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Biomedical subjects

M M Kelly

Publications and source records attributed to M M Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1996

Autonomic control of heart rate after brain injury in children.

OBJECTIVES: To study sequential changes in heart rate, respiratory rate, blood pressure, heart rate power spectra, and plasma catecholamine concentrations in patients with acute brain injury and correlate these variables with the severity of neurologic dysfunction and patient outcome. DESIGN: Prospective, clinical study. SETTING: Pediatric intensive care unit. PATIENTS: Thirty-seven pediatric patients with acute brain injury caused by trauma, anoxia/ischemia, hemorrhage, or infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We found significant associations between low-frequency (0.01 to 0.15 Hz) heart rate power and severity of neurologic dysfunction (as assessed by the admission Glasgow Coma Scale) (p < .001) and patient outcome (as assessed by the Glasgow Outcome Scale) (p = .05). The admission (p = .05) and maximum (p < .001) values for low-frequency heart rate power and the minimum value for high-frequency (0.15 to 0.50 Hz) heart rate power obtained during hospitalization (p = .001) predicted an increased likelihood of survival. Ten brain-dead patients had significantly decreased low-frequency heart rate power (p = .008) and plasma norepinephrine (p = .015), epinephrine (p = .03), and dopamine (p = .04) concentrations when compared with six non-brain-dead patients with a Glasgow Coma Scale score of 3. CONCLUSIONS: Our results imply that autonomic nervous system control of heart rate is disrupted in proportion to the degree of neurologic insult in children after acute brain injury. Thus, heart rate power spectral analysis and plasma catecholamine concentrations may prove to be useful adjuncts in determining severity of neurologic injury and prognosis for recovery in children suffering from brain injury. In addition, these techniques may aid in the determination of brain death.

Adolescent↗
PubMed1996

Improved bacterial expression of the human P form phenolsulfotransferase. Applications to drug metabolism.

Bacterial expression of human phenol phenolsulfotransferase (P-PST) has provided the opportunity to understand better the catalytic properties and biological role of this enzyme. However, as the yield of pure protein from the currently used expression system was low, we subcloned the P-PST c-DNA into pET-15b, a vector containing an oligohistidine domain, for improved expression. The fusion protein, His-P-PST, was isolated from the bacterial cytosol in a single affinity chromatography step, using a Ni2+ agarose column. The yield of His-P-PST from the pET-15b vector was improved 12-fold, compared with P-PST from the original vector. The purity was > 99%, as established by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and densitometry scanning. The enzyme was stable for at least 3 weeks when stored in 20% glycerol at -80 degrees C. A very rapid deterioration of the enzyme during 37 degrees C incubations was effectively prevented by the addition of bovine serum albumin. The sulfonation of several substrates was very similar for His-P-PST and P-PST, with Vmax/KM values (first order rate constants) for the high-affinity substrate p-nitrophenol of 143 +/- 27 and 120 +/- 25 ml min-1 microgram-1 PST [mean +/- SE; not significant (NS)], respectively, and for the low-affinity substrate acetaminophen of 0.21 +/- 0.11 and 0.14 +/- 0.07 ml min-1 microgram-1 PST (NS). The Vmax/KM for the sulfonation of the isoproterenol enantiomers showed a (+)/(-)-enantiomer ratio of 6.2 for His-P-PST and 7.4 for P-PST. Interestingly, 3- to 10-fold higher apparent KM values were obtained for these substrates with the crude human liver cytosol, compared with the recombinant P-PSTs, suggested to be due to endogenous or dietary P-PST inhibitors in the liver. In addition, the inhibition of acetaminophen sulfonation by quercetin was very similar for His-P-PST and P-PST, with IC50 values of 0.10 +/- 0.03 and 0.05 +/- 0.01 microM (NS), respectively. The additional amino acid residues in the His-P-PST, compared with the recombinant P-PST, thus did not significantly alter the catalytic properties. This bacterial expression system should lend itself to routine use in studies of the metabolism of drugs and environmental chemicals.

Arylsulfotransferase↗
PubMed1995

Molecular characterization of EAP-300: a high molecular weight, embryonic polypeptide containing an amino acid repeat comprised of multiple leucine-zipper motifs.

In this study we report the biochemical and initial molecular characterization of EAP-300, a developmentally regulated embryonal protein that has been shown previously to be expressed by radial glia in various regions of the CNS, including putative glial barriers. In the present study we have shown that the 300 kDa EAP-300 polypeptide is developmentally regulated in all tissues expressing the protein, which include various PNS and CNS tissues and muscle. In neural tissue the protein is readily detected during early embryogenesis, subsequently down-regulated at later stages, and is not detected in the adult. In contrast to neural tissue, small amounts of the protein are expressed in heart, consistent with earlier studies which showed that EAP-300 expression was maintained in the Purkinje cells of the heart conduction system. Metabolic labeling demonstrates that EAP-300 is a phosphoprotein, and is fatty acylated based on incorporation of [3H]palmitate. We also show that the normal developmental down-regulation of EAP-300 by glia does not occur in vitro, and these data therefore suggest that the signal(s) that regulates EAP-300 gene expression during development in vivo is absent in dissociated cell cultures. We have also initiated molecular studies of EAP-300 by screening embryonic brain cDNA expression libraries with a mixture of EAP-300 monoclonal antibodies. Sequence analysis of partial EAP-300 cDNAs indicate that the protein is related, if not identical, to IFAPa-400, a developmentally regulated intermediate filament-associated protein in chick that is proposed to participate in cell differentiation. These studies also indicate that EAP-300 mRNA is developmentally regulated and is expressed by glial cells in putative CNS barrier structures. Our studies also suggest that two pools of EAP-300 may exist in cells, implying that unlike IFAPa-400 the EAP-300 protein may not always be associated with intermediate filaments. Interestingly, our studies demonstrate that EAP-300 contains a novel repeat amino acid domain comprised of multiple leucine-zipper motifs, which may contribute to its function during glial differentiation.

Amino Acid Sequence↗
PubMed1993

Autonomic cardiovascular state after severe brain injury and brain death in children.

OBJECTIVE: To study and compare the autonomic cardiovascular state of children after severe brain injury and brain death. DESIGN: Prospective clinical study. SETTING: Pediatric ICU. PATIENTS: Pediatric patients suffering severe brain injury caused by trauma, anoxia, or hemorrhage. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We analyzed cardiorespiratory parameters, heart rate power spectra, plasma catecholamine concentrations, and the response to the cold pressor test in nine brain-dead patients and compared the results with the test findings of 11 patients with severe brain injury. Low-frequency total heart rate power (p < .03), peak amplitude (p < .02), and plasma catecholamine concentrations (p < .001) were different with no overlap of values between groups. Cold pressor testing in patients with severe brain injury showed changes in respiratory rate and low-frequency heart rate power that were +/- 20% to 100% from baseline values; however, there were no measurable changes in brain-dead patients. CONCLUSIONS: Our results support the concept of a damaged sympathetic cardiovascular system in severe brain injury and complete interruption of the autonomic cardiovascular pathways in brain death. Since determination of brain death may be difficult, our findings have implications for corroborating brain death using autonomic cardiovascular testing.

Brain Death↗
PubMed1993

Inflicted versus accidental head injury in critically injured children.

OBJECTIVES: To assess the frequency of inflicted head injury in critically injured children; the severity of neurologic injury; the neurologic outcome; and the historical, socioeconomic, physical, and radiologic factors associated with inflicted head injury. DESIGN: Prospective clinical study. SETTING: Multidisciplinary pediatric intensive care unit (ICU). PATIENTS: Consecutive cases (n = 40) of severe head injury admitted to a pediatric ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fourteen (35%) of 40 cases of head injury were due to inflicted head injury. Eleven (79%) of 14 inflicted head injury cases were due to child abuse and three (21%) were due to neglect. The severity of neurologic injury, as measured by the admission Glasgow Coma Scale, was worse in cases of inflicted head injury (7.1 +/- 0.7 [SE] [inflicted] vs. 9.9 +/- 0.8 [accidental]; p = .04). Glasgow Outcome Scores were worse after inflicted head injury (2 +/- 1 inflicted] vs. 4 +/- 1 [accidental]; p = .004). In victims of child abuse, we found the combination of any two of the following three factors was associated with inflicted head injury: an inconsistent history/physical examination; retinal hemorrhages; or parental risk factors (alcohol or drug abuse, previous social service intervention within the family, or a past history of child abuse or neglect). CONCLUSIONS: This study confirms that severity of neurologic injury and neurologic outcome in cases of inflicted head injury are worse than in any other type of childhood head injury. We believe that a combination of any two of the above three risk factors may prove to be a reliable marker of inflicted head injury in children admitted to a pediatric ICU and will lead to an early and definitive diagnosis.

Accidents↗
PubMed1992

The catecholamine response to multisystem trauma.

We studied the catecholamine response in two groups of patients with multisystem injuries according to the presence (group 1, N = 124) or absence (group 2, N = 82) of head injury. Markers of injury severity included the injury Severity Score, the Glasgow Coma Scale, the need for intubation, admission hypotension, the amount of blood products and fluid expanders administered during the first 24 hours, and patient outcome. In group 1, higher norepinephrine levels always and epinephrine concentrations usually were associated with worsening indexes of injury severity. The best correlations were between the Injury Severity Score and the Glasgow Coma Scale and norepinephrine concentrations. In group 2, despite elevated catecholamine levels, such associations were seldom present. Thus, circulating catecholamine levels, especially norepinephrine levels, significantly correlated with the severity of injury in patients who had suffered multisystem injury, but only if the injury included the brain.

Adolescent↗
PubMed1991

Integration of cognitive and behavioral treatment strategies in a group family-oriented partial hospitalization program for adolescents, children, and their families.

This article describes a partial hospitalization program for seriously emotionally disturbed children and adolescents in a public mental health setting. The article focuses on the integration of cognitive and behavioral treatment strategies in a group and family therapy based program. The literature on recent advances in the application of cognitive techniques in treating child and adolescent behavior problems is briefly reviewed. Specific cognitive and behavioral interventions that have proven useful with typical behavior problems in a partial hospitalization setting are outlined.

Adolescent↗
PubMed1983

Jejunal diverticulosis. A heterogenous disorder caused by a variety of abnormalities of smooth muscle or myenteric plexus.

We analyzed the clinical, radiographic, esophageal manometric, and pathological features of 10 patients referred with jejunal diverticulosis. Nine patients were over age 59 yr and had symptoms of intestinal pseudoobstruction of 5-43 yr duration. Seven had surgery for mechanical obstruction, although none was found. Eight had diarrhea, steatorrhea, and weight loss. Five had Raynaud's phenomenon and heartburn, and 2 had dysphagia. At radiography, 9 had jejunal diverticula with or without duodenal or ileal diverticula, or both. Two each had abnormal structure or motility of the esophagus or stomach. At manometry, 3 of 7 had a nonspecific motor abnormality, and 1 other had low amplitude peristaltic waves. Light microscopy of small intestinal tissue in 7 patients showed that 4 had fibrosis and decreased numbers of normal-appearing muscle cells, findings consistent with progressive systemic sclerosis. Two others had fibrosis associated with degenerated smooth muscle cells, findings consistent with a visceral myopathy. The seventh patient had neuronal and axonal degeneration and neuronal intranuclear inclusions, findings consistent with a visceral neuropathy. We conclude that (a) intestinal pseudoobstruction is a major clinical manifestation of jejunal diverticulosis, (b) jejunal diverticulosis is a heterogenous disorder associated with at least three abnormalities of the smooth muscle or myenteric plexus, (c) in contrast to intestinal pseudoobstruction without diverticulosis, the esophagus, stomach, and colon are less frequently involved in jejunal diverticulosis, and (d) some patients with jejunal diverticulosis probably have clinically inapparent progressive systemic sclerosis.

Adult↗
PubMed1982

Nucleotide sequences from the adenovirus-2 genome.

The sequence of 15,441 nucleotides from the adenovirus-2 genome has been determined and includes the regions between coordinates 0-32% and 89-100%. These regions contain the early (E) transcription units E1A, E1B, E2B, and E4, the genes for polypeptides IVa2 and IX, the COOH terminus of fiber polypeptide, as well as the two virus-associated RNAs and the leader sequences for the major late mRNAs. Analysis of tryptic peptides from the terminal protein and its precursor (Smart, J. E., and Stillman, B. W. (1982) J. Biol. Chem. 257, 13499-13506) has allowed the gene for the precursor terminal protein to be positioned between coordinates 28.0 and 23.5 on the 1-strand. A minimum Mr = 74,500 is predicted. A second, longer open reading frame is also found on the 1-strand between coordinates 22.9 and 14.2 and predicts a polypeptide of at least Mr = 120,000. Many open reading frames longer than 10,000 exist within this sequence although less than half of them can be assigned to previously characterized polypeptides. As with other viral genomes, the available coding information is highly compressed. Intergenic distances are very short and examples are found of genes which overlap either on the same strand or the complementary strand.

Adenoviruses, Human↗
PubMed1982

Pathogenic mechanisms of heterotopic neural tissue associated with anencephaly.

Central nervous tissue was found in both the lung and the abdominal surface of the diaphragm in an anencephalic baby with gastroschisis. These findings support the hypothesis that the heterotopic neural tissue in anencephalic babies is due to transamniotic implantation. It thus appears that the pathogenic mechanism of the heterotopic neural tissue in the lung is aspiration.

Anencephaly↗
PubMed1975

Inhibition of xenogeneic cell-mediated cytotoxicity in the rat by antiglobulin sera.

Differences can be demonstrated between the lysis of xenogeneic target cells by lymphocytes of injected rats, which is inhibited by antiglobulin serum, and the lysis of antibody-coated xenogeneic target cells by normal rat lymphoid cells, which is much less readily inhibited. This difference is demonstrated by the dilution of antiglobulin which is effective, and by the fact that inhibition of lysis produced by allergic lymphocytes can be shown if the lymphocytes are treated with antiglobulin and then washed. Differences can also be shown in the time course of inhibition, since to be effective antiglobulin must be present at the time of mixing normal lymphocytes and antibody-coated target cells, whereas addition of antiglobulin to allergized lymphocytes 4 h ater mixing with target cells still produces significant inhibition. These results are compatible with the hypothesis that allergic lymphocytes have immunoglobulin on their surfaces and kill by a different mechanism from the lymphoid cells which lyse antibody-coated target cells.

Agglutination Tests↗