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Biomedical subjects

W Romen

Publications and source records attributed to W Romen.

At least 19 recordsLinked to original sources

Intraglomerular proteinase activity in adriamycin-induced nephropathy.

Adriamycin (ADR)-induced nephropathy is characterized by focal and segmental glomerulosclerosis and is supposed to be an ideal model of chronic progressive renal disease. The aim of our study was to investigate whether there might be an altered activity of glomerular proteinases in ADR nephropathy, thereby aggravating glomerular protein accumulation as an important initiating hallmark of glomerulosclerosis. In fact, we could demonstrate significantly enhanced levels of intraglomerular protein and DNA content in the experimental animals at week 7, 12 and 22 after administration of ADR. When relating intraglomerular proteinase activity, which was measured in ultrasonically destroyed isolated glomeruli, obtained by differential sieving techniques, to the intraglomerular protein and DNA content, this enzyme activity was significantly reduced throughout the observation period. Based on these data, we suggest that this relatively decreased proteinase activity in glomeruli exposed to ADR might play a pathogenetic role in the development of glomerular hypertrophy, an important harbinger of glomerulosclerosis.

Animals

Proteinase activity in isolated glomeruli of Goldblatt hypertensive rats.

In Goldblatt rats, the kidney exposed to high blood pressure reveals glomerulosclerosis. Moreover, in preexisting parenchymal renal disease, the development of glomerulosclerosis is accelerated in the unclipped kidney. Up to now, the pathogenetic mechanism underlying the development of glomerulosclerosis due to systemic hypertension has not completely been resolved. Traditionally, hemodynamic mechanisms have been discussed. This study was performed to investigate whether there might be a decreased activity of glomerular proteinases in the unclipped kidney of Goldblatt rats as a potential pathogenetic factor for glomerulosclerosis. 20 weeks after the surgical intervention, we found a reduced proteinase activity in ultrasonically destroyed isolated glomeruli obtained by differential sieving technique in comparison with the contralateral clipped kidney and the kidneys of sham-operated normotensive controls. This could be confirmed, when proteinase activity was related to DNA instead of protein. When investigating glomerular cathepsin B-content, a lysosomal enzyme, which is able to degrade glomerular structural as well as non-structural proteins, we found a decreased level in the kidney of Goldblatt rats exposed to systemic hypertension in comparison with normotensive control animals. Basing on these results we presume that glomerular protein accumulation and concomitant glomerulosclerosis due to systemic hypertension might be a result of a synergistical interaction between hemodynamic factors and biochemical ones; we suggest one of the latter to be a decreased glomerular proteinase activity.

Animals

[Sudden death caused by a heart tumor].

Primary cardiac tumors in infancy and childhood are extremely rare. In the young age group the clinical symptoms often are variable and can make diagnosis difficult. Depending on the histological character and especially the localisation of the mass the clinical appearance may lead to the first diagnosis or at least to further investigation. While myocardial tumors (rhabdomyomas and fibromas) mainly cause rhythmic disturbances, the intracavitary tumors (like myxomas) frequently disturb hemodynamics. Echo-cardiography is the main diagnostic technique, followed by angiocardiography, computertomography and nuclearmagneticresonance imaging.

Child

Ehlers-Danlos syndrome type IV (EDS IV) as model of a defective biopolymer composite material.

The connective tissue of a lethal EDS IV case was investigated for the reasons of the manifested disturbances of the arterial wall. This functional disorder was attributed to the mechanical decoupling of elastin and collagen, with the premise of a composite material consisting of cellular, fibrillar, lamellar and other matrix components. A conceivable relation between the manifested deficiency of type III collagen and a disturbed anchoring of elastin is shown. These findings are supported by biochemical, morphological, x-ray and mechanical data.

Adult

Capillary rarefaction characteristic of the skeletal muscle of hypertensive patients.

There is evidence that the rarefaction of the capillary bed is typical for the skeletal muscle of spontaneously hypertensive rats. We were therefore interested to learn whether there is also a rarefaction in skeletal muscle of human hypertensives. The number of capillaries was morphometrically analysed and counted in the quadriceps and the pectoralis major muscles of human normotensives (n = 12) and hypertensives (n = 15). The clinical diagnosis and certain pathological criteria, such as blood pressure (with or without antihypertensive therapy), heart weight, left ventricular wall thickness, the state of kidney arterioles and brain, and heart vessels, were used to classify the patients into two groups. The dissected tissue samples were prepared according to the GMA method and the capillary numbers per area were counted using light microscopy (250 x). The quadriceps muscle had a capillary density (per 2.5 mm2) of 442 +/- 51 in normotensives and 277 +/- 41 in hypertensive patients; in the pectoralis major muscle we counted 477 +/- 30 in controls and 232 +/- 28 in hypertensives. The rarefaction in the quadriceps muscle ranged by about 37%, in the pectoralis major muscle by about 51%. It is suggested that the reduction of the capillary surface area caused by the capillary rarefaction reduces the transcapillary fluid exchange and in that way prevents an overperfusion of the terminal vascular bed.

Capillaries

Nocardial endocarditis after aortic valve replacement. Reports of two cases.

Nocardial sepsis occurred after aortic valve replacement in two patients. A septic suture aneurysm of the aortotomy was resected and the prosthesis exchanged in one of them. The other received conservative treatment for sternal osteomyelitis and local mediastinitis. Clinical cure was followed by relapse and death from cerebral infarction, and necropsy revealed a septic suture aneurysm of the aortotomy. Radical surgical revision seems to be necessary for lasting cure in such infections.

Aged

[Five simultaneous neoplasms].

One case of five independent tumors is reported: Fibrosarcoma of the right thigh, bilateral carcinoma of breast, papillary carcinoma of thyroid, and basalioma below the left clavicula. A synopsis of literature containing the rare cases of more than three primary tumors is presented. The difficulties concerning localization, origin and registration of multiple primary malignancies and their differentiation to recurrencies and metastases are discussed.

Adenocarcinoma

[Mixed freeze preserved heterologous/autologous full-thickness transplants following 3d degree burns in animal experiments].

On five minipigs third-degree burns were applied. The surgical skin coverage was established after escharectomie by freeze-preserved heterological/autological intermingled full-thickness skin grafts. The freeze-preservation of the Makaka-skin (full-thickness skin) was achieved in a commercially available freezer at -27 degrees C. We could not observe a accelerated or even complete re-epithelialization as it is described in the Chinese papers. The burnwunds healt in form of scare areas covering about half of the previously burned area.

Animals

Tissue specific, acute toxic effects of the carcinogen trans-4-dimethylaminostilbene.

The acute toxicity of the carcinogen trans-4-dimethylaminostilbene was studied in Wistar rats. The animals die after oral administration of 50 mg/kg (LD50) with a latency period of 11 days. Specific lesions of the stomach epithelium together with acute bone marrow incapacity and toxic effects on peripheral blood cells lead to acute anemia, which is considered to be the cause of death. Histological observations indicate that the stomach lesions develop in three phases. Firstly, necroses appear in the proliferative area predominantly in the antrum. This leads, secondly, to cystic transformation of the antrum, cardia, and Brunner's glands and further to peptic erosions and ulcerations. Thirdly, mitotic activity increases. With lethal doses, cell replacement remains incomplete. There ist a correlation between the proliferation rate of different cell types and their susceptibility; but this cannot entirely account for the tissue-specific, systemic effects of trans-4-dimethylaminostilbene. Metabolic activation is also involved, since enzyme induction with methylcholanthrene inhibits toxicity. The study disclosed a new target tissue which may now be used to investigate the mechanism of action of reactive metabolites of an aromatic amine in acute experiments. The same stomach lesions were also observed with adriamycin. With this compound, however, the intestine is also involved.

Acute Disease

[Application of mixed homologous/autologous full-thickness skin transplants preserved by freezing following 3d degree burns in animal experiments].

In 5 white piglets 3rd-degree burns were applied. After escharectomy the wound-dressing was done by intermingled homo/autografts. In variation of the Chinese method reported, in our experiments the homografts consisted of full-thickness skin preserved by freezing (-27 degrees C). In all piglets this procedure caused a perfect epithelialization and brought good cosmetic and clinical results.

Animals

Syncarcinogenic effects on the initiation of rat liver tumors by trans-4-acetylaminostilbene and 2-acetylaminofluorene.

Two carcinogenic aromatic amines with different organotropism were tested for syncarcinogenic effects in rat liver in an initiation-promotion experiment. Trans-4-acetylaminostilbene (AAS) and 2-acetylaminofluorene (AAF) were administered as initiators in four doses each either alone or sequentially combined in both orders. The promotion phase was started by partial hepatectomy and continued by adding phenobarbital (250 p.p.m.) to the drinking water for 26 weeks. The number/cm2 of tissue section and average size of hyperplastic foci, glucose-6-phosphatase-deficient and gamma-glutamyl-transpeptidase-positive foci were determined and a total area of lesions calculated during the promotion phase after 18 and 31 weeks, and in the post-promotion phase after 42 and 47 weeks. The synergistic effects of AAS and AAF were clearly more than additive if compared with the sum of the effects exerted by each compound individually. The sequence in which both initiators were administered remarkably influenced the development of lesions. They developed more rapidly and persisted longer in the post-promotion phase when AAS was administered first and AAF second. In the final stage, enzyme altered foci increased in the livers of both combination groups, but to a greater extent in the AAS-AAF group. It is concluded that the two arylamides damage DNA independently. In addition, however, the results suggest that AAS acts predominantly as an initiator, and AAF as a weak initiator and a strong promoter in what is considered the initiation phase of this experiment.

2-Acetylaminofluorene

[In vivo study of the effects of i.v. immunoglobulin therapy. Tissue distribution of native and enzyme-treated human immunoglobulin fractions given i.v. in man].

The tissue distribution of intravenously injected native and enzyme-treated human gammaglobulin has been investigated in human rectum mucosa. FITC-labelled antibodies to human gammaglobulin were used to locate the injected antibody preparation. Three hours after application of these different gammaglobulin-preparations no enrichment in the mucosa was found. Neither the native gammaglobulin nor the enzyme-treated gammaglobulin showed any concentration in the lamina propria of the large bowel mucosa or an intracellular enrichment in the epithel. This study shows that the quicker elimination of enzyme-treated gamma-globulin from the circulation cannot be explained by an intracellular increase.

Animals

Diffuse glomerulosclerosis--a dysfunction of the mesangium? A morphometric study of the rat's kidney.

The phagocytic capacity of the glomerular mesangial cells in 42 rats was inhibited by the prolonged injection of PVA. Morphometric evaluation of electron microscopic sections showed that this treatment leads to an accelerated thickening of the lamina densa of the glomerular basement membrane and of the mesangial matrix (early glomerulosclerosis). This suggests that a disturbance of lysosomal degradation can lead to glomerulosclerosis, and that the possibility of mesangial dysfunction should always be considered as a possible factor in the pathogenesis of all types of diffuse glomerulosclerosis.

Animals