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Biomedical subjects

H G Klein

Publications and source records attributed to H G Klein.

At least 37 records · Page 2Linked to original sources
PubMed1998

Marfan Database (third edition): new mutations and new routines for the software.

The Marfan database is a software that contains routines for the analysis of mutations identified in the FBN1 gene that encodes fibrillin-1. Mutations in this gene are associated not only with Marfan syndrome but also with a spectrum of overlapping disorders. The third version of the Marfan database contains 137 entries. The software has been modified to accommodate four new routines and is now accessible on the World Wide Web at http://www.umd.necker.fr

Computer Communication Networks↗
PubMed1998

A novel mutation in the neonatal region of the fibrillin (FBN)1 gene associated with a classical phenotype of Marfan syndrome (MfS). Mutations in brief no. 163. Online.

Marfan Syndrome (MfS) is an autosomal dominant inherited connective tissue disorder with variable phenotypic expression of cardiovascular, skeletal and ocular manifestations. Cardiovascular complications, such as aortic aneurysm and dissection drastically reduce life expectancy of individuals with MfS, whereas preventive surgery substantially improves the prognosis of these patients. A number of mutations in the fibrillin 1 (FBN1) gene associated with MfS have been identified to date, demonstrating considerable molecular heterogeneity. One region, however, located around exon 24, exhibits a striking clustering of mutations, which are associated with a severe, socalled neonatal form of MfS. Here we report the first mutation (G2950A) in exon 24 of the neonatal region of the FBN1 gene, associated with a classic MfS phenotype. The mutation leads to the subsitution of valin by isoleucin (V984I), both uncharged amino acids, which only differ in a single methyl group. This defect was identified in a proband with cardiovascular manifestations of MfS by SSCP analysis of PCR-amplified genomic DNA, direct PCR sequencing and RFLP analysis. The substitution was neither detected in the unaffected 4-year old daughter of the proband, nor in 3 of his healthy family members nor in 108 allels from control individuals, suggesting that this mutation is causative for MfS in the patient. Since no other family member of the proband is affected by MfS, the defect described is sporadic. In summary, we identified a novel defect in exon 24 of the neonatal region of the FBN1 gene in a patient with a classic phenotype of MfS, suggesting that conservative substitutions in this region may lead to a less severe phenotype of the disease. This finding further demonstrates the remarkable phenotypic heterogeneity associated with FBN1 mutations and stresses the significance of modifying genes and individual alterations in protein function for the pheontypic expression of the disease.

Child, Preschool↗
PubMed1998

Long-term prognosis of surgically-treated aortic aneurysms and dissections in patients with and without Marfan syndrome.

OBJECTIVE: Aortic aneurysms and dissections are the leading causes of premature death in Marfan syndrome (MfS). This study aims to compare long-term results of surgically treated aortic aneurysms and dissections in patients with and without MfS in respect to early and late prognosis. METHODS: From March 1975 to August 1994, 33 patients with classic MfS (group A, age 34.2 +/- 9 years) and 298 patients with non-fibrillinopathic aortic disease (group B, age 54 +/- 13 years) underwent aortic surgery. Acute dissections occurred in 57.6 (A) versus 37.9% (B). A total of 54.6% of patients in group A were treated with a composite graft versus 16.4% in B. The aortic arch and the descending aorta was replaced in 30.4% of MfS patients and 24.9% of patients without MfS. RESULTS: We observed 7 (25.0%, A) versus 35 (14.2%, B) late deaths among the 28 (A) versus 247 (B) early survivors. In 5 patients (17.9%) of A and 8 patients (3.2%) of B, late death was caused by redissection or recurrent aneurysm (P < 0.001). Long-term survival after 5, 10 and 15 years in group A was 82 +/- 7, 60 +/- 11 and 30 +/- 22%, and 75 +/- 3, 69 +/- 3 and 64 +/- 4% in group B. A total of 22 reoperations were performed in 11 MfS patients, 17 reoperations were due to recurrent aortic diseases. Three of the 8 patients underwent reoperation after Wheat procedure because of sinus valsalva aneurysm. None of the patients with composite graft replacement needed reoperation in this segment, but 3 patients suffered from redissection at the proximal aortic arch. In group B, reoperations were significantly less frequent (10.7%) compared to MfS patients (66.7%; P < 0.001). CONCLUSIONS: Surgical treatment of aortic disease in MfS patients is associated with a high risk of redissection and recurrent aneurysm. If the ascending aorta needs to be replaced, we recommend the composite graft technique and a more aggressive approach to reduce the frequency of distal reoperations. In order to reduce the high reoperation rate in MfS patients, frequent clinical follow-up may contribute to improve life expectancy in MfS patients.

Adult↗
PubMed1998

Peripheral expansion of pre-existing mature T cells is an important means of CD4+ T-cell regeneration HIV-infected adults.

The CD4+ T-cell pool in HIV-infected patients is in a constant state of flux as CD4+ T cells are infected and destroyed by HIV and new cells take their place. To study T-cell survival, we adoptively transferred peripheral blood lymphocytes transduced with the neomycin phosphotransferase gene between syngeneic twin pairs discordant for HIV infection. A stable fraction of marked CD4+ T cells persisted in the circulation for four to eighteen weeks after transfer in all patients. After this time there was a precipitous decline in marked cells in three of the patients. At approximately six months, marked cells were in lymphoid tissues in proportions comparable to those found in peripheral blood. In two patients, the proportion of total signal for the transgene (found by PCR analysis) in the CD4/CD45RA+ T-cell population relative to the CD4/CD45RO+ population increased in the weeks after cell infusion. These findings indicate that genetically-marked CD4+ T cells persist in vivo for weeks to months and that the CD4+ T-cell pool in adults is maintained mostly by the division of mature T cells rather than by differentiation of prethymic stem cells. Thus, after elements of the T-cell repertoire are lost through HIV infection, they may be difficult to replace.

Adult↗
PubMed1998

Cationic amino acid transporter mRNA expression in rat kidney and liver.

Expression of rat cationic amino acid transporter 2 (r-CAT-2) mRNA was studied in kidney and liver using Northern blot analysis and nonradioactive in situ hybridization with a probe identifying both the r-CAT-2alpha and -2beta splice variants. Expression of r-CAT-2 mRNA was higher in the liver than in the kidney. Within the kidney, r-CAT-2 mRNA was more abundant in the outer and inner medulla than in the cortex. In the liver lobule, the intensity of the hybridization signal in hepatocytes decreased between the portal area and the central vein. In the kidney, hybridization signals were detected in parietal cells of Bowman's capsule, various tubule cells of outer and inner medulla, in endothelial and interstitial cells of inner medulla, and in papillary epithelial cells.

Amino Acid Transport Systems, Basic↗
PubMed1997

Enumeration of CD34+ hematopoietic progenitor cells in peripheral blood and leukapheresis products by microvolume fluorimetry: a comparison with flow cytometry.

There is increasing interest in both standardization and simplification of methods for enumeration of CD34+ hematopoietic progenitor cells (HPC) to facilitate cellular therapies and to improve interinstitutional comparison of clinical and laboratory results. We evaluated a novel method for CD34+ cell enumeration based on microvolume fluorimetry (MVF) compared with our laboratory's routine flow cytometric method on samples of peripheral blood and leukapheresis products. The MVF method is semiautomated and uses a 633-nm light from a helium-neon laser to scan fluorochrome-labeled cells held in stasis in a capillary known volume. The performance of the MVF assay for enumeration of CD34+ cells was found to be comparable to our routine flow cytometric assay in linearity and accuracy in the range of 5-1500 cells per microliter. Precision of MVF for replicate assays on the same instrument was demonstrated by coefficient of variation (CV) values of 8.4% at a CD34+ cell concentration of 284/microliters for a sample volume of 0.8 microliters, and 15.7% at 12/microliters for a sample volume of 3.2 microliter. Precision among three different instruments was demonstrated, using sample volumes of 1.6 microliters, by CV values of 44% at 6 cells/microliters and 4.6% at 733 cells/microliters. In a field sample evaluation, precision of the entire assay system for paired measurements on 0.8-microliter sample volumes was demonstrated by CV values of 50%, 31%, and 15% for peripheral blood samples with concentrations of 0-10, 10-20, and 20-100 CD34+ cells/microliters, respectively, and 6.3%, 8.1% and 6.5% for leukapheresis samples with concentrations of 0-100, 100-1,000, and 1,000-2,500 CD34+ cells/microliters, respectively. The MVF assay was easy to perform, required minimal technical training time, and had a turnaround time of 40 min, of which less than 10 min was actual technical time. These observations suggest that the MVF method for CD34+ cell enumeration may prove useful to clinical laboratories providing support for HPC collection, processing, and transplantation services that require relatively simple, rapid assays for product quality control or to guide real-time clinical decisions.

Antigens, CD34↗
PubMed1996

New insights into the management of anemia in the surgical patient.

Although the safety of allogeneic blood transfusion has increased dramatically in recent decades, some risks remain. Contamination with infectious agents-including viruses, bacteria, spirochetes, and parasites-is still possible, although recent advances in blood screening and testing have decreased the risk. The principal noninfectious complication of blood transfusion is immunomodulation. Clinical manifestations of transfusion-related immunomodulatory activity include hemolytic and allergic reactions, graft-versus-host disease, the possible decreased survival in patients with cancer, as well as increased susceptibility to postoperative infection, activation of latent infection, improvement in organ allograft survival, decreased frequency of spontaneous abortion, and moderation of immune inflammatory disease. The cause of transfusion-related immunosuppression is not yet known, but possible contributing factors are the development of a suppressor cell network, formation of anti-idiotype antibodies, clonal deletion, macrophage paralysis, up-regulation of cells with latent infections, cytokine infusion, and contamination by infectious and noninfectious agents.

Anemia, Hypochromic↗
PubMed1996

Growth factors and their impact on transfusion medicine.

Hematopoietic growth factors, glycoproteins that stimulate self-renewal, differentiation, and proliferation of responsive hematopoietic cells, promise to revolutionize transfusion medicine. Recombinant DNA technology has made several of these cytokines available at pharmacologic doses, and new candidate agents for clinical application appear regularly. Growth factors prescribed for patients have already reduced the requirement for red blood cell and granulocyte transfusions in selected clinical circumstances. A lineage-specific thrombopoietin will likely limit the need for platelet transfusions. Hematopoietic cytokine injections have also been used to increase the number of red blood cells, granulocytes and circulating primitive progenitor cells in blood donors. Cytokine-stimulated peripheral blood progenitor cell infusions have complemented and, in some instances, replaced bone marrow for adjunctive cancer chemotherapy and for bone marrow transplantation. Finally, synergistic combinations of cytokines can effect ex vivo expansion of lymphocytes and of progenitor cells to provide novel blood components. Hematopoietic growth factors are still expensive and their long-term effects remain to be determined. However, as the biologic activities of cytokines and the physiology of hematopoietic progenitor cells become better understood, the clinical application of novel cellular components may redefine the concept of blood transfusion.

Blood Transfusion↗
PubMed1995

A controlled comparison of the efficacy of hetastarch and pentastarch in granulocyte collections by centrifugal leukapheresis.

Compared with hetastarch (HS), the low molecular weight analog pentastarch (PS) has been reported to be equally effective for granulocyte collection by centrifugal leukapheresis, to result in fewer adverse donor reactions (ADR), and to have a more rapid elimination profile. We prospectively compared the granulocyte collection efficiency (GCE), granulocyte yield, and ADR in 72 randomly paired granulocytapheresis procedures from 36 volunteer donors using the model CS-3000 Plus Blood Cell Separator (CS) and either PS or HS as the sedimenting agent. Paired collections from each donor allowed us to compare the two agents directly while controlling for intrinsic donor differences. In 33 of 36 (92%) donors, HS procedures were significantly more efficient than PS procedures (P < .001). As an average, HS collections yielded 2.3 +/- 0.67 x 10(10) granulocytes at 58% +/- 8.8% GCE, whereas PS procedures resulted in 1.4 +/- 0.76 x 10(10) granulocytes at 33% +/- 15% GCE. No starch-induced ADR were seen with either agent. For granulocyte harvests using the CS, (1) in most donors, using HS as the red blood cell sedimenting agent during centrifugal leukapheresis results in significantly higher (nearly twofold) GCE and larger granulocyte yields in comparison with using PS, (2) ADR were not observed with either agent, and (3) the potential benefit of more rapid PS elimination should be balanced against significantly lower granulocyte yields.

Adsorption↗