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1.
Zhonghua Yi Xue Za Zhi ; 103(6): 431-435, 2023 Feb 14.
Article in Chinese | MEDLINE | ID: mdl-36775267

ABSTRACT

Objective: To investigate the effect of methylene blue tracing on the effect of surgical resection and the prognosis of gastric cancer patients in D2 radical surgery under laparoscope. Methods: In this retrospective cohort study, 160 patients with advanced gastric cancer who underwent surgical treatment in Xinxiang Central Hospital, the 4th Clinical College of Xinxiang Medical College from January 2016 to January 2019 were selected for retrospective analysis. Among them, 84 patients underwent laparoscopic D2 radical gastrectomy for gastric cancer combined with methylene blue labeling operation (labeling group), and the other 76 patients underwent only laparoscopic D2 radical gastrectomy for gastric cancer (control group). The difference of intraoperative and postoperative recovery, lymph node dissection, and postoperative 3-year cumulative survival rate between the two groups were analyzed. Results: The age of patients in the labeled group and the control group were (64.9±7.8) and (66.0±8.3) years old, respectively (P=0.389); And the male patients accounted for 61.9% (52 cases) and 55.3% (42 cases), respectively (P=0.394); The operation time in the labeled group was (218.5±19.6) min, which was shorter than that in the control group (230.1±17.4) min (P<0.001). There was no significant difference between the labeled group and the control group in the amount of bleeding during operation, the time of anal exhaust after operation, the time of eating after operation, the time of hospitalization after operation, and the average diameter of lymph nodes (P>0.05). The total number of dissected lymph nodes, D1 lymph nodes and D2 lymph nodes in the labeled group were significantly higher than those in the control group (all P values<0.05). The operative complication rate in the labeled group was 11.9% (10 cases), which was lower than that in the control group (25.0%, 19 cases) (P=0.032); There was no statistical significance in 3-year cumulative survival rates of patients between the labeled group (61.9%) and the control group (52.6%) (χ2=3.46,P=0.065). Conclusion: The use of methylene blue tracing in laparoscopic D2 radical surgery for gastric cancer is beneficial to reduce the operation time, improve the lymph node clearance rate, and reduce surgical complications.


Subject(s)
Laparoscopy , Stomach Neoplasms , Humans , Male , Retrospective Studies , Methylene Blue , Laparoscopes , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Prognosis , Lymph Node Excision , Gastrectomy
2.
Zhonghua Zhong Liu Za Zhi ; 43(11): 1156-1163, 2021 Nov 23.
Article in Chinese | MEDLINE | ID: mdl-34794217

ABSTRACT

Objective: To investigate the effect of miR-369-3p targeting ACTN4 expression on proliferation and apoptosis of hepatocellular carcinoma cells. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expression levels of miR-369-3p and ACTN4 in hepatocarcinoma tissues and adjacent tissues. MiR-369-3p mimics, miR-negative control (NC), si-ACTN4, and si-NC were transfected into hepatocellular carcinoma MHCC97H cells by liposome method. Cell proliferation was detected by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-dipheny-ltetrazolium bromide (MTT) assay. Flow cytometry was used to detect cell cycle and apoptotic rates. The dual luciferase reporter assay was used to verify the targeted regulation of ACTN4 by miR-369-3p. Western blot was used to detect the expressions of cyclin D1, p21, Bcl-2 and Bax. Results: The expression level of miR-369-3p in liver cancer tissue was lower than that in adjacent tissues [(0.46±0.04) vs (1.00±0.08), P<0.001)], while the expression level of ACTN4 was higher than that in adjacent tissues [mRNA (3.12±0.29) vs (1.01±0.09); protein (0.61±0.06) vs (0.25±0.03), P<0.001]. Overexpression of miR-369-3p significantly decreased the cell viability[(0.71±0.06) vs (1.26±0.11), P<0.001)], increased cell apoptosis rate [(20.16±2.11)% vs (6.25±0.64)%, P<0.001], increased the proportion of cells in G(1) phase [(31.14±3.36)% vs (51.56±5.23)%, P<0.001], decreased the proportion of cells in S phase [(32.44±3.56)% vs (14.33) ±1.45)%, P<0.001], increased the levels of p21 and Bax protein (P<0.001), and decreased the levels of cyclin D1 and Bcl-2 protein (P<0.001). Inhibition of the expression of ACTN4 significantly reduced the cell viability [(0.78±0.07) vs (1.24±0.12), P<0.001], increased the apoptosis rate [(6.58±0.66)% vs (18.32±1.82)%, P<0.001], increased the proportion of cells in G(1) phase [(48.69±4.21)% vs (30.33±3.01)%, P<0.001], decreased the proportion of cells in S phase [(36.21±3.42)% vs (18.54±1.61)%, P<0.001], increased the protein levels of p21 and Bax (P<0.001), and decreased the levels of cyclin D1 and Bcl-2 protein (P<0.001). Compared with the miR-369-3p+ pcDNA group, overexpression of ACTN4 increased the proliferation ability of hepatocellular carcinoma MHCC97H cells at 72 hours of culture[(1.12±0.11) vs (0.68±0.06), P<0.001], significantly reduced the proportion of cells in G(1) stage [(38.81±3.24)% vs (51.80±4.57)%, P<0.001], significantly increased the proportion of S-phase cells [(31.65±3.11)% vs (15.69±1.44)%, P<0.001], decreased cell apoptosis rate [(13.86±1.37)% vs (22.69±2.24)%, P<0.001], increased protein expressions of cyclin D1 and Bcl-2 (P<0.001), decreased the protein expressions of p21 and Bax (P<0.001). Conclusion: MiR-369-3p can induce cell cycle arrest in G(1) phase, inhibit the proliferation and promote apoptosis of liver cancer cells by regulating the expression of ACTN4.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Actinin/genetics , Apoptosis , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , MicroRNAs/genetics
3.
Eur Rev Med Pharmacol Sci ; 22(20): 6991-6998, 2018 10.
Article in English | MEDLINE | ID: mdl-30402866

ABSTRACT

OBJECTIVE: To investigate the possible role of hox transcript antisense intergenic RNA (HOTAIR) in the pathogenesis of atherosclerosis and its underlying mechanism. PATIENTS AND METHODS: The expression of HOTAIR in peripheral blood lymphocytes of atherosclerosis (AS) and healthy controls was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR). In vitro AS model was established by ox-LDL induction in Raw264.7 cells. Viability of Raw264.7 cells after ox-LDL induction was detected by cell counting kit-8 (CCK-8) assay. Levels of TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol) and HDL-C (high density lipoprotein cholesterol) in Raw264.7 cells were detected by enzyme-linked immunosorbent assay (ELISA). Overexpression plasmid of HOTAIR was constructed. Levels of TG, TC, LDL-C, and HDL were detected again after HOTAIR overexpression by ELISA. CD68+ cells and CD168+ cells in Raw264.7 cells were detected by flow cytometry. Protein expressions of pro-inflammatory and anti-inflammatory genes were detected by Western blot. Lipid metabolism in Raw264.7 cells was evaluated by oil red O staining and Western blot, respectively. Finally, rescue experiments were conducted to explore the specific mechanism of HOTAIR in regulating AS development. RESULTS: HOTAIR was lowly expressed in peripheral blood lymphocytes of AS patients and Raw264.7 cells induced by ox-LDL. Overexpression of HOTAIR upregulated adipose genes (PPARα and CPT-1) and downregulated lipogenesis genes (SREBP-1c and ACS). Besides, overexpression of HOTAIR decreased expressions of pro-inflammatory cytokines (TNF-α and IL-1ß), but increased expressions of anti-inflammatory cytokines (IL-4 and IL-10). In the in vitro AS model, FXR1 was remarkably downregulated in Raw264.7 cells. HOTAIR reduced inflammatory response via promoting FXR1 expression in Raw264.7 cells. Rescue experiments showed that the effect of HOTAIR on nuclear factor-kappa B (NF-κB) pathway was reversed by FXR1 knockdown. CONCLUSIONS: We found that TAIR was lowly expressed in AS patients. Overexpression of HOTAIR can reduce the lipid accumulation and inhibit inflammatory response by suppressing FXR1 via NF-κB pathway.


Subject(s)
Atherosclerosis/pathology , Cytokines/metabolism , Lipoproteins, LDL/metabolism , RNA, Long Noncoding/genetics , Animals , Atherosclerosis/blood , Down-Regulation , Humans , Interleukin-1beta/metabolism , Lipid Metabolism , Mice , NF-kappa B/metabolism , RAW 264.7 Cells , RNA-Binding Proteins/genetics , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation
4.
Genet Mol Res ; 14(2): 3767-74, 2015 Apr 22.
Article in English | MEDLINE | ID: mdl-25966146

ABSTRACT

Numerous studies have evaluated the association between the T174M polymorphism in the angiotensinogen (AGT) gene and myocardial infarction (MI) risk. However, the specific association remains controversial because of small sample sizes and varied study designs among different studies. We performed a meta-analysis to assess this correlation. A comprehensive search was conducted to identify all published articles regarding the association between the AGT gene T174M polymorphism and MI risk from different databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and heterogeneity and publication bias were assessed. A total of 1032 patients with lung cancer and 1286 controls from 6 comparative studies were included in this meta-analysis. The results revealed a significant association between the AGT gene T174M polymorphism and MI risk (MM vs TT: OR = 2.87, 95%CI = 1.71-4.83; dominant model: OR = 1.57, 95%CI = 1.10-2.25; recessive model: OR = 0.41, 95%CI = 0.25-0.66). In subgroup analysis by nationality, we observed a significant association between the AGT gene T174M polymorphism and susceptibility to MI in both Caucasian and Asian populations. In conclusion, the T174M polymorphism in the AGT gene may be related to an increased risk of MI. Further larger studies are needed to confirm these conclusions.


Subject(s)
Angiotensinogen/genetics , Amino Acid Sequence , Case-Control Studies , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Myocardial Infarction/genetics , Polymorphism, Genetic , Risk
5.
Thorac Cardiovasc Surg ; 50(3): 182-3, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12077695

ABSTRACT

Redo operations after coronary artery bypass surgery have been on the rise, and myocardial and graft injury during resternotomy a catastrophe. Closure of pericardium after a traditional midline incision may lead to graft distortion. In this report, we will describe a technique of pericardial closure and thymus coverage to protect bilateral internal mammary artery grafts from damage.


Subject(s)
Coronary Artery Bypass/methods , Internal Mammary-Coronary Artery Anastomosis , Pericardium/surgery , Humans , Reoperation/methods , Sternum/surgery
6.
Chemosphere ; 44(5): 1153-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11513403

ABSTRACT

The object of this research was to study the formation of disinfection by-products by using chlorine dioxide (ClO2) as a disinfectant reacting with different properties of organic substance in natural aquatic environment. The adsorbent resin (XAD-4, XAD-7) was used to divide the organic matters in raw water into three groups. The influence of the function groups on structure, reaction tendency, and formation of disinfection by-products generated by the reaction of these organic substances with chlorine dioxide was explored. The experimental results show that the three different organic groups formed using adsorbent resin were hydrophobic substance, hydrophilic acid, and non-acid hydrophilics in proportions of 43%, 41%, and 16%, respectively. Within the raw water in our study, the hydrophilic substance had a higher distribution proportion than that described in general articles and journals, which indicates that this water was contaminated with pollution from human beings. The exploration of the reactivity of the three different organic substances with chlorine dioxide shows that the unit consumption of disinfection agent per unit organic matters (represented by ClO2/DOC) is in the following sequence hydrophobic substance > hydrophilic substance > non-acid hydrophilics. It indicated that larger molecular organic precursors had larger consumption of disinfectant. We also discovered that after the reaction of the three different organic substances with chlorine dioxide, the largest amount of disinfection by-products were generated by the non-acid hydrophilics.


Subject(s)
Chlorine Compounds/chemistry , Dental Disinfectants/chemistry , Oxides/chemistry , Water Pollutants, Chemical/analysis , Adsorption , Environmental Monitoring , Humans , Organic Chemicals , Resins, Plant , Sewage , Solubility
7.
Article in English | MEDLINE | ID: mdl-11381786

ABSTRACT

Cr, Ni, and Cd adsorption-desorption on five characterized Taiwan soils was studied. The potential for toxicity and the fate of metals in the soils is dependent upon the ability of the metals to desorb into the aqueous phase. To simulate field conditions, the soils were subjected to wet-dry cycles. The amount and rate of desorption was found to decrease with increasing number of cycles. The wet-dry cycle effect in the desorption of metals from soils is related to the soil composition, with desorption being easiest from sandy soil with low organic content. The desorption process is much slower than adsorption process. More than 95% of each metal adsorption takes place within one hour, and the amount of metal adsorbed from solution reached equilibrium in one day. In contrast, less than 20% metal desorption could be attained after 3 days each of four wet-dry cycles for Cr, Ni, and Cd.


Subject(s)
Cadmium/chemistry , Chromium/chemistry , Nickel/chemistry , Soil Pollutants , Adsorption , Kinetics , Water
8.
J Hazard Mater ; 79(1-2): 89-102, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11040388

ABSTRACT

In this study, chlorine dioxide (ClO(2)) was used as an alternative disinfection agent with humic acid as the organic precursor in a natural aquatic environment. The major topics in this investigation consisted of the disinfection efficiency of ClO(2), the formation of disinfection by-products (DBPs), and the operating conditions. The results indicated that the pH value (pH 5-9) did not affect the efficiency of disinfection while the concentration of organic precursors did. The primary DBPs formed were trihalomethanes (THMs) and haloacetic acids (HAAs). The distribution of the individual species was a function of the bromide content. The higher the ClO(2) dosage, the lower the amount of DBPs produced. The amount of DBPs increased with reaction time, with chlorite ions as the primary inorganic by-product.


Subject(s)
Chlorine Compounds/metabolism , Dental Disinfectants/metabolism , Oxides/metabolism , Water Pollutants, Chemical/metabolism , Disinfectants , Hydrogen-Ion Concentration , Water Supply
9.
Acta Paediatr Taiwan ; 41(2): 85-9, 2000.
Article in English | MEDLINE | ID: mdl-10927945

ABSTRACT

Aortic valve is often replaced if valvular stenosis fails to be balloon dilated. Aortic valve reconstruction was performed on 4 patients from August 1993 to 1999. Their ages ranged from 1 month to 15 years (mean 8.3 years). Unicuspid aortic valve was present in three of them and bicuspid in the other one. Two patients were associated with a patent arterial duct, one aortic regurgitation, and one pulmonary stenosis. Commissurotomy was done in three of them to transform the aortic valve into tricuspid except one, in whom bicuspid valve was preserved. In one case with unicuspid aortic valve, a piece of tanned autologous pericardium was used to augment one myxomatous and retracted leaflet. The sinus of Valsalva was molded together with a bulging shape of its aortic leaflet. All four were weaned from cardiopulmonary bypass smoothly. Transesophageal echocardiography in one case prompted rebypass to decrease the degree of regurgitation from moderate to mild by further shaping of the leaflet and sinus of Valsalva. In one patient chylopericardium was complicated and subsided in 5 days after conservative treatment. All patients were doing well on follow up at 56.8 +/- 34.4 months after surgery, with trivial to mild systolic pressure gradient (20 +/- 26 mmHg; preoperatively: 88 +/- 36 mmHg) and mild regurgitation. Aortic valve reconstruction is feasible in the setting of congenital aortic stenosis in our limited experience; repair instead of replacement is recommended even when regurgitation is present.


Subject(s)
Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Adolescent , Child , Echocardiography , Follow-Up Studies , Humans , Infant, Newborn
10.
J Pediatr ; 132(4): 717-20, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9580777

ABSTRACT

Carbonic anhydrase (CA) II deficiency is characterized by osteopetrosis, renal tubular acidosis, cerebral calcification, and usually severe mental retardation. We describe an Italian boy with this disease whose mental retardation was relatively mild and whose renal tubular acidosis had only a distal component. A novel mutation of a gt-->tt change of splice donor site at the 5' end of intron 6 was demonstrated. Comparison of this patient with two previous Italian families with different mutations illustrates the clinical and molecular heterogeneity of this disease. The identification of the mutation in this family provided the opportunity for prenatal diagnosis in a subsequent pregnancy.


Subject(s)
Acidosis, Renal Tubular/genetics , Carbonic Anhydrases/deficiency , Intellectual Disability/genetics , Osteopetrosis/genetics , Prenatal Diagnosis , Acidosis, Renal Tubular/diagnosis , Carbonic Anhydrases/genetics , Child, Preschool , Female , Humans , Infant, Newborn , Intellectual Disability/diagnosis , Introns/genetics , Male , Mutation , Osteopetrosis/diagnosis , Polymorphism, Single-Stranded Conformational , Pregnancy
12.
Intensive Care Med ; 22(9): 933-6, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8905428

ABSTRACT

OBJECTIVE: To evaluate the risk factors for postextubation laryngeal stridor and its prevention by hydrocortisone in adult patients. DESIGN: Prospective, randomized, double-blind, placebo controlled study. SETTING: Medical and surgical ICU of a tertiary teaching hospital. PATIENTS: 77 consecutive patients of both sexes, who had undergone tracheal intubation for more than 24 h and fulfilled the weaning criteria, were eligible for the study. Patients were excluded if they were less than 15 years of age, had a disease or the surgery of the throat, or had been extubated during the current hospitalization. INTERVENTION: The control group received placebo (normal saline 3 cc) and the experimental group received hydrocortisone 100 mg by intravenous infusion 60 min before extubation. MAIN OUTCOME MEASURES: Patients were observed 24 h after extubation for symptoms or signs of laryngeal edema or stridor: prolonged inspiration with accessory usage of respiratory muscles or crowing sound with inspiration or reintubation. RESULTS: The overall incidence of postextubation stridor was 22% (17/77). Only one patient (1%), who belonged to the control group, needed reintubation. 39% of female patients and 17% of male patients developed stridor. The relative risk of females developing this complication was 2.29. 7/39 of the hydrocortisone group and 10/38 of patients in the control group developed postextubation stridor. CONCLUSIONS: Hydrocortisone did not significantly reduce the incidence of postextubation laryngeal edema or stridor. From the risk factors evaluated, we were unable to demonstrate a statistical correlation between postextubation stidor and the duration of the intubation, the patient's age, the internal diameter of the endotracheal tube, or the route of intubation. However, female patients were more likely to develop this complication.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Hydrocortisone/therapeutic use , Intubation, Intratracheal/adverse effects , Laryngeal Edema/drug therapy , Laryngeal Edema/etiology , Premedication , Aged , Double-Blind Method , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies , Respiratory Sounds/etiology , Risk Factors , Time Factors
13.
Proc Natl Acad Sci U S A ; 92(6): 2136-40, 1995 Mar 14.
Article in English | MEDLINE | ID: mdl-7892236

ABSTRACT

A single-base-pair deletion in exon 7 of the human carbonic anhydrase II gene was found to be the molecular defect in a group of independently ascertained, clinically heterogeneous, Hispanic carbonic anhydrase II-deficient patients, all of whom had ancestors from the Caribbean islands. This mutation predicts a +1 frameshift at codon 227 and incorporation of 12 missense amino acids before an early stop codon at position 239 produces a 27-kDa truncated carbonic anhydrase II. Expression of the Hispanic mutant cDNA in bacteria produced predominantly the 27-kDa protein, which was inactive. However, a minor 29-kDa polypeptide species was also produced that had 10% the specific activity of the wild-type enzyme after affinity purification. Amino acid sequencing showed that the 29-kDa mutant protein was produced by two frameshift events: a +1 frameshift at codon 227 due to the single-base deletion and a -1 ribosomal frameshift at codon 237 that restored the original reading frame after 11 missense amino acids were incorporated. Antibody against the 11-amino acid frameshift peptide detected the 29-kDa mutant protein in lysates of transfected COS cells. These results indicate that ribosomal frameshift can partially rescue the human carbonic anhydrase II frameshift mutation and suggest a mechanism whereby a compensatory ribosomal frameshift can ameliorate the consequences of certain frameshift mutations. Whether individual differences in efficiency of ribosomal frameshift contribute to clinical heterogeneity in patients with such mutations deserves further study.


Subject(s)
Carbonic Anhydrases/biosynthesis , Carbonic Anhydrases/genetics , Frameshift Mutation , Hominidae/genetics , Amino Acid Sequence , Animals , Base Sequence , Blotting, Western , Carbonic Anhydrases/isolation & purification , Cell Line , Chlorocebus aethiops , Cloning, Molecular , DNA, Complementary , Electrophoresis, Polyacrylamide Gel , Escherichia coli , Exons , Humans , Immunoglobulin G/isolation & purification , Isoenzymes/biosynthesis , Isoenzymes/genetics , Isoenzymes/isolation & purification , Kidney , Kinetics , Molecular Sequence Data , Mutagenesis, Site-Directed , Peptide Fragments/chemistry , Peptide Fragments/isolation & purification , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification , Reference Values , Restriction Mapping , Ribosomes/metabolism , Transfection
14.
Annu Rev Biochem ; 64: 375-401, 1995.
Article in English | MEDLINE | ID: mdl-7574487

ABSTRACT

Carbonic anhydrases (CAs I-VII) are products of a gene family that encodes seven isozymes and several homologous, CA- related proteins. All seven isozymes have been cloned, sequenced, and mapped, and the intron-exon organization of five genes established. They differ in subcellular localizations, being cytoplasmic (CA I, II, III, and VII), GPI-anchored to plasma membranes of specialized epithelial and endothelial cells (CA IV), in mitochondria (CA V), or in salivary secretions (CA VI). They also differ in kinetic properties, susceptibility to inhibitors, and tissue-specific distribution. Structural and kinetic studies of recombinant natural and mutant CAs have greatly increased our understanding of the structural requirements for catalysis. Studies of the effects of CA inhibitors over many years have implicated CAs in a variety of physiological processes. Analyses of human and animal CA deficiencies provide unique opportunities to understand the individual contributions of different isozymes to these processes.


Subject(s)
Carbonic Anhydrases/deficiency , Carbonic Anhydrases/metabolism , Amino Acid Sequence , Animals , Binding Sites , Carbonic Anhydrases/genetics , Chromosome Mapping , Disease Models, Animal , Female , Humans , Isoenzymes/metabolism , Macaca nemestrina , Male , Mice , Molecular Biology , Molecular Sequence Data , Molecular Structure , Sequence Homology, Amino Acid , Syndrome
15.
Am J Hum Genet ; 54(4): 602-8, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8128957

ABSTRACT

To date, three different structural gene mutations have been identified in patients with carbonic anhydrase II deficiency (osteopetrosis with renal tubular acidosis and cerebral calcification). These include a missense mutation (H107Y) in two families, a splice junction mutation in intron 5 in one of these families, and a splice junction mutation in intron 2 for which many Arabic patients are homozygous. We report here a novel mutation for which carbonic anhydrase II-deficient patients from seven unrelated Hispanic families were found to be homozygous. The proband was a 2 1/2-year-old Hispanic girl of Puerto Rican ancestry who was unique clinically, in that she had no evidence of renal tubular acidosis, even though she did have osteopetrosis, developmental delay, and cerebral calcification. She proved to be homozygous for a single-base deletion in the coding region of exon 7 that produces a frameshift that changes the next 12 amino acids before leading to chain termination and that also introduces a new MaeIII restriction site. The 27-kD truncated enzyme produced when the mutant cDNA was expressed in COS cells was enzymatically inactive, present mainly in insoluble aggregates, and detectable immunologically at only 5% the level of the 29-kD normal carbonic anhydrase II expressed from the wild-type cDNA. Metabolic labeling revealed that this 27-kD mutant protein has an accelerated rate of degradation. Six subsequent Hispanic patients of Caribbean ancestry, all of whom had osteopetrosis and renal tubular acidosis but who varied widely in clinical severity, were found to be homozygous for the same mutation.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Acidosis, Renal Tubular/genetics , Carbonic Anhydrases/deficiency , Frameshift Mutation , Hispanic or Latino/genetics , Osteopetrosis/genetics , Adult , Amino Acid Sequence , Animals , Base Sequence , Brain Diseases/genetics , Calcinosis/genetics , Carbonic Anhydrases/genetics , Caribbean Region/ethnology , Cell Line, Transformed , Child , Child, Preschool , Chlorocebus aethiops , Deoxyribonucleases, Type II Site-Specific , Electrophoresis, Polyacrylamide Gel , Female , Humans , Male , Molecular Sequence Data , Pedigree , Point Mutation , Polymerase Chain Reaction , Restriction Mapping , United States
16.
N Engl J Med ; 327(27): 1899-905, 1992 Dec 31.
Article in English | MEDLINE | ID: mdl-1280771

ABSTRACT

BACKGROUND: Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. METHODS: In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. RESULTS: Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. CONCLUSIONS: Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.


Subject(s)
Hepatitis C , Adolescent , Adult , Antigens, Viral/immunology , Base Sequence , Chronic Disease , Female , Follow-Up Studies , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis Antibodies/analysis , Hepatitis C/epidemiology , Hepatitis C/immunology , Hepatitis C/transmission , Hepatitis C Antibodies , Hepatitis C Antigens , Hepatitis, Chronic/complications , Humans , Male , Molecular Sequence Data , Prospective Studies , RNA, Viral/analysis , Time Factors , United States/epidemiology
17.
Hum Mutat ; 1(4): 288-92, 1992.
Article in English | MEDLINE | ID: mdl-1301935

ABSTRACT

Clinical manifestations in patients with carbonic anhydrase (CA) II deficiency include osteopetrosis, renal tubular acidosis, and cerebral calcification. Of the 39 reported cases of the carbonic anhydrase II deficiency syndrome, 72% were patients from North African and Middle Eastern countries, most, if not all, of whom were of Arabic descent. We have analyzed DNAs from members of six unrelated Arabic kindreds and found five to be homozygous and one heterozygous for a novel splice junction (donor site) mutation at the 5' end of intron 2. These findings suggest that a common "Arabic" mutation may be the predominant cause of CA II deficiency in this region. The mutation introduces a new Sau3A1 restriction site which allows polymerase chain reaction (PCR)-based diagnosis of this mutation that should be useful in diagnosis, carrier detection, and prenatal diagnosis. The presence of mental retardation and relative infrequency of skeletal fractures distinguish the clinical course of the patients with the Arabic mutation from those of the American and Belgian patients with the His 107-->Tyr mutation.


Subject(s)
Carbonic Anhydrases/genetics , Osteopetrosis/enzymology , Osteopetrosis/genetics , Acidosis, Renal Tubular/complications , Acidosis, Renal Tubular/enzymology , Acidosis, Renal Tubular/genetics , Base Sequence , Carbonic Anhydrases/deficiency , DNA/genetics , DNA Mutational Analysis , Female , Humans , Introns , Male , Middle East , Molecular Sequence Data , Osteopetrosis/complications , Pedigree , Phenotype , RNA Splicing/genetics
18.
JAMA ; 264(17): 2231-5, 1990 Nov 07.
Article in English | MEDLINE | ID: mdl-2170702

ABSTRACT

The Centers for Disease Control conducted intensive surveillance for acute non-A, non-B hepatitis in four sentinel counties over a 7-year period. Testing for antibody to hepatitis C virus was performed with the newly developed enzyme immunoassay. The incidence of non-A, non-B hepatitis remained relatively stable (average, 7.1 cases per 100,000, but there were significant changes in disease transmission patterns. The proportion of patients with a history of blood transfusion declined from 17% to 6%, but the proportion with a history of parenteral drug use increased from 21% to 42%. The proportion of patients with histories of sexual exposure (6%), household exposure (3%), occupational exposure to blood (2%), or hemodialysis (0.6%) did not change over time. Antibody to hepatitis C virus was found in 45% of patients within 6 weeks of onset of illness and in 68% of patients followed up for at least 6 months. Patients with no history of transfusions were just as likely to be positive for antibody to hepatitis C virus as patients with transfusion-associated hepatitis, indicating that hepatitis C virus is the major causative agent of all non-A, non-B hepatitis in the United States.


Subject(s)
Hepacivirus/immunology , Hepatitis Antibodies/analysis , Hepatitis C/etiology , Acute Disease , Adolescent , Adult , Female , Hepatitis C/epidemiology , Hepatitis C/immunology , Hepatitis C/microbiology , Humans , Immunoglobulin M/analysis , Incidence , Male , Middle Aged , Population Surveillance , Risk Factors , Socioeconomic Factors
19.
JAMA ; 263(9): 1218-22, 1990 Mar 02.
Article in English | MEDLINE | ID: mdl-2304237

ABSTRACT

To determine trends in the incidence and epidemiology of acute hepatitis B in the United States we conducted intensive surveillance for viral hepatitis in four sentinel counties from October 1, 1981, to September 30, 1988. The overall incidence of hepatitis B remained relatively constant throughout the study period (average, 13.2 cases per 100,000 population), but disease transmission patterns changed significantly. The proportions of hepatitis B cases accounted for by homosexual activity and health care employment decreased 62% and 75%, respectively; the proportions of cases accounted for by parenteral drug use and heterosexual exposure increased 80% and 38%, respectively. The percentage of patients for whom no risk factor was identified (30% to 40%) did not change over time. These patients tended to belong to minority populations, and their socioeconomic level was low. The decline in the number of hepatitis B cases among homosexual men probably results from the modification of high-risk sexual behavior; the decline among health care workers is due mostly to hepatitis B immunization. The current strategy for prevention of hepatitis B, which targets high-risk groups for immunization, has failed to have a significant impact on the incidence of disease.


Subject(s)
Hepatitis B/epidemiology , Vaccination/methods , Acute Disease , Adolescent , Adult , Female , Hepatitis B/ethnology , Hepatitis B/etiology , Hepatitis B/prevention & control , Humans , Incidence , Male , Middle Aged , Population Surveillance , Risk Factors , Sex Factors , United States/epidemiology , United States/ethnology
20.
Shengzhi Yu Biyun ; 5(2): 32-4, 1985 May.
Article in Chinese | MEDLINE | ID: mdl-12313957

ABSTRACT

Using home-made match kits and radioimmunoassay, both serum luteinizing hormone (LH) and testosterone (T) were measured in 53 healthy adult males using microwave contraception and 76 normal fertility males as control. The results showed that in contraceptive group the serum T level was significantly decreased (p 0.0001), while serum LH was apparently elevated (p 0.01) as compared whith the normal controls. Furthermore, the longer exposure duration the lower serum T declined and the higher serum LH increased (p 0.001). The present study suggests that the microwave dose used for contraception seems to cause damage in Leydig cell function in terms of T production, and then influence endocrine function of testis. The progressively increased LH level also indicates certain degree damage of the Leydig cells. However, the damage might be reversible. The results may be useful for further clinical investigation.


Subject(s)
Androgens , Contraception , Contraceptive Agents, Male , Family Planning Services , Gonadotropins, Pituitary , Gonadotropins , Hormones , Luteinizing Hormone , Reproductive Control Agents , Testosterone , Biology , Contraceptive Agents , Endocrine System , Physiology , Research
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