Oropharyngeal mycosis fungoides.
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Biomedical subjects
Publications and source records attributed to V Prabhu.
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In an attempt to understand the molecular basis for the immunological memory response, we have used cDNA microarrays to measure gene expression of human memory and naive CD4+ T cells at rest and after activation. Our analysis of 54,768 cDNA clones provides the first glimpse into gene expression patterns of memory and naive CD4+ T cells at the genome-scale and reveals several novel findings. First, memory and naive CD4+ T cells expressed similar numbers of genes at rest and after activation. Second, we have identified 14 cDNA clones that expressed higher levels of transcripts in memory cells than in naive cells. Third, we have identified 135 (130 known genes and 5 expressed sequence tags) up-regulated and 68 (42 known genes and 26 expressed sequence tags) down-regulated cDNA clones in memory CD4+ T after in vitro stimulation with anti-CD3 plus anti-CD28. Interestingly, the increase in mRNA levels of up-regulated genes was greater in memory than in naive CD4+ T cells after in vitro stimulation and was higher with anti-CD3 plus anti-CD28 than with anti-CD3 alone in both memory and naive CD4+ T cells. Finally, the changes in expression of actin and cytokine genes identified by cDNA microarrays were confirmed by Northern and protein analyses. Together, we have identified approximately 200 cDNA clones whose expression levels changed after activation and suggest that the level of expression of up-regulated genes is a molecular mechanism that differentiates the response of memory from naive CD4+ T cells.
OBJECTIVES: The AO nail mounted 'distal locking aiming device', developed to obtain radiation independent distal locking, has an unproven efficacy in a large clinical setting. This prospective study compares the efficacy and learning curve of the distal aiming device with the popular 'free hand technique'. MATERIALS AND METHODS: Distal locking in thirty cases of statically locked intramedullary femur nailing using the distal aiming device for rotationally stiff unslotted AO SUN nails was prospectively compared with the same number using the free-hand technique with regard to duration, radiation exposure, accuracy of screw placement, and learning curve. RESULTS AND DISCUSSION: For the free-hand technique and the distal aiming system respectively, the average distal locking time was 35.8+/-18.6 versus 19.3+/-9.8 minutes, and the average number of images taken to achieve distal locking was 11.5+/-3.4 versus 3.8+/-3.5. The decrease in average distal locking time by 46.1% and in radiation by 70.0% with the distal aiming system is statistically significant at P<0.001. There were three failures of the distal aiming device and these were converted to the free-hand technique. The learning curve for the distal aiming device was shorter and more predictable than that with the free hand technique. We also analyse the failures and associated pitfalls with the system. CONCLUSIONS: We found the AO distal locking aiming device to be an accurate, radiation-independent jig with a short and predictable learning curve.
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Infection with high-risk human papillomaviruses (HPVs) represents a major risk factor for the development of cervical cancer. The HPV-16 E6 and E7 proteins are highly expressed in differentiating keratinocytes, where they inactivate the p53 and retinoblastoma (pRb) proteins, two important transcriptional regulators. We have used cDNA expression arrays to identify global alterations in gene expression induced by E6 and E7 in differentiating cultures of human cervical keratinocytes. We show that E6 and E7 decrease expression of TGF-beta2 mRNA and alter expression of multiple TGF-beta-responsive genes involved in cell cycle regulation, apoptosis, and tissue remodeling. E6 and E7 inhibited expression of TGF-beta2 RNA 7-fold (relative effectiveness, E6/ E7 > E6 > E7 > control) and decreased secretion of biologically active TGF-beta2 by 70-80% (reduced from 70 to 10 pg/10(6) cells/24 h). Downregulation occurred through p53- and pRb-dependent pathways. In contrast, E6 and E7 did not alter expression of TGF-beta1 and TGF-beta3. Down-regulation of TGF-beta2 was biologically relevant because the addition of recombinant cytokine (10-200 pg/ml) to E6/E7-expressing cells restored expression of TGF-P-responsive genes, inhibited growth of keratinocytes, and decreased immortalization by E6 and E7. These results suggest that TGF-32- and TGF-3-responsive genes are important targets for the HPV-16 E6 and E7 oncoproteins in differentiating cervical keratinocytes.
BACKGROUND: Intraperitoneal adhesions, obesity, and distorted abdominal anatomy in shunt-dependent hydrocephalic patients are patient characteristics that increase distal ventriculoperitoneal (VP) shunt failure rates. The use of laparoscopic-aided placement of the distal VP catheter as a technique to decrease the failure rate is evaluated in these patients. METHOD: Thirteen hydrocephalus patients considered to either have intra-abdominal adhesions, be obese, or have distorted abdominal anatomy underwent laparoscopic-aided distal VP catheter placement or revision. Two had shunts placed for the first time and eleven had revisions. Eight patients had revisions performed by both the standard minilaparotomy and laparoscopic methods, but at different times. The average surgical times for both techniques were looked at for these eight patients. Case illustrations are presented. RESULTS: In patients who had both types of abdominal approaches, the average surgical time was 81 min for the laparoscopic-aided technique versus 116 min for the minilaparotomy procedure. The only complication related directly to the laparoscopic procedure was one wound infection. CONCLUSION: In patients with intra-abdominal adhesions, obesity, or distorted abdominal anatomy, laparoscopic-aided distal shunt insertion increases the success rate by its direct visual capability and the ability to lyse abdominal adhesions and position the distal end of the catheter in a desired place.
In C3 plants large amounts of photorespiratory glycine (Gly) are converted to serine by the tetrahydrofolate (THF)-dependent activities of the Gly decarboxylase complex (GDC) and serine hydroxymethyltransferase (SHMT). Using 13C nuclear magnetic resonance, we monitored the flux of carbon through the GDC/SHMT enzyme system in Arabidopsis thaliana (L.) Heynh. Columbia exposed to inhibitors of THF-synthesizing enzymes. Plants exposed for 96 h to sulfanilamide, a dihydropteroate synthase inhibitor, showed little reduction in flux through GDC/SHMT. Two other sulfonamide analogs were tested with similar results, although all three analogs competitively inhibited the partially purified enzyme. However, methotrexate or aminopterin, which are confirmed inhibitors of Arabidopsis dihydrofolate reductase, decreased the flux through the GDC/SHMT system by 60% after 48 h and by 100% in 96 h. The uptake of [alpha-13C]Gly was not inhibited by either drug class. The specificity of methotrexate action was shown by the ability of 5-formyl-THF to restore flux through the GDC/SHMT pathway in methotrexate-inhibited plants. The experiments with sulfonamides strongly suggest that the mitochondrial THF pool has a long half-life. The studies with methotrexate support the additional, critical role of dihydrofolate reductase in recycling THF oxidized in thymidylate synthesis.
Dihydropteroate synthase (DHPS) (EC 2.5.1.15) was extracted from leaves of Arabidopsis thaliana and purified 21-fold by ion-exchange chromatography. This enzyme preparation was then characterized for several of its properties. Michaelis-Menten constants for the substrates, p-aminobenzoic acid and dihydropteridine diphosphate were estimated to be 2.5 and 91 microM, respectively. In an optimized assay, the reaction product, dihydropteroic acid, competitively inhibited the enzyme activity with a Ki of 81 microM. However, neither dihydropteroic acid nor tetrahydrofolate, products further downstream in the biosynthetic pathway inhibited enzymatic activity. This appears to be the first report of product inhibition of DHPS from a higher plant. The relative inhibitory properties of several sulfonamides, analogues of p-aminobenzoic acid, were also examined. The substitutions on the amide nitrogen of the sulfonamides influenced the degree of inhibition; thus I50 values for the inhibition of the DHPS activity by sulfanilamide, sulfacetamide and sulfadiazine were estimated to be 18.6, 9.6 and 4.2 microM, respectively. The competitive pattern of inhibition was shown in experiments with sulfadiazine.
Vertebral artery injuries associated with blunt trauma to the cervical spine are rare. Five cases of vertebrobasilar complications after blunt trauma to the cervical spine are reported. Four were involved in motor vehicle accidents, and one suffered a diving injury. All of these patients had documented cervical spine fractures. For two patients, the diagnosis of vertebral artery thrombosis was made on the basis of magnetic resonance angiography (MRA), and for the remaining three, cervical four-vessel arteriograms (CFVAs), were used. All the patients had occlusion of flow in either the vertebral artery or in the vertebrobasilar circulation. The patients presented with acute, non-specific changes in neurological status. Two patients had infarctions in the vertebrobasilar tertiary, one had an infarction in the middle cerebral artery territory, and two did not show evidence of cerebral infarction. Three of the patients were treated with anticoagulants. Of these, two showed a stabilization of their neurological status, and one died. The four surviving patients improved with early physical and occupational therapy. Although CFVA remains the "gold standard" for diagnosing these injuries, newer modalities, such as MRA, may be useful adjuncts. Early stabilization of the cervical spine injury and anticoagulation are beneficial.
In C3 plants, serine synthesis is associated with photorespiratory glycine metabolism involving the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC) and serine hydroxymethyl transferase (SHMT). Alternatively, THF-dependent serine synthesis can occur via the C1-THF synthase/SHMT pathway. We used 13C nuclear magnetic resonance to examine serine biosynthesis by these two pathways in Arabidopsis thaliana (L.) Heynh. Columbia wild type. We confirmed the tight coupling of the GDC/ SHMT system and observed directly in a higher plant the flux of formate through the C1-THF synthase/SHMT system. The accumulation of 13C-enriched serine over 24 h from the GDC/SHMT activities was 4-fold greater than that from C1-THF synthase/SHMT activities. Our experiments strongly suggest that the two pathways operate independently in Arabidopsis. Plants exposed to methotrexate and sulfanilamide, powerful inhibitors of THF biosynthesis, reduced serine synthesis by both pathways. The results suggest that continuous supply of THF is essential to maintain high rates of serine metabolism. Nuclear magnetic resonance is a powerful tool for the examination of THF-mediated metabolism in its natural cellular environment.
To determine the prevalence and clinical significance of a mixed anxiety-depressive (MAD) syndrome in primary care, a two-stage sampling design was applied to 796 consecutive clinic attendees without known psychiatric illness. Among 78 systematically interviewed subjects, 10.3% (n = 8) had a depressive disorder alone, 12.8% (n = 10) had an anxiety disorder alone, 19.2% (n = 15) had a comorbid anxiety and depressive disorder and 12.8% (n = 10) had a combination of subsyndromal anxiety and depressive features that fulfilled either ICD-10 or our own operational criteria for MAD. Patients with MAD rated their disability as being comparable to that of patients with anxiety or depressive disorders. These findings lend support to the notion that there is a sizeable subgroup of patients in primary care who appear to be suffering from a psychiatric syndrome with an admixture of subsyndromal depressive and anxiety features. Questions about the temporal stability of MAD and preferred approaches to treatment have yet to be answered.
The effect of acute and subchronic administration of an alcoholic extract of the roots of Nardostachys jatamansi on norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), gamma-aminobutyric acid (GABA), and taurine were studied in male albino Wistar rats. The acute oral administration of the extract did not change the level of NE and DA but resulted in a significant increase in the level of 5-HT and 5-HIAA. A significant increase in the level of GABA and taurine was observed in the drug-treated groups when compared to the controls. A 15-day treatment resulted in a significant increase in the levels of NE, DA, 5-HT, 5-HIAA, and GABA. These data indicate that the alcoholic extract of the roots of N. jatamansi causes an overall increase in the levels of central monoamines and inhibitory amino acids.
A review of 12 cases of bony tumors involving the talus is presented. Giant cell tumor was the most common tumor. Malignant tumors should be treated by surgical ablation followed by chemotherapy. There are good results after excision or curettage and bone grafting in the treatment of benign neoplasms. Giant cell tumors, if diagnosed early, can be treated by curettage and bone grafting, but if there is talar collapse, a talectomy can be performed.
Seven cases of Ewing's sarcoma presenting with primary lesions of the foot bones are described. Difficulty and delay in making the initial diagnosis are the hallmarks of the problems encountered at this site. Although radiation therapy plays an important role for control of disease in Ewing's sarcoma, surgery along with chemotherapy appears to give better results. Lesions of the forefoot are amenable to surgery; however, no guidelines are available in the literature for hindfoot lesions. Chemotherapy has revolutionized the outcome, and its use along with surgical intervention is recommended in all cases of Ewing's sarcoma of foot bones.
In the wake of a large number of studies seeking biological markers for a variety of psychiatric disorders including affective disorders, the enthusiasm over Cortisol Secretion and Dexamethasone Suppression test lead the authors to review critically the data collected so far. The research designs involved, the samples studied and the reliability of the data collected along major variables such as diagnostic criteria, sampling characteristics, procedural differences, length of follow-up and the role of environmental stressors were evaluated. A useful exercise was to compare the literature published in the 50's and 60's with the more recent publications. The potential usefulness of DST as a diagnostic and management tool remains open for scrutiny. Whether the abnormalities in cortisol levels and DST responses evidenced by many researchers are an epiphenomenon or have a diagnostic and management value still remains unclear. From their analysis, the authors point out the lack of well controlled sequential studies using standardized procedures, and large age specific samples. Difficulty arising from the use of various terminologies and criteria for diagnosis of depressive disorders is recognized. The limitations of the use of DST in general clinical practice along with directions for future research are outlined.
The medical legal debate concerning committal is outlined and the recent scientific contributions to the committal debate are evaluated. It is noted that scientific surveys have made few significant contributions to the debate. Suggestions are made for further research in the hope that an increased contribution of scientific fact may help diffuse the heated exchange between the supporters and detractors of the committal process for the better care of a significant portion of our mentally ill.