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Biomedical subjects

N Richter

Publications and source records attributed to N Richter.

At least 19 recordsLinked to original sources

Antihypertensive effect of 0.1-Hz blood pressure oscillations to the kidney.

BACKGROUND: Physiological blood pressure (BP) fluctuations with frequencies >0.1 Hz can override renal blood flow autoregulation. The influence of such immediate changes in renal perfusion pressure (RPP) on daily BP regulation, eg, via shear stress-stimulated liberation of renal endothelial NO, however, is unknown. Thus, we studied the effects of such RPP oscillations on renal function and on systemic BP during the onset of renal hypertension. METHODS AND RESULTS: Seven beagles (randomly assigned to each of the following protocols) were chronically instrumented for the measurement of systemic BP, RPP, and renal excretory function. An inflatable cuff was used to reduce and to oscillate RPP over 24 hours in the freely moving dog. Reducing RPP to 87+/-2 mm Hg diminished excretion of sodium and water and doubled plasma renin activity (PRA, n=7, P<0. 01) but had no significant effect on urinary nitrate excretion (n=6), a marker of NO generation. Superimposing 0.1-Hz oscillations (+/-10 mm Hg) onto the reduced RPP blunted hypertension, returned fluid excretion almost to control levels, and doubled renal sodium elimination. Nitrate excretion peaked at 8 hours, only to return to control values shortly thereafter. PRA, conversely, was significantly reduced during the last third of the experimental protocols. CONCLUSIONS: BP fluctuations transiently stimulate NO liberation and induce a reduction in PRA, which enhances 24-hour sodium and water excretion and markedly attenuates the acute development of renovascular hypertension.

Animals↗

Interferon gamma production in blood lymphocytes correlates with disability score in multiple sclerosis patients.

The proinflammatory cytokine interferon gamma (IFG) is elevated in body fluids of multiple sclerosis patients but its variation range is broad. The reason for this wide scatter of IFG production is not yet known. We looked for the relation between clinical parameters such as disability, exacerbation frequency, disease duration, course of the disease and IFG producing blood lymphocytes. Forty-one consecutive, clinically stable multiple sclerosis patients with primary relapsing course of the disease and without immunomodulatory or immunosuppressive treatment in the last 3 months were investigated for IFG in blood lymphocytes by flow cytometry. A significant positive correlation between IFG production and disability (r = 0.45, P<0.01, Spearman's rho coefficient) was found. Pathophysiological implications and therapeutical relevance of this unexpected finding are discussed.

Adult↗

Detection of an approximately 100 kD protein with strong immunoreactivity to antibodies specific for inducible nitric oxide synthase (iNOS) but without NOS activity in neutrophils of patients suffering from sepsis: results of a preliminary study.

OBJECTIVE: The study was designed to evaluate the expression of inducible nitric oxide synthase (iNOS) in activated human neutrophils. SUBJECTS AND METHODS: By Western blotting and immunocytochemical staining, iNOS expression was analyzed in neutrophils from patients with sepsis who we classified by high plasma nitrate as subjects with activated NO metabolism. For comparison, rats treated with Zymosan documented to induce iNOS were analyzed. RESULTS: Strong immunoreactivity to antibodies for iNOS was detected in leukocytes of Zymosan treated rats and in neutrophils of septic patients. Such immunoreactivity was absent in untreated rats and healthy subjects. In rats, the immunoreactivity was associated to the 130 kD protein as expected for iNOS. In contrast, the intense iNOS staining in neutrophils of septic patients was associated to an approximately 100 kD protein. Despite the iNOS staining, no increased NOS activity could be demonstrated in the neutrophils of septic patients. CONCLUSIONS: The detection of an approximately 100 kD protein with immunoreactivity to antibodies recognizing human iNOS but without NOS activity in neutrophils of patients with sepsis should initiate studies to elucidate the origin and function of this protein.

Animals↗

[Atypical gallstone ileus: radiologic and sonographic findings].

We report on a case of an atypically located gallstone ileus as a rare complication of cholecystolithiasis. A 61-year old lady with a history of diabetes type II and nephrolitiasis presented with abdominal pain lasting for 8 days and with vomiting and diarrhoea. Physical examination revealed a palpable tumour and pain in the left lower abdomen. An extensive elevation of blood sugar, CRP and leukocytosis was found. Initially X-ray of the abdomen and sonography showed signs of a subileus. Additionally a 5 x 2 cm mass with dorsal shadowing was detected by ultrasound. Gallbladder and the biliary system were normal. The sonographic suspicion of a gallstone ileus was confirmed by a subsequent CT scan. Under operation the gallstone was found in the distal Jejunum. A gallstone ileus must be included in the differential diagnosis of a tumour in the left lower abdomen. A tumour with dorsal shadowing and signs of a subileus may be the only sonographic findings of a gallstone ileus.

Cholelithiasis↗

Langerhans cell histiocytosis in children: does soluble interleukin-2-receptor correlate with both disease extent and activity?

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by monoclonal proliferation of activated Langerhans cells. Neither etiology nor pathomechanism of this disorder is presently known. However, despite monoclonality LCH might represent a reactive clonal disorder induced by immune dysfunction rather than a malignant process. To investigate a putative cytokine dysregulation in the pathogenesis of this disorder and searching for parameters of both disease activity and prognosis, serum concentrations of proinflammatory and T-cell derived cytokines were evaluated in LCH patients. MATERIALS AND METHODS: Serum levels of IL-1 beta, IL-2, sIL-2R and TNF-alpha were determined by ELISA in seven children with different types of LCH: Three children (aged 6, 10 and 14 years, respectively) with single system/single bone disease; one child (11 years) with recurrent single system/multiple bone disease and three children (1, 2 and 2 years, respectively) with multisystem disease. RESULTS: sIL-2R was elevated at diagnosis in seven children as compared to healthy adults (mean +/- SEM: 5,256 +/- 3,751 U/ml vs. 73 +/- 5.5 U/ml; P < 0.005) or healthy children (mean +/- SEM: 10,195 +/- 2,798 pg/ml vs. 2,638 +/- 156 pg/ml; P < 0.01). A positive correlation between serum levels of sIL-2R and extent of the disease could be observed. During remission, sIL-2R levels declined. IL-1 beta, IL-2, and TNF-alpha remained within the normal range during the study period. CONCLUSIONS: Elevated sIL-2R levels seem to correlate positively with both extent and activity of LCH, thus indicating a pathological T-cell activation as a pathogenetic factor. sIL-2R level is a promising parameter to monitor disease activity in LCH and may also be of prognostic relevance.

Adolescent↗

Expression of the MCP-1 gene and the HPV 16 E6/E7 oncogenes in squamous cell carcinomas of the cervix uteri and metastases.

Monocyte chemoattractant protein 1 (MCP-1) plays an important role in the recruitment of monocytes in solid tumors. Previously, for cervical carcinoma cell lines an inverse correlation between the expression of the MCP-1 gene and the human papillomavirus (HPV) oncogenes E6/E7 was described. In this study paraffin-embedded biopsy specimens from 25 squamous cell carcinomas of the cervix uteri were analyzed for the expression of the MCP-1 gene and the HPV 16 E6/E7 oncogenes by RNA/RNA in situ hybridization. Similar to in vitro analyses, in our material a negative correlation between the transcription of these genes in tumor cells could be demonstrated in 19/25 cases, whereas in 6 cases both MCP-1 gene and HPV oncogene transcription could be detected. Interestingly, the same results regarding MCP-1 gene and HPV oncogene expression were observed in the majority of corresponding metastases. On the other hand, in stromal cells MCP-1-specific transcripts could be detected in all cases. In most of them intra- and/or peritumoral macrophages were observed. Our findings support the hypothesis that HPV oncoproteins are negative regulators of MCP-1 transcription.

Carcinoma, Squamous Cell↗

[Graner operation in therapy of semilunar bone necrosis. Review of the literature and personal results].

Intercarpal arthrodesis with interposition of the capitate osteotomized in Graner's technique is performed in the treatment of stage III Kienböck's disease. Although clinical results are satisfactory, there are complications such as necrosis of the capitate, pseudarthrosis of the capitate, and arthrosis of the radiocarpal joint. From 1992 to 1995, twenty patients were treated for Kienböck's disease by Graner's technique in the Clinic of Hand Surgery II in Bad Neustadt/Saale. Seventeen patients were submitted to follow-up studies. The range of motion (extension/flexion) of the wrist was 55 degree. The grip strength was 67% of the other hand. Four patients continued to complain of pain. Necrosis of the capitate was found in four cases, pseudarthrosis in two cases, and arthrosis of the radiocarpal joint in five cases. Based on the poor X-ray results found in this review, the authors feels there is no indication for Graner's technique. They favor STT arthrodesis in stage III of Kienböck's disease.

Adult↗

High-performance liquid chromatographic determination of nitric oxide synthase-related arginine derivatives in vitro and in vivo.

In this paper we present a sensitive and reproducible method for the extraction and quantification of the nitric oxide (NO) synthase (NOS)-related basic amino acids L-hydroxyarginine (L-NHA), L-arginine (L-Arg), L-monomethylarginine (L-NMA), and L-dimethylarginine (L-NDA) in human serum samples by high-performance liquid chromatography (HPLC) analysis. We demonstrate that the serum level of L-NHA can be used as a sensitive and highly specific index of a systemic increase in NOS activity in vivo whose serum concentration, unlike that of the NO degradation products nitrite and/or nitrate, is not influenced by dietary intake. First, we measured L-NHA formation by a recombinant NOS preparation and by lipopolysaccharide-stimulated alveolar macrophages to demonstrate that this amino acid is produced by NOS in vitro. HPLC determination of L-NHA in human serum, however, proved to be difficult due to the presence of amino acids interfering with its detection. Therefore, we developed a clean-up procedure for the extraction of basic amino acids from these serum samples by using a cation-exchange cartridge. The isolated amino acids were subjected to precolumn derivatization with o-pthaldialdehyde and analyzed using a short reversed-phase column which allowed the baseline separation of L-NHA, L-Arg, L-NMA, and L-NDA within 16 min. By using this technique, the average concentrations of L-NHA, L-Arg, L-NMA, and L-NDA in the serum of healthy human subjects were determined to be 9.1, 96.1, 0.1, and 0.4 microM, respectively.

Animals↗

Allogeneic lymphocyte chimerism after clinical lung transplantation.

Donor lungs contain large amounts of passenger leukocytes which are transferred to the recipient by organ transplantation. In this study we have analysed the fate of these cells and have studied the populations of donor leucocytes detectable in the blood circulation of ten lung transplanted patients during the first postoperative weeks. To this aim we have applied immunocytological as well as flow cytometric analyses using monoclonal antibodies against polymorphic HLA class I antigens that differed between donor and recipient as well as antibodies against cell differentiation markers. The results demonstrate that donor cells can be detected in the circulation of all lung transplanted patients but there is a considerable interindividual variability between 0.9% and 17.5% (mean 5.1%) on postoperative day 3. Cells were usually detectable for 2-4 weeks and had disappeared in all patients after 1 month. The circulating donor cells consisted exclusively of lymphocytes. T cells were the predominant population, most of which seemed to be CD45R0+, but B and NK (natural killer) cells were also present. Probably due to the small numbers of patients studied no correlation between clinical parameters and the extent of donor lymphocyte persistence; there were no clinical graft-versus-host reactions. The findings demonstrate the regular existence of a transient (macro)chimerism due to passenger lymphocytes in the early phase after lung transplantation. The immunological function and the relation between this phenomenon and the long-term microchimerism which frequently develops after solid organ transplantation remain unclear.

Adult↗

Transmission of donor lymphocytes in clinical lung transplantation.

Passenger mononuclear cells in organ grafts are known to influence the alloimmune response to the graft. To assess their relevance in clinical lung transplantation, we studied the amount, distribution, cell types, and surface marker expression of mononuclear cells in human donor lungs. Two major compartments of mononuclear cells could be differentiated: lymph nodes containing resting T and B lymphocytes, and the lung tissue itself, containing mainly activated lymphocytes as well as monocytes/macrophages. Tissue-associated mononuclear cells make up 20-40 x 10(9) cells per lung, about 30-50% of which are lymphocytes. Tissue-associated lymphocytes are predominantly T and NK cells; most of the T cells are CD8+ CD45R0+ and express HLA-DR. Strong expression of the adhesion molecules LFA-1 and ICAM-1 is present on infiltrating cells as well as on resident cells of the organ. Moreover, the lymphocytes inside the lung tissue are functionally highly active, with a strong stimulatory as well as alloreactive potency. Thus, large numbers of allogeneic mononuclear cells and particularly large numbers of functionally active lymphocytes are obviously transmitted by human lung allografts. The immunological in vivo relevance of these cells after lung transplantation may include allostimulation and graft-versus-host activity, but also beneficial immunomodulatory effects.

Antigens, CD↗

Persistence of donor lymphocytes in liver allograft recipients.

Occasional cases of graft-versus-host disease after liver transplantation indicate a transfer of donor lymphocytes by human liver grafts. However, little is known about the usual fate and potential function of passenger lymphocytes in clinical liver transplantation. In this study, we have analyzed liver graft recipients for the presence of donor lymphocytes in the early course after transplantation. The presence of such cells in blood, the graft, and, occasionally, the skin was studied by the use of mAb to polymorphic HLA class I determinants and double-staining techniques in flow cytometry and immunocytology. The findings were compared with the clinical courses and with the results of routine graft biopsies. Within the first week after transplantation, in all 16 patients, between 1% and 24% donor lymphocytes (T, NK, and B cells) were detectable in blood, and in 14 of 22 patients (64%), between 2% and 23% donor T cells were found in the graft. After more than 2 weeks, donor cells were still present in blood in 2 of 14 patients at very low numbers. The presence of donor lymphocytes in the graft was associated with intragraft immune activation in 5 of 15 patients, but no clinical rejection occurred in these cases; mild graft-versus-host disease was observed in one patient. These findings demonstrate that donor lymphocytes regularly persist in liver-grafted patients for some time; this transient mixed lymphoid chimerism is only rarely associated with clinical graft-versus-host disease and some evidence even suggests that these donor-derived lymphocytes may exert beneficial immunomodulatory properties.

Adult↗