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Biomedical subjects

Z Khan

Publications and source records attributed to Z Khan.

At least 109 records · Page 6Linked to original sources

Relative usefulness of physical examination, urodynamics and roentgenography in the diagnosis of urinary stress incontinence.

Stress urinary incontinence is a common problem in women. Accurate diagnosis of this condition is necessary for successful surgical treatment. Currently, many tests are popular. The relative value of these tests, in terms of usefulness, accuracy and practicality, has not been tested in the past. With this aim, we have compared the results from three of the most commonly performed tests, namely physical examination, urodynamics and roentgenography. It is our opinion that physical examination in the standing position is the simplest and most accurate test. Cystometrogram is important, although the yield is small. We do not advise the routine use of urethral pressure profile. For accurate determination of anatomic deformity, roentgenographic examination is the most accurate test.

Adult↗

Evidence for the involvement of DNA topoisomerase II in neutrophil-granulocyte differentiation.

Agents that slow cellular proliferation usually stimulate myeloid differentiation. The demonstration in this report of an anomalous inhibitory behavior of the epipodophyllotoxin VP16-213, an agent known to inhibit the enzyme DNA topoisomerase II, prompted us to investigate the role of this enzyme in both changes in DNA supercoiling and in DNA strand breakage and reunion events occurring during the induction of neutrophil-granulocyte differentiation. We recently reported that retinoic acid, an inducer of granulocytic differentiation, stimulates transient relaxation of DNA supercoiling. We now show that this is associated with the formation of small numbers of protein-linked DNA breaks (a characteristic of topoisomerase reactions). Both events are perturbed by VP16-213, and since this agent inhibits subsequent differentiation, these observations raise the possibility of a role for DNA topoisomerase II in granulocytic differentiation. The possible relevance of these findings to mechanisms of leukemogenesis is discussed.

Cell Differentiation↗

Contrasting patterns of DNA strand breakage and ADP-ribosylation-dependent DNA ligation during granulocyte and monocyte differentiation.

Previous studies have shown that structural changes in DNA, including the ligation of pre-existing DNA breaks and the opening and closure of new breaks, occur shortly after exposure of granulomonocytic precursors (CFU-GM) to granulocyte-macrophage colony stimulating activity (GM-CSA). Monocytic differentiation of CFU-GM is selectively inhibited by compounds known to inhibit the nuclear enzyme ADP-ribosyl transferase (ADPRT). Since this enzyme, which transfers ADP-ribose units to chromatin proteins, is known to activate DNA ligase, we attempted to determine whether ligation of one or both types of DNA break is required for monocytic differentiation. Breaks in DNA were examined using the nucleoid sedimentation technique in which DNA breaks cause loss of DNA supercoiling in nucleoids and concomitant changes in their sedimentation through neutral sucrose gradients. We here report that two distinct patterns of DNA strand breakage and ligation are associated with differentiation to the granulocyte and monocyte lineages. Monocytic inducers (phorbolester and vitamin D3) predominantly produce closure of pre-existing strand breaks, whereas granulocytic inducers (granulocyte colony stimulating activity, G-CSA; retinoic acid) cause opening and closure of new breaks. Only ligation of the pre-existing breaks is highly sensitive to inhibition by 3-methoxybenzamide (a potent ADPRT inhibitor), and only monocytic differentiation is impaired by addition of this compound. These findings suggest that DNA structural changes may be directly involved in granulocyte-macrophage switching.

Adenosine Diphosphate Ribose↗

Essential structural requirements for triggering of mast cells by a synthetic peptide comprising a sequence in the C epsilon 4 domain of human IgE.

A range of synthetic analogues of the peptides Lys-Thr-Lys-Gly-Ser-Gly-Phe-Phe-Val-PheNH2 (human IgE epsilon-chain 497-506 decapeptide) and Lys-Thr-Lys-Gly-Ser-Gly-Phe-PheNH2 (epsilon-chain 497-504 octapeptide) were tested for activity as releasers of 5-hydroxytryptamine from rat peritoneal mast cells. The following structural modifications were found to abrogate activity: N-acetylation of the alpha-amino group of the N-terminal lysine residue; substitution of the two lysine residues by either serine or glutamine; depletion of the two C-terminal hydrophobic residues (Val-Phe) of the decapeptide; and substitution of phenylalanine by alanine in the C-terminal position of the octapeptide. These observations point to a requirement for positively charged amino acids and hydrophobic amino acids at the N- and C-terminus respectively for triggering of mast cells by these short-chain peptides. Releasing activity was also found to depend on the stereospecific conformation of the positively charged region, since substitution of L-isomeric amino acids by D-isomeric forms in the three N-terminal positions of the decapeptide led to loss of potency. Inactive analogues of the decapeptide and octapeptide, at concns up to 10(-4) M, failed to antagonise the mediator-releasing effects of the active decapeptide at concns of 3 X 10(-6) - 10(-4) M.

Animals↗

The Valsalva maneuver: a test of autonomic nervous system function in pregnancy.

Four hundred forty-two studies of the Valsalva maneuver were performed on 282 pregnant subjects and 37 nonpregnant female control subjects. A fetal monitor was used for graphic presentation of the subject's beat-to-beat heart rate changes. The Valsalva ratio was calculated, defined as maximum tachycardia divided by maximum bradycardia during a Valsalva maneuver. The data from the studies on pregnant subjects were grouped according to weeks of gestation: less than 13, 13 to 16, 17 to 20, 21 to 24, 25 to 28, 29 to 32, 33 to 36, and greater than 36. The mean Valsalva ratio for control subjects is higher than the mean for every gestation group, and there is a definite downward trend in the means for each successive gestation group through 29 to 32 weeks. The tendency for pregnant women to have an "abnormal" Valsalva ratio (that is, less than 1.5) also appears to be related to gestation. This exploratory study demonstrates that the Valsalva ratio is sensitive to physiologic changes associated with pregnancy. This test might have use as a noninvasive indicator of certain types of abnormalities associated with pregnancy.

Adolescent↗