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Biomedical subjects

J M Wright

Publications and source records attributed to J M Wright.

At least 181 records · Page 10Linked to original sources

Cortisol succinate is slowly hydrolysed in organ cultures of porcine articular tissues and is not equivalent to cortisol.

The pro-drug cortisol succinate is frequently used as a substitute for cortisol in organ cultures. We found, however, that in Dulbecco's modified Eagle's medium the time taken for the ester to undergo 50 per cent hydrolysis (t1/2) to cortisol was 75 h. When 15 per cent heat-inactivated normal rabbit serum was present t1/2 decreased to 47 h, but the rate of hydrolysis was not further increased in the presence of porcine articular cartilage or minced synovial tissue. When frozen and thawed synovium was present t1/2 decreased to 33 h, presumably due to the release of carboxyl-esterases from the disrupted cells. The level of tetrahydrocortisol was low in all of the cultures. The slow hydrolysis of cortisol succinate resulted in the exposure of the tissues to undesirable fluctuations in the concentration of active hormone, which decreased to low levels at each medium change. Thus, in co-cultures of porcine synovium and articular cartilage, cortisol had a greater inhibitory effect than cortisol succinate on the breakdown of cartilage matrix caused by synovial tissue.

Animals↗

Transcription of the speC (ornithine decarboxylase) gene of Escherichia coli is repressed by cyclic AMP and its receptor protein.

The speC gene encoding ornithine decarboxylase (ODC) in Escherichia coli is negatively regulated by cAMP and the cAMP receptor protein (CRP). In minicells transformed with the plasmid pODC bearing speC, cAMP supplementation repressed ODC synthesis. In a cell-free protein synthesizing system directed by pODC, cAMP at 10(-5) M repressed ODC synthesis by 90%. This repression required a functional CRP as cAMP failed to repress ODC synthesis in vitro in an extract prepared from a crp- strain; the addition of purified CRP to the crp- extract restored the ability of cAMP to repress ODC synthesis. In a prototroph transformed with the plasmid pCOD bearing a speC::tet chimeric gene, cAMP supplementation decreased tetracycline (Tc) resistance. In contrast, in crp- strains transformed with pCOD or pTET (TcR), cAMP supplementation did not change their Tc resistance. When a cya- strain was supplemented with 2 mM cAMP, steady state levels of ODC mRNA were repressed by 80%. However, when a isogenic crp- strain was supplemented with 2 mM cAMP, no repression of ODC mRNA was observed. These results indicate that the cAMP-CRP complex exerts negative transcriptional control of ODC synthesis as a function of the speC promoter.

Cyclic AMP↗

Lack of comparability of two automated blood pressure monitors in a hypertensive population.

Two frequently used automated, blood pressure monitors, the Arteriosonde and the Dinamap, were compared with each other and with a standard mercury sphygmomanometer. Fifteen patients with elevated blood pressure were studied: 5 were untreated, 5 received a diuretic alone, and 5 received a beta blocker alone. One hundred and twenty blood pressure measurements were taken from each subject with two different instruments (one on each arm) in a 2 (supine or standing position) X 2 (left or right arm) X 3 (three different sets of pairwise instrument comparisons) X 5 (five one-minute interval measurements per phase) factorial design. A reasonable inter-instrument comparability for systolic blood pressure was found with mean deviations of +1.3 mmHg and -3.8 mmHg from the mercury sphygmomanometer for the Dinamap and Arteriosonde, respectively. Differences between instruments for diastolic pressure however, were significantly larger. The Arteriosonde systematically obtained higher diastolic pressure values (+7.4 mmHg) than the mercury sphygmomanometer or the Dinamap (10.7 mmHg). Diastolic pressure on the Dinamap was on average 5.2 mmHg lower than on the mercury sphygmomanometer. Left/right arm differences and differences for the treatment conditions were not observed. Findings clearly suggest that these two automated blood pressure monitors cannot be used interchangeably with each other or with the mercury sphygmomanometer in either a research or clinical setting. Overall the Dinamap approached mercury sphygmomanometer measures more closely than did the Arteriosonde.

Adrenergic beta-Antagonists↗

Subacute splenic abscess. Appearance on indium-111 leukocyte, gallium-67, and technetium-99m sulfur colloid imaging.

A case of a 23-year-old man with an encapsulated, anaerobic splenic abscess is reported. Both the In-111 leukocyte and Tc-99m sulfur colloid scans demonstrated an intrasplenic defect. The Ga-67 citrate scan revealed uptake in the rim of the abscess only where the abscess cavity was relatively photon-deficient. The combined Tc-99m sulfur colloid/In-111 leukocyte/Ga-67 scan appearance of a subacute splenic abscess has not been described previously. In cases suspected to be splenic abscesses the combined In-111 leukocyte/Tc-99m sulfur colloid imaging is the most useful.

Abscess↗

Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse.

C57 black mice given a single injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 40 mg/kg, developed marked reduction of striatal dopamine content and loss of dopaminergic neurons in the zona compacta of the substantia nigra. However, pretreatment with any one of four different antioxidants, alpha-tocopherol, beta-carotene, ascorbic acid or N-acetylcysteine, significantly decreased MPTP-induced striatal dopamine loss, and alpha-tocopherol prevented neuronal loss in the substantia nigra. Four chemical analogues of MPTP (cinnamaldehyde, N,N-dimethylcinnamylamine, arecoline and 2-methyl-1,2,3,4-tetrahydro-6,7-isoquinolinediol) were all found to lack dopaminergic nigrostriatal neurotoxicity in the mouse.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its metabolite, N-methyl-4-phenylpyridinium ion, on dopaminergic nigrostriatal neurons in the mouse.

A single subcutaneous injection in the C57 black mouse of 40 mg/kg of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a 90% depletion of striatal dopamine, as well as loss of 33% of neuronal cell bodies in the substantia nigra, zona compacta. By 4.5 months, there appears to be partial recovery of striatal dopaminergic function. After injection into mice, the MPTP metabolite, N-methyl-4-phenylpyridinium ion (MPP+) enters the striatum, and through some unknown mechanism is even more toxic than MPTP. However, repeated injections of maximally tolerated amounts of MPP+ do not damage dopaminergic nigrostriatal neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Isolation and sequence of cDNA clones coding for a member of the family of high mobility group proteins (HMG-T) in trout and analysis of HMG-T-mRNA's in trout tissues.

A specific oligonucleotide has been used to isolate a cDNA prepared from the mRNA for a trout High Mobility Group (HMG) protein closely related to trout HMG-T and bovine HMG 1 and 2 proteins. The sequence isolated more closely resembles bovine HMG-1 than the previously sequenced HMG-T protein in regions corresponding to the N terminal half of the protein. Northern blot analysis at low stringency indicated that 2 related sequences are expressed in total trout testis mRNA. Southern blots of total trout DNA indicate that several different forms of the homologous sequence are present in the trout genome and an estimate of copy number by dot-blot shows 4 HMG-T genes per trout sperm DNA equivalent. Analysis of mRNA from several trout tissues, including testis, liver and kidney indicates that expression of genes for histones and the larger HMG proteins in trout is not closely coupled.

Amino Acid Sequence↗

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) does not destroy nigrostriatal neurons in the scorbutic guinea pig.

Guinea pigs were injected subcutaneously with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in maximal tolerated doses (8 mg/kg, once daily) for 10 or 15 days. No neurological effects were noted, other than sedation and hypotonia lasting a few hours after each injection, either in animals maintained on normal diet or in animals fed an ascorbate-deficient diet and rendered severely scorbutic. Subsequent chemical analyses of the striatum showed no evidence of lasting damage to nigrostriatal dopaminergic neurons in MPTP treated guinea pigs on normal diet, and minimal evidence of permanent damage to these neurons in scorbutic animals. MPTP was undetectable in the urine of MPTP-treated animals, although a metabolite, presumably 1-methyl-4-phenylpyridinium ion (MPP+) was regularly present in urine. The relative lack of neurotoxicity of MPTP in the guinea pig remains unexplained. This species clearly is not a suitable small animal for MPTP-induced parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Osteogenesis imperfecta with unusual skeletal lesions: report of three families.

Thirteen individuals with osteogenesis imperfecta (OI) from three families were evaluated. All examined persons with OI had multilocular radiolucent, radiopaque, or radiolucent-radiopaque lesions of the maxilla and mandible. In most patients, the lesions involved the tooth bearing areas, but in two, the rami also were involved. Teeth were normal. Radiologic findings in the extragnathic skeleton included marked coarseness of trabeculae and diffuse osteopenia. It is proposed that these patients represent yet another dominantly inherited OI syndrome.

Adolescent↗

Use of the polyethylene glycol adduct of L-asparaginase for the treatment of hyperasparaginemia in a schizophrenic patient.

A man with hyperasparaginemia, presumably due to chronic deficiency of asparaginase activity, had been schizophrenic and unresponsive to antipsychotic drugs for at least 22 years. He was given repeated injections of bacterial L-asparaginase rendered relatively nonimmunogenic by covalent binding to polyethylene glycol (PEG). PEG-asparaginase lowered plasma asparagine concentrations from 4 to 5 SD above normal down to undetectable levels, and eliminated asparagine from the cerebrospinal fluid. Despite biochemical correction lasting at least 55 days, the patient did not improve psychiatrically. Experience limited to this single patient suggests that PEG-asparaginase therapy is relatively innocuous, but does not clarify whether there is an etiological relationship between hyperasparaginemia and psychiatric illness.

Adult↗

The effect of homogeneous versus heterogeneous stimuli on the confrontation-naming performance of aphasics.

The effect of semantic grouping on confrontation-naming performances of 16 fluent and 10 nonfluent aphasics was examined. Subjects were tested under two testing conditions: homogeneous stimuli within one semantic category and heterogeneous stimuli from several semantic categories. Both the response latencies and the number of correct responses were considered, as well as the types of naming errors produced. Performances of the aphasics were not uniformly facilitated in one naming condition over the other. Some of the individual patients, however, did appear to display performance discrepancies between the two conditions. Clinical and theoretical implications of these results are discussed.

Adult↗

HR 810 and BMY-28142, two new cephalosporins with broad-spectrum activity: an in-vitro comparison with other beta-lactam antibiotics.

The in-vitro activity of the new parenteral cephalosporins, HR 810 (HR) and BMY-28142 (BMY), was compared with that of other beta-lactam antibiotics, including cefotaxime, against a total of 315 recent clinical isolates and characterized beta-lactamase producers. An agar dilution procedure was used to determine MICs and two inocula (10(4) and 10(6) cfu) were used throughout. Against all species of the Enterobacteriaceae tested, both HR and BMY were as active as, or slightly more active than, cefotaxime. HR differed from cefotaxime mainly in being eight-fold more active against Pseudomonas aeruginosa and two-fold more active against Staphylococcus aureus. BMY was also eight-fold more active than cefotaxime against Ps. aeruginosa but was two-fold less active than the latter against Staph. aureus. Both new compounds had good activity against Haemophilus influenzae, including the beta-lactamase producing strains of that species, and both had poor activity against the Bacteroides fragilis group (MIC90 greater than 128 mg/l).

Anti-Bacterial Agents↗

Expression of the cloned genes encoding the putrescine biosynthetic enzymes and methionine adenosyltransferase of Escherichia coli (speA, speB, speC and metK).

The speA, speB and speC genes, which code for arginine decarboxylase (ADCase), agmatine ureohydrolase (AUHase) and ornithine decarboxylase (ODCase), respectively, and the metK gene, which encodes methionine adenosyltransferase (MATase), have been cloned. The genes were isolated from hybrid ColE1 plasmids of the Clarke-Carbon collection and were ligated into plasmid pBR322. Escherichia coli strains transformed with the recombinant plasmids exhibit a 7- to 17-fold overproduction of the various enzymes, as estimated from increases in the specific activities of the enzymes assayed in crude extracts. Minicells bearing the pBR322 hybrid plasmids and labeled with radioactive lysine synthesize radiolabeled proteins with Mrs corresponding to those reported for purified ODCase, ADCase and MATase. Restriction enzyme analysis of the plasmids, combined with measurements of specific activities of the enzymes in crude extracts of cells bearing recombinant plasmids, clarified the relative position of speA and speB. The gene order in the 62- to 64-min region is serA speB speA metK speC glc.

Carboxy-Lyases↗