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Biomedical subjects

K Ghosh

Publications and source records attributed to K Ghosh.

At least 163 records · Page 9Linked to original sources

Endogenous versus exogenous IL-10 in postoperative intraperitoneal adhesion formation in a murine model.

BACKGROUND: Modulation of the immune response to peritoneal injury may prevent postoperative adhesion formation. Exogenous interleukin-10 (IL-10) limits postoperative adhesion formation. The objective of the present study is to determine (I) the IL-10 dose most effective at adhesion prevention, (II) the presence of endogenous IL-10 in peritoneal fluid, and (III) the ability of an anti-IL-10 monoclonal antibody to modify postoperative intraperitoneal adhesion formation. MATERIALS AND METHODS: Within parts I, II, and III of the study 8-week-old Swiss Webster mice were randomized to have no surgery or to undergo a standardized adhesion-inducing peritoneal injury. Animals were further randomized to different dosing schedules of IL-10 (10 ng/kg to 100 micrograms/kg; part I), different times of euthanasia and peritoneal lavage after surgery (part II), or intraperitoneal (i.p.) treatment with phosphate-buffered saline vehicle (1 ml), IL-10 (1 microgram/kg), or anti-IL-10 (1 microgram/kg; part III). All i.p. injections were given immediately after surgery and then every 24 hr for a total of four injections. Animals were sacrificed 7 days after surgery and adhesion formation was assessed. RESULTS: Maximal adhesion-limiting effects of exogenons IL-10 were reached at doses of 1 microgram/kg. Mean detectable endogenous IL-10 levels in the peritoneal fluid varied from 145 to 220 pg/ml throughout the postoperative course. There were significant (P < 0.0005) differences in adhesion scores between mice treated with IL-10 (3.39; 95% CI 0.39-6.39) or PBS postoperatively (7.46; 95% CI 5.28-9.64), untreated surgical control animals (5.98; 95% CI 2.55-9.41), or anti-IL-10-treated animals (10.11; 95% CI 8.50-11.72). CONCLUSION: Interleukin 10 is effective at reducing postoperative intraperitoneal adhesion formation. Low levels of endogenous IL-10 are detectable in peritoneal fluid throughout the postoperative course, not correlating with adhesion scores. Anti-IL-10, when administered daily postoperatively in pharmacologic doses, does not appear to significantly increase postoperative adhesion formation. This puts into question if endogenous IL-10 production indeed plays a role in nonadhesiogenic peritoneal healing.

Animals↗

Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature.

BACKGROUND: The standard treatment for endometrial carcinoma is staging laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy. In an attempt to preserve childbearing potential, selected patients with endometrial carcinoma were treated with progestin alone as primary therapy. METHODS: Patients were identified through searches of tumor registries and solicitation of consulting gynecologic oncologists at the affiliated institutions of the University of California-Los Angeles Center for the Health Sciences. Only those patients with a diagnosis of endometrial carcinoma treated with progestin alone as primary therapy were included in the study. Independent pathologic review was performed by a recognized expert gynecologic pathologist to exclude cases of endometrial hyperplasia. A MEDLINE search was conducted to identify reports of similarly treated patients. RESULTS: Seven patients were treated with progestin alone for endometrial carcinoma at the study institution. Fourteen additional patients were identified through the literature search. Combining the data for all patients, 13 of 21 patients (62%) had an initial response to progestins. Three initial responders later developed recurrent disease, one of whom was found to have extrauterine disease at laparotomy. Eight of 21 patients (38%) did not respond to progestins and underwent more definitive treatment. None of these patients later developed recurrent disease. Six viable infants were delivered of three patients after therapy. Nineteen of 21 patients were alive without evidence of disease at last follow-up. CONCLUSIONS: The results of this study show that premenopausal women with endometrial carcinoma may be treated successfully with progestin therapy alone as primary therapy to preserve childbearing potential.

Adenocarcinoma↗

Fibrinolysis, inhibitors of blood coagulation, and monocyte derived coagulant activity in acute malaria.

Different parameters of fibrinolytic systems like t-PA, PAI, D-dimer, and inhibitors of blood coagulation, i.e., protein C (PC), protein S(PS), and antithrombin III (AT-III), have been studied in cases of acute malaria due to Plasmodium falciparum and plasmodium vivax infection, and these patients were followed up. It was observed that the plasma PAI-1 was very high in cases of P. falciparum malaria infection as compared to normal controls and P. vivax infection. The changes in complicated cases of P. falciparum were remarkable as compared to uncomplicated ones. The PC, PS, and AT-III levels were also low in P. falciparum, particularly so in complicated cases, and were normal in P. vivax infection. The factor VIII R:Ag levels were invariably high in acute malaria. On follow-up of some of these cases the values came back to normal after the antiparasite treatment. The monocyte procoagulant activity was found to be significantly higher in P. falciparum infection as compared to that of P. vivax infection. All these findings therefore contribute towards the production of a hypercoagulable state in P. falciparum infection and partly explain the complications of P. falciparum infection like cerebral malaria.

Antithrombin III↗

Factor VIII and IX gene polymorphisms and carrier analysis in Indian population.

The efficacy of the three common intra- and extragenic polymorphic sites of the factor VIII and IX genes has been examined in the Indian population, with an aim to develop a strategy that would be accurate and informative, yet economical. The approach for hemophilia A carrier detection includes tests for BclI, XbaI, and TaqI polymorphic sites for introns 18 and 22 and the extragenic locus St 14, respectively, whereas for hemophilia B, tests include detection of TaqI, DdeI, and HhaI polymorphic sites for introns 4 and 1, and the 3' flanking region of the factor IX gene, respectively. In hemophilia A, the cumulative efficiency of these three polymorphisms has been found to be 100%, since all 37 tested families were informative for at least one of these three polymorphisms. It is of interest to note that a case of recombination between St 14 and the factor VIII gene was also observed. Of the 47 unrelated X chromosomes examined (normal = 10, factor VIII:C deficiency = 37), heterozygosity for BclI, XbaI, and St 14 was found to be 47%, 36%, and 86%, respectively, in the factor VIII gene. However, when 37 unrelated X chromosomes (normal = 10, factor IX:C = 27) were analyzed for polymorphism with TaqI, DdeI, and HhaI, it was found that the polymorphism detection rate was only 18% for the TaqI site but 45% each for the DdeI and HhaI sites, in the factor IX gene. This indicates a low effectiveness of the TaqI restriction site in carrier analysis of hemophilia B families in our population.

Alleles↗

The history of geriatric medicine in Scotland.

The concept that care of elderly people required special facilities and training started early this century but was only implemented with the advent of the NHS in 1948. In Scotland the speciality gradually evolved and grew in stature and prominence. The early pioneers in Scotland are described.

Aged↗

Patterns of genetic variability in colonized strains of Lutzomyia longipalpis (Diptera: Psychodidae) and its consequences.

The genetic qualities of laboratory colonies of phlebotomine sand flies have not been compared with field specimens despite 1) probable genetic shifts due to the colonization process and 2) the problems associated with the extrapolation of experimental data derived from colonized organisms to field populations. The present study compared the genetic profiles of five laboratory colonies of geographic strains of the New World sand fly Lutzomyia longipalpis, and contrasted them with field populations. The profiles were based on the variability exhibited with polyacrylamide gels at 14 enzyme loci. A general pattern of a loss of infrequent alleles and decreased heterozygosity emerged as an apparent consequence of colonization. The average number of alleles per locus ranged from 1.2 to 1.6, and the average heterozygosity ranged from 4% to 11%. The field collection from Lapinha Caves (near Belo Horizonte, Brazil) averaged 2.1 alleles with a heterozygosity of 16%. In contrast, the LAPINHA laboratory colony established from that site 24 years earlier showed very low values (1.2 alleles/locus and 4% heterozygosity) and fixation for alleles not present or rare in the field collection from the same site. The genetic differences between the other Brazilian colonies and the Lapinha Caves field samples were due to presence of both different alleles and highly diverged allelic frequencies. Biological inferences based on colonized sand flies must be tempered by recognizing that the colony may represent a highly skewed genetic subsample of the L. longipalpis field genome.

Alleles↗

Deferoxamine improves spatial memory performance following experimental brain injury in rats.

Traumatic brain injury (TBI) causes impairments of both motor and spatial memory performances. Research is only beginning to reveal the biochemical mechanism(s) underlying these deficits. It has been postulated that reactive oxygen species such as the superoxide and hydroxyl radicals, as well as the peroxynitrite anion, are generated by injury and may play a critical role in the observed memory deficits. The highly reactive hydroxyl radical, which is thought to contribute to neuronal toxicity, can be generated by an iron-catalyzed reaction. The source of this iron (or iron-bound proteins) could be a compromise of the blood-brain barrier, which can occur following TBI. In this report, we investigate the ability of deferoxamine, a scavenger of free iron, the hydroxyl radical and the peroxynitrite anion, to facilitate behavioral recovery following a controlled cortical impact of rats. Intraperitoneal administration of this drug prior to the injury did not affect the rate of recovery from motor deficits in comparison to vehicle (saline)-injected animals. However, deferoxamine-treated animals showed significant improvement in spatial memory performance in a Morris water maze task. Volumetric analysis of cortical tissue loss showed no significant differences between vehicle- and drug-injected animals. Similarly, histological examination of the hippocampus did not reveal any gross differences between the two groups. These results indicate that deferoxamine improves spatial memory performance, possibly through protection from neuronal dysfunction.

Animals↗

Vaccination with alum-precipitated recombinant Ancylostoma-secreted protein 1 protects mice against challenge infections with infective hookworm (Ancylostoma caninum) larvae.

Ancylostoma-secreted protein 1 (ASP-1) is the major protein secreted by infective hookworm larvae (Ancylostoma caninum). The Escherichia coli-expressed recombinant protein was evaluated as a vaccine antigen in a mouse model of ancylostomiasis. A. caninum larvae migrate through mouse lungs, with maximal migration occurring 48-54 h after oral infection. Quantitative larval recovery from the lungs at this time was used as an end point for vaccine evaluation. All mice developed antibodies to recombinant ASP-1 (rASP-1) after immunization and boosting with the alum-precipitated protein. The immunized mice had their worm burden reduced 79% (P < .0001) compared with controls. Immunization with rASP-1 in the presence of Corynebacterium parvum adjuvant also showed a vaccine effect (63% protection; P < .0001). The possibility that this protective effect resulted from delayed larval lung entry was excluded. rASP-1 offers promise as a hookworm vaccine antigen.

Adjuvants, Immunologic↗

Osteoporosis and vertebral collapse following low-dose, low molecular weight heparin therapy in a young patient.

Osteoporosis is a well-recognized complication of long-term heparin (unfractionated) therapy. It has been suggested that the low molecular weight heparins (LMWH) have a lower potential to cause osteopenia than the unfractionated preparations. We report a case of a 29-year-old woman who developed osteoporosis and pathological fracture of lumbar vertebrae following treatment with low dose LMWH (dalteparin) for 3 months. The aim of this report is to alert clinicians to the potential risk of this complication with the prolonged use of LMWH preparations--an increasingly popular choice for long-term anticoagulation.

Adult↗

Molecular approaches to vaccinating against hookworm disease.

Anthelminthic drug chemotherapy has failed as an acceptable approach to hookworm control in the less developed countries of the tropics. The development of a genetically engineered vaccine against hookworm infection would be a major advance in our efforts to control this parasitic disease. We have produced several lead recombinant hookworm vaccine antigens. Their development is based on scientific principles that were generated almost 70 years ago when investigators first began to attenuate living infective hookworm larvae. Those early studies on attenuated live vaccines highlighted the importance of secreted larval antigens for eliciting protective immunity in dogs challenged with Ancylostoma caninum. The two major secreted larval antigens have been recently identified as Ancylostoma secreted protein-1 (ASP-1) and ASP-2. The predicted amino acid sequences of the ASP cDNAs together with experimental immunogenicty data using the expressed recombinant protein suggest that the ASPs are promising vaccine antigens. Preliminary hookworm challenge data in mice immunized with recombinant ASP-1 helps to validate this assumption. Alternative vaccines based on either genetic immunization (DNA vaccines) or immunization with recombinant molecules expressed from adult hookworm cDNAs are also under evaluation. Optimization of vaccine route, delivery system, and adjuvant formulations will be required before future planned phase I testing in humans. Vaccine development for a target population living in rural areas of less developed countries will require innovative solutions to financing and manufacture.

Amino Acid Sequence↗

Evaluation of the Pall RC100 leucocyte removal filters and the effect of air introduction on its performance.

We evaluated the efficiency of Pall RC100 leucocyte removal filters in processing two units of concentrated red cells for transfusion. Our results show that the filter is very effective in processing the first unit. However, 32% (5/16) of the filters evaluated allowed a leak of substantial numbers of white cells towards the end of the transfusion of the second unit of blood. Air introduction experiments showed that as little as 2 ml of air in the filter may cause major deterioration of the filter function.

Air↗