Expression of matrix metalloproteinases in gastric carcinoma and possibility of clinical application of matrix metalloproteinase inhibitor in vivo.
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Acetamides↗
Biomedical subjects
T Kubota
Publications and source records attributed to T Kubota.
Pt L3-edge XANES studies about the hydrogen adsorption on small Pt particles.
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Journal Article↗
Cloning, expression, and characterization of a novel UDP-galactose:beta-N-acetylglucosamine beta1,3-galactosyltransferase (beta3Gal-T5) responsible for synthesis of type 1 chain in colorectal and pancreatic epithelia and tumor cells derived therefrom.
The sialyl Lewis a antigen is a well known tumor marker, CA19-9, which is frequently elevated in the serum in gastrointestinal and pancreatic cancers. UDP-galactose:N-acetylglucosamine beta1, 3-galactosyltransferase(s) (beta3Gal-Ts) are required for the synthesis of the sialyl Lewis a epitope. In the present study, a novel beta3Gal-T, named beta3Gal-T5, was isolated from a Colo205 cDNA library using a degenerate primer strategy based on the amino acid sequences of the four human beta3Gal-T genes cloned to date. Transfection experiments demonstrated that HCT-15 cells transfected with the beta3Gal-T5 gene expressed all the type 1 Lewis antigens. In gastrointestinal and pancreatic cancer cell lines, the amounts of beta3Gal-T5 transcripts were quite well correlated with the amounts of the sialyl Lewis a antigens. The beta1,3Gal-T activity toward agalacto-lacto-N-neotetraose was also well correlated with the amounts of beta3Gal-T5 transcripts in a series of cultured cancer cells, and in Namalwa and HCT-15 cells transfected with the beta3Gal-T5 gene. Thus, the beta3Gal-T5 gene is the most probable candidate responsible for the synthesis of the type 1 Lewis antigens in gastrointestinal and pancreatic epithelia and tumor cells derived therefrom. In addition, beta3Gal-T5 is a key enzyme that determines the amounts of the type 1 Lewis antigens including the sialyl Lewis a antigen.
Amino Acid Sequence↗
Acute fatal poisoning cases due to furathiocarb ingestion.
Seven cases involving acute fatalities due to ingestion of furathiocarb, a carbamate insecticide, are presented. Furathiocarb was detected in the gastric contents using thin layer chromatography (TLC) and gas chromatography/mass spectrophotometry (GC/MS), and quantified in the blood using a gas chromatograph equipped with a nitrogen-phosphorus detector (NPD). The fatal levels of furathiocarb in the blood ranged from 0.1 to 21.6 micrograms/ml.
Acute Disease↗
In Vitro and In Vivo Modulation of Growth Regulation in the Human Breast Cancer Cell Line MCF-7 by Estradiol Metabolites.
BACKGROUND: The natural estrogen 17 beta-estradiol (E2) functions as a potent tumor promoter during tumorigenic transformation of the mammary gland. From amongst the various pathways of E2 metabolism upregulation of C16 alpha-hydroxylation of E2 has been associated with carcinogenesis. In the present study in vitro and in vivo experiments were performed on estrogen receptor positive human breast cancer MCF-7 cells to examine whether the natural estrogen E2 and its metabolites 16 alpha-hydroxyestrone (16 alpha-OHE1) and 2-hydroxyestrone (2-OHE1)function as modulators of tumor cell growth. METHODS: An anchorage-independent growth assay was used for in vitro study bycounting the number of tri-dimensional colonies formed by MCF-7 cells suspendedin 0.33% agar. In vivo experiments examined the effect of implanting metabolitematerial pellets into female nude mice. RESULTS: In the anchorage-independent growth assay (AIG), continuous 14-day exposure to E2 and to 16 alpha-OHE1 at 200 ng/ml induced a 59.4% and a 105.9% increase (P= 0.001)respectively in the number of colonies of MCF-7 cells. Identical treatment with 2-OHE1, however, failed to increase AIG relative to that seen in the solvent treated control cultures. In the in vivo tumorigenicity assay, treatment of nude mice with 1.5 mg E2 or 16 alpha-OHE1 resulted in a 335.4% and a 384.1% increase (P< 0.0002) in tumor growth, while identical treatment with 2-OHE1 failed to exhibit any increase relative to the control group. CONCLUSION: These results suggest that the 16 alpha- and 2-hydroxylated metabolites of E2 may directly affect in vitro growth of MCF-7 cells via an autocrine mechanism and in vivo growth via paracrine mechanisms. Thus, E2-mediated growth regulation in MCF-7 cells may in part be due to distinct effects of specific E2 metabolites on the breast cancer cells.
Journal Article↗
Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure.
The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors. Between June 1990 and June 1999, 106 patients underwent living-related liver transplantation (LRLT) at Shinshu University Hospital. Among them, 8 patients had FHF and 6 had SFHF; these 14 patients are the subjects of this report. The graft volumes (GV) ranged from 231 mL to 625 mL, corresponding to 35% to 105% of the recipients' standard liver volume (SLV). The postoperative courses of all donors were uneventful. Following liver transplantation, all grafts functioned favorably, with normalization of serum total bilirubin within 3 to 5 days and normalization of coagulation profiles within 4 to 7 days. Thirteen of the 14 recipients are still alive. The actuarial 6-month, 1-year, and 5-year survival rates were 100%, 90%, and 90%, respectively. In the present study, when the ratio of the GV to the recipient's SLV was more than 35%, the graft was able to support the patient's metabolic demand after liver transplantation for FHF or SFHF. Because of the urgent nature of liver transplantation in this clinical condition, concerns over informed consent may be even greater than for elective LRLT. Nevertheless, the high success rate and low donor risk may justify this option for pediatric patients, as well as for a limited population of adult patients suffering from FHF or SFHF.
Adolescent↗
Effects of ketamine and pentobarbital on noradrenaline release from the medial prefrontal cortex in rats.
PURPOSE: To determine the effects of ketamine and pentobarbital on noradrenaline release from the medial prefrontal cortex. METHODS: In 14 male Wistar rats, a microdialysis probe with a 2 mm long semipermeable membrane was implanted in the medial prefrontal cortex. The dialysis probe was perfused at a rate of 1 microl x min(-1) with an artificial cerebrospinal fluid solution. The rats were randomly allocated to two groups: ketamine (group K, n=7) and pentobarbital (group P, n=7). Each rat was subsequently given 0 (saline), 1, 10 and 100 mg x kg(-1) ketamine i.p. in group K, and 0 (saline), 0.5, 5 and 50 mg x kg(-1) pentobarbital i.p. in group P. Sixty minutes elapsed between administration. Noradrenaline concentration was measured by HPLC with an electrochemical detector at 20 min intervals. (detection limit: 250 fg x 20 microl(-1), coefficient variation of the assay: 4.9%). The data in the 20-40 min after each dose of ketamine or pentobarbital i.p. were used for the statistical analysis. RESULTS: Noradrenaline release after 100 mg x kg(-1) ketamine increased by 7.7 +/- 2.0 (SEM) pg x collection(-1) compared with 2.7 +/- 0.7, 3.3 +/- 1.0 and 4.2 +/- 0.8 pg x collection(-1) after saline, 1 and 10 mg x kg(-1) ketamine, respectively (P < 0.05). Noradrenaline release did not change after pentobarbital. CONCLUSION: This study suggests the ketamine and pentobarbital have different effects on noradrenergic neurons in the medial prefrontal cortex. The stimulating effect of ketamine on noradrenaline release from the cortex might contribute to unique clinical features of ketamine anesthesia.
Adjuvants, Anesthesia↗
Partial median sternotomy as a minimal access for the closure of subarterial ventricular septal defect. Feasibility of transpulmonary approach.
BACKGROUND: Minimally invasive techniques in congenital heart surgery have evolved steadily over the past few years, but documentation in the literature is rare. The majority of reported techniques involve thoracoscopic approach and partial sternotomy. We have employed a lower partial sternotomy as a minimal-access procedure for the closure of subarterial ventricular septal defect, for situation where this approach would be unsuitable for adequate exposure of the pulmonary artery. The purpose of this study is to demonstrate the feasibility and safety of this technique and report its superior cosmetic result. SUBJECTS AND METHODS: Beginning in 1997, we began approaching the closure of subarterial ventricular septal defect through a lower sternal split incision using a 6 to 10 cm skin opening, associated with a reversed L incision at the left second intercostal space. A total of consecutive 12 patients (6 male and 6 female) have been operated on using this approach. The patients ranged in age from 6 to 21 years (mean, 12.8 +/- 5.0 years). The straight cannula with stylet was used for aortic cannulation. RESULTS: There was no mortality or morbidity, except for late pericardial effusion in 4 cases. The durations of cardiopulmonary bypass and aortic cross-clamping ranged from 94 to 206 (mean, 131 +/- 33) minutes and from 40 to 122 (mean, 70 +/- 26) minutes, respectively. Ten of 12 patients were extubated in the operating room, and no patient required blood transfusion. The postoperative hospital stay ranged from 8 to 21 (mean, 13.4 +/- 4.2) days. No patient developed deterioration of aortic regurgitation or residual ventricular septal defect. CONCLUSIONS: Our experience demonstrates that the lower partial sternotomy for the closure of subarterial ventricular septal defect is technically feasible and can be used with excellent cosmetic results and safety. Although experience is limited and follow-up is relatively short, this less invasive surgical technique may become a beneficial option for the management of subarterial ventricular septal defect.
Adolescent↗
Curative laparoscopic surgery for early gastric cancer: five years experience.
Sixty-one patients who were diagnosed with mucosal gastric cancer have been successfully treated with two laparoscopic techniques at our institute from March 1992 to March 1997. One is laparoscopic wedge resection of the stomach using a lesion-lifting method for lesions of the anterior wall, the lesser curvature, and the greater curvature of the stomach. The other is laparoscopic intragastric mucosal resection for lesions of the posterior wall of the stomach and near the cardia or the pylorus. Indications are as follows: (1) preoperatively diagnosed mucosal cancer; (2) <25 mm diameter elevated lesions; and (3) <15 mm diameter depressed lesions without ulcer formation. Patients were discharged in 4 to 8 days uneventfully. There was no major complication or mortality. The resected specimens had sufficient surgical margins horizontally (16 +/- 5 and 8 +/- 4 mm, respectively) and vertically. In one patient histologic examination revealed slight tumor infiltration into the submucosal layer with lymphatic invasion. He underwent gastrectomy with lymph node dissection 1 month after surgery. Otherwise, histologic examination revealed curative surgery. All patients in the series have survived during the 4- to 65-month follow-up period. There have been two recurrences in the series, both of which were found near the staple line 2 years after the initial surgery and were still mucosal lesions. They were successfully treated by open gastrectomy and laser irradiation. A separate early gastric cancer was found 2 years after the initial surgery in one patient, who then underwent curative open gastrectomy. In conclusion, if the patients are selected properly, these laparoscopic procedures are curative, minimally invasive treatment for early gastric cancer.
Adult↗
Effects of sedatives on noradrenaline release from the medial prefrontal cortex in rats.
RATIONALE: N-Methyl-d-aspartate (NMDA) receptor antagonism and GABA(A) receptor activation are believed to be critical targets for general anesthetic action. However, as NMDA antagonism of intravenous anesthetic agents causes post-anesthetic emergence reactions such as hallucination and agitation, while the GABA(A)-mimetic intravenous anesthetic agents do not, these two classes of intravenous anesthetic agents produce differential clinical profiles. OBJECTIVE: We have investigated the differential effects of the GABA(A) agonists propofol and midazolam and the NMDA antagonist ketamine on noradrenaline release from the medial prefrontal cortex of the rat using microdialysis, as noradrenergic neurons have a role to play in anesthesia and are known to be important in the control of sleep, attention and learning. METHODS: Twenty-one male Wistar rats (200-270 g) were randomly allocated into three groups: ketamine 100 mg x kg(-1) (n = 6), propofol 60 mg x kg(-1) (n = 8) and midazolam 5 mg x kg(-1) (n = 7) IP. A unilateral guide cannula was implanted stereotaxically into the medial prefrontal cortex under pentobarbital anesthesia (50 mg x kg(-1) IP). Forty-eight hours later, a dialysis probe was inserted through the guide cannula, and perfused with an artificial cerebrospinal fluid solution containing 1 mM pargyline. Following an equilibration period, samples of dialysate were collected every 10 min. Noradrenaline content was measured by high-performance liquid chromatography using an electrochemical detector. RESULTS: Anesthesia times, defined as the duration between the loss of righting reflex and recovery, were 24.7+/-5.6 (SEM), 20.5+/-1.9 and 25.2+/-1.5 min for propofol, midazolam and ketamine, respectively (no significant between-group differences). Both GABA(A )agonists, propofol and midazolam, significantly decreased noradrenaline release (75% and 71% of basal release, respectively). The NMDA antagonist ketamine markedly increased noradrenaline release (413% of basal). CONCLUSION: These data suggest that different clinical profiles observed with these two classes of sedatives may result from changes in noradrenaline release from the medial prefrontal cortex.
Animals↗
Fetal polycystic kidney disease in oro-facio-digital syndrome type I.
We report a girl with oro-facio-digital syndrome type I (OFD I) associated with polycystic kidney disease (PKD), which was identified on fetal US and fetal MRI. After birth, the diagnosis of this X-linked dominant disorder, which is lethal in males, was achieved by recognition of facial dysmorphism, lingual hamartomas, postaxial polydactyly, brain malformations, and the existence of her deceased male sibling with similar malformations. Adult PKD is a common feature in heterozygous females with OFD I. However, fetal PKD has been reported only in a lethal homozygous male. Our observation expands our knowledge about the phenotypic variations of PKD in OFD I.
Female↗
Forensic toxicological implication of acute fatal poisoning cases due to benfuracarb ingestion.
We describe here three cases involving acute fatalities due to benfuracarb ingestion and the forensic toxicological implications. Benfuracarb, a carbamate insecticide and its main metabolite carbofuran, were detected using thin layer chromatography (TLC) and gas chromatography/mass spectrophotometry (GC/MS) after extraction with ethyl acetate and then quantified using gas chromatography (GC) equipped with NPD. The blood levels of benfuracarb and carbofuran were in the range of 0.30-2.32 microg/ml and 1.45-1.47 microg/ml, respectively. Benfuracarb was not detected in urine, but carbofuran was detected in the range of 0.53-2.66 microg/ml.
Adult↗
Histopathological changes in iridocorneal angle of inherited glaucoma in rabbits.
BACKGROUND: We examined morphologically the angular region of eyes affected by inherited glaucoma in rabbits genetically developed by crossbreeding in order to investigate the etiologic changes in the iridocorneal angle and to establish whether this strain of rabbit is a suitable animal model of goniodysgenetic glaucoma in humans. METHODS: The angular regions of both normal and glaucomatous eyes from four rabbits having unilateral inherited glaucoma were observed with light and electron microscopy. RESULTS: In the glaucomatous eyes angular region, the aqueous plexus corresponding to Schlemm's canal in humans was open and located far peripherally to the peripheral margin of the anterior chamber angle, although the plexus of one glaucomatous eye was poorly developed with a small lumen. In the angular meshwork, which corresponds to the trabecular meshwork in humans, a thick abnormal tissue with round cells embedded in the extracellular matrix was located just beneath the plexus. A large amount of extracellular matrix of basal lamina-like material was observed in the thick tissue. In the normal eyes, the angular region consisted of well-developed trabecular sheets with neither a thick tissue nor accumulations of extracellular matrix in the angular meshwork. CONCLUSION: The findings observed in the glaucomatous eyes are much the same as those observed in goniodysgenetic glaucoma in humans, suggesting that this strain of inherited glaucoma rabbits is a suitable animal model of goniodysgenetic glaucoma in humans. The present study also supports the hypothesis that the presence of a thick subcanalicular tissue due to maldevelopment of the iridocorneal angle is one of the main causes of this type of glaucoma.
Animals↗
A G to A transition at the last nucleotide of exon 6 of the gamma c gene (868G-->A) may result in either a splice or missense mutation in patients with X-linked severe combined immunodeficiency.
We report here that a defect of the interleukin common gamma subunit (gamma c) in X-linked severe combined immunodeficiency (XSCID) previously known as a missense mutation resulted instead in exon skipping in a Japanese XSCID patient. The phenotype of the patient was consistent with that of typical XSCID, and his Epstein-Barr virus-transformed B cells accordingly entirely lacked surface expression of gamma c . On analysis by the reverse transcription-polymerase chain reaction (RT-PCR), a single but small gamma c mRNA species was detected. Exon 6, which encodes the transmembrane domain of gamma c, was skipped in the mRNA. A G to A mutation was found at the last nucleotide of exon 6 of the gamma c gene (868G-->A). The predicted consequence of the exon skipping is a frameshift resulting in a premature stop codon, and the mutated gamma c presumably loses association with the cell membrane. In XSCID, this mutation (868G-->A) is known as a missense mutation that results in R285Q [corrected]. Previously reported patients with the same mutation apparently had no aberrant or alternative splicing but did have the R285Q [corrected] exchange. Similar mutations at the last nucleotide of an outskipped exon have been reported. However, such mutations do not always cause exon skipping. Analyses of RNA structural changes induced by the mutations supported the variability of consequences of the mutations. Taken together, our findings suggest that the 868G-->A mutation of the gamma c gene may affect gamma c transcripts differently, i.e., generating missense or exon skipping, in XSCID patients with the same mutation. Patient-specific variation in splicing thus appears to occur.
Adenine↗
A new assay for the analysis of X-chromosome inactivation based on methylation-specific PCR.
The pattern of X-chromosome inactivation in females is currently evaluated by assays of differential methylation in the genes between the active and the inactive X chromosomes, with methylation-sensitive enzymes. We report a new assay in the human androgen receptor (HUMARA) locus involving a methylation-specific polymerase chain reaction (M-PCR) technique, independent of the use of restriction enzymes. The assay involves the chemical modification of DNA with sodium bisulfite and subsequent PCR. By using the assay with specific primers for the methylated allele, we obtained an X-inactivation pattern based on the ratio of the maternal inactive X to the paternal inactive X. These patterns were consistent with those obtained by conventional PCR assay at the same locus in 48 female cases. We also obtained another X-inactivation pattern based on the ratio of the maternal active X to the paternal active X by using specific primers for the unmethylated allele. The latter pattern was complementary to the former pattern, and a combination of these patterns produced a reliable X-inactivation pattern. The assay revealed that 12 (11%) of the 105 normal females had non-random inactivation patterns (>80:20 or <20:80). Four patients with an X; autosome translocation showed extremely non-random patterns, and these results were consistent with those obtained by previous molecular/cytogenetic studies. We conclude that M-PCR provides an accurate assay for X-inactivation and that it can be performed on various DNA samples unsuitable for restriction digestion.
Cell Line, Transformed↗
Liver transplantation for primary sclerosing cholangitis.
Although the development of interventional radiology and biliary surgical techniques has prolonged the survival time of patients with primary sclerosing cholangitis, liver transplantation remains the only effective treatment for patients with primary sclerosing cholangitis with liver cirrhosis. Several prognostic survival models have been establised for this disease, and the efficacy of actual liver transplantations has been reported in comparison with these survival models. One- and 5-year actuarial patient survivals after liver transplantation for primary sclerosing cholangitis were shown to be greater than and approximately equal to 90%, respectively. An association with cholangiocarcinoma is the most adverse factor affecting survival after liver transplantation for primary sclerosing cholangitis, while the association of inflammatory bowel disease or previous bili-ary surgery does not adversely affect the outcome of the liver transplantation. Recurrent sclerosing cholangitis is an important issue for posttransplant patients with primary sclerosing cholangitis, and occurs in 10%-20% of such patients. Although our understanding of recurrent sclerosing cholangitis is still in the early stages, its potential occurrence indicates the need for a longer follow-up period after liver transplantation.
Bile Duct Neoplasms↗
Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation.
Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft.
Adolescent↗
First case of cadaveric liver transplantation in Japan.
The first case of liver transplantation from a brain-dead donor in Japan is described. The recipient was a 43-year-old man with familial amyloid polyneuropathy who manifested various neuropathic symptoms and autonomic dysfunction at the time of transplantation. The graft had three arteries, for which a single trunk was created at the back table. A side-to-side cavacaval anastomosis was performed as an outflow reconstruction. To avoid portal congestion, a temporary shunt between the right posterior branch of the portal vein and the vena cava was constructed, instead of a venovenous bypass. The graft preservation time was 7.2 h and the operation time was 12.2 h. Although sufficient blood flow in the hepatic artery, portal vein, and hepatic vein was confirmed intra- and postoperatively, using Doppler ultrasound, transient graft dysfunction was observed immediately after surgery, but there was spontaneous improvement. The patient was discharged 100 days after transplantation.
Adult↗