Biomedical subjects

R Singh

Publications and source records attributed to R Singh.

At least 217 records · Page 12Linked to original sources

PubMed2000

Effect of Kombucha tea on chromate(VI)-induced oxidative stress in albino rats.

The effect of Kombucha tea (KT) on oxidative stress induced changes in rats subjected to chromate treatment are reported. KT feeding alone did not show any significant change in malondialdehyde (MDA) and reduced glutathione (GSH) levels, but did enhance humoral response and delayed type of hypersensitivity (DTH) response appreciably over control animals. Chromate treatment significantly enhanced plasma and tissue MDA levels, decreased DTH response considerably, enhanced glutathione peroxidase and catalase activities; however, no change in GSH, superoxide dismutase and antibody titres was noticed. KT feeding completely reversed the chromate-induced changes. These results show that Kombucha tea has potent anti-oxidant and immunopotentiating activities.

Animals↗

PubMed2000

Phacoemulsification in eyes with a small pupil.

PURPOSE: To evaluate the intraoperative difficulties and long-term outcome of phacoemulsification through a small pupil using minimal iris manipulation. SETTINGS: Iladevi Cataract & IOL Research Centre, Ahmedabad, India. METHODS: This prospective study included 30 consecutive eyes with a maximally dilated pupil size of 4.0 mm or smaller. Except synechiolysis and occasional pupil retraction with a chopper, no iris manipulation was performed. The phacoemulsification technique included creation of deep central space, use of a low aspiration flow rate with appropriate vacuum, and step-by-step chop in situ and lateral separation of the nucleus. Patients were examined 1 day, 1 week, 1 and 3 months, and 1 year postoperatively. Specular microscopy was performed at 1 month and 1 year. RESULTS: Fourteen eyes had chronic iritis, 12 had glaucoma surgery, 2 had pseudoexfoliation, and 2 had a rigid pupil. Mean follow-up was 13.6 months. Eighteen eyes (60%) had hard cataract. Mean preoperative pupil size was 2.80 mm +/- 0.75 (SD). Mean pupil size before the capsulorhexis was initiated was 4.42 +/- 0.58 mm. The iris was bruised in 10 eyes during cortex removal. Trace amounts of cortex were left in 4 cases. Two eyes had increased intraocular pressure in the early postoperative period. Six patients had a minimal amount of retained viscoelastic material (pseudofibrin), and 2 patients developed a sterile hypopyon. Sixteen eyes had cell deposits on the IOL surface and 12 eyes, fine uveal pigments. In 2 eyes with previous glaucoma surgery and in all eyes with iritis except 2, posterior synechias reformed. CONCLUSIONS: Successful phacoemulsification was done with minimal or no pupil-widening maneuvers, restoring the preoperative pupil configuration.

Adult↗

PubMed2000

Ketotifen for asthma in children aged 5 to 15 years: a randomized placebo-controlled trial.

BACKGROUND: The prophylactic agent ketotifen has been studied in mild-to-moderate asthma. Various trials showed benefit from 10 to 12 weeks of therapy, but no trial in children with followup beyond 12 weeks of the drug is available. OBJECTIVES: We studied the efficacy of ketotifen, 1 mg twice a day, orally as a prophylactic drug in children with asthma. METHODS: The double-blind, placebo-controlled trial studied 120 asthmatic children of either sex between the ages of 5 to 15 years at a tertiary care hospital. After an observation period of 4 weeks, children were randomly assigned to receive either ketotifen, 1 mg twice a day, or placebo for 6 months. Antiasthma drugs were continued as required. Main outcome measures included average duration for regular antiasthma drugs, average symptom scores, symptom free days, peak expiratory flow rate, FEV1, and need for emergency room visits. RESULTS: Of the 120 children enrolled, 13 could not complete the trial. Thus 58 children remained in the treatment group and 49 were in the placebo group. Both groups were comparable in their baseline characteristics. The average number of days that required antiasthma drugs were significantly less in the treatment group: salbutamol (27+/-4.7 versus 37+/-3.5 P < .05), theophylline (37+/-4.7 versus 51+/-4.8 P < .05), oral steroids (2+/-0.4 versus 5+/-1.6 P < .05), and inhalation steroids (18+/-2.7 versus 16+/-10.8 P < .05). The average symptom scores and symptom free days for cough, wheeze, and breathlessness also favored the ketotifen group. Emergency room visits were also significantly lower in the ketotifen group (20 versus 10 P < .05). Statistically significant improvement in all the above parameters were observed after 14 weeks of therapy. The mean PEFR, FEV1 and side effects of medications were comparable between the two groups. CONCLUSIONS: Ketotifen, 1 mg twice a day, is an effective prophylaxis for asthma in children between 5 to 15 years. Significant clinical improvement is evident after 14 weeks of therapy.

Adolescent↗

PubMed2000

Hepatitis B and C viral infections in Indian kala-azar patients receiving injectable anti-leishmanial drugs: a community-based study.

BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis B and hepatitis C viruses have emerged as major blood-borne infections. Several cases of infections through the use of unsterile injection needles also are on record. Kala-azar, or visceral leishmaniasis, is a hemoparasitic disease caused by Leishmania donovani. All the anti-kala-azar medications require multiple intramuscular injections of the anti-leishmanial drugs. To find whether these patients were at higher risk of contracting blood-borne infection, than those who were not on medication, a community-based study was conducted in the kala-azar-endemic state of Bihar, India. METHODS: Five villages (4050 families) of three highly endemic districts of Bihar were included in this study. The sociodemographic data of the affected families and their annual income were determined as per Government of India guidelines. The diagnosis of kala-azar and its sequelae, post-kala-azar dermal leishmaniasis (PKDL), was made, and their therapeutic details were noted. All the leishmania-infected patients, their spouses, family members, and villagemates were tested for hepatitis B surface antigen, hepatitis C virus antibodies, and anti-HIV (1 + 2) antibodies, using commercially available kits. RESULTS: Of the 4050 families, 61 (1.5%) were found affected with kala-azar or PKDL. These 61 families had 77 cases of leishmaniasis, of which 64 (83%) had kala-azar and 13 (17%) PKDL. The most affected (4.5%) age group was 11 to 40 years. Of the 61 families, 57 (93.4%) families belonged to so-called untouchable castes, and 9 of them could not afford to have any anti-kala-azar treatment. Only 64 patients received treatment in the form of injectables. The number of injections received by these patients ranged from 3 to 120. Hepatitis B and C viral infections were found to be significantly more prevalent in those who received multiple injections. Compared to their male counterparts infected with L. donovani, females who received injectable medicines were at higher risk of contracting hepatitis B infections (20% vs. 11.3%) and hepatitis C virus infection (26.7% vs. 18.9%). Overall, hepatitis C virus infections were more common (20.6%) than hepatitis B virus infection (13.2%) in this group of patients. Villagemates with a history of injections for other ailments also were found to have a high rate of infection with hepatitis viruses. One patient with kala-azar was found to be co-infected with HIV, although probably not related to injections. CONCLUSIONS: The treatment of Indian kala-azar and post-kala-azar dermal leishmaniasis consists of multiple intramuscular injections of sodium stibogluconate, pentamidine, or amphotericin B. Though the original disease gets cured, all these therapeutic regimens were found to carry a significantly high risk of transmitting yet more dangerous blood-borne infections, such as HIV and hepatitis B and C viruses, through the shared use of unsterile injection needles. All needles should be appropriately sterilized, if they are to be re-used.

Adolescent↗

PubMed2000

Differential recognition of the polypyrimidine-tract by the general splicing factor U2AF65 and the splicing repressor sex-lethal.

The polypyrimidine-tract (Py-tract) adjacent to 3' splice sites is an essential splicing signal and is recognized by several proteins, including the general splicing factor U2AF65 and the highly specific splicing repressor Sex-lethal (SXL). They both contain ribonucleoprotein-consensus RNA-binding motifs. However, U2AF65 recognizes a wide variety of Py-tracts, whereas SXL recognizes specific Py-tracts such as the nonsex-specific Py-tract of the transformer pre-mRNA. It is not understood how these seemingly similar proteins differentially recognize the Py-tract. To define these interactions, we used chemical interference and protection assays, saturation mutagenesis, and RNAs containing modified nucleotides. We find that these proteins recognize distinct features of the RNA. First, although uracils within the Py-tract are protected from chemical modification by both of these proteins, modification of any one of seven uracils by hydrazine, or any of eight phosphates by ethylnitrosourea strongly interfered with the binding of SXL only. Second, the 2' hydroxyl groups or backbone conformation appeared important for the binding of SXL, but not U2AF65. Third, although any of the bases (cytosine >> adenine > guanine) could substitute for uracils for U2AF65 binding, only guanine partially substituted for certain uracils for SXL binding. The different dependence on individual contacts and nucleotide preference may provide a basis for the different RNA-binding specificities and thus functions of U2AF65 and SXL in 3' splice site choice.

Amino Acid Motifs↗

PubMed2000

Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells.

We have investigated whether dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can trigger B cells to produce antigen-specific antibodies without CD4+ T-cell help. Dendritic cells modified with a recombinant adenovirus vector to express CD40 ligand and pulsed with heat-killed Pseudomonas induced naive B cells to produce antibodies against Pseudomonas in the absence of CD4+ T cells in vitro, initiated Pseudomonas-specific humoral immune responses in vivo in wild-type and CD4-/- mice, and protected immunized wild-type and CD4-/-, but not B-cell -/- mice, from lethal intrapulmonary challenge with Pseudomonas. Thus, genetic modification of dendritic cells with CD40 ligand enables them to present a complex mixture of microbial antigens and establish CD4+ T cell-independent, B cell-mediated protective immunity against a specific microbe.

Animals↗

PubMed2000

High risk genes predisposing to prostate cancer development-do they exist?

There is evidence for genetic predisposition to prostate cancer. However, prostate cancer genes have been more difficult to find than genes for some of the other common cancers, such as breast and colon cancer. The reasons for this are discussed in this article and it is now becoming clear that prostate cancer is probably due to multiple genes, many of which are moderate or low penetrance. The advances in the Human Genome Project and technology, especially that of robotics, will help to overcome these problems. Prostate Cancer and Prostatic Diseases (2000) 3, 241-247

Journal Article↗

PubMed2000

A study of concurrent radiochemotherapy with paclitaxel in glioblastoma multiforme.

Despite advances in neurosurgery and radiotherapy, the prognosis of patients with glioblastoma multiforme remains poor. Reports in the literature about the radiosensitizing properties of paclitaxel stimulated the authors to conduct a study using paclitaxel concurrently with radiation in a group of 18 patients who had residual disease postoperatively. Paclitaxel was delivered weekly as an intravenous infusion in a dose of 60 mg/m2 along with radiation to the primary lesion. A total of 108 cycles of paclitaxel was given. All the patients tolerated the treatment well. The main side effects were haematological, and neuropathy which was self-limiting. The overall 1-year survival rate was 70%, with 12 patients alive at 13 months. The median survival has not yet been reached although it is more than 13 months. Thus, paclitaxel can be safely delivered concomitantly with radiation in patients with glioblastoma multiforme. Larger, randomized trials are required to establish the comparative efficacy of paclitaxel as a radiosensitizer in glioblastoma multiforme.

Brain Neoplasms↗

PubMed2000

Role of angiotensin II in diabetic nephropathy.

Considerable evidence suggests that the intrarenal renin-angiotensin system plays an important role in diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (Ang II) receptor blockers (ARBs) can attenuate progressive glomerulosclerosis in disease models and can slow disease progression in humans. Because agents that interfere with Ang II action may decrease glomerular injury without altering glomerular pressures, it has been suggested that Ang II has direct effects on glomerular cells to induce sclerosis independent of its hemodynamic actions. To study nonhemodynamic effects of Ang II on matrix metabolism, many investigators have used cell culture systems. Glucose and Ang II have been shown to produce similar effects on renal cells in culture. For instance, incubation of mesangial cells in high-glucose media or in the presence of Ang II stimulates matrix protein synthesis and inhibits degradative enzyme (e.g., collagenase, plasmin) activity. Glucose and Ang II also can inhibit proximal tubule proteinases. Glucose increases expression of the angiotensinogen gene in proximal tubule cells and Ang II production in primary mesangial cell culture, which indicates that high glucose itself can activate the renin-angiotensin system. The effects of glucose and Ang II on mesangial matrix metabolism may be mediated by transforming growth factor-beta (TGF-beta). Exposure of mesangial cells to glucose or Ang II increases TGF-beta expression and secretion. Their effects on matrix metabolism can be blocked by anti-TGF-beta antibody or ARBs such as losartan, which also prevents the glucose-induced increment in TGF-beta secretion. Taken together, these findings support the hypothesis that the high-glucose milieu of diabetes increases Ang II production by renal, and especially, mesangial cells, which results in stimulation of TGF-beta secretion, leading to increased synthesis and decreased degradation of matrix proteins, thus producing matrix accumulation. This may be an important mechanism linking hyperglycemia and Ang II in the pathogenesis of diabetic nephropathy.

Angiotensin II↗

PubMed2000

Visually-guided irrigation in patients with early knee osteoarthritis: a multicenter randomized, controlled trial.

OBJECTIVE: To determine if visually-guided arthroscopic irrigation is an effective therapeutic intervention in patients with early knee osteoarthritis. DESIGN: Ninety patients with knee osteoarthritis were randomized in a double-blind fashion to receive either arthroscopic irrigation with 3000 ml of saline (treatment group) or the minimal amount of irrigation (250 ml) required to perform arthroscopy (placebo group). The primary outcome variable was aggregate WOMAC score. RESULTS: The study did not demonstrate an effect of irrigation on arthritis severity as measured by aggregate WOMAC scores, the primary outcome variable; the mean change in aggregate WOMAC score at 12 months was 15.5 (95% CI 7.7, 23.4) for the full irrigation group compared to 8.9 (95% CI 4.9, 13.0) for the minimal irrigation group (P=0.10). Full irrigation did have a statistically significant effect on patients' self-reported pain as measured by the WOMAC pain subscale and by a visual analog scale (VAS) (the secondary outcome variables). Mean change in WOMAC pain scores decreased by 4.2 (95% CI -0.9, 9.4) for the full irrigation group compared with a mean decrease of 2.3 (95% CI -0.1, 4.7) in the minimal irrigation group (P=0.04). Mean VAS pain scores decreased by 1.47 (95% CI -1.2, 4.1) in the full irrigation group compared to a mean decrease of 0.12 (95% CI 0.0, 0.3) in the minimal irrigation group (P=0.02). A hypothesis-generating post-hoc analysis of the effect of positively birefrigent intraarticular crystals showed that patients with and without intraarticular crystals had statistically significant improvements in pain assessments and aggregate WOMAC scores at 12 months; patients with crystals had statistically greater improvements in pain. CONCLUSIONS: Visually-guided arthroscopic irrigation may be a useful therapeutic option for relief of pain in a subset of patients with knee OA, particularly in those who have occult intraarticular crystals.

Adult↗

PubMed2000

No evidence of linkage to chromosome 1q42.2-43 in 131 prostate cancer families from the ACTANE consortium. Anglo, Canada, Texas, Australia, Norway, EU Biomed.

Genetic linkage studies worldwide have proposed various chromosomal localizations for prostate cancer susceptibility genes. A recent study found evidence for linkage to chromosome 1q42.2-43. The aim of our study was to attempt to confirm these findings by performing linkage analysis in 131 families with multiple prostate cancer cases selected from the ACTANE (Anglo, Canada, Texas, Australia, Norway, EU Biomed) Consortium. Parametric and non-parametric linkage (NPL) analyses were performed. Two-point LOD scores failed to show evidence of linkage at any marker (maximum two-point LOD score = 0. 40 at recombination fraction theta = 0.2 with marker D1S2850). Using a multipoint heterogeneity analysis, the estimated proportion of families linked to this putative locus (alpha) was 0% (95% CI = 0. 00-0.33). Non-parametric linkage analysis also found no evidence of linkage (maximum NPL score = -0.12, P = 0.55). This analysis of 131 ACTANE families does not support the presence of a locus for a prostate cancer susceptibility gene at 1q42.2-43. Although we cannot rule out the existence of such a locus, analysis indicates that less than 16% of families could be linked to this region. These findings may be a reflection of the locus heterogeneity involved in this disease indicating that there are still other major susceptibility loci to be identified.

Aged↗

PubMed2000

7H-benzo[c]fluorene: a major DNA adduct-forming component of coal tar.

Coal tar is a complex mixture that exhibits high carcinogenic potency in lungs of animals when administered in the diet. Studies have noted that lung tumor induction does not correlate with the benzo[a]pyrene content of coal tar, suggesting that other hydrocarbons may be involved in the observed tumorigenicity. Our previous studies have demonstrated that a major 'unknown' chemical-DNA adduct is formed in the lung of mice exposed to coal tar. We have used an in vitro rat microsomal activation system to generate the 'unknown' adduct with neat coal tar and fractions of coal tar obtained by chemical fractionation and HPLC. Chemical-DNA adduct formation was evaluated by (32)P-postlabeling using both multi-dimensional TLC and HPLC. GC-MS analysis of the coal tar fractions obtained from HPLC, which produced the 'unknown' adduct in vitro, demonstrated that the adducting hydrocarbon had a mass of 216. A careful evaluation of candidate hydrocarbons led to the conclusion that a benzofluorene derivative may be responsible for forming the 'unknown' chemical-DNA adduct. Comparative in vitro and in vivo studies on the adducting properties of all three isomers of benzofluorene indicated that 7H-benzo[c]fluorene is responsible for producing the 'unknown' adduct observed in the lung of mice ingesting coal tar. Animal feeding studies also demonstrated that 7H-benzo[c]fluorene formed considerably more lung DNA adducts than 11H-benzo[a]fluorene and 11H-benzo[b]fluorene. These data indicate that the four-ring polycyclic aromatic hydrocarbon 7H-benzo[c]fluorene, a hydrocarbon not previously shown to form DNA adducts in lung, is in fact a potent lung DNA adductor and is a candidate PAH for causing lung tumors in animals treated with coal tar.

Animals↗

PubMed2000

Intralamellar dissection techniques in lamellar keratoplasty.

PURPOSE: To evaluate and compare the efficacy of the four adjunctive agents to facilitate recipient bed intralamellar dissection in cases of lamellar keratoplasty. METHODS: Forty eyes with partial-thickness corneal opacities were recruited for this prospective, randomized clinical trial. The cases were divided into four groups per the intralamellar injection (i.e., air [group I], 2% hydroxypropyl methylcellulose [HPMC] [group II], balanced saline solution [BSS] [group III], and no adjunct [group IV] used to facilitate recipient intralamellar dissection). The intraoperative parameters evaluated were initial preparation time, dissection time, and total time. At each follow-up, visual acuity, refractive status, keratometry, and endothelial cell counts were also analyzed. RESULTS: Initial preparation time, dissection time, and total time were significantly decreased with the use of an adjunct (p < 0.05) and were found to be least with the use of BSS. No difference in these time frames was noted between group I and group II. Corneal haze and incomplete air insufflation were seen in group I, and difficulty in injection of 2% HPMC and its incomplete spread were noted in group II. The mean spherical equivalent, astigmatism, endothelial cell counts, and visual acuity did not show any significant difference between any group. CONCLUSION: Hydrodelamination with BSS is easy to perform and should be undertaken routinely to facilitate recipient intralamellar dissection.

Adult↗

PubMed2000

Chemotherapy in recurrent epithelial ovarian cancer (EOC): an analysis of prognostic factors.

OBJECTIVE: Prognosis of patients with recurrent epithelial ovarian cancer (EOC) is generally poor. Cisplatin is the most effective drug. We used three cisplatin based chemotherapeutic (CT) regimens and retrospectively analyzed the data to determine the response rate, toxicity, survival and the impact of various prognostic factors on the outcome. PATIENTS AND METHODS: Between August, 1989 and September, 1997, 102 patients were diagnosed to have recurrent EOC. Sixty-five of 102 patients received CT every 3 weeks using cisplatin 75 mg/m2 i.v. day 1 plus cyclophosphamide 750 mg/m2 i.v. day 1 (CP, Group A, n = 29), cisplatin 75 mg/m2 i.v. day 1, plus adriamycin 40 mg/m2 i.v. day 1 and cyclophosphamide (CAP, Group B, n = 22) and paclitaxel 135 mg/m2 i.v. day 1 plus cisplatin 75 mg/m2 i.v. day 1 (TP, Group C, n = 14). Twelve patients received single agent CT and were not analyzed. Remaining 25 patients refused CT treatment and were followed for survival. RESULTS: The overall response rate (complete and partial) was 59.2% for patients receiving CP (Group A), 45% for CAP (Group B) and 76.9% for those receiving TP (Group C), p = ns. Response rate was significantly higher for patients with platinum sensitive disease compared to those with platinum resistant disease; 55.76 vs 39%, p < 0.007. CT was generally tolerated well; 2 patients died of CT toxicity, one each in Group A (CP) and C (TP), respectively. The median survival from the date of relapse for patients receiving chemotherapy was 15 months compared to 4 months for those who did not receive chemotherapy, p < 0.001. Chemotherapy responders had a significantly higher median survival than chemotherapy non-responders, 24 months vs 10 months, p < 0.01. The median overall survival was not significantly different in the 3 groups; Group A--15 months, Group B--12 months and 15 months in Group C, p = 0.738. On univariate analysis--time since last CT (< 6 months vs > 6 months, p < 0.037, response to previous CT, p < 0.0183, cisplatinum sensitivity vs resistance, p < 0.032, number of sites (< 2 vs > 2) of recurrence, p < 0.004 and response to salvage CT, p < 0.01 were associated with survival benefit. On multivariate analysis, 2 factors--platinum sensitivity and response to salvage CT attained significance. CONCLUSIONS: Our study confirms the benefit of platinum based chemotherapy in recurrent EOC. Patients with platinum sensitive disease, and those responding to salvage chemotherapy benefit most.

Adult↗

PubMed2000

Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves.

This study evaluated whether increased release of nitric oxide (NO) from the nitrergic component of the nonadrenergic, noncholinergic (NANC) nerves may be partly responsible for the decrease in gastrointestinal motility observed during pregnancy. Segments of fundal strip, ileum, and colon were obtained from nonpregnant rats, rats in midpregnancy (days 9-11), and rats in late pregnancy (days 18-20). NANC activity was studied by assessing changes in tone after application of electric field stimulation (EFS). The role of NO was determined by observing the effects of EFS in the presence and absence of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the reversibility of the effects of L-NAME by L-arginine. The magnitude of change in cGMP levels in the tissues after application of EFS was also assessed. Our studies indicate that there was increased magnitude of relaxation of isolated strips of rat gastric fundus and rat colon, after application of EFS to tissues obtained only from animals in late pregnancy. These results paralleled the changes in cGMP levels in tissues. NOS activity in the gastric fundus was significantly increased in animals in late pregnancy compared with nonpregnant controls. Our studies suggest that the delay in gastric emptying and increase in colonic transit time observed in rats during pregnancy may be caused in part by increased activity of the nitrergic component of the NANC nerves innervating these organs.

Acetylcholine↗

PubMed2000

Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema.

We hypothesized that the angiogenic mediator, vascular endothelial growth factor (VEGF), known to be expressed in the lung and to be capable of inducing local edema in skin, might evoke the development of lung edema if expressed in excess amounts. To test this hypothesis, we developed an in vivo model of VEGF overexpression in the lung on the basis of delivery to the respiratory epithelium of the VEGF165 complementary DNA by an E1(-) adenovirus vector (AdVEGF165). Administration of AdVEGF165 by the intratracheal route (10(9) plaque-forming units [pfu]) to C57Bl/6 mice showed increased expression of VEGF messenger RNA in lung tissue by Northern analysis. Overexpression of VEGF protein in the lung at Days 1 to 10 was confirmed by enzyme-linked immunosorbent assay. Intratracheal administration of AdVEGF165 resulted in a dose-dependent increase in lung wet/dry weight ratios over time, lung histology showed widespread intra- alveolar edema, and pulmonary capillary permeability was significantly increased as quantified by the Evans blue dye assay and [(131)I]albumin permeability. To confirm the specificity of these observations, mice were pretreated with intranasal administration of an adenovirus vector expressing a truncated soluble form of the VEGF receptor flt-1 (Adsflt). Adsflt (10(9) pfu) pretreatment completely abrogated the increased lung wet/dry weight ratio caused by AdVEGF165 administration, whereas an identical adenovirus vector with an irrelevant transgene had no effect upon subsequent AdVEGF165-induced pulmonary edema. Together, these data suggest that overexpression of VEGF in the lung may be one mechanism of increased pulmonary vascular permeability in the early stages of acute lung injury.

Administration, Inhalation↗

PubMed2000

The viral anti-inflammatory chemokine-binding protein M-T7 reduces intimal hyperplasia after vascular injury.

Chemokines and IFN-gamma function as central regulators of inflammatory responses to vascular injury. Both classes of cytokines are upregulated during restenosis, a response to vascular injury that leads to recurrent atherosclerotic plaque growth, but the relative impact of each class of cytokines remains undetermined. M-T7 is a secreted myxoma viral immunomodulatory glycoprotein that functions both as a species-specific inhibitor of rabbit IFN-gamma and as a chemokine-binding protein, interacting with a wide range of C, C-C, and C-X-C chemokines in a species-nonspecific fashion. We wished to (a) assess the efficacy of purified M-T7 protein in inhibiting intimal hyperplasia after angioplasty injury and (b) exploit unique species-specific functions of M-T7 in order to judge the relative importance of each cytokine class on plaque growth. Anesthetized New Zealand white rabbits and Sprague-Dawley rats received either M-T7 or control at the time of arterial angioplasty injury. Histological analysis at 28 days demonstrated significant reductions in intimal hyperplasia with M-T7 treatment in both models, with an associated early inhibition of inflammatory cell invasion. Purified M-T7 protein inhibits intimal hyperplasia after angioplasty injury in a species-nonspecific fashion, thus implicating the chemokine-binding activity as more critical for prevention of plaque growth after vascular injury.

Animals↗

PubMed2000

Attitudes and attraction: a new test of the attraction, repulsion and similarity-dissimilarity asymmetry hypotheses.

Dissimilarity and similarity between attitudes of the participants and a stranger were manipulated across two sets of issues to test the attraction, repulsion and similarity-dissimilarity asymmetry hypotheses. Participants (N = 192) judged social (liking, enjoyment of company) and intellectual (intelligence, general knowledge) attractiveness of the stranger. The similarity in the first set of attitudes x similarity in the second set of attitudes effect emerged in social attraction, but not in intellectual attraction. Stated simply, dissimilarity had a greater weight than similarity in social attraction, but equal weight in intellectual attraction. These results support the similarity-dissimilarity asymmetry hypothesis that predicts dissimilarity-repulsion to be stronger than similarity-attraction. However, they reject (1) the attraction hypothesis that dissimilarity and similarity produce equal and opposite effects on social attraction; and (2) the repulsion hypothesis that only dissimilar attitudes affect social attraction by leading to repulsion. An equal weighting of dissimilarity and similarity in intellectual attraction further suggested that the similarity-dissimilarity asymmetry on social attraction is reflective of a stronger avoidance response in the Darwinian sense.

Adolescent↗