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Biomedical subjects

C Kennedy

Publications and source records attributed to C Kennedy.

At least 181 records · Page 10Linked to original sources

The nifU, nifS and nifV gene products are required for activity of all three nitrogenases of Azotobacter vinelandii.

Strains with mutations in 23 of the 30 genes and open reading frames in the major nif gene cluster of A. vinelandii were tested for ability to grow on N-free medium with molybdenum (Nif phenotype), with vanadium (Vnf phenotype), or with neither metal present (Anf phenotype). As reported previously, nifE, nifN, nifU, nifS and nifV mutants were Nif- (failed to grow on molybdenum) while nifM mutants were Nif-, Vnf- and Anf-. nifV, nifS, and nifU mutants were found to be unable to grow on medium with or without vanadium, i.e. were Vnf- Anf-. Therefore neither vnf nor anf analogoues of nifU, nifS, nifV or nifM are expected to be present in A. vinelandii.

Azotobacter vinelandii↗

Changes in retinal pigment epithelial cell autofluorescence and protein expression associated with phagocytosis of rod outer segments in vitro.

The accumulation of autofluorescent lipofuscin was quantified in cultured human retinal pigment epithelial (RPE) cells phagocytosing bovine rod outer segments (BROS) and the expression of proteins in these cells was investigated. Results showed a steady increase in autofluorescence of RPE cells over a 4-week period as measured by fluorophotometric flow cytometry. A significantly greater increase in autofluorescence was found in the cultured RPE cells from a 7-year-old donor compared with those from a 47-year-old donor. Within both groups the BROS-challenged cells had significantly higher fluorescence readings than the control cells which were not challenged. Autoradiography of 35S-labelled proteins separated by polyacrylamide gel electrophoresis (PAGE) revealed a small distinct band at 102 kDa in BROS-challenged RPE cells of both bovine and human origin that did not appear in control or microsphere-phagocytosing RPE cells. The intensity of the signal was unrelated to the duration of the challenge period.

Aging↗

Quantitative and qualitative analyses of clock drawings in Alzheimer's and Huntington's disease.

Although visuoconstructive impairment has been reported in both Alzheimer's (DAT) and Huntington's (HD) disease, there is little knowledge concerning how this cognitive deficit differs quantitatively and qualitatively in these two progressive dementias. To address this issue, the present study compared performances on the Clock Drawing Test (CDT: command and copy) of 25 DAT patients, 25 equally demented HD patients, and 25 elderly normal controls (NC). In the command condition, both patients groups were significantly impaired compared to the NC group. Although there was no significant difference between DAT and HD patients' total quantitative scores, a qualitative error analysis revealed a number of dissociations between the two patient groups. Graphic difficulties, very common in HD patients, were virtually absent in DAT patients; in contrast, conceptual errors were almost exclusively seen in DAT patients and were related to the severity of their dementia. Perseveration and "stimulus-bound" responses were also more frequent in DAT patients, and both groups made visuospatial errors. In the copy condition, the DAT, but not the HD, patients evidenced a marked improvement in performance. These results indicate that while both DAT and HD patients have significant visuoconstructive difficulties even in the early stages of their disorders, the specific cognitive processes underlying their quantitative impairments are quite different. It is possible that the DAT patients' conceptual errors are yet another indicator of the deterioration of their semantic knowledge.

Aged↗

Chronic exposure to morphine does not induce dependence at the level of the calcium channel current in human SH-SY5Y cells.

mu-Opioid receptors mediate inhibition of the N-type calcium channel current in the human neuroblastoma cell line SH-SY5Y. We have previously shown that chronic exposure to morphine induces homologous tolerance to this effect. Here we show that chronic incubation with morphine (1 microM for three to seven days) does not, however, induce physical dependence at the level of the calcium channel current. Initial experiments were performed using the whole cell voltage-clamp technique. Chronically treated cells were bathed in superfusate which also contained morphine (1 microM). On washout of morphine the current amplitude increased by 12% and this was reversed by re-addition of morphine. Naloxone (1 microM) elicited a similar increase. However, this increase is most likely due to a reversal of the residual inhibitory effect of morphine on the calcium channel current rather than being a novel withdrawal response. Chronic exposure to morphine did not change the voltage-sensitivity of the calcium channel current or induce the appearance of a current sensitive to the L-type calcium channel agonists Bay K 8644 (3 microM) and S(+)-PN 202-791 (1 microM). In a further series of experiments the nystatin-perforated patch technique was employed in order to prevent washout of any L-type current in these cells. Under these conditions a Bay K 8644-sensitive, L-type current was unmasked following treatment with omega Conus Toxin GVIA. The peak current was depressed by omega Conus Toxin GVIA (1 microM) by approximately 90% both in control cells and cells chronically exposed to morphine. Now Bay K 8644 (3 microM) almost doubled the remaining current but the effect was equal in both groups of cells. It is concluded that chronic exposure to morphine does not induce physical dependence and a withdrawal syndrome in the human SH-SY5Y neuroblastoma cell line by changing either N-type or L-type calcium channel activity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Cutis marmorata telangiectatica congenita.

The authors describe ten cases of cutis marmorata telangiectatica congenita (CMTC). All of these cases were sporadic. The incidence of associated anomalies was relatively low, and three patients had skin manifestations (cutaneous atrophy and nevus telangiectaticus). In two patients, the right leg was shorter and thinner. Another two showed neurologic symptoms without lasting neurologic damage. New associated anomalies, such as tendinitis stenosans and bowing of the lower legs, did not provide additional information regarding the cause of CMTC. The authors suggest that Happle's lethal gene hypothesis for Klippel-Trenaunay and Sturge-Weber syndromes also could be applied to CMTC.

Child, Preschool↗

Analysis of HLA class II allogenotyping in Australian aborigines and Papua New Guinea populations.

Human leukocyte antigen (HLA) class II allogenotyping has been applied to investigate the polymorphism of the DRB, DQB1, DQB2, DQA1, and DQA2 genes in Aborigines from the East Coast of Australia and in Melanesians from the Papua New Guinea North-East Coast and Highlands. Three new DR/DQ arrangements were observed, DRw14/DQB1-2b/DQA1-1a and DRw5Nauru/DQB1-3a/DQA1-2 (n Australian Aborigines), and DRw5Nauru/DQB1-1a/DQA1-1b (in Madang). DQA2 and DQB2 allogenotyping with TaqI and PstI digested genomic DNA revealed little polymorphism among the Papua New Guineans, with DQA2-Xa1 and DQB2-Xb1 the most common alleles in all the groups. However, the presence of DQA2-Xa2 in Papuans and Australian Aborigines reflects the degree of admixture with Caucasoids while the DQA2-Xa4 allele in Madang is probably a marker of Mongoloid origin.

Asian People↗

Excretion of ammonium by a nifL mutant of Azotobacter vinelandii fixing nitrogen.

A mutation in the gene upstream of nifA in Azotobacter vinelandii was introduced into the chromosome to replace the corresponding wild-type region. The resulting mutant, MV376, produced nitrogenase constitutively in the presence of 15 mM ammonium. When introduced into a nifH-lacZ fusion strain, the mutation permitted beta-galactosidase production in the presence of ammonium. The gene upstream of nifA is therefore designated nifL because of its similarity to the Klebsiella pneumoniae nifL gene in proximity to nifA, in mutant phenotype, and in amino acid sequence of the gene product. The A. vinelandii nifL mutant MV376 excreted significant quantities of ammonium (approximately 10 mM) during diazotrophic growth. In contrast, ammonium excretion during diazotrophy was much lower in a K. pneumoniae nifL deletion mutant (maximum, 0.15 mM) but significantly higher than in NifL+ K. pneumoniae. The expression of the A. vinelandii nifA gene, unlike that of K. pneumoniae, was not repressed by ammonium.

Ammonia↗

Duplex Doppler ultrasound in the investigation of occult nephropathy following haemolytic uraemic syndrome.

Duplex doppler ultrasound has been reported to be of value in the detection of raised vascular resistance, particularly in the renal tract. A prospective single blind study investigating the use of duplex Doppler ultrasound to measure resistive index (RI) in patients with impaired renal function and a history of diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) was performed. There was considerable overlap in the range of RIs, with RIs greater than 70% in children with normal renal function and in those with renal impairment following D+ HUS. There was no significant difference in the mean RI between the groups studied. We feel that the RI is not of value in predicting the presence of occult nephropathy following haemolytic uraemic syndrome.

Child↗

Identification of sulfurtransferase enzymes in Azotobacter vinelandii.

Rhodanese and 3-mercaptopyruvate sulphurtransferase have been identified in A. vinelandii. Two distinct active fractions of the two sulphur transferases were obtained after FPLC ion-exchange chromatography of material partially purified from crude extracts. Rhodanese has been purified to homogeneity, and it consists of one polypeptide chain of Mr ca 25,000. A partial purification of 3-mercaptopyruvate sulphurtransferase was obtained.

Azotobacter↗

Phenotypes, proliferative responses, and suppressor function of lung lymphocytes during Toxoplasma gondii pneumonia in mice.

Toxoplasma gondii pneumonia has emerged as an important problem in immunocompromised patients, especially those with AIDS. The characteristics of lung lymphocytes, including their phenotypes, proliferative responses, and suppressor function during T. gondii pneumonia were studied. During primary acute T. gondii infection, the numbers of T lymphocytes in the lungs increased even though mice lacked histologic evidence of pneumonia. As mice recovered from acute toxoplasmosis, numbers of lung CD4+ cells and the ratio of CD4+ to CD8+ cells decreased. Subsequently, T. gondii infection reactivated, manifested as pneumonia. During pneumonia, lung T lymphocytes, especially CD8+ cells, increased even more. Lung lymphocytes from mice with T. gondii pneumonia decreased the proliferative responses of splenocytes from T. gondii-immune mice to both concanavalin A and T. gondii lysate antigens in vitro. The striking increase in lung CD8+ cells and suppressor activity appear to be integral to the pathogenesis of T. gondii pneumonia.

Acute Disease↗

Temperature-Dependent Regulation by Molybdenum and Vanadium of Expression of the Structural Genes Encoding Three Nitrogenases in Azotobacter vinelandii.

Temperature affects the expression of the three different nitrogenases in Azotobacter vinelandii. Molybdenum repressed the vnfH and anfH operons relatively more at 30 degrees C than at 20 degrees C; at 14 degrees C molybdenum did not repress these genes at all. Similarly, V repressed the anf operon at 30 degrees C but not at 20 or 14 degrees C. Mo was poorly transported into cells grown at the lower temperatures. A. vinelandii thus has the potential to synthesize any of the three nitrogenases at 14 to 20 degrees C regardless of the presence of Mo or V.

Journal Article↗

The product of the nitrogen fixation regulatory gene nfrX of Azotobacter vinelandii is functionally and structurally homologous to the uridylyltransferase encoded by glnD in enteric bacteria.

We sequenced the nitrogen fixation regulatory gene nfrX from Azotobacter vinelandii, mutations in which cause a Nif- phenotype, and found that it encodes a 105-kDa protein (NfrX), the N terminus of which is highly homologous to that of the uridylyltransferase-uridylyl-removing enzyme encoded by glnD in Escherichia coli. In vivo complementation experiments demonstrate that the glnD and nfrX products are functionally interchangeable. A vinelandii nfrX thus appears to encode a uridylyltransferase-uridylyl-removing enzyme, and in this paper we report the first sequence of such a protein. The Nif- phenotype of nfrX mutants can be suppressed by a second mutation in a recently identified nifL-like gene immediately upstream of nifA in A. vinelandii. NifL mediates nif regulation in response to the N status in A. vinelandii, presumably by inhibiting NifA activator function as occurs in Klebsiella pneumoniae; thus, one role of NfrX is to modify, either directly or indirectly, the activity of the nifL product.

Adenine↗

Determining disability due to mental impairment: APA's evaluation of Social Security Administration guidelines.

OBJECTIVE: APA evaluated the Social Security Administration's (SSA's) medical standards and guidelines for determining disability due to mental impairment to determine how well the standards and guidelines operationalize the statutory definition of disability in a manner consistent with current psychiatric practice. METHOD: Seventy-two psychiatrists were trained in one of two procedures: those in the sequential evaluation condition were trained in the process and forms used by the SSA's reviewing medical consultants, and those in the statutory definition condition were trained in the statutory definition of disability and application of clinical judgment according to this standard. Decisions regarding claimant's ability or inability to work were recorded on an instrument designed for the study. Each condition consisted of 12 panels of three members. They reviewed 732 actual claims for disability benefits. The panelists reviewed claims independently, then rendered panel judgments. Each claim was reviewed by one panel in each condition. RESULTS: The proportion of agreement between conditions for panel decisions (0.77) was higher than chance agreement (kappa = 0.46). The high level of agreement on claims judged to have good medical evidence and on which confident decisions were made (proportion of agreement = 0.96, kappa = 0.78) suggests that disagreements largely reflected ambiguities in application of the standards and guidelines to more complex cases or those with inadequate information. CONCLUSIONS: The SSA's revised medical standards and guidelines reflect clinical decisions about ability to work based on the statute and, with procedural modifications, should be retained. The SSA should be involved in further systematic studies to develop a field of scientific inquiry into disability and psychiatric disorders.

Adult↗