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Biomedical subjects

M Kelly

Publications and source records attributed to M Kelly.

At least 289 records · Page 16Linked to original sources

Comparing urban and rural hospice services.

Hospice care has flourished in the past 20 years and now provides a wide range of services. This study compares the operation of an urban hospice with that of a smaller rural hospice. The implications of the underuse of some of the services are discussed.

Adult↗

Identification of epidermal growth factor as a component of the rat urinary bladder tumor-enhancing urinary fractions.

Using the heterotopically transplanted rat urinary bladder, we have shown that normal rat urine has a potent tumor-enhancing effect on bladder carcinogenesis. In an attempt to isolate tumor-enhancing factor(s), urine was fractionated by Bio-Gel P-100 column chromatography and each eluate fraction was examined for inducibility of ornithine decarboxylase (ODC) in a target rat bladder carcinoma cell line, 804G. We have identified two ODC-inducible peaks, one located in a high molecular weight region designated as Fraction I (Fr. I) and the second in a low molecular weight region designated as Fraction II (Fr. II). Fr. I consisted of two principal elements, transferrin and a component which induced ODC. The present investigation was conducted to characterize the ODC-inducible activity in Fr. I and II. Chromatographic analysis of Fr. I by Sephacryl S-200 and Fr. II by Bio-Gel P-10 chromatography separated several ODC-inducible peaks. However, the major ODC inducibility was due to a high concentration (460 ng/mg Fr. I residue, approximate Mr 54,000, and 580 ng/mg Fr. II residue, approximate Mr 6,100) of epidermal growth factor (EGF) as determined by radioimmunoassay. Aliquots obtained from these peaks competed with mouse EGF for EGF receptors in A431 cells. Preincubation of Fr. I and II with rabbit anti-rat EGF IgG significantly reduced ODC inducibility. Transforming growth factor alpha activity as determined by radioimmunoassay was also demonstrated in both Fr. I (34 ng/mg) and Fr. II (9 ng/mg). The results of the present study together with our previous data indicate that the majority of the ODC-inducing activity in the tumor-enhancing urinary components Fr. I and Fr. II is due to EGF itself and EGF-related growth factors of high molecular weight and that Fr. I also contains transferrin.

Animals↗

Synthesis, modification, and flotation properties of rat hepatocyte apolipoproteins.

We have studied apolipoprotein synthesis, intracellular modification and secretion by primary adult rat hepatocyte cultures using continuous pulse or pulse chase labeling with [35S]methionine, immunoprecipitation and two-dimensional isoelectric focusing/polyacrylamide gel electrophoresis. The flotation properties of the newly secreted apolipoproteins were studied by discontinuous density gradient ultracentrifugation and one- and two-dimensional polyacrylamide gel electrophoresis. These studies showed that rat hepatocyte apoE is modified intracellularly to produce minor isoproteins that differ in size and charge. One of these minor isoproteins represents a monosialated apoE form (apoE3s1). Similarly, apoCIII is modified intracellularly to produce a disialated apoCIII form (apoCIIIs2), whereas newly synthesized apoA-I and apoA-IV are not glycosylated and overlap on two-dimensional gels with the proapoA-I and the plasma apoA-IV form, respectively. Both unmodified and modified apolipoproteins are secreted into the medium. Separation of secreted apolipoproteins by density gradient ultracentrifugation has shown that 50% of apoE, 80% of apoA-I, and more than 90% of apoA-IV and apoCIII are secreted in a lipid-poor form, whereas apoB-100 and apoB-48 are 100% associated with lipids. ApoB-100 floats in the VLDL and IDL regions, whereas apoB-48 is found in all lipoprotein fractions. ApoE and small amounts of apoA-I, apoA-IV and apoCIII float in the HDL region. Small amounts of apoE and apoCIII are also found in the VLDL and IDL regions, and apoE in the LDL region. Ultracentrifugation of nascent lipoproteins in the presence of rat serum promoted flotation of apoA-I and apoA-IV in the HDL fraction and resulted in increased flotation and distribution of apoE and apoCs in VLDL, IDL and LDL regions. These observations are consistent with the hypothesis that intracellular assembly of lipoproteins involves apoB-48 and apoB-100 forms, whereas a large portion of apoA-I, apoCIII and apoA-IV can be secreted in a lipid-poor form, which associates extracellularly with preexisting lipoproteins.

Amino Acid Sequence↗

Relationship between menarcheal age and adult height.

Many factors contribute to the attainment of adult height, including genetic and environmental variables. To assess the relationship between menarcheal age and adult height, measured adult height and recalled menarcheal age were compared by regression analysis in 425 women. The overall regression equation, Height = 158.14 + .4321 (Age) - .1667 (Age - 13)2, was significant (P less than .003), as was the coefficient for the quadratic term (P not equal to .014). After exclusion of those in whom menarche occurred after age 16, the overall linear regression equation for the remaining 416 patients, Height = 153.95 + .7353 (Age), was still significant (P not equal to .001), but the coefficient for the quadratic term was not. These data suggest that menarcheal age significantly correlates with adult height as an independent variable.

Adult↗

Glucose turnover rate and peripheral insulin sensitivity in alcoholic patients without liver damage.

Glucose intolerance is frequently found in alcoholic patients and an impaired insulin response has been documented in them. To look for alternative mechanisms that could explain this intolerance, a glucose turnover using tritiated glucose and an euglycemic glucose clamp were performed to measure the glucose production rate and peripheral insulin sensitivity, respectively. Two groups of recently abstinent chronic male alcoholic patients without evidence of liver damage were studied. The glucose turnover technique showed a higher basal glucose production rate in alcoholics, compared with normal volunteers (2.83 +/- 0.29 vs. 1.84 +/- 0.22 mg/kg/min); an intravenous ethanol load significantly increased this rate. The euglycemic glucose clamp did not show peripheral insulin resistance in alcoholics, compared with controls.

Adult↗

The Omnibus Budget Reconciliation Act of 1987. A policy analysis.

The Omnibus Reconciliation Act of 1987 set forth new provisions for Medicare and Medicaid sections related to new standards for care in the nursing home setting. One major provision was for nurse aide training. Within that provision there are four specified requirements: (1) nurse aide training for 75 hours, (2) competency evaluation of newly trained nurse aides, (3) competency evaluation of nurse aides already providing care, and (4) a registry for nurse aides. The primary implications of the these requirements center on the responsibility of the individual nurse or nurse community in ensuring appropriate implementation of the new requirement. Without appropriate implementation, some of the provisions increase the liability of the nurse and the risk to the public. The reality of OBRA 1987 and its intent of bringing a measure of quality assurance to the nursing home industry should only serve as an impetus for the nursing community to better translate the nurse role and its contribution in the nursing home setting to policy makers at local, state, and federal levels.

Competency-Based Education↗

Nutritional support in hospitalized patients with alcoholic liver disease.

The effects of a nutritional support in hospitalized patients with alcoholic cirrhosis and liver failure were studied in a controlled protocol. Thirty-six patients were included, 17 were randomly assigned to an experimental group and the rest to a control group. Experimentals received a diet aiming at 50 kcal (209 kJ)/kg bodyweight/d and 1.5 g protein/kg bodyweight/d (as proteins of high biological value). Controls received the standard diet prescribed by the attending physician. The severity of liver failure and the nutritional status on admission were similar in both groups. The measured energy intake in controls was 1813 +/- 121 kcal/d (7589 +/- 506 kJ/d) and 2707 +/- 71 kcal/d (1131 +/- 297 kJ/d) in experimentals (P less than 0.001). The protein intake in controls was 47 +/- 3.8 g/d and in experimentals 80 +/- 3 g/d (P less than 0.001). There were seven deaths during the study period (two experimentals and five controls). No differences were observed in the evolution of liver failure, hepatic encephalopathy or nutritional status between both study groups. It is concluded that a higher energy and protein intake in these patients does not have adverse effects and is associated with a non-significant reduction in mortality.

Body Weight↗

The effect of alignment of the implant on fractures of the patella after condylar total knee arthroplasty.

The results in thirty-six knees that had a fracture of the patella after a total condylar arthroplasty were reviewed, and were analyzed according to the type of fracture and the alignment of the implant and the limb. Most of the fractures occurred two years or less after the initial operation. Fourteen knees were rated fair or poor and twenty-two, good or excellent. None of the thirty-six implants had been aligned in the neutral range. In sixteen knees, the alignment had a minor variation from the neutral range--that is, the knees were in minor malalignment. In general, these knees had the least severe fractures and the best over-all results. All had a good or excellent result except one, which was revised because of a loose patellar component. That knee was rated as fair at the latest follow-up. There was a major discrepancy in the alignment of twenty implants. These knees had more severe fractures and less satisfactory results than those in the other group. In two of these knees, the fracture was treated non-operatively; one had a good and the other, a poor result. Twelve of the remaining knees, which were treated surgically, were rated as fair or worse. Two knees that had revision of three components and restoration of alignment to the neutral range had an excellent result. The results of this study indicate that the alignment and fit of a component are important in determining the severity of a fracture of the patella after condylar total knee replacement and the long-term results after treatment of the fracture.

Adult↗

Picket-fence porphyrins as potential phototherapeutic agents.

The synthetic "picket fence" porphyrin, tetra(o-acetamidophenyl)porphine (TAc), as a biological photosensitizer has been evaluated both in vitro and in vivo in mitochondria from the R3230AC mammary tumor. Studies in vitro, consisting of incubation of mitochondria with TAc at a concentration of 4.0 micrograms/ml followed by photolysis, result in the inhibition of cytochrome c oxidase, proton translocating ATPase, succinate dehydrogenase, and malate dehydrogenase. The diminution in activity of the first three enzymes is approximately 2-fold greater than that seen with Photofrin II under the same conditions. Although TAc exists as four isolable atropisomers, no differences among these different forms were observed in their photosensitized inhibition of mitochondrial enzymes. Administration to tumor-bearing rats of TAc i.p. at a dose of 25 mg/kg did result in accumulation of porphyrin within the mitochondria of the R3230AC tumor as determined by subsequent irradiation of isolated mitochondria. The potential utility of TAc and related porphyrins in cancer phototherapy is discussed.

Animals↗

Long-term dosing studies using mutagenic carcinogens indicate a highly significant correlation between elevations in the level of rat glutathione S-transferase P messenger RNA and liver tumours of hepatocellular origin.

We have investigated levels of transcript homologous with glutathione S-transferase P (GST-P; GST 7-7) in tumours and hyperplastic lesions induced in the livers of rats by long-term gavage dosing with diethylnitrosamine (DEN) and 6-p-dimethylaminophenylazobenzothiazole (6BT). Detailed histopathological examination of the livers of the 90 animals used in this study at 6-8 months after initiation of daily dosing revealed that, of the 30 animals treated with carcinogen, 15 had developed tumours or hyperplastic lesions. Of these, 11 were areas of fibrosarcoma/fibrous hyperplasia. The remaining four were hepatocellular carcinomas. Northern blotting of total RNA purified from these tissues revealed the presence of transcripts of 3 and 0.75 kb. Evidence is presented to indicate that the former is a hitherto-undetected precursor of the 3-kbp rat GST-P gene, the latter representing the previously characterized mature GST-P transcript. Large elevations of the 0.75-kb transcript (30-35-fold) were encountered in all of the hepatocellular carcinomas, but in none of the other lesions, indicating a highly significant correlation (P = less than 0.001) between high elevations in levels of GST-P mRNA and liver tumours of hepatocellular origin. Minor elevations in transcript level (less than or equal to 5-fold) were encountered in several of the non-hepatocellular lesions. In regenerating livers, small increases in the level of the 3-kb transcript (approximately 3-fold) were routinely detected in total RNA from all partial hepatectomies, a concomitant decrease of approximately similar magnitude occurring in the 0.75-kb transcript, suggesting that minor elevations in levels of GST-P transcript, where encountered in non-hepatocellular lesions, are related to pre-neoplasia rather than to the proliferative rate of hyperplastic cells per se. The data extend previous observations, carried out largely using short-term regimes, to an analysis of transcripts homologous with GST-P in hyperplastic, pre-neoplastic and neoplastic lesions induced by long-term dosing with genotoxic carcinogens, and strongly lend support to the concept that high (30-fold) elevations in GST-P transcript correlate most strikingly with tumours of hepatocellular origin.

Animals↗

Four mating-type genes control sexual differentiation in the fission yeast.

The mating-type region of fission yeast consists of three components, mat1, mat2-P and mat3-M, each separated by 15 kb. Cell-type is determined by the alternate allele present at mat1, either P in an h+ or M in an h- cell. mat2-P and mat3-M serve as donors of information that is transposed to mat1 during a switch of mating type. We have determined the nucleotide sequence of each component of mat. The P and M specific regions are 1104 and 1128 bp, respectively, and bounded by sequences common to each mating-type cassette (H1; 59 bp and H2; 135 bp). A third sequence is present at mat2-P and mat3-M but absent at mat1 (H3; 57 bp), and may be involved in transcriptional repression of these cassettes. mat1-P and mat1-M each encode two genes (Pc; 118 amino acids, Pi; 159 amino acids, Mc; 181 amino acids and Mi; 42 amino acids). Introduction of opal or frame-shift mutations into the open-reading-frame of each gene revealed that Pc and Mc are necessary and sufficient for mating and confer an h+ or h- mating type respectively. All four genes are required for meiotic competence in an h+/h- diploid. The transcription of each mat gene is strongly influenced by nutritional conditions and full induction was observed only in nitrogen-free medium. The predicted product of the Pi gene contains a region of homology with the homeobox sequence, suggesting that this gene encodes a DNA binding protein that directly regulates the expression of other genes.

Amino Acid Sequence↗

Hepatitis B virus markers and persistent antigenemia in adolescents.

Adolescents attending a municipal outpatient adolescent clinic in New York City were evaluated for the prevalence of hepatitis B virus (HBV) markers and persistent antigenemia. Among 313 teenagers tested in 1 year, 11.8% were HBV marker positive, and 4.8% had persistent antigenemia. Hispanic teens had a marker rate of 6.4% and an antigenemia rate of 1.4%. Dominican Republic teens had a significantly higher marker rate than Puerto Rican teens. Among Hispanics, sexual activity status and foreign- vs. U.S.-born status were not significantly related to the presence of HBV markers. Asian teenagers had a 50% marker rate and a 27.2% rate for persistent antigenemia. Marker and antigenemia rates were highest in the most recent immigrants. Unexplained persistent hematuria occurred more frequently in patients with HBV markers than in patients without markers. We recommend routine hepatitis B surface antigen screening in Hispanic and Asian adolescents. The greatest at-risk groups are Asians, especially recent immigrants, immigrants from the Dominican Republic, and probably patients with unexplained persistent hematuria.

Adolescent↗

Case reports of individuals with oligospermia and methylene chloride exposures.

Between December 7, 1984 and June, 1986, 34 men with exposure to methylene chloride were evaluated at the Greater Cincinnati Occupational Health Center (GCOHC). Their primary complaint involved problems associated with central nervous system dysfunction. However, 8 of the 34 men complained of testicular, epididymal or lower abdominal pain (found on exam to be prostatic in origin) and had clinical histories consistent with infertility. Semen specimens from four volunteers were found to be in the subfertile or infertile range with regard to motility, morphology and sperm density.

Adult↗

A species comparison of acute hyperplasia induced by the peroxisome proliferator methylclofenapate: involvement of the binucleated hepatocyte.

The acute hyperplastic response induced by methylclofenapate (MCP) was studied in several rodent species with different responsiveness to the hypertrophic and hyperplastic effects caused by this chemical. The species, in descending order of responsiveness, were: mouse, rat, hamster and guinea-pig, the latter species being non-responsive. Animals were dosed at daily intervals with MCP (25, 12 or 5 mg/kg by gavage) and killed at intervals from 12 h to 240 h. The parameters of ploidy, nuclearity and DNA synthesis were examined in isolated hepatocytes. The hyperplastic response elicited by MCP in rodent livers as detected by the occurrence of S-phase cells, was almost exclusively confined to the 2 x 2N (binucleated) hepatocyte population. At the same time the proportion of 2 x 2N cells was reduced in a time and dose-dependent manner, while the fraction of 4N cells increased. These observations indicate that the 2 x 2N cells responding to MCP undergo S-phase followed by amitotic cytokinesis to form 4N cells. The response in rats, mice and hamsters was quantitatively different but qualitatively similar, while the guinea-pig was non-responsive. In a given responsive species the areas under the curves are similar for different doses, indicating that the size of the responsive population is limited. The data also indicate that although the response in the mouse was greater than in the rat, because the total number of responsive 2 x 2N cells is larger, the percentage of responsive 2 x 2N cells is higher in the rat than in the mouse. The ploidy analysis reveals that there is no detectable change in the ratio of (4N + 2 x 2N):2N hepatocytes, but only 1-2% change would be expected, despite the number of 4N cells produced, due to the increase in total cell number.

Animals↗