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Biomedical subjects

A Hussain

Publications and source records attributed to A Hussain.

At least 181 records · Page 10Linked to original sources
PubMed1989

Differentiation of human variant small cell lung cancer cell lines to a classic morphology by retinoic acid.

Variant small cell lung cancer (SCLC) is distinguished from the classic histology by changes in growth characteristics and morphology, c-myc amplification, a loss of some biochemical markers, and relative chemo- and radioresistance. Three variant SCLC lines were incubated in 1 microM all-trans retinoic acid. After 8-10 days, a marked change in morphology was noted in all three lines, with tight cell aggregation and central necrosis of large floating spheroids similar to classic SCLC. The retinoid-treated cells demonstrated decreases in growth rate and cloning efficiency to levels comparable with classic SCLC cell lines. Retinoic acid incubation caused a reproducible decrease in c-myc expression in variant SCLC cells, but was not noted to increase L-dopa decarboxylase, an enzyme which biochemically distinguishes classic from variant SCLC cell lines. Retinoid exposure led to an increase in HLA and Leu-7 antigens, but a reduction of antibody binding to 3-fucosyllactosamine, a dominant SCLC glycolipid antigen. Clonogenic assays revealed that the variant cells, after incubation in retinoic acid, became more sensitive to etoposide, but more resistant to Adriamycin. We conclude that exposure of variant SCLC cells to retinoic acid can lead to a morphologic phenotype similar to classic SCLC, but with substantial differences in cell biology. ?

Antigens, Neoplasm↗
PubMed1989

Potentiation of interferon induction of class I major histocompatibility complex antigen expression by human tumor necrosis factor in small cell lung cancer cell lines.

The response of class I major histocompatibility complex antigen expression to in vitro administration of interferon and tumor necrosis factor alpha (TNF-alpha) was measured using class I major histocompatibility complex-deficient small cell lung cancer cell lines. Significant induction also was observed using gamma interferon (IFN-gamma) alone, whereas TNF-alpha alone yielded only modest induction. Classic small cell lung cancer cell lines NCI-H146 and NCI-H209 best demonstrated synergistic HLA and beta 2-microglobulin antigen induction with IFN-gamma and TNF-alpha with the following dose schedule: 3-6 days of TNF-alpha (200 units/ml) followed by 48 h of IFN-gamma (100 IU/ml). Induction was quantitated using an 125I-Protein A radioimmunoassay. Synergistic induction of the HLA and beta 2-microglobulin surface antigens on NCI-H146 was also possible with alpha interferon and TNF-alpha but required a higher concentration of the interferon, i.e., 3-6 days of TNF-alpha (200 units/ml) followed by 48 h of alpha interferon (1000 units/ml). Small cell lung cancer cell line NCI-H146 was further studied for expression of major histocompatibility complex messenger RNA using the optimal doses and sequence of addition of IFN-gamma and TNF-alpha as indicated above. A significant induction with IFN-gamma alone and synergistic induction with both IFN-gamma and TNF-alpha was quantitated for both HLA-A2 and beta 2-microglobulin transcripts using Northern blot analysis. Incubation with relatively low subcytotoxic doses of IFN-gamma and TNF-alpha also resulted in a marked synergistic decrease in c-myc message.

Animals↗
PubMed1989

Combined treatment of autoimmune MRL/Mp-lpr/lpr mice with cholera toxin plus irradiation. Combined treatment of autoimmune MRL/l mice.

MRL/Mp-lpr/lpr (MRL/1) mice spontaneously develop autoimmune diseases like systemic lupus erythematosus (SLE) from 2 months of age, accompanied by massive lymphadenopathy. Such mice of 2 months of age were treated with 1 microgram cholera toxin (CT) every 7 days and/or with 400 rad of one-shot 60Co irradiation. CT treatment alone markedly improved nephritis as evaluated by proteinuria and moderately suppressed lymphadenopathy and anti-DNA antibody production, while irradiation alone prominently improved lymphadenopathy but showed little effect on both nephritis and anti-DNA antibody production. On the other hand, when mice were treated with the combination of CT plus irradiation, autoimmune nephritis as well as anti-DNA production and lymphadenopathy were almost completely inhibited. Taken together, each agent exerts the improvement effect at the different points from each other in an abnormal immunological circuit displayed in MRL/1 mice. This kind of combined treatment may be applicable to the clinical use for autoimmune diseases.

Animals↗
PubMed1989

Nasal absorption of 17 alpha-ethinyloestradiol in the rat.

The bioavailability of 17 alpha-ethinyloestradiol was determined after intravenous, nasal, and intraduodenal, administration in the rat. The results showed that the bioavailability of nasally-administered and intraduodenally-administered drug was 80-85, and 15-25%, respectively, of that following intravenous administration. The study demonstrates that the nasal route for the administration of 17 alpha-ethinyloestradiol is superior to the oral route in this species, and may thus provide an alternative for the administration of this drug at lower doses.

Absorption↗
PubMed1989

Immunomodulatory effects of cholera toxin in mice.

Immunomodulatory effects of cholera toxin (CT) were investigated in a murine model using various immunological parameters. C3H/HeN mice were injected with 2 micrograms of CT at various intervals (from 6 h to 21 days) before the immunological assays. Thymocytes were markedly decreased in their absolute number, and the phenotypes in such cells were clearly shifted from Thy1.2high+ PNAhigh+ to Thy1.2low+ PNAlow+ 2-4 days after the CT treatment. Spleen T cells were relatively increased, while surface IgM positive B cells were rather decreased. Natural killer activity and in vivo and in vitro cytotoxic T lymphocyte activity were markedly suppressed during the early stages after the CT treatment but recovered completely within 21 days. Mixed lymphocyte reaction was profoundly suppressed at least for the 1st week after the CT treatment. Furthermore, EL-4 tumor of C57BL/6 origin grew progressively and killed the recipient C3H mice when such tumor cells were inoculated 6 h after the CT treatment. On the contrary, a marked augmentation of direct (IgM) and indirect (IgG) plaque-forming cell responses to sheep red blood cells was seen after CT treatment. Delayed footpad reaction to SRBC was also augmented after CT treatment. As the mechanisms, both direct augmentation of CD4+ T cells and direct suppression of CD8+ T cells appeared to occur at a time due to the CT treatment. An indirect effect of CT through the release of the endogenous steroids was dismissed in the present study. Taken together, CT appears to have differential immunomodulatory effects on various immune effector cells through various mechanisms.

Animals↗
PubMed1988

Cloning and characterization of a gene from Rhizobium melilotii 2011 coding for ribosomal protein S1.

A 7 kb chromosomal DNA fragment from R. melilotii was cloned, which complemented temperature-sensitivity of an E. coli amber mutant in rpsA, the gene for ribosomal protein S1 (ES1). From complementation and maxicell analysis a 58 kd protein was identified as the homolog of protein S1 (RS1). DNA sequence analysis of the R. melilotii rpsA gene identified a protein of 568 amino acids, which showed 47% identical amino acid homology to protein S1 from E. coli. The RS1 protein lacked the two Cys residues which had been reported to play an important role for the function of ES1. Two repeats containing Shine-Dalgarno sequences were identified upstream of the structural gene. Binding studies with RNA polymerase from E. coli and Pseudomonas putida located one RNA-polymerase binding site close to the RS1 gene and another one several hundred basepairs upstream. One possible promoter was also identified by DNA sequence comparison with the corresponding E. coli promoter.

Amino Acid Sequence↗
PubMed1988

Pulmonary infection with Nocardia caviae in a patient with diabetes mellitus and liver cirrhosis.

The first reported case of pulmonary infection with Nocardia caviae in Britain occurred in a 67 year old woman, in whom diabetes mellitus and liver cirrhosis probably contributed to impaired cell mediated immunity. She was successfully treated with gentamicin 60 mg eight hourly and sulphadimidine 500 mg six hourly for six months and then with sulphadimidine 2 g/day for a further three months. When Nocardia caviae is isolated from the sputum of a patient with chronic respiratory infection and fever, effective treatment should be started promptly.

Aged↗
PubMed1986

The cloning and nucleotide sequence of cDNA for an amplified glutamine synthetase gene from the Chinese hamster.

The nucleotide sequence for a glutamine synthetase (GS) mRNA from gene-amplified Chinese hamster (CHO) cells was determined from recombinant cDNA clones obtained from both pBR322 and lambda gt10 libraries and by primer extension. The sequence obtained contains about 1400 bp corresponding to a minor species of mRNA terminated by a poly A sequence. The mRNA contains 146 nucleotides of 5'-noncoding region, 1119 bp of coding sequence, and 108 bp of 3'-noncoding sequence with a 32 bp poly(A) tail. The polyadenylation site used shows little homology with efficient polyadenylation sites, but has considerable complementarity with U4 RNA. The predicted amino acid sequence, starting from an initiation codon with the preferred sequence surrounding it, indicates that Chinese hamster GS has high homology with published bovine brain GS peptides and enabled an ordering of these peptides. There is homology between the mammalian GS enzymes and glutamine synthetases obtained from plants and cyanobacteria but no obvious homology between the CHO cell GS sequence and that of other ATP hydrolysing enzymes.

Animals↗
PubMed1986

Within-breath changes of airway calibre in patients with airflow obstruction by continuous measurement of respiratory impedance.

We bench-tested a commercially available instrument for measuring respiratory impedance (Siregnost FD5: Siemens) and found that resistance (R) and phase changes were accurately recorded in models. In a single human subject, total respiratory resistance (R(l)) was closely comparable to resistance measured by the Mead-Whittenberger technique. The derived continuous variable (R(os)) was similar to R at less than 4 cmH2O . litres-1 . sec, but underestimated R at higher values. Ros was highly correlated with airways resistance by body plethysmography (R(aw)), but with a low slope and high intercept (R(os) = 1.38 + 0.59 R(aw): r = 0.89). Because of turbulence, both in model larynxes and in normal subjects, R(os) tends to rise with increases in flow in either direction. R(os) also tends to fall as lung volume rises, and vice versa, reflecting cyclic changes in airway calibre. We devised indices of expiratory narrowing of airways from the maximum flow-volume loop, and the plethysmographic alveolar pressure-flow loop, and compared them with the slope of the relation between R(os) and lung volume during tidal breathing, in nine normal subjects and 16 patients with airflow obstruction. Twelve of the 16 patients, all with abnormal flow-volume loops, had high R(os)-volume slopes, demonstrating excessive expiratory narrowing even during tidal breathing. We found no patients with normal inspiratory R(os) together with an abnormal R(os)-volume slope. Thus unstressed inspiratory calibre was never dissociated from airways narrowing on expiration.

Adult↗
PubMed1985

Hydrolysis of leucine enkephalin in the nasal cavity of the rat--a possible factor in the low bioavailability of nasally administered peptides.

In order to investigate the utility of intranasal administration of peptides for systemic medication, the nasal absorption of the model peptide, leucine enkephalin (Tyr-Gly-Gly-Phe-Leu), was studied in the rat. At a concentration of 60 micrograms/ml in Ringer's buffer the pentapeptide was found to undergo, extensive hydrolysis in the nasal cavity. The hydrolysis rather than the polarity of the pentapeptide appears responsible for limiting the nasal absorption of this model compound. In the presence of dipeptides, the hydrolysis of leucine enkephalin was significantly inhibited. These results suggest that the nasal administration of peptides may become an important route for drug administration provided that the peptidases in the nasal mucosa can be transiently inhibited via coadministration of pharmacologically inactive peptidase substrates.

Absorption↗
PubMed1985

Mechanism of nasal absorption of drugs I: Physicochemical parameters influencing the rate of in situ nasal absorption of drugs in rats.

The effect of rate of perfusion, volume, pH of the perfusate, and partition coefficient of the drug on the rate of in situ nasal absorption in rats was examined. The studies showed that the rate constant for the nasal absorption of phenobarbital was independent of the rate of perfusion above a value of 2 mL/min. The nasal absorption of benzoic acid was found to depend on the pH of the perfusate with the benzoate anion being absorbed at a rate one-fourth of that of benzoic acid. The effect of lipid solubility on the extent of nasal absorption was studied using a series of barbiturates. The rate and extent of absorption was found to be dependent on the chloroform-water partition coefficient of the barbiturate. The effect of the volume of the perfusate on the absorption rate constant of phenobarbital, phenol red, tyrosine, and propranolol was studied. The data obtained showed that a linear relationship existed between the rate constants of absorption and the reciprocal of the volume of the perfusate. Using this in situ relationship it was possible to predict in vivo absorption rate constants for propranolol and L-tyrosine when volumes of 0.1 mL were administered. The calculated values for these compounds were found to be close to those determined in in vivo experiments. This indicates that the in situ technique can be used to predict in vivo absorption rate constants.

Absorption↗
PubMed1985

Mechanism of nasal absorption of drugs. II: Absorption of L-tyrosine and the effect of structural modification on its absorption.

The nasal absorption of L-tyrosine and the effect of structural modification on that absorption have been studied using an in-situ experimental technique. The extent of nasal absorption of the amino acid was found to be the same at pH values of 4.0 and 7.4 but dependent on concentration in the range of 2.8 X 10(-4)-2.2 X 10(-3) M. O-Acyl-L-tyrosine esters, although possessing higher octanol-water (pH 7.4) partition coefficients, have the same rate of nasal absorption as the parent amino acid. N-Acetyl-L-tyrosine, on the other hand, was found to have both partition coefficient and nasal absorption rate similar to those of L-tyrosine. Esterification of the carboxyl moiety of L-tyrosine results in derivatives that hydrolyze in the in-situ perfusion medium generating the original amino acid. The rate of nasal absorption of these derivatives was, therefore, determined from an overall disappearance rate which accounted for the rate of hydrolysis to L-tyrosine. These carboxylic esters were absorbed 4 to 10 times faster than L-tyrosine. Although the carboxylic esters of L-tyrosine possess higher octanol-water partition coefficients than the parent amino acid, the differences in the rates of nasal absorption could not be attributed solely to partition coefficient. The enhancement in the rate of absorption observed for these esters was attributed instead to the absence of the negative charge on the carboxylate moiety. It is a result of this negative charge that the rates of nasal absorption of L-tyrosine, O-acyl-L-tyrosine esters and N-acetyl-L-tyrosine are similar, despite significant differences in their partition coefficients.

Absorption↗
PubMed1984

Is there a urodynamic equivalence to anterior urethra in the male?

To evaluate the role of the anterior urethra in the male in micturition dynamics, 9 patients with urethral strictures who were undergoing a two-stage Turner-Warwick urethroplasty were evaluated with flow and pressure flow measurements, pre- and post-second-stage urethroplasty. Any decrease in flow or increase in resistance after closure would suggest an anterior "urethral effect." None was found, indicating that the anterior urethra in the male functions as an inert conduit.

Humans↗
PubMed1984

Antibody and complement-mediated cytotoxicity for bovine parainfluenza-3 virus-infected cells.

An antibody-complement-mediated cytotoxicity assay was employed to determine whether susceptible host cells infected with bovine parainfluenza-3 virus could be destroyed by the humoral immune mechanism. The cytotoxicity assay yielded 21.5% to 76.9% specific release of 51Cr with sera collected from calves 28 days after inoculation with the virus. A multiplicity of infection of 5, a postinfection period of 2 days, an antibody dilution of 1:10, and an incubation period of 12 hours with antibody and complement were found to be optimal for this assay.

Animals↗