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Biomedical subjects

J T Lin

Publications and source records attributed to J T Lin.

At least 73 records · Page 4Linked to original sources

Loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in Taiwan.

Elucidation of the basic genetic changes of human hepatocellular carcinoma is important for the understanding and treatment of this cancer. We used microsatellite polymorphism markers to study 30 cases of hepatocellular carcinoma (34 tumours) on all human chromosomes. DNA from 34 pairs of hepatocellular carcinomas and corresponding non-tumour parts was prepared. Loss of heterozygosity (LOH) and microsatellite instability on 23 chromosomes were investigated by 231 sets of microsatellite markers. More than 20% LOH was shown for loci on 16q (47.1%), 13q (32.4%), 17p (32.4%), 5q (26.5%), 11p (23.5%) and 9p (20.6%). The commonly affected regions were mapped to 16q12.1, 16q12.2, 16q24, 13q12.1-32, 17p13, 5q32, 5q34, 5q3, 11p15, 11q23-24 and 9p21. Hepatitis B virus carriers had a significantly higher frequency of LOH on chromosomes 5q, 11p and 16q. Furthermore, larger tumour size tended to have higher frequency of LOH at D16S409 locus (16q12.1). Microsatellte instability was only found in 12 of 231 markers and the frequency is very low. These data suggest that the chromosomes 16q, 13q, 17p, 5q, 11p and 9p might participate in hepatocarcinogenesis. However, microsatellite instability might play little role in the development of this cancer in Taiwan.

Adult↗

Phalloplasty in female-to-male transsexuals using free radial osteocutaneous flap: a series of 22 cases.

From July 1994 to December 1996, 22 cases of primary female transsexualism received phalloplasty using free radial forearm osteocutaneous flaps in The Veterans General Hospital, Taipei, Taiwan. Follow-up period ranged from 6 months to 35 months. No complete flap loss and one partial loss (10% reduction) were noted after operation. The urethrocutaneous fistula rate was 40.9%, needing fistula repair surgery. Urethral stricture was noted in three cases (13.7%). Significant donor forearm morbidity was noted in two cases (9.1%) including one who suffered from radius bone fracture. All preserved 'clitorises' had intact erotic sensation and all neophalli gained protective sensation within 9 months. No 'penile fracture' was noted. In nine cases that have regular sexual activities, the sexual performance was rated as satisfactory. We share our experience and recommend that the free radial forearm osteocutaneous tubing flap is a promising choice for phalloplasty in female-to-male transsexuals.

Bone Transplantation↗

General nitrogen regulation of nitrate assimilation regulatory gene nasR expression in Klebsiella oxytoca M5al.

Klebsiella oxytoca can assimilate nitrate and nitrite by using enzymes encoded by the nasFEDCBA operon. Expression of the nasF operon is controlled by general nitrogen regulation (Ntr) via the NtrC transcription activator and by pathway-specific nitrate and nitrite induction via the NasR transcription antiterminator. This paper reports our analysis of nasR gene expression. We constructed strains bearing single-copy Phi(nasR-lacZ) operon fusions within the chromosomal rhaBAD-rhaSR locus. The expression of DeltarhaBS::[Phi(nasR-lacZ)] operon fusions was induced about 10-fold during nitrogen-limited growth. Induction was reduced in both ntrC and rpoN null mutants, indicating that Ntr control of nasR gene expression requires the NtrC and sigma(N) (sigma(54)) proteins. Sequence inspection of the nasR control region reveals an apparent sigma(N)-dependent promoter but no apparent NtrC protein binding sites. Analysis of site-specific mutations coupled with primer extension analysis authenticated the sigma(N)-dependent nasR promoter. Fusion constructs with only about 70 nucleotides (nt) upstream of the transcription initiation site exhibited patterns of beta-galactosidase expression indistinguishable from Phi(nasR-lacZ) constructs with about 470 nt upstream. Expression was independent of the Nac protein, implying that NtrC is a direct activator of nasR transcription. Together, these results indicate that nasR gene expression does not require specific upstream NtrC-binding sequences, as previously noted for argT gene expression in Salmonella typhimurium (G. Schmitz, K. Nikaido, and G. F.-L. Ames, Mol. Gen. Genet. 215:107-117, 1988).

Amino Acid Sequence↗

Glycogen synthase phosphatase interacts with heat shock factor to activate CUP1 gene transcription in Saccharomyces cerevisiae.

Upon heat shock, transcription of many stress-inducible genes is rapidly and dramatically stimulated by heat shock factor (HSF). A central region of the yeast HSF (designated HSFrr for "repression region") was previously identified and proposed to be involved in repressing the activation domain under non-heat-shock conditions. Here, we used the phage display system to isolate proteins that interact with HSFrr. This should identify factors that modulate HSF activity or directly participate in HSF-mediated transcriptional activation. We constructed a randomly sheared yeast genomic library to express yeast proteins on the surface of lambda phage. HSFrr binding phages were selected by cycles of affinity chromatography. DNA sequencing identified an HSFrr-interacting phage that contains the GAC1 gene. The GAC1 gene encodes the regulatory subunit for a type 1 serine/threonine phosphoprotein phosphatase, Glc7. Both gac1 and glc7 mutations had little effect on HSF activation of gene transcription of two heat shock genes, SSA4 and HSP82. In contrast, heat shock induction of CUP1 gene expression was completely abolished in a glc7 mutant and reduced in a gac1 mutant. The results demonstrate that the Glc7 phosphatase and its Gac1 regulatory subunit play positive roles in HSF activation of CUP1 transcription.

Bacteriophage lambda↗

Hypermethylation of the p16 gene in sporadic T3N0M0 stage colorectal cancers: association with DNA replication error and shorter survival.

Hypermethylation in the promoter region of the p16 gene was suspected to be involved in the tumorigenesis of colorectal cancers, although its clinical and biological significance remains obscure. In this study, we collected 84 T3N0M0 stage primary colorectal cancers that were curatively resected. The clinicopathologic data were reviewed. p16 hypermethylation was determined by a methylation-specific polymerase chain reaction (PCR). p53 overexpression was detected by immunocytochemistry (ICC). The point mutations in the 12 and 13 codons of the K-ras gene were screened by restriction enzyme analysis. Loss of heterozygosity (LOH) of the DCC (Deleted in Colorectal cancer) gene was examined by PCR using primers of the DCC (18q21) microsatellite marker. The DNA replication error (RER) was examined using 7 microsatellite markers at distinct chromosomal loci. p16 hypermethylation, regarded as an indication of p16 inactivation, was evident in 24 (28.6%) of the tumors. No correlation was found between p16 hypermethylation and various clinicopathologic factors, includinig age, sex, tumor location, tumor size, growth pattern, tumor differentiation, mucin production, vascular and/or lymphatic invasion, lymphocyte infiltration of the tumor, and serum level of carcinoembryonic antigen. There was no association between p16 hypermethylation of K-ras gene mutation, p53 overexpression and LOH of the DCC gene. However, p16 hypermethylation was significantly associated with DNA RER (p = 0.01). Survival analysis revealed a significant survival disadvantage of p16-hypermethylated versus non-p16-hypermethylated tumors (p = 0.0001). These findings indicate that p16 hypermethylation plays a role in the carcinogenesis of a subset of colorectal cancers; and the presence of p16 hypermethylation predicts shorter survival in T3N0M0 stage colorectal cancers.

Aged↗

Endoscopic mucosal resection for treatment of heterotopic pancreas in the stomach.

We report a case of a 30-year-old man who suffered from epigastralgia for 1 month. During an upper gastrointestinal endoscopic examination, a small nodule with a smooth surface was found at the greater curvature of the gastric antrum. Endoscopic ultrasonography showed focal thickening of the second and third layers of the stomach with slightly hypoechoic echotexture in the submucosa. The tumor was excised by means of endoscopic mucosal resection, with a cap-fitted panendoscope. Pathologic examination of the resected tissue revealed a heterotopic pancreas, which was subsequently removed. Heterotopic pancreas is often difficult to diagnose preoperatively. This is the first reported case in which endoscopic mucosal resection was used for both diagnosis and treatment heterotopic pancreas.

Adult↗

The role of gastric acid and Helicobacter pylori in the natural course of duodenal ulcer.

This study was conducted using roxatidine acetate or Mylanta combined with metronidazole and amoxicillin to evaluate the role of acid and Helicobacter pylori in the natural course of the duodenal ulcer. Eighty-three patients with H. pylori positive duodenal ulcers were randomly allocated into one of four treatment groups. Group A: roxatidine 75 mg hs for 8 weeks; Group B: the same as group A + metronidazole 250 mg and amoxicillin 250 mg qid for 1 week on the 3rd week; Group C: Mylanta (combined hydroxide of magnesium and aluminum) 20 ml qid for 8 weeks; Group D: the same as group C + metronidazole 250 mg and amoxicillin 250 mg qid for 1 week on the 3rd week. Repeated endoscopies were performed on the 8th week post the initial treatment and the sixth and 12th month post the termination of treatment, or, at the earliest recurrence of symptoms. Eradication of H. pylori was considered to be successful if the culture, histology and CLO test all showed negative. The ulcer healing rates of Groups A, B, C and D were 95%, 100%, 61% and 86%, respectively, with a significant difference between A and C. The eradication rates of groups B and D were 81% and 62%, respectively, without any significant difference. The 12 months cumulative ulcer recurrence rates were 72%, 15%, 80% and 22%, respectively, with a significant difference between each paired groups with and without antibiotics. In conclusions, roxatidine is effective in the healing of duodenal ulcer. One-week roxatidine-based triple therapy is powerful in the eradication of H. pylori. Potent acid suppression is sufficient to heal the duodenal ulcer. Eradication of H. pylori can potentiate ulcer healing under insufficient acid suppression. A causal role for H. pylori in recurrent duodenal ulcer is strongly supported by a much lower recurrence of ulcer in H. pylori free patients.

Adolescent↗

Impact of nonsurgical, invasive endoscopy of the diagnosis and therapy of gastrointestinal diseases.

In the last 2 decades, endoscopy has become the most reliable means of diagnosing gut disorders. With the aid of magnifying endoscopy and staining methods, gastrointestinal cancers and malignant diseases can be detected in the early stages. Endoscopic ultrasonography is currently indicated for staging digestive cancers, assessing submucosal tumors, and diagnosing biliary and pancreatic diseases. During the past decade, endoscopy evolved from a solely diagnostic tool to a therapeutic modality. Endoscopic heater probes, bipolar electrocoagulation, and laser therapy are all of effective for achieving immediate hemostasis and preventing rebleeding in actively bleeding lesions. Various ligation methods and endoscopic injection sclerotherapy safely achieve high rates of hemostasis. Endoscopic mucosal resection allows curative treatment of gastrointestinal cancer in the mucosal layer, and removal of precancerous lesions. Endoscopic balloon dilators have been developed for dilating gut stenoses. Various endoprostheses are used for palliation of malignant stenoses. Endoscopic sphincterotomy, balloon dilation, lithotripsy, and endoprosthesis placement are alternatives for biliary tract and pancreatic disease therapy. Endoscopic photodynamic therapy is useful in palliation of esophageal cancer or in ablation of dysplastic lesions in Barrett's esophagus. With advances in modern biotechnology, endoscopy continues to show value in treating or preventing diseases, with less discomfort and lower cost than other methods.

Endoscopy, Gastrointestinal↗

High-level expression of Na+/D-glucose cotransporter (SGLT1) in a stably transfected Chinese hamster ovary cell line.

The coding region of the high affinity Na+/d-glucose cotransporter (SGLT1) was inserted into the eukaryotic expression vector GFP-N1 under the control of a CMV promoter. The plasmid was then stably transfected into a Chinese hamster ovary cell line (CHO). Transcription and synthesis of SGLT1 were proved by Northern and Western blot analyses. Transport activities of the transfected cells (G6D3) were examined by measuring the sodium-dependent uptake of alpha-methyl[14C]d-glucoside (AMG). Kinetic analysis revealed a Vmax of 10.3 nmol/min/mg (total cell protein) and a Km of 0.26+/-0.09 mM, respectively. The concentration of phlorizin required to inhibit AMG uptake by 50% in the presence of 0.1 mM AMG was 2.35+/-1.84 microM. Electrophysiological studies showed that AMG induces a significant depolarization of membrane voltage in stably transfected CHO cells, suggesting an electrogenic Na-AMG symport. Immunoprecipitation with an antipeptide antibody yielded a nearly homogeneous polypeptide with a molecular mass of about 72 kDa. The amount of SGLT1 present in the CHO cell plasma membranes represents at least 1% of membrane protein, which is about 30-100 times higher than in natural sources, such as renal brush border membranes. In conclusion, the stably transfected G6D3 cells with a markedly high SGLT1 expression can serve as a promising model for studying cellular events related to Na+/d-glucose cotransport and for analyzing the structure and function of the cotransporter itself.

Animals↗

High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy.

BACKGROUND: In the past 4 years, the weekly 24-hour infusion of high dose 5-fluorouracil (5-FU) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospectively studied at the authors' institution. This has enabled them to explore the possibility that the level of expression of thymidylate synthase (TS), the target enzyme of 5-FU, is related to the drug sensitivity of gastric carcinoma to 5-FU-based chemotherapy. METHODS: To be eligible for this study, patients were required to have received high dose 5-FU and leucovorin chemotherapy (weekly 24-hour infusions of 5-FU, 2,600 mg/m2, and leucovorin, 300 mg/m2) and to have had adequate prechemotherapy gastric carcinoma tissues for immunohistochemical study. TS106 monoclonal antibody was used to detect the expression of TS. A visual scoring system, which ranged from 0 to 3+, was adopted by 2 independent pathologists to semiquantitate the intensity of TS expression. RESULTS: Between 1993 and 1996, a total of 30 patients, 18 men and 12 women, with a median age of 61.5 years, were enrolled. Of these patients, 16 (53.3%) and 14 (46.7%) had high and low expression of TS, respectively. Two of the 16 patients (12.5%) with high expression of TS and 13 of the 14 patients (92.9%) with low expression of TS responded to chemotherapy (P < 0.001, chi-square test). The median overall survival was 10 months for patients with low TS expression and 4 months for patients with high TS expression (P < 0.01, log rank test). CONCLUSIONS: The data from this study suggest that the expression of TS, as determined by immunohistochemistry, is a relatively reliable indicator of whether 5-FU should be used in the treatment of patients with gastric carcinoma.

Adenocarcinoma↗

ATP-Dependent human erythrocyte glutathione-conjugate transporter. II. Functional reconstitution of transport activity.

Purified dinitrophenyl S-glutathione (DNP-SG) ATPase was reconstituted into artificial liposomes prepared from soybean asolectin. Electron micrography confirmed the formation of unilamellar vesicles with an average radius of 0.25 micron. Intravesicular volume estimated by incorporation of radiolabled inulin into the vesicles was found to be 19.7 +/- 1.3 microL/mL reconstitution solution. Accumulation of the glutathione-conjugate of CDNB, DNP-SG, and of doxorubicin (DOX) in the proteoliposomes was increased in the presence of ATP as compared to equimolar ADP or adenosine 5'-[beta,gamma-methylene]triphosphate tetralithium. ATP-dependent transmembrane movement of DOX and DNP-SG into DNP-SG ATPase-reconstituted vesicles was saturable with respect to time, sensitive to the osmolarity of the assay medium, and temperature dependent. The energy of activation was found to be 12 and 15 kcal/mol for DNP-SG and DOX, respectively. Optimal temperature for transport was 37 degrees C. Saturable transport was demonstrated for DNP-SG (Vmax of 433 +/- 20 nmol/min/mg of protein, KmATP = 2.4 +/- 0. 3 mM and KmDNP-SG = 36 +/- 5 microM) as well as DOX (Vmax = 194 +/- 19 nmol/min/mg of protein, KmATP = 2.5 +/- 0.6 mM and KmDOX = 2.4 +/- 0.7 microM). The kinetic data for both DNP-SG and DOX transport were consistent with a random bi-bi sequential reaction mechanism. DOX was found to be a competitive inhibitor of DNP-SG transport with Kis of 1.2 +/- 0.2 microM and DNP-SG was found to be a competitive inhibitor of DOX transport with Kis of 13.3 +/- 2.6 microM.

Adenosine Triphosphatases↗

Clinicopathological significance of altered loci of replication error and microsatellite instability-associated mutations in gastric cancer.

Replication errors (RERs) judged by microsatellite instability and its associated mutations have been recognized as an important mechanism in tumorigenesis of gastric cancers (GCs). To gain a deeper insight into its significance, we examined the frequency of RERs using nine microsatellite markers and screened mutations in the polydeoxyadenine tract of the transforming growth factor beta type II receptor gene (TGF-betaRII) and polydeoxyguanine tracts of insulin-like growth factor II receptor and BAX genes. Twenty-four (30%) of 80 patients with GC had RERs, of which 3, 8, and 13 had one, two, and three or more loci, respectively. In 13 tumors with RERs in three or more loci, frameshift mutations of TGF-betaRII, insulin-like growth factor II receptor, and BAX were identified in 12, 3, and 2, respectively. Compared with GC with none, one or two RER-positive loci as a group, GC with RERs in three or more loci showed a significantly higher frequency of antral location (12 of 13 versus 35 of 67; P = 0.01), intestinal subtype (11 of 13 versus 30 of 67; P = 0.01), and previous Helicobacter pylori infection (12 of 13 versus 41 of 67; P = 0.05) and a lower incidence of lymph node metastasis (5 of 13 versus 49 of 67; P = 0.02) and tended to be in an advanced stage (12 of 13 versus 54 of 67; P = 0.28). These data indicate that GC with multiple RERs manifest distinct clinicopathological characteristics, and that a high frequency of frameshift mutations involving the TGF-betaRII gene may be causatively linked with tumorigenesis and progression.

Adult↗

Antibody to a Helicobacter pylori species specific antigen in patients with adenocarcinoma of the stomach.

This study attempted to identify a possible antibody response to Helicobacter pylori, which is associated with patients with adeno-carcinoma of the stomach. By using proteins of H. pylori as the antigen, pooled sera from gastric cancer and non-cancer patients were used as the first antibody for Western blot analysis. Antibody responses to a 26 kD secreted protein were observed in pooled cancer sera, but not in pooled sera from non-cancer patients. The protein was purified, while amino acid sequences revealed that it was a H. pylori species specific protein. The gene of this protein was cloned and a recombinant protein was expressed in E. coli. In addition, an antibody to the recombinant protein was tested in each individual patient using Western blot analysis. None of the forty non-gastric cancer patients were positive for the antibody to the recombinantly expressed 26 kD species specific protein. Meanwhile, six of the twenty four cancer patients tested positive (0/40 vs 6/24, p < 0.01). Results presented herein demonstrate that the species specific protein of H. pylori can be useful in detecting H. pylori associated with adenocarcinoma of the stomach.

Adenocarcinoma↗

Biosynthesis of triacylglycerols containing ricinoleate in castor microsomes using 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine as the substrate of oleoyl-12-hydroxylase.

We have examined the biosynthetic pathway of triacylglycerols containing ricinoleate to determine the steps in the pathway that lead to the high levels of ricinoleate incorporation in castor oil. The biosynthetic pathway was studied by analysis of products resulting from castor microsomal incubation of 1-palmitoyl-2-[14C]oleoyl-sn-glycero-3-phosphocholine, the substrate of oleoyl-12-hydroxylase, using high-performance liquid chromatography, gas chromatography, mass spectrometry, and/or thin-layer chromatography. In addition to formation of the immediate and major metabolite, 1-palmitoyl-2-[14C]ricinoleoyl-sn-glycero-3-phosphocholine, 14C-labeled 2-linoleoyl-phosphatidylcholine (PC), and 14C-labeled phosphatidylethanolamine were also identified as the metabolites. In addition, the four triacylglycerols that constitute castor oil, triricinolein, 1,2-diricinoleoyl-3-oleoyl-sn-glycerol, 1,2-diricinoleoyl-3-linoleoyl-sn-glycerol, 1,2-diricinoleoyl-3-linolenoyl-sn-glycerol, were also identified as labeled metabolites in the incubation along with labeled fatty acids: ricinoleate, oleate, and linoleate. The conversion of PC to free fatty acids by phospholipase A2 strongly favored ricinoleate among the fatty acids on the sn-2 position of PC. A major metabolite, 1-palmitoyl-2-oleoyl-sn-glycerol, was identified as the phospholipase C hydrolyte of the substrate; however, its conversion to triacylglycerols was blocked. In the separate incubations of 2-[14C]ricinoleoyl-PC and [14C]ricinoleate plus CoA, the metabolites were free ricinoleate and the same triacylglycerols that result from incubation with 2-oleoyl-PC. Our results demonstrate the proposed pathway: 2-oleoyl-PC-->2-ricinoleoyl-PC-->ricinoleate-->triacylglycerols. The first two steps as well as the step of diacylglycerol acyltransferase show preference for producing ricinoleate and incorporating it in triacylglycerols over oleate and linoleate. Thus, the productions of these triacylglycerols in this relatively short incubation (30 min), as well as the availability of 2-oleoyl-PC in vivo, reflect the in vivo drive to produce triricinolein in castor bean.

Ricinus communis↗

Pancreaticobiliary diseases associated with anomalous pancreaticobiliary ductal union.

BACKGROUND: Anomalous pancreaticobiliary ductal union (APBDU) is associated with different pancreaticobiliary diseases. The aim of this study is to clarify the frequency with which it occurs and its several subtypes in various pancreaticobiliary diseases. METHODS: Radiograms of 1752 subjects who underwent endoscopic retrograde cholangiopancreatography were reviewed independently by two endoscopists. APBDU was diagnosed using recently accepted criteria and divided into B-P and P-B subtypes according to the insertion of biliary and pancreatic ducts. RESULTS: Fifty-nine (8.7%) of 680 subjects with clearly visualized pancreaticobiliary radiograms had APBDU. APBDU was present in 93.8% of patients (15 of 16) with choledochal cyst, 62.5% (5 of 8) with gallbladder cancer, 33.3% (9 of 27) with common bile duct cancer, 50.0% (6 of 12) with gallbladder adenomyomatosis, 13.2% (7 of 53) with biliary pancreatitis, 3.4% (10 of 293) with cholelithiasis, 2.2% (2 of 89) with non-biliary pancreatitis, 2.1% (1 of 47) with hilar cholangiocarcinoma, 1.9% (1 of 54) with pancreatic cancer, and 10.2% (9 of 88) with other miscellaneous disorders. There were 25 patients (42.4%) with the B-P type and 34 patients (57.6%) with the P-B type of APBDU. Patients with choledochal cyst frequently had the B-P type, whereas gallbladder cancer, adenomyomatosis, or biliary pancreatitis frequently coexisted with the P-B type. CONCLUSION: APBDU is relatively common in patients undergoing endoscopic retrograde cholangiopancreatography at our center. There are a variety of pancreaticobiliary diseases that are associated with APBDU. Its role in these conditions is uncertain and needs to be further delineated.

Cholangiopancreatography, Endoscopic Retrograde↗

Nitrate assimilation by bacteria.

Nitrate is a significant nitrogen source for plants and microorganisms. Recent molecular genetic analyses of representative bacterial species have revealed structural and regulatory genes responsible for the nitrate-assimilation phenotype. Together with results from physiological and biochemical studies, this information has unveiled fundamental aspects of bacterial nitrate assimilation and provides the foundation for further investigations. Well-studied genera are: the cyanobacteria, including the unicellular Synechococcus and the filamentous Anabaena; the gamma-proteobacteria Klebsiella and Azotobacter; and a Gram-positive bacterium, Bacillus. Nitrate uptake in most of these groups seems to involve a periplasmic binding protein-dependent system that presumably is energized by ATP hydrolysis (ATP-binding cassette transporters). However, Bacillus may, like fungi and plants, utilize electrogenic uptake through a representative of the major facilitator superfamily of transport proteins. Nitrate reductase contains both molybdenum cofactor and an iron-sulfur cluster. Electron donors for the enzymes from cyanobacteria and Azotobacter are ferredoxin and flavodoxin, respectively, whereas the Klebsiella and Bacillus enzymes apparently accept electrons from a specific NAD(P)H-reducing subunit. These subunits share sequence similarity with the reductase components of bacterial aromatic ring-hydroxylating dehydrogenases such as toluene dioxygenase. Nitrite reductase contains sirohaem and an iron-sulfur cluster. The enzymes from cyanobacteria and plants use ferredoxin as the electron donor, whereas the larger enzymes from other bacteria and fungi contain FAD and NAD(P)H binding sites. Nevertheless, the two forms of nitrite reductase share recognizable sequence and structural similarity. Synthesis of nitrate assimilation enzymes and uptake systems is controlled by nitrogen limitation in all bacteria examined, but the relevant regulatory proteins exhibit considerable structural and mechanistic diversity in different bacterial groups. A second level of control, pathway-specific induction by nitrate and nitrite in Klebsiella, involves transcription antitermination. Several issues await further experimentation, including the mechanism and energetics of nitrate uptake, the pathway(s) for nitrite uptake, the nature of electron flow during nitrate reduction, and the action of transcriptional regulatory circuits. Fundamental knowledge of nitrate assimilation physiology should also enhance the study of nitrate metabolism in soil, water and other natural environments, a challenging topic of considerable interest and importance.

Bacteria↗

Gastric cancer risk in relation to Helicobacter pylori infection and subtypes of intestinal metaplasia.

Helicobacter pylori (H. pylori) infection and intestinal metaplasia (IM) are each associated with an increased risk of gastric cancer (GC). To explore further the influences of H. pylori and IM on GC, H. pylori and subtypes of IM were evaluated in 135 sex and age-matched case and control pairs. Odds ratios (ORs) with 95% confidence intervals of developing GC were calculated for each risk factor using multiple logistic regression analysis. ORs for H. pylori infection and IM were 2.43 (1.29-4.65) and 4.59 (2.58-8.16), respectively, and those for different IM subtypes gave values of 0.82 (0.28-2.36) for type I, 2.03 (0.95-4.34) for type II and 39.75 (14.34-110.2) for type III. Stratification analysis by histological subtype and stage of GC showed a particularly high OR for IM in intestinal type (12.8, 4.73-34.83) and early GC (6.40, 2.25-18.18). Our data indicate that both H. pylori and IM are related to GC risk. Type III IM is a more specific marker of premalignancy, with relevance, in particular, to the early and intestinal type of GC.

Adult↗

Overexpression of p53 in different subtypes of intestinal metaplasia and gastric cancer.

p53 immunostaining was evaluated in cancerous epithelia and adjacent intestinal metaplasia of 135 gastric cancer specimens. The differential p53 overexpression in different subtypes of intestinal metaplasia and gastric cancer suggests that type III intestinal metaplasia is the commonest lesion in dysplasia-carcinoma transition, particularly in the intestinal type of gastric cancer.

Humans↗