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Biomedical subjects

A B Miller

Publications and source records attributed to A B Miller.

At least 361 records · Page 20Linked to original sources
PubMed1970

Nature of the inactivation of the isocitrate dehydrogenase from an obligate halophile.

The nicotinamide adenine dinucleotide phosphate-specific isocitrate dehydrogenase (ICDH) of Halobacterium cutirubrum is rapidly inactivated at low NaCl levels. From sucrose gradient analysis, it was estimated that the active ICDH has an S(20,w) of 5.3 and a molecular weight of 75,000. The inactivation by removal of NaCl causes an unfolding of the protein yielding a less-compact conformer with an S(20,w) of 2.0. This inactivation apparently causes internal sulfhydryl groups to be exposed. Over 90% of the initial activity can be restored by dialyzing the inactivated ICDH against 4 m NaCl, provided that the exposed sulfhydryl groups are protected with dithiothreitol. The ICDH is permanently inactivated when the sulfhydryl groups are oxidized or alkylated. The alkylation of the inactive ICDH was demonstrated by treatment with (14)C-N-ethyl maleimide. Sucrose gradient analysis showed that (14)C was bound to a protein with sedimentation properties identical to that of reversibly inactivated ICDH, i.e., an S(20,w) of 2.0. Much less (14)C was bound when active ICDH was treated with (14)C-N-ethyl maleimide. The H. cutirubrum ICDH resembles other bacterial isocitrate dehydrogenases in being susceptible to concerted feedback inhibition by oxalacetate and glyoxalate.

Amides↗
PubMed1970

A second international co-operative investigation into thioacetazone side-effects. 1. The influence of a vitamin and antihistamine supplement.

As part of a large-scale international, co-operative investigation into the side-effects produced by thioacetazone employed in the treatment of tuberculosis, an evaluation has been made of a supplement incorporating vitamins and an antihistamine as a prophylactic.Over a 12-week period of treatment, the additive supplement failed to reduce the over-all frequency of side-effects or the frequency of side-effects leading to a major departure from prescribed treatment. There was also no evidence that the more serious side-effects, particularly rashes, jaundice and agranulocytosis, were reduced by the additives, although the occurrence of vomiting, which was however infrequent, was reduced.In view of this lack of appreciable benefit, as well as the higher cost and impaired keeping properties of tablets containing thioacetazone plus isoniazid when the supplement is added, the use of the supplement as a prophylactic cannot be recommended.

Adolescent↗
PubMed1969

Purification and reversible inactivation of the isocitrate dehydrogenase from an obligate halophile.

The nicotinamide adenine dinucleotide phosphate-specific isocitrate dehydrogenase of Halobacterium cutirubrum is rapidly inactivated at low NaCl levels. As much as 75% of the initial activity can be restored by dialyzing the inactive enzyme against 4 m NaCl. A mixture of 4 mm isocitrate and 10 mm MnCl(2) gives the same protection as 4 m NaCl but does not replace the NaCl requirement for reactivation. The reactivated and native enzymes have identical sedimentation rates on sucrose gradients, electrophoretic mobilities on polyacrylamide gels, and elution rates from Sephadex G-200. However, there are distinct differences between the active and inactive forms of the enzyme. Compared with the active enzyme, the inactive protein has a lower sedimentation rate, a lower electrophoretic mobility, and a faster elution rate from Sephadex. These differences indicate that inactivation causes a major conformational change in the protein. Presumably, the removal of NaCl permits the enzyme to expand into a less dense, inactive form. The isocitrate dehydrogenase was purified 69-fold by a procedure involving the following steps. When the enzyme is selectively protected with isocitrate and MnCl(2) at low ionic strength, most of the contaminating proteins are precipitated with (NH(4))(2)SO(4) at 0.9 saturation. The enzyme in the supernatant fluid is then inactivated at low NaCl levels, precipitated with 0.5 saturated (NH(4))(2)SO(4), and reactivated with 4 m NaCl. Minor impurities are removed by gel filtration on Sephadex G-200. The resulting preparation is more than 95% pure as judged by disc electrophoresis.

Centrifugation, Density Gradient↗
PubMedDate not supplied

Screening for cancer: state of the art and prospects for the future.

Effectiveness of screening has been established for two cancer sites: breast and cervix uteri. Only for these, therefore, are national policies applicable. The degree of effectiveness of such programs will depend on the coverage of the eligible population; organized programs are, therefore, essential. For cancer of the cervix, nearly maximal efficacy will be obtained by screening sexually active women from 25 to 60 years of age every 3 years. For cancer of the breast, current evidence only justifies screening from 50 years of age; most programs will stop at 70 years of age. Mammography every 2 years will provide nearly maximal efficacy. The place of breast self-examination and physical examination of the breasts is under investigation. In Japan, screening for stomach cancer is justifiable, although strict evidence of effectiveness is lacking. Screening for other cancers must still be regarded as experimental, including the use of sigmoidoscopy and fecal occult blood tests for colorectal cancer, and visual examination of the mouth for oral cancer. Because of organizational and other difficulties, screening seems unlikely to make a major contribution to reduction in overall cancer mortality by the year 2000. However, if organizational problems can be overcome, screening has the potential to control invasive cancer of the cervix, and to make a major contribution to reduction in breast cancer mortality.

Humans↗
PubMedDate not supplied

Breast cancer screening: who should be included?

The recommendations of the U.S. Preventive Services Task Force are reviewed in regard to screening for breast cancer. In contradistinction to those issued by some other national organizations, screening for breast cancer using mammography at ages 40-49 is not recommended. It is concluded that the scientific evidence is insufficient at present to recommend mammography screening for women aged 40-49. The recommendations of the task force are: all women over age 40 should receive an annual breast examination; all women should have mammography every one or two years beginning at age 50 and concluding at approximately age 75 unless disease has been detected; and it may be prudent to begin mammography at an earlier age for women at high risk of breast cancer. These recommendations are appropriate in light of the available evidence; though at present there is no evidence that clinical examination of the breasts at any age reduces breast cancer mortality; the upper age beyond which breast cancer screening no longer has a significant effect in reducing breast cancer mortality is unknown; and there is no evidence that women at high risk for breast cancer benefit to a different degree from screening than women not at high risk.

Adult↗