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Biomedical subjects

S Qasim

Publications and source records attributed to S Qasim.

9 recordsLinked to original sources
PubMed2006

Despite having a common P1 Leu, eglin C inhibits alpha-lytic proteinase a million-fold more strongly than does turkey ovomucoid third domain.

Results of the inhibition of alpha-lytic proteinase by two standard mechanism serine proteinase inhibitors, turkey ovomucoid third domain (OMTKY3) and eglin C, and many of their variants are presented. Despite similarities, including an identical P1 residue (Leu) in their primary contact regions, OMTKY3 and eglin C have vastly different association equilibrium constants toward alpha-lytic proteinase, with Ka values of 1.8 x 10(3) and 1.2 x 10(9) M(-1), respectively. Although 12 of the 13 serine proteinases tested in our laboratory for inhibition by OMTKY3 and eglin C are more strongly inhibited by the latter, the million-fold difference observed here with alpha-lytic proteinase is the largest we have seen. The million-fold stronger inhibition by eglin C is retained when the Ka values of the P1 Gly, Ala, Ser, and Ile variants of OMTKY3 and eglin C are compared. Despite the small size of the S1 pocket in alpha-lytic proteinase, interscaffolding additivity for OMTKY3 and eglin C holds well for the four P1 residues tested here. To better understand this difference, we measured Ka values for other OMTKY3 variants, including some that had residues elsewhere in their contact region that corresponded to those of eglin C. Assuming intrascaffolding additivity and using the Ka values obtained for OMTKY3 variants, we designed an OMTKY3-based inhibitor of alpha-lytic proteinase that was predicted to inhibit 10,000-fold more strongly than wild-type OMTKY3. This variant (K13A/P14E/L18A/R21T/N36D OMTKY3) was prepared, and its Ka value was measured against alpha-lytic proteinase. The measured Ka value was in excellent agreement with the predicted one (1.1 x 10(7) and 2.0 x 10(7) M(-1), respectively). Computational protein docking results are consistent with the view that the backbone conformation of eglin C is not significantly altered in the complex with alpha-lytic proteinase. They also show that the strong binding for eglin C correlates well with more favorable atomic contact energy and desolvation energy contributions as compared to OMTKY3.

Amino Acid Sequence↗
PubMed2001

Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases.

An additivity-based sequence to reactivity algorithm for the interaction of members of the Kazal family of protein inhibitors with six selected serine proteinases is described. Ten consensus variable contact positions in the inhibitor were identified, and the 19 possible variants at each of these positions were expressed. The free energies of interaction of these variants and the wild type were measured. For an additive system, this data set allows for the calculation of all possible sequences, subject to some restrictions. The algorithm was extensively tested. It is exceptionally fast so that all possible sequences can be predicted. The strongest, the most specific possible, and the least specific inhibitors were designed, and an evolutionary problem was solved.

Algorithms↗
PubMed2000

Surgery and community participation in a community-based programme in war situations.

The paper presents the results and the experience gained from three 'mass surgical interventions' conducted in the Alpha Civil Hospital, Billing in south Sudan in the period between October 1996 and November 1997. The results showed that surgical services can be provided safely and economically even under most difficult conditions provided professional experience plus community commitment and participation are there. Such interventions lead to the development of strong community self-reliance and willingness which are fundamental if the programme is to be sustained.

Community Health Services↗
PubMed1995

Primary squamous cell carcinoma of the endometrium.

All reported cases of primary squamous cell carcinoma of the endometrium and the effectiveness of the different treatment modalities in the world literature are reviewed. We present the first reported case of primary squamous cell carcinoma of the endometrium treated by radical hysterectomy, pelvic and para-aortic lymphadenectomy. The patient is without signs of disease 4 years after surgery. This is the longest follow-up of all reported cases. There are very few cases from which is to conclusively predict the best mode of therapy. The current standard of treatment is total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without pelvic and para-aortic lymph node sampling, depending on the histology and depth of the myometrial invasion. Adjuvant therapy includes radiation therapy according to the extent of disease.

Carcinoma, Squamous Cell↗
PubMed1995

Identification of hormonal parameters for successful systemic single-dose methotrexate therapy in ectopic pregnancy.

Single-dose methotrexate is an alternative to surgery in treating ectopic pregnancy. Because success rates vary, we sought to identify factors which predict treatment outcome. A total of 44 women with ectopic gestation were treated. The non-laparoscopic diagnosis of ectopic pregnancy was made following history, physical examination, ultrasound, endometrial biopsy and the measurement of serial beta-human chorionic gonadotrophin (HCG) and progesterone concentrations. Methotrexate (50 mg/m2 i.m.) was administered, with a second dose given 1 week later in patients with plateauing or rising beta-HCG concentrations. Of 44 patients, 23 (52.3%) were successfully treated with one dose. An additional 10 women (22.7%) were also successfully managed but required a second dose, giving an overall success rate of 75.0%. In all, 11 women (25.0%) required surgery, four of whom experienced tubal rupture. Receiver operator curves were constructed to optimally select pretreatment beta-HCG and progesterone cut-off concentrations for successful treatment. Using beta-HCG < 1500 IU/l or progesterone < 7.0 ng/ml (22.3 nmol/l) as a cut-off concentration produced a diagnostic test with a sensitivity of 87.5%, a specificity of 90.0%, a positive predictive value of 96.6% and a negative predictive value of 69.2%. Conversely, this model predicts that patients with serum beta-HCG concentrations > or = 1500 IU/l and progesterone concentrations > or = 7.0 ng/ml are at far greater risk of failing single-dose methotrexate therapy.

Adult↗
PubMed1992

Pedigree analysis and involvement of peroxidase in sickle cell disease.

Routine hematological tests were performed in a family which was at risk for sickle cell disease. Cellulose acetate electrophoresis and Triton PAGE were employed to differentiate between various variants of hemoglobin. Based on the data a pedigree was constructed which indicated that few members of the respectively had received the S gene, some of them were sickle cell disease while few were sickle cell trait. Elevated levels of peroxidase enzyme in affected individuals reflect its involvement in RBCs destruction. Statistical analysis strengthen this statement.

Anemia, Sickle Cell↗