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Biomedical subjects

M S Ali

Publications and source records attributed to M S Ali.

At least 37 records · Page 2Linked to original sources

Blepharocalyxins C--E, three new dimeric diarylheptanoids, and related compounds from the seeds of Alpinia blepharocalyx.

Three novel diarylheptanoids, blepharocalyxins C--E (5--7), together with four new (1--4) and one known (8) diarylheptanoids bearing a tetrahydropyran ring were isolated from the residual fraction of an EtOH extract of the seeds of Alpinia blepharocalyx. The structures and the stereochemistry at the chiral centers of the new diarylheptanoids were elucidated by spectroscopic techniques including 2D NMR spectroscopy. Blepharocalyxins C--E (5--7) have a novel carbon framework and are dimeric diarylheptanoids consisting of two diarylheptanoid units. Blepharocalyxin D (6) showed potent antiproliferative activity against murine colon 26-L5 carcinoma cells (ED(50), 3.61 microM), while against human HT-1080 fibrosarcoma cells, blepharocalyxin E (7) showed potent activity (ED(50), 9.02 microM).

Animals↗

Six new diarylheptanoids from the seeds of Alpinia blepharocalyx.

Chromatographic separation of part of an EtOH extract of the seeds of Alpinia blepharocalyx resulted in the isolation of six new (1-6) and two known (7, 8) diarylheptanoids together with 12 known compounds. The structures of the new compounds, including their absolute stereochemistry, were elucidated by spectroscopic and chemical methods as (3S,5S)- (1) and (3S,5R)-3-hydroxy-5-methoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (2), (3S,5S)- (3) and (3S,5R)-3-hydroxy-5-ethoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (4), (3S)-methoxy-1,7-bis(4-hydroxyphenyl)-6E-hepten-5-one (5), and 1,7-bis(4-hydroxyphenyl)hepta-4E,6E-dien-3-one (6). Among the isolated compounds, 5, (3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (8), 4'-hydroxy-5,6-dehydrokawain (14), and/or phloroglucinol (20) showed significant antiproliferative activity against murine colon 26-L5 carcinoma (ED(50): 5, 5.2 microM; 8, 12.8 microM; 14, 20.7 microM; 20, 26.4 microM) and human HT-1080 fibrosarcoma (ED(50): 5, 10.1 microM; 14, 20.1 microM; 20, 20.9 microM) cells.

Cell Division↗

Role of dietary habits in the development of esophageal cancer in Assam, the north-eastern region of India.

The etiology of esophageal cancer remains largely unknown. In recent years, the role of dietary habits in the development of esophageal cancer has received much attention. Prevalence of esophageal cancer in Assam is highest among all the states of India. To identify the possible risk factors, a hospital-based case-control study was conducted with 502 cases and 1,004 controls. "Kalakhar," a unique and locally made food item, has emerged as a significant risk factor (odds ratio = 8.0, 95% confidence interval = 5.1-11.5, p < 0.001). Consumption of very spicy foods, hot foods and beverages, a diet containing high amounts of chili, and leftover food was positively associated with the risk of esophageal cancer. Green leafy vegetables and fruits were protective for esophageal cancer. The risk factors associated with consumption of locally prepared food items, e.g., kalakhar, and some dietary practices did not decrease, even after adjustments with different confounding factors. However, further studies are required to conclusively implicate these factors in causation of esophageal cancer.

Case-Control Studies↗

Antiproliferative activity of diarylheptanoids from the seeds of Alpinia blepharocalyx.

The 95% EtOH extract of the seeds of Alpinia blepharocalyx (Zingiberaceae) showed significant antiproliferative activity towards human HT-1080 fibrosarcoma and murine colon 26-L5 carcinoma cells. Chemical investigation of the extract led to the isolation of forty-four new (1-44) and one known (45) diarylheptanoids, eleven phenolic compounds (46-56) together with beta-sitosterol glucoside (57). Almost all the isolated compounds showed significant antiproliferative activity in a concentration-dependent manner. Among the compounds, epicalyxin F (17) exhibited the most potent activity against the proliferation of colon 26-L5 carcinoma cells with an ED50 value of 0.89 microM, while calyxin B (2) exhibited the most potent activity against human HT-1080 fibrosarcoma cells with an ED50 value of 0.69 microM. Moreover, calyxins B (2) and K (11), epicalyxins F (17), I (20) and K (22), 6-hydroxycalyxin F (25), blepharocalyxin B (27) and mixtures of 7 and epicalyxin G (18) and of calyxin J (10) and epicalyxin J (21) possessed more potent activity than a clinically used anticancer drug, 5-fluorouracil, towards HT-1080 fibrosarcoma cells. Analysis of the structure activity relationship suggested that the position of the attachment of a chalcone or a flavanone moiety does not affect the activity, although their presence in association causes a substantial enhancement of the antiproliferative activity. Moreover, the conjugated double bond of the chalcone moiety and the phenolic hydroxyl group potentiate the antiproliferative activity of the compounds.

Animals↗

Brine shrimp bioassay of Phoenix sylvestris.

Brine shrimp bioassay is a simple method for natural product research. The procedure determines LD50 values in microg/ml of active compound and extract in the brine medium. Three different extracts (methanol, chloroform and butanol) of the male flower inflorescence of Phoenix sylvestris were subjected to this bioassay. The results showed that the methanolic and butanolic extracts exhibit significant toxicity to the shrimps, while the chloroform extract was found to be non-toxic.

Journal Article↗

Jak2 acts as both a STAT1 kinase and as a molecular bridge linking STAT1 to the angiotensin II AT1 receptor.

Angiotensin II activates the Jak-STAT pathway via the AT(1) receptor. We studied two mutant AT(1) receptors, termed M5 and M6, that contain Y to F substitutions for the tyrosine residues naturally found in the third intracellular loop and the carboxyl terminus. After binding ligand, both the M5 and M6 AT(1) receptors trigger STAT1 tyrosine phosphorylation equivalent to that observed with the wild type receptor, indicating that angiotensin II-mediated phosphorylation of STAT1 is independent of these receptor tyrosine residues. In response to angiotensin II, Jak2 autophosphorylates on tyrosine, and Jak2 and STAT1 physically associate, a process that depends on the SH2 domain of STAT1 in vitro. Evaluation of the wild type, M5, and M6 AT(1) receptors showed that angiotensin II-dependent AT(1) receptor-Jak2-STAT1 complex formation is dependent on catalytically active Jak2, not on the receptor tyrosine residues in the third intracellular loop and carboxyl tail. Immunodepletion of Jak2 virtually eliminated the ligand-dependent binding of STAT1 to the AT(1) receptor. These data indicate that the association of STAT1 with the AT(1) receptor is not strictly bimolecular; it requires Jak2 as both a STAT1 kinase and as a molecular bridge linking STAT1 to the AT(1) receptor.

Amino Acid Substitution↗

Human Kaposi's sarcoma cell-mediated tumorigenesis in human immunodeficiency type 1 tat-expressing transgenic mice.

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) transactivator (Tat) protein has been linked to the development and course of Kaposi's sarcoma (KS) associated with acquired immunodeficiency disease syndrome (AIDS-KS). Tat is an 86-101 amino-acid protein encoded by two exons. To evaluate the growth-promoting effects of Tat in AIDS-KS in vivo, we developed transgenic mice expressing the one-exon-encoded 72 amino-acid protein (Tat(72)) and the two-exon-encoded 86 amino-acid protein (Tat(86)). METHODS: Human KS SLK cells were injected subcutaneously into CD4(+) T-cell-depleted male mice, and the tumors that formed after 3-4 weeks were recovered and analyzed for the expression of Tat protein(s), different cytokine messenger RNAs (mRNAs), and matrix metalloproteinases (MMPs). All statistical tests were two-sided. RESULTS: The average tumor weight was maximum in Tat(86) mice ( approximately 600 mg) compared with Tat(72) ( approximately 200 mg) and nontransgenic ( approximately 100 mg) mice (P<.005). Histologic examination of tumors showed spindle-shaped SLK cells with prominent infiltrates of inflammatory cells. All of the tumors from Tat mice expressed abundant Tat mRNA, suggesting that the infiltrating mouse cells actively expressed Tat. A comparison of the growth-promoting cytokines in the tumors from Tat(86)-transgenic and nontransgenic mice showed that the expression of the following cytokines was substantially increased in the tumors of the Tat(86) mice: tumor necrosis factor-alpha, interleukin 6, interleukin 8, granulocyte-macrophage colony-stimulating factor, and basic fibroblast growth factor. Furthermore, these tumors showed abundant expression of a 105-kd MMP activity associated with infiltrates of host leukocytes in the lesions. CONCLUSION: Our in vivo data clearly suggest that extracellular Tat can contribute to the growth and tumorigenesis of human KS cells.

Animals↗

Chemistry of Zataria multiflora (Lamiaceae).

The hexane soluble part of Zataria multiflora afforded three new aromatic constituents which include two p-cymene derivatives: multiflotriol (1), multiflorol (2) and an aromatic ester of p-hydroxy benzoic acid (3). In addition to these three new compounds, three known compounds, dihydroxyaromadendrane, luteolin and alpha-tocopherolquinone, have also been isolated for the first time from the same source. The structures of all the isolated constituents were elucidated by means of spectroscopic methods including 2D-NMR techniques.

Flavonoids↗

Eleganoside-A, B and C from Pseudocalymma elegans, a native of Brazil.

The toxic methanol-soluble part of Pseudocalymma elegans (leaves), a native of Brazil, yielded three new iridoidglucosides (1a-3a) as their acetate-derivatives (1-3) named eleganoside-A (1a), B (2a) and C (3a) which have been characterized with the aid of spectroscopic techniques, including 2D NMR.

Glucosides↗

Two new diterpenoids from Salvia triloba.

Two new diterpenoids, trilobic acid (1) and trilobiol (2), have been isolated from the methanolic extract of Salvia triloba. Their structures were elucidated with the aid of NMR spectroscopy including two-dimensional-NMR techniques.

Diterpenes↗

Serum S100 protein as a marker of cerebral damage during cardiac surgery.

The identification of a serum marker to assist in the diagnosis of cerebral injury after cardiac surgery is potentially useful. S100 protein is an early marker of cerebral damage. It is released after cardiac surgery performed under cardiopulmonary bypass (CPB). Its level is correlated with the duration of CPB, deep circulatory arrest and aortic cross-clamping. Increased levels of S100 protein are correlated with the age of the patient and the number of microemboli, especially during aortic cannulation. Perioperative cerebral complications such as stroke, delayed awakening and confusion are associated with increased levels of S100 protein directly after bypass and from 15 to 48 h after it. In addition, increased levels of S100 protein are related to neuropsychological dysfunction after cardiac surgery. S100 protein has early and late release patterns after CPB; the early pattern may be due to sub-clinical brain injury. The late release pattern may be due to perioperative cerebral complications. Patients undergoing intracardiac operations combined with coronary artery bypass surgery are more susceptible to brain injury and have higher levels of S100 after CPB. Furthermore, adults and children undergoing deep circulatory arrest are more susceptible to brain injury, in terms of higher S100 protein release after CPB. Serum S100 protein levels are reduced after using arterial line filtration and covalent-bonded heparin to coat the inner surface of the CPB circuit.

Biomarkers↗

Bankart operation for recurrent anterior dislocation of the shoulder using suture anchor.

Between June 1989 and December 1994, a total of 19 patients (20 shoulders) underwent open repair of Bankart lesions using suture anchors. Subscapularis muscle and anterior capsule were cut as one layer and sutured end to end without overlap. Coracoid osteotomy was not necessary. Average follow-up was 53.6 months (range: 24-90 months). Clinical evaluation using the Rowe functional grading system showed 15 shoulders had excellent results, 3 shoulders had good results, and 1 patient was lost to follow-up. There were no complications and no failures with recurrence of dislocation.

Adult↗

Intestinal spore-forming protozoa among patients suffering from chronic renal failure.

Cryptosporidium parvum, Isospora belli, Cyclospora cayetanensis and Microsporidia are four intestinal spore-forming protozoa that cause diarrhoea in immuno-competent individuals and immuno-suppressed patients. Fresh stool samples were obtained from 120 patients suffering from CRF and attending the Dialysis Unit of Zagazig University Hospital. Also, stool samples were obtained from 40 immuno-competent individuals complaining of diarrhoea (control group). The stool samples were examined by direct smear and formol-ether concentration methods then stained by Giemsa, Modified Ziehl Neelsen (MZN) and Aniline carbol methyl violet stains. The four intestinal spore-forming protozoa were detected in 40/120 (33.3%) of patients with CRF and in 2/40 (5.0%) of the control group with a statistically highly significant difference (P < 0.001). C. parvum, Microsporidia, C. cayetanensis and I. belli were detected in 18/120 (15%), 10/120 (8.3%), 9/120 (7.5%) and 3/120 (2.5%), respectively. The four protozoa were found as mixed infections with other pathogens or as single infections confirming their role alone as a cause of diarrhoea. MZN stain was the most efficient simple, and not expensive.

Adult↗

The role of Ca2+ mobilization and heterotrimeric G protein activation in mediating tyrosine phosphorylation signaling patterns in vascular smooth muscle cells.

This work investigated the role of Ca2+ mobilization and heterotrimeric G protein activation in mediating angiotensin II-dependent tyrosine phosphorylation signaling patterns. We demonstrate that the predominant, angiotensin II-dependent, tyrosine phosphorylation signaling patterns seen in vascular smooth muscle cells are blocked by the intracellular Ca2+ chelator BAPTA-AM, but not by the Ca2+ channel blocker verapamil. Activation of heterotrimeric G proteins with NaF resulted in a divergent signaling effect; NaF treatment was sufficient to increase tyrosine phosphorylation levels of some proteins independent of angiotensin II treatment. In the same cells, NaF alone had no effect on other cellular proteins, but greatly potentiated the ability of angiotensin II to increase the tyrosine phosphorylation levels of these proteins. Two proteins identified in these studies were paxillin and Jak2. We found that NaF treatment alone, independent of angiotensin II stimulation, was sufficient to increase the tyrosine phosphorylation levels of paxillin. Furthermore, the ability of either NaF and/or angiotensin II to increase tyrosine phosphorylation levels of paxillin is critically dependent on intracellular Ca2+. In contrast, angiotensin II-mediated Jak2 tyrosine phosphorylation was independent of intracellular Ca2+ mobilization and extracellular Ca2+ entry. Thus, our data suggest that angiotensin II-dependent tyrosine phosphorylation signaling cascades are mediated through a diverse set of signaling pathways that are partially dependent on Ca2+ mobilization and heterotrimeric G protein activation.

Angiotensin II↗

Primary drug resistance pattern of mycobacterium tuberculosis in Dhaka, Bangladesh.

One thousand two hundred and eighty one clinically suspected untreated patients with pulmonary tuberculosis were studied from an urban tuberculosis clinic in Dhaka. Majority of the 1281 patients (77.6%) were from the age group of 14 to 44 years. Sputum, 106 (8.3%) were found positive for mycobacteria (both by Ziehl-Neelsen smear staining and culture to consider those as confirmed cases of mycobacterial infection. Out of these 106 cases, 101 (95.3%) were identified as M. tuberculosis and the rest 5 (4.7%) as Non-tuberculous Mycobacteria (NTM). Among the 101 M. tuberculosis strains, 30 (29.7%) were resistant to at least one drug; 16 (15.8%); to isoniazid, 11 (10.9%) to rifampicin, 07 (6.9%) to streptomycin, 03 (2.9%) to ethambutol and 04 (3.9%) to pyrazinamide. Multi-drug resistant tuberculosis (MDR-TB) was found in 5 (4.95%) cases. 5 (4.95%) cases were resistant to two drugs and 3 (2.97%) cases to three drugs. Ciprofloxacin was tested against 30 strains of M. tuberculosis; 2 (6.67%) of which were resistant. This is the first report of ciprofloxacin resistant Mycobacterium tuberculosis from Bangladesh. All the 5 strains of NTM tested for said 5 anti-tuberculous drugs, were found resistant to more than one.

Adolescent↗

Epicalyxin F and calyxin I: two novel antiproliferative diarylheptanoids from the seeds of Alpinia blepharocalyx.

[formula: see text] Epicalyxin F (1) and calyxin I (2), two novel diarylheptanoids, were isolated from a residual fraction of an EtOH extract of Alpinia blepharocalyx. Calyxin I (2) represented a new carbon skeleton, and epicalyxin F (1) possessed potent antiproliferative activity toward HT-1080 fibrosarcoma and colon 26-L5 carcinoma with ED50 values of 1.71 and 0.89 microM, respectively.

Antineoplastic Agents, Phytogenic↗

A catalytically active Jak2 is required for the angiotensin II-dependent activation of Fyn.

Recent work with interleukins has shown a convergence of tyrosine phosphorylation signal transduction cascades at the level of the Janus and Src families of tyrosine kinases. Here we demonstrate that activation of the seven-transmembrane AT(1) receptor by angiotensin II induces a physical association between Jak2 and Fyn, in vivo. This association requires the catalytic activity of Jak2 but not Fyn. Deletion studies indicate that the region of Jak2 that binds Fyn is located between amino acids 1 and 240. Studies of the Fyn SH2 and SH3 domains demonstrate that the SH2 domain plays the primary role in Jak2/Fyn association. Not surprisingly, this domain shows a marked preference for tyrosine-phosphorylated Jak2. Surface plasmon resonance estimated the dissociation equilibrium constant (K(d)) of this association to be 2.36 nM. Last, in vivo studies in vascular smooth muscle cells show that, in response to angiotensin II, Jak2 activation is required for Fyn activation and induction of the c-fos gene. The significance of these data is that Jak2, in addition to serving as a critical angiotensin II activated signal transduction kinase, also functions as a docking protein and participates in the activation of Fyn by providing phosphotyrosine residues that bind the SH2 domain of Fyn.

Angiotensin II↗