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Biomedical subjects

S K Jones

Publications and source records attributed to S K Jones.

At least 55 records · Page 3Linked to original sources

Alanine dehydrogenase from Streptomyces fradiae. Purification and properties.

Alanine dehydrogenase was purified to homogeneity from a cell-free extract of Streptomyces fradiae, which produces tylosin. The enzyme was purified 1180-fold to give a 21% yield, using a combination of hydrophobic chromatography and ion-exchange fast protein liquid chromatography. The relative molecular mass of the native enzyme was determined to be 210,000 or 205,000 by equilibrium ultracentrifugation or gel filtration, respectively. The enzyme is composed of four subunits, each of Mr 51,000. Using analytical isoelectric focusing the isoelectric point of alanine dehydrogenase was found to be 6.1. The Km were 10.0 mM for L-alanine and 0.18 mM for NAD+. Km values for reductive amination were 0.23 mM for pyruvate, 11.6 mM for NH4+ and 0.05 mM for NADH. Oxidative deamination of L-alanine proceeds through a sequential-ordered binary-ternary mechanism in which NAD+ binds first to the enzyme, followed by alanine, and products are released in the order ammonia, pyruvate and NADH.

Alanine Dehydrogenase↗

Decreased DNA repair in familial Alzheimer's disease.

Alterations in the capacity of a cell to repair DNA lesions play an important role in a number of human diseases. We and others have demonstrated defective DNA repair of alkylation damage in cells from patients with Alzheimer's disease. It has been hypothesized that this defect is related to the cause of Alzheimer's disease and results in the accumulation of lesions in the central nervous system neurons. One prediction of this hypothesis is that in dominantly inherited Alzheimer's disease, the repair defect will be present in half of the offspring of affected patients long before they develop symptoms of the disease. In order to test the hypothesis that decreased DNA repair is responsible for familial Alzheimer's disease and their at-risk offspring we have studied DNA repair in these individuals after exposure of lymphoblasts to alkylating agents. Our results indicate that cell lines from affected patients repair significantly less damage in 3 h than cell lines from healthy controls. A small number of at-risk individuals were also studied and some of these had lower levels of repair, although more cell lines from individuals in this group must be studied. These findings provide further support for defective DNA repair playing a role in the pathogenesis of Alzheimer's disease.

Adult↗

Exfoliative dermatitis due to nifedipine.

We report the case of a 63-year-old Caucasian female, with reno-vascular hypertension, who developed a generalized skin eruption with lichenoid histological features, induced by nifedipine. A repeat challenge with nifedipine confirmed that it was the causative agent.

Dermatitis, Exfoliative↗

Transmission of virus particles by cryotherapy and multi-use caustic pencils: a problem to dermatologists?

The possibility of transmission of virus particles from patient to patient by multi-use silver nitrate sticks and styptic pencils and by cotton wool swabs that have been dipped repeatedly into Dewar flasks of liquid nitrogen was studied. The results showed that transmission by the sticks and pencils is unlikely but that virus particles can be transferred into and out of a Dewar flask on cotton wool swabs. We suggest that swabs should not be dipped repeatedly into the flask of liquid nitrogen but that, instead, a small aliquot of nitrogen should be decanted into a smaller 'clean' vessel and a new cotton swab used for each patient.

Adenoviruses, Human↗

Cutaneous reaction to diltiazem resulting in an exacerbation of angina.

A 77-year-old woman developed a widespread erythematous rash after treatment with the calcium antagonist, diltiazem, which resulted in an exacerbation of the angina for which the drug was originally described. Drugs which may give widespread cutaneous side-effects should be used with caution in patients with compromised cardiac function.

Aged↗

DNA repair deficiency for alkylation damage in cells from Alzheimer's disease patients.

We have shown that fibroblasts, lymphocytes and lymphoblasts from patients with Alzheimer's disease (AD) are deficient in the repair of DNA damage induced by the alkylating agents methylmethane sulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Unscheduled DNA synthesis and alkaline elution studies of DNA repair using human skin fibroblasts obtained from patients coming to autopsy have shown that the cells from autopsy confirmed cases of AD have lower levels of DNA repair synthesis after exposure to varying concentrations of either MMS or MNNG. Lymphoblasts derived from individuals with dominantly inherited AD have also been used to study DNA repair. Alkaline elution analysis of DNA repair after exposure to 200 uM MMS or 6 uM MNNG indicates that there is significantly less repair in the lymphoblasts from AD patients. When healthy control cell lines repaired and cell lines from AD patients were exposed to MMS or MNNG respectively significantly less repair occurred in the AD cells. After studying five at risk individuals results indicate that cell lines from two of these people have low levels of DNA repair and three lines have normal repair. These findings support the hypothesis of a DNA repair deficiency in familial AD. Monocytes from healthy control subjects and putative AD patients were analyzed for mutant frequency and DNA repair capacity. Results of unscheduled DNA synthesis experiments using monocytes from 7 healthy controls and 9 presumed AD patients indicates that there is a decreased ability of AD cells to repair MMS and MNNG induced DNA damage.

Alkylating Agents↗

Detection of DNA damage and repair by alkaline elution using human lymphocytes.

The repair of DNA alkylation damage in human cells is poorly understood. We have adapted the alkaline elution technique for use with human peripheral blood lymphocytes in culture. We have also established conditions necessary for short-term culture of human lymphocytes. Lymphocyte growth which can be maintained for up to 30 days is dependent upon irradiated TK6 feeder cells and T-cell growth factor (crude TCGF). The amount of damage induced by a given concentration of methyl methane-sulfonate (MMS) is dependent upon cell number per ml of growth medium. The DNA damage measured, in lymphocytes, by alkaline elution is a composite of single strand breaks and alkali-labile lesions. Repair of this damage after appropriate recovery periods is also detectable. The irradiated feeder TK6 cells do not contribute to the number of strand breaks detected or the amount of recovery after treatment. This method offers a quick and reproducible means of detecting DNA damage and repair in human T-lymphocytes.

Cell Division↗

Effect of circumcision status on periurethral bacterial flora during the first year of life.

To determine whether bacterial colonization is a factor in the pathogenesis of urinary tract infection, we compared the periurethral bacterial flora of uncircumcised versus circumcised boys during the first year of life. Intraurethral and circumferential glans cultures were obtained from 25 circumcised and 25 uncircumcised infants at 2 days, 2 weeks, 2 months, 4 months, 6 months, and 12 months of age. Different children were used at each age (300 total). The types of bacteria and the total and specific colony counts were compared. The results of the glans cultures were similar to those from the urethra. Uncircumcised boys had significantly higher total colony counts (p less than 0.003) at all ages except 12 months. Escherichia coli was present significantly more often (p less than 0.01) in the urethras of uncircumcised boys at 2 weeks, 2 months, 4 months, and 6 months. Gram-negative uropathogenic organisms (Klebsiella-enterobacter, Proteus mirabilis, and Pseudomonas aeruginosa) were cultured more frequently (p less than 0.0005) from the urethras of uncircumcised boys at 2 months, 4 months, and 6 months. The specific colony counts for E. coli and the other uropathogenic organisms were significantly higher (p less than 0.05) at all ages except 12 months. We conclude that during the first 6 months of life, the presence of a foreskin is associated with a greater quantity of periurethral bacteria and a greater likelihood for the presence of, as well as higher concentrations of, potentially uropathogenic organisms.

Bacteria↗

Ro/SSA antigen in human epidermis.

It has been shown previously by an immunofluorescence technique, that whole serum from patients who have anti-Ro/SSA autoantibodies reacts with a component or components of the epidermis. We have now demonstrated by immunoblotting that the antigen identified in human epidermis by anti-Ro/SSA sera is Ro/SSA antigen, and that Ro/SSA antigen is present both in adult and in neonatal epidermis. The presence of this antigen in tissues which are injured in the anti-Ro/SSA-associated syndromes subacute cutaneous lupus erythematosus and neonatal lupus erythematosus supports the hypothesis that anti-Ro/SSA antibodies react with Ro/SSA antigen in the skin and are important in the initiation of tissue damage.

Adult↗

Perioral blisters in a bug-biting baby.

We report peri-oral blistering caused by biting a bug, Palomena prasina, commonly found in the U.K. This is just one of a number of insects commonly found in the U.K. which produce chemicals for defensive purposes that may injure human skin. Contact with insects should, therefore, be considered as a cause of blistering eruptions, even in Britain, especially in the young who are more likely to handle insects.

Animals↗