Application of commercial glasses for high dose measurement using the thermoluminescent technique.

Commercial glasses under this study showed linear thermoluminescence (TL) response in gamma dose range 100 Gy to 10 kGy, glow peaks between 175 and 200 degrees C, fading under dark and room light 2.86-7.36% and 10.42-20.82%, respectively, in 24h and 34.86-70.80% under sunlight in 5h after exposure. The TL glass dosimetric results have been found to be reproducible within +/- 6.0%. Glasses have been observed as thermally unstable and its TL sensitivity reduces after annealing. The TL response of the glasses has been found to reduce by 7.40-51.49% after first annealing of the samples at 400 degrees C for 15 min. The trace element study suggests that presence of impurities has no role in TL sensitivity of glasses rather imperfections and dislocations in the lattice are the major contributor in the formation of TL centers. Commercial glasses can serve as good TL material for gamma irradiator and gamma chamber dosimetry. The various radiation parameters for glass TL dosimetry have been studied in detail and presented.

Accidental gamma dose measurement using commercial glasses.

Commercial glasses have been investigated for their application in accidental gamma dose measurement using Thermoluminescent (TL) techniques. Some of the glasses have been found to be sensitive enough that they can be used as TL dating material in radiological accident situation for gamma dosimetry with lower detection limit 1 Gy (the dose significant for the onset of deterministic biological effects). The glasses behave linearly in the dose range 1-25 Gy with measurement uncertainty +/- 10%. The errors in accidental dose measurements using TL technique are estimated to be within +/- 25%. These glasses have shown TL fading in the range of 10-20% in 24 h after irradiation under room conditions; thereafter the fading becomes slower and reaches upto 50% in 15 d. TL fading of gamma-irradiated glasses follows exponential decay pattern, therefore dosimetry even after years is possible. These types of glasses can also be used as lethal dose indicator (3-4 Gy) using TL techniques, which can give valuable inputs to the medical professional for better management of radiation victims. The glasses are easy to use and do not require lengthy sample preparation before reading as in case of other building materials. TL measurement on glasses may give immediate estimation of the doses, which can help in medical triage of the radiation-exposed public.

Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.

Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis.

Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor models.

Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.

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.

Structure-activity relationships of novel hematoregulatory peptides.

Hematopoiesis is a lifelong cell renewal process regulated by a family of lineage specific hematopoietic growth factors. Several hematopoietic growth factors such as G-CSF, GM-CSF, and M-CSF have been clinically evaluated for enhancement of host defense in normal and immunocompromised patients and for the treatment of infectious diseases. This paper reports the structure-activity relationships of low molecular weight hematoregulatory peptides based on a nonapeptide (1, SK&F 107647). Like the macromolecular growth factors, these peptides modulate host defense. A molecular target for this class of compounds has not yet been identified. However, the structure-activity relationships established by this study implicate a very specific molecular recognition event that is pivotal for the biological activities of 1 and its analogues.

T cell subsets in acute rheumatic fever, rheumatic heart disease and acute glomerulonephritis cases.

T cell subsets were studied in 45 patients, 15 each of acute rheumatic fever, rheumatic heart diseases, and acute glomerulonephritis and compared with 10 normal control in the same age group. A significant depression in the OKT1 and OKT4 +ve cells and insignificant increase in the OKT8 +ve cells was noted in all these groups of cases.

The application of an improved solid phase synthetic technique to the delineation of an antigenic site of apolipoprotein A-II.

Previous studies have shown that the antigenic sites of human plasma high-density apolipoprotein A-II (apoA-II) are separate from their lipid-binding determinants in human high density lipoproteins (HDL). A specific radioimmunoassay has shown that three distinct antigenic sites are located in residues 4-23, 31-46, and 56-77; these studies suggested that an antigenic site might be restricted to residues 60-77 in the 56-77 fragment. To further delineate this site, we have developed a solid phase radioimmunoassay technique using an improved solid support on which selected sequences of peptides were synthesized, deprotected with HF, and the resulting peptidyl-resins tested for their capability of binding purified 125I-anti-apoA-II antibodies. Amino acid analyses and solid phase sequence analyses were performed to verify the sequence of the synthetic peptide on the solid support. Using this technique, 125I-anti-apoA-II antibodies had achieved 50% of maximal binding when residues 61-77 were attached to the solid support. The maximal binding was achieved by the addition of one more residue, Leu60, thus confirming our suggestion that a major antigenic site is located in residues 60-77. The binding to the peptidyl-resin was inhibited by a synthetic fragment corresponding to residues 60-77 indicating that the antibodies were specifically bound to the resin.

CGRP stimulates the adhesion of leukocytes to vascular endothelial cells.

Calcitonin gene-related peptide (CGRP) stimulates the adhesiveness of human umbilical vein endothelial cells for U937 cells and human neutrophils in a dose- and time-dependent manner. The onset of CGRP-induced adhesives of HUVEC was rapid (30 min), independent of protein synthesis, and lasted over 24 h in the continuous presence of the peptide. The stimulatory effect of CGRP was completely blocked by the CGRP antagonist, CGRP(8-37). The present study provides evidence in support of the potential role of sensory nerve-derived neuropeptides in the modulation of leukocyte adhesion to vascular endothelial cells.

Thrombolysis theraphy in patients with femoropopliteal synthetic graft occulsions.

BACKGROUND: The aim of this study was to evaluate the efficiency of thrombolysis in the presence of an occluded femoropopliteal synthetic graft. PATIENTS AND METHODS: Over a 3-year period, 46 occluded femoropopliteral grafts were treated with urokinase and reconstruction. The cases were divided into three groups: group 1 (n=25), complete thrombolysis followed by reconstruction or angioplasty or both; group 2 (n=5), complete thrombolysis alone; and group 3 (n=16), failure of thrombolysis requiring reconstruction or leading to amputation. Patients were completely observed after treatment for more than 1 year. RESULTS: There are no fatal complications among patients with thrombolytic therapy. In group 1, the 3-year patency rates were 12% and the 3-year limb salvage rates were 77%. In group 2, the 3-year patency rates and the limb salvage rates were 20% and 80%, respectively. The group 3 patency rates and the limb salvage were 8% and 40%, respectively. The best results were achieved in patients who had thrombolysis followed by reconstruction (group 1) and in those who had thrombolysis alone (group 2). limb salvage was poor in patients with failure of lytic therapy regardless of the reconstruction (P<0.01). CONCLUSION: The use of intra-arterial urokinase followed by secondary vascular reconstructive procedures was studied. The patient with synthetic graft occlusion still has a reasonably favorable prognosis for long-term limb salvage when thrombolysis is successful.

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.

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.

Effect of amphotericin B lipid formulation on immune response in aspergillosis.

The immune response against Aspergillus fumigatus has been studied during infection and therapy in order to understand the mechanism of pathogenesis and the effect of treatment with amphotericin B. With this in view an animal model of aspergillosis was developed in Balb/c mice by intravenous injection of an optimized dose of 3. 6x10(6) A. fumigatus spores. Infection due to Aspergillus was well established by histopathological examination and fungal load in the animal. Lesions and eosinophil infiltration was observed in the infected tissues which indicated the involvement of a Type I hypersensitivity response. Evaluation of serological parameters indicated high levels of interleukin-4 (IL-4) and A. fumigatus specific IgG antibodies. The reduction in fungal load and modulation of immune response in the infected mice was studied following treatment with amphotericin B/cholesterol hemisuccinate vesicles (ABCV). The results clearly indicated significant reduction in the fungal load, disappearance of eosinophils and lesions with the appearance of macrophages and neutrophils in the infected lung tissue, a decrease in IL-4 (fourfold) and a concomitant increase of interferon-gamma (IFN-gamma; twofold) with an improvement in general condition of mice. In the non-treated mice, the rise of IL-4 level indicated the association of T(H)2 cell response with susceptibility to infection while the increase of IFN-gamma in the treated group suggested that T(H)1 cell response may be involved in resistance to Aspergillus infection.

Liquid chromatographic determination of gentamicin in serum with spectrophotometric detection.

A simple, accurate, and specific liquid chromatographic procedure is described for the determination of gentamicin in 50 muL of serum. Gentamicin and sisomicin (IS) were converted into their trinitrophenyl derivatives by reaction with a water soluble derivatizing agent at 70 degrees C for 30 minutes. The derivatives were extracted from the crude mixture with chloroform, which was separated, evaporated, and the residue reconstituted in acetonitrile. Gentamicin was separated into three major isomers (C1, C2, and C1a) on a reversed-phase octyl column by eluting with a mobile phase. The eluted compounds were detected at 340 nm and quantified from their peak heights or peak areas. Chromatography was complete in less than 11.0 minutes. The lower limit of detection for gentamicin was less than 0.5 mg/L, analytical recoveries varied from 96.6% to 99.3%, linearity extended to 15.0 mg/L, and day-to-day precision was between 2.2% to 2.9%.

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.

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)

Thrombolysis of peripheral graft occlusion in patients with hypertension.

The objective of this study was to evaluate the effect of hypertension on the use of thrombolytic therapy in patients with occluded synthetic peripheral bypass grafts. Thrombolysis with urokinase was performed in 44 cases of occluded lower extremity bypass grafts. The cases were divided into two groups: Group I consisted of patients currently being treated for hypertension. Group II consisted of patients without a history of hypertension. A comparison of pre- or intra-lytic data revealed that there was no significant difference in each group. Complications occurred in 15 (32.6%) out of 46 cases. There was no significant increase in complication when the risk factors were compared. In Group I, the one, two, and three year patency rates were 42.7%, 23.0%, and 7.7% and the limb salvage rates were 93.3%, 73.9%, and 73.9% for one, two, and three years respectively. The Group II patency rates were 70.6%, 41.6%, and 41.6% and the limb salvage rates were 94.1%, 86.9%, and 86.9%. The patency rate was significantly reduced when Group I was compared to Group II (p < 0.05). There was no statistically significant difference in limb salvage rates between Groups I and II. In conclusion, hypertension is one of the important risk factors that reduce the patency rate after thrombolytic therapy in patients with peripheral arterial bypass graft.

Gamma-irradiated onions as a biological indicator of radiation dose.

Post-irradiation identification and dose estimation are required to assess the radiation-induced effects on living things in any nuclear emergency. In this study, radiation-induced morphological/cytological changes i.e., number of root formation and its length, shooting length, reduction in mitotic index, micronuclei formation and chromosomal aberrations in the root tip cells of gamma-irradiated onions at lower doses (50-2000 cGy) are reported. The capabilities of this biological species to store the radiation-induced information are also studied.

STUDY OF LOW BIRTH WEIGHT NEONATES.

Low birth weight neonates with 2000g or less birth weight constitute about 10% of live births with perinatal mortality as high as 32.4%. Perinatal morbidity is 19.3% with asphyxia neonatorum and neonatal jaundice heading the list. Epidemiological maternal factors include extremes of age and parity, lack of antenatal care, low socioeconomic status, illiteracy and underweight short women. Etiologic factors are obstetric complications, hypertensive disorders, systemic diseases or idiopathic. The scope of preventive measures include improvement of economic status and education about health and safe pregnancy. Proper antenatal care for early detection of high risk cases, adequate and timely management of complications and adequate facilities for neonatal care can reduce the perinatal morbidity and mortality.

Detection of DNA Sequence with Enhanced Sensitivity and Higher FRET Efficiency Using a Light-Emitting Polymer, Peptide Nucleic Acid Probe and Anionic Surfactant System.

An improved strategy has been developed for detection of DNA sequence by using water-soluble cationic conjugated polymer (PFP)/single-strand (ss) DNA and peptide nucleic acid labeled with fluorescent dye (PNAC*), where an anionic surfactant (sodium dodecyl sulphate, SDS) system has been used to improve the sensitivity of the sensor. The method of detection is simple to use, fast and cost-effective. This method uses the phenomenon of Forester Resonance Energy Transfer (FRET). The detection sensitivity of the biosensor has been improved by about ten times by using the anionic surfactant. It is observed that the effect of surfactant is to increase the photoluminescence (PL) intensity of the PNAC* when the sequence of the DNA is complementary (to that of PNA probe). On the other hand when the two sequences are non-complementary, the PL intensity of the PNAC* is further reduced as compared to the case when surfactant was absent.