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Biomedical subjects

S Akhtar

Publications and source records attributed to S Akhtar.

At least 109 records · Page 6Linked to original sources
PubMed1998

Evaluation of cell-mediated immunity and circulating immune complexes as prognostic indicators in cancer patients.

Cell-mediated immunity (CMI) and circulating immune complexes (CIC) were estimated in 55 cancer patients and 25 control volunteers to evaluate their prognostic significance. Cancer patients comprised head and neck cancer (11), breast cancer (13), gastrointestinal cancer (10), genitourinary cancer (11), and lymphomas and sarcomas (10). CMI was tested in vitro by early rosette-forming cells (ARFC) and total rosette-forming cell (TRFC) counts. ARFC count in control group was 758.1 +/- 78.09 cells/cumm. In advancing clinical stages of cancer (I-IV), ARFC counts were decreased (i.e., 601.12 +/- 74.96 [p < 0.01]; 494.8 +/- 71.83 [p < 0.001]; 432.44 +/- 36.05 [p < 0.001], and 438.55 +/- 69.99 [p < 0.001] cells/cumm, respectively). TRFC count in control group was 1029 +/- 88.39 cells/cumm. In cancer stages I through IV, these counts decreased significantly (i.e., 699.63 +/- 66.24; 597.55 +/- 82.9; 505.11 +/- 52.56; and 501.55 +/- 69.99 cells/cumm, respectively [p < 0.001]. Dinitrochlorobenzene cutaneous reactivity in vivo was 100% positive in control group, 62.5% positive in cancer stage I, 5% positive in stage II, and negative in stages III and IV. CIC of intermediate size were estimated by polyethylene glycol precipitation (PEG pptn) technique, which detects CIC in the ratio of 2:1 (Ag2Ab). Mean PEG index in control group was 39.5 +/- 4.65; sequential increase in CIC was observed in advancing clinical stages of cancer (I-IV)(i.e., 49 +/- 7.03 [p < 0.01]; 75.38 +/- 44.01 [p < 0.001]; 93.38 +/- 44.57 [p < 0.001]; and 216.00 +/- 147.05 [p < 0.001], respectively). Latex agglutination inhibition (LAI) titer was done to detect CIC as small as 8s, which constitute the opposite polar end of CIC spectrum. LAI titers in control group were nil. However, LAI titers in cancer stages I through IV were 1 +/- 2.64; 8.6 +/- 5.6 (p < 0.001); 12.00 +/- 8.11 (p < 0.001); and 25.77 +/- 9.06 (p < 0.001), respectively. Decrease in CMI and subsequent increase in CIC indicate unfavorable prognosis in cancer patients, and also precede clinical manifestation of increased tumor mass in vivo.

Adult↗
PubMed1998

Synthetic 2'-O-methyl-modified hammerhead ribozymes targeted to the RNA component of telomerase as sequence-specific inhibitors of telomerase activity.

Telomerase is a ribonucleoprotein that synthesizes tandem arrays of the hexameric DNA sequence TTAGGG at chromosome termini using its RNA component as a template. As most normal cells lack telomerase activity, a progressive shortening of chromosome length occurs with each cell division because of incomplete DNA replication. Cell senescence ensues when a critical telomere length is reached, but importantly, senescence bypass and life span extension occur in normal cells transfected with functional telomerase activity. Almost 90% of all tumors express telomerase activity, implying that telomerase is an important determinant in tumor progression and cell immortalization. However, the exact role and regulation of the individual components of the telomerase complex are not fully understood and would benefit from the availability of specific inhibitors. In this study, we investigated the potential use of chemically stabilized, catalytic RNA molecules (hammerhead ribozymes) to inhibit telomerase activity by cleaving the RNA component in a sequence-specific manner. Catalytically competent (active) hammerhead ribozymes containing 2'-O-methyl ribonucleotides for enhanced biologic stability and designed to be complementary to the RNA component of human telomerase exhibited dose-dependent inhibition of telomerase activity in human glioma U87-MG cell lysates with an IC50 of around 0.4 microM. Catalytically incompetent (inactive) ribozymes or mismatched ribozymes with reduced hybridization capability to telomerase RNA did not inhibit telomerase activity, as detected by a PCR-based telomeric repeat amplification protocol (TRAP) assay. In vitro cleavage reactions using short substrates and RT-PCR analyses of the full-length RNA substrate in U87-MG cell lysates confirmed a sequence-specific catalytic cleavage of the targeted RNA component of telomerase. Exogenously administrable, synthetic ribozymes may have important uses in further understanding the role and regulation of this ribonucleoprotein in normal and diseased tissues as well as in the potential therapy of telomerase-positive tumors.

Base Sequence↗
PubMed1998

Development of a sustained-release biodegradable polymer delivery system for site-specific delivery of oligonucleotides: characterization of P(LA-GA) copolymer microspheres in vitro.

Development of a Sustained-Release Biodegradable Polymer Delivery System for Site-Specific Delivery of Oligonucleotides: Characterization of P(LA-GA) Copolymer Microspheres In Vitro Antisense oligodeoxynucleotides (ODNs) can selectively inhibit individual gene expression provided they gain access to and remain stable at the target site for a sufficient period of time. Biodegradable sustained-release delivery systems may facilitate site-specific delivery and also prevent degradation of ODNs by nucleases whilst delivering the nucleic acid in a controlled manner to the desired site of action. In this study, we have characterized biodegradable poly (lactide-co-glycolide) (P(LA-GA)) 50:50 microspheres for the potential delivery of antisense oligonucleotides in vivo. Phosphodiester (PO) oligonucleotides complementary to either c-myc proto-oncogene or the tat gene in HIV-RNA were adequately incorporated within P(LA-GA) microspheres with entrapment efficiencies up to 60% depending on particles size. In vitro release profiles of antisense nucleic acids from 10-20 microm size microspheres over 56 days in physiological buffer were triphasic. Profiles were characterised by an initial burst effect during the first 48 hours (phase 1) of release followed by a more sustained release (phase 2) with an additional increased release (phase 3) being observed after 25 days which corresponded with bulk degradation of the copolymer matrix. The release profiles were influenced by microsphere size, copolymer molecular weight, ODN loading, ODN length and by the pH of release medium used. The serum stability of PO ODNs was significantly improved when entrapped within P(LA-GA) microspheres and the hybridization capability, as assessed by duplex melting (Tm) measurements, of released ODN was not impaired by the double-emulsion microsphere fabrication procedure used. Thus, P(LA-GA) microspheres appear to be promising candidates for improving site-specific delivery profiles for ODNs and are worthy of further evaluation in vivo.

Base Sequence↗
PubMed1998

Viscosity studies on Mestranol.

The viscosity of 1x10(-4) M to 4x10(-4) M solution of Mestranol (synthetic oestrogenic steroidal hormone) in ethanol was measured at 32 degrees, 40 degrees and 50 degrees C in a viscometric bath. The viscosity rates are maximum at 30 degrees C as compared to 40 degrees and 50 degrees C. The disappearance rate of Mestranol at higher temperature and lower viscosity is due to triplet state of species transitions at higher thermal conditions.

Journal Article↗
PubMed1998

From simplicity through contradiction to paradox. The evolving psychic reality of the borderline patient in treatment.

The thesis of this paper is two-fold. First, it proposes that the psychic reality of the borderline patient evolves in a three-step process during the analytic treatment. These steps include: (i) experiencing and presenting disparate psychic states without the awareness of inherent contradictions, (ii) observing, acknowledging, and mending the splits responsible for these contradictions, and (iii) developing a capacity for feeling and accepting paradox, i.e. coexistence of multiple meanings at different levels of abstraction. Second, the author suggests that this three-step movement vis-à-vis the associative material takes place first within the analyst's reverie and then in the patient's psychic reality. The analyst's holding, unmasking, bridging and depth-rendering interventions (and the vicissitudes of identification) make the patient's advance possible. The author presents two clinical vignettes, highlighting these hypotheses and their technical implications. A vignette from the non-clinical realm of a mother's interaction with her children is also included in the hope of demonstrating a developmental 'Anlage' of the analyst's interventions outlined above. The paper concludes with the observation that the practising analyst also needs to traverse a 'simplicity-contradiction-paradox' sequence in his view of the divergent theoretical approaches to the analytic understanding and treatment of severe character pathology.

Borderline Personality Disorder↗
PubMed1997

Interaction of oligonucleotide-conjugates with the dipeptide transporter system in Caco-2 cells.

Oligonucleotide-based therapies represent novel strategies for manipulating the expression and function of target proteins and are undergoing clinical evaluation for the treatment of viral diseases and malignancies. However, poor biological stability and cellular delivery represent potential limitations to the therapeutic development of oligonucleotides. Conjugation of oligonucleotides to lipophilic groups can improve delivery to cells but the enhanced cellular binding may also facilitate nonspecific interactions. In this report, we show that phosphorothioate oligonucleotides conjugated to lipophilic groups, either tocopherol (Vitamin E) or 2-Di-O-hexadecyl-3-glycerol, can significantly inhibit the functioning of the dipeptide transporter system (DTS) in cultured Caco-2 intestinal cells. Because the DTS mediates the binding and absorption of nutrient peptides and important drugs, such as the cephalosporin and penicillin antibiotics, this finding has important implications in relation to the potential toxicity of lipophilic conjugates in vivo. It also suggests a potential drug interaction with lipophilic oligonucleotide-conjugates if they were to be delivered orally.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Modification of rat brain Kv1.4 channel gating by association with accessory Kvbeta1.1 and beta2.1 subunits.

We have examined the effects of co-expression of Kvbeta1.1 and Kvbeta2.1 subunits on the gating of rat brain Kv1.4 channels, expressed in Xenopus oocytes. Expression of Kv1.4 subunits alone produced a rapidly inactivating "A" type current, which activated at potentials beyond -60 mV in a solution containing high levels of rubidium. Current activation curves obtained from tail current measurements were fitted with a Boltzmann function, with V1/2 = -47 mV and k = 10 mV. Neither the Kvbeta1.1 nor Kvbeta2.1 subunits altered the voltage dependence of activation. Both subunits accelerated the activation time constant of Kv1.4, without affecting its voltage dependence. Surprisingly, the Kvbeta2.1 subunit, which lacks an N-terminal inactivation domain, was almost as effective as the Kvbeta1.1 subunit in speeding up Kv1.4. Steady-state inactivation of Kv1.4 was unchanged upon co-expression with either Kvbeta1.1 or Kvbeta2.1 subunits. Kv1.4 recovered from inactivation with two time constants; apart from an approximately 50% lengthening of the slow time constant with a high Kvbeta2.1 injection ratio, neither time constant was altered by either the Kvbeta1.1 or Kvbeta2.1 subunits, suggesting little interaction with recovery from C-type inactivation. Clearly, beta subunits have the potential to modify the gating of Kv1.4 channels in the brain more subtly than has been suggested previously.

Animals↗
PubMed1997

Bluetongue virus seropositivity in sheep flocks in North West Frontier Province, Pakistan.

The objectives of this study were to describe the prevalence and distribution of serum antibodies to Bluetongue virus (BTV) in a sample of 38 sheep flocks in northern areas of the North West Frontier Province of Pakistan and to identify demographic and productivity variables that are associated with BTV seropositivity. Blood samples were taken from a random sample of ewes in each flock in April 1995. The owners of the flocks were interviewed regarding some demographic, husbandry and productivity variables of the flocks on the day of blood sampling. A competitive enzyme-linked immunosorbent assay was conducted to test the serum samples for BTV group-specific antibodies. BTV seropositive reactions were obtained in 184 (48.4%) out of 380 tested sera, and in 89.5% (34/38) of the flocks. In the 34 seropositive flocks, the prevalences ranged from 12.5 to 100% (median = 47). A multivariable logistic analysis was carried out to study the influence of demographic and productivity variables on the BTV serological status of the sheep flocks. Abortion risk in the previous lambing season was mildly associated with the serological status of the flock (adjusted odds ratio = 1.16, P = 0.07). For the seropositive flocks, a linear multiple regression showed that distance travelled by the flock during transhuman movement was significantly associated with percent seropositivity (partial regression coefficient (+/- SE) = -0.091 +/- 0.045).

Abortion, Veterinary↗
PubMed1997

A sero-epidemiological study of Haemophilus somnus infection in dairy cattle.

Five repeated cross-sectional serological surveys of 790 dairy cattle in 4 dairy herds between December 1985 and February 1987 provided an opportunity to study the changes in the seroprevalence of Haemophilus somnus across the 5 surveys and with respect to some demographic and disease variables. The demographic variables included were age (heifers or cows) and farm, representing two groups of herds (two herds in each group, located in the Central and Northern Valleys of California). The serological status of cattle as either negative or positive against H. somnus, Campylobacter fetus and Leptospira hardjo were determined with enzyme linked-immunosorbent assays. Logistic regression analysis was used to compute maximum likelihood estimates of adjusted odds ratios and their respective 95% confidence intervals. The baseline risk of being H. somnus seropositive in the cattle observed at first sampling did not vary significantly during the study period after adjustment for the effects of covariates. Only at first sampling were cows about twice as likely to be H. somnus seropositive than heifers. At samplings 1 and 3, but not at 2 and 5, being in the herds of the Central Valley appeared protective. In contrast, at sampling 4 the cattle in herds in the Central Valley were about 7 times more likely to be H. somnus seropositive. C. fetus-positive cattle were about 3 times more likely to be H. somnus seropositive at sampling 1 only. The relationship between H. somnus status and L. hardjo was not significant during the study period.

Animals↗
PubMed1997

Cellular uptake properties of a 2'-amino/2'-O-methyl-modified chimeric hammerhead ribozyme targeted to the epidermal growth factor receptor mRNA.

Catalytic RNA or ribozymes have important potential applications as molecular biological tools in the study of gene expression and as therapeutic inhibitors of disease-causing genes. Very little is known, however, about the cellular uptake mechanisms of exogenously delivered synthetic ribozymes. In this study, we have characterized the uptake properties of a synthetic, 2'-O-methyl-modified ribozyme containing U4/U7 amino groups within the catalytic core of the hammerhead motif. The cellular uptake of the internally [32P]-radiolabeled hammerhead ribozyme in U87-MG glioma cells was temperature, energy, and pH dependent and involved an active process that could be competed with cold ribozyme of the same chemistry and sequence, an all 2'-O-methyl-modified ribozyme of the same sequence, antisense PS-ODNs, and a variety of other polyanions (salmon sperm DNA, spermidine, dextran sulfate, and heparin). Subcellular distribution studies of fluorescently labeled ribozymes confirmed an extranuclear, punctate localization similar to that observed for an endosomal marker, dextran. Our study highlights that hammerhead ribozymes, despite exhibiting a defined secondary structure, enter cells by an endocytic mechanism that appears to be similar to that reported for a variety of antisense ODNs. These observations should facilitate the development of more efficient delivery systems.

Base Sequence↗
PubMed1997

Sero-epidemiological studies on Toxoplasma gondii infection in man and animals in Bangladesh.

Sera from randomly selected 49 professional blood donors, 617 pregnant women, 14 butchers, 528 slaughtered goats and 24 domestic cats in the district of Mymensingh were tested for the presence of T. gondii antibodies using a Latex agglutination test (LAT). Overall 12.4% blood donors, 11.18% pregnant women, 50.00% butchers, 12.88% slaughtered goats and 33.33% cats had diagnostically significant antibody titers (> or = 1:64) to T. gondii. Epidemiological studies on T. gondii infection with LAT were conducted in 25 family members with sero-positive cats and 9 family members with 2 sero-positive women without cats in the family. Significantly (p < 0.01) higher sero-positivity rate was recorded in the family members (24.00%) with positive cats in comparison to family members (11.11%) without cats. The epidemiologic study indicates that infected cats and goat meat might be significant sources of T. gondii infection for humans in Bangladesh.

Animals↗
PubMed1996

Direct inhibitory effects of an antisense oligodeoxynucleotide upon the volume-sensitive chloride current in rat osteoblast-like (ROS 17/2.8) cells.

The effects of a 15-mer antisense c-myc phosphorothioate modified oligodeoxynucleotide (OdN) upon the volume-sensitive Cl- current in ROS 17/2.8 cells were investigated using the whole-cell configuration of the patch clamp technique. At 5 microM, the OdN reversibly inhibited the current in a voltage- and time-dependent fashion. This was evident from the reduction in the peak current as assessed at the termination of each voltage pulse and an acceleration of the time-dependent inactivation present at strongly depolarised potentials. The kinetic modifications induced by the OdN suggest it may act by blocking the pore of open channels when the cell membrane potential is depolarised.

Animals↗
PubMed1996

Epidemiologic association between antibody titres against bovine virus diarrhoea virus, rinderpest disease virus and infectious bovine rhinotracheitis virus in a buffalo herd.

The association between antibody titres against bovine virus diarrhoea virus (BVDV), infectious bovine rhinotracheitis virus (IBRV) and rinderpest disease virus (RPDV) in buffaloes was investigated in a cross-sectional study. Thirty-six lactating buffaloes from a herd in Landhi Cattle Colony, Karachi were bled and serum samples subjected to a micro-neutralisation test at the Plum Island Animal Disease Center, USA, to categorise each buffalo either as positive or negative against each of 3 viral antigens. Log-linear analysis was used to evaluate the association among 3 categorical variables. The "best-fitting" log-linear model was the model of complete independence. This model includes all 3 main effects (BVDV, IBRV, RPDV), suggesting that the seropositivity of buffaloes against these viral antigens tended to occur independently. Estimates of parameters of the model showed that the proportion of buffaloes seropositive (97.2%) to RPDV antigen tended to be higher than expected, whereas the proportion of BVDV seropositive (30.6%) and IBRV seropositive (16.7%) buffaloes tended to be smaller than expected.

Animals↗