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A procedure has been developed to assess chemically induced DNA repair in freshly isolated, primary cultures of human bronchial epithelial (HBE) cells. HBE cells were isolated from eight samples of autopsy material or surgical specimens and incubated with test chemicals and [3H]thymidine. Viability as measured by trypan blue exclusion averaged 90%. Chemically induced DNA repair was assessed as unscheduled DNA synthesis (UDS) by quantitative autoradiography. The direct-acting agent methyl methanesulfonate induced DNA repair in HBE cells in all eight cases studied, indicating that the cultures were viable and capable of DNA repair in response to DNA damage. Benzo(a)pyrene induced DNA repair in all cultures whereas dimethylnitrosamine failed to induce UDS in any culture, suggesting an organ-specific pattern of metabolic activation. 1,6-Dinitropyrene was positive in cultures prepared from autopsy material but negative in cultures prepared from surgical specimens. Formaldehyde did not induce UDS in any sample examined. This system may be useful in assessing the genotoxic potential of environmental chemicals in human bronchial epithelial cells, give an indication of interindividual variability, and provide valuable information for comparison to proposed animal models for the human bronchus.

Certain A + T-rich DNA sequences (C-type inducing sequences) cause adjacent inverted repeats to undergo cruciform extrusion by a particular pathway (C-type extrusion), which is characterized by large activation energies and extrusion at low salt concentrations and relatively low temperatures. When they are supercoiled, these sequences become reactive toward the normally single-strand-selective reagents bromoacetaldehyde, glyoxal, osmium tetraoxide, and sodium bisulfite. The following evidence is presented: (1) The most reactive sequences are those to the left of the inverted repeat. (2) Chemical reactivity is suppressed by either sodium chloride or micromolar concentrations of distamycin. The suppression of reactivity closely parallels that of C-type cruciform extrusion. (3) Chemical reactivity requires a threshold level of negative supercoiling. The threshold superhelix density depends on the prevailing salt concentration. (4) Analysis of temperature dependences suggests that reaction with osmium tetraoxide involves transient unstacking events, while bromoacetaldehyde requires larger scale helix opening. Thus a variety of opening events may occur in the supercoiled A + T-rich sequences, from small-amplitude breathing to low-frequency, large-amplitude openings. The latter appear to be responsible for C-type cruciform extrusion.

Diethyl pyrocarbonate reacts with the single-stranded loops of cruciform structures with great selectivity. Adenine bases are carbethoxylated, as a result of which the backbone may be cleaved with piperidine, and the level of chemical modification at each base may be determined. We have studied the ColE1 and (A-T)34 cruciforms of pColIR315 and pXG540. In each case we observe maximal modification at the most central adenosine of the loop, and an overall pattern of modification corresponding to a total loop size of about six bases. The results may be interpreted in terms of a model in which the loop has a defined tertiary structure. No modification was detected at either cruciform four-way junction, suggesting that this region is fully base-paired.

Double aneuploidy involving Down syndrome and Turner syndrome is a rare chromosomal abnormality presumed to occur with a frequency of about 1 in 2 million births. Twenty-one cases of this combined anomaly have been reported and two infants were born with this anomaly after a mistake in prenatal diagnosis. We report the first prenatal diagnosis of Down syndrome combined with Turner mosaicism and suggest that this polysyndrome may be more common than previously estimated. We, therefore, wish to alert cytogenetic laboratories performing prenatal diagnoses of the potential risks of misdiagnosis of this polysyndrome if banding is not performed and if a sufficient number of mitotic cells are not analysed.

We report on a patient with various connective tissue abnormalities suggesting a distinctive disorder combining some features of the Marfan syndrome with craniosynostosis and other anomalies. A comparison is made with the Marfan syndrome and other phenotypically similar conditions.

Five hundred consecutive admissions to the rheumatism service of a large hospital were reviewed in an effort to establish criteria for accurate differential diagnosis in rheumatic disorders. Forty-one per cent of the patients presented evidence of articular involvement or arthritis; 28 per cent had non-articular rheumatism, embracing the various types of fibrositis; 7 per cent had musculoskeletal neuroses, and 24 per cent had a variety of diseases unrelated to the musculoskeletal system. A working classification of the various causes of musculoskeletal pain is presented and criteria for the differentiation of the individual diseases are suggested.

Cough is a complex defensive reflex whose purpose is protection of the respiratory tract. There are many nonrespiratory causes, particularly pulmonary congestion from heart disease. Coughs may be useful, useless, or harmful. Treatment based on etiology and type of cough requires only a few medications whose efficiency has been demonstrated. The meaning of cough as a symptom must be carefully determined before rational treatment can be planned. Recent researches on the physiology of the cough reflex, the bronchi, and the mechanisms of bronchial secretion have made it possible for a physician to plan a treatment program on a firm, scientific basis, rather than on tradition.