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Biomedical subjects

D Agrawal

Publications and source records attributed to D Agrawal.

At least 19 recordsLinked to original sources
PubMed2006

Anterior encephaloceles: a series of 103 cases over 32 years.

Anterior encephalocele is a rarely reported CNS malformation with a geographical predilection for South-East Asia. The paucity of literature prompted us to analyse our results with hemiorbital advancement and classical Tessier's operation in 103 cases over 32 years (1971-2002). In our series, the frontoethmoidal subtype was the most common (80%), followed by the orbital (8%), transethmoidal (8%), transsellar (3%) and interfrontal types (1%). All patients with classical frontoethmoidal encephalocele had swelling over the nose or inner canthus since birth, with varying degrees of hypertelorism; and those with the nasopharyngeal subtype commonly presented with nasal obstruction and cerebrospinal fluid (CSF) rhinorrhoea. Neurofibromatosis was present in seven patients, all of whom had an orbital encephalocele. The diagnostic workup included a computerised tomography scan of the head in 96 patients and magnetic resonance imaging of the brain in 16 patients. The associated findings on imaging were hydrocephalus (15%), corpus callosum agenesis (7%), arachnoid cyst (3%), porencephalic cyst (3%) and single ventricle (3%). A classical Tessier's operation was performed in the initial 30 cases. However, since 1988, we have been performing a single stage hemiorbital advancement and repair of the encephalocele. There were three deaths, one due to pneumonia and two due to fulminant meningitis. Twenty-two patients (22%) had postoperative CSF leak, of which five required lumboperitoneal shunt placement. We believe that hemiorbital advancement offers satisfactory results with less morbidity than the Tessier's operation.

Adolescent↗
PubMed2006

Technetium Tc-99m ethyl cysteinate dimer brain single-photon emission CT in mild traumatic brain injury: a prospective study.

PURPOSE: To explore the role of single-photon emission CT (SPECT) in initial diagnostic evaluation of patients with mild traumatic brain injury (MTBI) and to identify subgroups in which it may serve as a useful diagnostic tool. MATERIALS AND METHODS: Patients with MTBI seen during a 14-month period were prospectively included in this study. All patients had a CT of head within 12 hours of injury and SPECT by using technetium Tc99m ethyl cysteinate dimer (Tc99m-ECD) within 72 hours of injury. Both SPECT and CT findings were compared with clinical features such as posttraumatic amnesia (PTA), postconcussion syndrome (PCS), and loss of consciousness (LOC). RESULTS: Ninety-two patients with MTBI underwent SPECT in the study period. There were 28 children and 64 adults, with male-to-female ratio of 4.5 to 1. CT findings were abnormal in 31 (34%) and SPECT in 58 (63%). The most common abnormality was hypoperfusion in the frontal lobe(s) in adults and the temporal lobe in children. A significantly higher number of perfusion abnormalities were seen in patients with PTA (P = .03), LOC (P = .02), and PCS (P = .01) than in patients without these symptoms. Compared to CT, SPECT had a much higher sensitivity for detecting an organic basis in these subgroup, of patients (P < .05). CONCLUSION: Tc99m-ECD SPECT can be used as a complementary technique to CT in initial evaluation of patients with MTBI. It is particularly useful in patients having PCS, LOC, or PTA with normal CT scan.

Adolescent↗
PubMed2005

Fusiform aneurysm of a persistent trigeminal artery.

OBJECTIVE: Fusiform aneurysms of the persistent trigeminal artery are rare and endovascular treatment of these aneurysms has not been attempted previously. We describe a case of persistent trigeminal artery with a fusiform aneurysm in its middle third, managed using Guglielmi detachable coils (GDC). CLINICAL PRESENTATION: A 50-year-old, diabetic and hypertensive patient presented with sudden onset headache and neck stiffness. On examination, she was conscious but disoriented, without cranial nerve or sensorimotor deficits. Four-vessel cerebral digital subtraction angiography revealed a fusiform aneurysm of the middle third of a persistent trigeminal artery on the left side with adult type posterior cerebral arteries. INTERVENTION: Guglielmi detachable coils were used for occlusion of the persistent trigeminal artery. RESULTS: The procedure was well tolerated but delayed ischemic neurological deficits developed due to vasospasm. CONCLUSIONS: (1) In spite of angiographically documented independence of the anterior and posterior cerebral circulation, occlusion of a persistent trigeminal artery using endovascular techniques may result in posterior circulation stroke due to a number of factors, including occlusion of brainstem perforators taking origin from the persistent trigeminal artery or vasospasm. (2) The timing for endovascular intervention following aneurysmal rupture remains poorly defined.

Cerebral Angiography↗
PubMed2004

Efficacy and results of expansive laminoplasty in patients with severe cervical myelopathy due to cervical canal stenosis.

AIMS AND OBJECTIVES: To assess the efficacy and results of expansive laminoplasty in advanced (Nurick's Grade III or greater) cervical myelopathy. MATERIALS AND METHODS: We reviewed data in 24 patients who underwent cervical laminoplasty from January 1999 to December 2002. Nuricks grading was used for quantifying the neurological deficits and outcome analysis was done using Odom's criteria. A modified Hirabayashi's open door laminoplasty was done using Titanium miniplates and screws in 22 patients, autologous bone in one and hydroxyapatite spacer in one patient. OBSERVATIONS: There were 3 females and 21 males with a mean age of 56 years (range 39-72 years). Four patients presented in Nuricks Grade III, 15 in Grade IV and five in Grade V. MR imaging showed MSCS in 21 cases, OPLL in nine cases and ligamentum flavum hypertrophy in nine cases with cord signal changes being present in 19 cases. RESULTS: All patients with duration of symptoms less than three years, and 50 % with duration ranging from three to six years had improvement by at least one Nurick's grade following surgery. Eighty-seven per cent Grade IV patients (ambulatory with support) improved to Grade III (ambulatory without support) following laminoplasty. Using Odom's criteria, 23 patients (95.8%) had a good to fair outcome. CONCLUSIONS: Cord decompression with expansive laminoplasty using titanium miniplate fixation may improve the neurological outcome even in patients presenting late, and improvement by even one grade may have major 'quality of life' benefits for these patients.

Adult↗
PubMed2003

Immunogenicity of a recombinant human immunodeficiency virus (HIV)-canarypox vaccine in HIV-seronegative Ugandan volunteers: results of the HIV Network for Prevention Trials 007 Vaccine Study.

In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n = 20), control vector containing the rabies virus glycoprotein G gene (n = 10), or saline placebo (n = 10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients.

AIDS Vaccines↗
PubMed2003

Evaluation of antigen-specific responses using in vitro enriched T cells.

Antigen-specific lymphocytes are important in the immune response to viral infection. Peripheral blood mononuclear cells (PBMC) are traditionally used as a source of effector cells in most immunological studies. We described here the use of the bispecific monoclonal antibodies (BSMAB) anti CD3:CD8 (CD3,8) and anti CD3:CD4 (CD3,4B) to expand and selectively enrich CD4+ and CD8+ T cells populations, respectively. The expanded cells demonstrated >90% CD3+CD4+ or CD3+CD8+ by 14 days. We measured HIV- and CMV-specific responses of these subset-enriched T cell and found that sensitivity and specificity is similar or higher when compared to PBMC in various cellular immunology assays (CMI). Vbeta analysis of BSMAB-enriched cells demonstrated comparable repertoire to the parent PBMC. Although both CD45RA(hi) and CD45RO(hi) cell populations were expanded with the BSMAB, selective subset depletion demonstrated that the antigen-specific T cell responses were restricted to the initial CD45RO(hi) memory effector subgroup. In conclusion, BSMAB in vitro enrichment of T cells allows significant expansion of the cell population without loss of specificity. This technique of cell expansion permits studies of T cell subset function in situations where the initial cell source is scarce, and presents an alternative for viable and functional T cells in immunological assays.

Antibodies, Bispecific↗
PubMed2003

Spontaneous subdural hematoma in a young adult with hemophilia.

We report a case of spontaneous acute subdural hematoma in a 30-year-old man, who was diagnosed with hemophilia during his hospital stay. He developed an extradural hematoma following evacuation of the acute SDH, which was also evacuated. He had a good outcome. Management of such a patient is discussed.

Acute Disease↗
PubMed2001

p27Kip1 regulates T cell proliferation.

Our studies addressed the mechanism by which serum acts in conjunction with T cell receptor (TCR) agonists to promote the proliferation of primary splenic T cells. When added to resting splenocytes, TCR agonists initiated G(0)/G(1) traverse and activated cyclin D3-cdk6 complexes in a serum-independent manner. On the other hand, both TCR agonists and 10% serum were required for the activation of cyclin E-cdk2 and cyclin A-cdk2 complexes and the entry of cells into S phase. Serum facilitated cdk2 activation by maximizing the extent and extending the duration of the TCR-initiated down-regulation of the cdk2 inhibitor, p27(Kip1). Although p27(Kip1) levels were reduced (albeit submaximally) in cells stimulated in serum-deficient medium, nearly all of the cdk2 complexes in these cells contained p27(Kip1). In contrast, in cells receiving TCR agonist and 10% serum, little if any p27(Kip1) was present in cyclin-cdk2 complexes. Unlike wild-type splenocytes, p27(Kip1)-null splenocytes did not require serum for cdk2 activation or S phase entry whereas loss of the related cdk2 inhibitor, p21(Cip1), did not override the serum dependence of these responses. We also found that cdk2 activation was both necessary and sufficient for maximal expression of cdk2 protein. These studies provide a mechanistic basis for the serum dependence of T cell mitogenesis.

Animals↗
PubMed2000

Analysis of cyclin D3-cdk4 complexes in fibroblasts expressing and lacking p27(kip1) and p21(cip1).

Our studies examined the effects of p27(kip1) and p21(cip1) on the assembly and activity of cyclin D3-cdk4 complexes and determined the composition of the cyclin D3 pool in cells containing and lacking these cyclin-dependent kinase inhibitors. We found that catalytically active cyclin D3-cdk4 complexes were present in fibroblasts derived from p27(kip1)-p21(cip1)-null mice and that immunodepletion of extracts of wild-type cells with antibody to p27(kip1) and/or p21(cip1) removed cyclin D3 protein but not cyclin D3-associated activity. Similar results were observed in experiments assaying cyclin D1-cdk4 activity. Data obtained using mixed cell extracts demonstrated that p27(kip1) interacted with cyclin D3-cdk4 complexes in vitro and that this interaction was paralleled by a loss of cyclin D3-cdk4 activity. In p27(kip1)-p21(cip1)-deficient cells, the cyclin D3 pool consisted primarily of cyclin D3 monomers, whereas in wild-type cells, the majority of cyclin D3 molecules were complexed to cdk4 and either p27(kip1) or p21(cip1) or were monomeric. We conclude that neither p27(kip1) nor p21(cip1) is required for the formation of cyclin D3-cdk4 complexes and that cyclin D3-cdk4 complexes containing p27(kip1) or p21(cip1) are inactive. We suggest that only a minor portion of the total cyclin D3 pool accounts for all of the cyclin D3-cdk4 activity in the cell regardless of whether the cell contains p27(kip1) and p21(cip1).

3T3 Cells↗
PubMed1998

Primary keratinocytes have an adhesion dependent S phase checkpoint that is absent in immortalized cell lines.

In order to understand the mechanism through which loss of anchorage inhibits growth, we have investigated the events that occur in murine keratinocytes upon substratum detachment utilizing both primary cells and established immortalized cell lines. Our data has revealed that while both primary and immortalized cells undergo growth arrest in suspension, the nature of this arrest is markedly different. Primary cells exhibit a growth arrest that is characterized by rapid cessation of DNA synthesis resulting in a static S phase population. In contrast, an immortalized non-tumorgenic cell line, Balb MK, exhibits growth arrest as measured by thymidine incorporation, but does not prevent cells that have entered S phase from continuing into G2/M, and accumulating as a 4N population. In contrast to both primary and MK cells, the tumorigenic SLC-1 cell line did not accumulate in a specific cell cycle interval and were able to undergo continuous growth in suspension. Examination of cyclin A protein and its associated activity revealed that cyclin A protein levels decreased in primary but not MK cells; suggesting the continued presence of cyclin A may allow continued DNA synthesis observed in MK cells. Furthermore, we demonstrate the accumulation of suspension cultured MK cells as a 4N population correlated with the loss of cyclin A/cdk2 kinase activity, which in turn occurred through the accumulation of p27kip1, whereas neither p27kip1 accumulation nor loss of cyclin A activity was observed in SLC-1 cells. Our results clearly reveal that the process of growth inhibition in suspension cultured cells may occur in several forms with distinct characteristics that are dependent on the status of cyclin/cdk complexes and CKI proteins. Tumor derived cells in suspension did not lose cyclin A dependent kinase activity and thus continued to grow and divide.

Animals↗
PubMed1998

The role of cyclin D3-dependent kinase in the phosphorylation of p130 in mouse BALB/c 3T3 fibroblasts.

We have observed that cyclin D3-dependent kinase activity is increased in the late G1 phase in BALB/c 3T3 fibroblasts. The profile of cyclin D3-associated activity closely parallels that of cyclin D1, which is also induced after mitogenic stimulation of quiescent cells. These activities correlate with the appearance of hyperphosphorylated p130, an Rb family member important in regulating E2F-4 and E2F-5 activity in fibroblastic cells. We demonstrated, however, that only the cyclin D3 activity efficiently phosphorylated p130 in an in vitro kinase assay. This apparent specificity was further demonstrated by experiments which demonstrated that cyclin D3 was physically associated with p130 at the times when D3-dependent kinase activity and p130 hyperphosphorylation were observed. Examination of E2F by electrophoretic mobility shift assay revealed that E2F-4 DNA binding activity existed in a p130.E2F complex at times before D3-dependent kinase activity was apparent and in a free E2F-4 complex after D3 activity developed. Thus, our data suggest that cyclin D3 preferentially phosphorylates p130 and is thereby specifically targeted to overcoming growth-suppressive control mediated through p130 pathways.

3T3 Cells↗
PubMed1998

Cyclin D3-associated kinase activity is regulated by p27kip1 in BALB/c 3T3 cells.

We report that cyclin D3/cdk4 kinase activity is regulated by p27(kip1) in BALB/c 3T3 cells. The association of p27(kip1) was found to result in inhibition of cyclin D3 activity as measured by immune complex kinase assays utilizing cyclin D3-specific antibodies. The ternary p27(kip1)/cyclin D3/cdk4 complexes do exhibit kinase activity when measured in immune complex kinase assays utilizing p27(kip1)-specific antibodies. The association of p27(kip1) with cyclin D3 was highest in quiescent cells and declined upon mitogenic stimulation, concomitantly with declines in the total level of p27(kip1) protein. The decline in this association could be elicited by PDGF treatment alone; this was not sufficient, however, for activation of cyclin D3 activity, which also required the presence of factors in platelet-poor plasma in the culturing medium. Unlike cyclin D3 activity, which was detected only in growing cells, p27(kip1) kinase activity was present throughout the cell cycle. Since we found that the p27(kip1) activity was dependent on cyclin D3 and cdk4, we compared the substrate specificity of the active ternary complex containing p27(kip1) and the active cyclin D3 lacking p27(kip1) by tryptic phosphopeptide mapping of GST-Rb phosphorylated in vitro and also by comparing the relative phosphorylation activity toward a panel of peptide substrates. We found that ternary p27(kip1)/cyclin D3/cdk4 complexes exhibited a different specificity than the active binary cyclin D3/cdk4 complexes, suggesting that p27(kip1) has the capacity to both inhibit cyclin D/cdk4 activity as well as to modulate cyclin D3/cdk4 activity by altering its substrate preference.

3T3 Cells↗
PubMed1998

Alterations in rat erythrocyte membrane due to hexachlorocyclohexane (technical) exposure.

1. Hexachlorocyclohexane (HCH), an organochlorine pesticide having hydrophobic molecule is known to act on membranes. HCH mediated alterations in erythrocyte membrane occur through disorganization of the lipid bilayer. Therefore the changes in erythrocyte membrane fluidity, osmotic fragility and certain membrane bound enzymes were studied. Administration of HCH (technical) to rats at 5 mg/kg, orally, 5 days a week for 1, 2 and 3 months caused marked increase in erythrocyte membrane fluidity, osmotic fragility and decrease in levels of Na+, K(+)-ATPase, acetylcholinesterase in erythrocytes and glutathione in blood. 2. These changes indicate that HCH adversely affects membrane structure and function.

Acetylcholinesterase↗
PubMed1998

Phenytoin dosage.

Explore the source record for details and available documents.

Child, Preschool↗
PubMed1998

STAT3 activation accompanies keratinocyte differentiation.

The signal transducers and activators of transcription (STAT) family of transcription factors has been demonstrated to play key roles in a variety of cell types under conditions that promote differentiation or cell cycle exit. We report our studies of primary murine keratinocytes in which we demonstrate activation of STAT3 during growth arrest and differentiation. In adherent cells, STAT3-specific DNA binding activity was detected in quiescent cultures, down-regulated upon mitogenic stimulation, and found to reaccumulate as cells reentered quiescence. Suspension culturing of proliferating keratinocytes, which induces differentiation, also resulted in induction of STAT3 activity. Furthermore, induction of STAT3 after suspension culturing did not occur in MK cells, an immortalized murine keratinocyte cell line that does not undergo differentiation. Because STAT3 activation in these cells corresponded tightly with the growth status, we examined whether there was a relationship between the cell cycle machinery and STAT3 activation by inhibiting p27kip1 accumulation, which is observed during growth arrest, with antisense oligonucleotides and by using keratinocytes lacking functional p27kip1. In both cases, there was a loss of STAT3 activation and a concomitant delay in terminal cell cycle withdrawal and in the expression of the differentiation specific marker, keratin 1. Thus, in addition to controlling transcription mediated through E2F, our data demonstrate that alterations in the cell cycle machinery are required for appropriate up-regulation of STAT3 activity that occurs during keratinocyte differentiation.

Animals↗
PubMed1997

p107 and p130 associated cyclin A has altered substrate specificity.

We demonstrate that p107 and p130 immune complexes exhibit kinase activity. We have tested such immune complexes with four substrates commonly utilized to assay Cdk activity, including all three known members of the retinoblastoma family. Immunodepletion revealed this kinase activity could be abolished by removal of either cyclin A or Cdk2 but was unaffected by removal of Cdk4 or any D-type cyclin. The appearance of p107 associated activity followed the accumulation of p107 protein. In contrast, the kinase activity associated with p130 immune complexes became apparent after mid-G1, coincident with p130 hyperphosphorylation. GST-Rb, GST-p107, and GST-p130 (where GST indicates glutathione S-transferase) were equally suitable substrates in p107 and p130 immune complex kinase assays, yielding activity equal to 25% of the cyclin A activity present. The p107 and p130 associated activity was unable to phosphorylate histone H1, suggesting the p107 and p130 associated cyclin A/Cdk2 may represent a distinct pool with a distinct substrate specificity. The p107 and p130 associated activity was released from the immune complexes upon incubation with ATP and Mg2+ and exhibited the same substrate preference observed with the untreated immune complex. Our data suggest that p107 and p130 recognize, or form by association, a distinct pool of cyclin A/Cdk2 that preferentially phosphorylates retinoblastoma family members.

3T3 Cells↗