High-resolution loading tests in the study of genetic heterogeneity in gangliosidosis fibroblasts

Summary GM₁- and GM₂-gangliosides were isolated from brain and radio-labelled. The labelled moieties were localized by hydrolysis with lysosomal enzymes, followed by thin-layer chromatography of the products. High-resolution loading tests with labelled gangliosides were developed and found to differentiate infantile and juvenile forms of GM₁- and GM₂-gangliosidoses as well as the identification of B, O and AB types of GM₂-gangliosidosis.     

Adverse ocular effects associated with niacin therapy.

In a retrospective survey of patients taking medication for hyperlipidaemia, those taking niacin (nicotinic acid) were more likely (p < 0.05) to report sicca syndromes, blurred vision, eyelid oedema, and macular oedema compared with those who never took niacin. Additionally, 7% of those taking niacin discontinued the drug owing to adverse ocular side effects, while none of the other lipid lowering agents were found to cause these side effects (p = 0.016). Data from spontaneous reporting systems support a possible association of decreased vision, cystoid macular oedema, sicca-like symptoms, discoloration of the eyelids with or without periorbital or eyelid oedema, proptosis, loss of eyebrow or eyelashes, and superficial punctate keratitis with the use of niacin in high doses. Decreased vision may be marked, and if the drug is not discontinued, may progress to cystoid macular oedema. All ocular side effects listed above are reversible if the association with niacin is recognised and the drug is discontinued; both the incidence and severity of the ocular side effects seem to be dose dependent.     

Gram negative aerobic bacillus pneumonia in oral and maxillofacial surgery--a case for comment.

A case illustrating the potentially fatal complication of endogenous Gram Negative Aerobic Bacillus (GNAB) septicaemia secondary to nosocomial pneumonia is presented along with current theories as to its aetiology. The technique of selective decontamination of the digestive tract is designed and advocated to prevent such occurrences; oral and maxillofacial surgeons should be aware of this approach. It may be, however, that by using much simpler manoeuvres such as changes in policy regarding gastric stress ulcer prophylaxis, the already small risk of such an occurrence will be further reduced. Awareness of this condition will allow a higher index of suspicion when presented with catastrophic septic complications on the ITU and aid in more rational planning of antimicrobial therapy.     

Body Weight, Fat Storage, and Alcohol Metabolism

Ethanol account for a significant fraction of the energy intake of persons consuming even moderate amounts of alcohol. A recent study has shown that although alcohol does not reveal itself as a layer floating at the top of a drink, metabolically it behaves more like oil than sugar.     

Intracellular metabolism of 5-formyl tetrahydrofolate in human breast and colon cell lines.

This report describes the intracellular metabolism of 5-formyltetrahydrofolate into the various one-carbon substituted folate and polyglutamate pools in a human breast (MCF-7) and colon (HCT 116) carcinoma cell line. Metabolism into the one-carbon substituted pools was found to be time and dose dependent over a concentration range up to 50 microM. A 3-fold increase in total intracellular folate was noted over a 50-fold concentration range (1-50 microM) of 5-formyltetrahydrofolate tested in the colon cell line, while in the breast line, a 6-fold increase was detected over a 500-fold concentration range (0.1-50 microM). The level of 5, 10-methylenetetrahydrofolate, which was detectable only in the breast cell line, was found to increase by a factor of 10 (1.8 pmol/mg to 17.9 pmol/mg) over the concentration range studied. The majority of metabolism was into the 10-formyltetrahydrofolate and tetrahydrofolate pools in the breast cells and into the 5-methyltetrahydrofolate pool in the colon cells. Polyglutamation was also time and dose dependent, with a significant proportion of the total pool represented by the higher polyglutamate forms (Glu3-Glu5) after 24 h of continuous exposure to 5-formyl tetrahydrofolate. Pentaglutamate was the highest level noted in both cell lines. The intracellular half-life of the polyglutamate forms was inversely related to the length of the polyglutamate tail with half-lives of 71, 131, 143, 441, and 1167 min for the mono- through pentaglutamate, respectively. Finally, up to a 20:1 ratio of the biologically inactive (6R) isomer to active (6S) isomer of 5-formyltetrahydrofolate resulted in no effect on metabolism into the one-carbon substituted folate pools and only minimal decreases in metabolism to the polyglutamate forms. These studies suggest that prolonged exposure to even relatively low doses of 5-formyltetrahydrofolate may be optimal for intracellular metabolism to the most biologically relevant forms for ternary complex formation with thymidylate synthase and fluorodeoxyuradylate, since longer exposures result in a greater accumulation of the higher polyglutamates.     

Effects of hyperthermia on blood flow and cis-diamminedichloroplatinum(II) pharmacokinetics in murine mammary adenocarcinomas.

The effect of localized hyperthermia on blood flow and cis-diamminedichloroplatinum(II) (CDDP) pharmacokinetics in 7,12-dimethylbenz[a]anthracene-induced mammary adenocarcinomas was studied. Blood flow was determined in rat tumors and normal tissue immediately and 1, 2, and 3 h after local hyperthermia treatment (43 degrees C, 1 h) as well as in unheated tumors of rats. The rate of blood flow in the tumor was increased 1.9 times at the end of treatment relative to control values and returned to the control values by 3 h after hyperthermia. Similarly, the rate of blood flow in the peripheral skin around the tumor immediately after hyperthermia was 2.2 times greater than that of unheated skin and returned to near normal values by 3 h after heating. Tumor-bearing rats received CDDP 1 h before, at the beginning of, at the end of, and 1 h after hyperthermia administration. The CDDP plasma concentration versus time profiles for rats did not vary statistically between treatment groups. Two h after CDDP administration, the mean tumor CDDP concentration of the rats which received drug at the beginning of hyperthermia was statistically greater (P less than 0.05) than tumor CDDP concentrations in rats which received drug at the end of heat treatment. The latter group was given CDDP when tumor blood flow was the greatest; however, mean tumor drug concentration was lowest of all the groups. The mean drug concentration in tumor tissues of rats which received drug 1 h after hyperthermia was comparable to rats which received drug at the beginning of hyperthermia. This suggests that drug delivery or uptake in tumors may be altered when local hyperthermia is administered concurrently or sequentially.     

Anticarcinogenic action of diallyl sulfide in hamster buccal pouch and forestomach.

The anticarcinogenic action of the garlic constituent diallyl sulfide (DAS), was examined in the hamster buccal pouch and forestomach. Groups of hamsters were topically treated, for up to 14 weeks, with a 0.5% solution of the buccal pouch and forestomach carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Prior to, during and after DMBA treatment, groups of hamsters were also treated, on alternate days, with a 1% solution of DAS. In addition to tumor formation, the induction of gamma-glutamyl transpeptidase (gamma GT) buccal pouch epithelial lesions served as an additional presumptive index of in vivo carcinogenesis/anticarcinogenesis. DAS resulted in a significant reduction in buccal pouch tumor frequency, buccal pouch tumor burden, buccal pouch gamma GT lesion frequency and forestomach tumor frequency. In a separate experiment, DAS also reduced the level of autoradiographically quantified unscheduled DNA repair synthesis (UDS) in pieces of hamster buccal pouch concurrently exposed in vitro to the potent buccal pouch carcinogen N-methyl-N-benzylnitrosamine (MBN). This study demonstrates that DAS is an effective anticarcinogenic agent in squamous mucosa of the hamster and suggests novel cost-effective strategies for the rapid identification of tissue-specific anticarcinogens and a quantitative assessment of their efficacy.     

Assessment of post-vaccination tuberculin sensitivity in Lagos-Nigeria.

An increase in the number of cases of tuberculosis, especially in children, has been observed recently. Post-vaccination conversion rate in babies immunised with BCG was assessed. Sensitization was detected as early as 4 weeks after BCG inoculation. Although 84.2% had physical evidence of BCG inoculation only 69.8% had developed detectable sensitization to the tubercle bacilli as shown by the Mantoux test.