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Biomedical subjects

M A Ritter

Publications and source records attributed to M A Ritter.

At least 73 records · Page 4Linked to original sources
PubMed1998

Echocontrast enhanced transcranial colour-coded duplex offers improved visualization of the vertebrobasilar system.

OBJECTIVES: By means of transcranial colour-coded duplex sonography (TCCD) through the foramen magnum, the intracranial vertebral arteries (VAs) and the basilar artery (BA) can be investigated. In this study we evaluated the additional diagnostic value of echocontrast administration in patients with an insufficient pre-contrast TCCD investigation of the vertebrobasilar system. MATERIAL AND METHODS: In 22 patients the intracranial VAs and the proximal, middle and distal BA were evaluated before and after the application of 4 g of the echocontrast agent Levovist. The length of the different vessel segments visualized on colour mode before and after echocontrast, and the diagnostic benefit and the diagnostic confidence were assessed. RESULTS: Echocontrast enlarged in each vessel segment the length that could be visualized. Using echocontrast, in 5/22 patients (23%) definite and probable pathological findings unnoted in the native scans were detected. In 12 additional patients (55%) the investigator and the clinician became confident with the vascular diagnosis by echocontrast to a degree that angiography could be avoided. In only 3/22 patients (14%) no gain and in 2/22 patients (9%) an insufficient diagnostic gain was noted. CONCLUSIONS: Our study demonstrates that echocontrast provides effective Doppler signal enhancement and considerably increases the diagnostic gain of TCCD in the intracranial vertebral and basilar vasculature.

Adult↗
PubMed1998

K21-antigen: a molecule shared by the microenvironments of the human thymus and germinal centers.

The mouse IgG1 monoclonal antibody (mAb) K21 recognizes a 230-kD molecule (K21-Ag) on Hassall's corpuscles in the human thymus. This mAb also stains cultured thymic epithelial cells as well as other epithelial cell lines, revealing a predominant intracellular localization. Further analysis with mAb K21 on other lymphoid tissues showed that it also stains cells within the germinal centers of human tonsils, both lymphoid (B) cells and some with the appearance of follicular dendritic cells. Double immunostaining of tonsil sections shows that K21-Ag is not expressed by T cells, whereas staining with anti-CD22 and -CD23 mAb revealed some double-positive cells. A subpopulation of the lymphoid cells express the K21-Ag much more strongly. This K21++/CD23++ subpopulation of cells is localized in the apical light zone of germinal centers, suggesting that K21-Ag may be an important marker for the selected centrocytes within germinal centers and may play a role in B-cell selection and/or development of B-cell memory. Flow cytometric analysis showed that K21-Ag is expressed on the surface of a very low percentage of thymocytes, tonsillar lymphocytes, and peripheral blood mononuclear cells. Analysis of purified/separated tonsillar T and B lymphocytes showed that T cells do not express the K21-Ag; in contrast, B cells express low levels of the K21-Ag, and this together with CD23 is upregulated after mitogenic stimulation. Our data therefore raise the possibility that the K21-Ag may play a role in B-lymphocyte activation/selection.

Animals↗
PubMed1998

Maximizing cost-effectiveness while minimizing complications in total hip replacement.

Between July 1989 and June 1994, a consecutive series of 651 cemented total hip arthroplasties were performed in 577 patients using relatively inexpensive implants and standardized surgical and postoperative protocols. We set out to determine what effect these cost-saving measures have on the overall success and complication rate after total hip replacement surgery. Surgical results remained excellent, and perioperative, early, and late complications, including infection, loosening, and revision hip surgery, remained minimal, indeed, below usual complication rates. We concluded that cost-effective measures can be implemented while maintaining the overall excellent results of hip replacement surgery without the risk of increasing complication rates.

Adult↗
PubMed1998

Epoetin alfa. A bloodless approach for the treatment of perioperative anemia.

Under normal physiologic conditions the level of circulating red blood cells is regulated precisely by the glycoprotein erythropoietin. In major elective surgery, patients who are participating in preoperative autologous blood donation or who are anemic may not have the capacity to manufacture sufficient red blood cells in response to increases in endogenous erythropoietin that is sufficient to avoid perioperative allogeneic blood transfusion. In these patients pharmacologic doses of recombinant human erythropoietin (Epoetin alfa) have been shown to accelerate erythropoiesis, thereby increasing preoperative red blood cell production, hematocrit level, and hemoglobin concentration and reducing exposure to allogeneic blood transfusion. In four large multicenter studies, 869 patients undergoing major elective surgery were treated with a daily regimen (300 or 100 IU/kg x 14 or 15 doses) or a weekly regimen (600 IU/kg x 4 doses) of subcutaneous Epoetin alfa beginning either 2 or 3 weeks before surgery, respectively. Although all Epoetin alfa regimens were effective at accelerating erythropoiesis and increasing red blood cell production, the weekly regimen was the most patient friendly, cost effective regimen for treating preoperative anemia and minimizing patient risk of allogeneic blood transfusion.

Anemia↗
PubMed1997

Immuno-electron microscopy of the thymic epithelial microenvironment.

Normal T cell development depends upon interactions between progenitor cells and the thymic microenvironment. Monoclonal antibodies (Mabs) have been used to define subtypes of thymic epithelium by light microscopy (clusters of thymic epithelial staining [CTES]). We have now used a range of these Mabs together with gold-coupled reagents in immuno-electron microscopy to study the fine cellular distribution of the molecules to which the antibodies bind. Anti-cytokeratin antibodies were used to identify all thymic epithelial cells, while the distribution of MHC class II molecules was revealed with Mabs to shared nonpolymorphic determinants. MR6, a CTES III Mab, shows strong surface labelling of cortical epithelial cells and thymic nurse cells and very weak surface staining of thymocytes, medullary macrophages, and interdigitating cells. Mab 8.18 (CTES V) also labels a cell surface molecule; this is present on Hassall's corpuscles and associated medullary epithelial cells. The molecules detected by Mabs MR6 and 8.18 are therefore located in a position where they are available to interact with external cellular and soluble signals within the thymus. In contrast, Mabs MR10 and MR19 (CTES II) recognise intracellular molecules within subcapsular, perivascular, and medullary epithelium. A similar distribution was seen with Mab 4beta, directed against the thymic hormone thymulin, although, in addition to the expected intracellular epithelial staining, large lymphoblasts in the subcapsular zone showed surface positivity, indicating the presence of thymulin bound to surface receptors on these early lymphoid cells. As expected, MHC class II molecules were expressed on some medullary and essentially all cortical epithelial cells. However, although most subcapsular epithelium was class II-negative, some cells did express these MHC molecules on their apical surface and on the surface of their cytoplasmic extensions into the cortex. Interestingly, some cortical epithelial cells surrounding capillaries were positive for both MR6 (CTES III) and for MR10, MR19, and 4beta (CTES II). Double-labelling experiments, using MR6 and MR19 simultaneously, revealed a double-positive perivascular epithelial cell population in the thymic cortex. The possibility that these cells represent a thymic epithelial progenitor population is discussed.

Animals↗
PubMed1997

Assessment of cell proliferation by AgNOR scores and Ki-67 labeling indices and a comparison with potential doubling times.

The potential doubling time (T[pot]) has been proposed as a pretreatment estimator of intratreatment tumor proliferative capacity. The assay has several limitations, however, including the inability to discriminate between host and tumor cells in diploid tumors and the need for prospective labeling of patients with a halogenated pyrimidine. Often a separate biopsy is needed as well. In this study, Ki-67 immunostaining and AgNOR silver staining were examined as possible alternative methods by comparing them with the T[pot] in an in vitro system using two different cell lines under varying growth conditions. Using CaSki cells, nutritional status was varied to alter proliferation rates, and a strong correlation was found between Ki-67 labeling index and AgNOR scores (r = 0.927, P = 0.0003). Both Ki-67 labeling index and AgNOR scores had statistically significant inverse correlations with cell doubling time (T[d]), length of S phase (T[s]), and T(pot), as well as a positive correlation with iododeoxyuridine (IdUrd) labeling index. As an alternative method of inhibiting proliferation, 4-hydroxytamoxifen (4OH-TAM), the potent anti-estrogenic metabolite of tamoxifen, was used to inhibit the proliferation of estrogen-dependent MCF-7 cells. Treatment with the anti-estrogen resulted in decreased Ki-67 labeling index and AgNOR scores of MCF-7 cells, correlating with a decrease in IdUrd labeling index and inversely correlating with T(pot). The significant correlations among Ki-67 labeling index, AgNOR scores, and these other measures of proliferation suggest their potential value as indicators of proliferative activity. Retrospective markers, such as Ki-67 labeling index or AgNOR score, may be particularly attractive clinically in that prospective labeling of patients with halogenated pyrimidines could be avoided; however, extensive clinical testing will be required before the clinical usefulness of these markers can be established.

Cell Division↗
PubMed1997

Importance of the linker in expression of single-chain Fv antibody fragments: optimisation of peptide sequence using phage display technology.

We have investigated the potential for enhancing the production of functional single-chain Fv antibody fragments (sFv), by altering the sequence of the linker that joins the variable domains of the molecule. To identify new functionally improved linkers we have used a phage display library containing a random sequence of six amino acids in the linker. Multiple rounds of panning on the antigen led to the selection of six different linker sequences that enhanced the binding of phage to the antigen. Five of the linkers also improved the secretion of soluble sFv by approximately five-fold. Analysis of the predominant linker sequence isolated showed that this improvement is not due to an increased affinity for the antigen, nor to alterations in the toxicity to bacteria. However the linker did affect the denaturation of the sFv in urea. It is therefore possible that the novel sequence helps in the refolding or secretion of the molecule.

Amino Acid Sequence↗
PubMed1997

Inhibition of growth and enhancement of differentiation of colorectal carcinoma cell lines by MAb MR6 and IL-4.

We have previously shown that expression of gp200-MR6, a molecule that is functionally associated with the interleukin-4 receptor (IL-4R), is lost from breast carcinoma cells as malignancy increases. Here we have analysed a series of colorectal carcinoma cell lines and show a similar decrease with increasing malignancy. Moreover, analysis of the HRA-19 cell line, which can exhibit a poorly or a well-differentiated phenotype according to culture conditions, shows that gp200-MR6 is weakly expressed on the former but strongly expressed on the latter. Functional analysis using either IL-4 or monoclonal antibody (MAb) MR6 and the well-differentiated cell line SW1222 revealed that MAb MR6 acts as an agonist for IL-4, with both reagents causing a dose-dependent inhibition of cell division, but greatly enhancing the glandular differentiation of SW1222 in three-dimensional collagen gels. These observations suggest that the gp200-MR6 molecule may act as the product of a tumour suppressor gene and that its loss may be a primary event in tumourigenesis.

Antibodies, Monoclonal↗
PubMed1997

Comparison of collared and collarless femoral components in primary uncemented total hip arthroplasty.

Two hundred three consecutive primary uncemented total hip arthroplasties were prospectively randomized using collared and collarless versions of an identical titanium stem. Identical 28-mm titanium heads were implanted in all cases. One hundred three collared hips were compared with 100 collarless hips. Follow-up periods averaged 45.7 months in both groups. Intraoperative, early, and late complications were similar. Hip scores, including thigh pain, at final follow-up visit were also similar. No significant differences were noted in acetabular or femoral radiolucencies, subsidence, osteolysis, or proximal femoral remodeling. At 5 years, more collarless stems revealed pedestal formation (57.1% vs 33.9%). The presence of a collar had no effect on the adequacy of fixation, proximal femoral osteopenia, or clinical scores at 5 years.

Adult↗
PubMed1997

Postoperative pain after total knee arthroplasty.

Pain, an uncommon complication following a total knee arthroplasty, has been associated with infections, loosening, reflex sympathetic dystrophy, and occasionally litigation. Radiographic abnormalities such as the anatomic alignment, size of the prosthesis, and tilt of the prosthesis after surgery have been implicated as other sources of pain. It is shown that there is no correlation between the above abnormalities and pain.

Humans↗
PubMed1997

Selection of antibodies to cell surface determinants on mouse thymic epithelial cells using a phage display library.

The network of thymic epithelium contributes significantly to the thymic stromal cell environment, which plays a vital role in the generation and maturation of thymocytes. Monoclonal antibodies (mAb) have revealed considerable heterogeneity within this epithelial component of the mouse thymic microenvironment, but many of these antibodies recognize epitopes that are located inside the cell and so cannot be used in functional studies. As an alternative approach to isolate antibodies specific to thymic epithelium, we used a phage display library expressing single chain Fv antibodies. For selection, a thymic cell suspension was incubated with the phage display library, and major histocompatibility complex class II positive cells, the majority of which are epithelial, were then specifically selected. Phage bound to these cells were eluted and the selection procedure was repeated for a further five rounds. Immunohistochemical analysis revealed that these phage antibodies show differential staining of thymic epithelial subsets. Flow cytometric analysis of a thymic epithelial cell line using a panel of these antibodies demonstrated that they recognize epitopes on the cell surface. Furthermore, some of these antibodies also labelled human thymic epithelium, suggesting that the epitopes recognized by these antibodies are conserved between human and rodent thymus. Our approach therefore provides a rapid method to select antibodies specific for thymic epithelial cell surface determinants in their native configuration.

Animals↗