduced in TATA(+)/Inr(+) PPRs and in the PPRs of ubiquitously expressed genes. In the PPRs of the CGM2 gene, the DRA gene, and the TM30pl genes, which showed highly colon specific expression patterns, the consensus sequences of E boxes were commonly observed. The PPRs were also useful for exploring promoter SNPs.

Base Sequence↗
PubMed2001

Identification and characterization of two distinct GnRH receptor subtypes in a teleost, the medaka Oryzias latipes.

We report the identification and characterization of two distinct GnRH receptor (GnRH-R) subtypes, designated GnRH-R1 and GnRH-R2, in a model teleost, the medaka Oryzias latipes. These seven-transmembrane receptors of the medaka contain a cytoplasmic C-terminal tail, which has been found in all other nonmammalian GnRH-Rs cloned to date. The GnRH-R1 gene is composed of three exons separated by two introns, whereas the GnRH-R2 gene has an additional intron and therefore consists of four exons and three introns. The GnRH-R1 and GnRH-R2 genes, both of which exist as single-copy genes in the medaka genome, were mapped to linkage groups 3 and 16, respectively. Inositol phosphate assays using COS-7 cells transfected with GnRH-R1 and GnRH-R2 demonstrated that they had remarkably different ligand sensitivities, although both receptors showed highest preference for chicken-II-type GnRH. Phylogenetic analysis showed the presence of three paralogous lineages for vertebrate GnRH-Rs and indicated that neither GnRH-R1 nor GnRH-R2 is the medaka ortholog to mammalian GnRH-Rs that lack a cytoplasmic tail. This, together with an observation that medaka-type GnRH had low affinity for GnRH-R1 and GnRH-R2, suggests that a third GnRH-R may exist in the medaka.

Amino Acid Sequence↗
PubMed2001

A mainstay of functional food science in Japan--history, present status, and future outlook.

The development of food science in the near future probably depends on the advance in functional food science, the concept of which was proposed first in Japan nearly 15 years ago. The new science has been internationally distributed and accepted as conceptually being beyond nutrition. In Japan, however, it traced a unique path of progress in the form of a product-driven rather than concept-driven science. Actually, a number of substances and products with potential for disease risk reduction rather than simply for health maintenance have been investigated for their body-modulating functions. Some of them have been applied in practice to the industrialization of functional foods in terms of "foods for specified health uses" legally defined by new legislation. A variety of sophisticated methods have been introduced as well, including the so-called "XYZ" evaluation system, database construction for assessment of the function, and even the DNA microarray technique. The Ministry of Agriculture, Forestry, and Fisheries (MAFF) and the Ministry of Health and Welfare (MHW) also commenced their scientific as well as political activity, with its spread to industries which almost simultaneously began to vigorously investigate functional food products for enlargement of the food market. With all of this as a background, the Japan Liaison of the International Union of Food Science and Technology (IUFoST) hold a function food science symposium on behalf of related scientific bodies including the Japan Section of the International Life Science Institute (ILSI). This paper is an overview compiled from 12 presentations made in the symposium, with the aim of internationally publicizing the activity of functional food science in Japan.

Animals↗
PubMed2001

Superoxide- and 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities of soyasaponin beta g related to gallic acid.

Soyasaponin beta p g at 1 mm had 8% scavenging activity for O2-, and 25 microM beta g scavenged 20.9% for the DPPH radical (IC50: 63.8 microM). In the soyasaponin beta g-gallic acid system, synerigistic effects were observed at a low level of gallic acid concentration. The spin density distribution calculated by the MNDO/AM1 method showed unpaired electron localization on the carbons at C-4 and C-6, and on the ketone group at C-4 of the DDMP moiety. Furthermore, for soyasaponin beta g, the MNDO/AM1 method gave an ionization potential of 8.38 eV, electron affinity of 1.16 eV and Mulliken electronegativity of 4.77 eV. Based on this evidence, the synergistic antiradical effects of the soyasaponin beta g-gallic acid system are assumed to involve two-electron reduction from gallic acid.

Bepridil↗
PubMed2001

Chemiluminescence of hemoglobin and identification of related compounds with the hemoglobin chemiluminescence in plasma.

A low level of chemiluminescence by hemoglobin (Hb) was detected in the reaction with H2O2 and hydrogen donors such as gallic acid and catechins. The photon intensity was affected by the ferric state of Hb (methemoglobin > oxyhemoglobin), and was roughly correlated with the radical-scavenging potential of catechins. We hypothesized the reversible activation reaction of Hb as the chemiluminescence mechanism of the H2O2/gallic acid/Hb system. It is indicated that the oxidized-Hb (Hb-OOH) formation was a chemiluminescence-rate-determining step and one-electron reduction by a hydrogen donor of the compound-I-type intermediate ([.XFeIV] = O) proved a chemiluminescence-specificity-determining step. Spectral analysis showed that the photon emission from the H2O2/gallic acid/Hb system was produced without singlet oxygen generation. The concentration dependence of photon intensity suggests a high consumption ratio of H2O2 leading to protection from H2O2 toxicity. Albumin was defined as a hydrogen donor by the isolation of chemiluminescent substance in plasma using this chemiluminescence system.

Catechin↗
PubMed2001

Tubeless cutaneous ureterostomy: the Toyoda method revisited.

PURPOSE: Cutaneous ureterostomy is a less invasive method of urinary diversion and an attractive option especially in patients at high risk. We retrospectively examined the long-term outcome of the method introduced by Toyoda. MATERIALS AND METHODS: Since 1983 the Toyoda cutaneous ureterostomy has been performed in 61 patients (103 renal units) with a minimum of 3 months of followup. The ureteral patency rate was reviewed. RESULTS: Of the 92 renal units (89%) that achieved a tubeless condition 53 (51%) had no hydronephrosis, 23 (22%) had mild to moderate hydronephrosis without the need for treatment, 14 (14%) were not evaluated during followup and 2 (2%) were removed due to subsequent renal pelvic and/or ureteral carcinoma. CONCLUSIONS: A high ureteral patency rate was achieved with the Toyoda cutaneous ureterostomy. This procedure is a reasonable alternative to other forms of urinary diversion.

Adult↗
PubMed2001

Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis.

This study examined the effects of different types of calcium channel antagonists on renal haemodynamics and natriuresis. The intravenous infusion of nifedipine (L-type blocker), efonidipine (L/T-type blocker) or mibefradil (predominant T-type blocker) into anaesthetized dogs elicited similar, albeit modest, reductions in blood pressure. Nifedipine (1 microgram.min(-1).kg(-1)) increased renal plasma flow (RPF) (23+/-6%; P<0.05) and glomerular filtration rate (GFR) (25+/-5%; P<0.05) (all values are means+/-S.E.M., n=7). Efonidipine (0.33 microgram .min(-1).kg(-1)) also elevated RPF (18+/-6%; P<0.05), and tended to increase GFR (17+/-8%; P=0.08). These antagonists exerted contrasting actions on the filtration fraction (FF), with an increase being elicited by nifedipine, whereas efonidipine had no effect. Furthermore, mibefradil (0.01-1 microgram.min(-1).kg(-1)) slightly elevated RPF (between 5+/-3% and 8+/-3%), but failed to alter GFR, resulting in a decrease in FF. Nifedipine slightly increased urinary sodium excretion (U(Na)V) (29+/-16% increase at 1 microgram .min(-1).kg(-1)) and fractional sodium excretion (FE(Na)) (18+/-14%), whereas efonidipine (0.33 microgram .min(-1).kg(-1)) elicited marked elevations in U(Na)V (110+/-38%; P<0.05) and FE(Na) (102+/-44%; P<0.05). Mibefradil (1 microgram .min(-1).kg(-1)) exerted a moderate natriuretic action [U(Na)V, +60+/-32% (P=0.1); FE(Na), +67+/-20% (P<0.05)]. Furthermore, although a positive correlation was observed between U(Na)V and urinary nitrate/nitrite excretion, no differences were noted between the various calcium channel antagonists. Collectively, this study demonstrates that the glomerular haemodynamic and natriuretic actions of these calcium channel antagonists, which possess diverse blocking activities on L/T-type channels, vary. Based on the divergent actions on FF (i.e. increase, no change and decrease by nifedipine, efonidipine and mibefradil respectively), the natriuretic action of calcium channel antagonists is possibly attributed to the inhibition of tubular sodium reabsorption associated with increased post-glomerular blood flow, rather than increased GFR.

Animals↗
PubMed2001

[Clinical efficacy of magnetic resonance cholangiopancreatography in the diagnosis of biliary tract diseases].

This study was carried out to clarify the efficacy of magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of biliary tract diseases, Three hundred and eleven patients who underwent MRCP and ERCP during the period from January 1999 to December 1999 at our institution were included in the study. Two gastroenterologists who were blinded to results of direct cholangiography and final diagnoses interpreted MRCP images prospectively. The biliary duct was visualized by MRCP and ERCP in 99.4% and 89.5% of the cases, respectively. The sensitivity, specificity, and accuracy of MRCP in the diagnosis of choledocholithiasis were 95%, 97%, and 97%, respectively. MRCP depicted the presence of strictures with a sensitivity, specificity, and accuracy of 97%, 96%, and 96%, respectively. There were three false-positive cases because of artifacts from arterial compression, The accuracy of MRCP and ERCP in differentiation of benign strictures from malignant ones was 85% and 96%, respectively. Based on these results, it is concluded that MRCP has high capability in visualization of the biliary tree, and in detection of stones and strictures, To avoid over and under-diagnosis, awareness of some pitfalls inherent in, MRCP is important. We suggest that MRCP should be recommended for patients with suspicion of biliary tract diseases in the initial stage of making diagnosis.

Adult↗
PubMed2000

A novel form of gonadotropin-releasing hormone in the medaka, Oryzias latipes.

The present study has identified three molecular forms of gonadotropin-releasing hormone (GnRH) in the brain of a teleost, the medaka, by isolation of their cDNAs. This species has a novel GnRH, which is here named medaka-type GnRH (mdGnRH), in addition to two characterized forms, chicken-II-type GnRH (cGnRH-II) and salmon-type GnRH (sGnRH). Phylogenetic analysis showed that mdGnRH is a medaka homolog of and seabream-type GnRH (sbGnRH) and mammalian-type GnRH (mGnRH) in other species, and suggested that all vertebrates have three distinct GnRHs. Furthermore, in situ hybridization revealed that the mdGnRH gene is expressed only in neurons clustered within the preoptic area as sbGnRH and mGnRH genes in other species are, while the genes for cGnRH-II and sGnRH are only in the midbrain tegmentum and nucleus olfactoretinalis, respectively. This result suggested that mdGnRH is a hypophysiotropic factor and the other two forms are involved in other physiological events as neuromodulators or neurotransmitters.

Amino Acid Sequence↗