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Biomedical subjects

P Ross

Publications and source records attributed to P Ross.

At least 91 records · Page 5Linked to original sources
PubMed1990

Intermittent cyclical etidronate treatment of postmenopausal osteoporosis.

BACKGROUND: To determine the effects of etidronate (a bisphosphonate that inhibits osteoclast-mediated bone resorption) in the treatment of postmenopausal osteoporosis, we conducted a prospective, two-year, double-blind, placebo-controlled, multicenter study in 429 women who had one to four vertebral compression fractures plus radiographic evidence of osteopenia. METHODS: The patients were randomly assigned to treatment with phosphate (1.0 g) or placebo twice daily on days 1 through 3, etidronate (400 mg) or placebo daily on days 4 through 17, and supplemental calcium (500 mg) daily on days 18 through 91 (group 1, placebo and placebo; group 2, phosphate and placebo; group 3, placebo and etidronate; and group 4, phosphate and etidronate). The treatment cycles were repeated eight times. The bone density of the spine was measured by dual-photon absorptiometry, and the rates of new vertebral fractures were determined from sequential radiographs. RESULTS: After two years, the patients receiving etidronate (groups 3 and 4) had significant increases in their mean (+/- SE) spinal bone density (4.2 +/- 0.8 percent and 5.2 +/- 0.7 percent, respectively; P less than 0.017). The rate of new vertebral fractures was reduced by half in the etidronate-treated patients (groups 3 and 4 combined) as compared with the patients who did not receive etidronate (groups 1 and 2 combined) (29.5 vs. 62.9 fractures per 1000 patient-years; P = 0.043); the effect of treatment was most striking in the subgroup of patients with the lowest spinal bone mineral density at base line, in whom fracture rates were reduced by two thirds (42.3 vs. 132.7 fractures per 1000 patient-years; P = 0.004). The addition of phosphate provided no apparent benefit. There were no significant adverse effects of treatment. CONCLUSIONS: Intermittent cyclical therapy with etidronate for two years significantly increases spinal bone mass and reduces the incidence of new vertebral fractures in women with postmenopausal osteoporosis.

Aged↗
PubMed1990

Protein synthesis and secretion in the human epididymis and immunoreactivity with sperm antibodies.

The synthesis and secretion of proteins in the different regions of the human epididymis were studied in vitro. Epididymal tissues obtained from patients undergoing castration for prostatic carcinoma or from cadavers were incubated in the presence of [35S]methionine, and the resulting radiolabeled proteins were analysed on SDS-PAGE. The corpus region was found to be the most active segment in total protein synthesis. Significant qualitative and quantitative changes were observed in the pattern of proteins secreted from the different epididymal regions. To establish those epididymal proteins that interact with maturing sperm, the secreted products were immunoreacted with antibodies raised against a Triton X-100 extract of ejaculated human sperm heads. The antibodies react mainly with the head region of ejaculated spermatozoa as judged by indirect immunofluorescence. Protein A-gold labeling of freeze-fracture images showed gold particle distribution on the sperm plasma membrane. Western blot analysis of the secreted proteins revealed four bands (66, 37, 32, and 29 kDa) in the proximal regions and six additional bands (80, 76, 48, 27, 22, and 17 kDa) in the distal part of the epididymis. Immunoprecipitation of the secreted proteins with these antibodies revealed six radioactive bands of 170, 80, 76, 60, 48, and 37 kDa, which indicates that certain proteins of epididymal origin bind to the sperm plasma membrane.

Adult↗
PubMed1990

Aging bone loss from the femur, spine, radius, and total skeleton.

In order to establish a comprehensive model for involutional bone loss, the following measurements were made of healthy white women: total body calcium by neutron activation analysis, bone density of the distal radius by single-photon absorptiometry, and dual-photon absorptiometry of the lumbar spine and femur (neck, Ward's triangle, and intertrochanteric areas). Longitudinal measurements were made for each of these skeletal sites except the femur. Evidence for a curvilinear component to the pattern of bone loss with aging was found for total body calcium and bone density of the radius, but not for the other measurements on analysis of cross-sectional data. Longitudinal studies confirmed that substantial bone loss begins only after menopause for the radius, whereas there is substantial premenopausal loss of bone from the lumbar spine. Prevention of vertebral osteoporosis requires maximizing bone mass before menopause. If longitudinal data confirm the model of linear rates of bone loss for the femur, there will be important implications for prevention of hip fractures.

Adult↗
PubMed1990

Cloning and characterization of the thymidylate synthase gene from Lactococcus lactis subsp. lactis.

The thymidylate synthase (thyA) gene has been isolated from Lactococcus lactis subsp. lactis. The cloned gene was strongly expressed in Escherichia coli both in vivo and in vitro (maxicells and cell-free transcription and translation systems) and complemented E. coli thyA mutants. DNA-DNA hybridizations demonstrated that the thyA gene is encoded by the chromosome of L. lactis subsp. lactis. By sequential deletion of DNA outside the complementing region, the thyA gene was localized to a 1.1-kilobase DNA fragment. The nucleotide sequence of the lactococcal thyA gene was determined by the dideoxy-chain termination technique. The derived amino acid sequence indicated a protein size of 32,580 daltons, which is in good agreement with results obtained from maxicell and in vitro transcription and translation experiments. The primary sequence is homologous to 12 other thyA proteins from a variety of other organisms. Upstream from the structural gene, -10 and -35 promoter sequences which were almost canonical sigma-70 promoter sequences were identified, which may explain the strong expression of the thyA gene observed in E. coli. An A-T-rich sequence characteristic of gram-positive promoters was also noted adjacent to the -35 region. The thyA gene has potential as a marker for plasmid maintenance and selection in food systems.

Amino Acid Sequence↗
PubMed1990

Thymidylate synthase gene from Lactococcus lactis as a genetic marker: an alternative to antibiotic resistance genes.

The potential of the thymidylate synthase thyA gene cloned from Lactococcus lactis subsp. lactis as a possible alternative selectable marker gene to antibiotic resistance markers has been examined. The thyA mutation is a recessive lethal one; thyA mutants cannot survive in environments containing low amounts of thymidine or thymine (such as Luria-Bertani medium) unless complemented by the thyA gene. The cloned thyA gene was strongly expressed in L. lactis subsp. lactis, Escherichia coli, Rhizobium meliloti, and a fluorescent Pseudomonas strain. In addition, when fused to a promoterless enteric lac operon, the thyA gene drove expression of the lac genes in a number of gram-negative bacteria. In transformation experiments with thyA mutants of E. coli and conjugation experiments with thyA mutants of R. meliloti, the lactococcal thyA gene permitted selection of transformants and transconjugants with the same efficiency as did genes for resistance to ampicillin, chloramphenicol, or tetracycline. Starting from the broad-host-range plasmid pGD500, a plasmid, designated pPR602, was constructed which is completely free of antibiotic resistance genes and has the lactococcal thyA gene fused to a promoterless lac operon. This plasmid will permit growth of thyA mutant strains in the absence of thymidine or thymine and has a number of unique restriction sites which can be used for cloning.

Cloning, Molecular↗
PubMed1990

Angiographic embolization of traumatic hepatic artery pseudoaneursym.

The development of hepatic artery pseudoaneurysm represents a difficult therapeutic challenge as a vascular complication of hepatic trauma. Depending on the location of the pseudoaneurysm, this complication may represent a substantial technical challenge: recently hepatic artery pseudoaneurysms have been managed nonoperatively in selected patients. We report definitive control of a traumatic hepatic artery pseudoaneurysm with angiographic placement of detachable silicone balloons that allowed precise proximal and distal occlusion. Follow-up arteriogram at four weeks confirmed complete occlusion of the isolated segment without recurrence. The use and fate of detachable silicone balloons are discussed.

Accidents, Traffic↗
PubMed1989

Immunodetectable galactosyltransferase is associated only with human spermatozoa of high buoyant density.

Human ejaculated spermatozoa are heterogeneous and can be separated into two distinct populations according to their respective buoyant densities. In order to investigate the functional differences between these two types of spermatozoa, we have searched for the presence of galactosyltransferase. A Western blot of sperm proteins following their electrophoresis was probed with an anti-galactosyltransferase serum revealing that this enzyme is present in human spermatozoa. Furthermore, galactosyltransferase is detectable only in those proteins isolated from the head of high density spermatozoa. These results suggest that ejaculated spermatozoa consist of two populations that are functionally different.

Animals↗
PubMed1989

Cardiac contusion. The effect on operative management of the patient with trauma injuries.

Sixty-four patients with cardiac contusion documented by electrocardiographic changes and creatine kinase MB fraction assay following blunt chest injury were reviewed to assess the impact of cardiac contusion on subsequent management. Fifty-eight patients had elevated creatine kinase MB levels; 35 patients had electrocardiographic abnormalities, including ST-segment and T-wave changes (25), premature ventricular contraction (ten), right bundle-branch block (nine), atrioventricular block (three), atrial fibrillation (three), and premature atrial contraction (two). Thirty patients underwent general anesthesia. There were only four perioperative complications: ventricular ectopy, ventricular fibrillation, nodal rhythm, and pulmonary edema. There were no deaths attributable to cardiac contusion. In summary, patients with blunt trauma who have sustained a cardiac contusion can undergo elective operation with a low incidence of complication. In the emergency setting, however, hemodynamic monitoring for early detection of arrhythmias is indicated.

Adolescent↗
PubMed1989

Cloning of a gene involved in cellulose biosynthesis in Acetobacter xylinum: complementation of cellulose-negative mutants by the UDPG pyrophosphorylase structural gene.

Three cellulose-negative (Cel-) mutants of Acetobacter xylinum strain ATCC 23768 were complemented by a cloned 2.8 kb DNA fragment from the wild type. Biochemical analysis of the mutants showed that they were deficient in the enzyme uridine 5'-diphosphoglucose (UDPG) pyrophosphorylase. The analysis also showed that the mutants could synthesize beta(1-4)-glucan in vitro from UDPG, but not in vivo from glucose. This result was expected, since UDPG is known to be the precursor for cellulose synthesis in A. xylinum. In order to analyze the function of the cloned gene in more detail, its biological activity in Escherichia coli was studied. These experiments showed that the cloned fragment could be used to complement an E. coli mutant deficient in the structural gene for UDPG pyrophosphorylase. It is therefore clear that the cloned fragment must contain this gene from A. xylinum. This is to our knowledge the first example of the cloning of a gene with a known function in cellulose biosynthesis from any organism, and we suggest the gene be designated celA.

Cellulose↗
PubMed1989

Effects of ultrasound exposure in vitro on neuroblastoma cell membranes.

Mechanisms of action of ultrasound on cell membranes were studied on two murine C1300 neuroblastoma cell lines of minimum genetic diversity. Cavitation was established in rotating polystyrene centrifuge tubes by 1 MHz cw ultrasound; exposure time was 5 minutes. NS20Y and N2A cells exposed in suspension responded similarly by 86Rb+ transport and Na+-K+-ATPase activity assays, but differently by trypan blue dye exclusion and lysis assays. This indicates similar overall damage to the cell membranes, despite use of trypsin to release N2As only. Primary evidence of damage was lysis of NS20Ys and permeabilization of N2As. These results indicate that the same ultrasound exposure conditions can produce different effects in cells that differ in their membrane properties.

Animals↗
PubMed1989

Thrombus associated with central venous catheters in infants and children.

From 1978 to 1987, 350 infants and children had silicone central catheters placed for long-term venous access. Real time echocardiography showed a catheter tip thrombus in 16 patients, including 12 premature infants and four children. Catheters had been in place for eight to 560 days. Thirteen patients were receiving total parenteral nutrition (TPN) at the time thrombus was identified, and one patient had received TPN 2 weeks previously. Indications for echocardiography included sepsis (7), respiratory insufficiency (6), evaluation of heart disease (3), and catheter malfunction (1); several patients had multiple indications. Treatment was individualized and included atriotomy (2), systemic heparin and thrombolytic agents with or without catheter removal (8), catheter removal only (3), and observation (3). Four of eight patients treated with thrombolysis had complete clot lysis and four had partial dissolution. Two patients managed expectantly had resolution of the thrombus. None of the patients suffered further complications or died as a result of the thrombus, but ten of the 16 died 1 to 12 weeks later from their underlying disease. Forty-seven asymptomatic patients were studied by echocardiography to assess the incidence of unsuspected right atrial thrombus. Their catheters had been in place for a mean of 200 days and only 11 had been used for TPN. None of these patients had identifiable thrombus at the catheter tip. The incidence of catheter tip thrombus, which is higher than previously suspected, is related to prematurity, TPN, and continuous catheter use, but not duration of catheterization. The incidence is low in asymptomatic patients. Treatment regimen must be individualized and this series reflects a trend toward more conservative management.

Catheterization, Central Venous↗
PubMed1989

Sulfated oviductal glycoproteins in the rabbit: quantitation by competitive enzyme-linked immunosorbent assay.

The rabbit oviductal epithelium synthesizes and secretes a family of antigenically related, sulfated oviductal glycoproteins (SOG). Anti-SOG monoclonal antibodies (Mabs) were produced and two (Mab 1 and Mab 2) were selected for further characterization. Periodate oxidation of Western blots of oviductal fluid did not affect the binding of Mab 1 or Mab 2, thus suggesting that these antibodies recognized protein rather than carbohydrate epitopes on SOG. The specificity of Mab 1 was determined by Western blot analysis of tissues obtained from estrous rabbits and from the male rabbit reproductive tract. SOG was identified in tissue extracts of both the oviductal ampulla and isthmus. Cervix was the only non-oviductal tissue with which Mab 1 cross-reacted. Mab 1 was used to isolated SOG from whole oviductal fluid by immuno-affinity chromatography. Affinity-purified SOG and Mab 1 were used to develop a quantitative, SOG-specific, competitive enzyme-linked immunosorbent assay. This assay was used to quantify SOG in rabbit oviductal fluid collected during estrus and pseudopregnancy. SOG secretion during pseudopregnancy was resolved into two transient episodes of increased secretion. Maximum SOG secretion (X = 1039 +/- 199 micrograms/day) occurred within 48 h of the induction of pseudopregnancy. A second period of enhanced SOG secretion (X = 308 +/- 46 micrograms/day) occurred during the fifth and sixth days of pseudopregnancy. Baseline SOG secretion occurred during estrus at approximately 60% of maximum postovulatory secretion.

Animals↗
PubMed1989

Overview of a workshop on quantitative models for developmental toxicity risk assessment.

A workshop was held to discuss potential advancements to improve the precision of risk estimates for developmental toxicity. This paper presents an overview of the discussions at the workshop, focusing on the risk assessment process and science policy considerations important in the use of quantitative models. Some of the pertinent biological considerations are reviewed, particularly those related to the repair capacity of the developing organism and how this affects the concept of a threshold for developmental toxicity effects, as well as the maternal and litter influences on developmental toxicity outcomes. Finally, the current status of use of quantitative approaches is described, possible short-term approaches are discussed, and future research needs in this area are outlined.

Abnormalities, Drug-Induced↗
PubMed1988

Tyrosine phosphorylation of the human T cell antigen receptor zeta-chain: activation via CD3 but not CD2.

TCR stimulation by Ag or anti-receptor antibodies in murine T cells results in the activation of two independent protein kinases, protein kinase C (PKC) and a protein tyrosine kinase. Similarly, stimulation of murine Thy-1 or Ly-6 with mAb also results in activation of both of these kinase pathways. Tyrosine phosphorylation in all cases occurs on the TCR zeta-chain. It is known that Ag and anti-receptor antibodies activate PKC in human T cells. In this study we demonstrate that mitogen or anti-CD3 antibodies activate tyrosine phosphorylation of the human TCR-zeta-chain. PMA, which activates PKC, does not result in zeta-chain tyrosine phosphorylation. Stimulation of human T cells by antibodies that bind the CD2 molecule is an alternate mode of inducing T cell proliferation. These antibodies surprisingly do not induce tyrosine phosphorylation of the zeta-chain. Thus, different methods of cellular activation can result in distinguishable patterns of receptor-mediated biochemical signaling events.

Antibodies, Monoclonal↗
PubMed1988

Evidence for two forms of phospholipase A2 in human semen.

The molecular weight of the active unit of phospholipase A2 (PA2) in human seminal plasma and spermatozoa was determined using the radiation inactivation technique. Fresh spermatozoa possess more than one form of PA2 activity as judged by the biphasic nature of the curve obtained during enzyme inactivation. However, when stored frozen for several months followed by a period of heating for 60 min at 60 degrees C prior to irradiation, the sperm exhibited PA2 activity, which corresponded to a single low molecular mass form of 12,000 d when radioactive phosphatidylcholine (PC) was used as substrate and 8,000 d when radioactive phosphatidylethanolamine (PE) was used as substrate. In fresh seminal fluid, only one active form of PA2 was detected as judged by the linear nature of the curve obtained during enzyme inactivation by irradiation. Using PC as substrate, the active unit was again estimated to be 12,000 d, whereas it corresponded to 18,000 d when PE was used. The PA2 activity associated with normal spermatozoa exhibited a 60% decrease in activity after storage at -20 degrees C for 48 hr followed by a heating period of 10 min at 60 degrees C. Long-term storage of spermatozoa at -20 degrees C also resulted in a similar decrease in the deacylation of PC. No further loss of activity was observed during subsequent heat treatment at 60 degrees C. Seminal plasma, however, showed no loss of activity following short (48 hr at 4 degrees C or -20 degrees C) or long-term storage and subsequent heat treatment. Thus, the behavior of PA2 when the effect of temperature was studied and in radiation inactivation experiments indicates that the low molecular weight component in the seminal plasma as well as in spermatozoa is temperature resistant. However, in fresh spermatozoa, a second form of PA2 was found and was sensitive to changes in temperature.

Drug Stability↗
PubMed1988

Protein synthesis by neuroblastoma cells is enhanced by exposure to burst-mode ultrasound cavitation.

We observed enhancement of protein synthesis, compared to control cells, 24 h after exposing C1300 neuroblastoma cells (N2A) in rotating tubes at 37 degrees C to 1-MHz ultrasound tone bursts [1:1; durations from 6 to 600 ms; 3.4 W/cm2 spatial-peak burst-average intensity; 5 min total treatment duration (on + off periods)]. Protein synthesis was measured by uptake of 3H-leucine and normalized for cell proliferation by measured uptake of 14C thymidine. The similarity between results for enhanced cavitation-stimulated iodine-release reported by Ciaravino and our results for cellular protein synthesis suggests that cavitation causes this biological effect.

Acoustics↗
PubMed1988

beta-Glucoside Activators of Mung Bean UDP-Glucose: beta-Glucan Synthase : I. Identification of an Endogenous beta-Linked Glucolipid Activator.

Heat-stable activators of membranous beta-glucan synthase have been isolated from the supernatant fraction of crude mung bean (Vigna radiata) extracts by DEAE-cellulose and silica-gel chromatography. One of the activators has been partially purified and characterized on the basis of susceptibility to various enzymes and by analysis of the products formed upon total acid hydrolysis, alkaline-methanolysis, and beta-glucosidase digestion. This activator has the characteristics of a 1,2-dioleoyl diglyceride containing beta-linked glucose residue(s) at the C-3 position. When expressed per mole of glucosyl residues, the maximal K(a) value of the activator is estimated to be 25 micromolar. Both the intact glucosyl and fatty acid moiety are essential to the stimulatory effect of the activator.

Journal Article↗