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Biomedical subjects

M Hameed

Publications and source records attributed to M Hameed.

26 records · Page 2Linked to original sources
PubMed1993

Characteristics of DNA replication in isolated nuclei initiated by an aprotinin-binding protein.

Isolated cell nuclei were used as the source of template DNA to investigate the role of a cytosolic aprotinin-binding protein (ADR) in the initiation of eukaryotic DNA replication. Computerized image cytometry demonstrated that the DNA content of individual nuclei increased significantly following incubation with ADR-containing preparations, and the extent of DNA synthesis is consistent with that allowed by the limiting concentration of dTTP. Thus, dTTP incorporation into isolated nuclei represents DNA synthesis and not parent strand repair. We found that dTTP incorporation into the isolated nuclei is dependent on DNA polymerase alpha (a principal polymerase in DNA replication) but that DNA polymerase beta (a principal polymerase in DNA repair processes) does not play a significant role in this system. Finally, neither aprotinin nor a previously described cytosolic ADR inhibitor can block the replication of nuclease-treated calf thymus DNA, while both strongly inhibit replication of DNA in isolated nuclei. This result, coupled with the relative ineffectiveness of nuclease-treated DNA compared with nuclear DNA to serve as a replicative template in this assay, argues against a significant contribution from repair or synthesis which initiates at a site of DNA damage. These data indicate that ADR-mediated incorporation of 3H-dTTP into isolated nuclei results from DNA replicative processes that are directly relevant to in vivo S phase events.

Aprotinin↗
PubMed1989

Intracellular mechanisms of lymphoid cell activation.

Activation of lymphocytes for proliferation is associated with the appearance of an intracellular factor (ADR) that can induce DNA synthesis in isolated quiescent nuclei. ADR plays a role in the sequence of intracellular events leading to activation for IL-2-mediated proliferation. Because of the nature of the defining assay, the locus of ADR action appears to be near the terminal end of the transduction pathway. Interestingly, although lymphocytes from aged individuals respond poorly to proliferative stimuli, they appear to produce normal to above-normal levels of ADR. In contrast, their nuclei are only poorly responsive to stimulation by ADR. Preparations rich in ADR activity have proteolytic activity as well. In addition, aprotinin, as well as a variety of other protease inhibitors, suppresses ADR-induced DNA synthesis in a dose-dependent manner. ADR activity can be removed from active extracts by absorption with aprotinin-conjugated agarose beads, and can be removed from the beads by elution at pH 5.0. This latter suggests that ADR itself is a protease. However, its endogenous substrate is not yet known. We have also detected an inhibitor of ADR activity in the cytoplasm of resting lymphocytes. This is a heat-stable protein of approximately 60,000 Da. In addition to suppressing the interaction of ADR with quiescent nuclei, the inhibitor can suppress DNA synthetic activity of replicative nuclei isolated from mitogen-activated lymphocytes. Interestingly, these preparations had little or no activity on replicative nuclei derived from several neoplastic cell lines. The resistance of tumor cell nuclei to spontaneously occurring cytoplasmic inhibitory factors such as the one described here may provide one explanation for the loss of growth control in neoplastic cells.

Animals↗
PubMedDate not supplied

Sudden painless visual loss.

Common signs and symptoms of temporal arteritis include headache, scalp tenderness, jaw claudication, anemia, and an elevated sedimentation rate (ESR). Severe complications can include blindness, retinal artery occlusion, and optic neuropathy. While temporal arteritis may be suggested by patient history, other causes that can mimic its presentation must be considered, especially when visual loss occurs in the setting of a normal funduscopic exam. We report a case of invasive sino-orbital aspergillosis that mimicked the clinical signs and symptoms typically associated with temporal arteritis. A high index of suspicion and appropriate radiological and laboratory studies prevented delays in formulating the correct diagnosis and treatment plan.

Aged↗
PubMedDate not supplied

Presence and quantification of macrophages in squamous cell carcinoma of the cervix.

Cervical cancer is a major cause of morbidity and mortality in women. The presence of macrophages as well as other inflammatory cells has been noted in many of these tumors. Intratumoral macrophages/monocytes induce anergy to cytokine therapy and cause apoptosis in natural killer(NK) and T cells. The aim of this study was to better evaluate and quantify the presence of macrophages in these tumors. Twenty-four cases of squamous cell carcinoma of the cervix seen at our institution were evaluated. Sections were stained with CD68, a marker for macrophages. Staining was graded microscopically by two reviewers together on a scale of 0-4+, with 4+ representing the greatest number of positive cells. Image analysis was conducted to quantify the percent area stained in a given lesion. For each lesion, 10 fields were evaluated, and a mean percentage area stained was calculated. 4+ staining was observed in five cases, 3+ in zero cases, 2+ in three cases, 1+ in six cases, 1-2+ in one case, and nine cases were negative. Image analysis results correlated well with the light microscopic scoring. Presence of a prominent infiltrate of macrophages did not correlate with tumor grade or with histologic lymph node status, but showed a strong negative correlation with tumor stage. Some squamous cell carcinomas of the cervix show a prominent macrophage component in the tumor-associated inflammatory infiltrate. The presence of this prominent infiltration of macrophages did not correlate with tumor grade or lymph node status, but showed a strong negative correlation with tumor stage. The results suggest that immunotherapy may have a potential role in the treatment of cervical carcinoma. Computerized image analysis appears to be a valid measure to assess macrophage counts in such lesions.

Adult↗
PubMedDate not supplied

Lack of proliferative activity of surface epithelial inclusion cysts of the ovary.

Surface epithelial inclusion cysts (SEICs) of the ovary are epithelial inclusions in the ovarian cortex believed to form from invagination of the surface epithelium at the time of ovulation. It has long been theorized that SEICs are related to the development of epithelial ovarian cancer. Ki-67 antigen is a marker of cell proliferation and has been shown to be prognostic in epithelial ovarian cancer. The purpose of this study was to evaluate Ki-67 activity in SEICs to evaluate their possible connection to ovarian neoplastic proliferation. A retrospective review of benign ovaries removed at the time of pelvic surgery was performed. Slides were immunostained with Ki-67. Proliferation index, expressed as the percent of cells staining in SEICs, was calculated. Proliferative activity was scored as negligible, low, moderate, or high, at <5%, 5-10%, 11-40%, and >40%, respectively. Eighteen ovaries from 18 women were evaluated. The percentage of Ki-67 positive cells ranged from 0% to 7%. Ki-67 activity in SEICs of the ovary is negligible to low. Proliferative activity as assessed by Ki-67 staining does not explain any possible relationship of SEICs to epithelial ovarian cancer.

Adult↗
PubMedDate not supplied

Hypolipidemic effect of beta, beta'-tetramethyl hexadecanedioic acid (MEDICA 16) in hyperlipidemic JCR:LA-corpulent rats.

Short-term treatment of male and female obese JCR:LA-corpulent rats with beta,beta'-tetramethyl hexadecanedioic acid (MEDICA 16) resulted in a marked decrease (as much as 80%) in plasma triglyceride values, with a concomitant decrease in the highly elevated very low density lipoprotein (VLDL) levels of the corpulent rat. There were modest decreases in cholesterol levels and increases in low density lipoprotein and high density lipoprotein lipids. The concentrations of apolipoproteins C-II and C-III were decreased in both the whole-serum and the VLDL fractions. Food consumption, rate of weight gain, fasting insulin levels, and the integrated insulin response to an intravenous glucose load remained unaffected. The decrease in plasma VLDL may be accounted for by inhibition of liver long-chain fatty acid synthesis at the level of ATP citrate lyase, with a concomitant reduction of VLDL triglyceride production by the liver. This decrease in plasma VLDL production was accompanied by a twofold to threefold increase in the triglyceride and cholesterol components of the low density lipoprotein and high density lipoprotein fractions, together with a twofold to fourfold decrease in plasma apolipoprotein, indicating that activation of plasma VLDL catabolism may further account for the overall hypolipidemic effect induced by MEDICA 16. The overall hypolipidemic effect of MEDICA 16 may be expected to inhibit the spontaneous atherogenic sequelae induced in the corpulent rat by severe VLDL hyperlipidemia.

Acetyl Coenzyme A↗
PubMedDate not supplied

Myxoid chondrosarcoma of the abdominal aorta.

In this case report we present a 64 year old man who underwent resection of his infrarenal abdominal aortic aneurysm. Thrombus of unusual color, texture and consistency was noted within this aneurysm which upon histopathologic analysis had the characteristics of a myxoid chondrosarcoma. Primary myxoid chondrosarcoma of the abdominal aorta is very rare and to our knowledge this report represents the first recorded case. The clinical presentation of our patient was dominated by hypertension and severe lower extremity claudication associated with microembolization to the left fourth toe.

Aorta, Abdominal↗