Jan Lindsten

DNA repair and frequency of x-ray and u.v.-light induced chromosome aberrations in leukocytes from patients with Down's syndrome.

DNA‐repair and the frequency of chromosome aberration after u.v. and X‐ray irradiation was studied on leukocytes from patients with Downs syndrome.

Chromosome analysis of lymphocytes from cadmium workers and Itai-itai patients.

Abstract Chromosome analysis was made on cultured lymphocytes from five cadmium exposed Swedish workers, four Japanese Itai-itai patients, and seven Japanese and Swedish control subjects. In contrast to previous reports no evidence was obtained to indicate that cadmium induces chromosome damage in vivo in man. The Itai-itai patients as well as the Japanese control subjects demonstrated a significantly higher frequency of chromosomally abnormal cells than the cadmium-exposed Swedish workers and control subjects.

Data and theory for a revised chiasma map of man

SummaryChiasma maps appropriate to chiasma conservation and terminalization are derived from new data on chiasma distributions and high-resolution banding. Here detailed data for arms with and without a terminal chiasma and improved estimates of mapping parameters are given. Utility of chiasma maps is limited by uncertainty about the nature and extent of chiasma movement. These results are being integrated with genetic data and physical assignments.

Genetic regulation of melatonin excretion in urine

The melatonin excretion in urine was determined in 107 individuals from 23 nuclear families. Complex segregation analysis showed that the melatonin production might be regulated by an additive major gene.

A new variant translocation (19q+, 22q−) in chronic myelocytic leukemia☆

Abstract A translocation between chromosome 19 and chromosome 22 was found in one out of nine patients with CML. All the remaining eight patients demonstrated a translocation between chromosomes 9 and 22. The clinical pattern of the disease was similar in the patient with the translocation between chromosomes 19 and 22 and in the other CML patients. Thus the presence of the Ph 1 chromosome appears to be more important for the course and pattern of the disease than the location of the translocated fragment.

Genetic regulation of the kinetics of glucose-induced insulin release in man. Studies in families with diabetic and non-diabetic probands

Insulin release and sensitivity were estimated from glucose and insulin curves obtained at a glucose infusion test performed on altogether 601 subjects belonging to 155 nuclear families. Ascertainment was through one of the parents, and 96 of the probands had diabetes with clinical onset after the age of 30 years, while 59 were healthy subjects. Three variables obtained by a computer model were analysed, i.e. the glucose regulation of insulin release by a direct stimulatory event (KI) and time‐dependent modulatory events (KP) as well as insulin sensitivity (KG). Complex segregation analysis revealed that the variables are genetically regulated, but there was no evidence for a major locus. The children of the diabetics did not differ from those of the non‐diabetics as far as insulin release is concerned.

DNA polymorphisms within the porphobilinogen deaminase gene in two Swedish families with acute intermittent porphyria.

SummaryTwo unrelated families with acute intermittent porphyria (AIP), an autosomal dominant disease related to a defect in porphobilinogen deaminase (PBG-D, EC 4.1.3.8.), were studied with regard to three restriction fragment length polymorphisms (RFLPs) (MspI, PstI, BstNI) within the PBG-D gene. The results indicate that linkage analysis of RFLPs within the gene can be used as a complement to PBG-D analysis for the diagnosis of gene carriers in families with AIP.

Late side effects of chemotherapy in ovarian carcinoma: A cytogenetic, hematologic, and statistical study

Late side effects of chemotherapy were studied in 51 women who had received at least 300 mg of melphalan for ovarian cancer and had survived for at least three years. Hematologic, statistical, and cytogenetic methods were employed. Six cases of iatrogenic leukemia were found. They appeared to represent a hematologic entity that is fairly difficult to recognize. The risk of iatrogenic leukemia in women who survived for three years or more after melphalan treatment was calculated to be 950 times greater than the leukemia risk in the total female population. The cylogcnetic changes were studied with three methods focused on sister chromatid exchange, chromosome aberrations, and DNA damage. The sister chromatid exchange frequency showed a marked increase, but it was corrected within a few months. Chromosome aberrations expressed by chromosome rearrangements were increased in the peripheral lymphocytes and may persist for several years. The frequency of DNA strand breaks was decreased indicating the presence of DNA cross‐links. Any of these types of genetic alteration could be the initiating event in carcinogenesis.

Evidence for an autosomal recessive gene regulating the persistence of the insulin response to glucose in man

The significance of genetic factors for insulin release after glucose infusion was studied in 155 nuclear families of which 59 were control families and 96 had been ascertained through a parent with onset of diabetes after 30 years of age. Fasting insulin and glucose as well as three principal components of the insulin and glucose curves were submitted to path analysis and complex segregation analysis. The three principal components were considered to reflect the magnitude, the degree of response and the persistence of the curves. The genetic heritability of the insulin variables varied between 0.47–0.93 and that of the glucose variables between 0.20–0.54. There were considerable intergenerational differences in the genetic heritability for the persistence of the glucose curve and for the degree of response and persistence of the insulin curve. The cultural heritability was found to be of minor importance, while the non‐transmitted sibling environment was large. There was significant evidence for a major locus for the persistence of the insulin curve. The best fit was for a completely recessive autosomal gene with the gene frequency 0.21. The phenotype distribution of this variable showed significant kurtosis which could simulate a major locus. However, the significant evidence for such a locus remained after an analysis using partial quantitation. The diabetics were significantly different from the non‐diabetics for all the variables studied, but a complete discrimination between the diabetics and non‐diabetics could not be obtained. There was no significant difference between the children of the diabetics and non‐diabetics for any of the variables studied.

Significance of genetic factors for the plasma insulin response to glucose in healthy subjects.

The intravenous glucose tolerance and plasma insulin response to glucose infusion were analysed in a twin and family material, comprising 279 healthy subjects. The relation between the blood glucose and plasma insulin values was studied by an analysis of the principal eigenvalues. The variables obtained were corrected for sex, age and weight, and standardized with regard to mean and variance. The results showed that at least four of the variables have appreciable familial correlations, corresponding to a heritability (h2) varying between 0.38 and 0.72. These correlations could not be accounted for by common environment alone. Thus, the beta cell function in normal man, as measured by a glucose challenge test, appears to be genetically regulated.