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Biomedical subjects

G Mall

Publications and source records attributed to G Mall.

At least 109 records · Page 6Linked to original sources

[Sialadenosis of the parotid gland after chronic nicotine use].

The effect of chronic nicotine consumption on the morphology of the rat parotid gland was investigated. After nicotine-loading for 90 days with an average serum nicotine concentration of 78 +/- 10 ng/ml a significant increase of acinar cell volume was observed. The acinar cells contained an increased number of enlarged light, immature secretory granules. These findings were confirmed by morphometric analysis. Further an increase of the granular endoplasmatic reticulum, an enlargement of the Golgi complexes and an oedematous swelling of intraglandular autonomous nerves were found. Similar findings have been observed in the parotid gland of animals and also of humans chronically treated with the beta-adrenergic drugs aludrin and isoproterenol, and have been termed "sialadenosis". It seems likely that the observed morphological alterations are caused by a stimulation of glandular beta-adrenoceptors via a nicotine-induced release of catecholamines from the adrenals.

Administration, Oral↗

Natural history of Coxsackievirus B3-induced myocarditis in ACA/Sn mice: viral persistence demonstrated by quantitative in situ hybridization histochemistry.

Enteroviruses are considered to be the major aetiological agents of myocarditis in humans. Recent in situ hybridization studies on endomyocardial biopsies and autopsy hearts indicate that enterovirus RNA can be detected (pattern of persistent infection) not only in acute myocarditis (pattern of acute infection), but also in chronic dilated cardiomyopathy. Our experimental studies on murine coxsackievirus B3 myocarditis provided evidence that persistent infection may also occur in mice. Quantitative in situ hybridization and immunohistochemistry as well as electron microscopical in situ hybridization experiments were performed on ACA/SnJ mice 3-30 days after infection. The pattern of acute infection (days 3-9 p.i.) is characterized by rapid progression of myocardial lesions, an increasing number of inflammatory cells and a high number of infected myocytes. Hallmarks of the persistent pattern (days 15-30 p.i.) are reduced inflammation, reduced numbers of persistently infected cells and a slow progression of myocardial lesions. Infection is primarily restricted to degenerated, atrophic myocytes and to fibroblasts.

Animals↗

Expression of 1,25-dihydroxyvitamin D3 receptors in normal and psoriatic skin.

Increasing evidence suggests an immunoregulatory function of the potent steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) which has been successfully applied for treatment of psoriasis. The skin is both a site of production and a target of 1,25(OH)2D3. In vitro, 1,25(OH)2D3 inhibits proliferation and stimulates differentiation of keratinocytes. We investigated the in situ expression of vitamin D-receptors (VDR) in normal and psoriatic skin by immunochemical methods. The VDR were visualized using the monoclonal antibody (MoAb) 9A7g to the VDR and the labeled avidinbiotin technique. Immunoreactivity was consistently confined to nuclei in all skin biopsies. In normal skin specimens (n = 10) VDR antigens were expressed in keratinocytes of all epidermal layers (except those of the stratum corneum) and in cells of the epidermal appendages. Double labeling experiments with MoAb to cluster-defined antigens indicated that melanocytes and approximately 75% of Langerhans cells exhibit 1,25(OH)2D3 receptors in normal skin biopsies (n = 5). Depending on their localization in skin compartments 42-62% of CD11b+ positive macrophages and 45-75% of CD3+ T lymphocytes expressed VDR. Non-lesional psoriatic skin specimens (n = 8) revealed nearly identical staining patterns. Lesional psoriatic skin specimens (n = 8) exhibited a significant increase of VDR expression both in basal and suprabasal epidermal layers as measured by computer-assisted morphometry and showed a remarkable change of the immune cell pattern: the densitity and proportion of VDR positive T lymphocytes and macrophages were higher in the epidermal and the perivascular papillary loop compartment. These in vivo findings strongly support the hypothesis that 1,25(OH)2D3 modulates immune response and cell proliferation/differentiation in human skin.

Adult↗

Hyperparathyroidism and abnormal 1,25(OH)2 vitamin D3 metabolism in experimental lead intoxication.

Clinical evidence points to disturbed calcium metabolism in lead (Pb) intoxication. To further clarify the mechanisms involved, serum levels of 1,25(OH)2D3, receptors for 1,25(OH)2D3 as well as size and ultrastructure of parathyroid glands were examined in Wistar Kyoto rats exposed to 1% lead (Pb) acetate in drinking water for 10 weeks (short-term study) or 0.001-1% Pb acetate for 24 weeks (long-term study). After administration of Pb for 10 weeks, bone Pb was significantly increased (641 +/- 66.9 (SD) vs. 0.648 +/- 0.39 mg kg-1 ash in controls). Total serum calcium and ionized Ca2+ (1.15 +/- 0.031 vs. 1.25 +/- 0.03 mmol l-1) were significantly decreased. Renal function (Ccr) was unchanged, but urinary cAMP excretion and circulating 1,25(OH)2D3 (177 +/- 10.9 vs. 232 +/- 18.9 pmol l-1) were diminished. Specific binding of 1,25(OH)2D3 was increased in parathyroids (Bmax 128 +/- 4.7 vs. 108 +/- 0.6 fmol mg-1 protein) and intestinal muscosa; Bmax failed to adequately rise in response to pretreatment with 1,25(OH)2D3 (2 x 10 ng day-1 for 4 d) in Pb-exposed animals. Receptor characteristics (sedimentation constant, KD, DNA affinity) were unchanged. Parathyroid weight was significantly increased (178 +/- 25 vs. 96 +/- 34 micrograms) with no change of estimated nuclear volume, cell volume or cell ultrastructure. After 24 weeks of Pb exposure, a dose-dependent but non-linear increase of parathyroid weight was noted between 0.001% and 1% Pb in drinking fluid. The present study documents secondary hyperparathyroidism associated with, and presumably caused by, hypocalcaemia and low 1,25(OH)2D3 levels, in experimental Pb intoxication.

Animals↗

[Clinical morphology of the sternum].

The length, width and thickness of the sternum were measured in 74 adult specimens with the aim of optimizing the dimensions of staples used after sternotomy. This article describes the experimental procedure and presents the results. Sex differences were confined mainly to the length, with males measuring 16.5 cm, and females 15 cm. Width and thickness maxima (7.4 cm and 1.7 cm, respectively) are measured at the proximal and distal ends of the manubrium, while the width and thickness of the corpus (2.7-3.5 cm and 1.0-1.4 cm, respectively) show relatively minor differences.

Aged↗

[Diagnosis by endomyocardial biopsy: angina pectoris as a manifestation of lupus erythematosus].

A 64-year-old female patient with a prosthetic mitral valve suffered from recurrent typical angina and dyspnea. Left heart catheterization excluded a dysfunction of the prosthesis and coronary artery disease (CAD). A stress thallium scan demonstrated an ischemic reaction. An antimyosin scintigram was positive, indicating myocytal membrane disruption. Serological tests were suspicious for systemic lupus erythematosus (SLE). Therefore, an endomyocardial biopsy (EMB) was performed and a severe alteration of an intramyocardial artery, comparable with chronic SLE, was diagnosed. EMB is a useful diagnostic tool in patients with typical chest pain, positive thallium and anti-myosin scintigrams, however exclusion of CAD.

Angina Pectoris↗

The surface to volume ratio of mitochondria, a suitable parameter for evaluating mitochondrial swelling. Correlations during the course of myocardial global ischaemia.

Cellular changes occurring in the left ventricular myocardium during ischaemia after different methods of cardiac arrest have been evaluated by morphological and morphometric parameters: volume densities of mitochondria (VVMi), sarcoplasm (VVSp), myofibrils (VVMf), surface densities of mitochondria (SVMi). The surface to volume ratio of mitochondria (SVratioMi) has been used as an independent parameter of mitochondrial swelling. Since ischaemic swelling of myocardial cells increases the volume of the reference space and ischaemic swelling of mitochondria decreases the free sarcoplasm, VVMi and VVSp cannot be considered as reliable indicators of the degree of oedema. SVMi/VVMf remains nearly constant after different forms of cardiac arrest, demonstrating the integrity of mitochondrial outer membranes. The inverse linear ratio between SVratioMi and the mean mitochondrial volume indicates that the increase in mitochondrial volume is achieved by surface smoothing. Loss of matrix structure and fragmentation of cristae occur at an SVratioMi of about 5.8, cristolysis at 5.5 to 5.6 and amorphous matrix densities at an SVratioMi of less than 5.5 micron2/micron3. The SVratioMi is a suitable parameter for evaluating mitochondrial swelling both at the onset and during global myocardial ischaemia, independent of the method of cardiac arrest used. It serves as an indicator of the state of structural preservation of mitochondria during ischaemia.

Animals↗

Ultrastructural effects induced by global ischaemia on the AV node compared with the working myocardium. A qualitative and morphometric investigation on the canine heart.

The cardiac conduction system is considered to be particularly resistant to ischaemia. Nevertheless, following open heart surgery with short periods of ischaemia disturbances in AV conduction or ventricular arrhythmia have been reported. We compared the ultrastructure of AV node and working myocardium following 30 min global ischaemia at 25 degrees C, during pure ischaemia and with HTK cardioplegia qualitatively and morphometrically. After 30 min of pure ischaemia, interstitial and intracellular oedema together with considerable changes in organelles in AV nodes predominate over mainly cellular oedema in working myocardium. Sometimes irregular overcontractions of sarcomeres occur in the AV node, though very seldom in working myocardium. In pure ischaemia, mitochondrial swelling is comparable in both types of tissue. Following HTK cardioplegia and 30 min ischaemia, cellular oedema and mitochondrial swelling are significantly reduced in AV nodal cells and working myocardium, but remain more extensive in the AV nodes. Irregularities in the contractile state of sarcomeres are not observed. The extent of the ultrastructural alterations corresponds to the degree of metabolic change in the working myocardium. Thus, despite considerable differences during pure ischaemia and HTK cardioplegia, ultrastructurally the AV nodal cells do not display a greater resistance to ischaemia than working myocardium.

Animals↗

Lyme carditis in immunodeficient mice during experimental infection of Borrelia burgdorferi.

Recently, we described the severe combined immunodeficiency (scid) mouse as a laboratory model for B. burgdorferi infection. Scid mice inoculated with the virulent low-passage tick isolate Borrelia burgdorferi ZS7 developed a severe pancarditis involving endocardium, myocardium and epicardium in the absence of functional B- or T-cells. Soon after inoculation perivascular infiltration was observed, later diffuse infiltration of the interstitium of the subendocardial and subepicardial areas was seen. The infiltrate was mainly mononuclear and predominantly composed of Mac-1+ cells. Concomitantly, fibroblast proliferation and augmented collagen deposition occurred in the interstitium. This was associated with the presence of B. burgdorferi organisms. The histopathological and ultrastructural findings observed in scid mice resemble those observed in human Lyme carditis. The data emphasize the suitability of the scid mouse as a model in which to study the role of the immune system in the pathogenesis of Lyme carditis.

Animals↗

Changes in heart function and cardiac cell size in rats with chronic myocardial infarction.

Myocardial infarctions were induced in rats by ligation of the left anterior descending (LAD) coronary artery. After 4 weeks, parameters of left (LV) and right ventricular (RV) function and of peripheral circulation were measured in the intact, anesthetized animals. The morphology of the heart chambers was examined at the macroscopic and cell size level. In animals with slight reduction in LV function, LVEDP was elevated from 3.4 +/- 0.8 to 8.8 +/- 1.5 mmHg, LV stroke work was reduced by 14%, and dP/dtmax of both ventricles was depressed by 10% compared with sham-operated controls. Myocytes isolated from the LV and RV were elongated to some extent and had a greater cell volume, but there was no change in heart weight. These rats had infarctions that were small or medium in size. In rats with severe depression in left heart function, cardiac output, LVSP, LV stroke work, mean arterial pressure, and the LV weight/body weight ratio were markedly lower than in sham-operated controls. LVEDP was elevated up to 32 +/- 2 mmHg. These rats had large infarctions. RVSP, RV weight/body weight ratio, and the volume of myocytes isolated from the RV were doubled. RV stroke work was increased by 58%. Myocytes from the LV, RV and from the septum were elongated to about the same extent. The septum had developed a 23% hypertrophy. Histological examination of the lungs revealed marked thickening of the tunica medica of small pulmonary arteries with narrowing of the lumen. These changes are considered to represent the morphological basis for the increased pulmonary vascular resistance that was associated with RV pressure overload and hypertrophy.

Animals↗

[Lipomatous atrophy of the parotid gland in chronic alcohol consumption].

The effect of chronic ethanol consumption on the morphology of the rat parotid gland was investigated. After feeding an ethanol diet containing 36% of total calories as ethanol for 90 days light microscopic and electron microscopic investigations of the parotid gland tissue showed a striking fat accumulation compared to control rats. Besides interstitial fat tissue dispositions, fat droplets of various size occurred in most of the acinar cells. Additional morphometric investigations revealed a decrease in mean acinar cell volume (-21.9% p greater than 0.001). The latter finding reflects an atrophy of the secretory parenchyma and appears to be responsible for the impaired saliva secretion after chronic ethanol consumption which has been observed in former studies.

Alcohol Drinking↗

Diffuse intermyocardiocytic fibrosis in uraemic patients.

At post-mortem we examined heart tissue of (i) 31 patients with uraemia not on dialysis, (ii) 42 patients on haemodialysis for less than 6 months, (iii) 60 patients on haemodialysis for more than 6 months, (iv) 16 patients after renal transplantation, and (v) 11 patients on CAPD. Patients with stenosing coronary lesions were excluded. Diffuse non-coronary intermyocardiocytic fibrosis, assessed by a score system in trichrome-stained sections, was found in 91% of chronically uraemic patients, but not in non-hypertensive, non-diabetic controls. The lesion was present even in non-dialysed uraemic patients; in dialysed patients its severity was related to the duration of dialysis; it was demonstrable even years after renal transplantation. On electron-microscopy, collagen fibres were seen, while beta 2-M amyloid was consistently absent. Logistic regression analysis showed that uraemia was a determinant of intermyocardiocytic fibrosis independent of hypertension, diabetes mellitus, anaemia, heart weight, and presence or absence of dialysis procedure.

Anemia, Aplastic↗

Cardiac changes in uraemia and their possible relationship to cardiovascular instability on dialysis.

In the past, cardiac changes in renal failure have commonly been ascribed to hypertension and poorly specified toxic effects ('uraemic cardiomyopathy'). Our recent experimental and clinical studies suggest (a) that cardiac hypertrophy can be dissociated from hypertension and that blood pressures may have only a permissive role, (b) that experimental uraemia is associated with specific activation of pericytes and intermyocardiocytic fibrosis. Cardiac hypertrophy not correlated with elevated blood pressure, and intermyocardiocytic fibrosis not observed in similarly hypertensive non-uraemic patients, have recently been documented in dialysis patients. The implications of these findings may be (a) electrical instability and predisposition to a sudden cardiac death and (b) diastolic cardiac malfunction with impaired LV filling and predisposition to dialysis hypotension. Some evidence for the latter possibility is provided.

Cardiomegaly↗

Estimation of surface area and length with the orientator.

The orientator is a new technique for the estimation of length and surface density and other stereological parameters using isotropic sections. It is an unbiased, design-based approach to the quantitative study of anisotropic structures such as muscle, myocardium, bone and cartilage. A simple method for the practical generation of such isotropic planes in biological specimens is described. No special technical equipment is necessary. Knowledge of an axis of anisotropy can be exploited to optimize the efficiency. To randomize directions in space, points are selected with uniform probability in a square using various combinations of simple random, stratified random, and systematic random sampling. The point patterns thus produced are mapped onto the surface of a hemisphere. The mapped points define directions of sectional planes in space. The mapping algorithm ensures that these planes are isotropic, hence unbiased estimates of surface and length density can be obtained via the classical stereological formulae. Various implementations of the orientator are outlined: the prototype version, the orientator-generated ortrip, two systematic versions, and the smooth version. Orientator sections can be generated without difficulty in large specimens; we investigated human skeletal muscle, myocardium, placenta, and gut tissue. Slight practical modifications extend the applicability of the method to smaller organs like rat hearts. At the ultrastructural level, a correction procedure for the loss of anisotropic mitochondrial membranes due to oblique orientation relative to the electron beam is suggested. Other potential applications of the orientator in anisotropic structures include the estimation of individual particle surface area with isotropic nucleators, the determination of the connectivity of branching networks with isotropic disectors, and generation of isotropic sections for second-order stereology (three-dimensional pattern analysis).

Animals↗

Influence of pretreatment on interstitial and intracellular space of canine left-ventricular myocardium.

In this study, the interstitial space and myocytes were investigated qualitatively and morphometrically in samples from beating, fibrillating as well as from cardioplegically HTK-arrested hearts fixed by immersion or perfusion. The size of tissue clefts separating bundles of myocytes and that of the interstitial space within bundles of myocytes depend on the functional state and on the kind of fixation. Cellular preservation is significantly better in HTK-arrested hearts compared to beating or fibrillating hearts. Thus, for the structural evaluation of myocytes and interstitium, the pretreatment constitutes a highly significant factor.

Animals↗

[New methods for the morphometric analysis of anisotropic tissues].

Some unbiased, design-based stereological methods that have recently been developed for the study of anisotropic tissues like muscle, myocardium, brain, cartilage, and skin, are briefly reviewed. Vertical sections permit the unbiased estimation of surface density and mean volume-weighted particle volume from microscopic sections. The available experience includes various studies on malignant melanomas. In addition, the surface area of total organs (e.g., the pleural surface area) can be determined with vertical sections, which was hitherto not feasible. The orientator is a simple method to generate isotropic sections in biological material. With the orientator method it is possible to determine not only the surface density, but also the length density of the objects. Thus the method is suitable for the study of fascicular systems (tubules etc.), and for the study of vascularisation in particular.

Animals↗