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S Sheikh

Publications and source records attributed to S Sheikh.

At least 19 recordsLinked to original sources
PubMed2001

Regulation of human papillomavirus type 1 replication by the viral E2 protein.

The E1 and E2 proteins encoded by papillomaviruses are required for viral replication. Earlier studies have shown that the viral E2 protein plays an important role in replication by targeting the E1 helicase to the origin of replication (ori). We have previously shown that the E1 protein of human papillomavirus (HPV) type 1 is sufficient for the in vivo replication of ori plasmids, although the E2 protein stimulates replication. In this study, we have further analyzed the role of the E2 protein in HPV-1 replication. The optimal ori of HPV-1 contains one putative E1 binding site (E1BS) and two putative E2 binding sites, E2BS-3 and E2BS-4. Plasmid pori171, containing the optimal ori, replicates to much higher levels than plasmid pori312, which includes an additional upstream E2 binding site, E2BS-2, located 75 nucleotides upstream of E2BS-3. To study the possible role of E2BS-2 and other upstream sequences in E2-dependent downregulation of replication, transient replication analysis was done in the presence of increasing levels of the E2 protein. Interestingly, inhibition of pori312 replication was more severe at higher levels of E2, suggesting that this protein may also negatively regulate HPV-1 replication. Deletion of sequences from pori312 containing an additional putative E2BS, E2BS-2A, relieved the repression of replication to a significant extent, while replacement of E2BS-2 with a different sequence of the same length had a modest effect. These results suggest that E2BS-2A plays a major and E2BS-2 a minor role in the negative regulation of HPV-1 replication at high E2 levels. Electrophoretic mobility-shift assays showed that the purified E2 protein bound with high affinity to E2BS-3 and weakly to the other putative E2BSs located within the viral long control region. EMSA using various ori fragments showed the formation of multiple E2-DNA complexes which likely represent binding of E2 to multiple E2BSs present within the HPV-1 ori. Our data are consistent with the assembly of ori-protein complexes at high E2 levels that are impaired for replication and further suggest that E2 may regulate HPV-1 replication by a mechanism involving interaction between the E2 protein bound to E2BSs at a distance.

Blotting, Western↗
PubMed2001

Evaluation of the wheezy infant.

BACKGROUND: The infant with persistent or recurrent wheezing during the first 2 years of life poses a diagnostic dilemma, which can be a source of anxiety to both physicians and parents. A suggested diagnostic approach to the causes of infantile wheezing is outlined. OBJECTIVES: 1. To review the physiologic considerations of the infant's airways that predispose to wheezing. 2. To discuss the key physical findings, family history, and risk factors associated with wheezing in infants. 3. To develop a rational approach to the differential diagnosis and management of infantile wheezing. DATA SOURCES: The MEDLINE database as well as our clinical experience pertaining to infantile wheezing. CONCLUSIONS: This review discusses the diagnostic evaluation and treatment of the wheezing infant. We suggest that infant pulmonary function testing may be used as one diagnostic aid in the workup of the wheezing infant.

Diagnosis, Differential↗
PubMed2001

Expression of insulin-like growth factor-I and placental growth hormone mRNA in placentae: a comparison between normal and intrauterine growth retardation pregnancies.

Intrauterine growth restriction (IUGR) is generally defined as the pathological restriction of fetal growth resulting in a fetus with birth weight below the 10th percentile for gestational age. Almost 75% of IUGR cases develop during third trimester. Studies on animals (rodents and sheep) as well as humans suggest that insulin-like growth factor-I (IGF-I), under the influence of placental growth hormone (PGH) plays crucial roles in fetal growth regulation during this period. Limited data are available with regard to IGF-I and PGH in placentae of normal and IUGR births. Therefore, in the present study, IGF-I and PGH mRNA expression has been studied in term placentae of normal (n = 10) and IUGR (n = 15) births by in-situ hybridization procedure. Their expression was also studied in first (n = 5) and second (n = 5) trimester placentae obtained from elective termination of normal pregnancies. Both IGF-I and PGH expression were found to be higher in the first and second trimester placentae compared to term placentae in normal pregnancies. However, IUGR term placentae showed increased expression of both IGF-I and PGH mRNA in comparison with normal placentae. Various mechanisms leading to the increased transcription of IGF-I and PGH mRNA in IUGR placenta are discussed. This increased transcription perhaps occurs in response to the reduction in the fetal growth.

Female↗
PubMed2001

Urinary leukotriene E(4) excretion during the first month of life and subsequent bronchopulmonary dysplasia in premature infants.

BACKGROUND: Inflammation plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD), but the exact nature of this inflammatory process is incompletely understood. Older infants with established BPD have higher levels of urinary leukotriene E(4) (LTE(4)) compared to healthy infants of the same age. This suggests that cysteinyl leukotrienes may play a role in the abnormalities seen in BPD. OBJECTIVES: To measure urinary LTE(4) levels during the first month of life in premature infants, and to determine whether there are significant differences in premature infants who develop BPD, as compared to those who do not develop BPD. DESIGN: Prospective, blinded, controlled study. SETTING: Neonatal ICUs of a tertiary-care university hospital. METHODS: Thirty-seven premature infants (< 33 weeks of gestational age) were enrolled prospectively at birth. Urinary LTE(4) levels were measured blinded, using a standard radioimmunoassay technique at 2 days, 7 days, and 28 days of life. At 1 month of age, infants were classified as with or without BPD, based on need for supplemental oxygen, and characteristic chest radiographs. Clinical features and urinary LTE(4) were compared between the two groups. RESULTS: Mean +/- SD gestational age was 29 +/- 2.6 weeks. None of the infants had a family history of asthma. Thirteen of 37 infants were classified as having BPD at 28 days after birth. Mean gestational age in infants who developed BPD was 27 +/- 2.4 weeks, compared to 30 +/- 2 weeks in infants who did not develop BPD (p < 0.05). In infants with BPD, mean urinary LTE(4) levels of urinary creatinine were 1,762 +/- 2,003 pg/mg, 1,236 +/- 992 pg/mg, and 5,541 +/- 5,146 pg/mg at days 2, 7, and 28, respectively, compared to 1,304 +/- 1,195 pg/mg, 1,158 +/- 1,133 pg/mg, and 2,800 +/- 2,080 pg/mg in infants without BPD. LTE(4) levels at 2 days, 7 days, and 28 days did not correlate with the subsequent development of BPD. LTE(4) levels at day 28 were significantly higher than LTE(4) levels at day 2 and day 7 in both groups, even after correcting for gestational age or birth weight (p < 0.05). There was significant inverse correlation between LTE(4) levels at day 2 with gestational age and birth weight (p < 0.05). All 13 infants with BPD received steroid pulses, compared to 3 of 26 infants without BPD. Gestational age and use of postnatal steroid pulses, diuretics, and theophylline (for apnea of prematurity) were significantly associated with each other and with the subsequent development of BPD. CONCLUSION: Urinary LTE(4) levels measured on the second day of life in very-low-birth-weight infants inversely correlate with gestational age and birth weight. Urinary LTE(4) levels may reflect lung injury and/or inflammation in premature infants, not necessarily related to BPD as it is presently defined.

Biomarkers↗
PubMed2001

Chronic aspiration without gastroesophageal reflux as a cause of chronic respiratory symptoms in neurologically normal infants.

OBJECTIVE: To describe 13 neurologically normal infants with chronic respiratory symptoms who had swallowing dysfunction with silent chronic aspiration without gastroesophageal reflux (GER) as the cause of their respiratory symptoms. BACKGROUND: Infants with neurologic disorders and infants with GER are known to have chronic respiratory symptoms. Isolated swallowing dysfunction and aspiration without GER in neurologically normal infants have not been widely reported. DESIGN: Retrospective chart review. SETTING: A tertiary pulmonary-care center at a children's hospital. PATIENTS: One hundred twelve otherwise healthy infants referred for respiratory symptoms who underwent esophageal pH studies and videofluoroscopic swallow studies (VSSs). METHODS: The records of infants referred between January 1997 and December 1999 to the Department of Pediatric Pulmonology who underwent 24-h esophageal pH monitoring and VSS as part of an evaluation for recurrent stridor and/or wheezing were reviewed. Significant GER was diagnosed if the percentage of time with esophageal pH < 4 was > 6%. Infants included in the study presented with recurrent respiratory symptoms, were born at term, were neurologically normal, had normal results of esophageal pH studies, but had abnormal results of VSSs (n = 13). RESULTS: All 13 infants presented with a variety of recurrent respiratory symptoms including wheezing and intermittent stridor. Ten of 13 infants had spitting and/or choking episodes with feeding. The mean (+/- SD) age at the onset of symptoms was 2.0 +/- 1.6 months, and the mean age at VSS was 5.9 +/- 3.4 months. All 13 infants had normal results of 24-h esophageal pH studies but had abnormal results for VSSs. All infants had evidence of swallowing dysfunction and direct silent aspiration of liquids with thin consistency. Six infants also were aspirating liquids with thick and/or semi-thick consistencies. None of the infants had evidence of structural anomalies on esophagograms. Nine infants were treated with thickened food, and in four infants oral feedings were stopped. Three of these infants required nasojejunal feeding, and one infant required gastrostomy tube feeding. VSSs were repeated every 3 months. In all infants, swallowing dysfunction resolved within 3 to 9 months. All infants tolerated the resumption of oral feeding. Videofluoroscopic documentation of the resolution of aspiration was followed by the resolution of respiratory symptoms in all infants. CONCLUSION: There is a subgroup of otherwise healthy infants, presenting with wheeze and/or stridor, who have isolated swallowing dysfunction and silent aspiration as the cause of their respiratory symptoms.

Chronic Disease↗
PubMed2000

Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteoblast dysfunction.

Connexin(Cx)43 is the major gap junction protein present in osteoblasts. We have shown that overexpression of Cx45 in osteoblasts expressing endogenous Cx43 leads to decreased cell-cell communication (Koval, M., S.T. Geist, E.M. Westphale, A.E. Kemendy, R. Civitelli, E.C. Beyer, and T.H. Steinberg. 1995. J. Cell Biol. 130:987-995) and transcriptional downregulation of several osteoblastic differentiation markers (Lecanda, F., D.A. Towler, K. Ziambaras, S.-L. Cheng, M. Koval, T.H. Steinberg, and R. Civitelli. 1998. Mol. Biol. Cell 9:2249-2258). Here, using the Cx43-null mouse model, we determined whether genetic deficiency of Cx43 affects skeletal development in vivo. Both intramembranous and endochondral ossification of the cranial vault were delayed in the mutant embryos, and cranial bones originating from migratory neural crest cells were also hypoplastic, leaving an open foramen at birth. Cx43-deficient animals also exhibited retarded ossification of the clavicles, ribs, vertebrae, and limbs, demonstrating that skeletal abnormalities are not restricted to a neural crest defect. However, the axial and appendicular skeleton of Cx43-null animals were essentially normal at birth. Cell to cell diffusion of calcein was poor among Cx43-deficient osteoblasts, whose differentiated phenotypic profile and mineralization potential were greatly impaired, compared with wild-type cells. Therefore, in addition to the reported neural crest cell defect, lack of Cx43 also causes a generalized osteoblast dysfunction, leading to delayed mineralization and skull abnormalities. Cell to cell signaling, mediated by Cx43 gap junctions, was critical for normal osteogenesis, craniofacial development, and osteoblastic function.

Animals↗
PubMed2000

Alpha-gal-independent dual recognition and activation of xenogeneic endothelial cells and human naïve natural killer cells.

BACKGROUND: Interaction between vascularized xenograft and host immune system is thought to occur via Galactose alpha (1,3) Galactose (Gala 1,3 gal) structures decorating the xenograft. METHODS: We raised anti-Gala 1,3 gal-BSA polyclonal antibodies in baboons and investigated effect(s) of these antibodies as well as soluble Gala 1,3 gal-BSA on human naive natural killer (NK) cell interactions with porcine aortic endothelial cells. RESULTS: We demonstrate that human naive (unstimulated) NK cells recognize xenogeneic endothelial cells under conditions where binding to the Gala 1,3 gal structures is minimized by the presence of blocking anti-Gala 1,3 gal IgG or soluble Gala 1-3 gal and in the absence of xenoreactive natural antibodies and complement. After xenogeneic encounter both endothelial cells and human NK cells are activated. Endothelial cell activation is rapid and is manifested initially by an intraendothelial calcium transient and subsequently by expression of P-selectin and vascular endothelial cell adhesion molecule-1 on the xenoendothelium surface. NK cell activation is manifested by increased expression of perforin and increased cytotoxicity towards the xenoendothelium. Neither recognition nor activation of the xenoendothelium was affected by the introduction of either anti-Gala 1,3 gal IgG or soluble Gala 1-3 gal. CONCLUSION: Our data provide evidence that innate immune cells, such as NK cells, recognize and activate xenoendothelial cells independently of Gala 1-3 gal structures and raise the possibility of novel interactive sites on both human naive NK cells and discordant xenogeneic endothelium.

Animals↗
PubMed2000

Relative abundance of different cadherins defines differentiation of mesenchymal precursors into osteogenic, myogenic, or adipogenic pathways.

Cadherins, a family of cell-cell adhesion molecules, provide recognition signals that are important for cell sorting and aggregation during tissue development. This study was performed to determine whether distinct cadherin repertoires define tissue-specific lineages during differentiation of immature C3H10T1/2 and C2C12 mesenchymal cells. Both cell lines expressed mRNA for N-cadherin (N-cad), cadherin-11 (C11), and R-cadherin (R-cad). After induction of osteogenesis by recombinant human BMP-2 (rhBMP-2) treatment, steady state N-cad mRNA slightly increased in C3H10T1/2 cells. Likewise, the abundance of C11 mRNA increased in both cell lines, although the changes were more remarkable in C2C12 cells. By contrast, R-cad expression was almost shut off by rhBMP-2. The immature but committed osteoblastic MC3T3-E1 cells exhibited only minor changes in N-cad and C11 mRNA abundance after rhBMP-2 treatment. Whereas adipogenic differentiation was associated with a net decrease of N-cad and C11 expression in C3H10T1/2 cells, induction of myogenesis in C2C12 cells resulted in up-regulation of N-cad, while R-cad mRNA became undetectable in either case. Similarly, the adipocytic 3T3-L1 cells expressed very low levels of all cadherins when fully differentiated. Therefore, the repertoire of cadherins present in undifferentiated mesenchymal cells undergoes distinct changes during transition to mature cell phenotypes. Although neither N-cad nor C11 represent strict tissue-specific markers, the relative abundance of these mesenchymal cadherins defines lineage-specific signatures, perhaps providing recognition signals for aggregation and differentiation of committed precursors.

3T3 Cells↗
PubMed2000

Fibromatoses of the extremities: clinicopathologic study of 36 cases.

BACKGROUND AND OBJECTIVES: Fibromatoses of the extremities are rare and often recalcitrant to treatment. We evaluated the clinical and pathologic features of a group of extremity fibromatoses treated by surgical excision with or without adjuvant therapy to determine if any clinical or pathologic parameters were predictive of clinical outcome. METHODS: Thirty-six extremity fibromatoses were evaluated. A number of clinical and histologic features were correlated with risk of local recurrence. RESULTS: The cohort included 19 females and 17 males with ages ranging from 11-72 years (mean: 35 years), with 12 tumors of the upper and 24 tumors of the lower extremity. Tumors ranged in size from 1.5-15.5 cm (mean: 7.5 cm).Histologically, 26 were infiltrative, 3 had pushing borders and 7 had both. Mitotic counts ranged from 0-5/50 high-power fields (mean: 0.74). Surgical margins were positive in 22 cases. Seventeen patients were treated with postoperative adjuvant therapy including radiation therapy and tamoxifen. Follow-up information was available in 34 cases (from 1-202 months; mean: 83 months). Nineteen patients (56%) had recurrences, including 11 with multiple recurrences (range to first recurrence: 5-61 months; mean 23 months). Seventy-one percent of patients with a positive surgical margin and clinical follow-up had a local recurrence, compared to 31%with a negative surgical margin (P < 0.05). None of the other clinical or histologic parameters correlated with the risk for local recurrence. CONCLUSIONS: Local control in fibromatoses of the extremities remains problematic. Aside from positive surgical margins, none of the other clinical or histologic parameters evaluated in this study were useful in predicting the risk of local recurrence.

Adolescent↗
PubMed2000

A cross-cultural study of mental health beliefs and attitudes towards seeking professional help.

BACKGROUND: This study sets out to examine the relationship between culture beliefs about the causes of mental distress and attitudes associated with seeking professional help for psychological problems. It was hypothesised that there is a meaningful and statistical relationship between these variables and that there will be a difference in this relationship between Asians and Westerners. Participants were 287 adults belonging to three groups (British Asian, western European and Pakistanis). METHOD: Participants completed two questionnaires: the Orientations to Seeking Professional Help (Fischer and Turner 1970) and the Mental Distress Explanatory Model Questionnaire (Eisenbruch 1990) and a demographic data sheet. RESULTS: Analysis indicated that positive attitudes toward seeking professional help for psychological distress were similar for British Asians, Westerners and Pakistanis. There were significant differences between the three groups in the causal attributions of mental distress. Although culture, as a variable, was not a significant predictor of a positive attitude to seeking professional help, causal beliefs of mental distress were significant predictors of attitudes to seeking help for the British Asian and the Pakistani groups. Beliefs were not significant predictors for attitudes to seeking help for the Western group. CONCLUSION: It was concluded that culturally determined causal beliefs of mental distress contribute to attitudes towards seeking professional help for psychological problems for Asians. Implications for both research and the provision of more appropriate health services for the British Asian minority group in the United Kingdom are discussed.

Adolescent↗
PubMed2000

Amelioration of the bleeding tendency of preoperative aspirin after aortocoronary bypass grafting.

BACKGROUND: Aspirin therapy is widely used in the treatment of cardiac disease. It has been recognized as a causative factor for increased bleeding and blood loss after open heart operations. METHODS: To determine whether high-dose aprotinin maintained its efficacy in reducing blood loss in the presence of aspirin pretreatment in patients undergoing aortocoronary bypass, we performed a double blind study on 60 adult patients. Half received high-dose aprotinin (Trasylol) and half placebo. RESULTS: Total hemoglobin loss, the primary efficacy variable was reduced from 36.1 +/- 31.4 g (mean +/- SD) to 14.1 +/- 16.0 g (p = 0.002). Blood loss was reduced intraoperatively and total loss was reduced from 837.3 mL +/- 404.9 mL to 368.7 mL +/- 164.3 mL (p < 0.001). The number of patients who did not receive any donor blood products was significantly higher in the aprotinin-treated patients (56.7% versus 23.3%, p = 0.008). Activation of the clotting cascade was significantly less in the treated patients toward the end of cardiopulmonary bypass both by measurement of thrombin-antithrombin III complex (p < 0.0001) and prothrombin fragment 1 + 2 (p < 0.0001). D-Dimer generation was significantly less from the onset of bypass and after reversal of heparin in the aprotinin-treated patients (p < 0.0001). CONCLUSIONS: High-dose aprotinin was highly effective in reducing bleeding in this high-risk group of patients. Biochemical analyses suggest the mechanism by which aspirin increases blood loss after cardiopulmonary bypass is different from the blood-preserving effects of aprotinin, which is acting as an antifibrinolytic agent.

Adult↗
PubMed2000

Asymmetrical targeting of type II Na-P(i) cotransporters in renal and intestinal epithelial cell lines.

Targeting of newly synthesized transporters to either the apical or basolateral domains of polarized cells is crucial for the function of epithelia, such as in the renal proximal tubule or in the small intestine. Recently, different sodium-phosphate cotransporters have been identified. Type II cotransporters can be subdivided into two groups: type IIa and type IIb. Type IIa is predominantly expressed in renal proximal tubules, whereas type IIb is located on the intestinal and lung epithelia. To gain some insights into the polarized targeting of the type II cotransporters, we have transiently expressed type IIa and type IIb cotransporters in several epithelial cell lines: two lines derived from renal proximal cells (opossum kidney and LLC-PK(1)), one from renal distal cells (Madin-Darby canine kidney), and one from colonic epithelium (CaCo-2). We studied the expression of the transporters fused to the enhanced green fluorescent protein. Our data indicate that the polarized targeting is dependent on molecular determinants most probably located at the COOH terminus of the cotransporters as well as on the cellular context.

Animals↗
PubMed2000

Can peak expiratory flow predict airflow obstruction in children with asthma?

STUDY OBJECTIVES: A recent trend in the treatment of asthma has been the widespread, independent use of peak expiratory flow (PEF). We examined whether PEF monitoring creates inaccuracies in assessment of children with moderate to severe asthma. METHODS: We compared the negative predictive value of PEF in relation to the forced expiratory volume in 1 second (FEV(1)), and to the forced expiratory flow between 25% and 75% of the vital capacity (FEF(25-75%)) at different levels of air trapping as determined by the residual volume over total lung capacity ratio (RV/TLC). RESULTS: The study included 244 patients, ages 4 to 18 years with all classes of asthma severity, with FEV(1) ranging from 28% to 134% of predicted value. We analyzed 367 sets of pulmonary function tests performed throughout a 3-year period. Thirty percent of patients with a normal PEF value had an abnormal FEV(1) or FEF(25-75%). As air trapping increased, the ability of a normal PEF to predict normal FEV(1) and FEF(25-75%) readings fell from 83% to 53%. The negative predictive value was significantly lower for patients with RV/TLC ratio >30 compared with patients with RV/TLC <30. CONCLUSIONS: The results of this study suggest that it might be possible to identify children for whom the PEF is likely to give false-negative results. As air trapping increases, it causes the PEF to give misleading reassurance of normal pulmonary function. Furthermore, poor predictiveness of PEF is obtained when values 80% of predicted for age are considered normal.

Adolescent↗
PubMed2000

Selected abstracts

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Journal Article↗
PubMed1999

Lung function in infants with wheezing and gastroesophageal reflux.

Eighty-four otherwise healthy infants with daily wheezing underwent infant pulmonary function tests (IPFTs) and 24-h esophageal pH probe studies. Fifty-four (64%) infants had positive pH probe studies, and 30 infants had negative pH probe studies. Many infants in both groups had evidence of peripheral airflow obstruction at tidal breathing and on forced expiration as measured by thoracoabdominal compression. In infants with gastroesophageal reflux (GER), only 9 of 54 (16.6%) responded to bronchodilator therapy compared to 20 of 30 (66.6%) in the group with negative pH probe studies (P < 0.0005). In infants with positive pH studies, family history of asthma (n = 16) correlated well with positive response to bronchodilators (P < 0.0005), and all infants exposed to maternal smoking (n = 11) had no response to bronchodilators. Forty-four percent of infants with a positive pH probe had no gastrointestinal symptoms suggestive of GER. In infants with a negative pH probe, family history of asthma (n = 24) correlated well with positive response to bronchodilators (P < 0.0005), and exposure to maternal smoking (n = 8) correlated well with no response to bronchodilator therapy (P < 0.0005). We conclude that silent GER is common in infants with persistent wheezing. Furthermore, infants with GER are less likely to respond to bronchodilator therapy, and exposure to maternal smoking and family history of asthma may be significant independent factors.

Asthma↗
PubMed1999

Moderate hemoptysis of unknown etiology.

The underlying cause and treatment of hemoptysis should be addressed promptly to avoid potentially life-threatening complications. We report on a previously healthy 11-year-old white boy who presented with acute hemoptysis. On bronchoscopy, bleeding was noted from the right upper and lower lobes. Right bronchial arteriography revealed multiple regions of abnormal "blushing" throughout the right bronchial arterial distribution which was successfully controlled by right bronchial arterial embolization. In spite of an extensive work-up, we were not able to determine the cause of bleeding. The patient has been followed for 18 months without any recurrence and without evidence of any systemic disease. Our patient does not fit any diagnostic category of pulmonary bleeding and further case reports are needed to delineate this entity.

Acute Disease↗