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Biomedical subjects

L Johansson

Publications and source records attributed to L Johansson.

At least 19 recordsLinked to original sources

Pseudodiploid karyotypes in adenosquamous carcinomas of the lung.

Pseudodiploid karyotypes with clonal structural rearrangements were observed in short-term cultures from two adenosquamous carcinomas (ASC) of the lung, a tumor type hitherto virtually uncharacterized cytogenetically. The karyotypes were 46,XX,der(1)t(1;14)(q44;q22),add(9)(q34) in the first tumor and 46,XX,i(17)(q10) in the second tumor. We suggest that ASC of the lung differ from other lung cancers by having pseudodiploid instead of massively aneuploid tumor stemlines.

Aneuploidy

Effective dose from radiopharmaceuticals.

The effective dose, as defined by the International Commission on Radiological Protection (ICRP 1991), provides a possibility of expressing the radiation risk to patients undergoing different radiodiagnostic procedures by means of a single figure. This has been obtained by introducing organ or tissue weighting factors reflecting the radiation sensitivity of the organs. Such weighting factors were first published by the ICRP in publication 26 (1977), and have now been revised in publication 60 (1991). The effective dose for almost all radiopharmaceuticals in clinical use has been recalculated using the new weighting factors from ICRP 60 (1991) and compared with results from former calculations. A slight decrease in the numerical value for the effective dose has been observed, on average 11%. However, this does not correspond to a decrease in the estimated risk from the irradiation, since this has been re-evaluated and found to be higher than earlier believed (NAS 1990; ICRP 1991).

Humans

Malignant melanoma of the nasal cavity and nasopharynx treated with cisplatin and accelerated hyperfractionated radiation.

Primary malignant melanoma of the nasal cavity and paranasal sinuses is an uncommon disease, accounting for only 0.5-2% of all malignant melanomas. The primary treatment has been surgery. The frequency of local recurrence is high and recurrence is also the major determinant of treatment failure. Here we report on six patients with locally advanced disease, four of whom were too advanced for surgery, who were treated with accelerated hyperfractionated radiation in combination with cis-platinum. Three of four patients treated for local recurrent disease achieved a local cure and died of disseminated disease after 9-21 months. One patient given preoperative cisplatin and radiation is still alive with no evidence of disease 34 months after the completion of treatment. The present protocol may be a useful approach to obtain local control with the possibility of long-term cure.

Aged

Immunohistochemical study of 158 lung carcinomas.

Lung carcinomas were studied immunohistochemically and the results were related to type of tissue sample (bronchoscopic biopsies, surgical specimens, autopsies). All cytokeratins (CAM 5.2, PKK-1, AE1/AE3) reacted with virtually all adenocarcinomas, most squamous, and 65% of the large cell carcinomas, while CAM 5.2 was most efficient with the small cell carcinomas. CEA stained 33% and 60% of the small and large cell carcinomas, respectively, most adenocarcinomas, and 84% of the squamous cell carcinomas, among which staining decreased with dedifferentiation and was often focal. EMA reacted with 90%, and NSE with 20% of all histological types. There was no staining for NF. All antibodies, except EMA, were more efficient with surgical specimens. Our study implies that the cytokeratins we used work better with surgical material, but are generally comparable to monospecific cytokeratin antibodies. Also, EMA is a reliable marker for epithelial differentiation with all types of tissue samples. Moreover, CEA negativity in several poorly differentiated lung carcinomas might have implications in the differential diagnosis against pleural mesothelioma.

Carcinoembryonic Antigen

Histological type of lung carcinoma in asbestos cement workers and matched controls.

Histological types of lung carcinoma were examined in a case series of workers exposed to asbestos cement dust (n = 29) and matched controls (n = 87). The proportion of adenocarcinomas was 31% among the exposed subjects and 15% among the controls (mid-p = 0.05). Among workers with high exposure the proportion of adenocarcinoma was even higher (45%, 5/11; mid-p = 0.03). The proportion of peripheral tumours tended to be higher among exposed cases than controls (24 v 12%, mid-p = 0.12). Lobe of origin did not differ, however, between exposed cases and controls. Thus the study indicates an association between the degree of exposure to asbestos and adenocarcinoma of the lung, and a peripheral rather than central localisation of the tumours, but with virtually the same distribution of lobe of origin as in the general population.

Adenocarcinoma

Treatment of the mucosa with local anaesthetics in ulcerative colitis.

A new paradigm for the treatment of ulcerative colitis has recently been presented: Treatment of the mucosa with lidocaine (2%) enemas for prolonged periods. This therapy was introduced based on the hypothesis that hyperreactive autonomic nerves may play a pathogenetic role in the disease. One hundred consecutive patients have now been treated and the results presented. The proctitis patients all responded to the treatment, despite previous therapeutic failures in more than two-thirds of the cases. They were treated for 3-12 weeks, but 68% had a relapse (observation period 20 months). Of the 49 patients with proctosigmoiditis, two-thirds had chronic symptoms resistant to previous therapy. One of these patients did not respond to lidocaine, but developed fulminant total colitis. The other patient had therapeutic failure with lidocaine but responded well to subsequent cortisone enemas. The patients were treated until the subsets of T-lymphocytes (OKT4+ and OKT8+) disappeared from the mucosa. This occurred in parallel with symptomatic relief and eventual healing in 83% of the patients after treatment for 6-34 weeks. Of all the patients with proctosigmoiditis, 42% presented with recurrent symptoms (observation period 16 months). Of the 17 patients with left-sided colitis, all went primarily into remission within 2-4 months, but 23% had a relapse (observation period 13 months). The 6 patients with total colitis had symptomatic relief and improvement of histology when treated over 3-8 months. One patient had recurrence after 12 months. Treatment with a local anaesthetic in ulcerative colitis is a new approach to mucosal inflammation. The beneficial effects may be due to blockade of certain neural effects, such as epithelial proliferation and shedding and congestion of the mucosal vasculature, with actions on cells of the immune system.

Adult

Preclinical neurophysiological signs of parkinsonism in occupational manganese exposure.

To study the effects from low level exposure to manganese, 30 men at steel smelting works and 60 nonexposed reference subjects, were neurophysiologically examined using: (i) Electroencephalogram (EEG), Event related auditory evoked potential (AEP/P300), Brain stem auditory evoked potential (BAEP) and diadochokinesometry. No group differences concerning EEG or BAEP were found. Diadochokinesis was slower and there was a tendency towards prolonged P300 latency in the exposed group as compared to the referents. These effects may be interpreted as early (subclinical) signs of disturbances of the same type as parkinsonism.

Adult

[The Norwegian diet is steadily improving].

The main goal of the Norwegian food and nutrition policy for the period 1975-1990 was to reduce the fat content in the diet to 35% of the energy supply. Our latest data on food supply and consumption show that this target has been reached, and that dietary fat now contributes to 34% of the energy. The dietary changes have probably contributed to the decrease in cardiovascular disease that has taken place since the early 1970s. It is most likely that public health continue to improve through further changes in diet, and the National Nutrition Council has prepared a strategy aimed at achieving a Norwegian diet with a fat content providing only 30% of the energy supply.

Dietary Fats

Rearrangement of 9p13 as the primary chromosomal aberration in adenoid cystic carcinoma of the respiratory tract.

Two adenoid cystic carcinomas, one of the nasal cavity, the other a bronchial tumor, were cytogenetically analyzed. The former had a t(6;9)(q21-22;p 13-21) as the sole karyotypic abnormality. The latter had two related abnormal clones, resulting in the mosaic karyotype 46,XY,t(9;17)(p13;p13)/46,Y,t(X;6)(p22;q23),t(9;17)(p13;p13). The karyotypic profiles of the two cases, the only respiratory tract adenoid cystic carcinomas that have been cytogenetically characterized, differ little from those of previously reported adenoid cystic carcinomas of the major salivary glands, underscoring the fundamental biologic similarity among these tumors even when they develop from different structures and in different anatomical sites and organs. Because in the second case the t(9;17) obviously must have preceded the t(X;6), we conclude that both tumors had rearrangement of 9p13 as the primary cytogenetic change. The data thus add to the evidence that 6q changes are frequent, albeit at least sometimes secondary, aberrations in malignant salivary gland tumors. A subset of adenoid cystic carcinomas instead have rearrangement of 9p as the primary, and presumably pathogenetically essential, abnormality.

Adult

Molecular analysis of 4p deletion associated with Wolf-Hirschhorn syndrome moving the "critical segment" towards the telomere.

We report molecular studies in 2 patients with Wolf-Hirschhorn syndrome, probing genomic DNA from the patients and their parents with markers that have been mapped to 4p16.3. One of the patients was heterozygous for alleles detected by probe F5.53, which maps to the centromeric end of the D4S10 locus, but hemizygous for loci located more distally. The region in common, which was deleted in both these patients, is within 4p16.3. This observation suggests that the gene(s) for Wolf syndrome may be contained within this region, and that the "critical segment" is located more distally than previous cytogenetic observations have suggested. Furthermore, we found that the deletion was of maternal origin in one patient, and of paternal origin in the other.

Abnormalities, Multiple

Estrogen treatment of tall girls: dose dependency of effects on subsequent growth and IGF-I levels in blood.

Three groups of girls with mean final height predictions of 185.3 cm were treated in 3-week cycles with 0.25, 0.5, or 1.0 mg of ethinylestradiol. The three groups were comparable with regard to chronological age, bone age, height prediction, and duration of treatment. Reduction in final height of 5.5-5.9 cm/group in comparison with the initial prediction was observed in all treated groups. This reduction appeared independent of estrogen dose. Subsequent height increases were limited to about 50% of the predicted gain in all cases. In a comparable group of untreated tall girls the prediction method overestimated the final height by 1.2 cm. In the groups receiving 1.0 and 0.5 mg EtE2 a significant reduction in IGF-I levels was achieved within three to six months after the start of estrogen therapy.

Adolescent

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the vitamin A status of Hartley guinea pigs, Sprague-Dawley rats, C57Bl/6 mice, DBA/2 mice, and Golden Syrian hamsters.

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic, renal, lung, and serum vitamin A levels were investigated in species/strains, which show highly variable susceptibility to TCDD toxicity. Young male Hartley guinea pigs, Sprague-Dawley rats, C57Bl/6 mice, DBA/2 mice, and Golden Syrian hamsters received single intraperitoneal doses, in the range 0.5-400 micrograms TCDD/kg body weight, aimed to produce a similar toxic and limited lethal effect in all species. Animals were sacrificed 1, 7, 14, 28, 56, and 112 days after TCDD injection. The time-related increase in hepatic vitamin A storage was inhibited by TCDD in all species studied, but the doses required to produce the inhibition were considerably varied due to species. The duration of the inhibition was dependent both on dose and species. All species, except for the guinea pig, managed to increase the liver reserves of vitamin A at the end of the study, as compared to the amount present at the time of TCDD treatment. A marked increase in renal vitamin A content, related to TCDD exposure, was observed in the rats, as opposed to a slight decrease in the guinea pigs and no effect in mice or hamsters. All species tested, except for the C57Bl/6 mouse, showed a marked TCDD-related decrease in pulmonary vitamin A. The rat was the only species which showed a consistent effect (a small increase) in serum vitamin A levels, as a result of exposure to TCDD. The effects of TCDD on the hepatic and pulmonary vitamin A contents correlated reasonably well with the observed toxic response in this study. However, the correlation could not be observed for the effects of TCDD on renal, and serum vitamin A levels.

Animals

Manganese exposure in steel smelters a health hazard to the nervous system.

In a study of the effects of low-level exposure to manganese (0.19-1.39 mg/m3 for 1-45 years) 30 men (aged 20-64 years) from two steel smelting works and 60 unexposed referents (aged 22-65 years) were examined with the use of a general health inquiry, electroencephalography, event-related auditory evoked potentials, brain-stem auditory evoked potentials, diadochokinesometry, simple and complex reaction time, finger tapping, digit span, mental arithmetic, vocabulary, a coding task, manual dexterity, symptoms, and mood scales, the diagnostic interview scheme, a dynamic rating scale for neurasthenic syndrome, and a comprehensive psychopathological rating scale. No group differences were found in the electroencephalography or the psychiatric examinations. However, there were increased frequencies of some symptoms, the diadochokinesis was slower, the P-300 latency and reaction time were increased, and finger-tapping and digit-span performance were impaired in the exposed group. These effects were interpreted as early (subclinical) signs of disturbances of the same type as parkinsonism.

Adult