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Biomedical subjects

B Klein

Publications and source records attributed to B Klein.

At least 253 records · Page 14Linked to original sources

Lack of capillary recruitment in the brains of awake rats during hypercapnia.

The present study investigates the question of whether increases in CBF induced by hypercapnia in awake rats are accompanied by increases in the number of perfused capillaries. For the detection of perfused capillaries, gamma-globulin-coupled fluorescein isothiocyanate was injected intravenously. In 10 brain structures the density of perfused capillaries per square millimeter was determined from coronal sections using a highly sensitive fluorescent microscopical method that, in contrast to others, avoided air drying of the frozen brain sections. The results showed an inhomogeneous local distribution of the density of perfused capillaries during normo- and hypercapnia. The density of perfused capillaries was unchanged during hypercapnia compared with normocapnia, although blood flow was markedly increased. It is concluded that a capillary recruitment does not exist in the brain during the high-flow situation of hypercapnia.

Animals↗

Vibrio fluvialis, an unusual pediatric enteric pathogen.

An infant with diarrhea was discovered to have Vibrio fluvialis, an enteric pathogen not previously reported in children in the United States. This patient had an uncharacteristically mild clinical course and did not require hospitalization or antibiotics. Clinicians treating patients with diarrhea should include this organism in the differential diagnosis if their patients or patients' contacts have eaten seafood or been near bodies of seawater.

Bacteriological Techniques↗

No preferential use of the VH(V) family in human multiple myeloma.

A recently described immunoglobulin VH family (the VH(V) family) close to the DH and JH genes is preferentially rearranged in immature B-cell tumours. The question of the emergence of multiple myeloma (MM) from a tumorous pre-B cell is not yet resolved. To draw a comparison with chronic lymphocytic leukaemia (CLL), we studied the VH(V) rearrangements in 28 MM patients. A rearranged Hind III-Bam HI fragment of 9.5 kb was detected in only one patient instead of the rearranged fragment of 8.5 kb described in CLL. Rearrangements of a member of the VH(V) family in a 9.5 kb fragment were also observed in two out of 20 lymphoblastoid cell lines obtained from peripheral blood of MM patients. We report here that the VH(V) family is not preferentially involved in this pathology and that the size of the only rearrangement obtained is larger than the 8.5 kb fragment observed in CLL. These results do not favour the hypothesis of a pre-B cell involvement in MM.

Blotting, Southern↗

No detectable malignant B cells in the peripheral blood of patients with multiple myeloma.

Previous studies have reported the presence of idiotypic B lymphocytes in the peripheral blood of patients with multiple myeloma (MM), suggesting that they may belong to the malignant clone. This led us to investigate by Southern blot analyses the presence of tumour-specific immunoglobulin-gene (Ig-gene) rearrangements in the peripheral-blood mononuclear cells of 21 MM patients. This method was shown to detect clonal cells when they represent as little as 2% of the cell population. B-cell-enriched fractions were also studied in nine cases. An occasional contamination by circulating malignant plasma cells was carefully evaluated using immunofluorescence. Clonal rearrangements were observed in only two cases, in which a contamination by myeloma cells was evident. In these cases the use of different endonucleases clearly demonstrated that these Ig-clonal rearrangements involved post-switched cells. No clonal rearrangement was found when contamination by myeloma cells was absent. Our results demonstrate the absence of detectable B cells involved in the myeloma clone in the peripheral blood of patients with MM.

Aged↗

The gene for the precursor of plastocyanin from the cyanobacterium Anabaena sp. PCC 7937: isolation, sequence and regulation.

The gene encoding plastocyanin (petE1) from Anabaena sp. PCC 7937 was isolated using two sets of mixed oligonucleotide hybridization probes derived from conserved regions in the protein. Plastocyanin is encoded as a preprotein of 139 amino acids. The amino-terminal extension of 34 residues has all the characteristics of a signal peptide and is probably involved in translocation of preplastocyanin over the thylakoid membrane. The level of the petE1 mRNA, a single transcript of about 740 bases, was found to be severely reduced under conditions of Cu2+ deficiency. The petE1 gene was transferred to the genome of Synechococcus sp. PCC 7942, which did not appear to contain a structural gene for plastocyanin itself. The integrated gene becomes expressed at the transcriptional level, regardless of the amount of Cu2+ available.

Amino Acid Sequence↗

Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias.

Using a specific and very sensitive (1 pg = 1 U) bioassay, we investigated the presence of IL-6, a potent myeloma cell growth factor, in the sera of 131 subjects with plasma cell dyscrasias. 22 had monoclonal gammopathy of undetermined significance (MGUS), 13 had smoldering myeloma (SMM), 85 had overt multiple myeloma (MM), and 11 had plasma cell leukemia (PCL). Significant serum IL-6 levels were detected in only 3% of the MGUS/SMM group, but in 35% of the overt MM group and 100% of the PCL group. During overt MM, IL-6 was detected in 37% of the patients at diagnosis, 13% of those with stable MM, and 60% of those with fulminating disease. These data demonstrate that serum levels of IL-6, a potent myeloma cell growth factor in vitro, correlate with disease severity in plasma cell dyscrasias. Serial studies performed in 3 patients and correlative studies with labeling index in vivo in 25 patients have confirmed this concept. Taken together, this suggests that this cytokine is probably involved in vivo during the progressive phase of MM. Thus, anti-IL-6 or anti-IL-6 receptor antibodies could be useful as therapeutic agents at this stage of the disease.

Humans↗

Antibody specificity of the human monoclonal immunoglobulins: the elusive target antigen.

Human monoclonal immunoglobulins (HMIGs) are encountered in different clinical conditions mainly including (auto)immune disorders, immunodeficiencies and B-cell malignancies. However, in some cases no associated-disease is evidenced and they are considered as "idiopathic". Their incidence increases with age. The factors involved in the emergence and regulation of the growth and differentiation of B-cell clones secreting HMIGs are unknown but might implicate T-cell dysfunction. One approach to elucidate the origin of such B-cell clones is to identify the putative target antigen. For this reason, we have reviewed the antibody (Ab) specificity of 8439 HMIGs described in the literature, the data coming from 24 systematic screenings. Very few HMIGs present anti-hapten activity (1%) or specificity for foreign antigens (0.3%). On the other hand, the data quoted strongly document an auto-Ab (Ab1 type) activity in a large percentage of the HMIGs, mainly of the IgM type (at least greater than 30%), with properties similar to those of naturally occurring auto-Abs. Furthermore, there is some evidence that HMIGs may express anti-idiotypic activity (Ab2) to human (auto)-Abs. Finally, many of the HMIGs which are devoid of detectable auto-Ab activity (i.e., mainly IgG, IgA) share cross-reactive idiotypes with natural auto-Abs. It may be speculated that some of these HMIGs actually represent either Ab of the Ab3 type i.e., anti-anti-idiotypic Ab to auto-Abs or Ab which have varied sufficiently to loose auto-or-foreign-antigen-binding activity but maintaining idiotype. As a whole, these data demonstrate that many HMIGs are the secretory products of the auto-reactive B-cell clones which produce natural auto-Abs (including anti-idiotypic and anti-anti-idiotypic Abs) and which are characterized by a very high degree of idiotypic connection. Since HMIGs arise from such clones, it may be postulated that the emergence of HMIGs might be due to a dysfunction of the system that normally regulates such an Ab production.

Antibodies, Anti-Idiotypic↗

Phenotypic analysis of human myeloma cell lines.

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation, primarily in bone marrow, of a clone of plasma cells. The nature of the stem cells feeding the tumoral compartment is still unknown. To investigate this special point, we have studied the phenotypes of nine well-known human myeloma cell lines (HMCLs) and compared them with those of normal lymphoblastoid cell lines (LCLs). Twenty-four clusters of differentiation involved in B lymphopoiesis were investigated using a panel of 65 monoclonal antibodies (MoAbs). For each cluster, the percentage of positive cells and the antigen density were determined, giving rise to a "quantitative phenotype". We thus classified the HMCLs into two different groups: those with cytoplasmic mu chains (c mu+) and those without (c mu-). In the first (c mu+) group, comprising seven cell lines, the HMCLs had a phenotype of pre-B/B cells close to that of Burkitt's lymphoma cell lines. They expressed low densities of surface mu chains, without detectable cytoplasmic or surface light chains. Three of them were infected with the Epstein Barr virus (EBV). These c mu+ HMCLs bore most of the B-cell antigens except CD23. They expressed the CALLA antigen (CD10) and lacked the plasma-cell antigen PCA1. In contrast, LCLs expressed surface light chains, high densities of CD23, low densities of PCA1 antigen, and no CD10 antigen. The c mu- HMCLs had a plasma-cell phenotype, lacking most of the B-cell antigens and expressing high densities of PCA1 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, B-Lymphocyte↗

Serious respiratory consequences of detergent ingestions in children.

After ingesting or inhaling laundry detergent powder, eight children required hospital admission. The predominant symptoms were stridor, drooling, and respiratory distress. All but one patient underwent endoscopy of the airways and the esophagus, five children were admitted to the intensive care unit, and four children required endotracheal intubation. Laundry detergent ingestions are generally considered to have minor consequences, and there exists a paucity of literature on the subject. Evidence of significant morbidity incurred because of ingestion or inhalation of sodium carbonate-containing laundry detergent powder is presented, together with a review of the existing literature.

Burns, Chemical↗

[Post-traumatic soft tissue defects of the heel].

Trauma induced soft tissue defects of the heel are likely to develop recurrent ulcerations along with osteitis of the calcaneus even after years of conservative treatment. Biomechanical as well as plastic surgical, traumatological and orthopedical shoe device problems which must be taken into consideration to manage the functional demands, are discussed.

Adolescent↗

The renal carcinogenic effect of Merpafol in the Fischer 344 rat.

Three groups of Fischer 344 rats were fed Merpafol (Makhteshim, Israel), an agricultural fungicide, in increasing concentrations for a period of 2 years. A control group was maintained under identical conditions, but without the addition of the fungicide in the diet. A range of nonneoplastic and neoplastic lesions were observed in the kidneys of rats fed Merpafol. The histogenesis of the renal tumors is discussed in relation to chemical-induced epithelial hyperplasia and cystic tubular dilation. Comparative aspects of renal cyst development and carcinoma in humans are also discussed.

Adenoma↗

[Results of fractionated radioiodine therapy in 696 patients with hyperthyroidism and 690 patients with non-toxic goiter].

During the course of twenty years 696 patients with hyperthyroidism and 690 cases of non-toxic goitre were treated with 131I in fractionated activities and controlled on an average 4,4 (1-18) years later. Treatment strategy included three special features: a. the first and any further activity amounted to not more than 1.85 MBq per g estimated thyroid weight; b. each therapeutic activity was accompanied by oral prednisone or prednisolone for 2-6 weeks; and c. after completion of radiotherapy each patient was put on thyroid medication which was not interrupted for purposes of control. Therefore, the rate of post-irradiation hypothyroidism could not be determined. All patients were found to be permanently euthyroid and none of the former hyperthyroid patients had relapsed. 84% of the hyperthyroid goitres and 78% of the non-toxic goitres had disappeared completely, 14% and 21%, respectively, were markedly reduced. Complete disappearance of the goitre was achieved with the first 131I activity in 35% of the patients with hyperthyroidism and in 48% of the non-toxic goitres, whereas 34% of the first and 35% of the second group required a second activity; the rest received three or more activities. The mean total activities of 131I necessary for complete reduction of the goitres depended on their size and amounted to 292, 507 and 1136 MBq, respectively, in euthyroid goitres with sizes, I, II and III. The corresponding figures in hyperthyroid goitres were 403, 577 and 1129 MBq, respectively. 314 patients had endocrine ophthalmopathy which was cured in 54% and significantly improved in 37%.

Adult↗

Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6.

To explore the mechanisms involved in the pathogenesis of human multiple myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a B-cell differentiation factor in humans, and a growth factor for rat/mouse heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay, we found that two well-documented human myeloma cell lines, RPMI 8226 and U266, did not secrete IL-6 and did not express RNA messengers for IL-6. Neutralizing antibodies to IL-6 did not inhibit their proliferation, and recombinant IL-6 did not stimulate it. Taken together, these data show that IL-6 is not the autocrine growth factor of these human myeloma cell lines. A high production of IL-6 was found in the bone marrows of patients with fulminating MM, compared with patients with inactive or slightly active MM, or to healthy donors. This IL-6 production was assigned to adherent cells of the bone-marrow environment but not to myeloma cells. A spontaneous proliferation of myeloma cells freshly isolated from patients was observed in short-term cultures. Recombinant IL-6 was able to amplify it two- to threefold. The spontaneous proliferation of the myeloma cells was inhibited by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3 weeks of culture, the myeloma-cell proliferation progressively declined and no IL-6-dependent myeloma cell lines could be obtained despite repeated additions of fresh IL-6 and costimulation with other cytokines such as tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6.

Aged↗

Interleukin-6 is a potent myeloma-cell growth factor in patients with aggressive multiple myeloma.

It has recently been demonstrated that interleukin-6 (IL-6) is a potent myeloma-cell growth factor in the majority of patients with multiple myeloma (MM). Using an anti-bromodeoxyuridine monoclonal antibody (MoAb) to specifically count myeloma cells in the S-phase (ie, labeling index, LI), we demonstrate that the IL-6 responsiveness of myeloma cells in vitro is directly correlated with their LI in vivo. Myeloma cells from all 13 patients with high LIs in vivo (greater than or equal to 1%) responded in vitro to IL-6, the strongest response occurring in cells from five patients with plasma-cell leukemia. In contrast, the cells of only two of eight patients with low myeloma-cell LIs in vivo (less than 1%) responded to IL-6 in vitro. After seven days of culturing with 1,000 U/mL recombinant IL-6 (rIL-6), the median LI value in the first group of patients (in vivo LI greater than or equal to 1%) was 11%, ie 11 times higher (P less than .01) than the median LI value (1%) in the second group of patients (in vivo LI less than 1%). Thus, the in vitro IL-6 responsiveness of myeloma cells is directly related to their in vivo proliferative status, and hence to the severity of the disease.

Cell Division↗

Production of B-cell growth factor interleukin 2 and gamma interferon by peripheral blood lymphocytes from patients with chronic lymphocytic leukemia of B-cell type.

Chronic lymphocytic leukemia of B-cell type (B-CLL) is a malignant disease characterized by monoclonal proliferation of small lymphocytes of B-cell origin, usually associated with suppression of polyclonal B-cell activation (i.e., proliferation and differentiation). Normal human B-cell proliferation is controlled by different T-cell-derived lymphokines, including interleukin 2 (IL2) and gamma interferon (gamma-IFN), that account for the majority of the B-cell growth factor (BCGF) activity produced by mitogen-activated peripheral blood mononuclear cells (PBMCs). We have previously shown an increased and dysregulated secretion of IL2 in peripheral blood from patients with B-CLL. BCGF, IL2, and gamma-IFN productions by phytohemagglutinin (PHA)-stimulated PBMCs were investigated in 13 patients with active untreated B-CLL and 11 healthy donors. B-CLL PBMCs produced a significant amount of BCGF (6 U/ml) despite the low percentage of T cells (10%) associated with this disease as compared with that found in healthy donors (61%). BCGF production in normal controls and B-CLL patients was tripled after irradiation of PBMCs or addition of indomethacin. gamma-IFN secretion in B-CLL patients was decreased when compared with normal controls. Therefore, when gamma-IFN was calculated per fixed number of T cells, production was significantly higher in B-CLL patients than in normal controls, showing a dilution of the productive cells. This study suggests that T cells from B-CLL patients are functional in terms of BCGF production despite their decreased percentage and abnormalities in surface markers.

Aged↗

Carcinoma of the nasopharynx in Northern Israel: epidemiology and treatment results.

Between 1968 and 1984, 49 patients with carcinoma of the nasopharynx were treated at the Northern Israel Oncology Center. There were 6 stage I-II patients (12%) and 43 stage III-IV patients (88%). According to ethnic origin, there were 27 (55%) non-Ashkenazi Jews, 9 (18%) Ashkenazi Jews, and 13 (27%) Arabs. This distribution is different from the percentages of these ethnic groups in Northern Israel. All patients received combined cobalt 60 and 8-10 MeV electron beam radiotherapy to the primary tumor and the entire neck. Twelve stage III-IV patients received three courses of chemotherapy using bleomycin, methotrexate, and cisplatin (BMP) prior to definitive radiotherapy. The following 5-yr actuarial survival figures were achieved: all patients, 42%; stage I-II, 63%; stage III-IV, 37%; Arabs, 53%, non-Ashkenazi Jews, 47%; Ashkenazi Jews, 22%; BMP+radiotherapy, 54%; radiotherapy alone, 42%. It is concluded that there is an ethnic-related pattern of nasopharyngeal carcinoma in Northern Israel. Prognosis is better in non-Ashkenazi Jews and Arabs with early-stage lymphoepithelioma or anaplastic carcinoma, younger than 45 yr old, and receiving more than 5,500 cGy. Chemotherapy by BMP improves initial control rates with questionable benefit to long-term survival.

Adolescent↗