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Biomedical subjects

P K Bhatnagar

Publications and source records attributed to P K Bhatnagar.

At least 37 records · Page 2Linked to original sources
PubMed1996

The impact of thrombolytic therapy on arterial and graft occlusions: a critical analysis.

BACKGROUND: The indications for intraarterial thrombolytic therapy of lower extremity native arterial and synthetic graft occlusions prior to vascular reconstructions requires further refinement before firm conclusions can be made. STUDY DESIGN: A retrospective review of 55 patients undergoing 81 lytic treatments with high dose urokinase from February 1989 to February 1993 was performed. The cases were divided into three groups: Group I: successful thrombolysis with residual defects followed by surgical reconstruction or percutaneous transluminal angioplasty (PTA); Group II: successful thrombolysis alone; and Group III: failure of thrombolysis requiring reconstruction or leading to amputation. No effort was made to analyze the particular type of reconstruction. Follow-up ranged from 1 to 1627 days (4 years and 5 1/2 months). RESULTS: One, two, and three year patency rates were 47%, 24%, and 8% for Group I; 57%, 46%, and 46% for Group II; and 24%, 10%, and 10% for Group III respectively. The one, two and three year limb salvage rates were 92%, 76%, and 76% for Group I; 82%, 82%, and 82% for Group II; and 48%, 37%, and 37% for Group III respectively. Forty-one complications occurred in 35 of the 81 (43%) lytic treatments. CONCLUSIONS: Intraarterial thrombolytic therapy can be regarded as a possible consideration in the initial management of acute lower extremity arterial and synthetic graft occlusions especially in patients with multiple prior vascular reconstructions. Unsuccessful thrombolysis results in a poor outcome despite surgical reconstruction in the majority of cases.

Aged↗
PubMed1995

Relationship of runoff vessels to results following thrombolysis and revascularization for synthetic graft occlusions.

The objective of this study was to evaluate the relation between runoff vessels and the prognosis in patients who have had an occlusion of a previously placed peripheral arterial bypass graft. Over a 4-year period 77 occluded synthetic grafts were treated with urokinase and reconstruction after angiographic study. Follow-up ranged from 1 to 1627 days. The cases were divided into three groups according to the number of patent tibial vessels. Group I consisted of patients who had no vessel runoff. Group II consisted of patients who had single vessel runoff. Group III consisted of patients who had two or three runoff vessels. In Group I, the 1, 2, and 3-year patency rates were 35.8%, 8.9%, and 8.9%; and the limb salvage rates were 50.2%, 40.2%, and 40.2% for 1, 2, and 3 years, respectively. The Group II patency rates were 31.2%, 26.0%, and 13.0% and the limb salvage rates were 72.3%, 62.9%, and 62.9%. The Group III patency rates were 50.0%, 26.1%, and 20.9%; and the limb salvage rates were 93.1%, 79.1%, and 79.1%. There is no statistically significant difference in patency rates among any of the groups. The limb salvage rate was significantly increased in Group III, compared to I (P < 0.01) and Group II (P < 0.05), and in Group II, compared to Group I (P < 0.05). These results indicate that the higher rate of limb salvage in this study statistically correlated with the number of runoff vessels.

Adult↗
PubMed1994

Evaluation of multiple vascular reconstructive procedures with synthetic graft occlusions.

The objective of this study was to evaluate the efficiency of multiple vascular reconstructive procedures in the presence of an occluded synthetic graft. Over a four year period seventy-seven occluded synthetic grafts were treated with urokinase and reconstruction. Follow-up ranged from 1 to 1627 days (4 years, 5 1/2 months). Kaplan-Meier and generalized Wilcoxon test were used to determine patency and limb salvage rates. The cases were divided into three groups according to the number of previous reconstructive events. Group I consisted of patients that had undergone one previous vascular reconstructive procedure. Group II consisted of patients that had undergone two previous vascular reconstructive procedures. Group III consisted of patients who had undergone three or more previous reconstructive procedures. In Group I, the one, two, and three year patency rates were 48.6%, 34.7%, and 26.0% and the limb salvage rates were 76.2%, 67.9%, and 67.9% for one, two, and three years respectively. The Group II patency rates were 41.9%, 24.4%, and 16.3% and the limb salvage rates were 73.7%, 66.3%, and 66.3%. The Group III patency rates were 31.8%, 5.5%, and 5.5% and the limb salvage rates were 76.6%, 54.8%, and 54.8%. The patency rate was significantly reduced when Group III was compared to Group I (p < 0.01). There was no statistically significant difference in limb salvage rates between any of the groups. These results indicate that the number of secondary vascular reconstructive procedures combined with thrombolysis had no correlation with the prognosis of limb salvage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

In vivo modulation of hematopoiesis by a novel hematoregulatory peptide.

The hematoregulatory peptide dimer, HP5B, enhances myelopoiesis by stimulating stromal cell cytokine production. However, the disulfide bridge of this peptide is susceptible to reduction, leading to the formation of monomeric pentapeptide, HP5, a direct-acting inhibitor of myelopoiesis. We have replaced the disulfide (S-S) bond of HP5B dimer with an isosteric ethylene (CH2-CH2) group, creating a new, nonreducible, metabolically more stable peptide (SK&F 107647). This novel peptide was tested in vitro and in vivo for hematopoietic effects. In vitro, SK&F 107647 has no direct colony-stimulating activity (CSA). Stimulation of murine stromal cells with SK&F 107647 results in production and release of CSA at concentrations as low as 0.01 ng/mL, at least 10-fold lower than observed with HP5B dimer. Injection of SK&F 107647 in normal mice results in a two- to six-fold increase in serum CSA, which becomes maximal at 6 hours postinjection. Administration of peptide daily over 4 days (q.d. x 4) by both parenteral and oral routes results in significant increases in absolute numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, as well as stimulating their cell cycle rates. A doubling in day 8 CFU-S was also observed in SK&F 107647-treated mice. Continuous subcutaneous (s.c.) infusion of SK&F 107647 in femorally cannulated rats demonstrated modest but significant elevation of peripheral blood neutrophil and monocyte counts within 7 days. SK&F 107647 represents a novel synthetic hematoregulatory peptide that shares biological and/or modulatory activities with natural hematopoietic cytokines.

Administration, Oral↗
PubMed1993

Serological findings in patients with allergic bronchopulmonary aspergillosis during remission.

The concentrations of total IgG, complement C3 and circulating immune complexes (CIC) were studied in 15 patients with allergic bronchopulmonary aspergillosis (ABPA) during remission and compared with those of 10 matched controls. The concentrations of complement and circulating immune complexes were similar to those of the controls but 33% of patients with ABPA in remission still had circulating immune complexes, mainly of IgG. Even so, the concentrations of IgG were significantly higher in patients during remission compared to controls but were lower than those observed during the acute stage of ABPA.

Acute Disease↗
PubMed1991

Expression of human preproendothelin-1 cDNA in COS cells results in the production of mature vasoactive endothelin-1.

Transient transfection of simian kidney (COS) cells with a recombinant plasmid encoding human preproendothelin-1 resulted in the production of biologically active endothelin-1. Conditioned medium from human preproendothelin-1 transfected cells demonstrated a significant increase in immunoreactive endothelin and big endothelin which co-eluted, when analyzed by reverse phase HPLC, with synthetic endothelin-1 and big endothelin-1, respectively. In addition, biological activity was confirmed by both inhibition of [125I]endothelin-1 binding to rat cerebellar and renal medullary membrane endothelin receptors and in vitro vasoconstriction of rabbit aorta. This is the first demonstration that human preproendothelin-1 is capable of being processed to a vasoactive form in a heterologous system and suggests that human preproendothelin-1 transfected COS cells may provide a useful model system for the study of endothelin biosynthesis.

Animals↗
PubMed1987

Investigation of synthetic Escherichia coli heat-stable enterotoxin as an immunogen for swine and cattle.

In its native form Escherichia coli heat-stable enterotoxin (STa) is nonantigenic; however, neutralizing antibodies are elicited in animals vaccinated with toxin-carrier conjugates. To study the immunogenicity of STa, peptides STa1-18 and STa5-18 were synthesized, characterized, and conjugated to carrier proteins. Pregnant gilts and heifers were hyperimmunized with the respective conjugates. Following parturition neonates were challenged with virulent E. coli (K99+ STa+). Peptides coupled to ovalbumin and emulsified with Freund adjuvant elicited antibodies that neutralized toxin-induced fluid accumulation in suckling mice. Peptides coupled to particulate carriers, with or without muramyl dipeptide adjuvant, failed to induce a measurable response. Peak antibody levels in sera were observed following three doses of conjugate and persisted for several weeks. The serological response in cattle was superior to that observed in swine; however, antibody levels in porcine colostrum were higher than those observed in cattle. Clinical observations of neonates from vaccinated dams indicated that passively obtained antibody provided partial protection from disease, but not as complete as that demonstrable with whole cell bacterins that induce antibody to pili. However, the data suggest the potential for utility of synthetically prepared antigens.

Animals↗
PubMed1986

Synthesis and antigenic activity of E. coli ST and its analogues.

Several enterotoxigenic E. coli (ETEC) are common causes of diarrhea in man and animals. These strains of E. coli produce two types of enterotoxins: heat-stable (ST) and heat-labile (LT). These toxins are peptides of molecular weight 2000 and 90,000 daltons, respectively. It is proposed that the synthetic analogues of these toxins could be effectively used as the vaccines against enterotoxigenic activity of E. coli. In this paper we report the isolation and chemical characterization of a heat-stable toxin STa. We also report the synthesis of this toxin and its analogues and their biochemical and immunological characterization.

Amino Acid Sequence↗
PubMed1986

Strategies for peptide synthesis.

The peptide chemists are facing formidable challenges borne by a continually increasing interest in the pharmaceutical uses of peptides. The successful realization of such challenges depends upon the development of technologies which allow multistage synthesis, purification, and characterization of complicated biologically active peptides. A number of peptide synthesis methods have evolved over the years. These methods can be categorized as chemical synthesis, enzymatic synthesis, biological synthesis and semisynthesis. In this overview the author briefly describes the current state-of-the-art, with major stress on the chemical synthesis of peptides.

Antigens↗
PubMed1983

Appraisal and prospects of a dimeric synthetic peptide coupled with tetanus toxoid for a bifunctional vaccine against hepatitis B virus infection.

Recovery from a hepatitis B virus (HBV) infection or vaccination with hepatitis B surface antigen (HBsAg) leads to a physiologic immune response specific for the alpha determinant, common to all subtypes of HBsAg. In contrast, an absence of immune response to the alpha determinant is characteristic of persistent HBV infection as well as of the nonresponders to vaccination. Therefore, our goal is to characterize the alpha determinant for synthesis of a bifunctional vaccine which may be useful for active immunization as well as for the safe termination of immune tolerance to HBsAg in carriers. Because the immunochemical activity of the alpha determinant of HBsAg is dependent upon cysteine and lysine residues that are localized in the hydrophilic stretch between amino acid sequence 121-160, we synthesized the following peptide analogues of HBsAg (HBsPA): 122-137, 128-134, 139-147, 139-158, 140-158, 145-158 and 150-158. Serologic inhibition of human antibodies against the alpha determinant indicated the antigenicity of the HBsPAs containing the Cys-Thr-Lys-Pro-Thr-Asp-Gly-Asn-Cys sequence. After coupling with keyhole limpet hemocyanin (KLH), carrier-peptide conjugates induced in rabbits anti-HBs which was neutralized equally by eight different serotypes of HBsAg. Therefore, HBsPA/139-147 represents an essential part of the alpha determinant. By substituting alpha-aminobutyric acid (Aba) for Cys at residue 147 a homogeneous dimeric form of this nonapeptide was prepared. After coupling with purified tetanus toxoid or KLH as a carrier by means of carbodiimide, the product induced sustained high level anti-HBs/alpha response in carrier-primed rabbits. Experiments in chimpanzees should validate our concept of a bifunctional synthetic vaccine against HBV infection.

Animals↗
PubMed1983

Liquid-chromatographic determination of tobramycin in serum with spectrophotometric detection.

We describe a simple, precise, accurate, and specific liquid-chromatographic procedure for determination of tobramycin in 50 microL of serum. Tobramycin and the internal standard (sisomicin) are quantitatively converted into their trinitrophenyl derivatives by reaction with a water-soluble derivatizing agent (2,4,6-trinitrobenzenesulfonic acid) at 70 degrees C for 30 min. The derivatives are extracted from the crude reaction mixture by using a reversed-phase Bond-Elut C18 column, and separated on a reversed-phase octyl column with a mobile phase consisting of an acetonitrile/phosphate buffer (70/30 by vol) at a flow rate of 3.0 mL/min. The eluted compounds are detected at 340 nm, and quantified from their peak areas. Chromatography is complete in less than 4.5 min at the optimum column temperature of 50 degrees C. The lower limit of detection for tobramycin is less than 0.2 mg/L. Analytical recoveries for tobramycin varied from 94 to 99%, linearity extended to 25 mg/L, and day-to-day precision (CV) was between 4.6 and 5.1%. Numerous drugs and antibiotics tested do not interfere. Results correlate well (r greater than 0.95) with those by radioimmunoassay and EMIT.

Anti-Bacterial Agents↗
PubMed1982

Immune response to synthetic peptide analogues of hepatitis B surface antigen specific for the a determinant.

Recovery from a natural infection with hepatitis B virus or vaccination with purified envelope protein leads to production of antibodies against the hepatitis B surface antigen (HBsAg). Such physiologic response in man is generally directed against the a determinant of HBsAg common to all serotypes of the virus. To define the immunochemical specificity of this determinant, the secondary structure of HBsAg was derived from its sequence of 226 amino acids. Hydrophilic stretches expected to contain the antigenic determinants were located between residues 32 and 76 and between residues 110 and 156. Loss of the antigenic activity after chemical modification of lysine residues of HBsAg indicated their critical importance in antigenicity. Because all lysines are located between residues 121 and 160, we selected this region for localization of HbsAg determinants. Solid-phase synthesis was used to prepare seven peptide analogues of HBsAg (PsAs): 122-137, 128-134, 139-147, 139-158, 140-158, 145-158, and 150-158. For experimental immunization of rabbits the synthetic peptides were coupled to keyhole limpet hemocyanin. We studied the antigenicity of each peptide analogue by serologic neutralization of human antibodies specific for the a determinant of HBsAg. Analogues 139-147, 139-158, and 140-158 showed antigenicity as well as function of anti-HBsAg. The rabbit antibodies were inhibited with each of the three peptide analogues and all serotypes of natural HbSag, having only the a determinant in common. These results indicate that the nonapeptide sequence 139-147 represents the total or an essential part of the a determinant of HBsAg.

Amino Acid Sequence↗
PubMed1981

Interactions between polymerized human albumin, hepatitis B surface antigen, and complement: I. Binding of polyalbumin to Clq.

There is considerable evidence that substances other than immunoglobulins can bind human Clq. Utilizing purified human Clq immobilized on polystyrene beads, we have demonstrated that polymerized human albumin (PHALB-125I) binds to human Clq in a direct binding assay. This interaction required a high degree of albumin polymerization as the percentage of binding was proportional to the polymer size and monomeric albumin was unreactive. Binding was species specific in the human Clq bound only human, and not xenogeneic, polyalbumins. Similarly, polymers of various other human plasma proteins were unreactive. To demonstrate that this interaction was not unique to immobilized Clq, soluble Clq was shown to inhibit PHALB-125I binding to solid phase Clq. Because aggregated IgG, poly(I):poly(C), dextran sulfate, polyglutamic acid, and polylysine have been previously shown to bind Clq, we used them in further blocking experiments and found them also to inhibit the interaction between Clq and PHALB. Anti-human Clq and, to a lesser extent, anti-PHALB antibodies inhibited the interaction. The Clq-PHALB binding was pH, ionic strength, and temperature dependent. In addition, human Clq was not observed to bind hepatitis B surface antigen (HBsAg) directly; however, in the presence of sufficiently polymerized human albumin a Clq-PHALB-HBsAg complex was formed. These interactions may be implicated in hepatocyte-HBsAg receptor function as well as in the host defense mechanisms involved in hepatitis B virus infection.

Animals↗