Search PubMed⌕ Search

Biomedical subjects

L Z Xu

Publications and source records attributed to L Z Xu.

At least 37 records · Page 2Linked to original sources

Hepatitis C virus genotype 4 is highly prevalent in central Africa (Gabon).

Following a survey of hepatitis C virus (HCV) infection recently carried in central Africa (Gabon), we cloned and sequenced PCR products of the 5' non-coding and capsid-encoding regions of HCV RNA from three randomly selected HCV RNA-positive Gabonese subjects. In the capsid-encoding region, the identity between the three Gabonese isolates was 91 to 98%. The three Gabonese sequences showed a divergence of 11 to 17% from published HCV genotypes I to IV (1a, 1b, 2a and 2b) isolates and of 6 to 11% from HCV genotype 4 isolates. Thus the Gabonese isolates, termed HC-G, belong to HCV genotype 4. Based on the sequences of the three isolates, a specific probe (cpsG) was designed to detect the HC-G genotype in 30 randomly selected anti-HCV-positive Gabonese subjects, 14 of whom were HCV RNA-positive. Analysis with cpsG showed that 10 of 14 of the HCV RNA-positive subjects were infected by the HC-G genotype. HC-G is therefore highly prevalent in the HCV RNA-positive Gabonese population. The availability of these Gabonese sequences should facilitate the design of specific serological tests for African HCV isolates.

Base Sequence↗

[Chemical constituents of Sageretia theezans Brongn].

Six compounds were isolated from Sageretia theezans and identified as friedeline (1), syringic acid (2), beta-sitosterol (3), daucosterol (4), gluco-syringic acid (5) and taraxerol (6) on the basis of spectral data (1H-NMR, IR, MS) and physico-chemical constants. Among them, compounds 5 and 6 were obtained from the species for the first time.

Benzoates↗

[Chemical constituents of Pogostemon cablin (Blanco) Benth].

Nine compounds were isolated from the herb of Pogostemon cablin. They were identified as patchouli alcohol (1), pogostone (2), friedelin (3), epifriedelinol (4), pachypodol (5), retusine (6), oleanolic acid (7), beta-sitosterol (8) and daucosterol (9) on the basis of spectral data (1H-NMR, IR, MS and UV). Compound 3, 4, 6, 7, 8 and 9 were obtained from the species for the first time.

Drugs, Chinese Herbal↗

Structure/function studies of human beta-cell glucokinase. Enzymatic properties of a sequence polymorphism, mutations associated with diabetes, and other site-directed mutants.

Glucokinase plays a key role in the regulation of glucose metabolism in insulin-secreting pancreatic beta-cells and in the liver. Recent studies have shown that mutations in this enzyme can lead to the development of a form of non-insulin-dependent diabetes mellitus that is characterized by an autosomal dominant mode of inheritance and onset during childhood. Here, we report the catalytic properties of five additional missense mutations associated with diabetes (Glu70-->Lys, Ser131-->Pro, Ala188-->Thr, Trp257-->Arg and Lys414-->Glu), one polymorphism present in both normal and diabetic subjects (Asp4-->Asn), and three site-directed mutations (Glu177-->Lys, Glu256-->Ala, and Lys414-->Ala). The Trp257-->Arg mutation generated an enzyme that had an activity that was less than 0.5% of that for native human beta-cell glucokinase. By contrast, the Glu70-->Lys, Ser131-->Pro, Ala188-->Thr, and Lys414-->Glu mutations had a Vmax that was 20-100% of normal but a Km for glucose that was 8-14-fold greater than the native enzyme. There was no effect of the Asp4-->Asn polymorphism or the Glu177-->Lys substitution on glucokinase activity. The Lys414-->Ala substitution had no effect on Vmax but increased the Km for glucose 2-fold and the Glu256-->Ala substitution caused a approximately 200-fold decrease in Vmax. These studies have led to the identification of additional residues involved in glucokinase catalysis and substrate binding.

Amino Acid Sequence↗

Glucokinase mutations associated with non-insulin-dependent (type 2) diabetes mellitus have decreased enzymatic activity: implications for structure/function relationships.

The glycolytic enzyme glucokinase plays an important role in the regulation of insulin secretion and recent studies have shown that mutations in the human glucokinase gene are a common cause of an autosomal dominant form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM) that has an onset often during childhood. The majority of the mutations that have been identified are missense mutations that result in the synthesis of a glucokinase molecule with an altered amino acid sequence. To characterize the effect of these mutations on the catalytic properties of human beta-cell glucokinase, we have expressed native and mutant forms of this protein in Escherichia coli. All of the missense mutations show changes in enzyme activity including a decrease in Vmax and/or increase in Km for glucose. Using a model for the three-dimensional structure of human glucokinase based on the crystal structure of the related enzyme yeast hexokinase B, the mutations map primarily to two regions of the protein. One group of mutations is located in the active site cleft separating the two domains of the enzyme as well as in surface loops leading into this cleft. These mutations usually result in large reductions in enzyme activity. The second group of mutations is located far from the active site in a region that is predicted to undergo a substrate-induced conformational change that results in closure of the active site cleft. These mutations show a small approximately 2-fold reduction in Vmax and a 5- to 10-fold increase in Km for glucose. The characterization of mutations in glucokinase that are associated with a distinct and readily recognizable form of NIDDM has led to the identification of key amino acids involved in glucokinase catalysis and localized functionally important regions of the glucokinase molecule.

Amino Acid Sequence↗

Prevalence of hepatitis C virus infection in asymptomatic anti-HIV1 negative pregnant women and their children.

The prevalence of hepatitis C virus (HCV) infection was studied prospectively in pregnant women in France and their children by detection of anti-HCV with second-generation ELISA (ELISA2). In ELISA2-positive women, anti-HCV was detected with second- and third-generation RIBA (RIBA2 and RIBA3) and serum HCV RNA was detected with PCR. Among 670 women, anti-HIV1-negative, 26 (3.9%) were positive with ELISA2. RIBA2 was positive in 13 and HCV RNA was found in 10. Ten ELISA2-positive women had a further evaluation with assessment of HCV infection in their children. Among the 10 children born to the index pregnancy, only one was positive with ELISA2 and RIBA2 but negative with RIBA3 and PCR; the nine other children were ELISA2, RIBA2, RIBA3, and PCR negative. All 26 siblings (2-16 years old), of whom 14 were born to PCR-positive mothers, were ELISA2 and RIBA2 negative. We conclude that among anti-HIV1-negative pregnant women with normal serum ALT levels, the prevalence of HCV infection is relatively high but the risk for mother-to-infant transmission of HCV seems to be low.

Adult↗

Chronic non-B, non-C hepatitis among blood donors assessed with HCV third generation tests and polymerase chain reaction.

Forty five blood donors with increased serum aminotransferases levels had liver histologic assessment and were tested for antibodies to hepatitis C virus (anti-HCV) with second and third generation ELISAs and RIBAs, and for HCV RNA with polymerase chain reaction (PCR) in serum and liver tissue. Twenty-nine of these 45 donors (65%) had steatosis without chronic hepatitis. Sixteen (35%) had chronic hepatitis. Twelve had evidence of HCV infection. Four had no evidence of HCV infection demonstrable by ELISA, RIBA or PCR. These four patients had no known cause of chronic hepatitis and no risk factor for parenterally acquired viral infection was found in them. This observation supports the hypothesis that a non-B, non-C virus might be implicated in chronic hepatitis. However, this hypothesis remains to be demonstrated.

Blood Donors↗

Rabies in China: recommendations for control.

Reviewed are the results of 15 years' experience with rabies at You-An Infectious Disease Hospital, Beijing, China. The purpose of the study was to determine whether there are any epidemiological or clinical features of rabies that are unique to China and which might be important in developing a strategy to control it. During the period under study, 64 patients with rabies were admitted to You-An Hospital. Exposure to dogs was associated with 61 cases, two involving the handling of dog carcasses that were being prepared for meals. All of the exposures occurred in rural areas, and none of the patients received adequate prophylaxis. Patients with proximal sites of exposure and with severe injuries developed rabies after short incubation periods (P less than 0.05, and P less than 0.02, respectively). Failed vaccination was also associated with a short incubation period (P less than 0.05). Haematemesis occurred in 20 patients and was associated with shorter incubation periods (P less than 0.02), facial exposure sites (P = 0.021), and severe injuries (P = 0.047). A strategy to control rabies in China should include efforts to educate the public about handling the carcasses of stray dogs, in addition to the currently recommended strategy of controlling the dog population and of vaccinating domesticated animals.

Adolescent↗

[Studies on the chemical constituents of Annona squamosa].

Twelve compounds were isolated from Annona squamosa. Their structures were identified as liriodenine (AS-1), moupinamide (AS-2), -(-)-kauran-16 alpha-ol-19-oic acid (AS-3), 16 beta, 17-dihydroxy-(-)-kauran-19-oic acid (AS-4), anonaine (AS-5), 16 alpha, 17-dihydroxy-(-)-kauran-19-oic acid (AS-6), (-)-isokaur-15(16)-en-17,19-dioic acid (AS-7), squamosamide (AS-8), 16 alpha-methoxy-(-)-kauran-19-oic acid (AS-9), sachanoic acid (AS-10), (-)-kauran-19-al-17-oic acid (AS-11), daucosterol (AS-12). Among them, AS-8 is a new amide, AS-9 is a new natural product.

Antineoplastic Agents↗

AGNORS in skin lesions of cutaneous malignant lymphomas and pseudolymphomas.

Nucleolar organiser regions (NORs) are loops of DNA situated on the short arms of acrocentric chromosomes 13, 14, 15, 21, and 22. They can be demonstrated in formalin-fixed paraffin-embedded sections by a one step silver technique; the resultant black structures are called AgNORs. The technique was used in 71 patients with cutaneous malignant lymphomas (CML) and 9 cutaneous pseudolymphomas (CPL). AgNORs in 200 nuclei were scored and the means, standard deviation and standard error of the means calculated. Counts were as follows: mycosis fungoides (MF) I (premycotic stage) 1.17 +/- 0.09, SEM = 0.01; MF II (infiltrating stage) 1.17 +/- 0.01, SEM = 0.02; MF III (tumor stage) 3.55 +/- 0.87, SEM = 0.43: cutaneous peripheral T cell lymphomas other than MF and Sezary's syndrome (SS) (CPTL) 2.55 +/- 1.11, SEM = 0.35; SS 1.52; cutaneous B cell lymphomas (CBCL) 2.18 +/- 0.18, SEM = 0.06; CPL 1.17 +/- 0.1, SEM = 0.03. There was a significant difference between counts for CML (MF III, CPTL, CBCL and SS) and CPL. Significant difference was also noted between scores for MF III and CBCL, and especially counts between tumor stage (MF III and CPTL) and pretumor stage (MF I and MF II) of cutaneous peripheral T cell lymphomas. Although the AgNOR technique is in the stage of research, it proves to be helpful in differentiating CML and CPL other than separating MF I and MF II from CPL.

Adolescent↗

Nucleolar organizer regions in aspirates of malignant lymphomas and benign disorders of the lymph nodes.

Silver staining of nucleolar organizer regions (AgNOR) was used to differentiate malignant lymphoma and chronic lymphadenitis. Aspiration smear samples from lymph nodes of 120 cases, including 43 non-Hodgkin's lymphoma, 3 Hodgkin's disease, 56 chronic lymphadenitis, 7 tuberculosis, 6 reactive hyperplasia and 5 samples from other diseases (epidermoid cyst, branchial cyst, mixed tumor, lymphoepithelioma and nodulous disease), were investigated. The number of AgNORs in 200 cells in each sample was counted, and the mean +/- SD in each disease was calculated: non-Hodgkin's lymphoma, 6.58 +/- 2.37; Hodgkin's disease, 4.22 +/- 0.5; chronic lymphadenitis, 1.16 +/- 0.1; tuberculosis, 1.13 +/- 0.14; reactive hyperplasia, 1.48 +/- 0.25; other diseases, 1.47 +/- 0.31. The results indicate that the AgNOR count in malignant lymphoma differed highly significantly from that in benign disease (P less than .001). The size of AgNORs in malignant lymphoma and chronic lymphadenitis was measured, and the maximum diameter and area of lymphocyte and lymphoma cell were: lymphocyte, 0.93 +/- 0.12 microns, 0.61 +/- 0.13 microns 2; lymphoma cell, 0.83 +/- 0.22 microns, 0.50 +/- 0.25 microns 2. The AgNOR sizes in malignant lymphoma were significantly smaller than in chronic lymphadenitis (P less than .001).

Adolescent↗

Expression and site-directed mutagenesis of hepatic glucokinase.

Soluble rat liver glucokinase was expressed at high levels at 22 degrees C in the BL21(DE3)pLysS strain of Escherichia coli. Aspartate-211 of yeast hexokinase has been implicated as a catalytic residue from crystallographic data. The corresponding residue in rat liver glucokinase, aspartate-205, was mutated to alanine and the expressed mutant had 1/500th of the activity of the wild type, with no change in the Km values for glucose or ATP. The results support a role for this residue as a base catalyst in the glucokinase reaction and, most probably, a similar role in the reactions of all members of the hexokinase family.

Animals↗

The polymerase chain reaction: basic methodology and applications.

The "polymerase chain reaction" (PCR) is a high-power molecular biology technique allowing in vitro enzymatic amplification of a given DNA sequence. This exponential amplification can reach 10(7)-10(9), even a single DNA molecule can be detected. Also the use of non-radioactive probes, considered to be less sensitive than their radioactive counterparts, is possible for the molecular hybridization, to retain a high level of sensitivity. PCR is defined as a "free bacteria" cloning technique, which has many applications in fundamental research and in the clinical analysis of genetic disease, infectious diseases and cancers. Thus PCR is a revolutionary method which is capable of greatly stimulating scientific research and modifying the diagnostic area in the near future.

Cloning, Molecular↗

An approach to establishing N-nitroso compounds as the cause of gastric cancer.

Although gastric cancer is the most common cause of mortality from cancer, its etiology is not yet clear. To elucidate the role of N-nitroso compounds, we investigated 30 cases of gastric cancer by determination of the contents of nitrate and ascorbic acid and by detection of mutagens in urine. Cases were paired 1:1 with patients with dysplasia and normal controls of the same sex and age group. In comparison with normal controls, the gastric cancer group had higher nitrate and lower ascorbic acid levels in urine. Mutagenicity was observed in the urines of 83.3% of the gastric cancer cases and in 16.6% of the dysplasia group, but in none of those from normal controls. When the N-nitroso compound content of gastric juice was determined, the levels in control subjects were significantly lower than those in persons with gastric cancer. These results support the hypothesis that the cause of gastric cancer may be N-nitroso compounds.

Ascorbic Acid↗

Cutaneous germinal center cell-derived lymphomas. A clinical histopathological and immunopathological study of 18 cases.

Eighteen cases of cutaneous germinal center cell-derived lymphomas (CGCCL) were classified into 3 types according to Kiel classification: centrocytic lymphomas (CC), 7; centroblastic-centrocytic lymphomas (CB/CC), 9; and centroblastic lymphomas (CB), 2. The duration of the disease was 3-14 months (median 9.5 months) after the first admission. In all cases, monomorphous cutaneous nodules were found as the initial manifestation of the disease. Twelve cases of CGCCL, especially those of CB and CB/CC, initially presented with normochromic anemia, a finding which is helpful in the diagnosis of the disease. Cytomorphologically, CB tumor cells were easily identified, white CC cells were hard to distinguish from the cells of nonepidermotropic cutaneous T cell lymphoma. In many cases, however, electron microscopic examination and cytochemical stains of skin biopsy tissue imprints are useful in diagnosing CGCCL. Immunoenzyme labelling (ABC method) with monoclonal antibodies indicated that B1, K and lambda positivity are very important markers for CGCCL. Our findings also showed a higher percentage of rK type in CGCCL as compared to the Western countries.

Adult↗