Inflammatory and non-inflammatory inclusion body myositis

Summary In ten patients with inclusion body myositis (IBM) five muscular biopsies showed profuse inflammatory exudates and three showed a few scattered inflammatory cells with partial invasion in some muscle fibers. No inflammatory cells were seen in two cases. In all patients, histopathological, histomorphometric and immunocytochemical studies were performed. Immunocytochemistry for the class I and class II major histocompatibility complex gene product (MHC) was performed in all cases and in ten control muscles including: normal muscles [3], dermatomyositis [3], polymyositis [3], scleroderma [1]. In the five cases of IBM with inflammatory exudates, subsets of lymphocytes were analyzed with a panel of monoclonal antibodies against B cells, T4 cells, T8 cells, K and natural killer cells and macrophages. Some muscle fibers expressed class I MHC antigens in the inflammatory cases of IBM. These fibers were near the inflammatory exudates and occasionally showed a partial invasion. No expression of class I MHC was found in normal muscles and in non-inflammatory cases of IBM. The antigen which triggers the mononuclear cells in the inflammatory forms of IBM is probably not the filamentous inclusions in rimmed vacuoles. In other inflammatory myopathies, expression of class I MHC was present on all fibers in polymyositis, only in the perifascicular area in dermatomyositis and in scleroderma. It could be suggested that the term inclusion body muscle disease be applied to cases with rimmed vacuoles and IBM-like filaments without inflammatory cells.     

Image alignment by integrated rotational and translational transformation matrix

Presents an algorithm to align 2D images with similar densitometric patterns in the spatial domain. It performs automatic identification of control points through local maxima in normalized image cross correlations computed through projections of an image function on 2D orthonormal bases over a predefined circular domain. The image is subsequently subjected to translational and rotational corrections through an integrated transformation matrix obtained by the least-squares minimization technique. The algorithm restricts the corrections required for alignment to rotation and translation only, and care is taken to see that the image does not go through scaling (isotropic or anisotropic) or nonlinear distortions. The least-squares method results in implicit equations in three variables, theta , h, upsilon , representing rotation, and translations along x and y axes. The present algorithm, on the other hand, is based on an approximation that results in a set of explicit equations that are easy to solve. The mathematical validity of this approximation is proved and the results obtained show that the algorithm performs well with similar biological (histological, autoradiographic, and tomographic) images. The algorithm is iterative, and its computer implementation is discussed.     

Effects of long-term treatment with trandolapril on augmented vasoconstriction in rats with chronic heart failure

Background:

Despite the clinical relevance of angiotensin I-converting enzyme (ACE)inhibitors, their effects on impaired vascular function in patients and animals with chronic heart failure (CHF) have not been fully understood. This study was undertaken to determine whether long-term treatment with an ACE inhibitor improved the altered contractile properties of vessels from rats with CHF.

Methods and Results:

Twelve weeks after coronary artery ligation, the rats were sacrificed and the isometric tension development of thoracic aorta, pulmonary artery, and mesenteric artery with and without endothelium was examined. Contractile responses to norepinephrine and prostaglandin F₂α were augmented in endothelium-intact, but not in endothelium-denuded, thoracic aorta and pulmonary artery segments of the rat with CHF. The contractile response to angiotensin II was augmented in endothelium-denuded mesenteric artery segments of the rat with CHF, which was attenuated by indomethacin or diclofenac sodium but not by bunazosin. Trandolapril (3 mg/kg/d) was administered orally from the 2nd to 12th week after the operation. Treatment with trandolapril reversed the augmented contractile response of the rat with CHF to norepinephrine, prostaglandin F₂α, and angiotensin II almost to the levels in the sham-operated rat.

Conclusions:

The results demonstrate that an ACE inhibitor is capable of reversing altered vascular function in the rat with CHF, suggesting that vascular beds are possible sites of action for ACE inhibitors in the therapy for CHF.     

Hexachlorophene and the central nervous system

Summary A study on hexachlorophene encephalopathy in mice and baboons is reported. By light microscopy, a severe spongiform lesion of the central nervous system (CNS) was localized in the white matter, without myelin breakdown or cellular reaction. By electron microscopy, the myelin alteration was characterized by wide intralamellar spaces or splitting developed in the intraperiod line of compact sheaths. The acute changes described were induced by administration of the drug by the digestive or cutancous routes at various dosage levels in an aqueous solution or in talcum powder. The toxic effects depended on the age of the animals, the survival times and the concentrations of hexachlorophene, i.e., 6%, 3%, and 0.5%. The findings are compared with previous reports on the neurotoxicity of hexachlorophene and other chemicals in humans and experimental animals. Hexachlorophene cannot be recommended for use in young infants because of its neurotoxicity in very low doses as demonstrated in the present report.     

Investigations on physiological values of blood in industrial workers. Report 3. Serum colloid reaction and enzyme activity values

The purpose of this study is establish the physiological values of serum colloid reaction and serum enzyme activities representing the liver function. 1,732 industrial workers (1,035 males aged 35-65 yr, and 697 females aged 35-60 yr) were examined by the serum zinc sulfate turbidity test (ZTT) and serum thymol turbidity test (TTT) according to the standard method of "The Japanese society of gastroenterology," serum alkaline phosphatase (ALP) by Kind-King method, serum gamma-glutamyl transpeptidase (gamma-GTP) by the modified Orlowski method, and serum glutamic oxaloacetic transaminase (GOT) and serum glutamic pyruvic transaminase (GPT) by UV method. Then frequency distributions, geometric means, several percentile values of these six laboratory data and correlations among the values were determined. The results are as follows: 1) Frequency distributions of serum ZTT, TTT, ALP, gamma-GTP, GOT, and GPT almost fitted to the log-normal distribution. 2) Geometric means and 0-95th percentile or 5-95th percentile values in bracket were 6.6 (3.7-11.7) Kunkel unit for ZTT in male, 8.2 (5.1-13.0) Kunkel unit for ZTT in female, 0.6 (0-2.8) Kunkel unit for TTT in male, 0.8 (0-2.8) Kunkel unit for TTT in female, 6.6 (4.1-10.4) King-Armstrong unit for ALP in male, 5.5 (3.2-8.9 for 49 year or less, 4.6-10.3 for 50 yr or more) King-Armstrong unit for ALP in female, 15.8 (0-45) mU/ml for gamma-GTP in male, 8.4 (0-17 for 44 yr or less, and 0-20 for 45 yr or more) mU/ml for gamma-GTP in female, 21.4 (0-39) Karmen unit for GOT in male, 20.8 (0-35) Karmen unit for GOT in female, 13.9 (0-29) Karmen unit for GPT in male, and 12.7 (0-32) Karmen unit for GPT in female. 3) Serum ZTT and TTT levels were higher in female than in male. Both ALP and gamma-GTP levels were higher in male than in female, and have become high according to aging in female. Serum level of GPT was higher in male than in female. 4) There were significant positive correlations between serum ZTT and serum TTT levels, and also between serum GOT and serum GPT levels.     

Mathematical/computational challenges in creating deformable and probabilistic atlases of the human brain

Striking variations in brain structure, especially in the gyral patterns of the human cortex, present fundamental challenges in human brain mapping. Probabilistic brain atlases, which encode information on structural and functional variability in large human populations, are powerful research tools with broad applications. Knowledge-based imaging algorithms can also leverage atlased information on anatomic variation. Applications include automated image labeling, pathology detection in individuals or groups, and investigating how regional anatomy is altered in disease, and with age, gender, handedness and other clinical or genetic factors. In this report, we illustrate some of the mathematical challenges involved in constructing population-based brain atlases. A disease-specific atlas is constructed to represent the human brain in Alzheimer's disease (AD). Specialized strategies are developed for population-based averaging of anatomy. Sets of high-dimensional elastic mappings, based on the principles of continuum mechanics, reconfigure the anatomy of a large number of subjects in an anatomic image database. These mappings generate a local encoding of anatomic variability and are used to create a crisp anatomical image template with highly resolved structures in their mean spatial location. Specialized approaches are also developed to average cortical topography. Since cortical patterns are altered in a variety of diseases, gyral pattern matching is used to encode the magnitude and principal directions of local cortical variation. In the resulting cortical templates, subtle features emerge. Regional asymmetries appear that are not apparent in individual anatomies. Population-based maps of cortical variation reveal a mosaic of variability patterns that segregate sharply according to functional specialization and cytoarchitectonic boundaries.     

Lung deflation impairs alveolar epithelial fluid transport in ischemic rabbit and rat lungs

BACKGROUND: Because the fluid transport capacity of the alveolar epithelium after lung ischemia with and without lung deflation has not been well studied, we carried out experimental studies to determine the effect of lung deflation on alveolar fluid clearance. METHODS: After 1 or 2 hr of ischemia, we measured alveolar fluid clearance using 125I-albumin and Evans blue-labeled albumin concentrations in in vivo rabbit lungs in the presence of pulmonary blood flow and in ex vivo rat lungs in the absence of any pulmonary perfusion, respectively. RESULTS: The principal results were: (1) lung deflation decreased alveolar fluid clearance while inflation of the lungs during ischemia preserved alveolar fluid clearance in both in vivo and ex vivo studies; (2) alveolar fluid clearance was normal in the rat lungs inflated with nitrogen (thus, alveolar gas composition did not affect alveolar fluid clearance); (3) amiloride-dependent alveolar fluid clearance was preserved when the lungs were inflated during ischemia; (4) terbutaline-simulated alveolar fluid clearance was preserved in the hypoxic rat lungs inflated with nitrogen; (5) lecithinized superoxide dismutase, a scavenger of superoxide anion, and N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide, preserved normal alveolar fluid clearance in the deflated rat lungs. CONCLUSION: Lung deflation decreases alveolar fluid clearance by superoxide anion- and nitric oxide-dependent mechanisms.     

Screening for medium chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry

OBJECTIVE: To establish criteria for the diagnosis of medium chain acyl-CoA dehydrogenase (MCAD) deficiency in the UK population using a method in which carnitine species eluted from blood spots are butylated and analysed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). DESIGN: Four groups were studied: (1) 35 children, aged 4 days to 16.2 years, with proven MCAD deficiency (mostly homozygous for the A985G mutation, none receiving carnitine supplements); (2) 2168 control children; (3) 482 neonates; and (4) 15 MCAD heterozygotes. RESULTS: All patients with MCAD deficiency had an octanoylcarnitine concentration ([C8-Cn]) > 0.38 microM and no accumulation of carnitine species > C10 or < C6. Among the patients with MCAD deficiency, the [C8-Cn] was significantly lower in children > 10 weeks old and in children with carnitine depletion (free carnitine < 20 microM). Neonatal blood spots from patients with MCAD deficiency had a [C8-Cn] > 1.5 microM, whereas in heterozygotes and other normal neonates the [C8-Cn] was < 1.0 microM. In contrast, the blood spot [C8-Cn] in eight of 27 patients with MCAD deficiency > 10 weeks old fell within the same range as five of 15 MCAD heterozygotes (0.38-1.0 microM). However, the free carnitine concentrations were reduced (< 20 microM) in the patients with MCAD deficiency but normal in the heterozygotes. CONCLUSIONS: Criteria for the diagnosis of MCAD deficiency using ESI-MS/MS must take account of age and carnitine depletion. If screening is undertaken at 7-10 days, the number of false positive and negative results should be negligible. Because there have been no instances of death or neurological damage following diagnosis of MCAD deficiency in our patient group, a strong case can be made for neonatal screening for MCAD deficiency in the UK.