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Biomedical subjects

W Kahn

Publications and source records attributed to W Kahn.

6 recordsLinked to original sources
PubMed2001

Repair of triplex-directed DNA alkylation by nucleotide excision repair.

Triplex-forming oligonucleotides (TFOs) are being investigated as highly specific DNA binding agents to inhibit the expression of clinically relevant genes. So far, they have been shown to inhibit transcription from the HER-2/neu gene in vitro, whereas their use in vivo has been studied to a limited extent. This study uses a TFO-chlorambucil (chl) conjugate capable of forming site-specific covalent guanine adducts within the HER-2/neu promoter. We demonstrate that nucleotide excision repair (NER) represents a mechanism of cellular resistance to TFO-directed DNA alkylation. In vitro repair assays demonstrate that triplex-directed chl-guanine adducts are substrates for repair by NER competent cell extracts but not XP12BE cell extracts deficient in NER. The degree of repair is estimated by a ligation-mediated polymerase chain reaction with a pre-formed triplex in a plasmid transfected into repair competent cells, indicating that approximately 25% of the guanine adducts are removed after 24 h. These data indicate that guanine adducts from TFO-directed alkylation are a substrate for NER and that DNA repair is a significant barrier to the intracellular persistence of target gene binding by TFOs.

Alkylation↗
PubMed1982

Peptic ulcer disease and the tar and nicotine yield of currently smoked cigarettes.

In order to examine the association of smoking cigarettes with a lower tar and nicotine yield to peptic ulcer disease, a common disease associated in past studies with cigarette smoking. We used questionnaire information provided by 9009 current regular cigarette smokers. The percentage who ever had peptic ulcer disease in smokers whose current cigarette yielded 0.00-0.81, 0.81-0.99, 1.00-1.27 and 1.28 + milligrams of nicotine per cigarette were 8.5, 9.2, 9.2 and 9.5, respectively . The percentages who ever has peptic ulcer in smokers whose current cigarette yielded 0.0-11.9, 12.0-15.9, 16.0-18.9 and 19.0+ milligrams of tar per cigarette were 8.6, 9.1, 8.9 and 10.8 per 100, respectively. In contrast, the percentages who ever had peptic ulcer disease increased with the smoking of a greater number of cigarettes, being 5.9, 8.8, 9.0, 11.8 and 10.5 in smokers of less than 10, 10-19, 20-29, 30-39 and 40+ cigarettes, respectively. In multiple logistic regression analyses, peptic ulcer disease was significantly (p = 0.002) associated with number of cigarettes (RR = 1.12 per 10 cigarettes; 95% CI 1.08, 1.16), age and sex. There was no significant association (both p's less than 0.10) either with the current cigarette's tar yield (RR = 1.09 per 10 milligrams; 95% CI 0.96, 1.25) or with its nicotine yield (RR = 1.15 per milligram; 95% CI 0.94, 1.42).

Adult↗
PubMed1982

A survey of personal habits, symptoms of illness, and histories of disease in man with and without vasectomies.

Using questionnaire information provided by 4.385 vasectomized and 13,155 matched, non-vasectomized men, we found no significant differences between them for a large number of symptoms and diseases, including those of the cardiovascular system. After taking into account differences in their martial status, past smoking habits, and physical activity at work, significant statistical associations of vasectomy with joint pain or swelling, back trouble, and a history of kidney or bladder infection persisted. Our data are inconsistent with the occurrence of large increases in the risks of many important diseases in vasectomized humans.

California↗
PubMed1981

Accuracy of information on smoking habits provided on self-administered research questionnaires.

In the setting of a prepaid medical care plan, self-administered questionnaires were an accurate source of information on smoking habits and the standard against which the physiologic measures of smoking, serum thiocyanate, and expired carbon monoxide, must be judged. Questionnaire responses were internally consistent and highly reproducible. In contrast, the physiologic measures had low overall sensitivity as tests of current tobacco exposure (0.72). Their sensitivity was improved by utilizing the self-reported information.

Adolescent↗
PubMed1978

Platelet satellitism--an ultrastructural study.

Ultrastructural studies by scanning and transmission electron microscopy were carried out on one of four cases of platelet satellitism. Adherence to the neutrophils was mainly by focal contact between small surface projections of the platelets and neutrophils. Phagocytosis was not seen with the neutrophils but was evident in the monocytes. The degree of satellitism noted increased with the time the blood anticoagulated with EDTA was left at room temperature. Mixing experiments with a patient's plasma and control cells and the patient's cells and control plasma were inconclusive but suggested that the abnormality may reside in the plasma.

Adolescent↗