Multiple sclerosis: myelin basic protein induced mRNA expression of proinflammatory cytokines in mononuclear cells is suppressed by interferon-β 1b in vitro

Beta-interferon (IFN-β) is a promising treatment in multiple sclerosis (MS), reducing the exacerbation rate and MRI lesion burden, as well as the disease progression in relapsing-remitting MS. IFN-β was originally defined by its antiviral effects, but the interest has recently been focused on its immunomodulatory properties. Myelin basic protein (MBP) is one of several autoantigens considered to be the target for autoaggressive immune responses, which eventually might lead to the development of MS. To study in-vitro effects of IFN-β1b on MBP induced cytokine expression, mRNA for the Th1 cytokines IFN-γ and TNF-α, the Th2 related IL-4 and IL-6, the cytolytic perforin and the immune response downregulating TGF-β was measured with in situ hybridization after culture of blood mononuclear cells (MNC) in the presence and absence of MBP. Numbers of cells expressing IFN-γ, TNF-α, perforin and IL-4 mRNA were significantly suppressed after culture with 10 U/ml IFN-β1b. No such effect was seen on MBP induced IL-6 or TGF-β mRNA expression. These observations suggest that one of the major effects of IFN-β1b is the induction of a shift in the cytokine mRNA profile towards a more immunosuppressive pattern. In parallel in vitro tests, the control substance dexametasone (40 μg/ml) reduced the numbers of cells expressing mRNA for all cytokines under study with the exception of TGF-β, to an extent equal to or even more pronounced than IFN-β1b.     

A "new" intraabdominal artery. The pedicled right gastroepiploic artery for myocardial revascularization.

The right gastroepiploic artery (GEA) was used as a pedicled conduit for direct coronary artery revascularization in 20 patients presenting with more or less exhausted saphenous vein resources. The early angiographic patency of the GEA conduit appears to be satisfactory when it is connected to the right coronary artery system. A distinct disadvantage of GEA grafting is the necessity to enter the abdominal cavity, which may lead to probably rare and as yet unrecognized morbidity. Future abdominal surgery may injure the GEA conduit unless its topographic relations to the prepyloric antrum, liver and diaphragm are properly recognized. The surgeon must then be prepared to encounter antegastric, retrogastric, antehepatic, transhepatic and retrohepatic routes of the redirected intraabdominal artery. The present paper addresses this problem. Preoperative angiography of the celiac trunk and superior mesenteric artery may be helpful in decision-making when a patient reports or records show that a graft has been harvested from the abdominal cavity.     

Vibration exposure and conditioning lesion effect in nerves: an experimental study in rats.

The effects of controlled vibrations of defined frequency (80 Hz), acceleration (32 m/s2 root mean square), and duration (5 hours daily, 2 or 5 days) induced to the hind limb of rats on the regeneration potential in the sciatic nerve after a test crush lesion were determined. Exposure to vibration induced a marked and significant increase in outgrowth length of axons from the crush injury as evaluated after 3 and 6 days with the pinch reflex test. This effect was still observed 1 month but not 3 months after exposure to vibration. Even such a short duration of vibration exposure as 2 days induced an increased length of outgrowth. Such a conditioning effect may be due to local changes in the environment of the axons or to changes in the nerve cell bodies in the dorsal root ganglion. The results indicate that an alarm reaction exists in the nerve at a time point where no structural changes are observed in the nerve. By inducing such a conditioning lesion to nerve tissue, vibration represents a trauma corresponding to a crush lesion or transection of the nerve.     

Natural killer cell activity and CSF monoamine metabolites in suicide attempters

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.     

Sequential scintigraphy and orthoradiographic measurement of femoral shortening after femoral neck fracture

The objective of the study was to assess scintigraphic patterns and femoral shortening after femoral neck fracture in order to select predictive parameters for late complications. Eighty-eight patients with osteosynthesized femoral neck fractures were followed for 2 years with regular scintigraphic evaluations and orthoradiographic measurements of femoral length shortening. Four different patient categories were identified with regard to the late outcome: two different groups with uneventful healing and two different groups with late complications. Accordingly, a high scintigraphic uptake at 1 month may eiher point to an uneventful healing if combined with minor femoral shortening or indicate failure if combined with a high degree of femoral shortening. In contrast, low scintigraphic uptake may either reflect primary fracture healing if accompanied by minor femoral shortening or predict failure if a high degree of femoral shortening is present. Compared with using scintigraphy alone, combined scintigraphic evaluation and assessment of femoral shortening increased the accuracy for prediction of late failures from 80% to 93%. Early scintigraphic patterns after osteosynthesis of femoral neck fractures have to be validated with care. Radiographic assessment of femoral shortening, which is less invasive, gives better prognostic accuracy and should therefore be preferred for this purpose.     

Continued surveillance of cancer incidence among Swedish smelter workers.

A cohort study of workers at a smeltery in northern Sweden showed an excess mortality, mostly due to deaths in cancer (especially in the respiratory organs) and circulatory diseases. Further follow-up of the cohort showed a decreasing trend in lung cancer incidence and mortality. The cohort studied has now been expanded and comprises 6,334 blue-collar workers first employed 1928-1979. They were followed in the cancer register up to 1987-01-01 and in the cause-of-death register up to 1988-01-01. The decreasing trend in lung cancer incidence and mortality continued but there was still an elevated lung cancer incidence among the workers when compared with Swedish males. The cumulative occurrence of lung cancer since time of first employment was analyzed by different employment cohorts and a higher occurrence of lung cancer was found among those earlier employed.     

Mammographic growth rate, DNA ploidy, and S-phase fraction analysis in breast carcinoma. A prognostic evaluation in a screened population.

BACKGROUND. The authors examined prognostic factors in 158 cases of breast carcinoma with known mammographic tumor volume doubling times (DT). METHODS. The tumors were retrospectively reexamined histologically and flow cytometric analysis of DNA ploidy and S-phase fraction (SPF) was performed on archival paraffin-embedded material in each case. Life tables and Cox multivariate analyses were used for statistical evaluation of prognostic factors. RESULTS. In univariate analysis of survival data, clinical and pathologic stage, histologic grade, the presence of axillary lymph node metastases, and SPF were significant prognostic predictors, but mammographic DT and DNA ploidy were not. SPF also contributed prognostic information in the subgroup of carcinoma cases detected by screening. In a Cox multivariate analysis, SPF, the presence of axillary lymph node metastases, and Stage II-III disease (as opposed to Stage I disease) were independent significant predictors of survival. In univariate analyses of distant disease-free survival, clinical and pathologic stage, tumor size, histologic grade, the presence of involved axillary nodes, DT, and SPF all were significant prognostic factors. CONCLUSIONS. SPF, stage, and lymph node status were important prognostic factors in this patient material with predominantly small and node-negative breast carcinomas, whereas DNA ploidy and mammographic DT provided less prognostic information. The prognosis of carcinoma detected during screening did not differ significantly from that of breast carcinoma discovered otherwise in this selected patient group.     

Expression of the homeobox engrailed gene during the embryonic development of the nervous system of the trout (Salmo fario L.).

The expression of the engrailed homeobox gene during trout embryogenesis has been examined using immunohistochemistry and the monoclonal antibody 'Mab 4D9'. Engrailed has been suggested to play an important role during development by controlling position-specific characteristics in the CNS of the early embryo. In the present study we have analyzed the expression of engrailed at 5 stages of embryonic development of the trout (Salmo fario L.). The earliest stage analyzed was when the optic vesicles appear. Engrailed was then expressed in the posterior mesencephalon and anterior metencephalon, in a caudorostrally decreasing gradient. As the embryo develops, the pattern of the engrailed expression increases in spatial complexity. Thus, in the later stages of development, just before hatching, engrailed was found in hypothalamic areas, the germinative matrix layer of the cerebellum, the mesencephalic tegmentum, the caudal optic tectum and in the area of the trigeminal motor nucleus. This is similar to the distribution of engrailed in embryos of amphibians, birds and mammals.