Distal duodenal surveillance in familial adenomatous polyposis.
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Biomedical subjects
Publications and source records attributed to S Rasheed.
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D-RNAi (Messenger RNA-antisense DNA interference), a novel posttranscriptional phenomenon of silencing gene expression by transfection of mRNA-aDNA hybrids, was originally observed in the effects of bcl-2 on phorbol ester-induced apoptosis in human prostate cancer LNCaP cells. This phenomenon was also demonstrated in chicken embryos and a human CD4(+) T cell line, H9. The in vivo transduction of beta-catenin D-RNAi was shown to knock out more than 99% endogenous beta-catenin gene expression, while the in cell transfection of HIV-1 D-RNAi homolog rejected viral gene replication completely. D-RNAi was found to have long-term gene knockout effects resulting from a posttranscriptional gene silencing mechanism that may involve the homologous recombination between intracellular mRNA and the mRNA components of a D-RNAi construct. These findings provide a potential intracellular defense system against cancer and viral infections.
Iodine deficiency disorders (IDD) are a serious public-health problem in Bangladesh and in other countries. Use of iodized salt has been promoted to solve the problem. A study was conducted in eight unions of Chakaria upazila in the Cox's Bazar district of Bangladesh during 1997-1998 to determine the prevalence of use of iodized salt, explore the reasons behind nonuse, and identify the socioeconomic correlates of its use. A quantitative survey was conducted to collect information from 21,190 households on socioeconomic status, demographic characteristics, and the kind of salt used. In-depth interviews and focus-group discussions were also conducted to understand the situation further. The results revealed that only 1.9% of the households used iodized salt. Strong barriers that limit their use of iodized salt included the wide availability of coarse salt, lack of knowledge about the link between iodized salt and IDD, and the high cost of iodized salt. Households in the salt-producing localities and those that are economically disadvantaged tend to use iodized salt less than others. Understanding of the prevalent situation will allow the policy-makers to take measures to improve the situation in the salt-producing areas.
Malaria is one of the most serious diseases of developing countries. In Bangladesh the estimated population at risk of malaria was calculated to be 103.7 million. This study, carried out in 1995 in villages of the malaria-endemic south-eastern part of Bangladesh aimed to identify the correlates of perceived malarial episodes and healthcare-seeking behavior. Data were collected from villagers and healthcare providers by interviewing. Seventeen percent of the study population reported an episode of malaria during the two months prior to the survey. Males reported more malarial episodes than females; irregular visitors to the jungle and day laborers reported higher prevalence of illness than their regular counterparts. Ninety-nine percent of those who reported suffering from malaria consulted a village healthcare provider within 21 days of the onset of symptoms. Contact rate was higher for those living in highlands, the economically better-off and those aged 10-14 years. The education of the household head, location of the house, the age of the individual, the duration of treatment and the kind of medication suggested were significantly associated with treatment compliance. There is a need to raise awareness about prevention and appropriate management of malarial episodes.
We have evaluated two commercially available kits (AMPLICOR MONITOR [Roche] and NASBA HIV-1 QT or NucliSens HIV-1 QT [Organon Teknika]) and two noncommercial methods for the accurate quantitation of human immunodeficiency virus type 1 (HIV-1) RNA in seminal plasma. The same panels of coded specimens were tested on four separate occasions. Laboratories using the commercial assays employed silica beads to isolate HIV-1 RNA, which removed inhibitory factors sometimes found in seminal plasma. Sensitivities and specificities, respectively, for each assay were as follows: AMPLICOR MONITOR, 100 and 73%; NASBA HIV-1 QT, 84 and 100%; NucliSens HIV-1 QT, 99 and 98%; and noncommercial assays, 91 and 73%. When results from the laboratory that was inexperienced with the silica bead extraction method were excluded from the analysis, specificity for the Roche assay increased to 100%. The commercial assays demonstrated highly reproducible results, with intra-assay standard deviations (measured in log(10) RNA copies/milliliter of seminal plasma) ranging from 0.11 to 0.32; those of the noncommercial assays ranged from 0.12 to 0.75. Differences in mean estimated HIV-1 RNA concentrations were </=0.67 log(10) and were greater at low viral loads. Suspension matrices that used blood plasma or seminal plasma did not make a difference in recovery of HIV-1 RNA, which suggested that blood plasma specimens can be used as external controls for seminal plasma assays. More variation in the HIV-1 RNA viral loads was observed in the seminal plasma values than in the blood plasma values when paired specimens from HIV-1-infected men were tested. Quantitation of HIV-1 RNA in seminal plasma can be reliably accomplished using two commercially available assays, and may be incorporated into the evaluations of HIV-1 seropositive men enrolled in clinical studies.
OBJECTIVES: Breast-feeding is on the decline. Very often the first introduction to bottle-feeding is facilitated in the maternity units. This reduces the chances for the mother to breast feed successfully. The objective of the study was to evaluate the knowledge, attitude and practices of breast-feeding amongst the nurses working in the maternity units. SUBJECTS: Nurses working in the maternity units of North Nazimabad, Karachi. DESIGN/METHODOLOGY: A cross-sectional study was conducted in the maternity units of North Nazimabad, Karachi. The Nurses were interviewed through a structured questionnaire. RESULTS: Out of 110 nurses working in the units, interviews of 70 nurses were obtained. The survey reveals that out of 70 nurses only 16 were qualified. The result shows that the nurses know little about successful lactation management and their role in the promotion and support of breast-feeding. There was a significant difference (P < 0.00) between qualified and non-qualified nurses as regards management of different aspects of breast-feeding. CONCLUSION: There is a huge gap between what is desired and what is available. Intensive training programs should be organized to enhance nursing activities for the required services in order to promote and support breast-feeding.
A monocyte-derived macrophage (MDM) culture assay was used to define the replication kinetics of HIV isolates. Ten-day-old MDMs were infected with HIV. Supernatants were collected and assayed for HIV p24 on days 3, 7, 10, and 14 post-infection (PI). In this assay, SF162 (macrophage tropic, NSI) produced increasing amounts of HIV p24 antigen with increasing time in culture. BRU (nonmacrophage tropic, SI) infection resulted in low levels of HIV p24 antigen with no increase in production during the culture period. A panel of 12 clinical isolates was evaluated. All isolates produced detectable levels of HIV p24 antigen in MDMs. However, the NSI viruses had significantly higher log10 HIV p24 antigen values at all times PI (P < 0.01). Co-receptor usage was determined for all 12 isolates (8 NSI and 4 SI). All SI isolates used CXCR4 for entry; two used CXCR4 only, one used CXCR4, CCR5, and CCR3, and one was a mixture of two isolates using CXCR4 and CCR5. None of the NSI viruses used CXCR4 for entry. All used CCR5 as their predominant co-receptor. Of the eight NSI isolates, three used CCR5 only, two used CCR5 and CCR2b, one used CCR5 and CCR3, and one used CCR5, CCR3, and CCR2b. Log10 HIV p24 antigen production on day 14 PI for viruses that used CCR5+CCR3 (3.79 + 1.40) was greater than for viruses that used CCR5+CCR2b (3.22 + 1.55) or CCR5 (3.32 + 1.49), and all were greater than those that used CXCR4 only (1.69 + 0.28), regardless of SI phenotype (P < 0.05). Thus, in these primary isolates, macrophage tropism and replication kinetics were closely linked to CCR5 utilization, whereas SI capacity was closely linked to CXCR4 utilization. Furthermore, viruses, which could use CCR5 and CCR3 for entry, had a replication advantage in macrophages, regardless of SI phenotype.
Bangladesh typifies many south-eastern countries where female children experience inferior health and uncertain survival, especially after the neonatal period. This paper attempts to study the gender inequality in nutritional status and the effects of various socioeconomic, demographic, and health-programme factors on gender inequality in a remote rural area of Bangladesh. Measurements of mid-upper arm circumference (MUAC) were taken from 2,016 children aged less than 5 years (50.8% male, 49.2% female) in 1994. Children were characterized as severely malnourished if MUAC was < 125 mm. Independent variables included various characteristics of children, households, and mothers. Average MUAC for all children was 130 mm; 33% were severely malnourished. Of the severely-malnourished children, 54.2% were female, and 45.8% were male. The gender gap persisted in the multivariate situation, with female 1.44 times more likely to be severely malnourished. Other variables with a statistically significant relationship included the age of children, acceptance of DPT1, and education of household heads. The persistence of such a gender discrimination now when the country has achieved a lot in terms of child survival is striking. The issue is important and demands appropriate corrective actions.
Thirteen laboratories evaluated the reproducibility of sequencing methods to detect drug resistance mutations in HIV-1 reverse transcriptase (RT). Blinded, cultured peripheral blood mononuclear cell pellets were distributed to each laboratory. Each laboratory used its preferred method for sequencing proviral DNA. Differences in protocols included: DNA purification; number of PCR amplifications; PCR product purification; sequence/location of PCR/sequencing primers; sequencing template; sequencing reaction label; sequencing polymerase; and use of manual versus automated methods to resolve sequencing reaction products. Five unknowns were evaluated. Thirteen laboratories submitted 39043 nucleotide assignments spanning codons 10-256 of HIV-1 RT. A consensus nucleotide assignment (defined as agreement among > or = 75% of laboratories) could be made in over 99% of nucleotide positions, and was more frequent in the three laboratory isolates. The overall rate of discrepant nucleotide assignments was 0.29%. A consensus nucleotide assignment could not be made at RT codon 41 in the clinical isolate tested. Clonal analysis revealed that this was due to the presence of a mixture of wild-type and mutant genotypes. These observations suggest that sequencing methodologies currently in use in ACTG laboratories to sequence HIV-1 RT yield highly concordant results for laboratory strains; however, more discrepancies among laboratories may occur when clinical isolates are tested.
The associations of CD4 cell count, plasma human immunodeficiency virus (HIV) type 1 RNA, infectious HIV titer in peripheral blood mononuclear cells, immune complex-disrupted (ICD) p24 antigen, and MT-2 assays with measures of disease progression after drug treatment were assessed in a subset of patients enrolled in AIDS Clinical Trials Group Study 175. Baseline plasma RNA levels and changes in RNA values at weeks 8 or 56 were more important predictors of disease progression than were baseline or changes in CD4 cell counts. Each 10-fold lower HIV RNA concentration at baseline and each 10-fold decrease in HIV RNA between baseline and week 8 was associated with increases of 49-61 CD4 cells/mm3 at weeks 56 and 104. In multivariate analyses, neither baseline values nor changes in infectious HIV titer nor ICD p24 antigen concentrations were associated with long-term changes in CD4 cell count. Plasma HIV-1 RNA appears to be the best predictor of long-term CD4 cell count responses and disease progression.
Virologic measurements are increasingly used to evaluate prognosis and treatment responses in human immunodeficiency virus (HIV) type 1 infection. Markers of HIV-1 replication, including infectious HIV-1 titer from peripheral blood mononuclear cells, serum HIV-1 p24 antigen, plasma HIV-1 RNA, CD4 cell numbers, and viral syncytium-inducing (SI) phenotype, were determined in 391 virology substudy participants in AIDS Clinical Trials Group study 175. The subjects had 200-500 CD4 cells/mm3. All markers of viral replication significantly correlated with one another and were inversely related to CD4 cell number. Disease progression to an AIDS-defining event or death or loss of >50% of CD4 cells was associated with infectious HIV-1 titer (P < .001), HIV-1 RNA (P < .001), and HIV-1 p24 antigen (P = .007). In multivariate proportional hazards models, p24 antigen was never significant when HIV-1 RNA level was included. In a model containing infectious HIV-1 titer (P = .038), HIV-1 RNA (P < .001), SI phenotype (P < .001), and CD4 cell number (P = .18), only the virologic parameters remained significantly associated with progression.
The rat leukemia virus (RaLV) is an endogenous retrovirus that is spontaneously released by Sprague-Dawley rat embryo cells. The overall structure of the RaLV genome resembles that of other simple, replication-competent retroviruses, but the sequence of the long terminal repeats (LTR) is unique and unrelated to the known retroviruses. Phylogenetically, the RaLV genome appears to be more closely related to the feline leukemia virus group of retroviruses than to the murine leukemia virus group. A remarkable feature of RaLV is that it is capable of transducing a ras proto-oncogene from rat tumor cells in the form of an acutely transforming virus, designated the Rasheed strain of the rat sarcoma virus (RaSV). With the exception of the c-ras sequence, the genomes of both RaLV and RaSV are collinear. The RaSV-encoded oncogene v-Ra-ras expresses a fusion protein with a molecular mass of 29 kDa, and it exhibits a unique structure that has not been described previously for any known virus. The 5' end of this gene is derived from sequences encoding RaLV matrix followed by 20 bp derived from the U5 region of the RaLV LTR (RS-U5 element) which is joined at its 3' end to sequences derived from all six (coding and noncoding) exons of the c-ras proto-oncogene at the 3' end. This recombinational event represents a novel mechanism among the acutely transforming viruses that have been studied.
This article delineates several parameters that can influence compartmentalized virus shedding in relation to organ-specific factors and cofactors in the blood and reproductive tract compartments of women infected with the human immunodeficiency virus type 1 (HIV-1). Because a wide variety of techniques is currently used for the collection, processing, and quantitation of HIV load in the female genital secretions, standard protocols for appropriate sampling and testing of these specimens are provided. Studies conducted in our laboratory have shown that the levels of cell-free HIV-1 RNA in the female reproductive tract and the blood plasma within HIV-1-infected women are different and therefore may represent independent events.
The adipose tissue hormone, leptin, and the neuropeptide glucagon-like peptide-1 (7-36) amide (GLP-1) both reduce food intake and body weight in rodents. Using dual in situ hybridization, long isoform leptin receptor (OB-Rb) was localized to GLP-1 neurons originating in the nucleus of the solitary tract. ICV injection of the specific GLP-1 receptor antagonist, exendin(9-39), at the onset of dark phase, did not affect feeding in saline pre-treated controls, but blocked the reduction in food intake and body weight of leptin pre-treated rats. These findings suggest that GLP-1 neurons are a potential target for leptin in its control of feeding.
OBJECTIVE: To assess the incidence of chronic postvasectomy testicular pain (CPTP) and evaluate the use of denervation of the spermatic cord in its management. PATIENTS AND METHODS: A retrospective postal survey of 560 patients (mean age 36 years, range 25-55; mean time since vasectomy 19 months, range 8-39) who underwent vasectomy between July 1992 and December 1994 was carried out to determine the incidence of CPTP. A prospective study was conducted in a further group of 17 patients (mean age 43 years, range 34-60), who had had CPTP for at least one year, to evaluate the effectiveness of nerve stripping of the spermatic cord in relieving pain. RESULTS: Of 396 replies, 108 (27.2%) patients complained of some testicular pain following their vasectomy operation. In 88 (82%) of these 108 patients the pain was brief and was not defined as CPTP, while 20 (19%) patients had pain for > 3 months; 33 (31%) patients required analgesics to control the pain. Of the 17 patients who underwent spermatic cord denervation, 13 reported complete relief of pain at their first follow-up visit and were discharged. Four patients had a significant improvement in the symptom score and were satisfied with the results. CONCLUSIONS: There is a small but significant incidence of CPTP and patients should be warned of this possibility when counselled before operation. Denervation of the spermatic cord seems to be a viable surgical option for patients with CPTP who fail to respond to conservative measures.
A double-blind phase II trial compared zalcitabine (0.03 mg/kg/day) in combination with zidovudine (720 mg/m2/day) and zidovudine monotherapy in 250 clinically stable, previously zidovudine-treated, human immunodeficiency virus-infected children. The combination was well-tolerated except for an increased incidence of neutropenia (14%) compared with that in children receiving monotherapy (5%). No differences were noted for time to first AIDS-defining illness or death, neuropsychologic status, or weight Z scores. In patients in the combination arm, the CD4 cell count decline was slower (13% per year) than in patients receiving monotherapy (25% per year) (P = .03), and quantitative peripheral blood mononuclear cell virus load remained lower at all time points (P = .08). Deaths were fewer in patients receiving combination therapy (4) compared with those in patients receiving monotherapy (10) (P = .083). Thus, administration of zidovudine with zalcitabine to children with prior zidovudine treatment did not result in a significant increase in toxicity compared with that resulting from zidovudine monotherapy and demonstrated improvement in immunologic and virologic surrogate markers.
BACKGROUND: We studied measures of human immunodeficiency virus (HIV) replication, the viral phenotype, and immune function (CD4 cell counts) and the relation of changes in these indicators to clinical outcomes in a subgroup of patients in a controlled trial of early antiretroviral treatment for HIV, the AIDS Clinical Trials Group Study 175. METHODS: The 391 subjects, each of whom entered the study with a single screening CD4 cell count of 200 to 500 per cubic millimeter, were randomly assigned to receive zidovudine alone, didanosine alone, zidovudine plus didanosine, or zidovudine plus zalcitabine. Plasma concentrations of HIV RNA were assessed in 366 subjects, and viral isolates from 332 subjects were assayed for the presence of the syncytium-inducing phenotype. RESULTS: After eight weeks, the mean (+/-SE) decrease from base line in the concentration of HIV RNA, expressed as the change in the base 10 log of the number of copies per milliliter, was 0.26+/-0.06 for patients treated with zidovudine alone, 0.65+/-0.07 for didanosine alone, 0.93+/-0.10 for zidovudine plus didanosine, and 0.89+/-0.06 for zidovudine plus zalcitabine (P<0.001 for each of the pairwise comparisons with zidovudine alone). Multivariate proportional-hazards models showed that higher base-line concentrations of plasma HIV RNA, less suppression of plasma HIV RNA by treatment, and the presence of the syncytium-inducing phenotype were significantly associated with an increased risk of progression to the acquired immunodeficiency syndrome and death. After adjustment for these measures of viral replication and for the viral phenotype, CD4 cell counts were not significant predictors of clinical outcome. CONCLUSIONS: Both the risk of the progression of HIV disease and the efficacy of antiretroviral therapy are strongly associated with the plasma level of HIV RNA and with the viral phenotype. The changes in the plasma concentration of HIV RNA predict the changes in CD4 cell counts and survival after treatment with reverse-transcriptase inhibitors.
We have isolated and characterized a new HIV-1 variant (HIV-1IbNg) from the peripheral blood mononuclear cells (PBMCs) of an inhabitant of Nigeria. This virus is highly cytopathic to PBMCs in culture, replicates in primary human T cells and macrophages/monocytes as well as in established human T cell and monocytic cell lines (i.e., it has a wide host range), and it does not induce syncytia in MT-2 cells.1 Because of these unusual infectivity parameters in vitro, we analyzed the genetic structure of the entire genome. Using cytoplasmic RNA from HIV-1IbNg-infected PBMCs, five overlapping DNA fragments were amplified by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique and cloned into pBluescript II SK(+). DNA sequencing of these fragments indicated that the entire HIV-1IbNg genome consisted of 9201 nucleotides and phylogenetic analysis of its env gene sequence revealed that this virus clustered with HIV-1 strains belonging to clade "A". In this article we present several genetic features unique to this virus, including (1) the presence of a 16-bp insert within the primer-binding site, (2) a large Rev open reading frame, (3) a Rev-responsive element that is predicted to form a different secondary structure than described for clade "B" viruses, (4) the potential to encode a heavily glycosylated Env protein, and (5) a frameshift, resulting in a stop codon, in the tat gene. This represents the first detailed analysis of the genetic structure of an HIV-1 strain from Nigeria.