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Biomedical subjects

M A Kelly

Publications and source records attributed to M A Kelly.

At least 109 records · Page 6Linked to original sources
PubMed1989

The total condylar prosthesis. 10- to 12-year results of a cemented knee replacement.

Over a two-year period 104 patients had 130 knee arthroplasties performed with the total condylar prosthesis at the Hospital for Special Surgery. At a 10- to 12-year review 58 patients (74 knees) had survived and were available for detailed clinical and radiographic evaluation. Of these, 38 knees (51.3%) were rated as excellent and 27 (36.5%) good. There were three (4.0%) fair and six (8.2%) poor results. Five of the six had had revision operations. The success of this early pattern of prosthesis supports the continued use of methacrylate cement for knee arthroplasties.

Adult↗
PubMed1987

Purification and mechanistic properties of an extracellular alpha-L-arabinofuranosidase from Monilinia fructigena.

1. The alpha-L-arabinofuranosidase isoenzyme designated AFIII [Laborda, Archer, Fielding & Byrde (1974) J. Gen. Microbiol. 81, 151-163] was purified by sequential isoelectric focusing, hydrophobic chromatography, gel filtration and chromatofocusing. 2. The enzyme is a monomer of Mr 40,000. 3. On inactivation of the enzyme with 3H-labelled 1-alpha-L-arabinofuranosylmethyl-3-p-nitrophenyltriazene, 0.64 mol of alpha-L-arabinofuranosylmethyl residues/mol of enzyme is estimated to become attached to protein. 5. Neither first-order nor second-order rate constants for hydrolyses of aryl alpha-L-arabinofuranosides are dependent upon leaving-group acidity [beta lg(V) = -0.16 +/- 0.11; Beta lg(V/K) = -0.11 +/- 0.07; n = 7; delta pKa = 4.5] 6. Bond-breaking is nonetheless rate-limiting, as is shown by a value of 18(V) of 1.030 +/- 0.007 for the hydrolysis of p-nitrophenyl arabinoside. 7. Proton-donation to the leaving group is thus far advanced at the rate-limiting transition state for this enzyme. 8. Four alpha-L-arabinofuranosyl pyridinium salts are substrates, and an approximate beta lg(V) value of -0.9 can be estimated. 9. The absolute rate enhancement with the 4-bromoisoquinolinium salt, 2.5 X 10(9), is comparable with that observed with pyranosidases. 10. Ring-opening mechanisms can therefore be dismissed, even though they are known in the acid-catalysed hydrolysis of arabinofuranosides.

Arabinose↗
PubMed1987

Electroencephalographic activity after brain death.

Fifty-six consecutive patients clinically diagnosed as brain dead were seen at Loyola University Medical Center, Maywood, Ill, from January 1984 through May 1986. Eleven (19.6%) of the 56 patients had electroencephalographic (EEG) activity following the diagnosis of brain death. The mean duration of the observed EEG activity was 36.6 hours (range, two to 168 hours). Three patterns of EEG activity were observed: (1) low-voltage (4 to 20 microV) theta or beta activity was recorded in nine (16.1%) patients as long as 72 hours following brain death. Neuropathologic studies in one patient showed hypoxic-ischemic neuronal changes involving all cell layers of the cerebral cortex, basal ganglia, brain stem, and cerebellum; (2) sleep-like activity (a mixture of synchronous 30 to 40 microV theta and delta activity and 60 to 80 microV, 10 to 12 Hz spindle-like potentials) was noted in two (3.6%) patients for as long as 168 hours following brain death. Pathologic studies in both cases demonstrated ischemic necrosis of the brain stem with relative preservation of the cerebral cortex; and (3) alpha-like activity (monotonous, unreactive, anteriorly predominant, 25 to 40 microV, 9 to 12 Hz activity) was observed in one (1.8%) patient three hours following brain death. Regardless of activity on the EEG, none of the patients recovered. The occurrence of EEG activity following brain death would suggest reliance on the EEG to confirm brain death may be unwarranted. The use of the EEG as a confirmatory test of brain death may be of questionable value.

Brain↗
PubMed1987

Continuous passive motion after total knee arthroplasty.

Sixty-two patients undergoing primary total knee arthroplasty were studied prospectively. There were 42 patients in whom continuous passive motion (CPM) was used after surgery and 20 controls. The two groups were comparable with respect to age, diagnosis, sex, weight, and preoperative deformity and motion. The mean length of time required for CPM patients to achieve 90 degrees of flexion (9.1 days) was shorter than that for the control group (13.8 days). At the time of discharge from the hospital, however, there was no significant difference between the groups in amount of either flexion or extension. All patients had venograms performed after arthroplasty; the incidence of positive studies indicating thrombophlebitis was 45% in CPM patients and 75% in controls. These data demonstrate that CPM after knee arthroplasty enables patients to recover motion more quickly and affords some protection against deep vein thrombosis.

Adult↗
PubMed1987

Saturation analysis of cellular retinoid binding proteins: application to retinoic acid resistant human neuroblastoma cells and to human tumors.

A method for saturation analysis of cellular retinoic acid and retinol binding proteins, CRABP and CRBP, respectively, in cultured cells and human tumor samples, and its application to a retinoic acid resistant subline of the human neuroblastoma LA-N-5 cell line is described. Assessment of retinoid binding was accomplished by incubation of cytosols with increasing concentrations of [3H]retinoid (28-43 Ci/mmol; 1 Ci = 37 GBq) for 24 h. Bound retinoid was separated from free retinoid by adsorption with dextran-coated charcoal. Nonspecific binding was quantitated in parallel incubations which had been treated with p-chloromercuribenzene sulfonate (PCMBS), resulting in selective elimination of sulfhydryl-dependent ligand binding to both CRABP and CRBP. Quantitation was accomplished by Scatchard analysis of specific (PCMBS sensitive) binding. Employing this technique, specific retinoid binding was attributed to the presence of 2S macromolecules which displayed the known properties of CRABP and CRBP, namely ligand specificity, saturability, high ligand affinity, and PCMBS sensitivity. The apparent dissociation constants (Kd) for retinoic acid binding in cytosols prepared from murine 3T6 fibroblasts, rat testes, and a human ovarian tumor were 7, 11, and 35 nM, respectively. These preparations also bound retinol with high affinity, exhibiting Kds of 12, 26, and 48 nM, respectively. A retinoic acid resistant subline of LA-N-5 cells designated LA-N-5-R9 was established by long-term culture in the presence of 10(-6) M retinoic acid. This subline is resistant to the effects of retinoic acid in that it requires a 10-fold higher concentration of retinoic acid for 50% inhibition of growth than the parent line and displays no retinoic acid induced morphologic differentiation. Saturation analysis of CRABP in the parent and resistant subline reveal no significant alteration in either CRABP content or affinity. These results indicate that resistance to retinoic acid induced differentiation in LA-N-5-R9 occurs distal to CRABP binding or that CRABP does not mediate this response to retinoic acid.

4-Chloromercuribenzenesulfonate↗
PubMed1987

cis-Retinoic acid stimulates the clonal growth of some myeloid leukemia cells in vitro.

We studied the effects of cis-retinoic acid (cisRA) on the clonogenic growth of samples of leukemic cells from 35 patients with acute nonlymphocytic leukemia (ANLL). We observed significant inhibition of leukemic colony growth in 17 samples by 10(-7) to 10(-6)M cisRA. However, we found that retinoid exposure resulted in striking stimulation of clonal growth in ten samples at the same drug concentrations. With the exception of cases with promyelocytic features, there was no morphologic or functional evidence that cisRA induced the leukemic blasts to differentiate. Both inhibition and stimulation were dose-dependent and observable at pharmacologically achievable levels of cisRA. Leukemic cells with monocytic features more frequently demonstrated a stimulatory response than did those without monocytic features. Depletion of T lymphocytes and monocytes did not alter the type of growth response. Assays for cellular retinoic acid-binding protein (CRABP) were performed on five samples (two with inhibitory growth responses, two with stimulatory responses, and one with no growth) and failed to reveal detectable levels of CRABP in any case. The addition of cisRA to liquid suspensions of leukemic cells produced no significant change in the number of viable cells. We conclude that the effects of cisRA on leukemic colony growth are not cytotoxic and not mediated by T lymphocytes, monocytes, or CRABP. More importantly, cisRA appears to enhance the growth of certain human leukemia cells in vitro. Taking into account the increasing use of retinoids in clinical trials for patients with leukemia, the latter findings may represent a significant cautionary note.

Bone Marrow↗
PubMed1987

Postpatellectomy extensive ossification of patellar tendon. A case report.

Ossification in the quadriceps mechanism after total patellectomy is a common finding. The relationship of knee symptoms and the extent of postpatellectomy ossifications is debatable. Reported is the case of a 74-year-old woman with extensive ossification in the patellar tendon following patellectomy and knee arthroplasty. The ossification was associated with only minimal discomfort. Functional results following patellectomy were not affected in patients previously observed by the authors.

Aged↗
PubMed1986

1,25-Dihydroxyvitamin D3 receptors: altered functional domains are associated with cellular resistance to vitamin D3.

1,25-Dihydroxyvitamin D3 receptors are cytosoluble proteins detectable in a variety of tissues responsive to 1,25(OH)2D3. They are DNA binding-proteins analogous to other steroid receptors and it is this functional property which is likely involved in the activation of hormone-sensitive genes. Utilizing 1,25(OH)2D3 and DNA binding assays, as well as anti-receptor monoclonal antibodies, we have probed the relationship between the 1,25(OH)2D3 receptor binding domains after selective cleavage with trypsin. These studies reveal that the hormone and DNA binding regions are separable, and are consistent with the finding that tissue resistance to 1,25(OH)2D3 is a result of structural defects in these domains. Recently, a primate model, the LLC-MK2 monkey kidney line, has been uncovered which may exemplify a hormone-binding defect. Here, 25-hydroxyvitamin D3-24-hydroxylase induction, a 1,25(OH)2D3 bioresponse, requires 100-fold higher concentrations of the hormone for maximal response. Concomitantly, this cell contains a variant receptor form which displays a correspondingly lowered apparent affinity for the hormone despite its seemingly normal DNA binding characteristics. Taken together, these studies suggest that the 1,25(OH)2D3 receptor is a macromolecule with multiple domains each of which may produce modified cellular resistance to 1,25(OH)2D3 if structurally altered.

Animals↗
PubMed1986

Patellectomy.

Patellectomy has been controversial for many years. The divergence of clinical and experimental data in the literature makes it difficult to draw definitive conclusions regarding the success of the procedure. This article reviews the available literature and compares the results of patellectomies in young and old patients at The Hospital for Special Surgery.

Arthritis↗
PubMed1985

A variant form of the 1,25-dihydroxyvitamin D3 receptor with low apparent hormone affinity in cultured monkey kidney cells (LLC-MK2). A model for tissue resistance to vitamin D.

Chandler et al. (Chandler, J.S., Chandler, S.K., Pike, J.W., and Haussler, M.R. (1984) J. Biol. Chem. 259, 2214-2222) previously demonstrated that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) caused the induction of 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) in a rhesus monkey kidney cell line (LLC-MK2) apparently deficient in the high affinity 1,25-(OH)2D3 receptor. We have re-examined this phenomenon and report here that 24-hydroxylase induction is mediated by a receptor variant in LLC-MK2 cells with low hormone affinity. Dose response analysis showed that in contrast to LLC-PK1 (a typical receptor-positive cell line), the LLC-MK2 line was less sensitive to 1,25-(OH)2D3 by 2 orders of magnitude. Employing optimal concentrations of 1,25-(OH)2D3 for 24-hydroxylase induction in each cell type, the early time courses of this bioresponse were identical in LLC-MK2 and LLC-PK1 and were consistent with a nuclear action of hormone-receptor complexes. Moreover, the rank order of potency of vitamin D3 congeners as inducers of 24-hydroxylase activity in LLC-MK2 cells agreed well with their relative affinity for the 1,25-(OH)2D3 receptor. An examination of 1,25-(OH)2D3 receptor content via DNA-cellulose chromatography in LLC-MK2 cells incubated at ligand concentrations 10-25-fold higher than the normal 2 nM revealed a minimum of 1600 receptor-like molecules/LLC-MK2 cell. These results show that LLC-MK2 cells possess a variant receptor form with apparent low affinity for 1,25-(OH)2D3. This system should serve as a model for clinical syndromes characterized by the requirement for massive doses of vitamin D to prevent rickets.

24,25-Dihydroxyvitamin D 3↗
PubMed1984

Identification and quantitation of intracellular retinol and retinoic acid binding proteins in cultured cells.

Although the mechanism whereby vitamin A mediates normal cell differentiation and inhibits tumor cell proliferation is unknown, intracellular receptor-like proteins for retinol and retinoic acid have been implicated in the molecular action of vitamin A. We have assayed these two binding proteins, cellular retinol binding protein (protein R) and cellular retinoic acid binding protein (protein RA), in the cytosolic fraction of various normal and tumor cells via sucrose density gradient centrifugation and saturation analysis. Employing charcoal separation of bound and free tritiated retinoid, the saturation analysis yields an approximate Kd for ligand binding and an estimate of the number of protein R and protein RA molecules per cell. Unique protein R and protein RA macromolecules sedimenting at 2 S with Kd values of 7-42 nM are detected in murine cells (1 degree epidermal, 3T6 fibroblasts and melanoma) and human neuroblastoma cells. Concentrations of the intracellular binding proteins range from 55 000 to 3 000 000 copies per cell. When one cell line (C-127 mouse mammary) is transformed by bovine papilloma virus, protein RA levels increase from undetectable to 193 000 copies per cell. Assessment of growth inhibition by 10(-6) M retinol or retinoic acid in the culture medium reveals that there exists a partial, but not absolute, correlation between the presence of protein R or protein RA and the antiproliferative effect of the particular retinoid in the tested cell lines. We conclude that the 2 S intracellular binding proteins for the retinoids are present in most vitamin A responsive cells, but may not be essential for biologic actions of the vitamin such as growth inhibition in monolayer culture.

Animals↗
PubMed1984

Fatal neurologic complication of parenteral feeding through a central vein catheter.

A 9-month-old male infant, born at 32 weeks' gestation, had neonatal necrotizing enterocolitis and required long-term parenteral nutrition. At 9 months of age, a central venous catheter was inserted through the left saphenous vein into the inferior vena cava, and the infant died nine days later. Shortly before death, a lumbar puncture yielded milky fluid with an extremely high glucose and protein content. A postmortem barium injection through the central catheter demonstrated free barium in the retroperitoneal cavity and epidural space, and autopsy findings confirmed that the catheter had entered an ascending lumbar vein with a large retroperitoneal abscess. This case emphasized the need to confirm central venous catheter position at the time of insertion and pointed out yet another risk of parenteral alimentation.

Abscess↗
PubMed1984

Retinoic acid-induced changes in epidermal growth factor binding and in biological responses mediated by phorbol ester tumor promoter.

We investigated the ability of retinoic acid (RA) to alter the binding of epidermal growth factor (EGF) to Rat-1 and Swiss mouse 3T3 cells, the EGF-related induction of ornithine decarboxylase (ODC) activity and DNA synthesis. Pretreatment of 3T3 cells with 10(-10)--10(-5) M RA produced a dose-dependent increase in EGF binding. The increased EGF binding appeared to result from an increased number of EGF receptors and did not occur in Rat-1 cells which, unlike 3T3 cells, possessed measureable amounts of cellular retinoic acid binding protein (CRABP). Both cell lines responded to RA pretreatment with an increase in EGF- and TPA-induced ODC activity, without a concomitant increase in DNA synthesis in either cell line. We suggest that the increase in EGF binding induced by RA in 3T3 cells is apparently unrelated to alterations in EGF-induced biological responses and to the presence of CRABP.

Animals↗
PubMed1984

Nasotracheal intubation in the neonate: physiologic responses and effects of atropine and pancuronium.

Thirty infants with birth weights from 580 to 3450 gm (25 to 40 weeks gestation) were prospectively studied during nasotracheal intubation. The infants were randomized to receive atropine 0.01 mg/kg, atropine 0.01 mg/kg plus pancuronium 0.1 mg/kg, or no medication (controls) prior to intubation. There was a significant decrease in transcutaneous PO2 (27.3 torr, P less than 0.02), associated with significant increases in mean arterial blood pressure (57%, P less than 0.01) and intracranial pressure (mean increase 18.9 cm H2O, P less than 0.01) with intubation in all three groups of infants. Only in control infants and infants receiving atropine was there significant decrease in heart rate (52.2 and 36.2 bpm, respectively, P less than 0.01) during intubation. Control infants experienced a significantly greater decrease in heart rate and demonstrated the lowest mean heart rate, compared with the other two groups. Pancuronium plus atropine was associated with lesser increases in intracranial pressure and with the least changes in heart rate in response to intubation. There was no significant difference between the groups for changes in systemic blood pressure or transcutaneous PO2. Further studies are required to determine the clinical consequences, if any, of these responses, and the use of pretreatment in the neonate requiring intubation.

Apnea↗