10 years survival of patient with lung cancer and cerebral metastasis

The authors describe the case of survival for the period of 10 years after brain metastasis surgery and removal of the left lung upper lobe due to adeno-squamous cells carcinoma. Surgery did not generate any complications. Within 8 years after the surgery the radiological examination showed infiltrations resembling changes typical for tuberculosis. Microbiological analysis showed a culture of Mycobacterium kansasi leading to diagnosis of mycobacteriosis. Hence the antituberculous treatment was extended to 12 months to be interrupted due to liver damage. Two years later the patient experienced incident of haemoptysis. Detailed examination and assessment of the respiratory tract condition revealed COPD without features of renewal of the neoplastic process or infection by Mycobacterium tuberculosis or mycobacterium other than tuberculosis. This case demonstrates that aggressive surgical approaches to lung cancer with solitary cerebral metastasis significantly improve patient survival and justifies its widespread use.     

Characterization of FimH adhesins expressed by Salmonella enterica serovar Gallinarum biovars Gallinarum and Pullorum: reconstitution of mannose-binding properties by single amino acid substitution

Recombinant FimH adhesins of type 1 fimbriae from Salmonella enterica serovar Gallinarum biovars Gallinarum and Pullorum, in contrast to those of Salmonella enterica serovar Typhimurium, did not bind to high-mannose oligosaccharides or to human colon carcinoma HT-29 cells. However, mutated FimH proteins from biovar Gallinarum and biovar Pullorum, in which the isoleucine at position 78 was replaced by the threonine found in S. enterica serovar Typhimurium, bound well to glycoproteins carrying high-mannose oligosaccharides and colon carcinoma cells. The loss of sugar-binding properties by biovar Gallinarum and biovar Pullorum FimH adhesins, which are a part of the type 1 fimbriae, is most probably the result of a single T78I mutation, as was proven by site-directed mutagenesis of FimH proteins.     

Spread of old and new clones of epidemic methicillin-resistant Staphylococcus aureus in Poland

Objective: To study the relatedness among methicillin-resistant Staphylococcus aureus (MRSA) isolates originating from two regions of Poland using different epidemiologic typing methods.
Methods: Forty-five MRSA isolates (19 from Warsaw and 26 from the Grajewo region) were collected between 1995 and 1996. For phenotypic epidemiologic analysis, antimicrobial susceptibility testing (AST) with a panel of 19 antibiotics was performed. For genotypic epidemiologic analysis, pulsed-field gel electrophoresis (PFGE) of Smal-digested chromosomal DNA, restriction endonuclease analysis of plasmid (REAP) DNA digested by Hin dIII, random amplification of polymorphic DNA (RAPD) and binary typing (BT) of genomic DNA by hybridization with five different RAPD-generated strain-specific DNA probes, were used.
Results: Six clusters of clonally related strains were found among the MRSA isolates analyzed. Three of these, identified in both regions, were related to previously described Polish epidemic clones, designated HeEMRSA-Pol1 (heterogeneously methicillin resistant—18 isolates) and HoEMRSA-Pol1 (homogeneously resistant—two clones, six isolates each). The remaining three clones, identified in the Grajewo region only, are previously undescribed. One of these, represented by 11 isolates, appears to be new epidemic heterogeneous MRSA clone (HeEMRSA-Pol2). Results of PFGE and BT in general showed good correlation, and, in some cases, RAPD using AP1 and AP7 primers could discriminate between isolates belonging to single PFGE or BT types. Broad AST and REAP can provide useful additional information concerning relatedness.
Conclusion: Evidence for the spread of previously recognized epidemic MRSA clones in Poland and the presence of a new epidemic heterogeneously resistant clone of MRSA in hospitals outside Warsaw is documented.     

White matter damage precedes that in gray matter despite similar magnetic resonance imaging changes following cerebral hypoxia-ischemia in neonatal rats

We hypothesized that the cerebral injury produced by hypoxia-ischemia (HI) in neonatal rats would differ in white compared with gray matter as detected histologically or with magnetic resonance (MR) imaging methods. Maps of T₂ and the apparent diffusion coefficient (ADC) of water were acquired in 1-week-old rats at times prior to cerebral HI (right carotid artery occlusion plus 1.5 h of hypoxia), within the last 5–10 min of HI, and 1 h or 24 h after HI. Near the end of HI, ADC decreased and T₂ increased in both cortical gray and subcortical white matter within the cingulum of the HI hemisphere. One hour after HI, ADC partially recovered, but T₂ remained increased and then increased further by 24 h post-HI. In contrast to the similar MR responses in white and gray matter, histological evidence for irreversible cell damage occurred in white matter earlier than in gray matter within the HI hemisphere. At 1 h post-HI, rarefied or disrupted nerve fibers and an increase in TUNEL-positive cells were observed within white matter in the cingulum, whereas neurons within the cortical gray matter appeared normal. By 24 h post-HI, damage was apparent in both white and gray matter. Thus, MR imaging detected acute tissue edema following cerebral HI in both gray and white matter but did not distinguish between the early irreversible tissue injury detected histologically in white but not gray matter in this rather severe model of neonatal encephalopathy.     

CD80 and CD86 expression on LPS-stimulated monocytes and the effect of CD80 and CD86 blockade on IL-4 and IFN-gamma production in nonatopic bronchial asthma

CD80 and CD86 seem to play an important role in the allergen-induced secretion of interleukin (IL)-5 and IL-13. Up to now, the expressions of CD80 (B7.1) and CD86 (B7.2) on monocytes and the kinetics of the expression of these molecules on lipopolysaccharide-stimulated monocytes in nonatopic asthma have not been defined. Using monoclonal antibodies, we have compared the expressions of CD80 (B7.1) and CD86 (B7.2) on the monocytes of healthy persons and nonatopic asthmatic patients. We have also assessed the effect of CD80 and CD86 inactivation on IL-4 and interferon (IFN)-gamma production in nonatopic asthmatics and healthy subjects. We found that a low expression of CD80 (1.64 +/- 0.65 vs. 3.53 +/- 1.43%) and a moderate expression of CD86 (41.25 +/- 13.4 vs. 49.46 +/- 11.49%) on the studied monocytes were characteristic for asthma. In nonatopic asthma patients inactivation of CD80 or CD86 blockade significantly reduced IFN-gamma production by T lymphocytes (p < 0.02; p < 0.03). In both the studied groups, anti-CD80 antibodies did not diminish T lymphocyte production of IL-4. However, anti-CD86 antibodies significantly (p < 0.04) reduced the IL-4 concentration in culture supernatants. Our results confirm that both the CD80 and CD86 molecules play an important role in the maintenance and amplification of the inflammatory process. It suggests that in the inflammatory process that occurs in nonatopic bronchial asthma, Th1 as well as Th2 lymphocytes are equally important.     

Effectiveness of divergent selection for open-field activity in rabbits and correlated response for body weight and fertility

Two lines deriving from the same rabbit stock were selected for 8 generations for high (H) or low (L) locomotor activity score in the open field (OFS). The divergent selection was most effective up to the 3rd generation in the H line and up to the 4th generation in the L line. In further generations a decrease of OFS in the H line and a floor effect (OFS = 0) in the L line were observed. The mean OFS increased significantly in consecutive trials in the H line, whereas this increase was non-significant in the L line. There was a negative and very high correlation between the latency to enter the open field and the OFS (–0.95 and –0.98 for the H and L line, respectively). The realized heritability of the OFS was 0.46 and 0.23 in generations 0–3 within the L and H line, respectively, and 0.44 and –0.06 in generations 0–8. As calculated on the basis of divergent selection, the heritability was 0.31 and 0.15 for generations 0–3 and 0–8, respectively. The L rabbits were heavier shortly before (4th wk, P < 0.001) and after (8th wk, P < 0.01) weaning, than those of the H line, whereas the H rabbits grew faster (P < 0.05) between the 4th and 20th wk of age. There was a tendency for decreasing weight gains in consecutive generations. Generally, a lower percentage of H females delivered litters than those of the L line, but this was due to a very low percentage of such females in the 3rd and 6th generations. It can be assumed that H and L lines represent different, i.e., active and passive, coping strategies. These lines of rabbits offer increased possibilities for physiologically and ethologically oriented studies, e.g., on the welfare of caged animals.     

Postischaemic changes in protein synthesis in the rat brain: effects of hypothermia

Protein synthesis, measured as [¹⁴C]-leucine incorporation into proteins, was studied in the normothermic rat brain following 15 min of transient cerebral ischaemia and 1 h, 24 h and 48 h of recirculation, and in the hypothermic (33°C) brain following 1 h and 48 h of recirculation. Ischaemia was induced by bilateral common carotid occlusion combined with hypotension. Following normothermic ischaemia, incorporation of [¹⁴C]-leucine was depressed by 40–80% at 1 h of recirculation in all brain regions studied. At 48 h postischaemia, incorporation returned to normal or above normal levels in the inner layers of neocortex, the CA3 region, the striatum and the dentate gyrus, while in the outer layers of neocortex and in the hippocampal CA1 region the incorporation was persistently decreased by 26% and 40% respectively. At 24 and 48 h postischaemia, protein synthesis in the CA1 region and the striatum could be attributed to proliferating microglia. Intra-ischaemic hypothermia ameliorated the persistent depression of protein synthesis in the CA1 region at 48 h postischaemia, and a two-fold increase compared to the normothermic group was observed both in the CA1 region and the striatum. In the cortex, eucaryotic initiation factor 2 activity transiently decreased at 30 min postischaemia. In animals subjected to intra-ischaemic hypothermia, the eucaryotic initiation factor 2 activity was reduced by 50% of control at 30 min of recirculation compared with 77% in normothermic animals. We conclude that the postischaemic depression of protein synthesis is in part caused by a decrease in eucaryotic initiation factor 2 activity. The early postischaemic depression may reflect a reaction of the tissue to stress, while the late persistent depression, which is normalised by intra-ischaemic hypothermia, may be related to the mechanism of cell death.     

Poly(oxyethylene)s terminated at both ends with phosphonium ion end groups, 2. Properties

Poly(oxyethylene)s with number-average degrees of polymerization (DP_n) ranging from ≈ 6 to ≈ 80, terminated at both ends with phosphonium ion end groups (diionic poly-EO), have been prepared and characterized as described in the preceding paper. Viscosities of diionic poly-EO were measured, both in solution and in bulk. In chloroform solution, at low concentration (< 1 g/100 mL), the viscosity of diionic poly-EO was lower than the viscosity of nonionic (terminated with HO-groups) poly-EO of the same DP_n. At higher concentrations, the viscosity of diionic poly-EO exceeded that of nonionic poly-EO and increased sharply with increasing concentration. At the constant weight concentration of ≈4 g/100 mL, the viscosities of short-chain diionic poly-EO were higher and those of longer chain diionic poly-EO were lower than the viscosities of the nonionic poly-EO of the same chain lengths. These results were attributed to a predominant intramolecular aggregation of terminal ionic groups at low concentration of ionic groups in solution and predominant intermolecular aggregation at higher concentration of ionic groups. The results of bulk viscosity measurements as well as the results of differential scanning calorimetry measurements of the dependence of the glass transition temperature on the DP_n of diionic poly-EO indicated that in bulk physically cross-linked networks were formed, due to intermolecular aggregation of terminal ionic groups.     

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.