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S Jamal

Publications and source records attributed to S Jamal.

49 records · Page 3Linked to original sources

Vascular abnormalities in experimental and human lymphatic filariasis.

Whereas clinical descriptions of grotesque lymphedema and standard light microscopy in human filariasis have elucidated the natural progression of this disease, the link between the nematode and vascular abnormalities including elephantiasis remains poorly understood. Accordingly, we examined the nature and distribution of lymphatic and blood vascular derangements in a variety of tissues and organs from 37 ferrets acutely and chronically infected with Brugia malayi and in 15 patients with Wuchereria bancrofti or Brugia malayi infestation (resected skin, subcutaneous tissue, and lymph nodes) using light and transmission electron microscopy, immunohistochemistry, and in vivo microscopy. In ferrets, eosinophilic abscesses and epithelioid and giant cell granulomas with fragmented worms in various stages of disintegration were found in multiple organs. Blood microvasculopathy consisted of endothelial hyperplasia, focal thickening and stenosis, vessel obliteration with marked perivascular infiltration of lymphocytes, plasma cells, eosinophils, and numerous large macrophages laden with a coarse golden-brown pigment. Endothelial ballooning and swelling, pavementing, denuding, scarring, and sludge formation were seen along with high endothelium in atypical locations. Dilated lymphatics were most prominent near adult worms and showed plump endothelium, thickened walls and valves, thrombus formation, and often perilymphangitis and adjacent tissue fibrosis. In vivo microscopy showed wriggling live adult worms in dilated incompetent sludge-filled groin lymphatics even when microfilaremia and peripheral edema were absent. In human tissues, in addition to "pachyderm" skin changes (keratosis, papillomatosis, acanthosis and collagen deposition), there was blood vessel and lymphatic vasculopathy similar to ferrets (angiocentric inflammation, congestion, vasculitis, thrombosis, thickened vessel walls, dilated lymphatics, lymphangitis, reactive lymph nodal hyperplasia and nodal fibrosis). These changes reflect generalized endothelial damage due to worm products, physical injury to valves and vessel walls from lymphatic-dwelling live worms, and host immune reactivity. Whereas adult worms target the lymphatic apparatus, their offspring and the host immune response primarily affects the blood microvasculature.

Animals↗

Transactivation of c-fos and beta-actin genes by raf as a step in early response to transmembrane signals.

A primary response to many growth factor-induced transmembrane signals is the rapid activation of transcription of the proto-oncogene c-fos and other early-response genes, including the beta-actin gene. The c-raf gene encodes a cytoplasmic serine/threonine kinase, raf-1, whose activity is also responsive to transmembrane signals and which in mutant form can transform cells. Here we show that in transient assays, the v-raf protein, which is a constitutively activated oncogenic counterpart of raf-1, can transactivate transcription from two early-response promoters, including the c-fos promoter from human and murine cells and the human beta-actin gene promoter. Multiple elements of the human fos promoter, including the dyad symmetry element necessary for growth-factor induction, an octanucleotide direct repeat element, and the region spanning the sequence from nucleotides -225 to -99 can all serve as targets for raf induction. The c-myc promoter and two adenovirus-2 early promoters are not induced. These findings indicate that raf kinase, when activated by a transmembrane signal or by mutation of a regulatory domain, can phosphorylate a factor(s) capable of regulating transcription of the c-fos and actin genes. The oncogenic form of raf may transform by constitutively activating early response protooncogenes such as c-fos.

Actins↗

Continuous venous oximetry during cardiopulmonary bypass: influence of temperature changes, perfusion flow, and hematocrit levels.

This study was performed in 11 patients undergoing cardiac surgery during cardiopulmonary bypass (CPB). A Bentley-10 oxygenator (American Bentley, Irvine, CA) was used during bypass, and 1,500 mL of Ringer's solution was used to prime the oxygenator. A perfusion flow of 2.4 L/min/m2 was used, and an equivalent flow of 100% oxygen was added to the oxygenator. The mixed venous oxygen saturation (SvO2) was monitored by continuous in-line venous oximetry using the Bentley Oxy-Stat Meter. Body temperature and SvO2 measurements were made at the venous blood port of the oxygenator. The authors investigated the correlation between SvO2 and changes of body temperature, perfusion flow, and hematocrit values. SvO2 correlated inversely, in a linear fashion, with the body temperature. The SvO2 was markedly decreased after rewarming, and was significantly affected during normothermia by changes in perfusion flow rates and hematocrit levels. An adequate SvO2 was found when the flow was greater than 2.4 L/min/m2 and the hematocrit was greater than 20%. In-line oximetry can help to optimize perfusion during CPB and to detect episodes of desaturation.

Aged↗

Selective up-regulation of endothelial cell class I MHC expression by cytokines from patients with lymphatic filariasis.

Local host immune responses to the lymphatic-dwelling filarial parasite Wuchereria bancrofti are important in the pathogenesis of the lymphangitis that leads to filarial elephantiasis. That the lymphatic endothelial cells may be important in this inflammatory process was shown by the ability of supernatants generated from filarial Ag-driven PBMC of individuals with filarial elephantiasis caused by W. bancrofti infection to up-regulate class I MHC expression on human umbilical vein endothelial cells when compared to unstimulated control supernatants from the same individual (relative fluorescence intensity = 159% +/- 13.5; p less than 0.001). In contrast, individuals with the same filarial infection but manifesting no lymphatic disease were unable to generate, in response to filarial Ag the cytokines required for this activation (relative fluorescence intensity = 93% +/- 2.6). Supernatants induced by a non-filarial Ag (purified protein derivative) were able to effect class I MHC up-regulation in both patient groups. The same filarial Ag-driven supernatants did not cause detectable class II MHC staining on human umbilical vein endothelial cells. These results suggest a likely role for parasite Ag-driven, cytokine-mediated endothelial cell activation in the pathogenesis of lymphatic inflammatory/obstructive filarial disease.

Adult↗

The effects of 5,6 benzo-[a]-pyrone (coumarin) and DEC on filaritic lymphoedema and elephantiasis in India. Preliminary results.

A randomized double-blind, placebo-controlled, trial of 5,6 benzo-[alpha]-pyrone (coumarin, '56 BaP') and of diethylcarbamazine (DEC) is being performed on patients with filaritic lymphoedema and elephantiasis over two years, using matched groups. In 169 patients there were significant (1% level) reductions in the amounts of oedema for the patients taking 56 BaP. The excess limb volumes were reduced from 40 to 25% over two years. A similar, but less significant (5% level), improvement was found for the circumference measurements. The rate of reduction was increased when the initial amount of oedema was greater. This therapy, while much slower than many other methods of treatment, does convert a slowly worsening condition into a slowly improving one. There were no significant reductions in the amount of oedema following DEC treatment.

Analysis of Variance↗

HIV infection does not require endocytosis of its receptor, CD4.

The T cell surface molecule CD4 interacts with class II MHC molecules on the surface of target cells as well as with the envelope glycoprotein of human immunodeficiency virus (HIV). Internalization of CD4 molecules is observed after exposure of CD4+ T cells to either phorbol esters or appropriate antigen-bearing target cells. To determine whether HIV entry proceeds via receptor-mediated endocytosis or direct viral fusion with the cell membrane, we have constructed two mutants in the cytoplasmic domain of the CD4 protein that severely impair the ability of CD4 molecules to undergo endocytosis. Quantitative infectivity studies reveal that HeLa cell lines expressing wild-type or mutant CD4 molecules are equally susceptible to HIV infection. In addition, HIV binding does not lead to CD4 endocytosis. These studies indicate that although the CD4 molecule can be internalized, HIV entry proceeds via direct fusion of the viral envelope with the cell membrane.

Acquired Immunodeficiency Syndrome↗

cDNA cloning and mapping of the human creatine kinase M gene to 19q13.

We describe the first isolation of a human creatine kinase M cDNA clone and its mapping of the gene to human chromosome 19. A human creatine kinase M cDNA clone, pJN2CK-M, harboring a 1,160-bp insert, was isolated by colony hybridization with a previously sequenced chicken creatine kinase M cDNA probe. The human cDNA was used as a probe in Southern transfers of TaqI-digested genomic DNA from mouse/human somatic-cell hybrids to localize the human creatine kinase-M gene to chromosome 19. In situ hybridization of the tritiated cDNA probe to metaphase chromosomes of peripheral blood lymphocytes from normal males revealed significant labeling to chromosome 19. These two independent methodologies assign the human creatine kinase-M gene to chromosome 19. Since greater than 69% of the grains of chromosome 19 label band q13, the human creatine kinase-M gene has been mapped to 19q13. On the basis of high-resolution G-banding, the predominant labeling site was 19q13.2-q13.3.

Animals↗

Lymphovenous anastomosis in filarial lymphedema.

Correction of established filarial edema requires lymphaticovenous by-pass, to overcome the lymphatic obstruction and debulking to reduce the lymphatic load. Lymphnodovenous shunt at inguinal area has given 90% success in the authors hand, proving the by-pass. However, in an enormously swollen leg the dilated distal lymphatics may not be adequately drained and hence a distal lymphaticovenous anastomosis should theoretically offer further reduction; and thereby make debulking effective. In this article 3 cases are reported in whom lymphovenous anastomosis was done, in 2 at the knee level and in 1 at the ankle, their result and rationale are discussed.

Elephantiasis↗