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Biomedical subjects

S Akhtar

Publications and source records attributed to S Akhtar.

At least 19 recordsLinked to original sources

Risk factors associated with hydropericardium syndrome in broiler flocks.

A prospective study was undertaken to identify the epidemiological factors associated with the development and spread of the hydropericardium syndrome in broiler flocks. Data were collected between July 1989 and April 1990 from 131 flocks in 105 broiler production units pertaining to their demography, management practices, prophylactic procedures and concurrent diseases. The incidence rate of the syndrome in the whole population was 46.6 per cent. There were significant associations between the incidence in a flock and visits by a poultry vaccination crew (P = 0.014), the number of flocks raised (P = 0.004) and the source of light and heat (P = 0.007). Flocks that had one or more visits by a poultry crew were 15 times more likely to be affected by the syndrome than flocks that had no such visits. Premises where one flock was raised were nearly three times more likely to be affected than premises where two flocks were raised, and the use of electricity as a source of light and heat entailed a much lower risk of hydropericardium syndrome than kerosene oil.

Animals

In situ cell cycle kinetics in bone marrow biopsies following sequential infusions of IUdR/BrdU in patients with hematopoietic malignancies.

Examination of the proliferative characteristics of myeloblasts was undertaken in situ in bone marrow (BM) biopsies of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) following sequential infusions of iodo- (IUdR) and bromodeoxyuridine (BrdU). The ability to identify S-phase cells which have incorporated both or either one of the labels in vivo by using two monoclonal antibodies in vitro permitted the measurement of labeling index (LI) and durations of S-phase (Ts) and the total cell cycle (Tc) both from the BM aspirates and biopsies. While the LI is 2-3 times higher in biopsies, Ts and Tc are fairly comparable in the two samples in 8/10 cases (p = 0.02 and 0.003 respectively). Advantages associated with the determination of cell cycle parameters in BM biopsies have been discussed at length.

Biopsy

Liposomes as a drug delivery system for antisense oligonucleotides.

Antisense oligonucleotides seem to provide a promising new tool for the therapy of viral diseases and of cancer. However, before the therapeutic potential of antisense compounds can be fulfilled, it will be necessary to overcome significant problems relating to their inefficient uptake by cells and their rapid loss from the body. Phospholipid vesicles (liposomes) have been widely used as a drug delivery system for standard anticancer and anti-infectious drugs. In this article we examine the potential role of liposomes as a drug delivery system for antisense oligonucleotides.

Antineoplastic Agents

Serological evaluation of Pasteurella multocida antigens associated with protection in buffalo calves.

Different antigens of Pasteurella multocida Carter's type 6:B including whole bacterium, antigen heated at 56 degrees C, antigen heated at 100 degrees C, sonicated antigen, capsular antigen, potassium thiocyanate extract, lipopolysaccharide and sodium salicylate extract were evaluated to assess protection in buffalo calves against haemorrhagic septicaemia. Sera from calves with known protection status in experimental challenge were titrated by enzyme-linked immunosorbent assay (ELISA) against all antigens. Capsular antigen extracted with 2.5% sodium chloride was superior to other antigens for assessing protection status of buffalo calves against P. multocida by ELISA. This capsular antigen was able to differentiate clearly between well-protected, protected and unprotected animals.

Animals

Mechanism of cellular uptake of modified oligodeoxynucleotides containing methylphosphonate linkages.

The cellular uptake and intracellular distribution of methylphosphonate oligonucleotides (15 mers) has been examined using both 32P labeled and fluorescent labeled oligonucleotides. The cellular uptake process for methylphosphonate oligonucleotides is highly temperature dependent, with a major increase in uptake occurring between 15 and 20 degrees C. Most of the label which becomes cell associated at 37 degrees C cannot be removed by acid washing or trypsinization and thus seems to be within the cell. Visualization of rhodamine labeled methylphosphonate oligonucleotides using digital imaging fluorescence microscopy reveals a vesicular subcellular distribution suggestive of an endosomal localization. There was extensive co-localization of rhodamine labeled methylphosphonate oligonucleotides with fluorescein-dextran, an endosomal/lysosomal marker substance. The apparent endocytotic uptake of labeled methylphosphonate oligonucleotides could not be blocked by competition with unlabeled methylphosphonate or phosphodiester oligonucleotides, nor by ATP. This contrasts with the situation for radiolabeled phosphodiester oligonucleotides whose uptake can be completely blocked with unlabeled competitor. Uptake of phosphodiester oligonucleotides, but not of methylphosphonate oligonucleotides, could be blocked by acidification of the cytosol. These observations suggest that the pathway of cellular uptake of methylphosphonate oligonucleotides involves fluid phase or adsorbtive endocytosis, and is distinct from the uptake pathway for phosphodiester oligonucleotides.

Animals

Interactions of antisense DNA oligonucleotide analogs with phospholipid membranes (liposomes).

Antisense oligonucleotides have the ability to inhibit individual gene expression in the potential treatment of cancer and viral diseases. However, the mechanism by which many oligonucleotide analogs enter cells to exert the desired effects is unknown. In this study, we have used phospholipid model membranes (liposomes) to examine further the mechanisms by which oligonucleotide analogs cross biological membranes. Permeation characteristics of 32P or fluorescent labelled methylphosphonate (MP-oligo), phosphorothioate (S-oligo), alternating methylphosphonate-phosphodiester (Alt-MP) and unmodified phosphodiester (D-oligo) oligodeoxynucleotides were studied using liposomal membranes. Efflux rates (t1/2 values) at 37 degrees C for oligonucleotides entrapped within liposomes ranged from 7-10 days for D-, S- and Alt-MP-oligos to about 4 days for MP-oligos. This suggests that cellular uptake of oligonucleotides by passive diffusion may be an unlikely mechanism, even for the more hydrophobic MP-oligos, as biological effects are observed over much shorter time periods. We also present data that suggest oligonucleotides are unlikely to traverse phospholipid bilayers by membrane destabilization. We show further that MP-oligos exhibit saturable binding (adsorption) to liposomal membranes with a dissociation constant (Kd) of around 20nM. Binding appears to be a simple interaction in which one molecule of oligonucleotide attaches to a single lipid site. In addition, we present water-octanol partition coefficient data which shows that uncharged 12-15 mer MP-oligos are 20-40 times more soluble in water than octanol; the low organic solubility is consistent with the slow permeation of MP-oligos across liposome membranes. These results are thought to have important implications for both the cellular transport and liposomal delivery of modified oligonucleotides.

Base Sequence

Stability of antisense DNA oligodeoxynucleotide analogs in cellular extracts and sera.

Antisense DNA oligodeoxynucleotides can selectively inhibit the expression of individual (undesirable) genes and thus, have potential in the treatment of cancer and viral diseases. A prerequisite to their use as therapeutic agents is information on the stability of oligodeoxynucleotides, and their structurally modified analogs, in the biological milieu. To this end, degradation of 5' end and internally [32P] labelled unmodified DNA oligodeoxynucleotide (D-oligo) and analogs containing phosphorothioate (S-oligo), methylphosphonate (MP-oligo), and novel alternating methylphosphonate and phosphodiester (Alt-MP-oligo) internucleoside linkages was studied in Hela cell nuclear extract, S100 cytoplasmic extract, normal human serum and calf serum at 37 degrees C. Both 5' end and internally labelled D-oligos showed complete degradation within 30 min incubation in human serum at 37 degrees C. In any given medium, the D-oligo was the least stable oligodeoxynucleotide to nuclease degradation whereas the Alt-MP, MP and S-oligos were generally of comparable stability and all relatively more stable than D-oligo. Interestingly, MP and Alt-MP-oligos also exhibited greater resistance to phosphatases in cellular extracts compared to D and S-oligos. Under the conditions of the experiments, increasing degradation for any given oligonucleotide was observed in the order: S100 cytoplasmic extract less than nuclear extract less than normal human serum less than calf serum. In a study involving alpha-MEM cell culture medium containing 10% heat inactivated fetal calf serum (heated to 56 degrees C for 1 hour), the D-oligo was found to be rapidly degraded (degradation evident within 10 mins) whereas degradation products for the S-oligo were observed within 1 hour. In contrast, the Alt-MP oligo remained stable throughout the 3 hour experiment. These results indicated that in cell culture medium containing heat inactivated serum Alt-MP oligo was more stable than D- and S-oligos.

Animals

XPS and SSIMS analysis of the surface chemical structure of poly(caprolactone) and poly(beta-hydroxybutyrate-beta-hydroxyvalerate) copolymers.

The surface chemical structures of poly(beta-hydroxybutyrate), poly(caprolactone) and poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) have been analysed using static secondary ion mass spectrometry and X-ray photoelectron spectroscopy. The X-ray photoelectron spectroscopy data confirm the purity of the polyester surfaces and there is close agreement between the stoichiometric and experimentally determined ratios of the peaks and different carbon environments within the C1s envelopes. The static secondary ion mass spectrometry analysis reveals general fragmentation pathways which permit the ready distinction between the different polyesters examined. The differentiation of the different monomer repeat units in the copolymer together with the detection of some ions representative of the random copolymer sequence are also possible in the static secondary ion mass spectrometry analysis.

Biocompatible Materials

Paranoid personality disorder: a synthesis of developmental, dynamic, and descriptive features.

Suspiciousness, feeling persecuted, and grandiosity constitute the classical triad associated with paranoid personality. However, a more important feature appears to be the discrepancy between the outer persona and the inner world of such individuals. The split is pervasive and involves self-concept, object-relations, affects, morality, sexuality, and cognitive style. Outwardly, paranoid individuals are demanding, arrogant, mistrustful, driven, unromantic, moralistic, and acutely vigilant towards the external environment. Internally, however, they are frightened, timid, self-doubting, gullible, inconsiderate, vulnerable to erotomania, and cognitively unable to grasp the totality of actual events. This way of conceptualizing the paranoid symptomatology is superior to ordinary check-list methods since it (1) links the phenomenological and psychostructural aspects of the condition, (2) helps in a more meaningful differential diagnosis of paranoid from other personality disorders, and most importantly, (3) hints at areas that require exploration in the psychotherapeutic management or psychoanalysis of such individuals.

Diagnosis, Differential

The literature on personality disorders, 1985-88: trends, issues, and controversies.

This review of the recent literature on personality disorders summarizes theoretical and methodologic issues, DSM-III-R criteria sets, nosological controversies, and current treatment approaches. Work in the personality disorders is burgeoning, with increasing attention to improved reliability and validity of diagnosis. Investigators are looking at such issues as the development of dimensional taxonomies, the effect of state variables, the problem of diagnostic overlap, the effect of comorbid conditions on course and treatment, the predictive power of criteria, and external validators. The DSM-III-R criteria sets, despite their polythetic format, may be no more reliable than their predecessors. Because treatment remains largely unresearched, the clinician must continue to rely on skillful assessment of each patient, with psychoanalytic psychotherapy and symptom-oriented drug trials providing the foundation of therapy.

Humans

Asneezia.

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Humans

Effect of reactor retention on the spread of brucellosis in Jersey cattle and buffalo herds.

The rate of spread of bovine brucellosis was investigated in buffalo and Jersey cattle herds maintained at a Livestock Research station in Pakistan. Reactor animals (identified by conventional serological tests) were either retained or culled because of advanced age or poor productivity. Reactors were housed, managed and fed separately from the rest of the herds. The initial seroprevalence of brucellosis among both the Jersey cattle and the buffalo tested was 21.4%, the difference being statistically insignificant (p = 0.218). For 34 months, the spread of brucellosis was limited to 25 new reactors in the 334 cows and 33 in the 442 buffaloes. The mean attack rate was 7.5% for both herds during the test intervals. Trend analysis of proportions positive at each testing revealed a significant decrease in the percentages observed at the first testing. The management practice of segregation offered some advantage in reducing the spread of brucellosis to negative animals. However, an epidemiological study covering a large number of herds would be required to identify risk factors responsible for perpetuating the disease.

Animals

Narcissistic personality disorder. Descriptive features and differential diagnosis.

This article brings the scattered literature on narcissistic personality disorder together and synthesizes its various descriptive aspects into a multifaceted profile of the condition. The disorder is viewed as consisting of characteristic "overt" and "covert" findings in six areas of psychosocial functioning: (1) self-concept; (2) interpersonal relations; (3) social adaptation; (4) ethics, standards and ideals; (5) love and sexuality; and (6) cognitive style. Overtly, and individual with narcissistic personality disorder is grandiose, exploitative, moralistic, often successful, seductive, charming, and impressively knowledgeable and articulate. Covertly, however, he is doubt ridden, deeply envious of others, chronically bored, corruptible, unable to love, forgetful of details, and inattentive to objective aspects of events. Such conceptualization is superior to ordinary checklist methods of diagnosis, as it combines descriptive and psychodynamic observations and correlates the behavioral and psychostructural (hence developmental) aspects of the narcissistic character pathology. This profile also helps in more meaningful differential diagnosis of narcissistic from related personality disorders.

Diagnosis, Differential

Four culture-bound psychiatric syndromes in India.

This paper describes four culture-bound psychiatric syndromes seen in India. It highlights their phenomenology and briefly comments upon the socio-cultural correlates of such symptom constellations.

Adult

The developmental context of internalized preoedipal object relations. Clinical applications of Mahler's theory of symbiosis and separation-individuation.

Mahler's theory of symbiosis and separation-individuation demonstrates the essential unity of drive, ego, and object relations psychologies. By highlighting the role that early dyadic relations play in psychic structure formation, her theory expands the understanding of human psychic development and its failures. This paper reviews Mahler's propositions and underscores their clinical importance by describing two cases where much preoedipal reconstructive work preceded the emergence of an analyzable oedipal transference neurosis.

Adult

Schizoid personality disorder: a synthesis of developmental, dynamic, and descriptive features.

Various views of schizoid personality disorder in descriptive psychiatry, psychoanalysis, DSM-III and DSM-III-R are reviewed and synthesized to develop a composite picture of the syndrome. The disorder is seen as consisting of characteristic deficits in six areas of psychosocial functioning: (1) self-concept, (2) interpersonal relations, (3) social adaptation, (4) ethics, standards and ideals, (5) love and sexuality, and (6) cognitive style. Such a view maintains historical continuity in the use of the term "schizoid," combines descriptive and psychodynamic observations and correlates the behavioral and psychostructural aspects of the schizoid pathology. The paper also identifies guidelines for distinguishing the schizoid personality from other personality disorders as well as areas needing continued research.

Humans