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Biomedical subjects

S T Oh

Publications and source records attributed to S T Oh.

At least 19 recordsLinked to original sources

Adjuvant chemotherapy with 5-fluorouracil, doxorubicin and mitomycin-C (FAM) for 6 months after curative resection of gastric carcinoma.

AIM: This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5-FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had undergone curative resection of gastric carcinoma. METHODS: From Nov 1999 to Jan 2002, 291 consecutive patients with stage IB-IIIB gastric adenocarcinoma were given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600 mg/m(2) (days 1, 8, 29 and 36), doxorubicin 30 mg/m(2) (days 1 and 29) and mitomycin-C 10 mg/m(2) (day 1), every 8 weeks for 6 months. RESULTS: The median follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1% for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB (p=0.002). The 5-year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage II, 53.3% for stage IIIA, and 39.2% for stage IIIB (p<0.001). A total of 769 cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was nausea/vomiting (11 patients), followed by stomatitis (3 patients). CONCLUSIONS: Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated comparable RFS and OS with an acceptable toxicity profile.

Adenocarcinoma↗

Phase II study of capecitabine and cisplatin as first-line combination therapy in patients with gastric cancer recurrent after fluoropyrimidine-based adjuvant chemotherapy.

To evaluate the efficacy and safety of capecitabine and cisplatin in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant therapy. Patients with histologically confirmed and measurable advanced gastric cancer that had relapsed after fluoropyrimidine-based adjuvant chemotherapy received oral capecitabine (1250 mg m(-2) twice daily, days 1-14) and intravenous cisplatin (60 mg m(-2) over 1 h, day 1) every 3 weeks. In total, 32 patients were enrolled, of whom 30 were evaluable for efficacy and 32 for safety. A median of 5 cycles (range 1-10) was administered. One patient achieved a complete response and eight had partial responses, giving an overall response rate of 28% (95% CI, 13-44%). The median time to progression and median overall survival were 5.8 months (95% CI, 4.1-7.5 months) and 11.2 months (95% CI, 5.5-16.9 months), respectively. Grade 3 neutropenia and thrombocytopenia were observed in 38 and 6% of patients, respectively. Grade 2/3 nonhaematological toxicities included diarrhoea (19%), stomatitis (19%) and hand-foot syndrome (31%). No grade 4 toxicity, neutropenic fever or treatment-related deaths occurred. Capecitabine in combination with cisplatin was effective and well tolerated as first-line treatment in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant chemotherapy.

Administration, Oral↗

Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer.

BACKGROUND: A phase II study was conducted to assess the efficacy and tolerability of combination therapy with capecitabine and cisplatin in patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic or unresectable measurable gastric adenocarcinoma received oral capecitabine 1250 mg/m(2) twice daily, days 1-14, and i.v. cisplatin 60 mg/m(2) on day 1. This cycle was repeated every 3 weeks. RESULTS: Forty-two patients were enrolled in this study. Of these, 38 patients were assessable for efficacy and 40 were assessable for toxicity. One patient achieved a complete response and 22 patients had partial responses, giving an overall response rate of 54.8% in the intention-to-treat population (95% confidence interval 39.8% to 69.8%). The median time to progression was 6.3 months and the median overall survival was 10.1 months. The principal adverse events were neutropenia and hand-foot syndrome. Grade 3/4 adverse events were neutropenia (32.5% of patients), thrombocytopenia (10%), stomatitis (2.5%) and diarrhea (5%). Grade 2 and 3 hand-foot syndrome occurred in 20% and 7.5% of patients, respectively. There were no treatment-related deaths. CONCLUSIONS: The combination of capecitabine and cisplatin is active and well tolerated in patients with advanced gastric cancer.

Adenocarcinoma↗

Desensitization to urine-derived gonadotropins in a woman with secondary infertility.

BACKGROUND: Urine-derived gonadotropins have been used to treat infertility but may cause allergic reactions. IgE-mediated hypersensitivity reactions can be treated with desensitization, especially when new therapies such as recombinant human gonadotropins are unavailable. OBJECTIVE: This case is described to highlight a successful intervention with desensitization in a woman with a complicated history of secondary infertility. She had been treated with ovulation-induction regimens, such as IVF-M (in vitro fertilization-human menopausal gonadotropin [hMG]) and IVF-C (human chorionic gonadotropin [hCG]), for intrauterine insemination. During treatment, however, she experienced reactions to IVF-M and IVF-C. Because she strongly wanted a baby and no alternative preparation was available, desensitization was attempted. METHODS: Intradermal tests with IVF-M and IVF-C using both negative and positive controls were performed on the patient and four normal control subjects. Immediate wheal-and-flare reactions occurred only in the patient. ELISA and ELISA inhibition tests showed positive responses to IVF-M and IVF-C, but not to highly purified hMG, hCG, or D-mannitol, a preservative in IVF-M and IVF-C. Desensitization to IVF-M and IVF-C was done with a protocol used for parenteral desensitization to penicillin. RESULTS: During the IVF-M desensitization, the intramuscular injections were well tolerated. For the next 2 days, daily administration of IVF-M was uneventful. Thirty-six hours later, desensitization to IVF-C was performed successfully. The patient had two intrauterine inseminations and became pregnant. CONCLUSIONS: Nongonadotropin proteins in urine-derived gonadotropins cause IgE-mediated hypersensitivity reactions. Acute desensitization to urine-derived gonadotropins can be performed effectively, as shown in our current case.

Adult↗

Supramolecular assembly and acid resistance of Helicobacter pylori urease.

Helicobacter pylori, an etiologic agent in a variety of gastroduodenal diseases, produces a large amount of urease, which is believed to neutralize gastric acid by producing ammonia for the survival of the bacteria. Up to 30% of the enzyme associates with the surface of intact cells upon lysis of neighboring bacteria. The role of the enzyme at the extracellular location has been a subject of controversy because the purified enzyme is irreversibly inactivated below pH 5. We have determined the crystal structure of H. pylori urease, which has a 1.1 MDa spherical assembly of 12 catalytic units with an outer diameter of approximately 160 A. Under physiologically relevant conditions, the activity of the enzyme remains unaffected down to pH 3. Activity assays under different conditions indicated that the cluster of the 12 active sites on the supramolecular assembly may be critical for the survival of the enzyme at low pH. The structure provides a novel example of a molecular assembly adapted for acid resistance that, together with the low Km value of the enzyme, is likely to enable the organism to inhabit the hostile niche.

Amino Acid Sequence↗

Telomerase activation by human papillomavirus type 16 E6 protein: induction of human telomerase reverse transcriptase expression through Myc and GC-rich Sp1 binding sites.

High-risk human papillomaviruses (HPVs) immortalize keratinocytes by disrupting the retinoblastoma protein (Rb)/p16 pathway and activating telomerase. The E7 oncoprotein targets Rb, while the E6 oncoprotein induces telomerase activity in human keratinocytes. This study has examined the mechanism by which E6 activates telomerase. Expression of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, was found to be increased in keratinocytes stably expressing HPV type 16 E6, suggesting that E6 acts to increase hTERT transcription. hTERT expression and telomerase activity were activated to significantly higher levels in cells expressing both E6 and E7 than in cells expressing E6 alone. This indicates that E7 may augment E6-mediated activation of hTERT transcription. In transient-transfection assays using hTERT reporters, the induction of hTERT expression by E6 was found to be mediated by a 258-bp fragment of the hTERT promoter, proximal to the ATG initiation codon. Previous studies have demonstrated that overexpression of Myc can activate hTERT expression, suggesting that Myc may be a mediator of E6-mediated hTERT induction. However, in cells stably expressing E6, no strict correlation between the level of Myc and the activation of hTERT was found. Consistent with this observation, mutation of the two Myc binding sites in the hTERT promoter only modestly reduced responsiveness to E6 in transient reporter assays. This indicates that activation of Myc-dependent transcription is not essential for E6-mediated upregulation of hTERT expression. The hTERT promoter also contains five GC-rich elements that can bind Sp1. Mutation of these sites within the 258-bp fragment partially reduced hTERT induction by E6. However, when mutations in the Sp1 sites were combined with the mutated Myc binding sites, all activation by E6 was lost. This indicates that it is the combinatorial binding of factors to Myc and Sp1 cis elements that is responsible for hTERT induction by E6.

Binding Sites↗

Cellular changes induced by low-risk human papillomavirus type 11 in keratinocytes that stably maintain viral episomes.

Infections by low-risk papillomavirus types, such as human papillomavirus (HPV) type 6 (HPV-6) and HPV-11, induce benign genital warts that rarely progress to malignancy. In contrast, lesions induced by high-risk HPV types have the potential to progress to cancer. Considerable information is available concerning the pathogenesis of high-risk HPV types, but little is known about the life cycle of low-risk HPV types. Although functionally distinct, both high- and low-risk virus types infect keratinocytes and induce virion production upon differentiation. This information suggests that they may share common mechanisms for regulating their productive life cycles. Using tissue culture methods developed to study high-risk HPV types, we examined the ability of HPV-11 to be stably maintained as episomes following transfection of normal human keratinocytes with cloned viral DNA. HPV-11 genomes were found to be maintained in keratinocytes for extended passages in cultures in 14 independent experiments involving transfection of cloned HPV-11 DNA. Interestingly, the HPV-11-positive cells exhibited an extended life span that averaged approximately twofold longer than that of control neomycin-transfected cells. In organotypic cultures, HPV-11-positive cells exhibited altered differentiation patterns, but the extent of disruption was less severe than that seen with high-risk HPV types. In addition, the amplification of HPV-11 DNA, as well as the induction of several viral messages, was observed following differentiation of transfected cells in semisolid media. To determine whether global changes in cellular gene expression induced by HPV-11 were similar to those observed with high-risk HPV-31 (Y. E. Chang and L. A. Laimins, J. Virol. 74:4174-4182, 2000), microarray analysis of 7,075 expressed sequences was performed. A spectrum of cellular genes different from that previously reported for HPV-31 was found to be activated or repressed by HPV-11. The expression of only a small set of genes was similarly altered by both high- and low-risk HPV types. This result suggests that different classes of HPVs have distinct effects on global cellular transcription patterns during infection. The methods described allow for a genetic analysis of HPV-11 in the context of its differentiation-dependent life cycle.

Cell Differentiation↗

A distinct tumor suppressor gene locus on chromosome 15q21.1 in sporadic form of colorectal cancer.

The SM1311 family is an Ashkenazi family with dominantly inherited predisposition to colorectal adenomas and carcinomas and has a high-penetrance locus in chromosome 15q, with a multipoint logarithm of the odds score of 3.06 at marker D15S118. In the present study, we performed a high-density loss of heterozygosity study with 13 polymorphic microsatellite markers, including D15S118, spanning 15q15.3-q22.1, on 70 cases of the sporadic form of colorectal tumors. Our deletion mapping data showed a locus at D15S968 in chromosomal sub-band 15q21.1 may harbor a tumor suppressor gene in an area <0.521 Mb in physical map distance defined by markers D15S514 and D15S222. THBS1, 0.185 Mb proximal to D15S968, is the nearest known gene to this specific narrow loss of heterozygosity region. Thus, we speculate that THBS1 might be the most probable candidate gene involved in colorectal cancer carcinogenesis.

Adenocarcinoma↗

Laparoscopy in the management of gastric submucosal tumors.

BACKGROUND: Gastric tumors, including early gastric cancers, can be safely removed laparoscopically. They do not require an open laparotomy. METHODS: From March 1995 to December 1998, we used laparoscopy to resect gastric submucosal lesions in 32 patients. There were 22 men and 10 women. The patients ranged in age from 23 to 67 years (median, 51.4 yr). The lesions were located in the upper third in one patient, in the middle third in 20 patients, and in the lower third in 11 patients. The tumors ranged in size from 2 to 6 cm in diameter. The operative procedures were wedge resection in 19 patients, wedge resection with gastrotomy in two patients, intragastric surgery in nine patients, intragastric surgery with gastrotomy in one patient, and proximal gastrectomy in one patient, using a four- or five-port technique. The exophytic mass was resected with an Endo-GIA, and the tumors on the mucosal surface were exposed via a gastrotomy and excised. The gastrotomy was closed with an intracorporeal suture. In all cases, the operation was finished after the confirmation of tumor-free margins on frozen-section biopsy specimens. RESULTS: The duration of the operation ranged from 80 to 180 mins. The final pathologic findings were leiomyoma in 24 patients, adenomyoma in three patients, hyperplastic polyp in two patients, lipoma in one patient, hamartoma in one patient, and leiomyosarcoma in one patient. One case (3.1%) was converted to a mini-laparotomy due to technical difficulty; in one other case, more margin was resected laparoscopically due to the tumor-positive margin; and in one further patient, leakage was repaired by laparoscopic suturing on the 1st postoperative day. There were no other major complications and no deaths. The hospital stay ranged from 6 to 7 days. The maximum follow-up to date in these patients, including a case of leiomyosarcoma, was 42 months. There has been no evidence of tumor recurrence. CONCLUSION: The application of laparoscopy to submucosal tumors of the stomach is technically feasible, safe, and useful. It should be considered a viable alternative to open surgery and gastroscopic management because of its low invasiveness and good postoperative results.

Adult↗

Toxic amebic colitis coexisting with intestinal tuberculosis.

A patient with a fulminant amebic colitis coexisting with intestinal tuberculosis had a sudden onset of crampy abdominal pain, mucoid diarrhea, anorexia, fever and vomiting with signs of positive peritoneal irritation. Fulminant amebic colitis occurring together with intestinal tuberculosis is an uncommon event and may present an interesting patho-etiological relationship. The diagnosis was proven by histopathologic examination of resected specimen. Subtotal colectomy including segmental resection of ileum, about 80 cm in length, followed by exteriorization of both ends, was performed in an emergency basis. Despite all measures, the patient died on the sixth postoperative day. The exact relationship of fulminant amebic colitis and intestinal tuberculosis is speculative but the possibility of a cause and effect relationship exists. Fulminant amebic colitis may readily be confused with other types of inflammatory bowel disease, such as idiopathic ulcerative colitis, Crohn's disease, perforated diverticulitis and appendicitis with perforation. This report draws attention to the resurgence of tuberculosis and amebiasis in Korea, and the need for the high degree of caution required to detect it.

Diagnosis, Differential↗

Crystal structure of a maltogenic amylase provides insights into a catalytic versatility.

Amylases catalyze the hydrolysis of starch material and play central roles in carbohydrate metabolism. Compared with many different amylases that are able to hydrolyze only alpha-D-(1,4)-glycosidic bonds, maltogenic amylases exhibit catalytic versatility: hydrolysis of alpha-D-(1,4)- and alpha-D-(1,6)-glycosidic bonds and transglycosylation of oligosaccharides to C3-, C4-, or C6-hydroxyl groups of various acceptor mono- or disaccharides. It has been speculated that the catalytic property of the enzymes is linked to the additional approximately 130 residues at the N terminus that are absent in other typical alpha-amylases. The crystal structure of a maltogenic amylase from a Thermus strain was determined at 2.8 A. The structure, an analytical centrifugation, and a size exclusion column chromatography proved that the enzyme is a dimer in solution. The N-terminal segment of the enzyme folds into a distinct domain and comprises the enzyme active site together with the central (alpha/beta)(8) barrel of the adjacent subunit. The active site is a narrow and deep cleft suitable for binding cyclodextrins, which are the preferred substrates to other starch materials. At the bottom of the active site cleft, an extra space, absent in the other typical alpha-amylases, is present whose size is comparable with that of a disaccharide. The space is most likely to host an acceptor molecule for the transglycosylation and to allow binding of a branched oligosaccharide for hydrolysis of alpha-D-(1,4)-glycosidic or alpha-D-(1,6)-glycosidic bond. The (alpha/beta)(8) barrel of the enzyme is the preserved scaffold in all the known amylases. The structure represents a novel example of how an enzyme acquires a different substrate profile and a catalytic versatility from a common active site and represents a framework for explaining the catalytic activities of transglycosylation and hydrolysis of alpha-D-(1,6)-glycosidic bond.

Amino Acid Sequence↗

Frequent somatic mutations of the beta-catenin gene in intestinal-type gastric cancer.

The increased level of cytoplasmic beta-catenin through the mutations to either beta-catenin or adenomatous polyposis coli (APC) has been proposed as an important oncogenic step in various tumors. Gastric cancer showed frequent genetic alterations of the APC gene, and the risk for gastric cancer in familial adenomatosus polyposis patients is 10 times higher than that in the general population. These findings raise the possibility that mutations of beta-catenin may also be associated with the development of gastric cancer. We detected seven somatic mutations in a portion of exon 3 encoding for the glycogen synthase kinase 3beta phosphorylation consensus region of the beta-catenin gene in 43 gastric cancers. All of these mutations were missense mutations, of which five are in the highly conserved aspartic acid 32 and two are in serine 29; all of these seven mutations were detected exclusively in intestinal-type gastric cancers (7 of 26; 26.9%), but not in the diffuse-type (0 of 17). We concluded that disruption of the APC/beta-catenin/T cell factor-lymphoid enhancer binding factor pathway might play an important role especially in the development of intestinal-type gastric cancer.

Base Sequence↗

Biphasic relaxation of the opossum lower esophageal sphincter: roles of NO., VIP, and CGRP.

Vasoactive intestinal polypeptide (VIP) and nitric oxide (NO.) are thought to mediate lower esophageal sphincter (LES) relaxation. Transverse muscle strips from the opossum LES were used to test this hypothesis. Electrical field stimulation (EFS) produced a biphasic LES relaxation: a rapid component during the stimulus was more prominent at lower stimulus frequencies, and a sustained component was more prominent at higher frequencies. N(omega)-nitro-L-arginine and hemoglobin inhibited the rapid component but affected the sustained component less. Exogenous VIP decreased LES tone. A number of purported VIP antagonists blocked neither VIP-induced nor EFS-induced relaxation of the LES. The calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) did not alter EFS-induced LES relaxation. EFS-induced relaxation of opossum LES muscle is biphasic, and the initial, rapid component of the relaxation is mediated primarily by NO. The mediator of the sustained component was not identified.

Animals↗

Differential effects of progesterone and its analogues on the contractility of the murine jejunum in vitro.

Epidemiological studies have demonstrated a higher prevalence of gastrointestinal motility disturbances in women compared with men. This may partly be due to the effects of sex hormones on smooth muscle cells. To further characterize the mechanisms by which sex hormones affect intestinal smooth muscle, we studied the effects of several structurally related progestins on intestinal contractility. Segments of the murine intestine oriented along the longitudinal axis were connected to force displacement transducers. We recorded the isometric tension generated by the murine jejunum spontaneously and after cholinergic stimulation. The baseline tension, amplitude of spontaneous contractions, and increase in tension after cholinergic stimulation were measured in the presence and absence of various steroid hormones. Progesterone dose dependently decreased the contractile activity of the murine jejunum. This effect occurred within less than 1 min and could not be inhibited by a specific blocker of the progesterone receptor, suggesting a nongenomic pathway. Experiments with several progestins demonstrated a stereoselectivity of this steroid hormone effect. This was most pronounced for dihydroprogesterone: the 5 alpha form did not affect intestinal contractility, while the stereoisomer 5 beta-dihydroprogesterone significantly inhibited smooth muscle tension. We conclude that progesterone significantly inhibits the contractility of the murine jejunum in vitro. The differential effects of various structural analogues argue against a nonspecific effect of the steroid hormones on the lipid bilayer with secondary functional alterations of membrane proteins. Rather, they suggest a specific interaction between the steroid hormone and a still unidentified protein that differs in its function and pharmacological profile from the known progesterone receptor.

20-alpha-Dihydroprogesterone↗

The development of a new method to detect the adulteration of commercial aloe gel powders.

Simple and accurate methods to detect the adulteration of commercial aloe gel powder were developed. Crude polysaccharide in aloe gel powder was isolated by precipitating with excess ethyl alcohol and total hexose in isolated polysaccharide was determined by Dubois assay. After hydrolysis of non-dialysable polysaccharides, resultant free sugar was determined by gas chromatography for sugar recognition and ash contents was considered simultaneously. In some products, the content of ash was very low while the content of total hexose was very high. And polysaccharides of these products revealed typical dextran pattern, therefore, these products could be identified that adulterated with commercial maltodextrin. The content of maltodextrin in adulterated product was determined by HPLC and TLC analysis which could be adopted as a part of a certification process.

Aloe↗

Determination of aloesin in plasma by high-performance liquid chromatography as fluorescent 9-anthroyl derivative.

A sensitive high-performance liquid chromatographic (HPLC) method for the determination of aloesin in plasma was developed. After solid-phase extraction from plasma and derivatization of aloesin and compound AD-1, which was prepared from aloesin as a internal standard, with 9-anthroylnitrile in the presence of quinuclidine, the derivatives were separated on a inertsil ODS-3 column using acetonitrile/methanol/water (3:1:6) as a mobile phase, and detected fluorimetrically at 460 nm with excitation at 360 nm. The detection limit of aloesin was 3.2 ng/ml in plasma (S/N = 3).

Anthracenes↗