Endocytosis by mature muscle cells of aggregates of parasitised erythrocytes and macrophages in severe malaria.
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Adult↗
Biomedical subjects
F Garcia
Publications and source records attributed to F Garcia.
Prospective evaluation of the macrolide antibiotic dirithromycin for the treatment of Helicobacter pylori.
BACKGROUND: Macrolide antibiotics are active in vitro and in vivo against Helicobacter pylori. We assessed a newer macrolide, dirithromycin, for the treatment of H. pylori in two separate studies. METHODS: Volunteers with H. pylori infection (by 13C-urea breath test) were randomly assigned to 2-week treatment regimens. Study 1: dirithromycin 500 mg q.d.s., dirithromycin 500 mg q.d.s. plus omeprazole 40 mg q.d.s., or dirithromycin 500 mg q.d.s. plus metronidazole 500 mg t.d.s. Study 2: dirithromycin 500 mg q.d.s. plus omeprazole 20 mg b.d., dirithromycin 1000 mg q.d.s. plus omeprazole 20 mg b.d., or amoxycillin 500 mg q.d.s. plus omepirazole 20 mg b.d. Four weeks after the completion of therapy a repeat 13C-urea breath test was done to assess for cure. RESULTS: No patient taking dirithromycin alone (n = 6) or in combination with omeprazole (n = 26) achieved cure of their infection. Eradication of H. pylori was seen in one of seven patients taking dirithromycin plus metronidazole. Five of 10 patients taking omeprazole-amoxycillin dual therapy had their H. pylori infection cured (P = 0.0007 vs. patients taking dirithromycin plus omeprazole). Eleven (47%) of 32 patients taking dirithromycin alone or combined with omeprazole reported side-effects, but only two (6%) stopped therapy prematurely as a result of side-effects. CONCLUSION: No subject taking dirithromycin alone or in combination with omeprazole had their H. pylori infection cured. Dirithromycin, in the regimen used, shows little promise in the treatment of patients with H. pylori infection.
Adult↗
Analysis of the in vivo activation of hemolysin (HlyA) from Escherichia coli.
Hemolysin (HlyA) from Escherichia coli containing the hlyCABD operon separated from the nonhemolytic pro-HlyA upon two-dimensional (2-D) polyacrylamide gel electrophoresis. The migration distance indicated a net loss of two positive charges in HlyA as a result of the HlyC-mediated activation (modification). HlyA activated in vitro in the presence of [U-14C]palmitoyl-acyl carrier protein comigrated with in vivo-activated hemolysin on 2-D gels and was specifically labelled, in agreement with the assumption that the activation is accomplished in vitro and in vivo by covalent fatty acid acylation. The in vivo-modified amino acid residues were identified by peptide mapping and 2-D polyacrylamide gel electrophoresis of mutant and truncated HlyA derivatives, synthesized in E. coli in the presence and absence of HlyC. These analyses indicated that the internal residues Lys-564 and Lys-690 of HlyA, which have recently been shown by others to be fatty acid acylated by HlyC in vitro, are also the only modification sites in vivo. HlyA activated in E. coli was quantitatively fatty acid acylated at both sites, and the double modification was required for wild-type hemolytic activity. Single modifications in mutant and truncated HlyA derivatives suggested that both lysine residues are independently fatty acid acylated by a mechanism requiring additional sequences or structures flanking the corresponding acylation site. The intact repeat domain of HlyA was not required for the activation. The pore-forming activities of pro-HlyA and singly modified HlyA mutants in planar lipid bilayer membranes suggested that the activation is not essential for transmembrane pore formation but rather required for efficient binding of the toxin to target membranes.
Acyl Carrier Protein↗
t(2;3) in a case of blastic transformation of essential thrombocythaemia.
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Aged↗
Structural features of the hydroxy- and keto-disubstituted bile salts: human serum albumin binding.
The binding of keto- and hydroxy bile salts to human serum albumin, the identity of the bile salts binding sites and the identification of the amino acids present in these sites were studied. The keto bile salts cholanate-3-one (C3), cholanate-3,6-dione (C3-6) and cholanate-3-hydroxy-6-one (KHC) were found to quench the native fluorescence emission of albumin. This suggested that the tryptophan residue of human albumin (residue 214) is accessible to the keto bile salts and not to the hydroxy parent compounds. The binding of the keto bile salts was characterized by a simple population of binding sites with Ka ranging from 22 x 10(4) M-1 for the mono keto bile salt (C3) down to 4 x 10(4) M-1 for the hydroxy-keto bile salt (KHC). The substitution of an oxo group at carbon C3 in C3-6 molecule for a hydroxy group (KHC) produce a significant decreasing of the interaction, suggesting that the hybridization state of the carbon at C3 in the steroid ring of the bile salt molecule is also an essential requirement for bile salts binding. It was found that bile salts are bound to the benzodiazepine binding site on human albumin (site II), producing a perturbation on site I, fatty acids and bilirubin binding site. The presence of only one substituent at C3 (oxo or OH) produce an important perturbation on the fatty acid binding sites, decreasing the polarity of the its microenvironment, while a little effect was observed for the dihydroxy and di-oxo-substituted BS, suggesting that the hydroxy substituents at C6, C7 and C12 do not interact in a significant manner with the fatty acid binding sites on HSA. The participation of specific amino acids in albumin-bile salt binding sites depends on the polar groups on the bile salt molecules as exemplified by the quantitatively different role of lysyl residues like those interacting with KHC, C3 and C3-6, and tyrosyl residue interacting with KHC. The following amino acids in human albumin were found to play a role in the bile salts-albumin interaction: lysyl 195 and 225, several arginyls, histidyl 146 and tyrosyl 411.
Bile Acids and Salts↗
Seroepidemiological study of hepatitis E virus in different population groups.
In order to determine the seroprevalence of hepatitis E virus, 1,993 sera (453 from healthy pregnant women, 491 from Moroccan subjects, 492 from blood donors, 321 from children, and 236 from intravenous drug users) were studied. IgG was measured by enzyme immunoassay (EIA), and positive results were confirmed by Western blot. The EIA detected antibodies in 3.96% of the subjects (5.6% of the Moroccans and drug users and 1.8% of the children). Fifty-four percent of these results were confirmed by Western blot, 11.4% were found to be negative, and 34.2% indeterminate. The overall prevalence after confirmation by Western blot decreased to 2.15%. When studying the Western blot pattern of the positive samples, 95% showed antibodies to SG-3, 65% to 8-5, and only 9.3% to CKS fusion protein. In the indeterminate Western blots, the results for these proteins were 96.3%, 62.9%, and 37%, respectively. When the epidemiological data were analysed, no statistically significant differences between women and men or between different age groups were found.
Adult↗
Epidemiological factors involved in hepatitis C virus infection in patients with renal disease.
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Adult↗
Evaluation of enzyme immunoassay for hepatitis B virus DNA based on anti-double-stranded DNA.
We have evaluated a new enzyme immunoassay technology to detect the products of PCR-based amplification that may be applicable to routine testing of hepatitis B virus (HBV) DNA. Two hundred eight serum samples were studied: 73 were basal samples and 135 were sequential serum samples from patients with chronic hepatitis, some of whom were being treated with alpha interferon. We compared the new detection method (PCR-DNA enzyme immunoassay [DEIA]) with dot blot hybridization performed without prior PCR amplification and with two other methods for detection of PCR products: agarose gel electrophoresis with ethidium bromide staining (PCR-EB) and dot blot (PCR-dot blot). For hepatitis B-antigen-positive basal samples, HBV DNA was detected in 70.4% by dot blot, 74.1% by PCR-EB, and 100% by PCR-DEIA and PCR-dot blot; for anti-hepatitis B e-antigen basal samples, HBV DNA was found in 10.5% by dot blot and PCR-EB and in 42.1% by PCR-DEIA and PCR-dot blot. Chi-square tests showed a strong association between dot blot and PCR-EB and between PCR-DEIA and PCR dot blot. Using PCR-dot blot as the reference, dot blot shows a 56.9% sensitivity and a 100% specificity, PCR-EB shows a 55.0% sensitivity and a 100% specificity, and PCR-DEIA shows a 95.4% sensitivity and a 97% specificity. We conclude that the technical advantages of the DEIA method and its high sensitivity and specificity may facilitate the use of PCR in routine testing for HBV DNA in clinical microbiology laboratories.
Base Sequence↗
The National Drug Control Strategy: the first-line approach to decreasing violence in our communities.
The National Drug Control Strategy is designed to address all aspects of drug abuse: drug use, drug trafficking, and drug-related crimes. The nine-pronged program encompasses efforts at the federal, state, and local levels, forming a partnership between government and the private and public sectors. The strategy includes prevention initiatives that reduce the demand for drugs; individualized treatment programs for high-risk groups; greater community policing efforts to reduce violent crimes by drug users and pushers; and education aimed at children and adults. It is a national strategy that strives to find solutions at the local level.
Adolescent↗
Septic knee from Ilizarov transfixation tibial pin.
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Adult↗
Selection for transport competence of C-terminal polypeptides derived from Escherichia coli hemolysin: the shortest peptide capable of autonomous HlyB/HlyD-dependent secretion comprises the C-terminal 62 amino acids of HlyA.
Escherichia coli hemolysin (HlyA) is secreted by a specific export machinery which recognizes a topogenic secretion signal located at the C-terminal end of HlyA. This signal sequence has been variously defined as comprising from 27 to about 300 amino acids at the C-terminus of HlyA. We have used here a combined genetic and immunological approach to select for C-terminal HlyA peptides that are still secretion-component. A deletion library of HlyA mutant proteins was generated in vitro by successive degradation of hylA from the 5' end with exonuclease III. Secretion competence was tested by immunoblotting of the supernatant of each clone with an antiserum raised against a C-terminal portion of hemolysin. It was found that the hemolysin secretion system has no apparent size limitation for HlyA proteins over a range from 1024 to 62 amino acids. The smallest autonomously secretable peptide isolated in this selection procedure consists of the C-terminal 62 amino acids of HlyA. This sequence is shared by all secretion-competent, truncated HlyA proteins, which suggests that secretion of the E. coli hemolysin is strictly post-translational. The capacity of the hemolysin secretion machinery was found to be unsaturated by the steady-state level of its natural HlyA substrate and large amounts of truncated HlyA derivatives could still be secreted in addition to full-length HlyA.
Antibodies, Bacterial↗
Epidemiology of hepatitis C virus infection in patients with renal disease.
This study was carried out to determine the prevalence of hepatitis C virus (HCV) antibodies and the epidemiologic factors associated with HCV infection in patients with chronic renal failure before the onset of ESRD. Sex, age, type of renal disease, level of renal function, and history of blood transfusions and invasive procedures were analyzed in 226 patients with renal disease, compared with a population of 1,244 normal subjects and 124 patients with impaired immunity (patients having autoimmune diseases and receiving chemotherapy treatment). Eighteen seropositive patients with renal disease (prevalence, 7.9%) were found, which was significantly higher than the prevalence in the normal population (1.03% in blood donors, 0.98% in pregnant women; P < 0.001, chi 2). There was no significant association of sex, number of blood transfusions, or history of invasive procedures with the presence of HCV antibodies. The prevalence of HCV antibodies was higher (16.6%) in patients with glomerulonephritis compared with patients diagnosed with interstitial nephritis, pyelonephritis, nephrosclerosis, diabetes mellitus, polycystic kidney, and miscellaneous renal diseases (P < 0.01, chi 2). There was a higher prevalence of HCV antibodies in patients with creatinine clearance lower than 30 mL/min (13%) compared with patients with creatinine clearance higher than 30 mL/min (2.7%) (P < 0.01, chi 2). These data suggest that HCV infection may be associated with the pathogenesis of glomerulonephritis. Alternatively, glomerulonephritis or severe renal insufficiency may increase the likelihood of HCV infection.
Adult↗
Critical evaluation of the present experience on microsurgical sperm aspiration.
Microsurgical epididymal sperm aspiration (MESA) and IVF techniques are indicated in those cases of bilateral congenital absence of the vas deferens (BCAVD) and in cases of epididymal obstruction (EO) of other aetiologies were vasoepididymostomy is not possible or has failed. Microsurgical deferential sperm aspiration (MDSA) is indicated in those cases where spermatogenesis and epididymal permeability are conserved but spermatozoa, for different causes, cannot reach the ejaculate and other therapies have failed. We have performed this procedure in 70 patients by two different human reproduction teams. Both teams achieved very similar results regarding fertilization rate: 5.5 and 7.2% in cases of BCAVD, 6.5 and 8.8% in cases of EO and 33.3 and 26.7% in cases of non-epididymal pathology (NEP). However, the fertilization rate per patient presents differences between both teams: 27 and 44.4% in BCAVD, 31 and 11% in EO and 80 and 100% in NEP. In spite of a better fertilization rate per patient in team two, it was in the other where pregnancies were achieved (7% in BCAVD, 15% in EO and 20% in NEP). One pregnancy in EO group was achieved by intracytoplasmatic sperm injection. The pregnancy rates per transfer were 25% in BCAVD, 50% in EO and 25% in NEP.
Epididymis↗
Radiopharmacological evaluation in dogs of a new renal function agent.
The hydrophilic penta-anionic complex [Technetium (Carboxymethylisocyanide)6]-5, [Tc(CNCH2COO-)6]-5 (Tc-CAMI) was synthesized to evaluate its potential as a renal function imaging agent. The compound contains six distally arranged carboxyl groups that can act as substrates for the organic acid receptor of the renal cell to effect tubular secretion of this agent. Dynamic gamma-camera imaging of 99mTc-CAMI was performed in normal dogs to compare its bio-distribution and pharmacokinetics with those of proven tubular secretion (99mTc-MAG3) and globular filtration (99mTc-DTPA) agents. The relative difference between the observed mean renal transit times (MRTT) of 99mTc-CAMI and 99mTc-MAG3 was 0.15 compared with 1.24 for 99mTc-CAMI and 99mTc-DTPA. Pathological models of obstructive uropathy, renal arterial stenosis and renal denervation were produced in the same animals to demonstrate the diagnostic potential of the agent. These experiments and data showing that probenecid competes with 99mTc-CAMI for renal transport indicate that this compound functions as a tubular secretion agent and may be useful for monitoring renal function in various disease states.
Animals↗
Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices.
OBJECTIVE: Comparison of the safety and efficacy of endoscopic sclerotherapy and ligation for the treatment of bleeding esophageal varices. DESIGN: Randomized, controlled trial. SETTING: An urban county hospital. PATIENTS: Patients with clinically severe bleeding from esophageal varices. INTERVENTION: A total of 77 patients were randomly assigned to receive sclerotherapy or ligation at the initial endoscopic examination. Treatment was repeated weekly until variceal obliteration was achieved. After eradication, patients had endoscopic examinations every 3 months or for any episode of rebleeding. Recurrent varices were treated with the originally assigned form of endoscopic therapy. MEASUREMENTS: Patients were assessed for further bleeding, for transfusion requirements, for time in hospital, for variceal eradication, for number of treatment sessions required, for complications, for treatment failure, and for risk of death. RESULTS: Rebleeding tended to be less frequent with ligation than with sclerotherapy: 10 of 38 (26%) compared with 17 of 39 (44%) (difference, 17% [95 CI, -4% to 38%]), but results in the two groups were comparable for blood transfusions, for length of hospital stay, and for risk of death. Comparison of Kaplan-Meier estimates of time to rebleeding and death showed no statistical differences between treatments. Complications were less common in the ligation group: fewer patients in the ligation group had esophageal strictures (0 of 38 compared with 13 of 39 [33%]; P < 0.001) and had complicated esophageal ulcers (1 of 38 [2.6%] compared with 6 of 39 [15%]; P = 0.11). In addition, fewer ligation treatments were required to achieve variceal eradication (4.1 +/- 0.3 compared with 6.2 +/- 0.4; P < 0.001). CONCLUSION: Endoscopic ligation causes statistically fewer local complications than sclerotherapy and achieves variceal eradication more rapidly. Ligation is a viable alternative to sclerotherapy and may have some advantages as a treatment for bleeding esophageal varices.
Adult↗
Biomarker and cytologic abnormalities in women at high and low risk for breast cancer.
Fine needle aspirates (FNA) from 106 high-risk women and 25 low-risk women were evaluated for overexpression of estrogen receptor (ER), epidermal growth factor receptor (EGFR), mutant p53, and HER-2/neu by immunocytochemistry, and for aneuploidy by image analysis. Aspirates were also classified cytologically as normal, apocrine metaplasia, epithelial hyperplasia (EH), or dysplasia. High-risk women were those with a first-degree relative with breast cancer (76%), precancerous breast disease (26%), prior cancer of the contralateral breast (9%), or multiple abnormalities (11%). Low-risk women had none of the above risk factors, nor a prior breast biopsy or clinical evidence of fibrocystic disease. The median 10-year Gail risk for the high-risk group was 4%, compared to 0.7% for the low-risk group. There were significant differences (p < 0.01) between high- and low-risk women in the prevalences of hyperplasia (55% versus 12%), dysplasia (19% versus 0%), aneuploidy (32% versus 0%), overexpressed EGFR (32% versus 4%), and overexpressed p53 (29% versus 4%). The prevalence of multiple biomarker abnormalities was also greater in high-risk than in low-risk women (28% versus 0%; p < 0.01). Four percent (4%) of FNAs from high-risk women with normal cytology, 29% of aspirates with hyperplastic cytology, and 60% of those with dysplasia were associated with two or more biomarker abnormalities. The differences in the prevalence of multiple biomarker abnormalities among various cytologic categories were statistically significant (p = 0.02, normal versus EH; p = 0.02, EH versus dysplasia; p < 0.01, normal versus dysplasia).(ABSTRACT TRUNCATED AT 250 WORDS)
Biomarkers, Tumor↗
Mutant p53 expression in prostate carcinoma.
The expression of the mutant p53 tumor suppressor gene was evaluated in 33 human prostate carcinomas. Using an immunohistochemical method with monoclonal antibodies PAb 1801 and PAb 240, 26 (79%) tumors demonstrated positive immunostaining for mutant p53. Only areas of glandular tumor were positive, with adjacent stromal elements and areas of glandular hyperplasia being negative. The predominant staining pattern was cytoplasmic. This pattern may be related to p53 binding to certain heat shock proteins (HSP 72/73), as a monoclonal antibody to these proteins demonstrated a cytoplasmic location as well. These results demonstrate that abnormal p53 expression is a frequent event in prostate cancer.
Adenocarcinoma↗
A butterfly vertebra or a wedge fracture?
Two patients, who had injuries to the dorsal spine with vertebral wedging, are described. In both a compression wedge fracture was diagnosed, but a careful study of the anteroposterior radiographs showed that the presumed injury was a butterfly vertebra. This rare congenital anomaly, which is usually without clinical significance, may be mistaken for a wedge fracture unless the anteroposterior view is correctly assessed.
Diagnosis, Differential↗