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Biomedical subjects

S Varghese

Publications and source records attributed to S Varghese.

At least 19 recordsLinked to original sources
PubMed2006

Glucosamine modulates chondrocyte proliferation, matrix synthesis, and gene expression.

OBJECTIVE: To investigate the effects of glucosamine (GlcN) on chondrocyte proliferation, matrix production, and gene expression for providing insights into the biochemical basis of its reported beneficial effects in osteoarthritis (OA). METHODS: Dose-dependent effect of GlcN on cell morphology, proliferation, cartilage matrix production and gene expression was examined by incubating primary bovine chondrocytes with various amounts of GlcN in monolayers (2D) and in cell-laden hydrogels (3D constructs). Histology, immunofluorescent staining and biochemical analyses were used to determine the effect of GlcN on cartilage matrix production in 3D constructs. The impact of GlcN on gene expression was evaluated with real-time polymerase chain reaction (PCR). RESULTS: GlcN concentration and culture conditions significantly affected the cell behavior. Quantitative detection of matrix production in cell-laden hydrogels indicated a relatively narrow window of GlcN concentration that promotes matrix production (while limiting cellular proliferation, but not cell viability). Notably, GlcN enhanced cartilage specific matrix components, aggrecan and collagen type II, in a dose-dependent manner up to 2 mM but the effect was lost by 15 mM. Additionally, GlcN treatment up-regulated transforming growth factor-beta1 (TGF-beta1) mRNA levels. CONCLUSION: Results indicate that culture conditions play a significant role in determining the effect of GlcN on chondrocytes, explaining both the previously reported beneficial and deleterious effects of this sugar. The ability of GlcN to alter TGF-beta1 signaling provides a biochemical mechanism for GlcN activity on chondrocytes that up to now has remained elusive. The observed anabolic effect of optimal GlcN concentrations on chondrocytes may be useful in formulating effective cartilage repair strategies.

Aggrecans↗
PubMed2006

Enhanced therapeutic efficacy of IL-12, but not GM-CSF, expressing oncolytic herpes simplex virus for transgenic mouse derived prostate cancers.

Replication competent oncolytic herpes simplex viruses (HSV) with broad-spectrum activity against various cancers, including prostate cancer, exert a dual effect by their direct cytocidal action and by eliciting tumor-specific immunity. These viruses can deliver immunoregulatory molecules to tumors so as to enhance the cumulative antitumor response. This is particularly desirable for prostate cancers, which are usually poorly immunogenic. Initial studies described herein comparing the efficacy of three different oncolytic HSVs (G207, G47Delta, and NV1023) to inhibit the growth of the poorly immunogenic TRAMP-C2 mouse prostate tumors demonstrated that NV1023 was most effective in treating established tumors. The expression of IL-12 on an NV1023 background (NV1042), but not the expression of GM-CSF (NV1034), further enhanced the efficacy of NV1023 in two murine prostate cancer models with highly variable MHC class I levels, Pr14-2 with 91% and TRAMP-C2 with 2% of cells staining. NV1042 also inhibited the growth of distant noninoculated tumors in both prostate cancer models. NV1042 treated tumors exhibited increased immune cell infiltration and decreased levels of angiogenesis. Thus, an IL-12 expressing oncolytic herpes virus, which is capable of direct cytotoxicity and can modulate the otherwise suboptimal immune response through concomitant expression of the cytokine at the site of tumor destruction, could serve as a valuable clinical agent to seek out both overt and occult prostate cancers.

Animals↗
PubMed2006

The role of biomaterials in stem cell differentiation: applications in the musculoskeletal system.

The capabilities of stem cells continue to be revealed, leading to excitement regarding potential new therapies. Regenerative medicine is an area in which stem cells hold great promise for overcoming the challenge of limited cell sources for tissue repair. Biomaterials play an important role in directing tissue growth and may provide another tool to manipulate and control stem cell behavior. Biomaterials are made from natural or synthetic polymers and can be processed into three-dimensional scaffolds designed to promote cell proliferation and/or differentiation that ultimately produces new tissue. Stem cells will have a significant impact on the fields of regenerative medicine and tissue engineering as a powerful cell source that will work, in conjunction with biomaterials, to treat tissue and organ loss. Herein, we survey our latest research on applying embryonic stem (ES) cells to hydrogel biomaterials for engineering musculoskeletal tissues, emphasizing the unique biomaterial requirements of ES cells for differentiation and tissue development.

Animals↗
PubMed2006

Healthcare and workloss costs associated with patients with persistent asthma in a privately insured population.

OBJECTIVE: The objective of this study was to estimate annual healthcare and workloss costs of patients with persistent asthma by severity. METHODS: A persistent asthma patient sample (<65 years) was selected from an employer claims database. Asthma persistence and severity were determined by a novel algorithm based on Health Plan Employer Data and Information Set criteria, Leidy's Reliever and Oral Steroid Method, and Global Initiative for Asthma guidelines. Healthcare costs were compared between asthma patients and demographically matched controls and by asthma severity. RESULTS: Average annual excess costs for persistent patients were $4412 for health care and $924 for workloss (P < 0.01). Although costs for severe patients were higher than moderate patients (P < 0.05), moderate patients' costs were similar to that for mild patients. Persistent use of inhaled corticosteroids was lower in mild (9.0%) relative to moderate (78.1%) and severe (86.4%) patients. CONCLUSIONS: Persistent asthma is expensive. Underutilization of inhaled corticosteroids is higher in patients with mild persistent asthma.

Adolescent↗
PubMed2004

In vitro evaluation of the XR-15 portable x-ray unit for forensic odontology.

The purpose of this research was to investigate if a portable, light-weight radiographic generator, Golden Engineering's XR-150, can be used in forensic odontology to aid identification. Dental periapical radiographs produced by the XR-150 were evaluated for diagnostic quality based on sharpness, detail, and whether the lamina dura, periodontal membrane space and bone trabeculae could be observed. Logistic regression was used to calibrate the evaluators for reliability and for comparison of impulse values within the different sites at p<0.01. Spearman's Correlation was used to test for significance between the four quadrants at p<0.01. The XR-150 produced statistically significant (p<0.01) diagnostic images between five and ten impulses in all locations tested: anterior maxilla, anterior mandible, posterior maxilla, and posterior mandible.

Alveolar Process↗
PubMed2001

Preclinical safety evaluation of G207, a replication-competent herpes simplex virus type 1, inoculated intraprostatically in mice and nonhuman primates.

G207, a replication-competent herpes simplex virus type 1 (HSV-1) virus, has been previously shown to be effective against human prostate cancer xenografts in mice. This study assesses its safety in the prostate of two animal models known for their sensitivity to HSV-1. BALB/c mice were injected intraprostatically with either HSV-1 G207 or strain F and observed for 5 months. None of the G207-injected animals exhibited any clinical signs of disease or died. However, 50% of strain F-injected mice displayed sluggish, hunched behavior and died by day 13. Histopathologically, the G207-injected prostates were normal whereas strain F-injected prostates showed epithelial flattening, sloughing, and stromal edema. Four Aotus nancymae monkeys were also injected with G207 intraprostatically and observed short term (up to 21 days) and long term (56 days). Safety was assessed on the basis of clinical observations, viral biodistribution, virus shedding, and histopathology. None of the injected monkeys displayed evidence of clinical disease, shedding of infectious virus, or spread of the virus into other organs. Except for minor histological changes unrelated to the study, no significant abnormalities were observed. These results demonstrate that G207 can be safely inoculated into the prostate and should be considered for human trials for the treatment of prostate cancer.

Animals↗
PubMed2001

Thyroid hormones regulate lipid peroxidation and antioxidant enzyme activities in Anabas testudineus (Bloch).

The role of thyroid hormones in metabolic pathways are well known. However, their involvement in lipid peroxidation and antioxidant enzyme activities is not known. In this study, the in vivo injection of 6-propylthiouracil (6-PTU) did not alter the concentration of malondialdehyde (MDA) and conjugated dienes in liver. The administration of triiodothyronine (T3) or diiodothyronine (T2) increased the peroxidation rate in hypothyroid fish. However, in normal fish, only a high dose of T2 caused increased malondialdehyde (MDA) production, rather than T3. SOD activity was higher in T2-treated groups in both experiments. Glutathione peroxidase (GPx) activity was also high in hypothyroid fish treated with T2. In normal specimens, injections of T3 and T2 had no effect on GPx activity. Glutathione reductase (GR) activity was not altered by hypothyroidism while T3 (1 microg) and T2 (1 microg) increased it. Glutathione content was low in 6-PTU treated fish and high in both T3- and T2-treated groups. Thus it can be concluded that not only T3 but also T2, formed by sequential monodeiodination of T4, is also effective in influencing lipid peroxidation and antioxidant enzyme activities in Anabas. Furthermore, hypothyroidism as well as hyperthyroidism affects lipid peroxidation in this teleost.

Animals↗
PubMed2001

Hypothyroidism and nutritional status alter 3,5,3'-triiodothyronine (T3) receptors in isolated liver nuclei of Anabas testudineus (Bloch).

T3 receptors are ligand-dependent transcriptional activators that can stimulate gene expression resulting in growth and development. In this study T3 binding sites on isolated liver nuclei are demonstrated in the teleost Anabas testudineus. The effect of hypothyroidism and feeding of polyunsaturated fatty acids (PUFA) on T3 receptor number and binding affinity was also studied. Hypothyroidism caused an increase in T3 receptor number and a decrease in receptor affinity. PUFA feeding also increased the T3 receptor number without any significant change in its receptor affinity.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Changes in lipid peroxidation and antioxidant enzyme activities by triiodothyronine (T3) and polyunsaturated fatty acids (PUFA) in rat liver.

Thyroid hormones play an important role in the control of metabolism of vertebrates. This investigation was carried out to examine the effects of triiodothyronine (T3) and polyunsaturated fatty acids (PUFA) on lipid peroxidation in rat liver. Male Wistar strain of rats treated with 6-propylthiouracil (6-PTU) showed no significant change in lipid peroxidation as evident from the generation of malondialdehyde and conjugated dienes. However, in PUFA fed animals as well as 6-PTU + PUFA + T3 treated groups, increased peroxidation products were found. Superoxide dismutase (SOD) activity was low in 6-PTU, 6-PTU + PUFA, PUFA, 6-PTU + PUFA + T3 treated animals while glutathione peroxidase (GPx) activity was high in these groups. Catalase activity was low in all treated groups except PUFA alone fed animals. Glutathione reductase (GR) activity was decreased by 6-PTU treatment and increased in PTU + PUFA fed rats. Cellular glutathione level was high in PUFA and low in PTU-treated groups. From these results it can be concluded that both T3 and PUFA have profound influence on lipid peroxidation and antioxidant enzyme activities in rat liver.

Animals↗
PubMed2001

Short-term effects of thyroid hormones on lipogenic enzymes and 14C-acetate incorporation into various lipid classes: in vivo and in vitro studies.

Short-term effect of 3,5,3'-triiodothyronine (T3) and 3,5-diiodothyronine (T2) on lipid metabolism in the liver of Anabas testudineus was examined. In vivo injections of both T3 and T2 at a concentration of 10 ng/g body weight increased malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) activity compared to 6-propylthiouracil (6-PTU) treated group. Treatment of 6-PTU results in the accumulation 14C-acetate into fat and thyroid hormones' treatment reduce it. In vitro experiments show that malic enzyme activity is augmented only by high concentration of T3 (10(-7) M) where as all concentrations of T2 increase its activity. In vitro studies with T3 showed a biphasic effect on cholesterol content. Conversely T2 in vitro, reduced cholesterol content with all concentrations. From these results it can be concluded that both T3 and T2 have short-term effect on lipid metabolism in Anabas.

Acetic Acid↗
PubMed2001

Polyunsaturated fatty acids (PUFA) regulate neurotransmitter contents in rat brain.

The effects of feeding of 6-propylthiouracil (6-PTU) and polyunsaturated fatty acids (PUFA) independently and in combination and administration (ip) of a single dose of triiodothyronine (T3) (2.5 microg/100 g body wt) along with feeding of 6-PTU and PUFA were studied in rat brain. Dopamine (DA), 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxy indole acetic acid (5-HIAA), norepinephrine (NE) and epinephrine (EPI) contents were assayed in the hypothalamus and cerebral cortex regions. It was found that 6-PTU feeding resulted in decrease in dopamine, 5-HT, 5-HTP and 5-HIAA in both regions. In animals fed with PUFA followed by administration of T3, the DA level was found normal.

Animals↗
PubMed2000

Long-term feeding of dietary oils alters lipid metabolism, lipid peroxidation, and antioxidant enzyme activities in a teleost (Anabas testudineus Bloch).

Anabas testudineus (climbing perch), average body weight 21+/-1 g, were maintained in culture tanks and fed a 35% protein feed plus an additional supplementation of three dietary oils (20% each of coconut oil, palm oil, or cod liver oil). Body weight gain was similar among all groups. However, several hepatic lipogenic enzymes such as malic enzyme (ME), NADP-isocitrate dehydrogenase (ICDH), glucose 6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and beta-hydroxy-1-methyl glutaryl CoA reductase (HMG CoA reductase) were assayed, and they responded differently. Hepatic ME and G6PDH activities showed a significant decrease in the coconut oil and palm oil groups, but there was no significant change in ICDH activity. The 6PGDH activities were reduced, whereas HMG CoA reductase activity was increased in the palm oil-treated group. Cholesterol synthesis in the liver and muscle increased in the palm oil-treated group, but liver phospholipids did not show any significant change in fish supplemented with oils rich in saturated fatty acids. Triacylglycerol and free fatty acid concentrations were high in the coconut oil- and palm oil-supplemented groups. Lipid peroxidation products such as thiobarbituric acid-reactive substances and conjugated dienes decreased in the same two groups. Antioxidant potential was high in all groups as evidenced by increased activity of superoxide dismutase, glutathione peroxidase, and glutathione content. The results of this study indicate that in fish, dietary lipids depress hepatic lipogenic activity as well as lipid peroxidation products by maintaining high levels of antioxidant enzymes.

Animals↗
PubMed2000

Basic fibroblast growth factor stimulates collagenase-3 promoter activity in osteoblasts through an activator protein-1-binding site.

Basic fibroblast growth factor (bFGF) stimulates collagenase-3 synthesis in fetal rat osteoblast-enriched (Ob) cells. In this study we examined the mechanism of collagenase-3 regulation in Ob cells. bFGF at 0.6 nM or more increased the transcriptional rate of collagenase-3 by 3- to 7-fold. bFGF at 0.6 nM increased the activity of collagenase-3 promoter-luciferase reporter deletion constructs from -721 to -53 nucleotides transiently transfected into Ob cells by 3- to 5-fold. The minimal bFGF response was retained within the -53 to +28 sequence. Mutational analysis revealed that the bFGF effect was mediated through an activator protein-1 (AP-1)-binding site located at -48 to -42 nucleotides in the promoter. bFGF stimulated the binding of nuclear factors to the collagenase AP-1 site by 3- to 4-fold, as determined by electrophoretic mobility shift assays. Supershift analysis of nuclear extracts revealed that bFGF stimulates the occupancy of AP-1 site by c-Jun, JunB, JunD, c-Fos, FosB, and Fra2. In conclusion, bFGF increases collagenase-3 gene transcription, an effect mediated through an AP-1 site, due to the induction or activation of Jun and Fos family transcription factors. The stimulation of collagenase-3 synthesis by bFGF may be critical in mediating the actions of this growth factor in bone remodeling.

Animals↗
PubMed2000

Alendronate stimulates collagenase 3 expression in osteoblasts by posttranscriptional mechanisms.

Bisphosphonates inhibit bone resorption by reducing osteoclastic cell number and activity. Alendronate is a nitrogen-containing bisphosphonate analog used in the treatment of postmenopausal osteoporosis. The effects of alendronate in osteoclasts are well documented; however, there is limited information on the actions of alendronate in osteoblasts (Ob's). In this study, we investigated the effects of alendronate at concentrations of 1-100 microM on the synthesis of collagenase 3 or matrix metalloproteinase 13 (MMP-13) and tissue inhibitors of MMPs (TIMPs) 1, 2, and 3 in primary Ob-enriched cells from 22-day-old fetal rat calvariae. Alendronate at concentrations higher than 10 microM markedly stimulated the synthesis of collagenase messenger RNA (mRNA) and immunoreactive protein in Ob's. Alendronate did not stimulate the transcriptional rate of the collagenase 3 gene. However, in transcriptionally arrested cells, alendronate prolonged the half-life of collagenase transcripts. Alendronate did not alter the expression of TIMP 1 and 2, but modestly stimulated the expression of TIMP 3. The actions of alendronate in Ob's suggest potential additional effects in bone remodeling.

Alendronate↗
PubMed2000

3,5,3'-triiodothyronine (T3) and 3',5'-diiodothyrone (T2) have short-term effects on lipid metabolism in a teleost Anabas testudineus (Bloch): evidence from enzyme activities.

As thyroid hormones are known to have long-term and short-term effects on metabolism and only the long term effects been examined in detail, in the present investigation a comparative study has been mad to elucidate the short-term effects of T3 and T2 on enzymes of lipid metabolism in a fish Anabas testudineus. The time dependent studies involved assays of specific, activities of lipogenic enzymes and membrane ATPase- Anabas responded to T3 treatment with a significant increase in the liver malic enzyme activity (after 1 hr) and the activity pattern was reversed after 6 hrs in low dose (0.25microg T3) treated group. T2 treatment also increased the malic enzyme activity within one hour after administration. T2 caused an Increase, in the activity of glucose-6-phosphate dehydrogenase under both time courses, HMG-CoA Reductase activity was reduced upon T3 and T2 administration except for T2 at one hour. T3 treatment significantly enhanced Na+K+-ATPase activity while T2 decreased it except by low dose at one hour. Both T3 and T2 treatment influenced the activities of enzymes of lipid synthesis in a dose and time dependent manner emphasising a short-term effect of these thyroid hormones in Anabas.

Animals↗
PubMed2000

Investigation of trunk and extremity movement associated with passive head turning in newborns.

BACKGROUND AND PURPOSE: Physical therapist examination of pediatric clients or clients with neurological conditions often includes the observation of stereotypical movement patterns such as the asymmetrical tonic neck reflex and righting reactions. The purpose of this study was to investigate whether extremity and trunk responses to passive head turning could be documented in newborn infants. SUBJECTS AND METHODS: Forty-two newborns with no known medical problems were videotaped within 5 days of birth while an investigator turned their heads left and right. Videotapes were stopped at 5-second intervals to record the direction of head turn with the rest of the body obscured. A second investigator recorded trunk and extremity position with the head obscured. RESULTS: The direction of head turning affected upper- and lower-extremity position, with extension stronger on the face side. The direction of trunk convexity was also affected by head position, with the trunk convex to the side to which the face was turned. CONCLUSION AND DISCUSSION: Extremity responses and trunk responses to passive head turning can be documented corresponding to patterns reported for the asymmetrical tonic neck reflex and righting reflexes in neonates with no known medical problems more frequently than would occur by chance.

Back↗
PubMed1999

Enhanced radiation late effects and cellular radiation sensitivity in an ATM heterozygous breast cancer patient.

We observed severe late effects in a patient treated with radiation therapy for breast cancer. Radiation survival studies of patient fibroblasts show an enhanced cellular radiation sensitivity (Do = 0.95 Gy). Genetic analysis reveals that the patient is heterozygous for a mutated ATM gene. Protein truncation test (PTT) and sequence analysis identified a truncation within the leucine zipper domain, corresponding to a fragment previously reported to exhibit dominant negative function. These findings demonstrate that ATM heterozygosity may be associated with enhanced clinical radiation sensitivity and suggest a clinical relevance to this truncation that results in a dominant negative-acting protein.

Adenocarcinoma, Mucinous↗