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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 235 records · Page 13Linked to original sources

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis.

CD105 and its ligand transforming growth factor beta (TGFbeta) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40-9.00) and 3.10 (range 0.90-8.00), respectively. Kaplan-Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFbeta1 and TGFbeta3 together with the receptor-ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFbeta1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFbeta1 level was noted in patients with carcinoma over the controls. Furthermore, TGFbeta3 and CD105/TGFbeta3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFbeta1 was expressed in cancer cells but TGFbeta3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFbeta1, TGFbeta3 and CD105/TGFbeta complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

Adult↗

Cross-reactivity between anti-cardiolipin, anti-high-density lipoprotein and anti-apolipoprotein A-I IgG antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome.

OBJECTIVES: Atherosclerosis is an important complication of patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). One suggested mechanism may be the action of autoantibodies directed against plasma lipoproteins. We studied the presence and patterns of cross-reactivity between antibodies directed against cardiolipin, high-density lipoprotein (HDL) and apolipoprotein A-I (Apo A-I) in patients with SLE and APS. METHODS: Sera from 50 patients (25 SLE and 25 APS) and 10 healthy controls together with three human immunoglobulin G anti-cardiolipin (CL) monoclonal antibodies (IS4, CL1 and CL24) were assessed for the presence of autoantibodies binding cardiolipin, HDL and Apo A-I. Classical inhibition assays were performed to study interference by HDL and Apo A-I in the binding of the human monoclonal antibody to CL. To determine the cross-reactivity patterns between these autoantibodies, sera from 12 patients were incubated on ELISA plates coated with the three different molecules and the captured antibodies were then tested for their activity towards each of the other antigens. RESULTS: All three monoclonals bound to CL. IS4 and CL1 also bound to HDL but only IS4 bound to Apo A-I. Anti-cardiolipin titres were higher in patients with APS than SLE and in healthy controls (P<0.03 and P<0.009 respectively). Titres of antibodies to HDL were higher in patients with SLE and APS than in controls (P<0.009 and P<0.03 respectively). There were no significant differences with respect to the presence of antibodies binding to Apo A-I. In the SLE population, anti-HDL antibody titres correlated with anti-Apo A-I (r=0.563, P<0.004), but not in patients with APS. In the cross-reactive assay, 11/12 (91.7%) of the samples containing isolated anti-CL antibodies reacted to HDL and 2/12 (16.7%) to Apo A-I. Samples containing isolated anti-HDL antibodies also reacted with CL and Apo A-I (7/12 and 3/12 respectively). All samples collected after incubation with Apo A-I bound to HDL and 6/12 (50%) to CL. There were no differences in the cross-reactivity patterns between patients with SLE and APS. CONCLUSIONS: Patients with SLE and APS have antibodies directed against HDL and Apo A-I. A high percentage of these antibodies cross-react with CL, suggesting the presence of different groups of antibodies with different targets. The study of the interaction between the immune response and the lipoprotein components and the correct characterization of the reactivity patterns of autoantibodies may be of relevance in the study of atherosclerosis in patients with SLE and APS.

Adult↗

Slow desiccation leads to high-frequency shoot recovery from transformed somatic embryos of cotton (Gossypium hirsutum L. cv. Coker 310 FR).

In Agrobacterium-mediated genetic transformation of cotton (Gossypium hirsutum L. cv. Coker 310FR) the frequency at which somatic embryos were converted to plantlets was significantly improved by subjecting the embryos to slow physical desiccation. We used Agrobacterium strain GV3101 containing the binary vector pGSFR with the nos-nptII gene for in vitro selection and the 35S gus-int fragment as a reporter to optimize the transformation protocol. Although the concentration of kanamycin was reduced during embryogenesis and embryo maturation, even at the lower levels somatic embryos were predominantly abnormal, showing hypertrophy and reduced or fused cotyledons or poor radicle ends. A majority of these embryos (more than 75%) were beta-glucuronidase (GUS)-positive. Embryos with an abnormal appearance showed a very poor conversion to plantlets. However, these embryos, when subjected to slow physical desiccation followed by transfer to fresh medium, regenerated single or multiple shoots from the cotyledonary end. These shoots could be grafted on wild-type seedling stocks in vitro, which, following their transfer to soil, developed normally and set seeds. Regenerated plants tested positive for the transgene by Southern analysis. An overall scheme for the high-frequency production of cotton transgenics from both normal and abnormal appearing somatic embryos is presented.

Cells, Cultured↗

Studies of the decay B+/- -->D(CP)K+/-.

We report studies of the Cabibbo-suppressed decay B+/--->D(CP)K+/-, where D(CP) denotes CP eigenstates of the D0-D0; system. The analysis is based on a 29.1 fb(-1) sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e(+)e(-) storage ring. We measure ratios of branching fractions, relative to Cabibbo-favored B+/--->D(CP)pi(+/-), of B(B--->D1K-)/B(B--->D1pi(-))=0.125+/-0.036+/-0.010 and B(B--->D2K-)/B(B--->D2pi(-))=0.119+/-0.028+/-0.006; the index 1 (2) denotes the CP=+1 (-1) eigenstate. We also extract the partial rate asymmetries for B+/--->D(CP)K+/-, finding A(1)=0.29+/-0.26+/-0.05 and A(2)=-0.22+/-0.24+/-0.04.

Journal Article↗

Measurement of the electroweak penguin process B-->X(s)l+l-.

We report the first measurement of the branching fraction for the inclusive decay B-->X(s)l(+)l(-), where l is either an electron or a muon, and X(s) is a hadronic recoil system that contains an s quark. We analyzed a data sample of 65.4 x 10(6) B meson pairs collected with the Belle detector at the KEKB e(+)e(-) asymmetric-energy collider. We find B(B-->X(s)l(+)l(-))=[6.1 +/-1.4(stat) +1.4-1.1(syst)] x 10(-6) for dilepton masses greater than 0.2 GeV/c(2).

Journal Article↗

Sacrococcygeal pilonidal sinus: historical review, pathological insight and surgical options.

Sacrococcygeal pilonidal disease is a common and well recognized entity. For many years the cause of sacrococcygeal pilonidal sinus has been matter of debate. When the treatment is considered, there was a frequent lack of success of the surgical methods of excision regarding morbidity, healing, recurrence and cure. All these factors rendered the acquired thesis of pilonidal sinus disease to be more accepted. In dealing with the pathogenesis of pilonidal sinus disease, Karydakis attributed the hair insertion process to three main factors: the invader, i.e. the loose hair; the force, which causes the insertion; and the vulnerability of the skin to the insertion of hair at the depth of the natal cleft. The sinus is initiated from a small midline opening lined by stratified squamous epithelium. Additional sinuses are frequent and have lateral openings. Malignant transformation is rare but cases of squamous cell carcinoma and verrucous carcinoma have been reported. Pilonidal sinus disease consists in a symptoms complex with presentations ranging from asymptomatic pits to painful draining lesions that are predominantly located in the sacrococcygeal region. Asymptomatic pits do not require treatment. Options for treatment of acute abscess include aspiration, drainage without curettage, and drainage with curettage. The choice of a particular surgical approach depends on the surgeon's familiarity with the procedure and perceived result in terms of low recurrence of sinus and a quick healing of resulting cavity or surgical wound. Conservative nonoperative management, closed methods, laying of track, wide excision and open drainage, wide excision and primary closure, and limited excision are the methods currently used. From the profusion of studies, it is apparent that various methods are being tried and no one method is universally acceptable. Recurrence rates vary with the technique, operator and length of follow-up. Primary closure with a lateral approach appears to give the best results.

Drainage↗

The effect of cooling rate on the survival of cryopreserved bull, ram, and boar spermatozoa: a comparison of two controlled-rate cooling machines.

Spermatozoa from three species, bovine, ovine, and porcine, were frozen using standard techniques in two controlled-rate cooling machines, a commercial instrument and a custom-built device. Ice crystallisation was induced mechanically by touching the straws with a pre-cooled rod. The sperm samples were stored 24h, and then thawed rapidly and evaluated for motility, viability, and acrosomal integrity in the membrane-intact population. The custom-built controlled-rate cooling machine proved significantly better at all cooling rates for all species. This was particularly evident for the ram and the boar spermatozoa. In general, -30 or -50 degrees C/min were better than -1 degrees C/min, with a slight advantage being evident for -30 degrees C/min. However, this became very apparent for boar spermatozoa. It is clear that the higher cooling rates are necessary for successful freezing of spermatozoa from these species, and that careful control of the cooling rate is essential for maximal recovery of viable and functional cells. This is best achieved when the cooling profile is controlled from within a dummy sample.

Animals↗

Prediction of perinatal asphyxia with nucleated red blood cells in cord blood of newborns.

OBJECTIVE: To determine normal level of nucleated red blood cells (NRBC) per 100 white blood cells (WBC) in cord blood of term non-asphyxiated newborns and to investigate variations in NRBC counts in perinatal asphyxia. METHODS: A total of 75 cases were studied. Levels of NRBC per 100 WBC in umbilical venous blood were compared between 26 asphyxiated newborns (group I) and 49 non-asphyxiated newborns (group II). Correlation with neonatal outcome was also evaluated. RESULTS: The mean (+/-S.D.) NRBC per 100 WBC level in umbilical blood of newborns in group I was 16.5+/-6.4, range 3-25; whereas that in group II was 8.6+/-7.01, range 1-26. This difference was statistically significant (P<0.001). A statistically significant negative correlation existed between NRBC level and markers of acute intrapartum asphyxia, Apgar score and umbilical arterial pH (r=-0.50, P<0.001 and r=-0.48, P<0.001, respectively). Positive correlation was demonstrated with evidence of chronic antepartum asphyxia, presence of pregnancy induced hypertension and intrauterine growth restriction (r=2.66, P=0.02). A high NRBC count in umbilical blood correlated with poor early neonatal outcome. CONCLUSIONS: The level of NRBC per 100 WBC correlates both with acute as well as chronic antepartum asphyxia. Further, it can be used as a reliable index of early neonatal outcome.

Apgar Score↗

Trophoblast deportation and the maternal inflammatory response in pre-eclampsia.

We have proposed that the maternal syndrome of pre-eclampsia is caused by a systemic inflammatory response involving both leucocytes and endothelium. This inflammatory response is present also in normal pregnancy, but in a milder form. The inflammatory stimulus is most likely to come from the placenta. Syncytiotrophoblast apoptotic debris, which is shed into the maternal circulation in normal pregnancy and in increased amounts in pre-eclampsia, may be the stimulus for this response. It may also contribute to the suppression of Th1 responses seen in pregnancy.

Endothelium, Vascular↗

Win-win opportunities and environmental regulation: testing of porter hypothesis for Indian manufacturing industries.

This paper studies the effect of environmental regulation on the productive efficiency of water polluting industries in India. The panel data of 92 firms belonging to sugar industry of India during the period 1996-99 are used to test the Porter hypothesis of having win-win opportunities for the firms subjected to the regulation. The main empirical result is that the technical efficiency of firms increases with the degree of compliance of firms to the environmental regulation and the water conservation efforts there by supporting the Porter hypothesis.

Conservation of Natural Resources↗

Immunization of crossbred cattle (Bos indicus x Bos taurus) with fractionated midgut antigens against Hyalomma anatolicum anatolicum.

Crossbred calves (Bos indicus x Bos taurus) were immunized with a fractionated midgut supernate antigen (GS-F Ag from Hyalomma anatolicum anatolicum). The first inoculation on day 0 was given intramuscularly after emulsification with Freund's complete adjuvant; the second was given subcutaneously on day 14 in incomplete Freund's adjuvant; and the third on day 35 was given subcutaneously without adjuvant. Each injection comprised 1 mg of antigen protein. Ten days after the last inoculation, the immunized calves were challenged simultaneously with 1000 larvae and 20 pairs (20 males and 20 females) of adult H. a. anatolicum on one ear and a similar number of Hyalomma dromedarii ticks on the other ear. There was a significant decrease in the percentage larval engorgement and larval rejection of up to 34% on the immunized calves. A significant increase in the engorgement and preoviposition periods and a significant decrease in the engorged weight, egg mass weight and reproductive index were observed for adult female ticks when fed on the immunized calves. The GS-F Ag also induced a considerable degree of cross-protection in calves against H. dromedarii larval ticks.

Animals↗

In vitro effects of acellular milk on the bactericidal components of caprine polymorphonuclear neutrophils.

The effects of acellular milk on the activity of the microbicidal cationic enzymes of the polymorphonuclear cells of goats were studied in an attempt to explain the phenomenon by which PMN functions fail in mastitis. Assays were undertaken on the myeloperoxidase, lysozyme and elastase activities in a polymorphonuclear cell (PMN) lysate, both in the presence and absence of acellular milk from homologous species. There was a significant decrease (p < 0.05) in the activity of lysozyme, myeloperoxidase and elastase in the presence of acellular milk. Superoxide and H2O2 production following activation of caprine PMNs by lipopolysaccharide (LPS) was significantly reduced (p < 0.05) in the presence of acellular milk. Thus, the microbicidal function of PMNs is significantly impaired in the presence of acellular milk and this may contribute to the development of mastitis in dairy animals.

Animals↗

Effect of allogeneic stem cell transplantation on bone marrow angiogenesis in chronic myelogenous leukemia.

Increased bone marrow angiogenesis is a poor prognostic marker in patients with chronic myelogenous leukemia (CML). Allogeneic stem cell transplantation (ASCT) can be curative for patients with CML. Studies in myeloma have shown persistent increased bone marrow microvessel density (MVD) after autologous transplantation. It is not clear if abnormal bone marrow angiogenesis persists following a curative intervention like allogeneic transplantation. We evaluated MVD from bone marrow samples obtained just prior to and at 3-5 months after ASCT in 24 patients with CML. The median MVD pre-transplant was 14 (4-37), with 11 patients having high-grade angiogenesis and 13 having low grade. The median post transplant MVD was 20 (range 5-36), with 12 patients having high-grade angiogenesis and 12 low grade. The median time between biopsies was 4 months (range 1-6 months). The microvessels in the post transplant bone marrow appeared morphologically different with striking dilatation and sinusoidal appearance compared to the pre-transplant marrow. However, there was no significant change in MVD following transplant (P=0.8, paired t-test). Abnormal bone marrow angiogenesis appears to persist in the bone marrow following ASCT for CML, at least in the short term.

Adult↗

Distinct promoter regions regulate spatial and temporal expression of the Drosophila caspase dronc.

DRONC is an apical Drosophila caspase essential for programmed cell death during fly development. During metamorphosis, dronc gene expression is regulated by the steroid hormone ecdysone, which also regulates the levels of a number of other critical cell death proteins. As DRONC protein levels are important in determining caspase activation and initiation of cell death, we have analyzed the regulation of the dronc promoter using transgenic flies expressing a LacZ reporter gene under the control of the dronc promoter. Our results indicate that dronc expression is highly dynamic during Drosophila development, and is controlled both spatially and temporally. We demonstrate that while a 2.3 kb dronc promoter region contains most of the information required for correct gene expression, a 1.1 kb promoter region is expressed in some tissues and not others. We further demonstrate that during larval-pupal metamorphosis, two ecdysone-induced transcription factors, Broad-Complex and E93, are required for correct dronc expression. Our data suggest that the dronc promoter is regulated in a highly complex manner, and provides an ideal system to explore the temporal and spatial regulation of gene expression driven by nuclear hormone receptors.

Animals↗