Morphology of the lymphoid tissue of the bronchus in healthy persons of various ages, and the effect of smoking

The results of 315 endonasal operations on the lacrimal duct with long intubation are analyzed. The most incident complication of long intubation of the lacrimal duct is formation of intubation granulomas, which are most often localized in the inferior lacrimal canaliculus; their etiology is sometimes allergic--they form as a response of adjacent tissues to the material of the intubation tube, and the findings of our recent histological study prove it. The diagnosis of intubation granulomas is easy in the majority of cases. The treatment consists in removal and obligatory adequate total and local antiallergic therapy decelerating the growth and relapses of granulomas. After removal of the intubation tube the growth of granulations ceases and a fine cicatrix forms.     

Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2alpha kinase homolog

Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2alpha kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2alpha phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA-regulated (PKR), an eIF2alpha kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.     

Heparin removal after cardiopulmonary bypass in a patient with adverse reaction to protamine

A 74-year-old man underwent elective coronary surgery under cardiopulmonary bypass. A few minutes after the protamine administration was started, he suddenly developed a severe hypotension necessitating cardiac massage and recannulation for pump assistance. A further test dose of protamine provoked an identical reaction. We installed a Heparin Removal Device, which allows for ex-vivo deheparinization. In 35 minutes ACT decreased from 480 sec to 180 sec and clots appeared in the operating field. This system provides an excellent alternative to protamine in patients with an adverse reaction to protamine.     

Seasonal variations in T-lymphocyte response to grass pollen allergens from pollen-allergic patients and healthy controls

Recurrence of membranous nephropathy after renal transplantation has been reported either anecdotally or in a few series. In the present study, the potential risk factors as well as hitherto unreported actuarial risk for recurrence and graft loss due to recurrence were evaluated by combining data of a series of transplanted patients with MN at Louvain Medical School (n = 12) and at Lyon (n = 18; previously reported by Couchoud et al. 1995) giving a total of 30 patients. No risk factor for recurrence was identified as there was no statistical difference between the patients with and without recurrence for duration of MN in native kidneys or of pretransplant hemodialysis, presence of HLA-DR3, graft origin and use of cyclosporin. Actuarial risk for recurrence reached 29% at 3 years, plateauing up to 10 years. The outcome of recurrence was poor since the actual risk for graft loss among patients with recurrent MN was 38 and 52% at 5 and 10 years, respectively.     

Modeling the cross-sectional relationships between religion, physical health, social support, and depressive symptoms

The authors examined models of the relationships between religious activities, physical health, social support, and depressive symptoms in a sample of 4,000 persons age 65 and over. Religious activity was examined first as a single composite construct and then split into three component variables that were examined individually. Religious activity as a single construct was correlated with both social support and good physical health but was unrelated to depression. Split into the three components, model fit was significantly increased. Frequency of church attendance was positively related to physical health and negatively related to depression, but was surprisingly unrelated to social support. Frequent churchgoers were about half as likely to be depressed. Private prayer/Bible reading was negatively correlated with physical health and positively correlated with social support, but unrelated to depression. Religious TV/radio listening was unrelated to social support, negatively related to good physical health, and, unexpectedly, positively associated with depression.     

Identification of a firefly luciferase active site peptide using a benzophenone-based photooxidation reagent

Firefly luciferase catalyzes the highly efficient emission of yellow-green light from substrate luciferin by a series of reactions that require MgATP and molecular oxygen. We prepared 2-(4-benzoylphenyl)thiazole-4-carboxylic acid (BPTC), a novel benzophenone-based substrate analog, intending to use it in photoaffinity labeling studies to probe the luciferase active site. Instead, we found that while BPTC was a potent photoinactivating reagent for firefly luciferase, it was not a photoaffinity labeling agent. Using proteolysis, reverse phase high-performance liquid chromatography, tandem high performance liquid chromatography-electrospray ionization mass spectrometry, and Edman sequencing, we identified a single luciferase peptide, 244HHGF247, the degradation of which was directly correlated to luciferase photoinactivation. Results of enzyme kinetics and related studies were consistent with this peptide being at or near the luciferin binding site. Further, peptide model studies and additional investigations on the nature of the photoinactivation process strongly suggested that BPTC catalyzed the formation of singlet oxygen at the active site of the enzyme. We describe here an uncommon example of active site-directed photooxidation of an enzyme by singlet oxygen.     

Tissue equivalent vessel phantoms for intravascular ultrasound

The presence of the non-selective protein kinase C (PKC) inhibitors, staurosporine (100 nM) and polymyxin B (100 microM) in cultured human RPE cells for more than 24 h triggers apoptotic death. Apoptosis is characterized by a diminishing number of cells, a labelling of nuclei by the TUNEL method and by observable morphological changes. An inhibitor of PKC and cyclic nucleotide-dependent protein kinases, 1-(5-isoquinolinesulphonyl)-2-methyl piperazine (H-7; 100 microM), was without effect, as was the specific PKC inhibitor, calphostin C (100 nM). The PKC-activating phorbol esters, phorbol-12-myristate-13-acetate (PMA; 1 microM) and phorbol-12,13-dibutyrate (PDB; 1 microM) and the non-tumour-promoting phorbol ester, 4 alpha-PMA (1 microM) were without effect, as was the diacyl glycerol analogue, 1,2-dioctanoyl-snglycerol (DOG; 10 microM). The PKC activators did not attenuate the apoptosis induced by staurosporine or polymyxin B. Furthermore, deprivation of glucose and oxygen (simulated ischemia) for 72 h induced apoptosis: this could be prevented by inclusion of 10% (v/v) foetal bovine serum (FBS) but not by a variety of PKC activators. Six PKC isoenzymes were shown to be present in RPE cells (alpha, beta 1, beta 2, delta, epsilon, E) and only the calcium-dependent cPKC levels changed after treatment with staurosporine or simulated ischaemia. Since only the less selective inhibitors of PKC induced apoptosis, it is suggested that PKC is not involved directly in the induction process of apoptosis in RPE cells. It is possible that the staurosporine and polymyxin B-induced effects of apoptosis in RPE cells are triggered by an unknown kinase-dependent pathway, but whether the 'ischaemia'-induced death is related to this same process remains to be elucidated.     

Solid-state REDOR NMR distance measurements at the ligand site of a bacterial chemotaxis membrane receptor

The Escherichia coli serine receptor senses serine levels in the environment and transmits this information across the bacterial inner membrane to modulate a protein phosphorylation cascade which controls swimming behavior. Solid-state nuclear magnetic resonance (NMR) has been used to characterize specific structural features of the ligand binding site interactions in the intact, membrane-bound Ser receptor. Rotational-echo double-resonance (REDOR) experiments on [15N]Ser bound to a [1-13C]Phe-receptor preparation are used to measure distances between the ligand amino group and the carbonyls of two phenylalanine residues in the ligand binding pocket. The results indicate two 4.0 +/- 0.2 A distances, in excellent agreement with the X-ray crystal structure of a soluble fragment of the homologous aspartate receptor [Milburn et al. (1991) Science 254, 1342-1347]. These results confirm the similarity of the binding sites of the Asp and Ser receptors, and demonstrate the feasibility of using solid-state NMR measurements to obtain specific structural information on the 120 kDa intact receptor for probing transmembrane signaling mechanisms.     

Centralized follow-up of patients treated for head and neck cancer

In a prospective study, the value of the clinical follow-up after treatment for head and neck cancer has been assessed. A total of 407 visits in 377 patients were recorded during a three month period in 1993 at the two major radiotherapy departments in Denmark. The results showed that 61% of follow-up visits included one or more problems either related to treatment morbidity or tumour recurrence. About 50% of all visits included treatment related normal tissue problems, and 30% had problems that required intervention. Although the majority of problems occurred within a few years after treatment, 47% of patients at three to four years observation time still had one or more problems. A total of 34 new tumour recurrences were found in the period, and of these 11 (32%) were asymptomatic. It is concluded that head and neck cancer patients have both tumour and normal tissue problems several years after the end of treatment. Since effective salvage treatment improves local control significantly, early detection of possible recurrence is important. A follow-up period of four to five years is recommended-preferably by qualified experts in the management of both recurrent disease and treatment morbidity.     

Fatal hand sepsis in Tanzanian diabetic patients

Hand infections are common presentations among diabetic patients admitted to hospital in Tanzania. The morbidity and mortality are high and patients' hospital inpatient stay tend to be prolonged because of suboptimal therapy. We describe four diabetic patients with hand infections and fatal outcomes. In contrast to patients with foot infections, none of our patients had clinical evidence of peripheral neuropathy or vascular disease. All four patients eventually died in hospital after acquiring hand sepsis and diabetic ketoacidosis which did not respond to prolonged courses of intravenous insulin and antimicrobials. Literature review suggests such infections are at least as likely to include Gram-negative organisms as Staphylococcus aureus. Primary management should have included aggressive surgery with limb amputation if necessary with adjunctive antimicrobial therapy.