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Biomedical subjects

F Ahmed

Publications and source records attributed to F Ahmed.

At least 37 records · Page 2Linked to original sources

The retinoblastoma family member, p107, is active in non-dividing monocyte-derived dendritic cells.

A member of the retinoblastoma family of cell cycle regulatory proteins, p107, is not normally expressed in non-cycling cells. We demonstrate here that p107 is expressed in monocytes as they differentiate into dendritic cells under the influence of granulocyte-macrophage colony-stimulating factor and interleukin 4, a process shown not to involve cellular proliferation. We show that p107 is localized to the nucleus of these cells and is active, in that it binds an E2F-DNA binding site, together with E2F transcription factors. These findings suggest a hitherto unknown role for p107 in non-proliferating dendritic cells that warrants further investigation.

Blotting, Western↗

Concomitant supplemental vitamin A enhances the response to weekly supplemental iron and folic acid in anemic teenagers in urban Bangladesh.

BACKGROUND: Iron deficiency is the most common micronutrient deficiency and affects >2 billion persons worldwide, leading to anemia in >40% of women of reproductive age in the developing world. OBJECTIVE: The objective was to determine whether weekly supplementation with iron and folate would reduce the frequency of anemia in teenage women in urban Bangladesh before they became pregnant. DESIGN: Participants with a hemoglobin concentration of 80-120 g/L were entered into a randomized, double-blind, placebo-controlled trial and received supplements of placebo, vitamin A, iron + folic acid, or iron + folic acid + vitamin A weekly for 12 wk. The supplements contained 2.42 mg vitamin A (retinol) as retinyl palmitate, 120 mg elemental Fe as ferrous sulfate, and 3.5 mg folic acid. RESULTS: Hemoglobin concentrations increased significantly more after supplementation with iron + folic acid or iron + folic acid + vitamin A than after either the placebo or vitamin A alone. There was a significantly greater increase in hemoglobin after iron + folic acid + vitamin A than after iron + folic acid, but the additional effect disappeared after adjustment for baseline hemoglobin, serum vitamin A, and ferritin and the number of supplements taken. Those with the lowest baseline hemoglobin had the greatest increase in hemoglobin. Compared with the placebo, iron + folic acid + vitamin A reduced anemia by 92%, iron deficiency by 90%, and vitamin A deficiency by 76%. CONCLUSION: There may be significant health benefits from a program that enhances the nutritional status of iron, folate, and vitamin A in poor urban young women before they become pregnant.

Adolescent↗

Quantification of the common deletion in human testicular mitochondrial DNA by competitive PCR assay using a chimaeric competitor.

The "common" 4977 bp deletion in mitochondrial DNA (Delta4977) is commonly used as an indicator of tissue deterioration in ageing and bioenergetic diseases. Deletion levels are normally measured by a serial dilution polymerase chain reaction (PCR) approach, where test reactions are compared with dilutions of control amplifications of DNA from a similar sized stable region of the mitochondrial genome. The end-point of this assay is the dilution that can just detect any PCR product; however, this is an inherently unstable measure. We constructed a chimaeric DNA construct that binds to both control and deletion primers with similar annealing properties. This was used in a competitive PCR assay to quantify Delta4977 in human testicular tissues that had been well-characterized using the serial dilution approach. We found the competitive assay to be highly replicable as it compares the PCR product of the construct with that of test DNA samples during the linear growth phase of the PCR reaction. Moreover, the serial dilution assay was shown to significantly overestimate the amounts of deleted mitochondrial DNA present. The assay promises to throw new light on the role of mitochondrial DNA deletions in tissue dysfunction and ageing, as such deletions can now be determined with high accuracy and repeatability and is much cheaper to apply than real-time fluorescent quantitative PCR.

DNA, Mitochondrial↗

Epidemiology of postshigellosis persistent diarrhea in young children.

BACKGROUND: Dysentery accounts for 20% of the 4.6 million diarrhea-associated deaths among children in developing countries, with the risk from death in dysenteric persistent diarrhea 10-fold higher than that in acute dysentery. Although Shigella accounts for the majority of dysenteric episodes, very little is known about the epidemiology of postshigellosis persistent diarrhea. METHODS: Rural Bangladeshi children younger than 5 years of age (n = 1,756) were followed for 1 month after exposure to sentinel cases of Shigella dysentery. The likelihood of an acute diarrheal episode becoming persistent was assessed. RESULTS: Diarrhea caused by Shigella was significantly associated with an increased risk of persistent diarrhea (age-adjusted relative risk, 1.83; 95% confidence interval, 1.19 to 2.81). Despite the use of nalidixic acid in dysenteric episodes, persistent diarrhea occurred in 23% of children with shigellosis. Infection by multiply antibiotic-resistant Shigella isolates (age-adjusted relative risk, 3.76; 95% confidence interval, 1.51 to 9.36) and occurrence of shigellosis during infancy were observed to be risk factors for initiation of Shigella diarrhea persistence. However, 88% of the persistent shigellosis episodes occurred in older children, 50% were associated with nondysenteric shigellosis and 79% were caused by Shigella species other than Shigella dysenteriae 1. CONCLUSIONS: These data demonstrate the importance of Shigella as a cause of persistent diarrhea and indicate that strategies to prevent postshigellosis persistent diarrhea must be broad-based, with a focus on older children as well as infants, management of nondysenteric as well as dysenteric disease and prevention of diarrhea caused by multiple Shigella species.

Bangladesh↗

Intragastric acidification reduces the occurrence of false-negative urea breath test results in patients taking a proton pump inhibitor.

OBJECTIVE: The aim of this study was to investigate whether reducing intragastric pH, at the time of urea ingestion, decreases the likelihood of false-negative (FN) urea breath test (UBT) results in patients taking a proton pump inhibitor (PPI). METHODS: Patients with active Helicobacter pylori infection underwent a baseline 14C-UBT (UBT-1) followed by treatment with lansoprazole 30 mg/day for 14 to 16 days. On day 13, patients returned for a repeat standard UBT (UBT-2). Between days 14 to 16, patients underwent a modified UBT (UBT-3), which included consuming 200 ml of 0.1 N citrate solution 30 min before and at the time of 14C-urea administration. Breath samples were collected 10 and 15 min after 14C-urea ingestion. Mean 14CO2 excretion and the number of FN and equivocal UBT results were compared for the three UBTs. RESULTS: A total of 20 patients completed the study. Lansoprazole caused a significant decrease in mean breath 14CO2 excretion (disintegrations per minute) between UBT-1 (2.96 +/- 0.23) and UBT-2 (2.08 +/- 0.52, p < 0.05). Lansoprazole caused six (30%) FN and eight (40%) equivocal UBT-2 results. Mean breath 14CO2 excretion for UBT-3 (677 +/- 514) was greater than for UBT-2 (234 +/- 327, p = 0.001). UBT-3 caused only two (10%) FN and three (15%) equivocal results. The 15-min breath sample caused fewer FN and equivocal results than the 10-min sample for both UBT-2 and UBT-3. CONCLUSIONS: Giving citrate before and at the time of 14C-urea administration increases mean breath 14CO2 excretion and decreases FN and equivocal UBT results in patients taking a PPI. These observations suggest that it may be possible to design a UBT protocol that will remain accurate in the face of PPI therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Changes in mRNA levels of the Myoc/Tigr gene in the rat eye after experimental elevation of intraocular pressure or optic nerve transection.

PURPOSE: To isolate the rat Myoc/Tigr gene and investigate changes in its expression pattern in normal eyes and in eyes with either pressure-induced optic nerve damage or optic nerve transection. METHODS: Expression pattern of the rat Myoc/Tigr gene was investigated by Northern blot hybridization. Optic nerve damage and death of ganglion cells in the retina were induced unilaterally, by injection of hypertonic saline solution, episcleral vein cauterization, or optic nerve transection. The levels of mRNA for Myoc/Tigr were compared between several tissues of the control and surgically altered eyes, by using semiquantitative RT-PCR, real-time PCR, and Northern blot analysis. RESULTS: The rat Myoc/Tigr gene is 10 kb long and contains three exons. Among the eye tissues analyzed, Myoc/Tigr mRNA was detected in the combined tissues of the eye angle, sclera, cornea, retina, and optic nerve head. With pressure-induced optic nerve degeneration, the level of Myoc/Tigr mRNA decreased in the retina and the combined tissues of the eye angle, but increased in the optic nerve head. After optic nerve transection, the level of Myoc/Tigr mRNA increased in the retina, but did not change in the combined tissues of the eye angle. CONCLUSIONS: The decreased level of Myoc/Tigr mRNA in the retina after induction of elevated intraocular pressure compared with that in the control retina cannot be explained by ganglion cell death alone. Differences in Myoc/Tigr mRNA levels in eye tissues after elevation of intraocular pressure or optic nerve transection may reflect the activation of different signaling pathways involved in regulation of this gene.

Animals↗

The ability of poloxamers to inhibit platelet aggregation depends on their physicochemical properties.

Poloxamers, block copolymers of polyethylene glycol (PEG) and polypropylene glycol (PPG), are thought to reduce cell-cell adhesion during vascular disorders. We examined how the amphiphilic nature of these polymers may contribute to their ability to inhibit ADP-induced platelet aggregation. Four Poloxamers (184, 188, 335 and 338) with varying PEG and PPG block lengths were examined. Of these, Poloxamer 184 at 2 mM markedly inhibited platelet aggregation. We observed that: i) Typically, less than 10% of the platelet surface is covered by Poloxamers, and greater than 99% of the polymer either remains in solution or binds soluble components in blood plasma. ii) Increasing the PEG side-chain length does not significantly augment the ability of Polox-amers to inhibit platelet aggregation. iii) Poloxamer 184, but not Polox-amers 188 and 335, significantly reduces the ability of stimulated platelets to bind fibrinogen and antibody PAC-1. The study demonstrates that the physical adsorption of some Poloxamers may allow them to inhibit platelet aggregation. The inhibition mechanism involves either binding of Poloxamers to platelet GPIIb-IIIa or inhibition of cellular activation pathways.

Adenosine Diphosphate↗

Rho family GTPases regulate mammary epithelium cell growth and metastasis through distinguishable pathways.

BACKGROUND: Relatively few genes have been shown to directly affect the metastatic phenotype of breast cancer epithelial cells in vivo. The Rho family of proteins, incluing the Rho, Rac and Cdc42 subfamilies, are related to the small GTP binding protein Ras and regulated diverse biological processes including gene transcription, cytoskeletal organization, cell proliferation and transformation. The effects of Cdc42, Rac and Rho on the actin cytoskeleton suggested a possible role for Rho proteins in cellular motility and metastasis; however, a formal analysis of the role of Rho proteins in breast cancer cellular growth and metastasis in vivo had not previously been performed. MATERIALS AND METHODS: We generated a panel of MTLn3 rat mammary adenocarcinoma cells that expressed similar levels of dominant inhibitory mutants of Cdc42-, Rac- and Rho-dependent signaling, to examine the contribution of these GTPases to cell spreading, guided chemotaxis, and metastasis in vivo. The ability of Rho proteins to regulate intravasation into the peripheral blood was determined by implanting MTLn3 cell stable dominant negative lines in nude mice and measuring the formation of breast cancer cell colonies grown from the peripheral blood. Serial sectioning of the lungs was performed to determine the presence of metastasis in mice in which mammary tumors expressing the dominant negative Rho family proteins had grown to a similar size. RESULTS: Cell spreading of MTLn3 cells was selectively abrogated by N17Rac1. N19RhoA and N17Cdc42 reduced the number of focal contacts (FCs) and disrupted the co-localization of vinculin with phosphotyrosine at FCs. While N17Rac1 and N17Cdc42 preferentially inhibited colony formation in soft agar, all three GTPases affected cell growth in vivo. To distinguish effects on tumorigenicity from intravasation into the bloodstream, implanted tumors were grown to the same size in nude mice. Each dominant inhibitory Rho protein reduced intravasation into the peripheral blood. Lung metastasis of MTLn3 cells was also abrogated by the dominant inhibitory Rho proteins, despite the presence of residual CFU. CONCLUSIONS: These studies demonstrate for the first time a critical role for the Rho GTPases involving independent signaling pathways to limit mammary tumor cellular growth and metastasis in vivo.

Adenocarcinoma↗

Guillain-Barré syndrome: An unusual presentation of West Nile virus infection.

West Nile fever is a mosquito-borne febrile illness seen in Africa, Asia, and Europe, but reported in North America only once. The recent outbreak in New York City represents the first time this virus has been detected in North America. West Nile virus usually causes mild symptoms, though rarely it can cause neurologic diseases, with a fatal outcome or permanent neurologic sequelae. We describe an elderly patient with West Nile virus infection who presented with Guillain-Barré syndrome.

Aged↗

Effect of clinical events on plasma HIV-1 RNA levels in persons with CD4+ T-lymphocyte counts of more than 500 x 10(6) cells/l.

OBJECTIVE: Immune stimulation of CD4 lymphocytes is thought to enhance HIV-1 replication in vivo. Therefore, we sought to define the impact of clinical events identified as putative immune activators on the variability of plasma HIV-1 RNA levels in persons with CD4 cell counts greater than 500 x 10(6) cells/l. DESIGN: We prospectively recorded clinical events and measured plasma HIV-1 RNA levels weekly for 24 weeks in 16 HIV-1-infected adults who were not receiving antiretroviral therapy and who had CD4 cell counts greater than 500 x 10(6) cells/l. METHODS: Standard weekly interviews were conducted to capture potential immune activators (e.g., infections, immunizations, and allergic reactions). All plasma HIV-1 RNA levels were measured using the Amplicor HIV-1 Monitor assay (Roche Diagnostics, Branchburg, New Jersey, USA) according to the manufacturer's instructions. RESULTS: Participants had remarkably stable viral loads during the 6 month study period. Infections were significantly more frequent during the 7 days prior to individual HIV-1 RNA measurements that exceeded the assay variation thresholds determined for this study (+/- 0.324 log) than during the comparable time periods preceding stable measurements (P = 0.023). As a group, the eight participants who had one to four HIV-1 RNA measurements that exceeded the thresholds experienced more infections and declining CD4 cell counts over the study course compared to the eight participants whose measurements all fell within the thresholds (P = 0.058 and 0.053 respectively). CONCLUSIONS: Our study suggests that in untreated HIV-1-infected persons with CD4 cell count greater than 500 x 10(6) cells/l, viral load is generally quite stable, although acute minor infections are associated with transient fluctuations generally lasting no more than 1 week.

Acquired Immunodeficiency Syndrome↗

Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi adults and children.

We have compared the B cell responses evoked in Bangladeshi, adults (n=11, median age 25 years) and children (n=21, median age 4.5 years), 7 days after intake of each of two doses of an oral, inactivated enterotoxigenic Escherichia coli (ETEC) vaccine composed of formalin-killed ETEC strains expressing the colonization factors, CFA/I, CFA/II and CFA/IV together with 1 mg of recombinant cholera toxin B-subunit (rCTB). The vaccine was well tolerated and only gave rise to negligible side effects. Peak antibody-secreting cell (ASC) response of the IgA isotype were seen 7 days after the first dose of the vaccine. The ASC responses to the different colonization factors (CFs) increased from a 29- to 46-fold (responder frequency 90-100%) in the adults and 13- to 24-fold (responder frequency 67-90%) in the children. The IgA-ASC response to rCTB also peaked after the first dose in the adults (426-fold, responder frequency 100%) and the children (46-fold, responder frequency 95%). Increased IgA antibody levels against CFA/I as well as IgA and IgG antibody levels to rCTB were seen in plasma after immunisation. About 86% of the children and 80% of the adults responded with faecal antibodies to rCTB, whereas about 67% of both groups responded to CFA/I. These results show that a single dose of the ETEC vaccine may elicit significant mucosal immune responses in both children and adults residing in an ETEC-endemic country such as Bangladesh.

Adult↗

Relationships between vitamin A, iron status and helminthiasis in Bangladeshi school children.

OBJECTIVE: To explore the relationships between biochemical indicators of vitamin A and iron status and the intestinal helminths Ascaris lumbricoides and hookworm in primary school children. SETTING: Two rural governmental schools in northwestern Bangladesh. DESIGN: Cross-sectional study. SUBJECTS: The sample consisted of 164 children in grades 3-5. METHODS: Serum retinol and beta-carotene (by high-performance liquid chromatography, HPLC), haemoglobin (HemoCue), ferritin (enzyme-linked immunoadsorbent assay, ELIZA) and height and weight were measured. Dietary intake of vitamin A was assessed using a food frequency questionnaire and faecal analyses were done using Stoll's egg-count technique. RESULTS: The mean serum retinol was 26.8 microg dl(-1) and 20% had a level of < 20 microg dl(-1), the cut-off value for low vitamin A status. There was a strong positive association between serum beta-carotene and serum retinol (r = 0.44, P < 0.001), suggesting those with higher retinol levels had a higher carotene intake. Thirty-one per cent were anaemic (Hb < 11.5 g dl(-1)), 30% had iron deficiency (serum ferritin < 12.0 microg l(-1)) and 14% were suffering from iron deficiency anaemia. Children with a serum retinol level of 20 microg dl(-1) had significantly lower ferritin (14.0 compared to 26.0 microg l(-1), P = 0.005) and Hb levels (11.7 compared to 12.4 g dl(-1), P = 0.005) than those with higher levels. The proportion of iron deficiency anaemia was significantly greater among children with hookworm. Our data suggest that hookworm exerts its impact on iron status independently of the vitamin A status of the host. CONCLUSIONS: Programmes to improve iron status should consider including both vitamin A prevention programmes and deworming.

Anemia, Iron-Deficiency↗

Anaemia in Bangladesh: a review of prevalence and aetiology.

OBJECTIVE: : This paper provides a comprehensive review of the changes in the prevalence and the extent of anaemia among different population groups in Bangladesh up to the present time. The report also focuses on various factors in the aetiology of anaemia in the country. DESIGN AND SETTING: : All the available data have been examined in detail, including data from national nutrition surveys, as well as small studies in different population groups. RESULTS: : Over the past three decades a number of studies including four national nutrition surveys (1962/64; 1975/76; 1981/82 and 1995/96) have been carried out to investigate the prevalence of anaemia among different population groups in Bangladesh, and have demonstrated a significant public health problem. Since the 1975/76 survey the average national prevalence of anaemia has not fallen; in 1995/96, 74% were anaemic (64% in urban areas and 77% in rural areas). However, age-specific comparisons suggest that the rates have fallen in most groups except adult men: in preschool children in rural areas it has decreased by about 30%, but the current level (53%) still falls within internationally agreed high risk levels. Among the rural population, the prevalence of anaemia is 43% in adolescent girls, 45% in non-pregnant women and 49% in pregnant women. The rates in the urban population are slightly lower compared with rural areas, but are high enough to pose a considerable problem. It appears that severe anaemia in the Bangladeshi population is less frequent, possibly present among only 2-3% of the population. The data on the aetiology of anaemia reveal that iron deficiency may be a substantial cause of anaemia in the Bangladeshi population. Other dietary factors in addition to parasitic infestations may also precipitate the high prevalence of anaemia. CONCLUSIONS: : While the overall prevalence of anaemia among the Bangladeshi population is still very high, the rates of severe anaemia are almost non-existent. A large proportion of anaemia can be attributed to iron deficiency. There is a need for a comprehensive strategy for the prevention and control of anaemia in Bangladesh.

Adolescent↗

Anaemia and iron deficiency among adolescent schoolgirls in peri-urban Bangladesh.

OBJECTIVE: To investigate the prevalence of anaemia and iron deficiency among adolescent schoolgirls in peri-urban Bangladesh, and to identify various factors associated with anaemia in this population. DESIGN: A cross-sectional design. SETTING: Girls' high schools in five sub-districts of Dhaka. SUBJECTS: Adolescent girls (n=548) aged 11-16 y from nine schools in Dhaka district participated in the study. Socio-economic, anthropometric and dietary information were collected. Blood haemoglobin (Hb), serum iron, total iron binding capacity (TIBC), transferrin saturation (TS), serum ferritin (SF) and serum retinol (vitamin A) were determined. RESULTS: The prevalence of anaemia (Hb<120 g/l) among the participants was 27%. Seventeen percent had depleted iron stores (SF<12 microg/l). Of all anaemic girls, 32% had iron deficiency anaemia (Hb<120 g/l and SF<12 microg/l). When the girls were classified by serum vitamin A, the third with the lowest serum retinol levels had significantly lower Hb and SF levels. Significant positive correlations were observed between Hb and serum iron, TS, SF and retinol, while there was a negative correlation with serum TIBC. Occupancy, frequency of consumption of large fish, serum iron, TIBC, TS, SF and serum vitamin A were strongly related to Hb by multiple regression analysis. For 1 microg/l change in SF concentration, there was a 0.046 g/l change in Hb, when adjusted for all other factors. CONCLUSION: Anaemia among these adolescent schoolgirls in peri-urban Bangladesh cannot be explained by iron deficiency alone, and other causes may also exist in this population.

Adolescent↗