PubMed Health⌕ Search

Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 127 records · Page 7Linked to original sources
PubMed1994

Crystallization of biosynthetic arginine decarboxylase from Escherichia coli.

Putrescine is the immediate precursor for the synthesis of polyamines and is normally generated by the action of ornithine decarboxylase. However, putrescine can also be produced by the conversion of arginine to agmatine by arginine decarboxylase (bADC) followed by the release of urea by agmatine ureohydrolase. Amino-acid sequence homology with the eukaryotic ornithine decarboxylases suggests that bADC may be a model for this group of decarboxylases. We report here the crystallization of arginine decarboxylase from E. coli. Crystals up to 1 mm in size are grown by vapor equilibration using Li(2)SO(4) and polyethylene glycols as precipitants. The crystals exhibit diffraction maxima beyond 3 A resolution and belong to space group P4(1(3))2(1)2 with a = 192.4 and c = 121.0 A. These unit-cell dimensions together with the estimated density of the crystals suggest the presence of one tetramer of bADC (71 kDa subunit(-1)) per asymmetric unit (V(m) = 2.0 A(3) Da(-1)).

Journal Article↗
PubMed1994

Repeated treatment with chimeric anti-CD4 antibody in multiple sclerosis.

We treated 21 multiple sclerosis patients with two to four doses of cM-T412, a chimeric monoclonal antibody against the CD4 antigen found on helper/inducer T lymphocytes. The mean number (+/- standard error) of circulating CD4 lymphocytes decreased from 888 (+/- 81) cells/mm3 at baseline to 246 (+/- 18) after treatment. At 1 year after the last treatment, the CD4 count had recovered to only 335 (+/- 32). The antibody had no effect on CD8 lymphocytes, B lymphocytes, or other leukocytes. Side effects were minimal. Despite the prolonged depletion of CD4 lymphocytes, no opportunistic infections occurred. Only 1 patient had a possible allergic reaction. Most patients were clinically stable, but a few progressed. We conclude that repeated treatment with cM-T412 is effective in reducing the number of circulating CD4 lymphocytes and has no limiting side effects.

Adult↗
PubMed1994

Emergence neophobia correlates with hippocampal and cortical glutamate receptor binding in rats.

Previous work from our laboratory indicated that emergence neophobia is highly correlated with perforant path long-term potentiation (LTP) in rats. In the present study, we examined the relationship between hippocampal and cortical alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors and emergence behavior in rats. Emergence neophobia was assessed in an exploratory task that provided a choice between a novel alley and a familiar nest box. Quantitative autoradiography using radiolabeled ligands specific for the AMPA subclass of glutamate receptors was performed on frozen brain sections. Both [3H]AMPA and [3H]CNQX (6-cyano-7-nitro-[3H]quinoxaline- 2,3-dione, an AMPA receptor antagonist) binding in the dentate gyrus (stratum moleculare), hippocampal area CA1 (stratum radiatum), and the parietal cortex overlying the hippocampus were significantly correlated with emergence behavior. The correlations indicated that neophobic rats, which had longer latencies to enter the novel alley, made fewer entries into the alley, and spent less time in the novel alley during a 10-min test than their neophilic counterparts, had higher levels of AMPA receptor binding. These results suggest that individual differences in specific hippocampal AMPA receptors reflect variability in a specific class of hippocampal-dependent behaviors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Optimal therapy for stress gastritis.

OBJECTIVE: The authors compared the results of sucralfate versus H2 blocker +/- antacid as prophylaxis for stress ulceration in an intensive care unit patient population. SUMMARY BACKGROUND DATA: Stress ulceration carries high morbidity and mortality for the patient who is critically ill. Gastric acid neutralization is an effective prophylaxis. The impact of increased gastric colonization with bacterial pathogens on nosocomial pneumonia after acid neutralization is unclear. The efficacy of sucralfate prophylaxis for stress ulceration and its the effect on the nosocomial pneumonia rate is controversial. The financial implications of sucralfate prophylaxis versus H2 blocker-based acid neutralization therapy has not been studied. METHODS: Ninety-eight injured patients who were critically ill and who required intubation and intensive care unit (ICU) support for at least 72 hours without gastric feeding were randomized and received either maximal H2 blocker infusion therapy (continuous infusion of ranitidine at 0.25 mg/kg/hr after a loading dose of 0.5 mg/kg) plus antacids (for persistent pH < 4) or sucralfate (1 g every 6 hours via nasogastric tube) for stress ulcer prophylaxis. Efficacy in preventing stress ulcer complications was determined. The impact of each therapeutic approach on development of nosocomial pneumonia was evaluated. The charges/cost for each approach was analyzed. RESULTS: Heme-positive gastric aspirates occurred in 99% of the patients, whereas 12 (7 in the H2 blocker group and 5 in the sucralfate group) were grossly positive for blood. However, only one from each group required transfusion, and one in the H2 blocker group required operation. Gastric colonization preceded tracheobronchial colonization in five patients in the H2 blocker group and one patient in the sucralfate group; simultaneous gastric/oropharyngeal colonization preceded positive tracheobronchial growth in six patients who received H2 blocker and one patient who received sucralfate. The overall pneumonia rate was 27.5% in the H2 blocker group and 20.8% in the sucralfate group (p = 0.48). Days on ventilator were 13.5 versus 9.1, (p = 0.06), ICU lengths of stay were 14.7 versus 10.2 (p = 0.06), and hospital lengths of stay were 27.8 versus 20.0 (p = 0.029) for the H2 blocker group and sucralfate group, respectively. Based on current charges and protocols for optimal H2 blocker and sucralfate prophylaxis, use of sucralfate rather than H2 blockers would decrease the annual cost by more than $30,000 per bed. CONCLUSIONS: Sucralfate is as efficacious as maximal H2 blocker therapy for stress ulceration prophylaxis, and may have a beneficial effect on the incidence of nosocomial pneumonia. Sucralfate has a major reduction on nursing requirements for stress ulcer prophylaxis and would save approximately $30,000 per ICU bed per year in patient charges.

Adult↗
PubMed1994

Typical and atypical NK1 tachykinin receptor characteristics in the rabbit isolated iris sphincter.

1. A contraction of the rabbit isolated iris sphincter smooth muscle follows activation of either tachykinin NK1 or NK3 receptors. We have here characterized the pharmacological activity profiles of various tachykinin receptor agonists considered to have NK1-receptor-preferring activity in this preparation. 2. Two groups of NK1-receptor-preferring agonists could be distinguished in terms of a common pharmacological profile. The first group (Group 1) included [Glp6,L-Pro9]-SP(6-11) (septide), [Glp6]-SP (6-11), substance P methyl ester, delta-aminovaleryl-[L-Pro9, N-MeLeu10]-SP(7-11) (GR73632), and [Apa9-10]-SP. The second group (Group 2) included [Pro9]-SP, substance P, physalaemin and ranamargarin. 3. Under control conditions, the responses to Group 1 agonists were relatively fast in offset (time for reversal of maximal responses, 11.2-18.2 min), and were antagonized by NK1-receptor-selective antagonists (range of pKB estimates vs various agonists; GR82334, 7.1-8.2; (+/-)-CP-96,345, 8.9-9.5; RP67580, 7.0-7.4). Following incubation of the tissue with phenoxybenzamine (20 microM, 10 min), the affinity of GR82334, tested against the Group 1 agonists, substance P methyl ester and septide, was not significantly different (P < 0.05; n = 7-18) to that determined in untreated tissues (substance P methyl ester pKB 7.5 +/- 0.1 and 7.2 +/- 0.2, respectively; septide 7.7 +/- 0.2 and 7.9 +/- 0.2, respectively). Further, response offset times (5.0-8.5 min) were little reduced as compared to those observed in untreated tissues. 4. Under control conditions, the response to Group 2 agonists was markedly slow in offset (times for reversal of maximal responses, 51.4-70.4min), and was not attenuated significantly by the NK1-receptor-selective antagonists GR82334 (I MicroM), (+/-)-CP-96,345 (0.1 MicroM) or RP67580 (1 MicroM). In contrast,after phenoxybenzamine pretreatment, responses to Group 2 agonists reversed rapidly (times for reversal of maximal responses, 13.1-24.2 min), and were now antagonized by GR82334 (pKB estimates, 6.4-7.1).5. The responses to the NK3-receptor-selective agonist Succ-[Asp6,Me-Phe8]-SP(6-l1) (senktide) were relatively fast in offset (time for reversal of maximal response was 18.6 +/- 1.7 min) and were not inhibited by GR82334 (10 MicroM; n = 5). The contractile response resulting from co-application of the Group 1 agonist, septide together with senktide, did not exhibit prolonged response offset kinetics.6. Assuming simple competition at equilibrium, these data from the rabbit iris smooth muscle could be explained either by interaction of the various ligands with two separately-existing NK1 receptor-subtypes or -isoforms; or alternatively by a preferential interaction of the two agonist groups with different binding domains on a common NK1 receptor.

Animals↗
PubMed1994

Distributional patterns of multiple sclerosis brain lesions. Magnetic resonance imaging--clinical correlation.

Forty-one patients with multiple sclerosis were studied with magnetic resonance imaging (MRI) and a battery of neuropsychological tests to determine the pattern of lobar distribution of lesions in the relapsing-progressive and relapsing-remitting forms of the disease. Correlation of lesions with the patient's cognitive and emotional dysfunction was also obtained. The results of this study indicate that patients with relapsing-progressive multiple sclerosis are characterized by the large or coalescent lesions located predominantly in the periventricular area. These lesions were more frequently found in the parietooccipital areas and were accompanied by significant cognitive dysfunction and severe personality changes. The patients with relapsing-remitting disease, however, were characterized by punctiform or small discrete lesions predominantly located in the intermediate and subcortical areas. These lesions were more frequently seen in the parietooccipital regions and the patients had significantly less severe cognitive and emotional involvement than did the patients with relapsing-progressive disease. Recognition of these patterns was easily accomplished by MRI. In this investigation MRI studies were utilized as an index of the pathological changes occurring at one point in time in the evaluation of the disease. Only repeated MRI studies and continuous clinical observation can establish the final diagnosis.

Adult↗
PubMed1994

Serological cross-reaction between Legionella spp. and Capnocytophaga ochracea by using latex agglutination test.

Cross-reactivity between Legionella spp. and Capnocytophaga ochracea was noted by latex agglutination tests (Serobact Legionella; Disposable Products, Adelaide, Australia). Four of 11 (36%) C. ochracea isolates agglutinated with latex reagents designed to identify Legionella pneumophila serogroups. C. ochracea isolated on buffered charcoal yeast extract media may give false-positive results in this Legionella latex agglutination assay.

Capnocytophaga↗
PubMed1994

Blood and brain temperatures of free-ranging black wildebeest in their natural environment.

Using miniature data loggers, we measured the temperatures of carotid blood and brain in four wildebeest (Connochaetes gnou) every 2 min for 3 wk and every 5 min, in two of the animals, for a further 6 wk. The animals ranged freely in their natural habitat, in which there was no shelter. They were subject to intense radiant heat (maximum approximately 1,000 W/m2) during the day. Arterial blood temperature showed a circadian rhythm with low amplitude (< 1 degree C) and peaked in early evening. Brain temperature was usually within 0.2 degrees C of arterial blood temperature. Above a threshold between 38.8 and 39.2 degrees C, brain temperature tended to plateau so that the animals exhibited selective brain cooling. However, selective brain cooling sometimes was absent even when blood temperature was high and present when it was low. During helicopter chases, selective brain cooling was absent, even though brain temperature was near 42 degrees C. We believe that selective brain cooling is controlled by brain temperature but is modulated by sympathetic nervous system status. In particular, selective brain cooling may be abolished by high sympathetic activity even at high brain temperatures.

Animals↗
PubMed1994

Prolonged endurance exercise and sleep disruption.

To determine whether exercise duration effects the recovery sleep following exercise, eight fit male endurance athletes, ages 23-42 yr, had their sleep electrophysiologically studied. This was done on four separate occasions: after a day on which no specific exercise was performed; after a day of a 15-km run; after a 42.2-km run day; after a day in which the athletes participated in a strenuous ultra-triathlon. Sleep patterns following the no exercise day and the 15-km and the 42.2-km run days were similar. The sleep pattern of the ultra-triathlon day when compared with the other three days showed significantly increased wakefulness and delayed and decreased rapid eye movement (REM) sleep. The duration of slow wave sleep (SWS) in the first 6 h after lights out, however, was no different. The increased wakefulness and decreased REM clearly indicate increased stress after the ultra-triathlon. REM sleep appears to be a more sensitive index of exercise induced stress than SWS.

Adult↗
PubMed1994

Compensation and turnover of direct-care staff in developmental disabilities residential facilities in the United States. II: Turnover.

A representative sample of more than 1,600 residential facilities nationwide was surveyed. Direct-care staff turnover was significantly higher in privately operated community facilities than in public institutions. Turnover was generally higher in private than in publicly operated community facilities. The most consistent correlate of turnover for all types of facilities was wages. Intra- and extra-organizational factors made unique contributions in predicting turnover.

Cross-Sectional Studies↗
PubMed1993

A UV-sensitive mutant of Arabidopsis defective in the repair of pyrimidine-pyrimidinone(6-4) dimers.

Plants are continually subjected to ultraviolet-B (UV-B) irradiation (290 to 320 nanometers) as a component of sunlight, which induces a variety of types of damage to the plant DNA. Repair of the two major DNA photoproducts was analyzed in wild-type Arabidopsis thaliana and in a mutant derivative whose growth was sensitive to UV-B radiation. In wild-type seedlings, repair of cyclobutane pyrimidine dimers occurred more slowly in the dark than in the light; repair of this photoproduct was not affected in the mutant. Repair, in the dark, of pyrimidine-pyrimidinone(6-4) dimers was defective in the UV-sensitive mutant.

Arabidopsis↗
PubMed1993

Selective and nonselective stages in homing of T lymphocytes to the central nervous system during experimental allergic encephalomyelitis.

The diversity of Ag-specific receptors on T cells homing to an inflammatory infiltrate in the central nervous system has been analyzed. Experimental autoimmune encephalomyelitis, a T cell-mediated inflammatory disease of the central nervous system, was induced in Lewis rats with a CD4+, CD8- T cell line specific for peptide 68-86 of myelin basic protein. Within the line a wide array of TCR V beta genes was transcribed including the V beta 8, V beta 10, V beta 15, V beta 16, and V beta 19 families. Accumulation of T cells at the site of inflammation was determined by using RNA-polymerase chain reaction amplification of rearranged TCR V beta transcripts derived from brain. By 8 to 10 h after i.p. infusion of the pathogenic T cell line, TCR V beta transcripts, including mainly V beta families that were predominantly rearranged by the line, could be identified in brains. Restricted TCR V gene transcripts with predominance of the V beta 8 family were identified in brain 48 h after injection, before onset of disease. Paralysis was apparent by 4 to 5 days after injection. At this time diverse V beta gene transcripts were detected in brain, reaching a maximum by day 9, when paralyzed rats have recovered. By day 14 a second stage of limited heterogeneity in the T cell infiltrate could be identified with predominant expression of V beta 8, V beta 9, V beta 10, and V beta 19. Interestingly, three out of these four V beta families were predominantly expressed within the encephalitogenic line. Thus, T cell migration to brain in experimental autoimmune encephalomyelitis is characterized by a rapid penetration of T cells followed by a selective trapping of T cells before the clinical manifestations of disease. When clinical disease was present the T cell infiltrate was diverse, whereas in the post-acute phase of disease the T cells in the central nervous system had limited heterogeneity with selective accumulation of T cells transcribing the same V regions that were detected in the line that incited disease.

Animals↗
PubMed1993

Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system in which a restricted cellular immune response has been observed. In order to establish whether such T cell responses are likely to be antigen-specific particularly with regard to myelin basic protein (MBP), we analysed T-cell receptor (TCR) gene rearrangements directly from MS brain plaques, using the polymerase chain reaction on reverse transcribed messenger RNA, and compared these with TCR of previously described MBP-specific T cell clones from MS and the rat model experimental allergic encephalomyelitis. Rearranged V beta 5.2 genes were detected in the brains of all patients who were HLA DRB1*1501, DQA1*0102, DQB1*0602, DPB1*0401. The V beta 5.2-D beta-J beta sequences in these MS brain plaques revealed five motifs. One of the common motifs was identical to that described for the VDJ region of a V beta 5.2 T-cell clone. This clone was from an MS patient who was HLA DRB1*1501, DQB1*0602, DPB1*0401, and it was cytotoxic towards targets containing the MBP peptide 89-106 (ref. 1). The deduced amino-acid sequence of this VDJ rearrangement, Leu-Arg-Gly, has also been described in rat T cells cloned from experimental allergic encephalomyelitis lesions, which are specific for MBP peptide 87-99 (ref. 2). VDJ sequences with specificity for this MBP epitope constitute a large fraction (40%) of the TCR V beta 5.2 N(D)N rearrangements in MS lesions. The capacity of rat T cells with these VDJ sequences to cause experimental allergic encephalomyelitis and the prevalence of such sequences in demyelinated human lesions indicate that T cells with this rearranged TCR may be critical in MS.

Amino Acid Sequence↗
PubMed1993

Dye-mediated photolysis is capable of eliminating drug-resistant (MDR+) tumor cells.

We evaluated the potential role of photoradiation therapy with a benzoporphyrin derivative, monoacid ring A (BPD-MA), and dihematoporphyrin ether (DHE), for the ex vivo purging of residual tumor cells from autologous bone marrow (BM) grafts. BPD-MA and DHE photosensitizing activity was tested against two human large-cell lymphoma cell lines and colony-forming unit-leukemia (CFU-L) derived from patients with acute myelogenous leukemia (AML). In mixing experiments, 4-log elimination of tumor cell lines was observed after 1 hour of incubation with 75 ng/mL of BPD-MA or 30 minutes of treatment with 12.5 micrograms/mL of DHE followed by white light exposure. By comparison, using the same concentration of BPD-MA, the mean recovery of normal BM progenitors was 4% +/- 0.8% (mean +/- SD) for granulocyte-macrophage colony-forming unit (CFU-GM) and 5% +/- 0.8% for burst-forming unit-erythroid (BFU-E). Similarly, DHE treatment resulted in the recovery of 5.2% +/- 2% and 9.8% +/- 3% of CFU-GM and BFU-E, respectively. Furthermore, equivalently cytotoxic concentrations of both DHE and BPD-MA and light were found not to kill normal pluripotent stem cells in BM, as demonstrated by their survival in two-step long-term marrow culture at levels equal to untreated controls. The T-lymphoblastic leukemia cell line CEM and its vinblastine (VBL)-resistant subline CEM/VBL, along with the acute promyelocyte leukemia cell line HL-60 and its vincristine (VCR)-resistant subline HL-60/VCR, were also tested. BPD-MA at 75 ng/mL was able to provide a greater than 4-log elimination of the drug-sensitive cell lines, but only a 34% and 55% decrease of the drug-resistant HL-60/VCR and CEM/VBL cell lines, respectively. On the contrary, 12.5 micrograms/mL of DHE reduced the clonogenic growth of all the cell lines by more than 4 logs. Further experiments demonstrated decreased uptake of both BPD-MA and DHE by the resistant cell lines. However, all the cell lines took up more DHE than BPD-MA under similar experimental conditions. Our results demonstrate the preferential cytotoxicity of BPD-MA and DHE toward neoplastic cell lines and CFU-L from AML patients. In addition, DHE was slightly more effective in purging tumor cells expressing the p-170 glycoprotein. These results suggest that photoradiation with DHE would be useful for in vitro purging of residual drug-resistant leukemia and lymphoma cells.

Bone Marrow↗
PubMed1993

Final height after treatment for childhood acute lymphoblastic leukemia: comparison of no cranial irradiation with 1800 and 2400 centigrays of cranial irradiation.

We analyzed growth and final heights in 127 patients (68 female patients) treated for childhood acute lymphoblastic leukemia. Central nervous system prophylaxis included either no cranial radiation therapy (CRT) (n = 38), irradiation with 1800 centigrays (cGy) (n = 36), or irradiation with 2400 cGy (n = 53). None of the patients received spinal irradiation. Mean (+/- SEM) age at diagnosis was 6.4 +/- 0.25 years, mean height standard deviation score (SDS) at diagnosis was 0.28 +/- 0.12, and mean age at final height was 18.26 +/- 0.19 years. The change in height SDS between diagnosis and achievement of final height was significant for all treatment groups: -0.49 +/- 0.14, no CRT; -0.65 +/- 0.15, 1800 cGy; and -1.38 +/- 0.16, 2400 cGy. Irradiated patients had a greater loss in height SDS compared with the nonirradiated patients (p < 0.01), and those treated with 2400 cGy CRT had a greater decrease in final height SDS than the patients treated with 1800 cGy (p < 0.01). Both younger age and female sex were significantly associated with a greater decrease in height SDS in the patients treated with CRT; girls < or = 4 years of age at diagnosis had a mean loss in height SDS that was more than twice that observed for others treated with the same dose of CRT. Thus, although modern regimens for acute lymphoblastic leukemia (no CRT or 1800 cGy CRT) appear overall to have only a modest impact on final height, patients, especially girls, treated with 1800 cGy CRT at a young age remain at risk for clinically significant growth failure.

Age Factors↗