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Biomedical subjects

M Witte

Publications and source records attributed to M Witte.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling.

The interferon alpha beta receptor (IFN alpha R) or type I IFN-R is formed by a 110-kDa alpha subunit or IFNAR and by a beta subunit, which has short and long forms (molecular masses of 55 and 95-100 kDa, respectively). In this report, we demonstrate that the IFN alpha/beta R cDNA recently cloned corresponds to the 55-kDa or short form of the beta subunit, while the 95-100-kDa species reported here corresponds to a longer form of the IFN alpha/beta R cDNA that is probably produced by alternative splicing of the same gene. Stable transfection of the alpha subunit with either form of the beta subunit results in the expression of low and high affinity receptors, while expression of either form of the beta subunit alone only produces low affinity receptors. More important, only expression of the alpha and long form of the human beta subunits in mouse L-929 cells reconstitutes the activation of the Jak kinases and the Stat factors, as well as the antiviral response to human type I IFNs.

Amino Acid Sequence↗
PubMed1995

Observations of energetic particles with EPAC on Ulysses in polar latitudes of the heliosphere.

Measurements with the Energetic Particle Composition instrument (EPAC) aboard Ulysses show particles from near the ecliptic that were apparently accelerated by shocks associated with a corotating interaction region. The particles were detected together with the shocks and even when shocks no longer arrived at Ulysses up to -65 degrees of heliographic latitude but not beyond. Particles could have reached these latitudes along magnetic fields; such connections to the outer lower latitude heliosphere evidently do not exist above that latitude. The accelerated streams have composition similar to solar wind abundances, no dispersion, and a net inward anisotropy. The underlying composition between the recurrent stream is similar to the anomalous component of cosmic rays. The channel sensitive to high-energy protons (> 230 megaelectron volts) shows a 26-day variation of the flux superimposed on the heliospheric modulation of galactic ions.

Acceleration↗
PubMed1995

The Thrombostat 4000. A sensitive screening test for von Willebrand's disease.

The determination of the bleeding time (BT) is an essential diagnostic tool for von Willebrand's disease (vWD). However, the standardized Simplate BT still displays many variables and disadvantages. The present study reports on the sensitivity of the in vitro bleeding test (IVBT) in 51 vWD cases of different types and severity in comparison to the Simplate BT, and the correlation of both to each other as well as to von Willebrand factor (vWF:RCo) activity. The IVBT was performed in two modifications (2 mmol/L CaCl2 and 4 mmol/L ADP) on the Thrombostat 4000. The IVBT, particularly with CaCl2, showed clearly higher sensitivity than the BT (CaCl2: 84.3%, ADP: 61.7%, CaCl2 + ADP: 86.3, BT: 52.9%). The BT even failed in one patient with severe (type 2B) and in three with moderate vWD. The IVBT only failed in very mild forms of the disease (vW-F:RCo > 25%). In addition, the IVBT with ADP showed a close correlation to the vWF:RCo activity (r2 = 0.73). The significantly lower correlation of the BT with vWF:RCo (r2 = 0.49) was particularly due to the poor results in vWD of type 2 (type 2:r2 = 0.29; types 1 and 3:r2 = 0.61). Finally, BT and IVBT-ADP correlated with each other (r2 = 0.53), a rather good correlation considering that both are complex functional tests. It can be concluded from our study that the IVBT not only may replace the BT for most applications, but is clearly superior to BT for the screening (IVBT-CaCl2) and control of therapy in vWD.

Bleeding Time↗
PubMed1995

Major basement membrane components in Kaposi's sarcoma, angiosarcoma and benign vascular neogenesis.

Recent cell biologic studies have emphasized the importance of the basement membrane (BM) and its molecular components in angiogenesis. We immunostained 60 angioproliferative lesions (angiosarcoma, sclerosing hemangioma of skin, pyogenic granuloma, capillary hemangioma, lymphangioma, glomangioma and granulation tissue) and 23 cases of Kaposi's sarcoma (KS) for the major macromolecular components laminin, collagen type IV, fibronectin and heparan sulfate proteoglycan (HSPG). Normal structures served as aggregate controls in each group, and semiquantitative scoring reflected the degree of consistency of staining about blood and lymphatic endothelium and vascular sheath (pericyte/smooth muscle) within and peripheral to each lesion. Benign and reactive vasoproliferations consistently maintained immunoreactivity for each BM component around endothelium and sheath components of blood vessels. Angiosarcoma showed from 20 to more than 60% less consistent immunoreactivity by comparison, although the score variances were greater than for non-malignant lesions. Staining about blood vessel endothelium was both strong and consistent among histologic stages in KS with the exception of HSPG, which was weakly immunoreactive in all stages. Marked selective HSPG loss was characteristic only of KS and normal lymphendothelium, and in the light of evidence for a role for HSPG in the assembly and maintenance of BM, suggests that reduced HSPG may be responsible for the loss of ultrastructural integrity of perivascular BM in both.

Basement Membrane↗
PubMed1995

Automated patient care documentation: what's in it for us? An expert system emergency drug card printout.

This article summarizes experiences to date for a collaborative approach, utilizing systems analysis and decision support methods, to design, develop, and implement automated patient centered documentation. Current manual methods for retrieving patient centered data for treatment activities and evaluation of practice are laborious, frustrating and often uneventful. Accessing specific patient information in an arrest or emergent situation, in the hospital and out patient clinical setting, is fraught with difficulties of data and information availability, reliability, legibility, integrity, security, and obsolescence. Treatment decisions made during an arrest or emergent situation, whether for an in-patient or clinical out patient, utilize Advanced Life Support guidelines and also may vary based on the heuristics of the lead practitioner on duty at the time. Walking the informatics talk of "managing and processing data to information to knowledge" lead to standardization for best practice of emergency drug calculations and treatments (1). An expedient and reliable method for retrieving patient specific data to calculate 26 medications, 3 treatments, and upwards of 40 criteria to consider during an arrest or emergent situation was achieved and implemented, as a by product of height and weight charting, across most all patient care areas at Primary Children's Medical Center in Salt Lake City Utah.

Attitude to Computers↗
PubMed1994

Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase.

Binding of type I interferons (IFNs) to their receptors induces rapid tyrosine phosphorylation of multiple proteins, including the alpha and beta subunits of the receptor, the polypeptides that form the transcriptional activator ISGF3 alpha (Stat113, Stat84, and Stat91), and the p135tyk2 and Jak-1 tyrosine kinases. In this report, we demonstrate that the alpha subunit of the type I IFN receptor (IFN-R) corresponds to the product of a previously cloned receptor subunit cDNA and, further, that the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit. Glutathione S-transferase (GST) fusion proteins encoding the different regions of the cytoplasmic domain of the alpha subunit can bind the p135tyk2 contained in human cell lysates. The association between the alpha subunit and Tyk2 was demonstrated by immunoblotting with anti-Tyk2 and antiphosphotyrosine antibodies and by using an in vitro kinase assay. Analogous experiments were then performed with recombinant baculoviruses encoding constitutively active Jak family tyrosine kinases. In this case, p135tyk2, but not Jak-1 or Jak-2 protein, binds to the GST-IFN-R proteins, suggesting that the interaction between these two proteins is both direct and specific. We also demonstrate that Tyk2, from extracts of either IFN alpha-treated human cells or insect cells infected with the recombinant baculoviruses, can catalyze in vitro phosphorylation of GST-IFN-R protein in a specific manner. Deletion mutants of the GST-IFN-R protein were used to localize both the binding and tyrosine phosphorylation site(s) to a 46-amino-acid juxtamembrane region of the alpha subunit, which shows sequence homology to functionally similar regions of other cytokine receptor proteins. These data support the hypothesis that the Tyk2 protein functions as part of a receptor complex to initiate intracellular signaling in response to type I IFNs.

DNA-Binding Proteins↗
PubMed1994

Alcohol, immunomodulation, and disease.

Recent research findings point to a spectrum of alcohol-induced immune dysfunctions in animal models and humans. Use of alcohol in vivo causes abnormalities in the function and/or structure of a broad array of cells involved in humoral and cellular immunity, including lymphocytes, Kupffer cells and other macrophages, as well as the endothelium of blood vessels and lymphatics. Regulatory cytokines and neuroendocrine factors can mediate some of these immunomodulatory effects which may be further re-phased, exaggerated or unbalanced by other drugs of misuse. A variety of animal models is available to study acute and chronic alcoholism, non-alcohol drug misuse, AIDS as well as other opportunistic infections, and neoplasias, which hold promise of clarifying the role of alcohol as an immunomodulator.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Absence of monoclonal antibody detectable Kaposi sarcoma-specific antigens on lesion-derived cultured cells.

To define the histogenesis and cell origin of Kaposi sarcoma (KS), we cultured KS cells without retrovirally conditioned media from three HIV seropositive AIDS patients and then attempted to raise mouse hybrid monoclonal antibodies (Mabs) specific to these AIDS-KS cells. After both in vivo and in vitro immunization trials, all putative Mabs reacted positively to KS cells but also non-specifically with other human (CH5 and OM) and non-human (RSE-1) control endothelial cell lines. To overcome this crossreactivity, we further "absorbed" previously cloned hybrids and pre-hybrid splenocytes by incubating them with the control endothelial cell lines to eliminate splenocytes and/or hybridomas reactive to normal endothelium. Whereas absorption successfully eliminated immunoreactivity to control endothelium, it also excluded reactivity to KS cells. These findings (lack of specific antigenicity and immunoresponsiveness of KS similar to non-KS control endothelium) suggest that AIDS-KS cells are neither antigenically transformed nor neoplastic, but instead represent dedifferentiated or transdifferentiated endothelium which retains immunogenicity of its original endothelial cell prototype.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Developmental disorders of the lymphatic system.

Approximately 67% of human conceptuses die prenatally. Of these, a significant number involve a disorder of the lymphatic system. A small number of live-born children also exhibit congenital lymphatic malformations, including an estimated 60% of patients with Turner syndrome. These observations have prompted a search for the genetic and dysmorphologic basis and the different patterns of congenital lymphedema and associated anomalies. In this article, we attempt to summarize available pertinent information on congenital disorders of the lymphatic system and to propose a conceptual overview of lymphatic development.

Adult↗
PubMed1991

Characterization of ascites present at cesarean section.

Ascites has been reported at cesarean section delivery in pregnancies complicated by preeclampsia. The frequency and composition of peritoneal fluid collections in pregnancy have not previously been described. This descriptive study evaluated presence, composition, and characteristics of ascites present in 41 women undergoing cesarean delivery for a variety of indications. Twenty-six women had sufficient quantities of peritoneal fluid to be collected immediately after opening the parietal peritoneum. The protein content of the fluid was analyzed. The presence of fluid was not related to labor preceding delivery. All preeclamptic women in this study had fluid obtainable at cesarean section. Large volume ascites was noted in five preeclamptic women whose fluid had low total protein content, consistent with a transudate. Intrahepatic portal hypertension is one possible explanation of the large volume and low protein ascites in some preeclamptic patients. Ultrasonic measurements in preeclamptic patients and normotensive pregnant women showed uniform portal vein diameters and Doppler-derived portal vein flow velocities in all patients. The physiology of peritoneal fluid production in complicated and normal pregnancy remains unexplained.

Adult↗
PubMed1991

Vascular abnormalities in experimental and human lymphatic filariasis.

Whereas clinical descriptions of grotesque lymphedema and standard light microscopy in human filariasis have elucidated the natural progression of this disease, the link between the nematode and vascular abnormalities including elephantiasis remains poorly understood. Accordingly, we examined the nature and distribution of lymphatic and blood vascular derangements in a variety of tissues and organs from 37 ferrets acutely and chronically infected with Brugia malayi and in 15 patients with Wuchereria bancrofti or Brugia malayi infestation (resected skin, subcutaneous tissue, and lymph nodes) using light and transmission electron microscopy, immunohistochemistry, and in vivo microscopy. In ferrets, eosinophilic abscesses and epithelioid and giant cell granulomas with fragmented worms in various stages of disintegration were found in multiple organs. Blood microvasculopathy consisted of endothelial hyperplasia, focal thickening and stenosis, vessel obliteration with marked perivascular infiltration of lymphocytes, plasma cells, eosinophils, and numerous large macrophages laden with a coarse golden-brown pigment. Endothelial ballooning and swelling, pavementing, denuding, scarring, and sludge formation were seen along with high endothelium in atypical locations. Dilated lymphatics were most prominent near adult worms and showed plump endothelium, thickened walls and valves, thrombus formation, and often perilymphangitis and adjacent tissue fibrosis. In vivo microscopy showed wriggling live adult worms in dilated incompetent sludge-filled groin lymphatics even when microfilaremia and peripheral edema were absent. In human tissues, in addition to "pachyderm" skin changes (keratosis, papillomatosis, acanthosis and collagen deposition), there was blood vessel and lymphatic vasculopathy similar to ferrets (angiocentric inflammation, congestion, vasculitis, thrombosis, thickened vessel walls, dilated lymphatics, lymphangitis, reactive lymph nodal hyperplasia and nodal fibrosis). These changes reflect generalized endothelial damage due to worm products, physical injury to valves and vessel walls from lymphatic-dwelling live worms, and host immune reactivity. Whereas adult worms target the lymphatic apparatus, their offspring and the host immune response primarily affects the blood microvasculature.

Animals↗
PubMed1989

Pain control.

1. There is a need for more data about the epidemiological nature of pain in older adults. Some evidence suggests that pain is a prevalent but under-reported symptom in this age group. 2. Some experimental studies have suggested that older adults have a different criteria for labeling a stimulus as painful. It is also likely that older adults attribute certain symptoms to aging, and this influences the coping responses to the symptoms. 3. The clinical presentation of pain in older adults may be modified by the presence of multiple diseases super-imposed on the aging process. 4. Effective pharmacological management of pain should consider the older adult's increased susceptibility to troublesome side effects, medication interactions, and low dose toxicity. 5. Nonpharmacological approaches such as an exercise program help improve functional ability as well as assist the individual to cope and live with the pain.

Aged↗
PubMed1989

[Biotransformation of B 24/76 in the rat, minipig, dog and man].

After oral administration of B 24/76 (1) on experimental animals (rat, minipig, dog) and human beings 11 metabolites could be isolated from urine, faeces and bile. The structure of 7 compounds was elucidated by means of TLC and MS. The investigated species are showing an analogues metabolic pattern with differences in the intensity and main metabolites. In phase II-reaction we could observe qualitative differences.

Adrenergic beta-Antagonists↗
PubMed1988

Whole body lymphangioscintigraphy in ferrets chronically infected with Brugia malayi.

Whole body lymphangioscintigraphy was performed after intradermal injection of 99mtechnetium human serum albumin or antimony colloid in the distal hindlimbs and forelimbs of ferrets chronically infected with Brugia malayi. The findings were compared with control ferrets and those with surgical interruption of the iliac lymphatics. While only one infected ferret manifested chronic hindlimb lymphedema, all exhibited delayed transport of radioisotope from the hindpaw with obstruction in the groin, poor or absent visualization of central lymphatic channels and regional lymph nodes, a picture similar to that following surgically induced lymphatic obstruction. In control ferrets, there was prompt visualization of peripheral lymphatic channels and regional lymph nodes with sharper and more extensive channel visualization after radiolabeled albumin and more intense sustained nodal visualization after radiolabeled antimony colloid. This noninvasive technique provides a readily repeatable investigative tool adaptable to small animals to study the evolution of lymphatic filariasis and other conditions associated with lymphatic obstruction.

Animals↗
PubMed1987

Lymphatic endothelial cell line (CH3) from a recurrent retroperitoneal lymphangioma.

An endothelial cell line derived from a massive recurrent chyle-containing retroperitoneal lymphangioma was isolated in monolayer culture. Scanning and transmission electron microscopy and immunohistochemistry confirmed a close resemblance to blood vascular endothelium with typical cobblestone morphology, positive immunofluorescence staining for endothelial marker Factor VIII-associated antigen and fibronectin, and prominent Weibel-Palade bodies. The endothelial cells also exhibited other ultrastructural features characteristic of lymphatic endothelium, including sparse microvillous surface projections, overlapping intercellular junctions, and abundant intermediate filaments. This endothelial cell line represents a new source of proliferating lymphatic endothelium for future study, including structural and functional comparison to blood vascular endothelium.

Adult↗