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Biomedical subjects

K W Wenzel

Publications and source records attributed to K W Wenzel.

At least 19 recordsLinked to original sources

Upregulation of gap junction protein connexin43 in alveolar epithelial cells of rats with radiation-induced pulmonary fibrosis.

The degree of immunoreactive connexin43 (C x 43) in rat lung was evaluated during the development of radiation-induced pulmonary fibrosis in rat by a double immunofluorescence technique using polyclonal antisera to Cx43 and monoclonal antibodies to cytokeratins on cryostat sections. In normal rat lungs, Cx43 was detected in pneumocytes type II and I, in large blood vessel endothelia, in peribronchial smooth muscle cells, and in some peribronchial and perivascular interstitial cells. As early as 1 week after irradiation, enhanced immunoreactivity for Cx43 in the epithelial cells was detected. In severely injured lungs (about 3 months after irradiation), Cx43 was found also in the cytoplasm of type II pneumocytes. These findings were confirmed by western blot data. Western blot analysis also revealed increased phosphorylation of Cx43. It remains to be investigated whether the increased content of Cx43 in irradiated rat lung may be due to an enhanced number of gap junctions between type I and II alveolar epithelial cells.

Actins

Disturbances of thyroid function tests by drugs.

Commonly prescribed drugs can variously cause changes in measuring serum T3 and T4 concentrations. Thus spuriously normal thyroid hormone levels may result in moderate hypo- or hyperthyroidism, or the influence of pharmacological substances may lead to a false diagnosis of thyroid disease in euthyroid subjects. On the other hand numerous pharmacological agents, especially those interacting with neurotransmitters, may influence TSH secretion, too. While generally such drug-induced abnormal thyroid tests do not correspond to clinical features of thyroid dysfunction, iodine containing drugs, especially amiodarone, may result in overt thyroid disease.

Amiodarone

Immunohistochemical evidence for loss of ICAM-1 by alveolar epithelial cells in pulmonary fibrosis.

ICAM-1 is an intercellular adhesion molecule of the immunoglobulin supergene family involved in adherence of leukocytes to the endothelium and in leukocytic accumulation in pulmonary injury. In the current study, the antigen retrieval technique was used to detect ICAM-1 immunohistochemically in paraffin sections of lungs from human, mouse and rat as well as in bleomycin- or radiation-induced fibrotic lungs from rat and human. In normal lung tissue, the expression of ICAM-1 on alveolar type I epithelial cells is stronger than on alveolar macrophages and on endothelial cells. Preembedding immunoelectron microscopy of normal rat, mouse and human lung samples revealed selective ICAM-1 expression on the surface of type I alveolar epithelial cells and, to a lesser extent, on the pulmonary capillary endothelium and on alveolar macrophages. In fibrotic specimens, both focal lack and strengthening of immunostaining on the surface of type I cells was found. Alveolar macrophages were found focally lacking ICAM-1 immunoreactivity. In some cases, rat type II pneumocytes exhibited positive immunoreactions for ICAM-1. Immunoelectron microscopy with preembedded rat lungs (bleomycin-exposed cases) confirmed the altered ICAM-1 distribution at the alveolar epithelial surface. In the alveolar fluid of fibrotic rat lungs, in contrast to that from untreated controls, soluble ICAM-1 was detected by western blot analysis.

Animals

Changes in epitope exposition of apolipoprotein A-I on the surface of high density lipoproteins after phospholipase A2 treatment.

The immunoreactivity of high density lipoprotein (HDL) modified by treatment with porcine pancreatic phospholipase A2 (PLA2) was studied in a competitive radioimmunoassay using 6 different monoclonal apolipoprotein (apo) A-I antibodies. The competition tests have shown that after PLA2 treatment the immunoreactivity of selected epitopes of apo A-I changed in different ways. While the binding behavior of two epitopes remained unchanged, three epitopes exhibited decreased immunoreactivities after phospholipids hydrolysis. In contrast to the latter epitopes, the immunoreactivity of an epitope located on the cyanogen bromide fragment 4 of apo A-I increased with the degree of lipolysis. A loss of apo A-I from HDL as a consequence of PLA2-treatment did not occur as shown by the determination of the apo A-I concentration in HDL before and after treatment with PLA2. Using overlapped synthetic decapeptides it could be shown that the epitope increasingly exposed on the particle surface of PLA2-modified HDL consists of the amino acid residues 162-173 and 212-229. These residues are characterized by high hydrophobic indices as determined by hydropathy analysis. Furthermore, these regions belong partially to the proposed receptor-binding domain of apo A-I. Thus, an increased exposition of this epitope might result in elevated cellular binding affinities of HDL occurring after modification of lipoproteins by PLA2-treatment.

Amino Acid Sequence

[Therapeutic results of radioiodine therapy of hyperthyroid thyroid gland diseases].

PATIENTS AND METHODS: The result of radioiodine treatment administered to 126 patients with hyperthyroidism between 1986 and 1991 were analysed retrospectively. The indications for radioiodine treatment were single hyperfunctioning nodules (n = 47), multinodular goitre (n = 33), diffuse goitre (n = 19) and Graves' disease (n = 27); the respective doses of 131I, calculated with the Doering and Kramer formula, were 300 Gy (30,000 rad), 150 to 200 Gy (15,000 to 20,000 rad), 100 to 120 Gy (100,000 to 120,000 rad) and 100 Gy (100,000 rad). The uptake of radioiodine was measured on a daily basis and in the case of 46 patients (36.5%) additional treatment given on the third day of treatment. RESULTS: For the patients undergoing regular follow-up, data were collected in 1992, at least six months post-therapy. Evaluation revealed a total applied dose of 131I of 20 +/- 12.4 mCi (median +/- SD) per patient. non-response to treatment making hospitalisation and renewed therapy necessary was observed in 1.6% of the group. In only two further patients did scintigraphy reveal compensated toxic adenoma. In 36% of patients with single hyperfunctioning nodules, 21% of those with multinodular goitre, 53% of those with diffuse goitre and 56% of those with Graves' disease hyperthyroidism was observed. In the great majority of cases, hypothyroidism occurred in the first year following treatment.

Adult

Localization of surfactant protein A (SP-A) in alveolar macrophage subpopulations of normal and fibrotic rat lung.

The colocalization of surfactant protein A (SP-A) and the alveolar macrophage markers ED1 and RM-1, as well as various lectins of the N-acetyl-galactosamine group [Maclura pomifera lectin (MPA), Dolichos biflorus lectin (DBA), soybean agglutinin (SBA)] and of the mannose group [Canavalia ensiformis lectin (ConA), Galanthus nivalis lectin (GNA)] was studied in normal and fibrotic rat lung tissues. In normal tissue, SP-A was located preferentially in the alveolar macrophage subpopulation lacking specific binding sites for lectins of the N-acetylgalactosamine group (DBA and SBA), although 50% of MPA-binding macrophages contained SP-A. The ED1-positive cells were SP-A-negative, whereas SP-A uptake could be detected among the RM-1 immunoreactive as well as the ConA and GNA binding macrophages. In fibrotic lung tissue, however, a small number of DBA and SBA binding macrophages contained SP-A and the percentage of GNA and ConA binding alveolar macrophages exhibiting SP-A immunoreactivity was reduced. Additionally, the number of ED1+/SP-A+ macrophages was found to be increased. Immunoelectron microscopy revealed accumulation of SP-A in the extracellular space. The differing SP-A content in different alveolar macrophage subpopulations suggests a more complex mechanism of uptake and degradation of surfactant proteins in normal and pathological conditions, which cannot simply be explained by the glycoconjugate pattern on the surface of alveolar macrophages.

Animals

[[111In]-DTPA-D-phenylalanine octreotide SPECT for the scintigraphic imaging of enhanced somatostatin-receptor density in endocrine ophthalmopathy].

Recently, [111In]-DTPA-D-phenylalanine-octreotide was introduced for clinical use. This radioligand binds specifically to somatostatin receptors and is suitable for SPECT examinations. The aim of this study was to clarify whether an increased somatostatin receptor density can be imaged and quantified in patients with endocrine ophthalmopathy (e.o.). 7 patients between 34 and 55 years with e.o. at stages III to VI and 4 controls between 38 and 63 years were examined. All patients and controls received approximately 200 MBq [111In]-DTPA-D-phenylalanine-octreotide by IV injection. A SPECT examination was performed 4 hours after injection and a normalised tracer uptake (A(n)) was calculated for both orbitae. In patients with e.o. the values of A(n) were significantly higher compared with controls (P = 0.002). There was a correlation between A(n) and exophthalmus stages according to Hertel with r = 0.844 (P = 0.001). These results indicate that [111In]-DTPA-D-phenylalanine-octreotide SPECT might be useful for the in vivo assessment of an increased somatostatin receptor density in e.o. These findings could have an impact on the treatment with somatostatin analogous in e.o.

Adult

[The course of the disease in endocrine orbitopathy. Magnetic resonance tomographic documentation].

MR imaging of the orbits was performed in 59 patients with untreated Graves' ophthalmopathy (follow-up exams were performed in 11 patients). T2-relaxation times of eye muscles were calculated and correlated with duration of disease. Elevated T2 times indicating eye muscle edema were found even if ophthalmopathy had been existing for more than one year. MRI documented specific eye muscle changes and transformation of oedema to fibrosis and fatty degeneration. MRI thus allows for standardized planning of therapy and follow-up in patients with Graves' ophthalmopathy.

Edema

Isoenzymes of pyruvate kinase, lactate dehydrogenase and alkaline phosphatase in epithelial cell lines of rat liver.

In cultured epithelial cells of rat liver the isoenzyme patterns of pyruvate kinase, lactate dehydrogenase and alkaline phosphatase were studied and compared with those of freshly isolated parenchymal and non-parenchymal liver cells. In all epithelial cell lines pyruvate kinase was not activated by fructose 1,6-bisphosphate, suggesting the absence of the L-isoenzyme. Cell lines derived from livers of newborn rats expressed LDH-4 and -5, whereas cell lines developed from fetal rat livers contained all 5 lactate dehydrogenase isoenzymes. In the latter case the pattern was found to depend on the state of confluence. All cell lines exhibited only a single alkaline phosphatase form, however, differences were found with respect to electrophoretic mobility.

Alkaline Phosphatase

Enzyme activities, isoenzyme pattern and alpha-1-adrenergic receptor number in primary cultured hepatocytes.

Changes in the activities of pyruvate kinase, tyrosine aminotransferase and adenylate cyclase as well as in the number of alpha-1-adrenergic receptors of hepatocytes maintained in primary culture were investigated. During the culture in the presence of insulin and dexamethasone the activity of tyrosine aminotransferase (TAT) increased. The increase was suppressed by 12-O-tetradecanoylphorbol-13-acetate (TPA). The basic activity of adenylate cyclase increased; however, a weaker stimulation of the enzyme by glucagon was found. A loss of stimulation of pyruvate kinase by fructose-1,6-bisphosphate may result from phosphorylation of the enzyme. The number of alpha-1-adrenergic receptors decreased during culture, an event not influenced by TPA.

Adenylyl Cyclases

[Recent parameters for diagnosis of challenging thyroid gland disorders: consequences for diagnosis and therapy].

The recognition of the peripheral state of thyroid hormones is often disturbed by factors like pharmacological interferences or non-thyroidal illness, especially borderline hyperthyroidism may often be misjudged. Some serological parameters like the measurement of sex hormone binding globulin, precollagen-peptid I and III, osteocalcin, angiotensin converting enzyme and fibronectin are often elevated in such states and can indicate thyrotoxicosis of certain tissues. Such thyrotoxicosis-like alterations can be shown also in TSH-suppressive therapy with levothyroxine. In contrast to early publications there is obviously only a minor influence of levothyroxine treatment on bone metabolism, where a decrease of bone mass is less probable. Recent developments of sensitive and specific modifications in estimating antibodies against thyroidal peroxydase in recognizing thyroid autoimmune disease and of thyroglobulin in the follow-up of differentiated thyroid cancer are becoming important tools in clinical medicine.

Blood Proteins

Ultrastructure and quantitative composition of isolated endothelial cells of rat liver.

Isolated endothelial cells (n 110; 350-540 microns3 in volume) of the sinusoid of rat liver were found to differ from in situ endothelial cells by their rounded shape with the nucleus usually in the centre and fenestrae of the sieve plates across the entire cytoplasm. Their volume density is 0.2814 (SE 0.0085). Some of them tend to form complex, ramified structures as well as clefts and vacuoles up to 1 micron in size. Dense bodies are other structures quite often seen in endothelial cells (Vv 0.0189, SE 0.0085). Mitochondria, on the other hand, are extremely rare (Vv 0.0023, SE 0.0009). Both the preservation and relocation of sieve structure after isolation may probably be due to the cytoskeleton which in vivo causes changes of size and number of endothelial cell fenestrae under physiological and pathological conditions.

Animals

[Magnetic resonance tomographic differentiation of ocular muscle changes in endocrine orbitopathy].

In 50 patients with Graves' Ophthalmopathy and 9 controls both orbits were examined by MR Imaging at 0.5 Tesla using a surface coil. T1-weighted spin-echo images were obtained in transverse and coronal orientation; additionally, a T2-image was calculated from a multi-echo sequence (8 echoes). Signal intensity of eye muscles on both T1-weighted and T2-weighted MR images was evaluated qualitatively. T2-times were then calculated for all inferior rectus muscles. Eye muscle enlargement was found in 28 out of 50 patients. T2-times of inferior rectus muscles in stage III and IV patients were evaluated significantly (p less than 0.05). Areas of high signal intensity were accordingly found in enlarged eye muscles in 19 out of 50 patients; they were interpreted as edematous tissue changes. Areas of low signal intensity were found in enlarged eye muscles of 5 out of 50 patients; these eye muscles were considered fibrotic. Differentiation of eye muscle changes by MR imaging might help to decide between antiinflammatory medication and surgical therapy in patients with Graves' Ophthalmopathy.

Adolescent

Lysosomal beta-galactosidase from rat liver: purification, molecular forms and association with neuraminidase.

A simple procedure for purification of lysosomal beta-galactosidase from rat liver was developed. The association state of the purified enzyme has been found to depend on pH and ionic strength. Under acidic conditions and at high ionic strength, the enzyme is aggregated into a high molecular weight complex having a molecular weight of about 700,000. Increasing pH and lowering the ionic strength favour the disaggregation of the complex to an enzyme species whose molecular weight is 160,000. These two enzyme forms differ markedly in their hydrophobicity, but no significant differences in kinetic properties have been found. Galactose and galactose-1-amine were competitive inhibitors of beta-galactosidase. Neuraminidase is associated with the multimeric form of beta-galactosidase, whereas the low molecular weight form did not show any neuraminidase activity. The stability of neuraminidase has been found increase in the presence of magnesium ions.

Animals