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Biomedical subjects

S K Mittal

Publications and source records attributed to S K Mittal.

At least 37 records · Page 2Linked to original sources
PubMed2001

Tissue distribution and genetic typing of porcine circoviruses in pigs with naturally occurring congenital tremors.

Congenital tremors (CT) type A2 is associated with porcine circovirus (PCV) and deficient and abnormal myelin. The aim of this study was to determine the tissue distribution and genetic type of PCV in 1-2-day-old pigs with naturally occurring CT type A2 using in situ hybridization, polymerase chain reaction (PCR), and indirect fluorescent antibody tests on frozen tissue sections. CT-affected and clinically normal pigs were selected from 4 farms in the midwestern USA that were undergoing outbreaks of CT type A2. All CT and most normal pigs were infected with PCV. PCV was widely distributed in tissues of infected pigs and was most common in tissues of the central nervous system and liver. In all infected pigs, there were more PCV-infected cells in brain and spinal cord than in nonneural tissues. CT pigs had many more PCV-infected cells in the brain and spinal cord than did clinically normal pigs because of a more diffuse distribution and a larger proportion of infected cells. The cells most commonly infected with PCV in brain and spinal cord were large neurons. In nonneural tissues, macrophages were the most frequent cell type infected. PCR analysis demonstrated only PCV type 2 and not PCV type 1 in all PCV-infected pigs on all 4 farms.

Animals↗
PubMed2001

Viral replication and lesions in BALB/c mice experimentally inoculated with porcine circovirus isolated from a pig with postweaning multisystemic wasting disease.

Eight-week-old BALB/c mice were either sham inoculated (control mice) or were inoculated intraperitoneally (IP) and intranasally (IN) with a single (sPCV mice) or multiple (mPCV mice) doses of porcine circovirus 2 (PCV2). Four control mice and 4 sPCV mice were sacrificed 7, 14, 28, and 42 days postinoculation (PI). All 4 mPCV mice were sacrificed 42 days PI. In addition, 7-day and 14-day pregnant BALB/c mice were either sham inoculated (control mice) or were inoculated IP and IN with a single dose of PCV2. Newborn mice were euthanatized 1, 8, and 15 days after birth. Necropsies were performed on all euthanatized mice and tissues were collected for histopathology, electron microscopy, in situ hybridization, and polymerase chain reaction (PCR). PCV2 replicated in 8-week-old BALB/c mice that were inoculated with PCV2 and caused fetal infection when inoculated into pregnant BALB/c mice at 7 days and 14 days of gestation. PCV was detected by in situ hybridization and PCR in sPCV mice on days 7, 14, 28, and 42 PI; in mPCV mice on day 42 PI; and in newborn mice from mothers inoculated with PCV at 7 days and 14 days of gestation at 1, 8, and 15 days after birth, but not in control mice. No clinical signs or gross lesions were found in sPCV or mPCV mice during the study. Microscopic lesions in sPCV mice and mPCV mice were characterized by expansion of germinal centers in lymphoid organs with large numbers of histiocytic cells and lymphoblasts, apoptosis of histiocytic cells in germinal centers, and mild lymphoid depletion of the paracortex. PCV nucleic acid was detected in the nuclei and cytoplasm of histiocytes and apoptotic cells in germinal centers in lymphoid tissues as well as in the nuclei of hepatocytes in the liver, in the nuclei of renal tubular epithelial cells, and in the cytoplasm of single lymphocytes in the thymus. Congenitally infected mice only had PCV nucleic acid detected in putative Kupffer cells in livers.

Animals↗
PubMed2001

[Three cases of postweaning multisystemic wasting syndrome (PMWS) due to porcine circovirus type 2 (PCV 2) in Switzerland].

Porcine circovirus type 2 (PCV 2) was found in three five- and nine-week-old pigs from two feeder pig producer farms. Clinical signs were persistent diarrhea and wasting. The animals showed histomorphologic changes characteristic for "Postweaning Multisystemic Syndrome" (PMWS). One animal had the typical basophilic intracytoplasmatic circoviral inclusion bodies in the Peyer's patches of the ileum. Circoviral DNA was detected in the lymphatic organs as well as in the liver. This case report is the first description of PCV 2 in Switzerland.

Animals↗
PubMed2000

Immunization with DNA, adenovirus or both in biodegradable alginate microspheres: effect of route of inoculation on immune response.

To determine the potential for biodegradable alginate microspheres to be used as a delivery vehicle for DNA based vaccines, we constructed a plasmid, pMNe-gal-SV40, containing the bacterial beta-galactosidase (LacZ) gene under the control of the murine cytomegalovirus (MCMV) immediate-early promoter and the simian virus 40 (SV40) polyadenylation signal. The effect of the route of administration and co-administration of adenovirus on systemic and mucosal immune responses were investigated. Mice were inoculated orally, intranasally (i.n.), intramuscularly (i.m.), subcutaneously (s.c.) or intraperitoneally (i.p.) on days 0, 14 and 28 with microspheres containing plasmid DNA, bovine adenovirus type 3 (BAd3) or plasmid DNA + BAd3. Systemic routes of immunization (i.m., s.c. and i.p.) resulted in higher LacZ- or BAd3-specific IgG ELISA titers compared to those obtained by mucosal routes of inoculation (oral and i.n.). Mucosal immunization led to slightly higher titers of LacZ- or BAd3-specific IgA at mucosal sites compared to those obtained by the various systemic routes. All the routes of immunization induced LacZ-specific lymphoproliferation. Co-administration of BAd3 enhanced the LacZ-specific IgG response irrespective of the route of administration.

3T3 Cells↗
PubMed2000

Circumvention of vector-specific neutralizing antibody response by alternating use of human and non-human adenoviruses: implications in gene therapy.

To determine whether non-human adenovirus-specific antibodies are cross-neutralizing, rabbit and mouse anti-human adenovirus type 5 (HAd5), anti-bovine adenovirus type 3 (BAd3), and anti-porcine adenovirus type 3 (PAd3) sera were used in cross-virus neutralization assays. Adenovirus neutralizing antibodies were found to be virus-specific, suggesting that virus neutralizing epitope differs significantly in HAd5, BAd3, and PAd3. To further investigate whether immunity to an HAd5-derived vector could be circumvented by the use of non-human adenoviruses in vivo, mice were first immunized either intranasally or intraperitoneally with HAd5, BAd3, PAd3, or BAd3 + PAd3, and after development of adenovirus-specific antibodies, animals were inoculated with the HAd5 recombinant (AdCA36lacZ) containing the bacterial beta-galactosidase gene under the control of murine cytomegalovirus immediate-early promoter. Virus-inoculated animals developed virus-specific IgG and IgA antibodies. LacZ expression in animals initially primed with HAd5 was significantly reduced (P < 0.05), suggesting that the immune response against the vector could prevent the transgene expression following subsequent inoculation of the same vector, whereas LacZ expression in mice initially primed with BAd3, PAd3, or BAd3 + PAd3 was significantly higher (P > 0.05) than that obtained in HAd5-primed animals. Our results suggest that HAd5-, BAd3-, or PAd3-based vectors may be used sequentially for human gene therapy or vaccine production as a means to avoid immunity to the vector.

Adenoviruses, Human↗
PubMed2000

Left side thoracoscopically assisted gastroplasty: a new technique for managing the shortened esophagus.

Laparoscopic antireflux surgery is the procedure of choice for gastroesophageal reflux disease (GERD). However, many clinicians have reservations about its application in patients with complicated GERD, notably those with esophageal shortening. In this report, we present our experience with the laparoscopic management of the shortened esophagus. A total of 235 patients with primary GERD underwent laparoscopic antireflux procedures, 38 of whom were suspected preoperatively to have a shortened esophagus. Of the 235 patients, 8 (3.4%) needed a left thoracoscopically assisted gastroplasty in addition to laparoscopic Toupet repair (n = 4) or Nissen fundoplication (n = 4). Complications included pleural effusion (n = 1), pneumothorax (n = 2), and minor atelectasis (n = 1). The average hospital stay was 3 days. Results were satisfactory in 7 of 8 patients, with a mean follow-up of 20.2 months (range, 9-34 months). The surgical management of the shortened esophagus is difficult. However, the role of minimally invasive techniques is justified. Early results are appealing, with less morbidity, satisfactory control of GERD related symptoms, and a shortened hospital stay.

Esophagus↗
PubMed2000

Indications for endo-organ gastric excision.

Intragastric surgery for benign and malignant conditions is a new form of minimally invasive surgery, to which the term endo-organ gastric surgery has been applied. This procedure may provide improved results for patients, but reported studies are small, and follow-up evaluation is limited. The indications for endo-organ surgery are evolving as technology and operative expertise begin to meet the need for continued advancements in miniaturized surgery. This new approach is applied primarily to the removal of gastric neoplasms poorly positioned or too large for standard transoral endoscopic excision. Gastric polyps, benign gastric wall tumors such as leiomyomas and carcinoids, and low-grade as well as high-grade malignancies can be removed. The history of endo-organ surgery, the background technology, and surgical experience are reviewed. In addition, current indications for endo-organ surgery and the rationale for algorithms are included. Intraluminal gastric surgery is not widely performed or studied, therefore a further understanding of its role is provided.

Gastrectomy↗
PubMed2000

The preoperative predictability of the short esophagus in patients with stricture or paraesophageal hernia.

BACKGROUND: Esophageal shortening is a known complication of advanced gastroesophageal reflux disease that may preclude a tension-free antireflux procedure. A retrospective analysis was performed to test the accuracy of preoperative testing. METHODS: From September 1993 to December 1998, 39 patients underwent esophageal mobilization with intraoperative length assessment. Patients were selected on the basis of irreducible hiatal hernia, stricture formation, or both. Patients in the upright position with a fixed hiatal hernia larger than 5 cm on an esophagram were considered to have a short esophagus. Manometric length two standard deviations below the mean for height was considered abnormally short. RESULTS: In 31 patients, intraoperative mobilization was sufficient to allow the gastroesophageal junction to lie 2 cm below the diaphragmatic crus, so no esophageal-lengthening procedure was required. Eight patients with a short esophagus required an esophageal-lengthening procedure after complete mobilization. Two patients subsequently underwent intrathoracic migration of the gastroesophageal junction (GEJ), with recurrence of symptoms and required gastroplasty during the second surgery. An esophagram had a sensitivity of 66% and a positive predictive value of 37%, whereas manometric length had a sensitivity of 43% and a positive predictive value of 25% for the diagnosis of short esophagus. The preoperative endoscopic finding of either a stricture or Barrett's esophagus was the most sensitive test for predicting the need for a lengthening procedure. CONCLUSIONS: Manometry and esophagraphy are not reliable predictors of the short esophagus. Additional tests and/or tests combined with other parameters are needed.

Esophageal Stenosis↗
PubMed2000

Sequence analysis of porcine adenovirus type 3 E1 region, pIX and pIVa2 genes, and two novel open reading frames.

The porcine adenovirus type 3 (PAd3) genome between map units 0 and 13.7 was sequenced and compared with similar regions of other adenoviruses. This region consists of the left inverted terminal repeat sequences involved in DNA packaging, the entire early region 1 (E1) and the protein IX (pIX) transcription unit. The lower strand contains the C-terminal end of IVa2 of the E2A transcriptional unit and two novel open reading frames (ORFs). The E1 transcription unit consists of ORFs for proteins homologous to the E1A, E1B-17k and E1B-55k of both human adenovirus type 5 (HAd5) and bovine adenovirus type 3 (BAd3). The predicted PAd3 pIX demonstrated homology with the N-terminal portion of the pIXs of HAd5 and BAd3. On the lower strand, immediately after the putative IVa2 ORF, there are two unique ORFs of 208 and 203 amino acid residues that showed homology with Epstein-Barr virus nuclear antigens and other cellular transcription factors.

Adenovirus E1A Proteins↗
PubMed1999

Generation of infectious genome of bovine adenovirus type 3 by homologous recombination in bacteria.

The widely used technique of generating adenovirus vectors by homologous recombination in mammalian cells is usually not very efficient. This communication describes a simple method of generating a plasmid containing the full-length genome of an adenovirus by homologous recombination in bacteria. Following transfection of a suitable mammalian cell line with the full-length adenovirus genome, infectious virus progeny could easily be generated. Using this technique the generation of adenovirus recombinants would be efficient and straightforward.

Animals↗
PubMed1999

Bone histology in patients with nephrotic syndrome and normal renal function.

BACKGROUND: The prevalence of metabolic bone disease in patients with nephrotic syndrome (NS) at normal level of renal function remains uncertain. METHODS: To address this issue, we studied 30 patients (20 men and 10 women, mean age 27.3 +/- 11.7 years) with NS who had normal renal function (mean creatinine clearance 103 +/- 4 ml/min). We evaluated their serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), vitamin D metabolites, urinary calcium, and skeletal survey. The extent of bone mineralization was analyzed by histomorphometric analysis of iliac crest bone biopsy specimens in all patients. The findings on bone histology were correlated with biochemical parameters. RESULTS: The mean duration of NS was 35.5 +/- 26.9 months, with a protein excretion of 7.3 +/- 3.2 g/24 hr and a serum albumin of 2.2 +/- 0.8 g/dl. Total serum calcium was 7.8 +/- 0.8 mg/dl, whereas ionized calcium was 5.7 +/- 0.7 mg/dl, phosphorus 3.2 +/- 1.2 mg/dl, and alkaline phosphatase 149 +/- 48.6 U/liter. Serum iPTH levels were normal in all except two patients. The mean serum 25-hydroxyvitamin D [25(OH)D] level was 3.9 +/- 1.2 ng/ml (normal 15 to 30 ng/ml), whereas 1,25-dihydroxyvitamin D was 24 +/- 4.7 pg/ml (normal 16 to 65). There was an inverse correlation between serum levels of 25(OH)D and the magnitude of proteinuria (r = -0.42, P < 0.05). The mean 24-hour urinary calcium excretion was 82 +/- 21 mg/day. The skeletal survey was normal in all patients. Bone histology was normal in 33.3% of the patients, whereas 56.7% had isolated osteomalacia (OSM), and 10% had an increased bone resorption in association with defective mineralization. The severity of OSM measured by mineralization lag time correlated linearly with the duration (r = 0.94, P < 0.0001) and the amount (r = 0.97, P < 0.0001) of proteinuria. All patients with NS for more than three years had histological changes. Patients with OSM had lower 25(OH)D and serum albumin as compared with those with normal histology (P < 0.005). Bone mineralization had no significant correlation with serum iPTH, divalent ions, or vitamin D levels. CONCLUSIONS: OSM is a frequent finding in adult patients with NS, even at a normal level of renal function. Its severity correlates with the amount and duration of proteinuria.

Adolescent↗
PubMed1999

Beneficial effects of iron therapy in renal failure patients on hemodialysis.

Iron deficiency is a common problem in patients treated with hemodialysis. If not detected and treated appropriately, the effectiveness of recombinant human erythropoietin therapy is compromised. Much has been learned in recent years with respect to iron therapy for hemodialysis patients. A series of studies have clearly defined the efficacy of intravenous iron compounds, and recently released clinical practice guidelines have set the appropriate clinical context for the use of these agents. The purpose of this article is to examine the beneficial effects of iron replacement therapy for hemodialysis patients.

Erythropoietin↗