PubMed Health⌕ Search

Biomedical subjects

C A Müller

Publications and source records attributed to C A Müller.

At least 127 records · Page 7Linked to original sources

Hybridization techniques provide improved sensitivity for HCMV detection and allow quantitation of the virus in clinical samples.

Hybridization techniques (slot-blot and in-situ hybridization assays) and immunostaining using murine monoclonal antibodies directed against different proteins of the human cytomegalovirus (HCMV) were compared for their sensitivity and specificity for detection of HCMV. A model system with HCMV infected human embryonic lung fibroblasts and lung biopsy specimens obtained from patients with culture positive HCMV interstitial pneumonia were used for evaluation of these techniques. The hybridization techniques were found to provide an improved sensitivity compared to immunostaining. Additionally a good correlation was found between the virus dose determined by TCID50 and the amount of viral DNA detected by slot-blot hybridization and by the number of autoradiographic silver grains per 100 cells per 2 weeks exposure time detected in the infected fibroblasts by in-situ hybridization. Thus, at least in the model system quantification of the virus was achieved by hybridization assays.

Cells, Cultured↗

The pathogenesis of chronic renal failure.

The pathogenesis of terminal renal failure is discussed. The following are distinguished: 1. Renal failure occurring against a background of decompensated benign nephrosclerosis, primary and secondary malignant nephrosclerosis, and stenosis of the renal artery. 2. Renal failure caused by loss of glomeruli. It is pointed out that in most glomerulopathies, including diabetic glomerulopathy and renal amyloidosis, terminal renal failure only develops when accompanying disease of the postglomerular vessels leading to interstitial fibrosis impairs the outflow of blood from the glomerulus to such an extent that no more urine is produced. 3. Renal failure in disease of the tubules themselves. It is emphasized that acute renal failure only becomes chronic when interstitial fibrosis develops from the interstitial edema occurring in the early stage of the disease. 4. Renal failure occurring in primary diseases of the renal cortical interstitium. The chronic sclerosing renal diseases arising from acute interstitial nephritis are dealt with, as also are reflux nephropathy, incomplete obstructive nephropathy, analgesic nephropathy, and chronic interstitial rejection reactions in transplanted kidneys.

Diabetic Nephropathies↗

Expression of HLA-DQ, -DR, and -DP antigens in normal kidney and glomerulonephritis.

Expression of the defined subtypes of HLA-class II antigens DQ, DR, DP, as well as of a putatively new HLA-class II determinant DY was evaluated with specific monoclonal antibodies on frozen sections of 15 normal kidneys, as well as of renal tissue of 65 patients with different forms of glomerulonephritis (GN). In normal kidney HLA-DR and/or -DY versus DQ or DP antigens were shown to be differentially expressed on subpopulations of glomerular and interstitial cells, as well as vascular endothelia. Normal proximal tubular epithelia lacked HLA-DQ and -DP antigens, but carried -DY and variably -DR products constitutively. In comparison, aberrant presence of HLA-DQ and/or -DP antigens was found on proximal tubular cells in the majority of patients with rapidly progressive (RPGN), membranoproliferative GN (MPGN), or focal glomerular sclerosis (FGS), but more rarely observed in other forms of proliferative or non-proliferative GN. In addition all cases with RPGN revealed reduction of HLA-DQ, -DR, -DP or -DY+ glomerular cells. Decline of HLA-DP and/or -DR+ glomerular cells was variably seen in mesangioproliferative glomerulonephritis (MesPGN) and MPGN, whereas in FGS HLA-DQ antigens appeared to be increased in glomeruli. HLA-DQ, -DR, -DY+ interstitial cellular infiltrates were present in RPGN, FGS and MPGN and only occasionally occurred in other forms of GN. Altered renal expression of HLA-class II antigens may indicate specific sites of immunologically-mediated kidney injuries in GN.

Antibodies, Monoclonal↗

[The pathogenesis of chronic renal failure].

The pathogenesis of terminal renal failure is discussed. The following are distinguished: 1. Renal failure occurring against a background of decompensated benign nephrosclerosis, primary and secondary malignant nephrosclerosis, and stenosis of the renal artery. 2. Renal failure caused by loss of glomeruli. It is pointed out that in most glomerulopathies, including diabetic glomerulopathy and renal amyloidosis, terminal renal failure only develops when accompanying disease of the postglomerular vessels leading to interstitial fibrosis impairs the outflow of blood from the glomerulus to such an extent that no more urine is produced. 3. Renal failure in disease of the tubules themselves. It is emphasized that acute renal failure only becomes chronic when interstitial fibrosis develops from the interstitial edema occurring in the early stage of the disease. 4. Renal failure occurring in primary diseases of the renal cortical interstitium. The chronic sclerosing renal diseases arising from acute interstitial nephritis are dealt with, as also are reflux nephropathy, incomplete obstructive nephropathy, analgesic nephropathy, and chronic interstitial rejection reactions in transplanted kidneys.

Amyloidosis↗

Significant association of acute lymphoblastic leukemia with HLA-Cw7.

Frequencies of all defined HLA-A, -B, -C (-DR) antigens were determined in 142 (59) Germans suffering from acute lymphoblastic leukemia (ALL) with differentiation of immunologically defined or age-related subgroups of the disease. A highly significant rise of the HLA-C locus antigen Cw7 was found in ALL patients, particularly those over the age of 11 in comparison with local German and Caucasian controls of the Ninth Int. Histocompatibility Workshop (WS). Only slight differences of HLA-Cw7 frequencies were observed within the four immunologically defined ALL subtypes of all or age-related patient groups. HLA-A, -B, or -DR antigens, as well as HLA-ABC three-locus haplotypes were similarly distributed in patients and their local or Caucasian controls. The results indicate HLA-linked genetic factors conferring susceptibility to ALL in adults, particularly those presenting with B-, T-, and Null-ALL.

Adolescent↗

High frequency of graft-versus-host-like syndromes following syngeneic bone marrow transplantation.

Occurrence of acute graft-versus-host reactivity-like (GvHR) syndromes has been shown in at least 3 and possibly in 4 further cases of 9 patients with bone marrow transplants from identical twin donors. The diagnosis of GvHR-like syndromes is based on clinical, immunologic, and histologic features indistinguishable from those observed in graft-versus-host disease (GvHD) grades I-III of patients receiving allogeneic major histocompatibility complex (MHC) matched bone marrow transplants. Induction of GvHR-like symptoms appeared to be correlated with reactivated viral infections after bone marrow transplantation (BMT) or, like in animal models, was due to specific conditioning therapy with cyclophosphamide. The high incidence of acute GvHR-like syndromes in the first months after syngeneic BMT suggests inability of the immune system to discriminate appropriately self from nonself antigens during a normal tolerance induction period after grafting.

Adolescent↗

Renal, major histocompatibility complex antigens and cellular components in rapidly progressive glomerulonephritis identified by monoclonal antibodies.

Identification of crescent-forming cells in rapidly progressive glomerulonephritis (RPGN) is very difficult, and controversial results on the participation of different epithelia as well as of monocytes have been reported. In the present study different monoclonal antibodies were used to analyze cellular infiltrates of crescents and the interstitium as well as the distribution of well-defined renal antigens and major histocompatibility complex (MHC) encoded antigens along the human nephron in cryostat sections of renal biopsies from patients with RPGN. The results demonstrate that monocytes/macrophages infiltrate Bowman's space and that cellular components of crescents present with phenotypes of parietal glomerular and proximal tubular cells. T lymphocytes are significantly found in glomeruli and also in interstitium with predominance for CD4+ lymphocytes. Reduction of MHC class-II antigens within diseased glomeruli correlates with changes in renal antigen expression. Tubular cells, however, often presented an abnormal expression of MHC class-II antigens. Differences of renal and MHC-encoded antigen expression may be due to rapid regeneration episodes of renal parenchymal cells in RPGN.

Adult↗

Differential expression of the HLA-B7 and the HLA-A2 gene in transfected mouse L(tk-) cells after stimulation by mouse interferon.

Mouse L(tk-) cells were transfected with recombinant genomic clones encoding the human major histocompatibility antigens HLA-A2 or HLA-B7. The exposure of 15 different transfected cell clones to mouse interferon resulted in an up to 2.9-fold enhancement of the HLA-A2 antigen at the cell surface but in an up to 5.5-fold enhancement of the HLA-B7 antigen as shown by quantitative radioimmunoassay with monoclonal antibodies directed against different HLA epitopes. Using the HLA-Bw6 specific monoclonal antibody 2BC4, an even higher increase of the HLA-B7 antigen (up to 12-fold) could be observed. This higher inducibility of an HLA-B versus HLA-A locus gene may reflect distinct regulatory mechanism controlling the expression of HLA class I subregion antigens.

Animals↗

[Importance of HLA systems in the regulation of hematopoiesis].

Human hematopoiesis is known to be influenced by local microenvironments, as well as by a large number of specific soluble inhibitory or stimulatory mediators. It has been suggested that the HLA system plays an important role in the regulation of physiological and pathological hematopoietic cell proliferation and differentiation. The quality and quantity of HLA-antigen expression have been shown to influence interactions of colony-inhibitory factors with hematopoietic precursor cells. It is also assumed that HLA antigens mediate regulatory mechanisms of T-lymphocytes on the production of hematopoietic factors, as well as on hematopoietic cell proliferation and differentiation. The HLA antigens may thus participate in regulatory functions of the immune system in hematopoiesis.

Cell Differentiation↗

Microimmunohistology of hematopoietic colonies.

A new method is described which allows immunohistological analysis of hematopoietic colonies grown in methylcellulose. With the use of a specific embedding technique, we prepared cryostat sections that facilitated multicell marker studies as well as the evaluation of the in situ organization of individual colonies.

Antibodies, Monoclonal↗

[Bone marrow transplantation in acute leukemia, chronic myeloid leukemia, severe aplastic anemia and stage IV neuroblastoma. Effect of antiviral prevention with anti-CMV-hyperimmunoglobulin and acyclovir].

Bone marrow transplantation was performed between IV/82 and X/85 in 64 patients with acute leukemia (n = 36), chronic myelogenous leukemia (CML; n = 13), severe aplastic anemia (n = 12), and neuroblastoma stage IV (n = 3). Of these patients 57 received allogeneic marrow from HLA-ABCDR identical, MLC-negative sibling donors. Six transplants were performed with syngenic marrow and one with autologous marrow. Of the 64 patients 48 survived 40-1,250 days after transplantation, resulting in a survival rate (SR) of 75% and a survival probability (SP) of 71%. Of the 36 patients suffering from acute leukemia (SR = 64%, SP = 51%), patients with acute myelogenous leukemia (AML) in first complete remission (n = 11; SR = 81%, SP = 76%), as well as patients with acute lymphatic leukemia (ALL) in 1st to 4th complete remission at the time of transplantation (n = 14; SR = 81%, SP = 76%) show a favorable prognosis. A poor survival rate was seen for patients with AML when transplanted in second or partial remission (1/5; SR = 20%), as well as for patients suffering from ALL and transplanted during relapse or partial remission (1/6; SR = 16%). Of 13 patients suffering from CML 12 survived the transplantation free of relapse (SR = 93%, SP = 92%), and one patient died from varicella zoster pneumonia. Of the transplanted patients with severe aplastic anemia, 12 of 13 are surviving with complete hematologic reconstitution; one patient, however, died on day 10 from a sepsis. In our patient group, the SR as well as the SP has been improved through changes in the irradiation protocol concomitant with prophylactic application of anti-CMV hypergammaglobulin, as well as through additional oral medication of Azyklovir. The 41 patients (BMT No. 7-47) with total body irradiation at one time show an SR of 44% and an SP of 41%. The following 46 patients (BMT No. 48-93) have reached an SR of 83% and an SP of 74% under the regimen of fractionated total body irradiation, plus prophylaxis with anti-CMV hypergammaglobulin and Azyklovir. Within this group, no fatal CMV pneumonia was encountered as opposed to six patients lost from CMV pneumonia in the first group.

Acyclovir↗

[Bone marrow transplantation in severe aplastic anemia].

Bone marrow transplantations were performed on 15 patients (aged 5-39 years) with severe aplastic anaemia. Twelve patients are alive 76-1930 days (median 668 d) after transplantation, with complete haematopoetic recovery. Total-body radiation with 3.6 Gy in four patients, cyclosporin A administration to ten patients and buffy-coat transfusion to nine patients entirely prevented early rejection. Two patients died of pneumonia (aspergillus; varicella-zoster virus), one patient died of bleeding from a splenic-artery aneurysm. In patients under the age of 40 years with severe aplastic anaemia bone marrow transplantation as early as possible after diagnosis is the treatment of choice if HLA-identical siblings are available as donors. In patients over 40 years treatment should at first be tried with antithymocyte globulin.

Acute Disease↗

Loss of differentiation features in trypsin separated heart muscle cells.

Loss of maturation features is demonstrated for 8-day-old chick embryo heart myocytes, once they have been completely dissociated by trypsin. In support of this statement a total of 65 sections of six isolated cells, fixed while still spherical or during early flattening, were examined under the electron microscope. Trypsin-separated heart muscle cells, even though originating from already differentiated embryonic heart tissue, can therefore in principle be used for differentiation experiments in culture. However, the same cell suspensions also yielded an appreciable quantity of nonisolated cells. In such cell complexes, one can find areas showing well-ordered fibrils and intercalated disks. From 27 sections of a cell pair incidentally transferred into culture undissociated and then fixed while still in the globular state, the fourth and fifth sections, starting from the substrate side of the culture, showed an intercalated disk. Because of its small diameter, this cell complex would hardly have been retainable by a gauze with meshes likely to allow passage of only single cells. Thus the availability of differentiation experiments in culture, starting with already differentiated heart tissue, is restricted to cases where, in a selected territory, each cell has been established without doubt as isolated.

Animals↗

Intramedullary pressure increase for different commercial and experimental reaming systems: an experimental investigation.

OBJECTIVE: To measure the differences in intramedullary (IM) pressure for commercial reamer systems. DESIGN: IM pressure values for the following systems were measured: AO, Biomet, Howmedica grey reamer, Richards, and Zimmer. To investigate the influence of shaft diameter, the AO reamer head was additionally connected to a small shaft (A6/A7). The pressures were measured in plexiglass tubes filled with a mixture of petroleum jelly and paraffin oil with flow properties at 20 degrees C equivalent to those of bovine medullary fat at 36 degrees C. The reaming assemblies were inserted into the tubes using a materials testing machine at a constant speed. In addition, pressure measurements were made using five pairs of human femora to compare Biomet reamers with the AO reamer with thin, flexible drives (A6/A7). RESULTS: The following pressure distributions were obtained (millimeters of mercury; mean value +/- standard deviation): 9.5-millimeter reamer: low for Biomet (272+/-39); moderate for Richards (810+/-101); and high for Howmedica (990+/-132), AO conventional (1,000+/-97), and Zimmer (1,140+/-183); 13.0-millimeter reamer: low for Biomet (132+/-21), Howmedica (204+/-45), and Zimmer (226+/-33); moderate for AO conventional (474+/-42); and very high for Richards (1,734+/-127). The second worst system (AO conventional: 1,000+/-97) became the second best system by simple reduction of the shaft diameter (A6/A7: 378+/-33). CONCLUSION: A comparison of shaft diameters and pressure increase clearly showed that the system with the thinnest shaft produced the lowest pressure values and vice versa.

Equipment Design↗

Cadherins and integrins in renal cell carcinoma: an immunohistochemical study.

AIMS AND BACKGROUND: The aim of this study was to determine the expression of cadherins and integrins in renal cell carcinoma (RCC) and their relationship with tumor morphology and TNM status. METHODS: Cadherin and integrin expression was investigated using an indirect immunoperoxidase technique, applying antibodies to E-, N-, P- and VE-cadherin and to alpha1, alpha2, alpha3, alpha4, alpha5, alpha6, and alpha(v) integrin subunits. Correlation of semiquantitatively scored adhesion molecule levels with histopathological parameters (cytology, growth pattern, nuclear grade) and TNM status was performed for 24 RCCs (17 clear cell, 3 granular, 3 spindle cell and 1 chromophobe cell type according to the WHO classification). RESULTS: E-cadherin and N-cadherin were present in most cases (88% and 67%, respectively) and were usually coexpressed. T3 RCCs displayed higher E-cadherin and N-cadherin levels than T1/T2 tumors regardless of tumor grade, suggesting that impairment of their function might exist without actual loss from tumor cells. P-cadherin was found focally in two RCCs only, while VE-cadherin was present on stromal vessel endothelium in five tumors, showing no differences with regard to cell type, growth pattern, tumor grade or TNM status. All integrins were present in the studied RCCs (ranging from 12% for alpha5 to 79% for alpha3), including those that are normally absent from adult kidney tissue (alpha4 and alpha5). Tumors of higher grade showed increased alpha(v) and decreased alpha6 levels, while RCCs with metastases less often showed diffuse alpha3 presence and never expressed alpha5 integrin. CONCLUSIONS: Our results suggest that the level of expression of N-cadherin and some integrins (most notably alpha3, alpha6 and alpha5) is associated with the capacity of RCC for local and distant spread, regardless of tumor grade.

Antigens, CD↗