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Biomedical subjects

A Pan

Publications and source records attributed to A Pan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prevalence of transmitted nucleoside analogue-resistant HIV-1 strains and pre-existing mutations in pol reverse transcriptase and protease region: outcome after treatment in recently infected individuals.

We retrospectively studied 38 Italian recently HIV-1-infected subjects who seroconverted from 1994 to 1997 to investigate: (i) the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection; (ii) the proportion of naturally occurring mutations in reverse transcriptase (RT) and protease regions of patients naive for non-nucleoside RT inhibitors (NNRTIs) and protease inhibitors (PIs); (iii) the drug-susceptibility to NRTIs and PIs in subjects with NRTI- and/or PI-related mutations; and (iv) the outcome of seroconverters treated with various NRTIs or NRTI/PI regimens. Baseline HIV-1 plasma viraemia and absolute CD4 count at baseline could not be used to distinguish patients with NRTI- and/or PI-related pre-existing mutations from those with wild-type virus (P = 0.693 and P = 0.542, respectively). The frequency of zidovudine-related mutations was 21% in the study period. The response to treatment was not significantly different in subjects with or without genotypic zidovudine-related mutations at primary infection (P = 0.744 for HIV-1 RNA and P = 0.102 for CD4 cells). Some natural variation (2.6%) was present within regions 98-108 and 179-190 of RT involved in NNRTI resistance. The high natural polymorphism in the protease region present in our patients was similar to that reported by others. In our study some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. As discrepancies between genotypic and phenotypic results may exist in recent seroconverters, our data suggest that the role of transmitted NRTI- and PI-resistant variants remain to be fully elucidated in vivo.

Anti-HIV Agents↗
PubMed2000

Epileptiform discharges in benign focal epilepsy of childhood.

The electroclinical syndrome of benign focal epilepsy of childhood has been the subject of intense investigation over the past fifty years. Characteristic findings, over the years, of its signature electroencephalographic discharge, including morphology, topography, field of distribution, activation and reactivity will be presented and discussed.

Brain↗
PubMed1999

Efavirenz, nelfinavir, and stavudine rescue combination therapy in HIV-1-positive patients heavily pretreated with nucleoside analogues and protease inhibitors.

Tolerability, activity, and pharmacokinetic parameters of a combination therapy with efavirenz (EFV), nelfinavir (NFV), and stavudine (d4T) were evaluated in this study. Forty-seven HIV-1-infected study subjects, naive to NFV and nonnucleoside reverse transcriptase inhibitors (NNRTIs), who had experienced virologic failure while being treated with combination antiretroviral therapies including protease inhibitors (PIs), were enrolled. At baseline, HIV-1 viral load in plasma was 4.8 log10, CD4+ count was 204 cells/microl (both mean values); patients had received a mean of 3.1 different treatments (range, 2-5 treatments). Study medications were generally well tolerated; 7 of 47 patients (14.8%) were dropped from the study because of related drug toxicity. At week 24, mean plasma viral load (pVL) was reduced by 1.9 log10, with mean CD4+ count increased to 324 cells/microl (+/-59% from baseline); pVL was below the limit of detection (500 copies/ml) in 46.1% of patients. An extended follow-up study was performed at 12 months. Results showed a reduction of 1.7 log10 in pVL from basal values that was consistent with values observed at months 3 and 6. A history of previous use of PIs represented a negative prognostic marker. Sequencing analysis, performed in a subset of patients, showed the presence of multiple point mutations associated with PI resistance. Pharmacokinetic analysis demonstrated a marked interindividual variability in NFV plasma concentrations, producing in 4 of 18 patients (22%) trough concentrations lower than minimum effective concentration. In pretreated patients, further studies are needed to characterize the pharmacokinetic factors that affect response to therapy and the association of these results with the 95% inhibitory concentration (IC95) determined by phenotyping.

Adult↗
PubMed1998

Codon usage in highly expressed genes of Haemophillus influenzae and Mycobacterium tuberculosis: translational selection versus mutational bias.

Biases in the codon usage and base compositions at three codon sites in different genes of A+T-rich Gram-negative bacterium Haemophillus influenzae and G+C-rich Gram-positive bacterium Mycobacterium tuberculosis have been examined to address the following questions: (1) whether the synonymous codon usage in organisms having highly skewed base compositions is totally dictated by the mutational bias as reported previously (Sharp, P.M., Devine, K.M., 1989. Codon usage and gene expression level in Dictyostelium discoideum: highly expressed genes do 'prefer' optimal codons. Nucleic Acids Res. 17, 5029-5039), or is also controlled by translational selection; (2) whether preference of G in the first codon positions by highly expressed genes, as reported in Escherichia coli (Gutierrez, G., Marquez, L., Marin, A., 1996. Preference for guanosine at first codon position in highly expressed Escherichia coli genes. A relationship with translational efficiency. Nucleic Acids Res. 24, 2525-2527), is true in other bacteria; and (3) whether the usage of bases in three codon positions is species-specific. Result presented here show that even in organisms with high mutational bias, translational selection plays an important role in dictating the synonymous codon usage, though the set of optimal codons is chosen in accordance with the mutational pressure. The frequencies of G-starting codons are positively correlated to the level of expression of genes, as estimated by their Codon Adaptation Index (CAI) values, in M. tuberculosis as well as in H. influenzae in spite of having an A+T-rich genome. The present study on the codon preferences of two organisms with oppositely skewed base compositions thus suggests that the preference of G-starting codons by highly expressed genes might be a general feature of bacteria, irrespective of their overall G+C contents. The ranges of variations in the frequencies of individual bases at the first and second codon positions of genes of both H. influenzae and M. tuberculosis are similar to those of E. coli, implying that though the composition of all three codon positions is governed by a selection-mutation balance, the mutational pressure has little influence in the choice of bases at the first two codon positions, even in organisms with highly biased base compositions.

Animals↗
PubMed1998

[The effect of brain-derived neurotrophic factor on the rat electroretinography after pressure-induced ischemic injury].

Brain-derived neurotrophic factor (BDNF) or normal goat serum (NGS) was injected intravitreously in each 11 wistar albino rats two days before the induction of ischemia. Retinal ischemia was induced in 22 rats by increasing intraocular pressure to the threshold level which extinguished the electroretinography (ERG) b-wave individually, and maintaining for 90 minutes. The ERG b-wave of the BDNF-treated rats recovered to 80.5 +/- 24.4% of their normal amplitude three days after ischemia, while that of the NGS-treated rats recovered only to 11.1 +/- 5.3%. Statistic analysis showed that the recovery level of ERG b-wave after ischemia in the BDNF and NGS treated rats was significantly different (P < 0.01). The results suggest that BDNF could promote the recovery of the retinal electrophysiologic function from ischemia induced by high intraocular pressure.

Animals↗
PubMed1997

Chaos game representation of proteins.

The present report proposes a new method for the chaos game representation (CGR) of different families of proteins. Using concatenated amino acid sequences of proteins belonging to a particular family and a 12-sided regular polygon, each vertex of which represents a group of amino acid residues leading to conservative substitutions, the method can generate the CGR of the family and allows pictorial representation of the pattern characterizing the family. An estimation of the percentages of points plotted in different segments of the CGR (grid points) allows quantification of the nonrandomness of the CGR patterns generated. The CGRs of different protein families exhibited distinct visually identifiable patterns. This implies that different functional classes of proteins follow specific statistical biases in the distribution of different mono-, di-, tri-, or higher order peptides along their primary sequences. The potential of grid counts as the discriminative and diagnostic signature of a family of proteins is discussed.

Algorithms↗
PubMed1997

Gradual phenotypic conversion associated with immortalization of cultured human mammary epithelial cells.

Examination of the process of immortal transformation in early passages of two human mammary epithelial cell (HMEC) lines suggests the involvement of an epigenetic step. These lines, 184A1 and 184B5, arose after in vitro exposure of finite lifespan 184 HMEC to a chemical carcinogen, and both are clonally derived. Although early-passage mass cultures of 184A1 and 184B5 maintained continuous slow growth, most individual cells lost proliferative ability. Uniform good growth did not occur until 20-30 passages after the lines first appeared. Early-passage cultures expressed little or no telomerase activity and telomeres continued to shorten with increasing passage. Telomerase activity was first detected when the telomeres became critically short, and activity levels gradually increased thereafter. Early-passage cultures had little or no ability to maintain growth in transforming growth factor-beta (TGFbeta); however, both mass cultures and clonal isolates showed a very gradual increase in the number of cells displaying progressively increased ability to maintain growth in TGFbeta. A strong correlation between capacity to maintain growth in the presence of TGFbeta and expression of telomerase activity was observed. We have used the term "conversion" to describe this process of gradual acquisition of increased growth capacity in the absence or presence of TGFbeta and reactivation of telomerase. We speculate that the development of extremely short telomeres may result in gradual, epigenetic-based changes in gene expression. Understanding the underlying mechanisms of HMEC conversion in vitro may provide new insight into the process of carcinogenic progression in vivo and offer novel modes for therapeutic intervention.

Adult↗
PubMed1997

Genetic analysis of the components of winterhardiness in barley (Hordeum vulgar L.).

Winterhardiness in cereals is the consequence of a number of complex and interacting components: cold tolerance, vernalization requirement and photoperiod sensitivity. An understanding of the genetic basis of these component traits should allow for more effective selection. Genome map-based analyses hold considerable promise for dissecting complex phenotypes. A 74-point linkage map was developed from one hundred double haploid lines derived from a winter x spring barley cross and used as the basis for quantitative trait locus (QTL) analyses to determine the chromosome location of genes controlling components of winterhardiness. Despite the greater genome coverage provided by the current map, a previously-reported interval on chromosome 7 remains the only region where significant QTL effects for winter survival were detected in this population. QTLs for heading date under 24 h light map to the same region. A QTL for heading date under this photoperiod regime also maps to chromosome 2. A distinct set of QTLs mapping to chromosomes 1, 2, 3 and 5 determined heading date under 8 h light. Patterns of differential QTL expression underscore the complexity of Winterhardiness.

Acclimatization↗
PubMed1996

[AIDS-related neoplasms: a clinico-radiological study].

Although high-grade non-Hodgkin's lymphoma (NHL) and an unusually aggressive form of Kaposi's sarcoma (KS) remain the most common malignancies seen in AIDS patients, other tumors such as cervical cancer, Hodgkin's disease and others, have been increasingly observed, probably because these patients now live longer. We report the imaging findings of 80 AIDS patients with pathologically confirmed neoplasms from a series of 340 AIDS patients examined 1986-1994. Twenty-four of 80 patients had NHL, 4 Hodgkin's disease, 31 KS, 4 cervical cancer, 2 leukemia, 2 testicular, 1 larynx, 2 lung, 2 breast, 1 esophagus, 1 stomach, 1 liver, 2 kidney and 3 adrenal carcinomas. Twenty of 24 NHLs exhibited extranodal involvement--to the liver (13/24), brain (9/24), lung (7/24) and gastrointestinal tract (6/24). Visceral KS involved the gastrointestinal tract (6/32), lung (4/32) and liver (2/32). The most accredited pathogenetic theories concerning the role of HIV infection in oncogenesis advocate the effect of multiple growth factors produced by HIV-infected lymphocytes (KS) or the disregulation of B-cells caused by T-cell destruction (NHL). The atypical morphostructural features of AIDS-related tumors are discussed--e.g., atypical presentation, occurrence in younger individuals, aggressive clinical course and poor response to conventional therapy--together with the differential diagnostic problems, especially vs. opportunistic infections.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Molecular cloning, sequencing, and expression in Escherichia coli of the chalcone synthase gene.

Flavonoids form a class of secondary metabolites that are abundant in all higher plants. They serve important functions in flower pigmentation. Chalcone Synthase (CHS) is a key enzyme in the biosynthesis of all classes of flavonoids; therefore, variation of the expression of CHS might change the color of flowers. We cloned CHS-A gene from Petunia hybrida, which has 99% sequence homology with those that have been cloned abroad. The sequence of the coding region is 1170bp and encodes a protein of 39kDa. CHS-A gene is also expressed high-efficiently in E. coli. All this work establishes a sound basis for future research on the impact of the CHS-A gene on flower pigmentation.

Acyltransferases↗
PubMed1994

Expression of mouse metallothionein-I gene confers cadmium resistance in transgenic tobacco plants.

Transgenic tobacco plants containing a mouse metallothionein-I (MT-I) gene fused to the cauliflower mosaic virus 35S (CaMV 35S) promoter and nopaline synthase (nos) polyadenylation site were obtained by transforming tobacco leaf discs with an Agrobacterium tumefaciens strain carrying the chimaeric gene. Transformants were directly selected and rooted on medium containing cadmium and kanamycin. A total of 49 individual transgenic tobacco plants were regenerated. Among them 20% showed a very high expression level and their growth was unaffected by up to 200 microM cadmium, whereas the growth of control plants was severely affected leaf chlorosis occurred on medium containing only 10 microM cadmium. The concentration of microM cadmium. The concentration of MT-I in leaves of control and transgenic tobacco was determined with Cd/haemoglobin saturation assay, a polarographic method and western blotting. In addition, seeds from self-fertilized transgenic plants were germinated on medium containing toxic levels of cadmium and scored for tolerance/susceptibility to this heavy metal. The ratio of tolerant to susceptible plants was 3:1 indicating that the metallothionein gene is inherited as a single locus.

Agrobacterium tumefaciens↗
PubMed1994

Alpha-domain of human metallothionein IA can bind to metals in transgenic tobacco plants.

With a view to exploring its use as a metal-binding factor in transgenic plants we prepared the alpha-domain of metallothionein by reconstitution of rabbit apometallothionein and proteolysis of MT-1 and MT-2 with subtilisin. The isolated alpha-domains were characterised by UV and CD spectroscopy Double-Stranded. DNA encoding the alpha-domain (106 bp) of the human MT-IA was constructed from chemically synthesized oligomers by repair synthesis and enzymatic ligation, cloned into pUC19 and sequenced. A expression construct containing the cloned alpha-domain was introduced into tobacco cells on a disarmed Agrobacterium tumefaciens Ti-plasmid. Transformed tobacco cells were selected and regenerated on medium containing cadmium and kanamycin. The growth of roots and shoots of transformants was unaffected by up to 100 microM cadmium, whereas control plants showed severe inhibition of root and shoot growth, and chlorosis of leaves on medium containing only 10 microM cadmium. Southern hybridization confirmed the presence of the transgene in the transformed plant tissues. The concentration of human alpha-domain peptides in transgenic tobacco leaves was determined by the Cd/hemoglobin saturation assay and polarography using the rabbit alpha-domain as standard. The results indicate that the alpha-domain, one of two domains in MT molecules, is not only stable in vitro, but is also expressed efficiently and functions independently in transgenic plant cells.

Agrobacterium tumefaciens↗
PubMed1994

Identification and characterization of cDNA clones encoding plant calreticulin in barley.

Two cDNA clones (CRH1 and CRH2) homologous to animal calreticulin, a major calcium storage protein in the lumen of the endoplasmic reticulum, were isolated from an ovary cDNA library of barley through differential screening. The two clones differ in the 3' untranslated region and the 5' region that encodes a putative N-terminal signal sequence. CRH1 was mapped to the minus arm of chromosome 1. CRH2 was mapped to the minus arm of chromosome 2. The deduced amino acid sequences share 50 to 55% identity with animal calreticulins and exhibit the same three-zone characteristic. Recombinant protein stained blue with Stains-all and bound 45Ca2+ when transferred to nitrocellulose membranes. A native protein of approximately 55 kD was identified in ovary extract. Elevated gene expression was observed in ovaries 1 day after pollination and during early embryogenesis. CRH1 was expressed at a higher level than CRH2. These studies demonstrate the presence of calreticulin in plant cells and its developmental regulation in fertilization.

Amino Acid Sequence↗
PubMed1993

Construction of multiple copy of alpha-domain gene fragment of human liver metallothionein IA in tandem arrays and its expression in transgenic tobacco plants.

Metallothioneins (MT) are low molecular weight, cysteine-rich, metal-binding proteins. An MT molecule contains two domains which appear to act independently--an alpha-domain, which is characterized by cadmium-binding, and a beta-domain, which binds preferentially to copper. Based on this conception, DNA duplex encoding the alpha-domain (106 bp) of human MT-IA was constructed from a chemically-synthesized oligomer by repair synthesis and enzymatic ligation and cloned into pUC19. The genes cloned were sequenced and found to be in the correct order as designed. Synthetic directional adapters were attached to the terminals of the alpha-domain gene fragment of human MT-IA to establish complete control over fragment orientation during ligation. The use of these directional adapters thereby ensured the production of multiple copies of the alpha-domain in tandem arrays. The successive alpha-domains were linked by a peptide linker consisting of 10 residues. A chimeric gene containing 12 cloned tandemly repeated copies of the 106 bp alpha-domain DNA was introduced into tobacco cells on a disarmed Ti-plasmid of Agrobacterium tumefaciens. A total of 10 different transgenic tobacco plants were generated, of which two showed root and shoot growth unaffected by up to 200 mg/l kanamycin and 100 microM cadmium, whereas root growth of control plants was severely inhibited and leaf chlorosis developed on media containing only 10 microM cadmium.

Agrobacterium tumefaciens↗
PubMed1993

Malignant duodenocolic fistula: a case report.

A 65 year-old female presented with diarrhea, body weight loss, malnutrition, elevated serum carcinoembryonic antigen (CEA) and electrolyte disturbances. A series of examinations showed colon cancer with a malignant duodenocolic fistula. Patient received extended right hemicolectomy with wide local excision of the duodenum (en bloc resection of the tumor). Recovery was smooth without local recurrence or metastasis after a six-month follow-up. Wide en bloc resection provides the only hope of cure in such cases. Treatment with extended right hemicolectomy with Whipple's procedure, or extended right hemicolectomy with extended local wide excision of duodenum, should be chosen, depending upon the extent of tumor invasion.

Aged↗