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Biomedical subjects

J Shah

Publications and source records attributed to J Shah.

At least 181 records · Page 10Linked to original sources
PubMed1993

The management of the clinically positive neck as part of a larynx preservation approach.

PURPOSE: For patients with squamous cell carcinoma of the head and neck with palpable neck node metastases, the standard management of the neck usually involves neck dissection and postoperative neck irradiation. A strategy of larynx preservation with induction chemotherapy and radiation therapy has been utilized for patients with locally advanced resectable cancer of the larynx, hypopharynx, and oropharynx. For patients treated in this non-surgical manner for the primary site, the optimal management of the clinically positive neck has not been clarified. To determine whether response to induction chemotherapy could help to select patients in whom neck dissection could be omitted in favor of definitive radiation therapy alone, we have analyzed our prospective larynx preservation experience. METHOD AND MATERIALS: Between 1983-1989, 80 patients were entered onto larynx preservation protocols involving 1-3 cycles of cisplatin based chemotherapy followed by radiation therapy with or without neck dissection. There were 54 patients with clinically positive necks to treatment, of whom 44% (24/54) had a complete response, and of whom 20% (11/54) had a partial response to chemotherapy in the neck. In 22 of these 35 patients with clinically positive necks who achieved a major neck response to chemotherapy, radiation therapy (median 66 Gy) was used as the only subsequent treatment of the neck. RESULTS: At a median follow-up of 25 months (range 7-83 months), neck control for this subset is 91% (20/22). Neck failure occurred in 20% (1/5) of patients with a partial response to chemotherapy treated without neck dissection and 6% (1/17) of node positive with a complete response. CONCLUSION: These results suggest that patients with clinically palpable cervical nodal metastases who have a complete response to chemotherapy and receive high dose radiation therapy have excellent neck control and may not need neck dissection. Further experience will be required to confirm these preliminary data and to determine if patients who achieve a partial response in the neck after induction chemotherapy can be treated with radiation therapy without neck dissection.

Adult↗
PubMed1993

Estimation of the secondary structure and conformation of bovine lens crystallins by infrared spectroscopy: quantitative analysis and resolution by Fourier self-deconvolution and curve fit.

The secondary structure of six bovine lens protein fractions (two alpha, three beta and one gamma-crystallin) are examined in solution and in solid forms for the first time using FTIR spectroscopy. Films of the nuclear and cortical regions of the bovine lens are also examined. The structure is quantitatively estimated from the vibrational analysis of the resolution-enhanced amide-I profile achieved by Fourier self-deconvolution and linear least-squares curve-fit algorithm. All the protein fractions fold predominantly in a beta-pleated sheet structure with little or no alpha-helical domains in solution or in lyophilized solid form. These proteins also retain their predominant beta-sheet conformation in the cellular phospholipid environment of the lens, in conformity with the structure obtained for all the mammalian species examined to date. Despite structural homology, vibrational data indicate subtle structural differences within each class of the crystallins probably due to presence of several minor substructures/subconformations. Substantial high amounts of turns (approx. 40%) observed in the beta-fractions may have a fundamental implication in stabilizing the tertiary structure of the uniquely folded-proteins vital for the transparency of the lens. These proteins in solid KBr-matrix undergo a major structural change, induced primarily by ionic interactions which refold them in a helical conformation. IR spectroscopy together with band-narrowing procedures has proven to be an effective tool to obtain structural information of proteins in solution, as solid substrates or in a complex biological tissue, such as ocular lens.

Algorithms↗
PubMed1993

Conversion of a silencer into an enhancer: evidence for a co-repressor in dorsal-mediated repression in Drosophila.

The dorsal (dl) protein gradient determines patterns of gene expression along the dorsal-ventral axis of the Drosophila embryo. dl protein is at peak levels in ventral nuclei of the embryo where it activates some genes (twist and snail) and represses others [zerknullt (zen), decapentaplegic and tolloid]. It is a member of the rel family of transcription factors and interacts with specific DNA sequences in the regulatory regions of its target genes. These sequences (dl binding sites), when taken from the context of either an activated or repressed promoter, mediate transcriptional activation of a heterologous promoter, but not repression. We found that T-rich sequences close to the dl binding sites in the silencer region of the zen promoter are conserved between three Drosophila species. Using this sequence information we defined a minimal element that can mediate repression of a heterologous promoter. This element interacts with at least two factors present in embryonic extracts, one of which is dl protein. The other factor binds to the T-rich site. Point mutations in either site abolish ventral repression in vivo. In addition, mutations in the T-rich site cause ectopic expression in ventral regions indicating that the minimal silencer was converted into an enhancer.

Animals↗
PubMed1993

A phase II trial of deoxyspergualin in recurrent squamous cell head and neck cancer.

Fifteen patients with recurrent squamous cell head and neck cancer were treated with deoxyspergualin. There were no objective responses in 14 evaluable patients. The most common toxicity was reversible hypotension, which prompted dose reduction in nine patients. Deoxyspergualin is not recommended for the treatment of squamous cell head and neck cancer.

Adult↗
PubMed1993

Optimal management of patent ductus arteriosus in the neonate weighing less than 800 g.

Between January 1988 and December 1990, 132 neonates weighing < 800 g were admitted to our neonatal intensive care unit. Of the 76 who survived initial resuscitation, 42 had developed a hemodynamically significant patent ductus arteriosus (PDA) (mean +/- SD): gestational age 25.3 +/- 1.9 weeks, birth weight 650 +/- 93 g. Two infants were referred for primary surgical ligation because of contraindications to indomethacin. Forty infants were initially treated with indomethacin. Seventeen of 40 (43%) were subsequently referred for surgical ligation because of indomethacin failure. Infants requiring surgical duct closure were a lower gestational age (24.6 +/- 1.3 v 25.7 +/- 2.0 weeks, P = 0.49) and had a greater left atrial-aortic (LA/Ao) ratio on echocardiography (1.71 +/- 0.28 v 1.46 +/- 0.26, P = .04) compared with those treated successfully with indomethacin. There were 6 deaths (15%), all of which occurred in infants receiving indomethacin (5 indomethacin alone, 1 indomethacin+ligation). Indomethacin was directly associated with intestinal perforation in 3 patients, and acute renal failure in 1; all 4 died. Surgery was associated with minimal morbidity (intraoperative transfusion in 1, postoperative pneumothorax requiring chest tube in 1). These data suggest that in the extremely premature neonate with a hemodynamically significant PDA: (1) indomethacin therapy is associated with a high failure rate and significant complications; (2) PDA associated with a large LA/Ao ratio is unlikely to close with indomethacin therapy; and (3) surgical duct closure is associated with minimal morbidity. We conclude that primary surgical ligation may provide the optimal management for PDA in carefully selected patients.

Ductus Arteriosus, Patent↗
PubMed1993

Physiological significance of Na+/K(+)-ATPase activity in the central nervous system and endogenous sodium-pump inhibitors in the neural regulation of arterial blood pressure.

In anesthetized Sprague-Dawley rats, cerebrolateral ventricular administration of potassium chloride solutions (KCl, 0.375-1.25 mumol, i.c.v.) produced concentration-dependent reductions in the arterial blood pressure and heart rate. These responses were significantly attenuated by prior i.c.v.-administration ouabain, a selective inhibitor of the Na+ pump, and by endothelin (ET-1), an endogenous peptide that is present in the CNS, suggesting that this peptide may participate in the neural regulation of arterial pressure via modulation of Na(+)-pump activity. Although both acute fluid volume expansion and/or osmotic stimulus have been shown to facilitate the release of the endogenous Na(+)-pump inhibitor(s) into the circulation, only volume expansion significantly attenuated the cardiovascular effects of i.c.v. potassium chloride. These observations collectively suggest that the Na+, K(+)-ATPase activity in CNS and Na(+)-pump inhibitors may play a significant role in the central regulation of arterial pressure under certain physiological conditions.

Animals↗
PubMed1993

Migration of Drosophila germ cells: analysis using enhancer trap lines.

Cell migration is a common feature of development. In order to understand more about the factors that control these movements we have embarked on further analysis of the migration of Drosophila germ cells. This process involves passage of the germ cells across the gut primordium and migration toward the mesoderm where the somatic gonad forms. We are particularly interested in the early phase of this migration when the germ cells interact with the amnioproctodeal invagination, the developing gut, before entering into association with the mesoderm. We will summarize the results of our and other studies of these events before describing a number of enhancer trap lines which show expression in the amnioproctodeal invagination during the early phase of germ cell migration. These reveal more about the complexity of this tissue and suggest this tissue is capable of guiding the early phase of germ cell migration.

Animals↗
PubMed1992

Circular dichroic studies of protein kinase C and its interactions with calcium and lipid vesicles.

Circular dichroism was used to study the secondary structure of protein kinase C (PKC) in aqueous solution and the conformational changes resulting due to the presence of its regulatory cofactors (e.g. Ca2+, phosphatidylserine (PS) and phorbol 12-myristate 13-acetate (PMA)). Computer analysis of the CD data for the estimates of secondary structure showed that PKC maintains a highly ordered structure containing 36% alpha-helix, 57% beta-sheet and 7% beta-turn. PKC displays a minor conformational change upon addition of Ca2+. However, a larger change is observed on adding phosphatidylserine vesicles in the presence of Ca2+. In this case, the alpha-helix content is decreased by approx. 35% and beta-sheet increased by approx. 16%. The protein does not experience further significant changes in conformation on adding PMA.

Adenosine Triphosphate↗
PubMed1992

Antagonism by endothelin of centrally mediated cardiovascular effects of potassium in anaesthetized rats.

1. We have previously demonstrated that cerebroventricular administration of potassium chloride (KCl) solutions produces dose-dependent reductions in blood pressure and heart rate in anaesthetized rats and that these effects are significantly attenuated by ouabain, a selective inhibitor of the Na(+)-pump. These observations suggest an important relationship between Na+,K(+)-ATPase activity in the central nervous system (CNS) and neural mechanisms involved in the regulation of cardiovascular function. 2. Since endothelin-1 (ET-1) has been shown to affect various ion transport mechanisms, including the Na(+)-pump, the present studies were conducted to evaluate whether this peptide would antagonize central effects of KCl. 3. The present studies demonstrate that cumulative doses of ET-1 (0.8-3.2 pmol, intracerebrolateral ventricular administration, i.c.v.) produced significant attenuation of hypotension and bradycardia produced by i.c.v. injections of KCl (0.75 mumol/5 microL, i.c.v.); in a separate series, a single high dose of ET-1 (4.0 pmol, i.c.v.) significantly reduced cardiovascular responses to various doses of KCl (0.375, 0.75, 1.25 mumol/5 microL, i.c.v.). 4. These studies suggest that endothelin may be involved in the regulation of arterial pressure since it is present in CNS and possesses a ouabain-like effect. However, it is not conclusive that ET-1 inhibits neuronal Na(+)-pump, since alternative mechanisms can also account for the efficacy of the peptide to antagonize central effects of potassium chloride.

Animals↗