Structural Characterization of Persistent Tympanic Membrane Perforations in Man

In the present structural study the authors investigated the border of permanent tympanic membrane (TM) perforations in patients selected for myringoplasty. Furthermore, a panel of monoclonal antibody markers that recognize different epitopes within glycosaminoglycans as well as antibodies to epidermal growth factor and fibronectin were applied to the sections. In half of the specimens the epithelial junction ended at the inside of the perforation border, whereas in the other half it was located at the perforation border itself. In the junctional area the keratinocytes were covered by a thick keratin layer which protruded as a spur centripetally in order to bridge the perforation. Epidermal cells formed papillae and contained remnants of keratinocyte nuclei that showed similarities to those of the skin in inflammatory conditions. The connective tissue layer was fibrous and showed areas containing sclerotic plaques. The inner epithelium of the TM had abundant ciliae, thus supporting the concept that cells of the mucosal lining of the TM are able to differentiate in inflammatory conditions into ciliated cells and secretory cells. The immunoreactivity of hyaluronan and other glycosaminoglycans, the immunoreactivity of epidermal growth factor, and the immunoreactivity of fibronectin, all of which are known to occur in healing wounds, were only scantily demonstrated; this could be one reason for the arrested healing and a reason why the natural drive to complete a mature closure is abandoned.     

The measurement of lipid peroxidation in isolated hepatocytes

Different techniques for the measurement of lipid peroxidation in isolated hepatocytes have been compared. Measurements of ethane production, chemiluminescence and fluorescent products correlated extremely well with those of malondialdehyde formation. Of the five different techniques studied, measurements of ethane production and chemiluminescence were found to be the most sensitive indices of lipid peroxidation. Incubation of hepatocytes for up to 4 hr in the presence of ethylmorphine and aminopyrine, at concentrations known to stimulate H202 production, completely failed to increase the amount of chemiluminescence, malondialdehyde or ethane produced in these cells, indicating that the drug-stimulated production of H₂O₂ did not lead to an increased rate of lipid peroxidation in liver cells under the experimental conditions employed. The relationship between lipid peroxidation, as measured by chemiluminescence and ethane production, and the cytotoxic effects of bromobenzene and carbon tetrachloride has also been studied. The results obtained further indicate that lipid peroxidation is an important event in carbon tetrachloride hepatotoxicity, but that it appears to be only a subsequent event in bromobenzene toxicity, possibly occurring only as a result ofglutathione depletion and cell death.     

Intracranial Myeloid Metaplasia in Myelofibrosis

In a man aged 62 years with a 14-year-history of polycythaemia vera progressing into a myelofibrotic stage symptoms and signs of an intracranial tumour with increased intracranial pressure developed. CT scan as well as angiography of the right internal carotid artery revealed richly vascularized masses within the meninges. The patient died in endocarditis and progressive heart failure and at autopsy the intracranial masses were shown to be due to meningeal myeloid metaplasia. The literature is reviewed and it appears that myeloid metaplasia within the central nervous system might be more common than has been hitherto anticipated. A CT scan is to be recommended in myelofibrosis whenever symptoms and signs suggesting intracranial disease are present.     

Dissociation between antidiuretic response and renal medullary cyclic AMP levels in the rat

Renal tubular bicarbonate reabsorption and acidification were evaluated in phosphate depleted rats (PD) and controls. After 33 days of phosphate depletion, urine pH of PD rats (N=5, 6.36±0.15) was significantly higher than control (N=5, 5.64±0.09,P<0.005) following an NH₄Cl load. Urinary titratable acid of PD rats (9.6±1.8) was significantly reduced compared to control (117.2±19.7 Eq/3 h,P<0.001), whereas NH ₄ ⁺ excretion was not different. The plasma HCO ₃ ^– thresholds at which bicarbonaturia occurred (approximately 25 mEq/l) were identical in controls and phosphate depleted rats during isotonic bicarbonate infusion. The higher urine pH of phosphate depleted rats following NH₄Cl administration was not due to low urinary phosphate as 3-day phosphate depleted rats could normally acidify urine after NH₄Cl (pH=5.86±0.09,N=6 vs. control 5.87±0.08,N=6,P=N.S.) despite urinary phosphate excretion as low as in 33-day PD rats. These data indicate the presence of impaired distal tubular acidification in chronically phosphate depleted rats.Former trainee of the Cardiovascular Research Program and currently a third year medical student at The University of Michigan Medical School.     

Incorporation of [14C] nicotine into growing melanin

Foetal eye melanin in pigmented mice showed much greater accumulation of injected [N-methyl-¹⁴C] nicotine-d-bitartrate than maternal eye melanin (ratio ca. 5:1). Nicotine seems to be accepted as a precursor in the formation of new melanin, due possibly to a structural resemblance to the main precursor of melanin, indole-5,6-quinone.     

Analysis of CD27 surface expression on T cell subsets in MS patients and control individuals

Within the peripheral blood, CD4⁺CD27⁻ T cells only reside within the CD45RAT ⁻(memory or primed) T cell subset. Cells with this phenotype have characteristics of specialized effector T cells according to their cytokine secretion profiles and the expression of tissue-specific adhesion molecules. This subset was previously found to be increased in certain diseases that are associated with immune activation. Therefore we analyzed CD27 expression of peripheral blood and CSF T cells in MS patients. Within the CD4⁺ T cell subset no differences were seen between MS patients and controls in proportions of CD45RA⁻CD27⁻ cells. However, when the CD3⁺ T cell compartment was analyzed, CD27⁻ cells were also found within the CD45RA⁺ subset. These cells, most likely CD8⁺, are significantly reduced in PBL and CSF of MS patients as compared with OND patients. In MS and OND groups the level of CD27⁻ cells in peripheral blood correlated significantly with that in CSF, indicating a balanced migration of CD27⁻ cells between the two compartments. In OIND patients, however, this equilibrium was lost. The correlation of the level of CD27⁺ cells with the amount of intrathecally produced IgG in MS patients may suggest that CD27⁺ cells are responsible for B cell help in this disease.     

Pituitary involvement in the sexual differentiation and 3-methylcholanthrene induction of rat liver microsomal monooxygenases

Liver microsomal monooxygenase activities with several drugs and model substrates were determined for male rats, that had been given a pituitary implant or which had been hypophysectomized and injected with 3-methylcholanthrene. The effect of implanting a male or female rat pituitary into an immature male rat was to cause a change to a more typically female pattern of monooxygenase activities, i.e. ethylmorphine and aminopyrine N-demethylases and ethoxycoumarin O-deethylase, which are less active in adult female than male rats, were suppressed and ethoxyresorufin O-deethylase, which is more active in females, was induced. The effects of pituitary implantation on the biphenyl and benzo(a)pyrene hydroxylases were apparently unrelated to sex-differences in the activities of these enzymes. The inducibility by 3-methylcholanthrene of cytochrome P448-catalysed reactions was decreased 2–3-fold by prior hypophysectomy of adult male rats.