Biomedical subjects

R M Shah

Publications and source records attributed to R M Shah.

At least 19 recordsLinked to original sources

PubMed1998

In vivo and in vitro assessment of mitogen activated protein kinase involvement during quail secondary palate formation.

Spatiotemporally regulated cell proliferation and differentiation are crucial for the successful completion of morphogenesis of the vertebrate secondary palate. An understanding of the mechanisms by which these cellular phenomena are regulated during palate development involves the identification of the various signal transduction pathways. In the present study, the presence and activation of mitogen-activated protein (MAP) kinases were investigated during the development of quail secondary palate. The palatal shelves were dissected on days 5-9 of incubation, homogenized, and centrifuged, after which the samples were separated by anion exchange fast protein liquid chromatography. The fractions were analyzed for myelin basic protein (MBP) phosphorylation. In addition, primary cultures of quail palate mesenchymal cells (QPMCs) were treated with epidermal growth factor (EGF) and prepared for MBP phosphorylation assays. A temporally regulated pattern of phosphotransferase activity, characterized by a three-fold increase in phosphotransferase activity toward MBP between days 5 and 8 of incubation, was observed during quail palate development. Western blotting, using MAP kinase antibodies, demonstrated the presence of a 42-kDa isoform between days 5 and 9 of incubation, during which the level of protein remained constant. Antityrosine immunoblotting with 4G10 also detected a 42-kDa protein. Phosphotransferase assays, using either a MAP kinase-specific substrate peptide (S5) or a protein kinase C inhibitor (R3), further confirmed the presence of a MAP kinase in the developing palate of quail. Because diverse biological processes occur concurrently during in vivo palate morphogenesis, the involvement of MAP kinase was explored further in primary cell culture. The data showed that EGF stimulated proliferation and activated 42-kDa MAP kinase in QPMCs. It is suggested that MAP kinase cascade may be involved in growth factor-regulated cell proliferation during morphogenesis of quail secondary palate.

Animals↗

PubMed1998

CT manifestations of human immunodeficiency virus (HIV)-related pulmonary infections.

The infectious pulmonary complications of acquired immunodeficiency syndrome (AIDS) are reviewed, with emphasis on the spectrum of CT imaging findings and diagnostic accuracy and limitations as reported in the current literature. Changes in epidemiologic trends for common AIDS-related infections and the associated ranges of CD4 lymphocyte counts, when these infections are typically encountered, are discussed.

AIDS-Related Opportunistic Infections↗

PubMed1998

CT angiogram sign: incidence and significance in lobar consolidations evaluated by contrast-enhanced CT.

OBJECTIVE: The CT angiogram sign--that is, the ability to see normal pulmonary vasculature within parenchymal consolidations--was initially reported as specific for the diagnosis of bronchioloalveolar cell carcinoma. Our purpose was to establish the frequency of this sign in lobar consolidations of varied causes as revealed by contrast-enhanced CT. We also sought to determine if the presence of this sign contributed to the specificity of radiographic diagnosis. MATERIALS AND METHODS: All consecutive contrast-enhanced thoracic CT examinations performed for evaluation of lobar consolidations between May 1994 and April 1997 were reviewed. The CT angiogram sign was considered present when segments of pulmonary vessels could be identified within alveolar consolidations. Medical records were reviewed to establish the causes of the consolidations. RESULTS: Fifty-one patients (24 women, mean age = 59 years; 27 men, mean age = 46 years) had lobar or multilobar consolidations due to pneumonia without central obstruction (n = 20), pneumonia or pneumonitis with central obstruction (n = 19), passive atelectasis (n = 7), and (one case each) mucus plugging, lipoid pneumonia, pulmonary lymphoma, bronchioloalveolar cell carcinoma, and pulmonary hemorrhage. The CT angiogram sign was present in 15 (29%) of 51 consolidations, including seven (37%) of 19 postobstructive consolidations, four (20%) of 20 cases of pneumonia without central obstruction, one (14%) of seven cases of passive atelectasis, and each single case of lymphoma, bronchioloalveolar cell carcinoma, and lipoid pneumonia. CONCLUSION: The CT angiogram sign is a common finding in lobar consolidations evaluated by contrast-enhanced CT. However, the sign does not add specificity to the radiographic diagnosis.

Contrast Media↗

PubMed1997

Developmental alterations in casein kinase 2 activity during the morphogenesis of quail secondary palate.

BACKGROUND: During the progression of avian secondary palate morphogenesis, the rate of cell proliferation declines, whereas the production and accumulation of extracellular matrices increases. To investigate the regulation of these events, we examined the quail secondary palate for the activity of casein kinase 2 (CK 2), a pleiotropic serine/threonine second messenger independent enzyme implicated in cell growth and differentiation. METHODS: Quail palatal shelves were dissected between days 5 and 9 of incubation, which is the period of palate morphogenesis in quail, and prepared either for light microscopic observations or homogenized, cleared by ultracentrifugation, and then subjected to fractionation on a MonoQ column by fast protein liquid chromatography and Western immunoblotting. RESULTS: Histological examination showed that the palatal shelves appeared on day 5 of incubation and approximated by day 8 of incubation. Fractionation of palate extract using a Mono-Q column revealed the presence of a major peak of phosvitin phosphotransferase activity which eluted with 0.5 M NaCl. This activity peak coincided with the presence of a 42 kDa subunit of CK 2 as determined by Western blotting with a CK 2 specific antibody. The CK 2 activity towards phosvitin was elevated on days 5 and 6 and then rapidly declined by day 9. The decrease in CK 2 activity did not correlate with a decrease in CK 2 protein during palate development indicating that the differential activity of the CK 2 enzyme observed during quail palate development may be due to post-translational modifications of the enzyme. A high positive correlation was found between the CK 2 phosphotransferase activity and both the proliferation index and DNA synthesis during palate development. CONCLUSION: On the basis of literature analysis and the results of the present study, it was suggested that the activity of CK 2 may be regulated along with protein kinase A to coordinate cell proliferation and the synthesis of extracellular matrices during palate development in quail.

Animals↗

PubMed1997

Image-guided localization for video-assisted thoracic surgery.

Video-assisted thoracic surgery (VATS) has become a useful diagnostic and therapeutic tool in the management of lung, pleural, and mediatstinal disease. Preoperative image-guided localization is performed to aid the surgeon in the thoracoscopic resection of small lung lesions that would otherwise be difficult to resect. This article describes the techniques of localization and reviews our experience with this procedure. While the majority of localization procedures are performed during an immediately preoperative computed tomography (CT), the use of intraoperative lesion localization using an endosonographic probe has been reported. The need for localization before resection is dependent on the skill and experience of the thoracoscopist and the characteristics of the lung lesions.

Endoscopy↗

PubMed1997

Necrotizing fasciitis: CT characteristics.

PURPOSE: To establish computed tomographic (CT) criteria for the diagnosis of necrotizing fasciitis. MATERIALS AND METHODS: Twenty CT scans in 20 patients with pathologically proved necrotizing fasciitis were reviewed retrospectively for fascial thickening, fat infiltration, focal fluid collection, soft-tissue gas, muscle involvement, and intra-abdominal extension; the findings were correlated with clinical factors, including associated illnesses, disease site, treatment, and outcome. RESULTS: Average patient age was 57.8 years; there were 13 men and seven women. Four patients (20%) died. Asymmetric fascial thickening and fat stranding were seen in 16 patients (80%). Gas tracking along fascial planes was present in 11 patients (55%), and abscesses were found in seven patients (35%). Infection sites were scrotum (n = 6), a lower extremity (n = 4), perineum (n = 4), neck (n = 2), back (n = 2), arm (n = 1), and abdomen (n = 1). Underlying illness (n = 17) was diabetes in 10 patients (50%), alcoholism in three (15%), chronic renal failure in two (10%), and drug abuse in two (10%). CONCLUSION: CT criteria of asymmetric fascial thickening and gas are valuable in assessing suspected necrotizing fasciitis. CT also can provide information on coexistent deep collections.

Abscess↗

PubMed1997

High-resolution CT in the acute exacerbation of cystic fibrosis: evaluation of acute findings, reversibility of those findings, and clinical correlation.

OBJECTIVE: The aims of this study were threefold: to compare high-resolution CT (HRCT) of adult patients with cystic fibrosis (CF) during acute exacerbations with asymptomatic patients with CF, to evaluate reversibility of HRCT abnormalities after exacerbations, and to correlate HRCT with clinical parameters. SUBJECTS AND METHODS: Nineteen symptomatic and eight asymptomatic patients were prospectively evaluated by HRCT and pulmonary function tests (PFTs). Symptomatic patients were reassessed 2 weeks after the exacerbation. Studies were independently reviewed by two radiologists using a modified Bhalla scoring system, noting the presence, extent, and severity of bronchiectasis, peribronchial thickening, mucus plugging, and atelectasis or consolidation. Modifications to the Bhalla system included evaluation of the presence and profusion of centrilobular nodules and air-fluid levels within bronchiectatic cavities. The highest possible score was 24 points. Higher scores indicated greater severity. Mosaic perfusion was noted but not included in the modified Bhalla HRCT score. Total modified Bhalla HRCT score and components of the HRCT score were correlated with corresponding PFT parameters. RESULTS: Bronchiectasis, peribronchial thickening, mucus plugging, centrilobular nodules, and mosaic perfusion were identified in symptomatic and asymptomatic patients. Air-fluid levels in bronchiectatic cavities, identified in two patients, represented the only finding limited to acute exacerbation. Reversible findings included air-fluid levels (100%), centrilobular nodules (36%), mucus plugging (33%), and peribronchial thickening (11%). Total HRCT severity scores of symptomatic and asymptomatic patients correlated with forced vital capacity (FVC) (r = .44, p = .01) and forced expiratory volume at 1 sec (FEV1) (r = .34, p = .04). Severity of bronchiectasis correlated with FVC (r = .50, p = .004) and FEV1 (r = .40, p = .02). Mucus plugging and centrilobular nodules did not correlate with PFT parameters. In the symptomatic patients, improvement in HRCT score correlated with changes in FEV1/FVC (r = .39, p = .049). CONCLUSION: Air-fluid levels in bronchiectatic cavities were the only parenchymal finding shown by HRCT that was limited to the acute exacerbation of CF in our study population. However, this finding was rare, being seen in two of 19 patients. Mucus plugging, centrilobular nodules, and peribronchial thickening were potentially reversible findings in symptomatic patients. HRCT accurately revealed disease severity in patients with CF. We also found that changes in HRCT scores correlated with clinical improvement as determined by PFTs.

Acute Disease↗

PubMed1997

The activation of MAP kinase during vertical palatal shelf development in hamster.

Mitogen-activated protein (MAP) kinase has been implicated in signal transduction pathways that regulate cell cycle progression during the proliferation of eukaryotic cells. Previous studies have shown that a rapid burst of cell proliferation is a major event of the development of mammalian palatal shelves in a vertical direction. The present study analyzed the involvement of MAP kinase during the vertical development of the secondary palate in hamster. Palates were dissected at various times between days 10:00 and 12:00 of gestation, homogenized, centrifuged and fractionated on a Mono Q column by fast protein liquid chromatography. The fractions were assayed for phosphotransferase activity toward myelin basic protein, and also toward a synthetic peptide APRTPGGRR (S5), which was more specifically utilized by MAP kinase. The data showed that MAP kinase activity increased during the initial phase, i.e., between days 10:00 and 11:12, and then decreased during the latter half of vertical palate development, i.e., between days 11:12, and 12:00 of gestation. Western blotting studies, using antibodies raised against the subdomain I ATP binding sequence (GEGA), subdomain III (ERK1-III), and the C-terminus (ERK1-CT) of MAP kinases, demonstrated the presence of both the 42-kDa and 44-kDa MAP kinase isoforms between days 10:12 and 12:12 of gestation. A monoclonal antibody (4G10), which detects phosphotyrosine, demonstrated phosphorylation of both the 42-kDa and 44-kDa isoforms. The amount of protein remained constant during vertical palatal shelf development indicating that the differential activity of MAP kinase was most likely due to post-translational modification (i.e., phosphorylation). There was a good correlation between the temporal expression of MAP kinase activity and the rates of cell proliferation in the developing vertical palate suggesting a possible involvement of MAP kinase in regulation of cell proliferation during secondary palate development.

Animals↗

PubMed1996

Changes in casein kinase 2 activity during development of the secondary palate in the hamster.

BACKGROUND: Casein kinase 2 (CK 2) is a serine/threonine kinase that has been ubiquitously conserved in all eukaryotic cells. The exact functions of this enzyme have not yet been clarified; however, studies have repeatedly suggested that it may play crucial roles in the regulation of cell proliferation. During the formation of the secondary palate in the hamster, bursts of cell proliferation occur during the initial half of vertical shelf development, which decrease during the subsequent steps of palate morphogenesis, thus indicating that the cell cycle in the developing vertical palate may be tightly regulated. METHODS: In the present study, palatal shelves were dissected at 12-hour intervals between days 10 and 12 of gestation, which is the period of vertical shelf development in the hamster. The palates were homogenized and cleared by ultracentrifugation and the resultant supernatants were fractionated on a Mono Q column by fast protein liquid chromatography. RESULTS: Using phosvitin as a substrate, the phosphotransferase activity in the fractionated samples decreased steadily from days 10 to 11, increased to a fivefold peak on day 11:12, and then decreased on day 12 of gestation. Western blot analysis using two CK 2 specific antibodies demonstrated that both the 42-kDa (alpha) and the 38-kDa (alpha') subunits of the CK 2 holoenzyme were found throughout the formation of the vertical palatal shelves in the hamster. The amount of alpha and alpha' subunits appears to remain constant, which suggested that the differential activity of the CK 2 enzyme may be due to posttranslational modifications. CK 2 activity correlated well with DNA synthesis (i.e., cell proliferation) rates from days 10 to 11, but not from days 11 to 12 of gestation. CONCLUSIONS: It is proposed that the activity of CK 2 may regulate the rate of cell proliferation by stimulation of progression through G1 phase of the cell cycle and may also relate to the effects of various growth factors during the vertical development of mammalian palate.

Animals↗

PubMed1996

In vivo/in vitro studies on the effects of cyclophosphamide on growth and differentiation of hamster palate.

A study was undertaken to examine the effects of cyclophosphamide (CP) on growth and differentiation of palatal tissues. An in vivo/in vitro approach was designed to analyze (1) whether the damage caused by in vivo administration of CP in the developing palate can be altered in vitro, and (2) to determine the effects of CP on the synthesis of collagen and glycosaminoglycan (GAG), which are essential for proper palate development. In addition, effects of vitamin B1 and/or B6 on in vivo modulation of CP teratogenicity was evaluated. Pregnant hamsters were given 30 mg/kg CP or 1 ml saline on day 10 of gestation. Control and CP-treated embryonic palates were dissected on day 11 of gestation and incubated in vitro in the presence or absence of CP. In order to allow metabolic activation of CP in vitro, either a slice of hamster liver or microsomal S9 fraction of liver was added to the culture medium. To study collagen and GAG synthesis, palates were obtained between days 10 and 13 of gestation, and incubated in growth medium supplemented with [14C]proline or [3H]glucosamine, as appropriate. The rates of collagen and GAG synthesis were determined. The results showed that, in the controls, the presence of a liver slice or S9 fraction in the culture medium had no effects on in vitro closure of palate. In vivo CP exposed palates did not fuse in vitro. When drug was given in vitro, or both in vivo and in vitro, palatal closure did not occur. CP reduced synthesis of both collagen and GAG in the vertically developing palate. The drug-treated shelves reoriented only after the rates of collagen and GAG synthesis were restored to the levels comparable to the control counterparts. Co-administration of vitamin B1 and B6 did not interfere with the teratogenicity of CP. It was suggested that CP treatment affected DNA synthesis and injured growing cells, which in turn reduced the synthesis of GAG and collagen and affected the expansion of shelf volume to delay the reorientation of the palatal shelves. Furthermore, it appears that in vivo treatment with CP changes the programming of palatal tissues to prevent the fusion process in vivo, which could not be altered in vitro.

Animals↗

PubMed1995

Superior vena cava syndrome caused by aneurysm of the innominate artery.

Isolated aneurysms or ruptures of the innominate artery are rare causes of the superior vena cava syndrome. We report on a patient who suffered an isolated acute expansion and rupture of an innominate artery aneurysm that precipitated a dramatic superior vena cava syndrome. Immediate repair using modern surgical techniques, cardiopulmonary bypass, profound hypothermia, circulatory arrest, and a Dacron graft rapidly cured the patient of this deadly syndrome.

Aged↗

PubMed1995

Role of thoracoscopy and preoperative localization procedures in the diagnosis and management of pulmonary pathology.

Video-assisted thoracic surgery is an important component of modern thoracic surgery, providing a safe, less invasive alternative to open thoracotomy in the evaluation of pleural, mediastinal, and parenchymal pathology. Advancements in endoscopic techniques and video-optics have permitted greater visualization of the thoracic cavity and allowed limited pulmonary resections with significantly reduced postoperative morbidity. Thoracoscopy is indicated for diagnosis of intrathoracic pathology when usual methods of diagnosis, including fine-needle aspiration and transbronchial biopsy, are inconclusive. The diagnostic accuracy of video-assisted thoracic surgery approaches 100%. Increasingly, the indications for thoracoscopy include therapeutic resections of pulmonary nodules in cases of limited lung metastases and bronchogenic carcinoma when pulmonary function is poor. Successful diagnostic and therapeutic resection by thoracoscopy requires intraoperative localization of the lesion within the collapsed lung. The indications and methods of thoracoscopic surgery and preoperative localization are discussed.

Biopsy, Needle↗

PubMed1995

Analysis of cell proliferation kinetics during the secondary palate development in quail.

A study was undertaken to analyze the spatio-temporal pattern of mesenchymal cell proliferation in the developing palate of quail. Quail embryos were grown in shell-less culture. The developing palates were labelled with 3H-thymidine between culture days 2-6 (which corresponded in vivo incubation days 5-9), and processed for light microscopic autoradiography. Percent labelled mesenchymal cells were determined. The data showed that, as in mammals, a high rate of random cell proliferation in mesenchyme was a major component of early palate development in quail. As the palate morphogenesis advanced, the rate of cell proliferation declined. Segmental analysis, however, indicated that, in contrast to mammals, the mesenchymal cell proliferation rates continually changed in various regions of quail palate during morphogenesis. It was suggested that the spatio-temporal changes in the distribution of dividing cells may reflect differences in the timings of cell cycles between various segments, thus resulting in a heterogeneous population of cells in the developing palate of quail. Further, the differences in the segmental pattern of cell proliferation between birds and mammals may form the basis for differences in the morphogenesis of their palates.

Animals↗

PubMed1995

Pulmonary complications of cystic fibrosis in adults.

The demographics of cystic fibrosis (CF) are continuously changing, with adults representing a growing percentage of the patient population, which is expected to reach 50% by the year 2000. Pulmonary complications are primarily responsible for the high morbidity and mortality in this disease. Although the radiographic findings are quite specific, the correct diagnosis may not be suggested in the adult patient because of a lack of familiarity with its pulmonary manifestations in this age group. High-resolution CT (HRCT) has contributed to our understanding of the radiographic findings, especially at the level of the small airways. The role of imaging, including chest radiography and HRCT, is discussed. Issues that remain controversial include imaging in the acute pulmonary exacerbation, and the routine use of imaging as part of clinical scoring and in monitoring responses to new treatment modalities.

Adult↗

PubMed1994

Effects of 5-fluorouracil on macromolecular synthesis during secondary palate development in quail.

A study was undertaken to examine the growth of normal and 5-fluorouracil-treated quail secondary palate during embryogenesis. The rates of DNA, RNA, and protein synthesis were measured in the developing quail palate by liquid scintillation counting of radiolabelled thymidine, uridine, or leucine. In addition, shelf volume was determined morphometrically. The results showed that in control palates the shelf volume increased rapidly between days 5 and 7 of incubation. Drug treatment on day 4 did not alter the shelf volume until day 9 of incubation, at which time the treated shelves were smaller than controls. In control palates, the rate of DNA synthesis decreased steadily between days 5 and 9 of incubation. A burst in RNA synthesis on day 7 of incubation was followed by an increase in protein synthesis. Administration of FU seems to exert its effect via disturbing the synthesis of RNA and protein, instead of disruption of DNA synthesis, to ultimately affect the shelf area, and thus palate morphogenesis in quail. Comparison of avian and mammalian data indicated that differences in their palate morphogenesis are also reflected in the different temporal patterns of various macromolecular synthesis.

Animals↗

PubMed1994

Carotid exploration for acute postoperative thrombosis.

To determine the incidence of carotid reoperation and to document operative findings and clinical results, the records of patients requiring early reoperation (after less than 24 hours) during a 10-year period were analyzed with respect to operative findings, clinical outcome, and arterial patency. Endarterectomy was performed in 920 patients, with 27 strokes (3%) and 10 deaths (1%). Early re-exploration was required for 27 patients (3%) for either expanding hematoma (6 patients) or suspected thrombosis associated with a new neurologic deficit (21 patients). Two patients bled from the arteriotomy and 4 bled from surrounding tissues. Exploration for new postoperative neurologic events confirmed thrombosis in 19 cases (91%). Two patients with patent arteries and normal operative arteriograms were felt to have distal embolization, and the arteriotomy was not opened. Causes of thrombosis were intimal flap in 6 patients and closure stenosis in 11; the cause was unknown in 2 cases. All arteries were repaired over a shunt with a patch. Follow-up studies were available for 16 arteries, all of which remained patent. Of patients explored for hemorrhage, there was one death (from myocardial infarction), no neurologic events, and no late infections. Of 21 patients who underwent a second operation for neurologic deficits, 2 died, 8 were unchanged, 2 had minor residual deficit, and 9 had completely resolved deficits. Severe contralateral disease was more common among patients with residual deficits (10 of 12) compared with patients without residual deficits (0 of 9; chi-square = 8.23, P < 0.005). Carotid re-exploration is most commonly undertaken for a new neurologic deficit, usually associated with thrombosis at the operative site. Thrombosis is more often due to arterial narrowing than to an intimal defect. Prompt repair will restore patency and result in improvement in 50% of cases. Neurologic recovery is related to the status of the contralateral artery.

Acute Disease↗

PubMed1994

Effects of 5-fluorouracil on collagen synthesis in the developing palate of hamster.

A study was undertaken to examine the effect of 5-fluorouracil (5-Fu) on collagen synthesis in the developing secondary palate. Pregnant hamsters were given 81 mg/kg 5-FU intramuscularly or 1 ml saline on day 11 of gestation. Control and treated embryonic palates, dissected from hamsters between days 11 and 13 of gestation, were incubated in a growth medium supplemented with [14C]proline. The rate of collagen synthesis, total protein and collagen isotypes were determined. The data showed that in control hamster palate the collagen synthesis peaked between days 12:00 (12 day: 0 h) and 12:04 of gestation, which is the period of shelf reorientation. In 5-FU-exposed hamster palates, the rate of collagen synthesis was lower than controls until day 12:04 of gestation followed by a rise on day 12:12 of gestation. In 5-FU-treated embryos palatal shelf reorientation took place between days 12:16 and 13:00 of gestation. Electrophoresis showed that only type I collagen was synthesized during palate development in both the control and 5-FU-treated hamster embryos. It was suggested that collagen synthesis may play a critical role in shelf reorientation in hamster since (i) new collagen was synthesized in both the control and 5-FU-treated hamster embryos prior to and during the period of normal reorientation, and (ii) in 5-FU-treated hamster embryos, a recovery in collagen synthesis precedes reorientation. Inhibition of collagen synthesis during abnormal development is only a step in the cascade of events of 5-FU-induced effects on protein synthesis.

Animals↗

PubMed1994

Effects of vincristine on developing hamster embryos.

Using dosages and a route of administration which resembled those used clinically in humans, the effects of vincristine on developing hamster embryos were evaluated. The results showed that the drug exerted a highly toxic effect in a dose-dependent manner; however, it exhibited only a sporadic teratogenic (gross malformation) effect. The data on DNA synthesis indicated involvement of internal organs and structures, which needs to be verified. Overall, the teratogenicity of the drug was more pronounced during pre-organogenesis than during the organogenesis period. It was suggested that, in contrast to the data reported in the literature, the different biological response to vincristine in hamster may relate to the use of the dose-route combination, and is potentially relevant to developmental and transplacental carcinogenesis studies.

Abnormalities, Drug-Induced↗