[Three years with Adel--some experiences. Shortages in medical care quality at certain nursing homes].
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Biomedical subjects
Publications and source records attributed to L Johansson.
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Mortality and cancer incidence were investigated among 901 workers at a Swedish company manufacturing graphite electrodes. Current and previous measurements of personal exposure to benzo[a]pyrene were used to calculate individual exposure estimates. Smoking habits were investigated by questionnaire. There were 42 deaths during the study period (1968-1989), whereas 32.3 would be expected, based on age, sex, time, and county-specific population statistics. Three cancers of the respiratory system were found vs 1.2 expected. The overall mortality was slightly elevated, mainly due to an increased number of deaths from external causes. Thus far, no excess risk of cancer has been documented in this cohort. The results indicate that an increased risk of respiratory cancer may be present, but influence from chance cannot be ruled out due to small numbers. The cohort will be under continued surveillance.
(Z)-3-(4-Bromophenyl)-3-(3-pyridyl)allylamine (CPP 200) is transformed to the corresponding chloroimine by hypochlorite ion (ClO-) formed in the presence of myeloperoxidase. A scheme for this transformation is given. The influence of various compounds on this process has been studied. Cysteamine, cysteine and 6-chloro-3-hydrazino-pyridazine inhibited the transformation of CPP 200, while some p-hydroxyphenyl derivatives increased the rate of transformation of CPP 200. The increase seen on addition of the p-hydroxyphenyl derivatives is not a chloride-dependent reaction. Various mechanisms for the inhibiting effect as well as for the activating effect on the transformation of CPP 200 are discussed.
Prostasomes isolated from human seminal plasma stimulated the forward motility of buffer-washed, and therewith immobilised, normal human spermatozoa in a dose- and time-related fashion. Albumin exhibited a similar capacity for stimulation. Combining prostasomes with 5 mmol/l of any of the hexoses fructose, glucose or mannose (but not galactose) resulted in a prolongation and improvement of the effect by prostasomes (or albumin) for the first 150 min. Hence, a dose-response effect at 60 and 120 min was obtained by prostasomes on sperm forward motility provided 5 mmol/l of fructose was present--otherwise not. Many substances besides the hexoses were examined for possible positive effects on sperm forward motility in concert with prostasomes with no additional effect. Enrichment of optimum concentrations of prostasomes and glucose with 2 mmol/l of adenine stimulated further the velocity parameters of the spermatozoa over time. The effect of adenosine was less evident under these conditions. Experiments carried out with prostasomes in the presence of divalent cations or chelators suggested that magnesium ions are essential for sperm forward motility. There appeared to be a safety margin concerning calcium ions, and zinc ions did not seem to be primarily involved in sperm forward motility in the presence of prostasomes.
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Cytogenetic analysis of 122 primary squamous cell carcinomas of the lung revealed clonal abnormalities in 56 tumors. Karyotypes with simple numerical changes were found in 32 tumors: 45,X,-Y in 28, 47,XY,+7/45,X-Y, in two, 47,XY,+Y/45,X,-Y and 47,XY,+20/45,X,-Y in one tumor each. A super-numerary ring chromosome was the sole anomaly in two tumors. Complex structural changes were found in 22 tumors. The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (15 tumors), 3, 7, and 11 (10 tumors each), 5 and 6 (nine tumors each), and 2, 8, and 12 (eight tumors each). The bands and regions most often affected were 1p11-13 and 5cen (six tumors each), 11p11, 14p11-13, 15cen, and 17p11-12 (five tumors each), and 12p13 and 13cen (four tumors each). The only recurrent changes were the whole-arm rearrangements i(5)(p10) (five tumors) and i(6)(p10), der(9;15)(q10;q10), and der(13;15)(q10;q10) (two tumors each). The most prominent genomic imbalances were, apart from losses of the Y chromosome, losses from 1p, 3p, 5q, 6q, 8p, 13p, and 14p and gains from 1q and 5p.
The development of neurons utilizing gamma-aminobutyric acid (GABAergic neurons) in prosencephalon and telencephalon from chicken embryonic days 4-14 (E4-E14) was studied by means of immunohistochemistry. Furthermore, routine histology and transmission electron microscopy. respectively, were performed in order to study the morphological development in the designated area. The main finding is that development of GABAergic neurons in the chick telencephalon is rapid; the GABA neurons are appearing in bulk at day 8, being "overexpressed" at days 10-11, decreasing in numbers thereafter and achieving mature morphology on day 14, which is considerably faster than in the rodent. Morphological analysis revealed that the prosencephalon mainly consisted of a thin layer of undifferentiated neuroblasts in the E4 embryo. By E6, the prosencephalon had increased in thickness and occasional cells outside the neuroepithelium showed a more mature morphology with a few cells weakly staining positive for GABA. At E8, the prospective granular and subventricular layers had developed. At E14, the appearance of the telencephalon is approximating that of the adult since both ependymal cells and morphologically mature neurons can be seen.
The virulence plasmid-encoded YopE cytotoxin of Yersinia pseudotuberculosis is secreted across the bacterial membranes and subsequently translocated into the eukaryotic cell. Translocation of YopE into target cells was recently shown to be polarized and only occurred at the zone of contact between the pathogen and the eukaryotic cell. Immunogold electron microscopy on cryosectioned Y. pseudotuberculosis revealed that YopE is secreted and deposited on the bacterial cell surface when the bacteria are grown in Ca(2+)-depleted media at 37 degrees C. No YopE was detected in the cytoplasm or in the membranes. In yerA mutants which are downregulated for YopE at a post-transcriptional level, the cytotoxin could only be detected in the cytoplasm. The overall recovery of YopE from the yerA mutant strain was, however, considerably lower than from the wild-type strain. yerA had no major effect on the translation of YopE, but was found to stabilize YopE in the cytoplasm. YerA was shown to specifically interact with YopE in the cytoplasm in vivo and this binding also correlated with YopE secretion. Targeting of YopE to the secretion loci as well as translocation of YopE into HeLa cells occurred also in the absence of YerA. Based on our findings, we suggest that YerA by binding to YopE stabilizes and maintains the cytotoxin in a secretion-competent conformation.
Roentgen treatment for painful benign conditions in the locomotor system as arthrosis and spondylosis was in Sweden very common up to the beginning of the 1960s. The mode of treatment differed from the British ankylosing spondylitis series as smaller parts of the red bone marrow were exposed and smaller doses were applied. A cohort of 20,024 such patients treated 1950-1964 at two hospitals in northern Sweden was analysed with regard to the risk of haematological malignancies. Average factors for conversion of prescribed skin doses to mean absorbed red bone marrow doses were estimated on random samples of the different treatment sites and then applied on the cohort in its whole. The standard incidence ratio (SIR) for leukaemia was 1.18 (95% CI: 0.98-1.42) and the standard mortality ratio (SMR) 1.25 (0.99-1.45). In the highest dose group (mean absorbed red bone marrow dose > 0.5 Gy) the corresponding values were 1.40 (1.00-1.92) and 1.50 (1.08-2.04). In the mortality analysis also a slightly increased myeloma risk was noted with SMR = 1.20 (0.99-1.56). Extension of the cohort and nested case-control studies are under progress.
A cohort study with regard to the risk of haematological malignancies was performed on about 20,000 patients who in 1950-1964 received roentgen treatment for benign conditions in the locomotor system. In order to estimate the mean absorbed red bone marrow dose the treatments were classified as concerning 10 sites (cervical spine, thoracic spine, lumbar spine, sacral region, shoulder, hip, elbow, wrist, knee and ankle). The four last-mentioned sites do not normally contain red bone marrow in adults and their contribution to the mean absorbed dose was regarded as zero. For the other 6 sites random samples consisting of 30 patients for each site were drawn from the cohort. By use of the treatment records and data from the literature on some physical parameters and red bone marrow distribution in normal adult persons, average conversion factors were calculated by which the subscribed surface dose could be converted into mean absorbed dose in red bone marrow. These conversion factors were then applied on the whole cohort and used for stratification of it according to different levels of exposure.
Temporal and dose-related effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic 7-ethoxyresorufin O-deethylase (EROD) activity were investigated in young male Hartley guinea pigs, Sprague-Dawley rats, C57Bl/6 mice, DBA/2 mice and Golden Syrian hamsters. Animals were terminated 1, 7, 14, 28, 56 and 112 days after the administration of a single i.p. dose of TCDD. The maximal induction of EROD activity, at doses producing a similar toxic and limited lethal effect in all species/strains, was 42-, 18-, 7- and 3-fold in rats, DBA/2 mice, C57Bl/6 mice and guinea pigs, respectively. No treatment-related induction of EROD activity was observed in hamsters. Generally, maximal induction occurred 1-4 weeks after injection in all species. The guinea pig alone maintained the same magnitude of induction of EROD activity throughout the study. Observed toxic effects, i.e., lethality, loss of body weight gain, liver enlargement and thymic atrophy, did not correlate with the TCDD-induced hepatic EROD activity. The obtained results suggest that the fold induction of cytochrome P450 1A1 activity is not a critical event for the expression of the lethal effect of TCDD in rodents.
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Cytogenetic analysis of short-term cultures from 26 primary bronchial large cell carcinomas and 1 metastasis from a primary large cell carcinoma revealed clonal chromosome abnormalities in 20 tumors and a normal karyotype in 6. No outgrowth was obtained in 1 case. Simple aberrations were present in 3 tumors; in 1, the only change was a reciprocal translocation between chromosomes 1 and 6, in another the sole anomaly was a supernumerary marker ring chromosome and in a third loss of the Y chromosome was the only clonal change. The remaining 17 tumors had complex karyotypes. The chromosomes most frequently involved in structural rearrangements were chromosomes 1, 2, 3, 5, 6, 7, 8, 10, 11, 13, 14 and 17. The bands most frequently affected were 1q11-12, 1p13, 7q11, and 17p11-13. The rearrangements led to repeated losses of 1p, 1q, 3p, 6q, 7q and 17p and gains of 5q and 7p. The emerging karyotypic picture of large cell lung carcinomas indicates more similarities with adenocarcinomas than with other pathologic subgroups of lung cancer.
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Several intrasplenic immunizations with batches of approximately 15 or approximately 30 zona-free, unfertilized mouse oocytes resulted in 200-300 hybrids, respectively, among which about 20 positive clones were selected from each fusion between splenic plasma cells and SP2/0 myeloma cells. When nonimmunized splenic plasma cells were used, only one antibody, showing weak immunoreaction, was obtained from approximately 370 hybrids collected from 2 fusions. From one immunization with a total of 12 zona-free, unfertilized mouse oocytes, 15 positive clones were selected for further study. Eleven of these 15 antibodies reacted with antigens only in unfertilized oocytes but not in fertilized, pronuclear stage oocytes. Three antibodies, which recognized antigens in paraffin-embedded oocyte sections, did not label growing ovarian oocytes, indicating that the antibodies were specific to ovulated, unfertilized oocytes. These antibodies did not detect any antigen epitopes in the panel of tissues examined. The molecular weight of one antigen, corresponding to a IgM antibody that is present both in ooplasma and zona pellucida, was approximately 116 kDa. Cross-reactivity to blots of unfertilized zona-free hamster oocytes was demonstrated by 6 antibodies and to unfertilized human oocytes by 7 antibodies. Three antibodies cross-reacted with both hamster and human oocytes. The study indicates that the intrasplenic immunization is an appropriate means of raising antibodies against unfertilized, zona-free mouse oocytes and that the method applied offers an easy way to select antibodies against human oocytes for functional studies.
Herein we report the clinicopathological features of four cases of pulmonary artery sarcoma that appeared at our institution during a period of 30 years. The patients, 2 males and 2 females, were 50-62 years old. Tumour was found in the pulmonary trunk and right pulmonary artery in all cases, in the pulmonary valve and left pulmonary artery in three of the four cases, and in the right ventricular outflow tract in one case. There was direct extension or metastases to the lungs in two cases, the heart in one case, mediastinum or lymph nodes in two cases and the pleura in one case. Ultrastructural examination in one case revealed cells with features of smooth muscle cells and myofibroblasts. Immunohistochemical examination of three cases gave the following results: vimentin and smooth muscle specific actin was positive in all three cases, desmin in one case and cytokeratin in one case. No positivity was found for Factor VIII. This and other studies indicate that histologically most pulmonary artery sarcomas are leiomyosarcomas or "undifferentiated spindle cell sarcomas". Immunohistochemical and ultrastructural examinations favour an origin from myofibroblasts, probably derived from multipotent (undifferentiated) cells in the wall of the vessel. Most lesions show extensive intrathoracic growth although they rarely metastasize outside the thoracic cavity. They have a poor prognosis although some cases are currently being diagnosed during life.