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Biomedical subjects

R Kao

Publications and source records attributed to R Kao.

34 records · Page 2Linked to original sources
PubMed1993

Delayed implantation of demineralized bone powder after local irradiation in rats.

Previous studies have shown that osteoinduction is inhibited when demineralized bone powder (DBP) is implanted within 48 hours of local irradiation (i.e., when the acute effects of radiation injury are present). This study sought to determine whether normal osteoinduction can proceed if the implantation of DBP is delayed until 21 days postirradiation. At 21 days, the acute effects of radiation injury are likely to have subsided, but the long-term effects have not yet appeared. Twenty-eight-day-old rats were administered a radiation dose of either 7 or 20 Gy over a localized area of one thigh. The contralateral, nonirradiated thigh served as a control. Demineralized bone powder was subcutaneously implanted 21 days later. Subcutaneous pellets were retrieved at various intervals thereafter (up to Day 45) and were histologically graded for evidence of osteoinduction. No difference in osteoinduction was detected at any time interval in pellets from the 7-Gy-treated sites, compared with controls. Pellets from the 20-Gy-treated sites, however, demonstrated significantly a lower osteoinductive response at each interval. These latter pellets showed small scattered areas of osteoinduction and reduced formation of marrow elements. Thus, although osteoinduction proceeds normally when the implantation of DBP is delayed for 21 days after irradiation with 7 Gy, this is not the case when 20 Gy are administered. Given the absence of gross impairment of tissue vascularity in irradiated sites, it is possible that inhibition of osteoinduction after higher doses of radiation results from permanent damage to mesenchymal precursor cells.

Animals↗
PubMed1992

Mammography and Papanicolaou smear use by elderly poor black women. The Harlem Study Team.

OBJECTIVE: To describe factors related to the use of mammography and Papanicolaou smears in low-income women aged 65 or more years to guide development of future interventions. DESIGN: A cross-sectional survey. SETTING AND PATIENTS: Elderly Black women attending a public hospital medical clinic. MEASUREMENTS: Information obtained in a face-to-face interview of a random sample of patients. RESULTS: Four-hundred and forty-five women (94%) consented to be interviewed; 74% reported a mammogram, and 85% reported a Papanicolaou smear in the past, although these early-detection tests were not obtained with any regularity after age 65. Concordance between self-reported screening use and blind chart review was more than 90%. The major reasons for non-use of both screening tests were that a physician hadn't recommended them or that the women didn't know they needed them. Levels of knowledge about breast and cervix cancer were low; 68% believed bumping or bruising the breast caused cancer, and only 25% knew that cancer risk increased with advancing age. In logistic regression models, health status, provider type, perceived benefit, life satisfaction, and knowledge of test intervals were each significantly associated with mammogram use. Age, health status, education, perceived susceptibility and benefit, life satisfaction, and knowledge of test intervals were independently related to Pap use (P < .05). CONCLUSION: This study illustrates that elderly, poor, minority women who are regular health-care users do use mammography and Pap smear screening services. Incorporating screening into routine primary care and physician and patient education could enhance the use of early cancer detection procedures in this age group.

Black or African American↗
PubMed1991

Left ventricular ejection fraction: single-plane and multiplanar transesophageal echocardiography versus equilibrium gated-pool scintigraphy.

The relative accuracy and precision of estimating left ventricular ejection fraction (EF) in dogs were assessed by two-dimensional transesophageal echocardiography (2D-TEE) and by three-dimensional transesophageal echocardiographic (3D-TEE) imaging and reconstruction. This assessment was accomplished by comparing each echocardiographic method to a gated equilibrium blood pool radionuclide (RN) standard. By using both correlation and regression analysis, 2D-TEE performed reasonably well in estimating RNEF (correlation coefficient [r] = 0.80, slope = 1.01, intercept = 6.37, standard error of the estimate [SEE], 8.98), but not as well as 3D-TEE (r = 0.86, slope = 0.83, intercept = 3.38, SEE, 5.74). Using Altman and Bland's methods of comparison analysis, it was found that 2D-TEE overestimated RNEF by 7% (standard deviation [SD], 8.8). This degree of overestimation was not consistent across the range of measurement. In contrast, 3D-TEE slightly underestimated RNEF by less than 3% and showed less variability (SD, 6.0). The accuracy of the 3D-TEE determinations was not dependent on the magnitude of EF. Additionally, a significantly higher proportion of the 2D-TEE measurements (0.30) compared with the 3D-TEE measurements (0.10) differed from RN values by more than 10% (P = 0.009, McNemar's test). At the clinically important low end of the EF range (RNEF less than or equal to 35%), 2D-TEE may be expected (with 95% confidence) to be within -15% to +28% EF of reference values, whereas 3D-TEE can be expected to be within -8% to +5% EF relative to RN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Mathematical analysis of perifusion data: models predicting elution concentration.

System models are constructed and analyzed for combined convective flow and for dispersion in distorting concentrations of a chemical signal as it passes through a packed column. We derive general analytical solutions for these models. The results have applications to analyses such as in biological experiments involving hormonal stimulation of perifused cells, elution chromatography, adsorption columns, and studies of groundwater flow. The models reveal that the column distorts an incoming signal (such as a change in solute concentration in the flowing liquid) at the inlet. This distortion is greatest at low values of the Peclet number of the flow and is small at larger values. We explore the effects of the approximations inherent in the mathematical models of the system. Specification of the boundary conditions of the problem are shown to be particularly important. With the use of incorrect models, it is possible to obtain accurate interpolations to data obtained from perfusion experiments. However, the parameters derived (in particular the dispersion constant and the peak concentration of a solute concentration pulse) may be considerably in error. This may lead to errors when these parameter estimates are used to predict results in other experimental situations.

Animals↗
PubMed1990

Ascorbic acid stimulates production of glycosaminoglycans in cultured fibroblasts.

The effect of ascorbic acid on collagen synthesis is well characterized. Proteoglycans and their attached glycosaminoglycans are components of the extracellular matrix closely associated with collagen fibers. We examined whether ascorbic acid also plays a role in glycosaminoglycan production. Synthesis and deposition of glycosaminoglycans into the extracellular matrix and secretion into the media were followed in human skin fibroblasts cultured in the presence and absence of ascorbic acid. Specific glycosaminoglycans were identified and quantitated by differential enzyme digestion, ion-exchange column chromatography, and cellulose-acetate electrophoresis. No major qualitative changes in glycosaminoglycans were observed. However, quantitatively, synthesis of glycosaminoglycans increased 30 to 90%, and deposition into the extracellular matrix increased 80% in the presence of ascorbic acid. This effect was only in part secondary to decreased levels of collagen, and the diminished capacity of underhydroxylated collagen to bind proteoglycans. The effect of ascorbic acid on extracellular macromolecules is thus more pervasive than previously assumed.

Ascorbic Acid↗
PubMed1989

Measurement of left ventricular ejection fraction and volumes with three-dimensional reconstructed transesophageal ultrasound scans: comparison to radionuclide and thermal dilution measurements.

A transesophageal, ultrasonic cardiac imaging probe was built that incorporated a mechanism for changing the angle of the imaging plane of a conventional phased array in a precise and known manner. This probe was used to acquire an angular spatial sequence of two-dimensional images of the left ventricular cavity over a series of cardiac cycles by sweeping the imaging plane through it stepwise. The endocardial borders of these images were manually outlined off-line and the application of a three-dimensional reconstruction algorithm was then used to compute the left ventricular end-diastolic and end-systolic volumes and ejection fraction. A study was conducted with seven anesthesized dogs to compare ultrasonic determinations by this method with determinations and measurements made using radionuclide and thermal dilution methods. Comparison of 33 ejection fractions, measured by the ultrasonic volume method and by the gated blood pool radionuclide approach, yielded a correlation coefficient of 0.87 and a standard error of the estimate of 5.7% measured over a range of 10% to 58% (average, 40%). Comparison of the ultrasonically measured volumes with those calculated from stroke volume (derived from thermal dilution cardiac output measurement) and ejection fraction (measured by radionuclide technique) produced a correlation coefficient of 0.92 and a standard error of the estimate of 10.3 mL over a range of 18 to 130 mL (average, 56 mL). The accuracy of volume and ejection fraction measurements with this new ultrasonic method seems comparable to that of other currently used clinical approaches such as radionuclide and angiography.

Animals↗
PubMed1987

Beneficial effects of cocarboxylase in the treatment of experimental myocardial infarction in dogs.

Cocarboxylase, or thiamine pyrophosphate, is an essential coenzyme in the catabolism of pyruvate. The authors evaluated the effects of a stable cocarboxylase solution in the treatment of an experimentally created acute myocardial infarction in 14 healthy mongrel dogs. The left anterior descending artery was ligated for 60 minutes and data were collected at the following points: A) prior to ligation, B) 15 minutes after ligation, C) 30 minutes after ligation, and D) 60 minutes after ligation. In one group (Group II), cocarboxylase (150 mgm/kg) was given systematically via a central line 15 minutes and 45 minutes after ligation, while in Group I an equal amount of D5W was given. Hemodynamic data include heart rate, systolic and mean arterial pressure, pulmonary wedge pressure, right arterial pressure, and cardiac output. Myocardial O2 consumption was determined by the method of Rooke and Feigl. Electrocardiographic data were also monitored throughout the experiment. In both groups, preligation (point A) hemodynamic data were similar. In Group II, there were beneficial hemodynamic changes versus Group I (expressed as percentage recovery of hemodynamic performance from preligation) at points C and D, with significant (P less than 0.05) decreases in heart rate, increased stroke volume, decreased systemic vascular resistance, and decreased myocardial O2 consumption. EKG criteria also showed improvement in Group II versus Group I. In conclusion, this experiment suggests that cocarboxylase may be beneficial to ischemic canine myocardium by virtue of its favorable systemic hemodynamic effects.

Animals↗
PubMed1986

A quantitative in vitro assay of polymorphonuclear leukocyte migration through human amnion membrane utilizing 111in-oxine.

A modified amnion chemotaxis assay is described for measurement of polymorphonuclear leukocyte(s) (PMNL) migration (random and directed) into a viable membrane. The primary modifications are the use of 111In-oxine-labelled PMNL and replacement of the nitrocellulose 'trap' filter with a type I collagen sponge. The modifications resulted in four important benefits: the quantification of PMNL migration was simplified; reader subjectivity was eliminated; the information gained of the migration process was enhanced; and the assay time was decreased. The amnion chemotaxis assay with the modifications reported should provide the means of evaluating several aspects of the inflammatory response of PMNL.

Amnion↗
PubMed1980

Inhibition of protein degradation in the energy-poor heart.

Hypoxia and anoxia were induced in isolated perfused rat hearts by reduction of perfusate oxygen. Ischemia was produced by restricting coronary flow in hearts working against high resistance. Protein degradation, estimated from release of phenylalanine into the perfusate in the presence of cycloheximide, was inhibited in both anoxic and ischemia as compared to aerobic hearts. The effect of ischemia was greater than that of anoxia. A similar inhibitory effect was observed in energy-poor hearts when insulin was present in the perfusate. Other experiments indicated that the effects of energy depletion were exerted at a step early in the degradative pathway, since peptide products of partial proteolysis did not accumulate. A graded reduction in perfusate oxygen tension (hypoxia) led to a significant inhibition of proteolysis with unaltered tissue levels of nucleotides and creatine phosphate. Protein degradation was inhibited in aerobic and anoxic hearts exposed to increasing extracellular levels of hydrogen ions and lactate, suggesting that reduced proteolysis in hearts that are provided limited oxygen may result from accumulation of metabolites as well as from energy depletion per se.

Adenosine Triphosphate↗
PubMed1978

Hormonal and metabolic control of proteolysis.

Proteolysis in heart muscle is regulated by hormonal and metabolic factors. In the absence of insulin, protein degradation accelerated, autophagic vacuoles appeared within the heart and latency of lysosomal enzymes decreased. Addition of insulin prevented or reversed these changes. Provision of leucine inhibited proteolysis in control hearts. Addition of the products of transamination and oxidative decarboxylation of leucine, isoleucine and valine had similar inhibitory effects. Protein degradation was inhibited in ischaemic or anoxic hearts, but latency of lysosomal enzymes was decreased. Inhibition of degradation in energy-poor tissue may represent both an energy-requirement for proteolysis and inhibition by accumulation of metabolic products, such as lactate.

Adenosylmethionine Decarboxylase↗
PubMed1976

Effects of anoxia and ischemia on protein synthesis in perfused rat hearts.

The effect of ischemia on synthesis of myocardial proteins was investigated using a model of perfusion in which low levels of coronary flow were provided to paced hearts worked against a closed aortic outflow tract. These conditions rapidly produced ischemia and ventricular failure, as evidence by reduced coronary flow, increased left atrial pressure, and decreased pressure development. Protein synthesis was inhibited in a subsequent 1-hour period, during which a minimal coronary flow was maintained by retrograde perfusion. ATP, GTP, and creatinine phosphate were depleted in ischemic hearts and AMP accumulated. Production and accumulation of lactate within the tissue increased, whereas palmitate uptake was inhibited. The inhibition of protein synthesis was not associated with reduced levels of intracellular amino acids. During ischemia, decreased levels of ribosomal subunits as compared to paced or unpaced aerobic hearts suggested that peptide chain elongation was slow relative to initiation. Provision of insulin further reduced subunit levels but did not increase protein synthesis, suggesting that the hormone did not prevent inhibition of peptide chain elongation in energy-poor hearts.

Aerobiosis↗
PubMed1975

Effects of hypophysectomy, growth hormone, and thyroxine on protein turnover in heart.

Cardiac atrophy following hypophysectomy was accompanied by decreased heart content of RNA and polysomes and increased levels of ribosomal subunits, suggesting that protein synthesis was restricted by a reduced supply of ribosomes and an imbalance between rates of peptide-chain initiation and elongation. During perfusion in vitro, provision of palmitate restored the normal balance between rates of initiation and elongation but protein synthesis was lower in hearts of hypophysectomized than normal rats, reflecting the lower RNA content of hearts from hormone-deficient animals. After the period of atrophy had passed, or after treatment with growth hormone and thyroxine, heart RNA content and rates of protein synthesis were equal to or greater than those found in normal hearts. When plasma levels of amino acids, glucose, fatty acids, and insulin, and rates of beating and ventricular pressure development observed in normal and hypophysectomized rats were simulated during in vitro perfusion, hearts from hormone-deficient rats had reduced rates of protein synthesis but unaltered rates of degradation. Cathepsin D activity in heart homogenates (+ Triton X-100) was elevated during cardiac atrophy when expressed per g of tissue but not when expressed per heart.

Acetylglucosamine↗
PubMed1975

Effect of insulin on protein turnover in heart muscle.

The effect of insulin on turnover of protein was investigated in isolated perfused rat hearts. The hormone lowered intracellular levels of nine amino acids and reduced or abolished net release of 10 amino acids and ammonia. The extent of the insulin effect on protein degradation was investigated by estimating the rate of dilution of the specific radioactivity of the free phenylalanine pool. Insulin concentrations greater than 200 microunits per ml reduced protein degradation and net phenlylalanine release. Protein degradation was estimated more directly by inhibiting reincorporation of nonradioactive phenylalanine from protein with cycloheximide. Addition of the inhibitor increased the estimated rates about 50%, but the magnitude of the hormone effect was similar. The latency of lysosomal enzymes in control and insulin-treated hearts was assessed by measuring activities of beta-acetylglucosaminidase and cathepsin D in heart homogenates in the presence and absence of Triton X-100. Perfusion with insulin-free buffer increased the activities assayable without detergent, but did not change total activities of these enzymes. Insulin decreased activities assayable without detergent and increased activities sedimenting in the 10-5 times g pellet. These studies showed that insulin restricted the rate of protein degradation in the isolated perfused rat heart. Concomitantly, the latency of lysosomal enzymes was increased when the hormone was provided.

Adenosine Triphosphate↗
PubMedDate not supplied

Fungal ribotoxins: a family of naturally engineered targeted toxins?

alpha-Sarcin, mitogillin, and restrictocin are small (approximately 17 kDa) basic robosome-inactivating proteins (RIPs) produced by the Aspergilli that catalytically inactivate the large ribosomal subunits of all organisms tested to date. These three fungal ribotoxins act as specific ribonucleases by hydrolyzing one single phosphodiester bond in the universally conserved alpha-sarcin domain of 23-28S rRNAs and are among the most potent inhibitors of protein synthesis known. Previous molecular studies of ribotoxins indicated that they belong to the superfamily of ribonucleases and analysis of the mitogillin gene employing PCR-mediated site-specific mutagenesis suggests that certain domains in ribotoxins, which share homologies with motifs in ribosome-related proteins, may be responsible for the targeting of ribotoxins to the ribosome. The applications of the ribotoxins as tools in research and their uses as therapeutic and diagnostic agents are also reviewed in this paper.

Amino Acid Sequence↗