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Biomedical subjects

W Lange

Publications and source records attributed to W Lange.

At least 19 recordsLinked to original sources
PubMed1992

Expression of bcl-2 in Burkitt's lymphoma cell lines: induction by latent Epstein-Barr virus genes.

The bcl-2 oncogene blocks programmed cell death (apoptosis). Epstein-Barr virus (EBV) can immortalize B lymphocytes into continuously growing lymphoblastoid cell lines (LCL) by the coordinate expression of at least 9 latent genes (EBV nuclear antigen [EBNA] 1-6, latent membrane protein [LMP], and terminal proteins [TP] 1 and 2). We analyzed transcription and expression of bcl-2 and latent EBV genes in Burkitt's lymphoma (BL) cell lines with a germinal center phenotype (group I) as well as activated BL cell lines (group III) and LCLs. We found high expression of bcl-2 as well as the full spectrum of latent EBV genes in LCLs and activated group III BL cell lines. Group I BL cells expressed little or no bcl-2, EBNA-2, and LMP. Superinfection with nondefective EBV or an EBNA-2-defective virus as well as transfection with EBNA-2- or LMP-carrying vectors into the EBV-negative cell lines RAMOS, DG75, U698, or BJAB induced upregulation of bcl-2 expression. The strongest effect on bcl-2 was obtained by transfection with LMP, or infection with the nondefective virus. No change of bcl-2 expression was observed with EBNA-1. Our data indicate that the immortalization capacity of EBV and the growth advantage of EBV-positive compared with EBV-negative BL cells in vitro may predominantly be mediated via induction of bcl-2 and the main effectors are EBNA-2 and LMP.

Antigens, Viral↗
PubMed1992

Human infections with Borna disease virus: seroprevalence in patients with chronic diseases and healthy individuals.

Borna disease virus (BDV) is as yet an unclassified infectious agent which causes a neurologic disease in horses and sheep and is transmissible to other animal species. Human sera were tested for BDV-specific antibodies by immunofluorescence and immunoprecipitation. The sera were collected from three thousand subjects in Europe, the USA, and Africa classified by clinical syndromes/infectious diseases, and from healthy controls. In all three continents, positive serum samples were detected which recognized the major BDV antigen of 38/40 KD present in the nuclei of infected cells. In contrast to 2% of seropositives among the normal population, significantly higher prevalences (13-14%) were present among patients with chronic progressive diseases of the brain and the immune system. In children, antibody frequencies were two to four times higher than in adults. The results suggest a latent infection with BDV in humans leading to low antigen expression in healthy subjects and frequent reactivation events in chronically ill patients.

Adult↗
PubMed1992

Isolation of DNA markers linked to a beet cyst nematode resistance locus in Beta patellaris and Beta procumbens.

In cultivated beet no useful level of resistance of the beet cyst nematode (BCN) Heterodera schachtii Schm. has been found, unlike the situation in wild species of the section Procumbentes. Stable introgression of resistance genes from the wild species into Beta vulgaris has not been achieved, but resistant monosomic additions (2n = 18 + 1), diploids of B. vulgaris with an extra alien chromosome carrying the resistance locus, have been obtained. Here we describe a new series of resistant monosomic fragment addition material of B. patellaris chromosome 1 (pat-1). We further describe the cloning of a single-copy DNA marker that specifically hybridizes with a monosomic addition fragment of approximately 8 Mb (AN5-90) carrying the BCN resistance locus. This marker and another fragment-specific, single-copy DNA marker probably flank the BCN locus on the addition fragment present in the AN5-203 material, which is approximately 19 Mb in size. Furthermore, several specific repetitive DNA markers have been isolated, one of which hybridizes to AN5-90 and also to DNA from a smaller DNA segment of Beta procumbens, present in line B883, carrying a BCN resistance locus introgressed into the B. vulgaris genome. This suggests that the specific repetitive marker is closely linked to the BCN locus.

Animals↗
PubMed1992

NADPH-diaphorase-positive cell populations in the human amygdala and temporal cortex: neuroanatomy, peptidergic characteristics and aspects of aging and Alzheimer's disease.

Previous studies have shown that nerve cells containing NADPH-diaphorase (NADPH-d) are relatively resistant to various damaging processes. NADPH-d has been found to be colocalized with somatostatin (SOM) and neuropeptide Y (NPY) in neuronal populations of several forebrain regions. We have investigated the anatomical distribution, morphology and cell sizes of NADPH-d neurons in amygdala and temporal cortex in Alzheimer's disease (AD) compared to controls of different age. NADPH-d cells and fibers were present in layers II-VI of the cortex and in the white matter below the cortical mantle. In the amygdaloid complex, NADPH-d cells and processes were observed in almost all subnuclei. In the amygdala of aged controls, only insignificant atrophic alterations of NADPH-d neurons and fibers were seen. In AD, a moderate, but significant shift towards an increased number of medium-to small-sized neurons was measured in amygdala and cortex, indicating cell shrinkage during the course of the disease. However, there were no differences when comparing NADPH-d staining in amygdaloid subregions in AD cases that contained numerous neuritic plaques (i.e., accessory basal nucleus) with areas that were relatively free of lesions (i.e., lateral nucleus). Analysis of cell size of SOM- and NPY-immunoreactive cells revealed only slight atrophic changes during aging. In AD, however, a significant atrophy of somatostatin neurons in temporal cortex was found, whereas no further cell shrinkage was noted for NPY as compared to aged controls. Colocalization tests demonstrated a large overlap between NPY, SOM and NADPH-d in the amygdala, whereas a subpopulation of cortical SOM neurons, predominantly localized in upper layers, showed a lack of NADPH-d. Our findings of a relative stability of a selective subclass of neurons during aging and AD support the hypothesis that cellular pathology may affect only specific neuronal populations while others might be spared.

Adult↗
PubMed1991

Fibrinogen gamma-chain mRNA is not detected in human megakaryocytes.

Human megakaryocytes and platelets contain counterparts of several plasma proteins. The origin of most of these alpha-granule proteins is unclear. Fibrinogen represents one of those molecules, being essential in hemostasis, thrombosis, and platelet aggregation. To study whether fibrinogen is endocytosed by megakaryocytes and packaged into alpha-granules or newly synthesized by these cells, we established a highly sensitive nested primer polymerase chain reaction for the detection of human fibrinogen gamma-chain mRNA. In enriched megakaryocyte fractions, as well as fluorescence-activated cell sorter-purified megakaryocytes from bone marrow samples of healthy volunteers, no fibrinogen gamma-chain mRNA could be detected, despite the presence of the corresponding fibrinogen gamma-chain DNA. We conclude that fibrinogen gamma-chain mRNA, as detectable by our amplification system, is missing in megakaryocytes. This finding suggests that fibrinogen might be acquired from plasma by endocytosis and sequestered in alpha-granules before reentering the circulation after platelet activation.

Base Sequence↗
PubMed1991

The role of cytokines in oncology.

The availability of sufficient quantities of recombinant human cytokines and promising preclinical data have led to their introduction into clinical trials. Cytokines have potential as new therapeutic agents in a variety of hematological disorders as well as in solid tumors. Only a few of the still increasing number of these glycoprotein hormones have been studied in humans so far, either as single agents or in combination with chemotherapy and other cytokines. Their clinical effects, beneficial role in supportive care, and use in the treatment of certain cancer patients are reviewed.

Cytokines↗
PubMed1991

Apparent decrease and elimination of BCR/ABL mRNA-expressing residual cells in patients with chronic myelogenous leukemia after allogeneic bone marrow transplantation.

A modified two-step polymerase chain reaction (PCR) was used for the amplification of BCR/ABL mRNA in 16 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation (BMT). At different intervals after BMT, patient cells were assessed for the presence of BCR/ABL mRNA by two subsequent rounds of PCR amplification; this procedure increased the sensitivity for the detection of one Ph+ cell in 10(4-5) to one cell in 10(5-6). Eight of 16 patients were negative by two-step PCR 1-39 months after BMT, suggesting an elimination of Ph-positive cells or a decrease below the threshold of detection. Although five patients showed negative results by the one-step PCR only, they were tested positive when nested primers were used, indicating a substantial decrease in the amount of BCR/ABL target mRNA compared with earlier pre- or post-transplant analyses. One patient who was still PCR positive 27 months after BMT became negative 12 months later. Persistence of BCR/ABL mRNA-expressing cells correlated with subsequent clinical relapse only when the transplantation was performed during blast crisis. All patients who underwent transplantation in chronic phase, including those with BCR rearrangement by PCR, are in clinical and hematological remission between 24 and 95 months after BMT. We conclude that aggressive chemotherapy combined with total body irradiation is unable to completely eradicate the malignant clone in all CML patients, and it might be speculated that other mechanisms (e.g., graft versus host reaction [GVHD] or graft versus leukemia effect [GVL]) may effectively eliminate residual leukemic cells.

Adolescent↗
PubMed1991

Medullary histiocytosis following treatment of severe aplastic anemia with recombinant human interleukin-3 in combination with antilymphocyte globulin, cyclosporin A, and methylprednisolone.

This case report describes the clinical use of recombinant human interleukin-3 as adjunct to immunosuppressive therapy with antilymphocyte globulin, cyclosporin A, and methylprednisolone for refractory severe aplastic anemia. Hematopoietic response to treatment was moderate and peripheral blood counts (neutrophils, eosinophils, monocytes, reticulocytes) increased only slightly. Unexpectedly, during the time of interleukin-3 administration a substantial bone marrow infiltration by macrophages became detectable, consistent with the diagnosis of medullary histiocytosis, that may have prevented recovery of normal hematopoiesis in this patient. This observation may indicate the need for careful use of interleukin-3 in patients with drug-induced immunodeficiency.

Adult↗
PubMed1991

Application of polymerase chain reaction assays to studies of herpes simplex virus latency.

We have amplified herpes simplex virus type 1 (HSV-1) DNA sequences from individual latently infected mouse trigeminal ganglia by polymerase chain reaction (PCR) assays. This report presents two useful modifications in the PCR technique. The first involves the use of two sets of closely spaced, oppositely oriented oligonucleotide primers and two rounds of 20-40 PCR cycles, first with the more widely spaced outer primers and then with the internal nested primers. This method enhanced the sensitivity of PCR detection as shown by assays of HSV-1 sequences in human brain. The second modification was designed to detect selectively HSV-1 sense or anti-sense RNA transcripts when both are present by adding a single primer during an initial reverse-transcriptase-mediated cDNA synthesis reaction. After destruction of the RNA template, standard PCR is initiated by the addition of the second primer and thermus aquaticus DNA polymerase (Taq). We show here applications of both of these modifications to amplify HSV-1 sequences from nervous system tissue.

Base Sequence↗
PubMed1991

[Selected factors influencing the in vitro maturation of oocytes of cattle].

Studies were conducted into hormonal additives to medium and culturing time and their effects on in vitro maturation of bovine oocytes. The best maturation results were ensured in vitro by substitution of TCM-199 with FSH, HCG, and 17 beta-oestradiol: The stage of fertilisation capability (telophase I or metaphase II) was reached by 86% of all oocytes (115 of 134). The rate of maturation was worse with significance in FSH-free medium (62% or 101 of 163), and the amount of degenerated oocytes was twice as high (18%). Maturation in hormone-substituted medium for 28 to 30 hours is recommended under the condition that immature oocytes were cultured from juvenile antral follicles (2--5 mm in diameter).

Animals↗
PubMed1991

[The influence of follicular factors on the in vitro maturation of bovine oocytes].

Immature oocytes from antral follicles of cattle were tested for the effect of follicular factors on maturation. In vitro maturation was accomplished by use of follicular fluid from small (2--5 mm) and large (above 15 mm) follicles and by addition to the medium of a granulose factor (GF) which had been isolated from the surface of granulosa cells. The parent material, with 84% (72/86) of oocytes at the germinal vesicle stage (GV-S) at the beginning of culturing, could be rated immature. 46% of all oocytes (41/89) had reached telophase I or metaphase II (full maturation) after 24 hours of maturation in hormone-free control medium (TCM 199 + 10% of foetal calf serum). 36% of oocytes (53/84), on the other hand, stayed between GV breakdown (GVBD) and anaphase I (incipient maturation). Full maturation was reached by as little as 14%. GF and follicular fluid from small antral follicles were found to inhibit GVBD in the oocytes. 59% (36/61) or 48% (61/127) of oocytes were blocked at GV stage. Positive determination of maturation inhibiting action of the above follicular components may provide a chance for their target-oriented use in control of the maturation process. The pool of immature oocytes of the ovaries, under such circumstances, might be more systematically utilised for in vitro manipulations.

Animals↗
PubMed1990

Distribution of neuropeptide Y in the prosencephalon of man and cotton-head tamarin (Saguinus oedipus): colocalization with somatostatin in neurons of striatum and amygdala.

The presence, chromatographic properties and localization of neuropeptide Y was demonstrated in postmortem human brain areas of neurologically and neuropsychiatrically normative controls using immunocytochemistry and high performance liquid chromatography combined with radioimmunoassay. NPY-immunoreactivity was found in many regions of the prosencephalon. Numerous perikarya and fibers were present in the neocortex, basal ganglia and limbic-hypothalamic areas. A moderate number of neurons and fibers was observed in the basal forebrain, including the septal complex. A comparative immunohistochemical investigation in perfusion-fixed brains of the old-world ape Saguinus oedipus revealed an almost identical distribution of NPY-immunoreactivity with only minor differences. Colocalization experiments on 1-2 microns thin consecutive paraffin sections revealed a large number of NPY neurons throughout the human neostriatum and amygdaloid complex that were also positive for somatostatin. Our findings indicate that detection of neuropeptides in fresh or fixed post-mortem human tissue by different immunochemical methods may actually reflect the in vivo conditions. In addition, the wide distribution of NPY throughout the human brain and its colocalization with other neurotransmitters suggests a physiological role as neuroactive substance, i.e. neuromodulator in the primate central nervous system.

Amygdala↗
PubMed1990

Peptidergic innervation within the prostate gland and seminal vesicle.

An immunohistochemical study in which antisera against several neuropeptides were used demonstrated the presence of neuropeptide Y(NPY) and vasoactive intestinal polypeptide (VIP) immunoreactivity in nerve fibers in the human prostate gland and seminal vesicle, whereas no immunostaining for substance P and calcitonin gene-related peptide was observed. The peptidergic innervation was found to be generally moderate to low. NPY- and VIP-immunoreactive fibers were localized in the subepithelial connective tissue as well as the smooth muscle layers in both organs, although the peptidergic fiber networks were more prominent in the seminal vesicle. Most NPY-immunoreactive fibers were observed in the musculature of the seminal vesicle. In addition, NPY- and VIP-immunoreactive fibers were demonstrated in the walls of blood vessels. The results of our study suggest that the innervation of the prostate gland and seminal vesicle by various neuroactive peptides may be involved in the autonomic regulation of these organs in adult man, as well as sympathetic and parasympathetic nerve fibers.

Adult↗
PubMed1990

Localization of atrial natriuretic peptide/cardiodilatin (ANP/CDD)-immunoreactivity in the lacrimal gland of the domestic pig.

The presence of atrial natriuretic peptic/cardiodilatin-immunoreactive material was demonstrated in the lacrimal gland of the domestic pig by high performance liquid chromatography and radioimmunoassay. The immunohistochemical localization revealed a distinct population of cuboid or spindle-shaped ANP/CDD-IR cells in the epithelium of the terminal portion of the secretory tubules. In addition, a moderate number of positive cells was localized intraepithelially in the intralobular ducts as well as the connective tissue between these ducts. Our findings provide a morphological indication that ANP/CDD may play a physiological role in the regulation of sodium transport and secretion in the lacrimal gland.

Animals↗
PubMed1990

Effect of immunomodulator adamantylamide dipeptide on antibody response to influenza subunit vaccines and protection against aerosol influenza infection.

Adamantylamide dipeptide (AdDP) is a novel synthetic compound combining the antiviral properties of amantadine and the essential adjuvant activity of immunomodulator muramyl dipeptide. Mice were immunized with influenza A/Taiwan/1/86 (H1N1), A/Sichuan/2/87 (H3N2) and influenza B/Beijing/1/87 subunit vaccines containing AdDP or aluminium hydroxide (Al(OH)3). Induction of homologous haemagglutination-inhibition (HI) antibodies and correlation to protection against lethal aerosol influenza A/PR/8/34 (H1N1) infection were investigated. Subunit vaccine containing A/Sichuan (H3N2) and Al(OH)3 stimulated high HI antibody titres but failed to provide protection against heterologous influenza A (H1N1) challenge infection following either the primary or the secondary immunizations. In contrast, similar treatment with A/Sichuan subunit vaccine containing AdDP conferred significant protection against heterologous challenge despite low levels of circulating antibody. Primary immunization with even influenza B/Beijing subunit vaccine containing AdDP, but not Al(OH)3, provided partial protection against influenza A challenge. These results suggest that appropriate immunomodulators like AdDP can convert restricted homotypic immunity induced by inactivated influenza subunit vaccines to advantageous cross-reacting type of heterologous response.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Muramyl dipeptide inhibits replication of human immunodeficiency virus in vitro.

In the search for compounds capable of inducing endogenous production of colony-stimulating factor (CSF) and possessing activity against human immunodeficiency virus (HIV), an immunomodulator, muramyl dipeptide (MDP), was investigated. MDP can enhance monocyte-macrophage CSF in serum and promote nonspecific resistance against a variety of microbial pathogens. MDP exhibited an inhibitory activity against HIV infection of CD4+ H9 lymphocytes and U937 monocytoid cells. An inhibitor of viral reverse transcriptase, 2', 3'-dideoxyadenosine, produced potent inhibition in cultures which were similarly infected with HIV. MDP could partially reduce antigen production in persistently HIV-infected KE37/1 lymphocyte cultures.

Acetylmuramyl-Alanyl-Isoglutamine↗