Biomedical subjects

M N Sharif

Publications and source records attributed to M N Sharif.

9 recordsLinked to original sources

PubMed2001

Unique function for carboxyl-terminal domain of Oct-2 in Ig-secreting cells.

The activity of Ig gene promoters and enhancers is regulated by two related transcription factors, Oct-1 (ubiquitous) and Oct-2 (B lineage specific), which bind the octamer motif (ATTTGCAT) present in these elements. As Ig promoter-binding factors, Oct-1 and Oct-2 each work together with a B lymphocyte-specific cofactor OCA-B/OBF-1/Bob-1 that interacts with them through their POU (DNA-binding) domains. Because both can mediate Ig promoter activity in B cells, there has been some question as to whether these two octamer-binding factors serve distinct functions in lymphocytes. We have shown previously that the silencing of B lymphocyte-specific genes in plasmacytoma x T lymphoma hybrids can be prevented by preserving Oct-2 expression. The pronounced effect of this transcription factor on the phenotype of plasmacytoma x T lymphoma hybrids established a critical role for Oct-2 not only in maintaining Ig gene expression, but in maintaining the overall genetic program of Ig-secreting cells. In the present study, we have explored the functional differences between Oct-1 and Oct-2 using chimeric Oct-1/Oct-2 proteins in cell fusion assays. Our results provide further evidence for an essential role for Oct-2 in Ig-secreting cells and identify the C-terminal domain of Oct-2 as responsible for its unique function in these cells.

Antibody-Producing Cells↗

PubMed1998

Changes in pacing lead impedance over time predict lead failure.

It has been suggested that a decrease in lead impedance may predict pacing lead failure, but there is limited prospective data about the relation of changes in lead impedance over time to lead performance. We monitored changes in lead impedance through implantable pulse generators with real-time telemetry data capability in 105 patients with Medtronic 4012 leads (n = 38) and Medtronic 4004 leads (n = 67). Pacing lead failure was documented by serial ambulatory electrocardiographic monitoring or intensified pacemaker clinic surveillance. A significant decrease in lead impedance was observed in patients with Medtronic 4012 and Medtronic 4004 leads with documented lead failure, whereas lead impedance remained stable over time in patients without documented lead failure. The sensitivity and specificity of a lead impedance decrease of > or =15% to predict lead failure were 69% and 70%, respectively. The sensitivity and specificity of a lead impedance decrease of > or =30% to predict lead failure were 36% and 90%, respectively. The positive and negative predictive values for a lead impedance decrease of > or =15% were 54% and 81%, respectively, and for a lead impedance decrease of > or = 30% were 65% and 73%, respectively. Thus, small decreases in lead impedance may identify failing leads. Serial measurement of pacing lead impedance over time is a useful tool to monitor pacing lead performance.

Aged↗

PubMed1998

Atrial fibrillation: overview of therapeutic trials.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia treated by physicians, and a plethora of therapeutic trials deal with selected aspects of its management. This overview attempts to categorize and summarize the available studies. A key to management of AF is a clinical classification schema that provides a framework for application of the available treatment modalities. Such a classification is provided. Antithrombotic trials have demonstrated the remarkable efficacy of warfarin and more modest effect of acetylsalicylic acid for prevention of stroke; these data are summarized. Cardioversion to restore sinus rhythm is an important aspect of management of AF, particularly of persistent and new onset AF. In this review pharmacological cardioversion is emphasized. The data concerning the use of various drugs for pharmacological cardioversion are reviewed. Many, but not all, agents have been shown to have efficacy in this regard, but efficacy with drugs is lower than that with electrical cardioversion and, in the case of amiodarone, may be delayed. For recurrent AF, the two major rhythm management approaches are maintenance of rhythm and heart rate control. Trials of pharmacological and nonpharmacological therapies for these purposes are reviewed and summarized. Management of AF is an active area of research, and the present review is intended as a foundation upon which new information can be added.

Age Factors↗

PubMed1996

Right ventricular nerve sheath tumour and patent foramen ovale presenting with transient ischemic attack.

A 66-year-old man presented with dyspnea and a transient ischemic attack. Echocardiography revealed a right ventricular mass and patent foramen ovale. During surgery the mass was found to be a malignant nerve sheath tumour. Several weeks later, the patient developed small bowel obstruction, and laparotomy disclosed multiple metastases involving the small and large bowel. The paper describes the clinical course and management of this patient and reviews the pertinent literature.

Aged↗

PubMed1994

Cough induced by quinapril with resolution after changing to fosinopril.

OBJECTIVE: To report a case of chronic, nonproductive cough secondary to the angiotensin-converting enzyme (ACE) inhibitor quinapril, with complete resolution after switching to another ACE inhibitor, fosinopril. DATA SOURCES: All relevant articles from January 1985 through February 1993 were identified, primarily through MEDLINE search and review of pertinent articles' bibliographies. CASE SUMMARY: A 68-year-old woman developed a dry, irritating cough within one month of starting quinapril therapy for the treatment of essential hypertension. The patient was a nonsmoker with no respiratory illnesses. The cough continued for the duration of therapy with quinapril. One month after changing to fosinopril therapy, the patient reported complete resolution of the cough. She remains cough-free to date. DISCUSSION: Cough induced by ACE inhibitors is a frequently documented adverse effect. It is severe enough to require discontinuation of therapy in 1-10 percent of patients. The cough is considered to be a class-related adverse effect with cross-reactions between ACE inhibitors routinely reported. At this time, changing to another ACE inhibitor or additive therapy with nonsteroidal antiinflammatory drugs is not recommended. Discontinuation of the ACE inhibitor results in rapid alleviation of the cough, although this is not always necessary, as most patients may experience a cessation or decrease in cough. We report a case of cough following the administration of quinapril, with complete resolution after changing to the alternative ACE inhibitor fosinopril in a patient with essential hypertension. CONCLUSIONS: Cough has been encountered commonly after the administration of ACE inhibitors. Frequency of cough is variable and although this complication has been described as a class effect, patients with a persistent, severe ACE inhibitor-induced cough may benefit from a trial of fosinopril therapy. This may be particularly useful in patients unable to tolerate an alternative class of antihypertensive agents.

Aged↗

PubMed1993

Hypoglycemia secondary to trimethoprim/sulfamethoxazole administration in a renal transplant patient.

OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced hypoglycemia in an immunosuppressed renal transplant patient. DATA SOURCE: English-language journal articles and reference texts identified via a MEDLINE search and a bibliographic review of pertinent data sources. DATA SYNTHESIS: Hypoglycemia resulting from the combination of sulfonylureas and sulfonamides is a recognized drug interaction. Hypoglycemia induced by sulfonamides alone may be encountered less frequently. Previously reported cases of TMP/SMX-induced hypoglycemia postulated that the sulfonamide mimics hypoglycemic sulfonylurea agents and stimulates pancreatic islet cells to secrete insulin. We report a case of hypoglycemia following the administration of high-dose TMP/SMX in a renal transplant patient. Elevated C-peptide concentrations following the hypoglycemic episode indicate that hypoglycemia resulted from increased endogenous insulin secretion. CONCLUSIONS: Hypoglycemia has been a rarely encountered result of TMP/SMX use. Patients receiving TMP/SMX, particularly those with impaired renal function and those receiving high doses, should be monitored closely for hypoglycemia.

Adult↗

PubMed1992

Diltiazem potentiates angiotensin II-mediated renal prostacyclin synthesis.

Diltiazem (DIL), a calcium antagonist, has variable effects on renal hemodynamics, and has been considered to act independently of renal prostaglandins (PGs). Angiotensin II (AII) constricts renal vasculature but also increases renal vasodilator PG synthesis. We examined interactions between AII and DIL on [14C]p-aminohippurate ([14C]PAH) clearance, mean arterial pressure (MAP), and urine 6-ketoprostaglandin F1 alpha excretion (U6k) in groups of seven to nine conscious Sprague-Dawley rats. We calculated the renal vascular resistance (RVR) as the ratio of MAP/[14C]PAH clearance. AII infusion (10 ng/kg/min i.v.) increased the RVR by 50-80% for at least 120 min. DIL (1 mg/kg plus 2 micrograms/kg/min) reversed this vasoconstriction but adding indomethacin to DIL prevented the reversal. DIL alone did not change the RVR at 30-60 min after starting an infusion but increased it by 22% at 90-120 min. Adding AII to the DIL infusion actually decreased the RVR and this decrease was abolished by indomethacin. DIL alone had no effect on U6k while AII increased it slightly (1.36 +/- 0.12 to 1.86 +/- 0.22 ng/30 min, n = 6, p less than 0.05), and adding DIL to AII increased it further (3.19 ng/30 min, n = 6, p less than 0.05). We conclude that DIL enhances AII-induced renal prostacyclin synthesis and that this is functionally relevant. This mechanism may explain the reported variability of the renal hemodynamic effects of DIL. Furthermore, DIL-enhanced renal vasodilator PG synthesis may help protect the kidney during vasoconstrictor stress.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Diltiazem increases renal prostacyclin.

We sought to determine whether the specific renal vasodilator effect of low dose diltiazem (D) was mediated by increased renal prostacyclin (PGI2) synthesis. Groups of 7-9 Sprague-Dawley rats were fitted with an indwelling transabdominal bladder cannula. Cannulae were placed in the jugular and femoral veins and the carotid artery and the rats allowed to recover for 24 h. Angiotensin II (AII) was infused intravenously at a rate (10 ng/kg/min) which increased mean arterial pressure (MAP) by 5-10%. After 30 min D(1 mg/kg and 2 micrograms/kg/min), D plus indomethacin (IND) (2 mg/kg and 33 micrograms/kg/min), IND plus vehicle or vehicle alone were added to AII. AII increased urinary 6-keto-prostaglandinF1 alpha (6-ketoPGF1 alpha) excretion from 1.36 +/- 0.12 to 1.86 +/- 0.20 ng/30 min (p less than 0.05) and D increased it further to 3.19 +/- 0.39 (p less than 0.05). Renal plasma flow (RPF) was estimated by 14C-PAH clearance (CPAH). Urinary excretion of 6-ketoPGF1 alpha was increased with AII indicating increased renal PGI2 synthesis. This increase in PGI2 was unable to prevent a reduction in RPF. D administration further increased the excretion of 6-ketoPGF1 alpha and reversed AII-induced renal vasoconstriction. IND augmented the AII response and prevented the effect of D, suggesting the renal vasodilator effect of D is, at least in part, PGI2-mediated. This mechanism may help maintain renal blood flow under conditions of vasoconstrictor stress.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

The effects of streptozotocin-induced diabetes on the peptidergic innervation and function of the rat parotid gland.

The effects of streptozotocin-induced diabetes on the function and pattern of innervation of the rat parotid gland were investigated. An in vitro preparation was used to measure amylase release and immunohistochemistry was used to examine the innervation of the gland. Basal amylase release and the response to field stimulation were reduced in diabetic animals. In the presence of atropine or a propranolol/phentolamine mixture both control and diabetic responses were attenuated. When all 3 antagonists were present the response to field stimulation (non-adrenergic, non-cholinergic [NANC] response) was about 30% of maximal in untreated rats but virtually abolished in diabetic animals. Substance P (SP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) all stimulated amylase release in untreated rats. However, in diabetic rats the responses to all 3 peptides were reduced. No differences in staining were observed between control and diabetic rats with antisera to tyrosine hydroxylase, substance P. VIP or calcitonin gene-related peptide. In contrast there was a marked reduction in NPY-like immunoreactivity in the acinar tissue of diabetic rats. These data suggest that the diabetic rats had a failure of NANC transmission which appears to be due to a reduced NPY innervation and a lack of responsiveness to peptidergic (SP, VIP and NPY) agonists.

Amylases↗