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Biomedical subjects

A Halpern

Publications and source records attributed to A Halpern.

At least 19 recordsLinked to original sources

Strand breaks in plasmid DNA, natural and brominated, by low-energy X-rays.

Single- and double-strand breaks were measured in Col E1 plasmid DNA, natural and partially brominated, irradiated with monoenergetic X-rays (from a synchrotron radiation source) on both sides of the K-absorption edge for Br. The fraction of the undamaged supercoiled form decreased exponentially with the photon dose; its yield in the brominated DNA did not exhibit any energy-dependence. This result is consistent with the calculated relative contributions of photoelectric interactions with individual component atoms which show that an electron flux originating in light atoms outweighs that from bromine. However, X-rays of energy above the Br K-edge appear slightly more efficient in producing double-strand breaks. This result, as well as those reported in the literature on the Auger enhancement of different biological endpoints in cells containing brominated DNA, seem to suggest that the positive charge and submolecular effects associated with the photo-absorption in bromine play some role in damaging processes, besides the initial distribution of deposited electron energy.

Bromine

Screening and surveillance of patients at high risk for malignant melanoma result in detection of earlier disease.

Screening, surveillance, and educational programs have been recommended for members of hereditary melanoma kindreds with dysplastic nevi, who are at very high risk for melanoma. For melanomas detected in a surveillance program offered to 555 such persons, the average thickness was 0.52 mm for 28 surveillance incident melanomas, 0.55 mm for 64 nonsurveillance incident melanomas, and 1.44 mm for 48 index lesions (p less than 0.001). The proportion of cases with level I or II invasion was 60.8%, 58.3%, and 36.2% respectively (p = 0.002). The nonsurveillance incident melanomas were diagnosed before entry into the surveillance program, but these patients were presumably aware of the earlier occurrence of two index melanomas in their families. These findings are consistent with a favorable effect of surveillance and education in a high-risk population and suggest that patient factors as well as physician factors may contribute to early diagnosis.

Dysplastic Nevus Syndrome

A monoclonal antibody to a cross-reactive idiotype on cationic human anti-DNA antibodies expressing lambda light chains: a new reagent to identify a potentially differential pathogenic subset.

Anti-double-stranded DNA antibodies are commonly found in the serum of patients with systemic lupus erythematosus (SLE). They are a heterogeneous group of antibodies thought to differ in pathogenicity. The degree of heterogeneity and the structural correlates of pathogenicity, however, remain poorly defined. To address these questions we have been generating anti-idiotypic antibodies to the anti-DNA antibodies found in the serum of SLE patients. In this paper we report the generation and characterization of a new murine monoclonal anti-idiotype, 8.12, that recognizes a subset of anti-DNA antibodies that is present in serum of approximately 50% of patients with SLE. The 8.12 anti-idiotype recognizes uniquely cationic anti-DNA antibodies, all of which express lambda light chains. In murine models of SLE, it has been suggested that cationic anti-DNA antibodies are preferentially deposited in the kidney. It may be, therefore, that 8.12 recognizes a subset of anti-DNA antibodies of particular pathogenic significance.

Antibodies, Anti-Idiotypic

Reduced serum thyroglobulin response to bovine TSH in malignant hypofunctioning solid thyroid nodules: comparison to benign nodular disease.

Forty-three euthyroid patients with a single, solid, nonfunctioning thyroid nodule were submitted to fine needle aspiration biopsy and serum thyroglobulin (Tg) was measured before and after (48h) 10 U of bovine TSH. Twenty-two normal subjects were also submitted to the bTSH test. Patients with nonfunctioning nodules were divided in two groups: (I) Benign or Suspicious Cytology (n = 32), (II) Malignant tissue (n = 11). In the latter group all patients underwent surgery and the pathology findings confirmed the presence of thyroid carcinoma. Twenty-one patients with benign or suspicious cytology were also operated upon and the diagnosis was colloid goiter (n = 16) and follicular adenoma (n = 5). In eleven other patients the nodule reduced significantly in size (8) or was no longer palpable after suppressive therapy (3). Normal individuals had a basal serum Tg mean +/- SD value of 12 +/- 7.2 ng/ml and a peak Tg value of 44 +/- 47 ng/ml. Serum Tg values were significantly higher (p less than 0.01) in patients with benign and malignant nodules. However the mean absolute increment (delta Tg) after bTSH was significantly lower (p less than 0.01) in patients with malignant nodules (7.2 +/- 4.8 ng/ml) as compared with normal subjects (22 +/- 16 ng/ml) or subjects with benign nodules (31 +/- 30 ng/ml). The relative (%) serum Tg increment was also significantly lower in patients with malignant tissues (14 +/- 11) as compared to those with benign nodules (77 +/- 86) or normal subjects (247 +/- 173).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Thyroid growth immunoglobulins in large multinodular endemic goiters: effect of iodized oil.

Iodized oil (IO) was administered to 10 goitrous patients recently emigrated to São Paulo (SP) from iodine deficiency areas and to 42 goitrous patients from 2 Brazilian chronic iodine deficiency regions, Loreto and Luziania (L). Thyroid growth-promoting immunoglobulin G (IgG) thyroid-stimulating antibody, serum thyroglobulin (Tg), TSH, and thyroid hormones were measured before and 1 yr after IO administration. In all patients there was a remarkable reduction of gland mass associated with a significant decrease (P less than 0.01) in both basal serum Tg and peak Tg levels after bovine TSH administration. The mean percent Tg increase after bovine TSH treatment was reduced to 82% above basal levels compared with 224% before IO. Mean serum TSH levels, elevated only in the L group [7.3 +/- 11 (+/- SD) microU/ml] decreased to the normal range after IO (2.5 +/- 2.1 microU/ml). Serum T3 and T4 concentrations did not change greatly. Tests for microsomal antibodies were negative before and after IO. IgG concentrates of serum obtained before and after IO were tested for their ability to stimulate incorporation of [3H]thymidine into DNA or to increase intracellular generation of cAMP in FRTL-5 cells. Thymidine incorporation activity was found in 8 of 10 patients from SP [316 +/- 37% (+/- SEM); range, 140-480%] and 25 of 42 patients in the L group (mean, 206 +/- 14; range, 120-500%) before IO. Stimulation of thymidine incorporation reflected true growth-promoting activity, as confirmed by experiments measuring cell number, was not accounted for by TSH in the preparation, and reflected IgG action because it was abolished by absorption with antihuman IgG. IgG from only 1 patient in group SP and 4 patients in group L stimulated intracellular production of cAMP in FRTL-5 cells. All patients except 1 in both groups had no IgG stimulation (less than 120%) of growth-promoting activity 1 yr after IO treatment. There was a significant positive correlation between thyroid growth-promoting activity and serum Tg concentrations (r = 0.58; P less than 0.001), but no significant correlation was found with other parameters (TSH, T4, and T3). We conclude that growth-promoting IgGs lacking ability to stimulate cAMP production may play a role in the large multinodular goiters due to chronic iodine deficiency.

Adenylyl Cyclases

Irradiation of micro-organisms with mono-energetic X-rays; biological consequences of the Auger effect.

The radiation resonance effect reported previously for isolated biomolecules has now for the first time been observed in a cellular system. Dried bacteria, Micrococcus denitrificans, in which TdR in DNA was partially substituted by BUdR, were subjected to mono-energetic X-rays of energies below or above the K-edge for Br. Subsequently, the colony-forming ability was assayed. For photon energy slightly above the K-edge, the lethality/rad was greater than that below the K-edge. This is interpreted in terms of the Auger effect initiated selectively by photo-absorption in constituent Br atoms. The differential absorption of low-energy photons in constituent atoms of DNA is also discussed.

Animals

Quantitative ESR-studies of decay-produced radicals in 5-iododeoxyuridine labeled with 125I, 131I or tritium: role of the Auger effect.

In view of the enhanced biological damage caused by the "Auger nuclide" iodine-125, we have carried out quantitative ESR-studies of the radical formation in polycrystalline 5-iododoeoxyuridine (IUdR) resulting from the following internal or external radiation sources: (1) Decay of 3H, 125I or 131I in labeled IUdR; (2) Lanthanum K-photons corresponding to the K-edge of iodine; (3) 60Co gamma-rays. The results clearly indicate that inner shell ionization with its accompanying Auger effect as caused by the lanthanum K X-ray produces about 30% more free radicals per unit dose absorbed than 60Co gamma-rays, when considering the long-lived secondary radicals. Similarly, the concentration of free radicals is by about 30% higher in 125I- than in 131I-labeled IUdR at comparable doses. In the case of 3H-labeled IUdR the dose curve is almost identical with that observed for 125I-labeled IUdR. The results are discussed in terms of a localized radiation damage from low energy electrons.

Cobalt Radioisotopes

Chemical and biological consequences of beta-decay. Part 2.

In Part 1 of this article physical and chemical effects of beta-decay in labelled molecules were reviewed and their potential importance for breaking predetermined and specific bonds were pointed out. After incorporation of labelled biomolecules in living systems, such as viruses, phages or cells, the radioactive decay of the label alters the biological behaviour of the system, in the extreme case causing loss of the ability to reproduce, the extent of these consequences depending strongly on the type of radioisotope. Now Part 2 includes a brief discussion of biological effects associated with beta-decay emphasizing the relative importance of local transmutation and internal radiation effects from the decay of 3H, 14C, 32P, 33P, 35S and 125I. Attempt is also made, whenever possible at the present stage of understanding, to correlate biological effects with chemical processes on a molecular level.

Animals

Chemical and biological consequences of beta-decay. Part 1.

Radioactive decay in a labelled molecule leads to specific chemical and biological consequences which are due to local transmutation effects such as recoil, electronic excitation, build-up of charge states and change of chemical identity, as well as to internal radiolytic effects. In the present paper these effects are reviewed emphasizing the relation of the chemical alterations on a molecular level to the biological manifestation. Potential importance of this type of research for biomedical applications is pointed out. In part 1 we review the underlying physical and chemical principles and consequences of beta-decay of 3H, 14C, 32P, 33P, 35S and 125I for gaseous and simple condensed organic systems. Part 2 which will appear in the next issue will include the discussion of biological effects associated with beta-decay.

Bromodeoxyuridine

Mechanism of action of phenethylbiguanide (phenformin) in man. III. interrelationship between ethanol and phenethylibiguanide (PBG) in normal and diabetic subjects.

A standard 4-hr ethanol infusion (236 mg/min) after a 3-day fast with and without phenformin (25 mg q.i.d.), with blood drawn every hour for 8 hr, was performed on five normal subjects, eight obese nondiabetics, seven obese chemical diabetics, and four nonobese diabetics. Control infusion induced in all subjects a decline in blood sugar levels during and/or after the alcohol challenge, with a parallel decrease in basal plasma insulin. Hypoglycemia and the decrease in insulin secretion were associated with increased plasma free fatty acid concentration. Addition of phenethylbiguanide (PBG) to the preparatory 3-day fast resulted in a greater drop in the blood glucose levels of the normal control subjects, obese and nonobese diabetics; in the obese nondiabetics, however, significantly lower degree of blood glucose decrease than control was elicited. Furthermore, obese nondiabetics altered their blood glucose-insulin interaction with apparent increased responsivess of the B cells of PBG. The results suggest that effects of phenformin on blood glucose levels are more dependent on the metabolic state of the patient than on a property of the drug itself.

Adolescent