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Biomedical subjects

A Gupta

Publications and source records attributed to A Gupta.

At least 19 recordsLinked to original sources
PubMed2007

Factors affecting the sagittal alignment of the lunate.

The lunate is described as having a tendency to rotate dorsally as a result of its wedge shape, with the apex towards the dorsum, but maintains an attitude of flexion in most individuals. The present study comprised CT scans of the wrist of 70 healthy volunteers. Sagittal measurements were drawn for the midcarpal and radiocarpal axes, alignment and various shape patterns of the lunate. The midcarpal axis was found to be dorsal, volar and collinear to the radiocarpal axis in 21 (30%), 29 (41%) and 20 (29%) subjects, respectively. The sagittal alignment of the lunate demonstrated significant correlation with measurements of the midcarpal and radiocarpal axes with no correlation with its various shape patterns. It is concluded that the relationship between the midcarpal axis and the radiocarpal axis in terms of dorso-volar displacement has a key role in determining the sagittal alignment of the lunate, while the shape of the lunate may be only a secondary consideration.

Adult↗
PubMed2007

Increase in weight induced by muraglitazar, a dual PPARalpha/gamma agonist, in db/db mice: adipogenesis/or oedema?

BACKGROUND AND PURPOSE: Muraglitazar, a dual PPARalpha/gamma agonist, caused a robust increase in body weight in db/db mice. The purpose of the study was to see if this increase in weight was due to oedema and/or adipogenesis. EXPERIMENTAL APPROACH: The affinity of muraglitazar at PPARalpha/gamma receptors was characterized using transactivation assays. Pre-adipocyte differentiation, expression of genes for adipogenesis (aP2), fatty acid oxidation (ACO) and sodium reabsorption (ENaCgamma and Na+, K+-ATPase); haemodilution parameters and serum electrolytes were measured to delineate the role of muraglitazar in causing weight gain vis a vis rosiglitazone. KEY RESULTS: Treatment with muraglitazar (10 mg kg(-1)) for 14 days significantly reduced plasma glucose and triglycerides. Reduction in plasma glucose was significantly greater than after similar treatment with rosiglitazone (10 mg kg(-1)). A marked increase in weight was also observed with muraglitazar that was significantly greater than with rosiglitazone. Muraglitazar increased aP2 mRNA and caused adipocyte differentiation in 3T3-L1 cells similar to rosiglitazone. It also caused a marked increase in ACO mRNA in the liver of the treated mice. Expression of mRNA for ENaCgamma and Na+, K+-ATPase in kidneys was up-regulated after either treatment. Increased serum electrolytes and decreased RBC count, haemoglobin and haematocrit were observed with both muraglitazar and rosiglitazone. CONCLUSIONS AND IMPLICATIONS: Although muraglitazar has a better glucose lowering profile, it also has a greater potential for weight gain than rosiglitazone. In conclusion, muraglitazar causes both robust adipogenesis and oedema in a 14-day treatment of db/db mice as observed in humans.

3T3-L1 Cells↗
PubMed2007

Moderation of psychosocial risk factors through dysfunction of the hypothalamic-pituitary-adrenal stress axis in the onset of chronic widespread musculoskeletal pain: findings of a population-based prospective cohort study.

OBJECTIVE: To test the hypothesis that abnormalities in the hypothalamic-pituitary-adrenal (HPA) stress-response system would act as an effect moderator between HPA function and the onset of chronic widespread pain (CWP). METHODS: We conducted a population-based prospective cohort study. Current pain and psychosocial status were ascertained in 11,000 subjects. Of the 768 eligible subjects free of CWP but at future risk based on their psychosocial profile, 463 were randomly selected, and 267 (57.7%) consented to assessment of their HPA axis function. Diurnal function was measured by assessing levels of salivary cortisol in the morning (9:00 AM) and evening (10:00 PM). Serum cortisol levels were measured after an overnight low-dose (0.25 mg) dexamethasone suppression test and a potentially stressful clinical examination. All subjects were followed up 15 months later to identify cases of new-onset CWP. RESULTS: A total of 241 subjects (94.9%) completed the followup study, and 28 (11.6%) reported the new onset of CWP. High levels of cortisol post-dexamethasone (odds ratio [OR] 3.53, 95% confidence interval [95% CI] 1.17-10.65), low levels in morning saliva (OR 1.43, 95% CI 0.52-3.94), and high levels in evening saliva (OR 2.32, 95% CI 0.64-8.42) were all associated with CWP. These 3 factors were found to be independent and additive predictors of CWP (OR for all 3 factors 8.5, 95% CI 1.5-47.9) in analyses controlling for age, sex, depression, sleep disturbance, recent traumatic life events, and pain status. One or more of these 3 HPA factors identified 26 (92.9%) cases of new-onset CWP. CONCLUSION: Among a group of psychologically at-risk subjects, dysfunction of the HPA axis helps to distinguish those who will and will not develop new-onset CWP.

Adult↗
PubMed2006

Lower energy levels adequate for effective transcleral diode laser cyclophotocoagulation in Asian eyes with refractory glaucoma.

PURPOSE: To study the treatment parameters for diode laser cyclophotocoagulation (DLCP) in Asian Indian eyes using laser energy titrated to clinical response. METHODS: This prospective interventional longitudinal study included 66 eyes of 66 patients with varied aetiology refractory glaucoma, no previous cycloablation, and minimum 1 year follow-up. DLCP was performed using the Oculight Diode laser system IRIS( Medical Instruments Inc., CA, USA). Power used per spot was titrated according to the audible 'pops' indicating tissue microexplosion. The mean laser energy delivered, post-laser intraocular pressure (IOP) reduction, complications, and requirement of re-treatment in various subgroups were analyzed. Differences in energy delivered in each subgroup were assessed by analysis of variance with post hocBonferroni corrections. Linear regression analysis was used to identify possible predictive factors for failure of cyclodiode therapy. RESULTS: The mean total energy delivered per eye was 87.80+/-31.8 J (range 105.4+/-36.8 J in neovascular glaucoma (NVG) to 61.5+/-8.8 J in uveitic glaucoma (P=0.134)). Mean pre treatment IOP was 36.4+/-10.7 mmHg, which reduced to 19.4+/-9.8 mmHg (P<0.001) at 1 week, and 15.6+/-6.6 mmHg at 1 year. At 1 year, 58 of 66 patients had IOP<22.0 mmHg (response rate 87.8%), and six patients had hypotony (success rate 78.8%). The uveitic glaucoma group had 100% success rate. NVG group required maximum re-treatments. CONCLUSIONS: DLCP with a titrated energy protocol needs resulted in lower energy in Asian Indian eyes compared to that reported in literature, and different energy levels are needed for different diseases. 'Standard treatment parameters' for DLCP may be inappropriate for all diseases and all races.

Adolescent↗
PubMed2006

The role of psychosocial factors in predicting the onset of chronic widespread pain: results from a prospective population-based study.

OBJECTIVE: Chronic widespread pain (CWP) is strongly associated with psychosocial distress both in a clinical setting and in the community. The aim of this study was to determine the contribution of measures of psychosocial distress, health-seeking behaviour, sleep problems and traumatic life events to the development of new cases of CWP in the community. METHODS: In a population-based prospective study, 3171 adults aged 25-65 yrs free of CWP were followed-up 15 months later to identify those with new CWP. Baseline data were available on their scores from a number of psychological scales including Illness Attitude Scales (IAS), Somatic Symptom Checklist (SSC), Hospital Anxiety & Depression Scale, Sleep Problems Scale, and Life Events Inventory. RESULTS: 324 subjects [10%, 95% confidence interval (CI) 9.2, 11.3] developed new CWP at follow-up. After adjustment for age and sex, three factors independently predicted the development of CWP: scoring three or more on the SSC [odds ratio (OR) 1.8, 95% CI 1.1, 3.1], scoring eight or more on the Illness Behaviour subscale of the IAS (OR 3.3, 95% CI 2.3, 4.8), and nine or more on the Sleep Problem Scale (OR 2.7, 95% CI 1.6, 3.2). Subjects exposed to all three factors were at 12 times the odds of new CWP than those with low scores on all scales. CONCLUSION: Subjects are at substantial increased odds of developing CWP if they display features of somatization, health-seeking behaviour and poor sleep. Psychosocial distress has a strong aetiological influence on CWP.

Adult↗
PubMed2006

Salicylate for the treatment of Kawasaki disease in children.

BACKGROUND: Kawasaki disease is the most common cause of acquired heart disease in children in developed countries. The coronary arteries supplying the heart can be damaged in Kawasaki disease. The principal advantage of timely diagnosis is the potential to prevent this complication with early treatment. Salicylate (acetyl salicylate acid (ASA), aspirin) and intravenous immunoglobulin (IVIG) are widely used for this purpose. Salicylate is largely otherwise avoided in children because of concerns about serious side effects, particularly the risk of Reyes syndrome. OBJECTIVES: The objective of this review was to evaluate the effectiveness of salicylate in treating and preventing cardiac consequences of Kawasaki disease in children. SEARCH STRATEGY: The Cochrane Peripheral Vascular Disease Group searched their trials register (last searched July 2006) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 3, 2006). We searched MEDLINE (January 1966 to July 2006), EMBASE (January 1980 to July 2006), and CINAHL (1982 to July 2006), and reference list of articles. In addition we contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) of salicylate to treat Kawasaki disease in children were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: We found one trial involving 102 children which was described as randomised, but it was not possible to confirm the method of treatment allocation. A second comparative study, possibly with a randomised treatment allocation, was also identified. The one randomised trial reported no association between the addition of ASA to IVIG treatment on the rate of coronary artery abnormalities at follow up, but with wide confidence limits. The second, possibly randomised trial did demonstrate a reduction in duration of fever with high dose ASA compared to low dose ASA, but was insufficiently powered to establish the effect on coronary artery abnormalities at follow up. AUTHORS' CONCLUSIONS: Until good quality RCTs are carried out, there is insufficient evidence to indicate whether children with Kawasaki disease should continue to receive salicylate as part of their treatment regimen.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Development of computational models for the purpose of conducting individual livestock and premises traceback investigations utilizing National Animal Identification System-compliant data.

Many of the efforts surrounding the development of the National Animal Identification System have encompassed the identification of livestock production and handling premises as well as individuals or herds of animals, whereas little effort has been directed toward the ultimate goal of animal traceback within 48 h. A mock data set representative of the Colorado cattle population was created for modeling of cattle traceability. Using this data set, algorithms were developed to complete rapid and accurate traceback and traceforward of animals or premises or both. On July 19, 2005, the Colorado Department of Public Health and Environment, in conjunction with the Colorado Department of Agriculture, conducted a test exercise pertaining to homeland security. The exercise team randomly identified animal number 926,583 (of the 2 million total animals) as a potentially infected animal of interest and requested a traceback of this animal. Traceback was accomplished in 215 s, and 540 primary coresident animals were identified. However, due to animal movements, the number of coresidents (animals exposed, directly or indirectly, to the animal of interest) expanded with coresidency level (level 1 = direct contact; level 2 = direct contact with an animal that had direct contact with the animal of interest; level 3 = direct contact with an animal that had contact with an animal that had direct contact with the animal of interest, etc.) to more than 1.2 million coresidents at level 4, and more than 90% of all animals identified as a coresident at some level. In addition to the coresidency results, the premises containing the coresidents were identified and sorted by the number of coresidents. Because of animal movement, all 19,391 premises included in the data set had coresidents at some level. This exercise demonstrated the capability of the developed algorithms to complete rapid traceback and the complexity of the resulting animal traceback output.

Agriculture↗
PubMed2006

Umbilical CSF fistula: a rare complication of ventriculoperitoneal shunt.

An umbilical CSF fistula following a ventriculoperitoneal shunt is an extremely rare complication. We report a 28-year-old man who presented with leak of clear fluid from the umbilicus, one month after a ventriculo-peritoneal shunt revision. Shuntogram revealed communication between umbilicus and abdominal end of the catheter. He was managed successfully with shunt exteriorization, antimeningitic treatment, and later shunt re-insertion.

Abdominal Injuries↗
PubMed2006

Pressure pain thresholds and tender point counts as predictors of new chronic widespread pain in somatising subjects.

BACKGROUND: Tender points are a general measure of distress both in the community and in clinic subjects. It has been suggested that multiple tender points should be regarded as the early stages of somatisation of distress. Similarly, recent evidence suggests that chronic widespread pain (CWP) is one manifestation of the somatisation of distress. OBJECTIVE: Given that a high tender point count and CWP are clinical hallmarks of the fibromyalgia syndrome, it was hypothesised that in somatising subjects, a high tender point count or a low pain threshold would predict the development of CWP in the future. METHODS: In this population-based prospective study, 245 adults aged 25-65 years, free of CWP, were identified on the basis of a detailed questionnaire on pain and a psychosocial questionnaire comprising the Somatic Symptom Checklist and the Illness Behaviour subscale of the Illness Attitude Scales. These subjects took part in a pain threshold examination with a Fischer pressure algometer. Tender point counts were computed by including all areas with a pain threshold<4 kg/cm2. Individuals were followed up at 15 months, at which time 231 (93% of subjects still living at their baseline address) provided data on pain status, using the same instruments. RESULTS: At follow-up, 26 (11%) subjects developed new CWP. Although subjects with a low baseline pain threshold were not at increased risk of developing symptoms, a high tender point count, adjusted for age, sex, baseline pain status and other confounding factors, predicted the development of new CWP. CONCLUSION: Subjects free of CWP are at an increased risk of its development if they have a high tender point count. However, a low-pressure pain threshold does not predict the onset of symptoms. Data from this population-based prospective study suggest that a low pain threshold in subjects with CWP is likely to be a secondary phenomenon as a result of pain or associated distress rather than the antecedent of symptoms.

Adult↗
PubMed2006

Amyand's hernia: a report of 18 consecutive patients over a 15-year period.

AIM: The presence of a vermiform appendix in an inguinal hernia sac is termed Amyand's hernia. It may present as a tender inguinal or inguino-scrotal swelling and is often misdiagnosed as an incarcerated or strangulated hernia. The purpose of this study was to review the management of Amyand's hernia at a single institution since 1991. MATERIAL AND METHODS: A retrospective analysis was undertaken of 18 consecutive patients with an Amyand's hernia operated upon at our institution from 1991 to 2005. Patients' demographics, treatment and postoperative outcome were analysed. RESULTS: There were 17 men and one woman. Their median age was 42 years. None of the patients was diagnosed preoperatively. The commonest presenting symptom was painful inguinal or inguino-scrotal swelling (83%). All patients, therefore, underwent emergency surgery with a presumptive diagnosis of either incarcerated or strangulated inguinal hernia. Operative findings included 11 normal appendices, four inflamed appendices and three perforated appendices in the inguinal hernial sac. Patients with a normal appendix (n = 11) had a mesh hernia repair without an appendicectomy. The rest of the patients (n = 7) with an abnormal appendix underwent emergency open appendicectomy followed by Bassini's sutured hernia repair. One patient died in the postoperative period of pneumonia. Only one recurrent hernia has been detected, with a median follow-up time of 6.4 years. CONCLUSION: The inflammatory status of the appendix determines the type of hernia repair and the surgical approach. Incidental appendicectomy in the case of a normal appendix is not favoured.

Adolescent↗
PubMed2006

Subcortical white matter abnormalities related to drug resistance in Wilson disease.

Wilson disease (WD) produces typical lesions in the brain, which can aid in diagnosis and therapy. The authors present a drug-resistant WD case with atypical cerebral lesions with marked involvement of white matter as visualized on MRI scans. The diagnosis was confirmed by identification of mutations in the ATP7B gene. The case demonstrates an uncommon pathology-related cerebral copper accumulation and emphasizes the importance of genetic screening in the diagnosis of WD.

Adenosine Triphosphatases↗
PubMed2006

Ventral herniorrhaphy: experience with two different biosynthetic mesh materials, Surgisis and Alloderm.

OBJECTIVE: The aim of this study was to compare the efficacy and the complications associated with the use of two new bioactive meshes, Surgisis Gold 8-ply mesh, a product obtained by the processing of porcine small intestine sub-mucosa (Cook Surgical, Bloomington, IN, USA), and Alloderm, processed cadaveric human acellular dermis (Life Cell Corporation, Branchburg, NJ, USA), for ventral herniorrhaphy. BACKGROUND: Ventral hernia repair in potentially contaminated or potentially infected fields limit the use of synthetic mesh products. In this scenario, biosynthetic mesh products that are absorbed and/or replaced with the body's own tissue reduce the incidence of post-operative chronic wound complications (Franklin et al. in Hernia 8(3):186-189, 2004; Franklin et al. in Hernia 6(4):171-174, 2002; Hirsch in J Am Coll Surg 198(2):324-328, 2004; Holton et al. in J Long Term Eff Med Implants 15(5):547-558, 2005; Buinewicz and Rosen in Ann Plast Surg 52(2):188-194, 2004). Rapid revascularization, repopulation, and remodeling of the matrix occur on contact with the patient's own tissue. Only limited, and mostly preliminary data, is available on the use of these types of mesh and concerning the potential complications associated with the use of these types of meshes. We publish our experience with the use of these mesh products, along with their associated complications. Furthermore, we have also provided suggestions for improvements in the mesh designs. METHODS: Between June 2002 and March 2005, 74 patients underwent ventral hernia repair using biosynthetic or natural tissue mesh. The first 41 procedures were performed using Surgisis Gold 8-ply mesh formed from porcine small intestine sub-mucosa, and the remaining 33 patients had ventral hernia repair with Alloderm. The patients had their first follow-up 7-10 days after discharge from the hospital. They were again seen at 6 weeks, or, if needed, earlier, and, thereafter, as needed. Patients who reported any complications to the office were followed up immediately within 1-2 days. Any signs of wound infection, diastasis, hernia recurrence, changes in bowel habits, and seroma formation were evaluated. RESULTS: Non-perforated Surgisis mesh resulted in significant seroma formation in 10/11 patients. The seroma complication was reduced, but not eliminated, with the use of the perforated Surgisis mesh (3/30 patients). Explanted material revealed separated layers of un-incorporated middle layers of the 8-ply Surgisis mesh. Three of the patients had the mesh placed in a contaminated field with no resultant sequela, and there were no hernia recurrences. Patients also had a significant degree of discomfort and pain during the immediate post-operative period. The use of the Alloderm mesh resulted in eight hernia recurrences. Fifteen of the Alloderm patients (15/33) developed a diastasis or bulging at the repair site. Seroma formation was only a problem in two patients. CONCLUSIONS: Seroma formation was a major problem with the non-perforated Surgisis mesh repair, as was the post-operative pain. On the other hand, post-operative diastasis and hernia recurrence were a major problem with the Alloderm mesh. Further design improvements are required in both forms of these new mesh products. Surgeons should be aware of these potential complications prior to the selection of either of these products and the patient should be informed and educated accordingly.

Biocompatible Materials↗
PubMed2006

Multi-class classification algorithm for optical diagnosis of oral cancer.

We report development of a direct multi-class spectroscopic diagnostic algorithm for discrimination of high-grade cancerous tissue sites from low-grade as well as precancerous and normal squamous tissue sites of human oral cavity. The algorithm was developed making use of the recently formulated theory of total principal component regression (TPCR). The in vivo autofluorescence spectral data acquired from patients screened for neoplasm of oral cavity at the Government Cancer Hospital, Indore, was used to train and validate the algorithm. The diagnostic algorithm based on TPCR was found to provide satisfactory performance in classifying the tissue sites in four different classes - high-grade squamous cell carcinoma, low-grade squamous cell carcinoma, leukoplakia, and normal squamous tissue. The classification accuracy for these four classes was observed to be approximately 94%, 100%, 100% and 91% for the training data set (based on leave-one-out cross-validation), and was approximately 90%, 90%, 85% and 88%, respectively for the corresponding classes for the independent validation data set.

Adult↗
PubMed2006

Predictors of outcome after temporal lobectomy for the treatment of intractable epilepsy.

To assess short- and long-term seizure freedom, the authors reviewed 371 patients who underwent anterior temporal lobectomy to treat pharmacoresistant epilepsy. The mean follow-up duration was 5.5 years (range 1 to 14.1 years). Fifty-three percent of patients were seizure free at 10 years. The authors identified multiple predictors of recurrence. Results of EEG performed 6 months postoperatively correlated with occurrence and severity of seizure recurrence, in addition to breakthrough seizures with discontinuation of antiepileptic drugs.

Anterior Temporal Lobectomy↗
PubMed2006

Pain relief following breast augmentation surgery: a comparison between incisional patient-controlled regional analgesia and traditional oral analgesia.

BACKGROUND AND OBJECTIVES: Postoperative pain is a common problem following ambulatory breast augmentation surgery. This study was performed to compare standard of care (oral analgesics) with patient-controlled incisional regional analgesia (PCRA) for postoperative pain management at home for 48 h. A second aim was to compare the analgesic efficacy of ropivacaine 0.25% vs. 0.5%. METHODS: Surgery was performed under local anaesthesia and monitored anesthesia care. Sixty adults (ASA 1-2) were randomized to one of two groups. Patients in Group PCRA could self-administer ropivacaine 0.25% 10 mL in the left breast and ropivacaine 0.5% in the right breast. Patients in Group T (tablets) received our standard of care treatment, i.e. oral paracetamol 1 g four times a day and oral ibuprofen 500 mg three times a day. Parameters measured included: analgesic requirements (in post-anesthesia care unit, PACU and post-discharge), pain intensity (visual analogue scale), patient satisfaction, global analgesia, side-effects, and quality of recovery. RESULTS: Pain scores were significantly lower in Group PCRA compared to Group T at all time periods (P < 0.05). No differences were found in pain scores between the right and left breasts. Significantly more patients in Group T requested analgesics in the recovery unit (27 vs. 7; P = 0.001) and also at home (20 vs. 11; P < 0.02). More patients in the tablet group had nausea and vomiting (10 vs. 3; P < 0.05). Global analgesia on day 2 was significantly better in PCRA group; however, patient satisfaction was similar in both groups. More patients in the tablet group had sleep disturbance and woke up at night due to pain. CONCLUSIONS: Pain relief after ambulatory breast augmentation is superior with incisional PCRA when compared to oral analgesic combination of paracetamol and ibuprofen. Incisional PCRA was associated with minimal side-effects and less sleep disturbance. There was no difference in the analgesic efficacy between ropivacaine 0.25% and 0.5%.

Administration, Oral↗
PubMed2006

Post-traumatic fungal endophthalmitis--a prospective study.

PURPOSE: To study the incidence, clinical presentation, and the response of anti-fungals in cases of fungal endophthalmitis following open globe injury. METHODS: This is a prospective study of eight cases of post-traumatic fungal endophthalmitis among 110 patients who presented to us with open globe injury between August 2003 and January 2005. Patients with panophthalmitis were eviscerated and rest received intravitreal amphotericin B. Pars plana vitrectomy along with intravitreal miconazole was given in patients with inadequate response to intravitreal amphotericin. RESULTS: Two patients had panophthalmitis at the time of presentation and were eviscerated. Six different organisms were isolated from the culture of intraocular specimen of eight patients. The yield of vitreous aspirate was 87.5% and that of aqueous aspirate was 66.6%. Aspergillus sp. and Fusarium sp. were isolated in 62.5% of cases. Minimum inhibitory concentration of amphotericin B and miconazole was less than 3 microg/ml for all organisms except for Paecilomyces lilacinus and Fusarium solani, respectively. In total, 37.5% of patient had final visual acuity of 20/400 or better. CONCLUSIONS: Fungal endophthalmitis is a relatively rare complication of open globe injury. The final visual outcome after fungal endophthalmitis is dismal. Aspergillus fumigatus was found to be the most virulent organism. All organisms were found to be sensitive to amphotericin B, except P. lilacinus, which was sensitive to miconazole. Repeated intravitreal injection may be required to control the infection. The virulence of the organism and the site of injury are the main determinants of final visual outcome.

Adolescent↗
PubMed2006

Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript.

MicroRNAs (miRNAs) are a class of small RNA molecules that regulate the stability or the translational efficiency of target messenger RNAs (mRNAs). The latency-associated transcript (LAT) of herpes simplex virus-1 (HSV-1) is the only viral gene expressed during latent infection in neurons. LAT inhibits apoptosis and maintains latency by promoting the survival of infected neurons. No protein product has been attributed to the LAT gene and the mechanism by which LAT protects cells from apoptosis is not yet known. Here we show that a miRNA encoded by the HSV-1 LAT gene confers resistance to apoptosis. Neuroblastoma cells transfected with a fragment of the LAT gene show reduced susceptibility to cell death. The anti-apoptotic function of LAT has been mapped to a region within the first exon. We have identified and characterized a microRNA (miR-LAT) generated from the exon 1 region of the HSV-1 LAT gene. The LAT miRNA was found to accumulate in cells transiently transfected with the LAT gene fragment or infected with a wild-type strain of HSV-1. A mutant virus in which a 372-nucleotide fragment encompassing the mature miRNA was deleted neither protected the infected cells from apoptosis nor generated an miRNA. miR-LAT exerts its anti-apoptotic effect by downregulation of transforming growth factor (TGF)-beta 1 and SMAD3 expression, both of which are functionally linked in the TGF-beta pathway. Our results suggest that the miRNA encoded by the HSV-1 LAT gene regulates the induction of apoptosis in infected cells by modulation of TGF-beta signalling and thus contributes to the persistence of HSV in a latent form in sensory neurons.

Apoptosis↗