Analysis of leukemic cells with monoclonal antibodies in acute myelomonocytic leukemia suggests abnormality at an early differentiation stage in certain cases.
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Publications and source records attributed to B Koch.
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Mononuclear cell (MNC) populations in tissue specimens from 11 colorectal adenocarcinomas and 1 mucinous adenocarcinoma were analyzed, applying different monoclonal antibodies (MoAB). Tumor epithelium could be characterized by MoAB VEP9, predominantly binding to mucus secreted by the tumor cells. In approximately 30%-50%, the tumor epithelium also reacted in a patchy pattern with the MoABs OKT10 and OKIa, which define in the peripheral blood activated and HLA-DR expressing cells. T-lymphocytes, as defined by the MoAB 9.6, and T-lymphocyte subpopulations, as characterized by the MoABs OKT4 and OKT8, were found in the intratumoral stroma and in peritumoral inflammatory areas. Quantifying the relative amounts of mononuclear cell subpopulations in the different stroma compartments, a predominance of OKT10- and OKIa-defined and MoAB-S39-reactive cells was observed. NK cells, as labelled by the MoAB Leu-7, were only demonstrated singularly in different areas of the stroma. Nonlymphoid structures such as vessel walls were shown to express antigens recognized by the MoABs OKIa, OKT10, and Leu-7. In some instances, nerve structures were labelled by the MoABs OKIa, OKT10, S39, and Leu-7. Using semiquantitative analysis, no correlation could be obtained between the intratumoral and peritumoral infiltration with T-lymphocytes, T-lymphocyte subpopulations and monocytic cells, and histopathological tumor grading and staging.
For 10 cases in which we detected cysts in the choledochus ourselves comparing traditional radiological methods (infusion-cholegram, ERC, scintigraphy, barium meal examination, angiography) with recent imaging procedures (ultrasound, CT, NMR) the following sequence of procedures proved to be favorable: Screening methods are ultrasound and infusion-cholegram. CT and NMR furnish good presentations of the intra- and extrahepatic dilatations of the bile duct. ERC still represents the best methods for demonstration of an extrahepatic cyst of the choledochus. Hepato-biliary functional scintigraphy is performed as a supplement. Barium meal examination and coeliacography furnish a small diagnostic contribution only.
Specificity of binding of 3H-labeled arginine vasopressin [( 3H]AVP), down-regulation of receptors, and desensitization were studied in anterior pituitary glands of both Wistar and Brattleboro rats. Studies using both crude membrane fractions and isolated cells of anterior pituitaries revealed the presence of a single population of binding sites with a Kd of approximately 1 nM. The receptor recognized the following peptides, with AVP = lysine vasopressin = vasotocin greater than oxytocin = 1-deamino-(8-D-AVP) greater than d-(CH2)5-Tyr-(Me)-Val4-AVP greater than 1-deaminopenicillamine-(Val4-D-Arg8)VP. Neither corticotropin-releasing factor (CRF) nor any of the neuropeptides tested, including AVP ring and tail fragments, competed for tracer binding. Increased extracellular vasopressin levels due to chronic injections or long term adrenalectomy decreased receptor density by 80%, while oxytocin was less effective than AVP. Comparing binding data in Brattleboro homozygotes and heterozygotes revealed that AVP levels within the physiological range could down-regulate pituitary receptors as well. This could not be caused by occupation of sites by endogeneous vasopressin, since injection of large doses of peptide decreased tracer binding by less than 10%. Loss of pituitary receptors reduced 1) enhancement by AVP of CRF-induced cAMP accumulation, 2) intrinsic CRF-like activity and 3) synergistic effect of AVP on ACTH secretion elicited by CRF. This study thus provides evidence for the presence of highly specific vasopressin receptors in the anterior pituitary, which may undergo homologous down-regulation and desensitization in terms of cAMP production and ACTH release.
The inhibition of gamma-aminobutyric acid (GABA) synthesis did not interfere with the suppressive effect of dexamethasone on the stress-induced rise of plasma corticosterone levels in vasopressin-deficient homozygous Brattleboro rats. In dexamethasone-treated heterozygous rats corticosterone and vasopressin secretion increased after stress provided GABA synthesis was inhibited. The results indicate that inhibition of corticotrophin secretion by corticosteroids may in part be mediated by enhancement of GABA synthesis and a consequent inhibition of vasopressin release.
Vigorous exercise is known to increase VIII:C and VIIIR:Ag levels transiently in normal individuals. Although exercise programs are frequently advocated in the management of hemophilia, the effects of exercise on coagulation parameters in these patients have not been well studied. Eleven hemophiliacs were exercised on a bicycle ergometer to maximum voluntary effort as evidenced by an increase in pulse, blood pressure, and plasma catecholamine (norepinephrine and epinephrine) levels. The effects of this exercise on coagulation parameters, including functional and antigenic components of the factor VIII molecule, were determined. The entire group demonstrated a decrease in mean prothrombin time (11.7 to 11.2 sec). Four mild hemophiliacs demonstrated an increase in mean VIII:C (14.5% to 17.3%), and VIII:CAg (12% to 17.8%). Changes in VIII:C and VIII:CAg were not noted in the seven severe hemophiliacs. Both severe and mild patients demonstrated significant changes in fibrinogen, factor II, and factor VII after exercise. This study indicates that submaximal exercise modifies coagulation parameters in patients with hemophilia.
Tissue specimens of synovial membranes from patients with rheumatoid arthritis (RA) and non-inflammatory joint diseases were analyzed with a panel of monoclonal antibodies directed towards T-lymphocyte subsets and natural killer (NK) cells. In the RA group, mononuclear cell infiltrations in the synovium presented a distinguished pattern as compared to the non-RA group. Inflammatory synovial membranes displayed an increased level of cells recognized by the monoclonal antibodies OKT4 and OKT8, especially attributable to the broadened layer of synoviocytes and to the fibrous synovial tissue. No significant difference in the RA patients was observed with regard to the percentage of OKT4 and OKT8 positive cells in different investigated compartments of the synovium, e.g., diffuse inflamed synovial tissue, fibrous synovial tissue, and perivascular infiltrations. OKT4 and OKT8 positive staining was additionally observed on spindle-shaped cells present in the fibrous and diffuse inflamed synovium. OKT10 binding cells were located in the deeper layers of synoviocytes, in the inflamed synovial tissue, and in one case in perivascular areas, whereas HNK 1 positive cells were scattered in the fibrous synovial and perivascular cells, as well as in lymphocyte clusters of synovium in RA patients.
The localization of transcortin (CBG) in pituitary cells of the rat was investigated using the peroxydase-antiperoxydase (PAP) technique. A rabbit antiserum against purified rat plasma transcortin was used as the primary antiserum. Transcortin-like (CBG-like) immunoreactive products were found in the cytoplasma of certain cells in the anterior pituitary, but not in the intermediate lobe and weakly in the posterior pituitary. It is postulated that the CBG-like molecules participate in the cellular uptake process of corticosterone, thereby modulating the feedback signal of this steroid on pituitary function.
The present investigation was aimed at examining whether interaction of aldosterone with specific mineralocorticoid receptors at the level of the pituitary gland may account for the inhibitory effect of that steroid on ACTH secretion. By using pituitaries from neonatal rats, which we show to completely lack specific mineralocorticoid receptors but to contain a functional glucocorticoid receptor system, we demonstrated the persistence of aldosterone-induced inhibition of ACTH release from perifused glands. Conversely, when the glucocorticoid receptors sites were blocked in pituitaries from mature rats by means of a potent antiglucocorticoid (RU 38486), thus leaving unaltered mineralocorticoid binder, aldosterone no longer dampened hormonal output. We conclude that the latter steroid affected corticotropic activity by interacting not with its proper and specific receptor, but rather with the glucocorticoid binding sites.
This study examines the effect of leu-enkephalin on K+, veratridine and isoproterenol stimulation of vasopressin (AVP) release from perifused neurointermediate pituitaries of rats. As opposed to catecholamine-evoked release of peptide, the secretory response to high K+ and veratridine involves Ca2+ influx, as the effect of both factors was blocked by Ca-chelation and the channel blocker D 600. Leu-enkephalin was found to antagonize AVP secretion induced by K+ and veratridine depolarization, by acting through a naloxone-sensitive receptor system. In contrast, the opiate failed to significantly affect isoproterenol-stimulated release of AVP, which we show to be correlated to cAMP accumulation in pure neurohypophyseal tissue. These results support the view that opiates modulate AVP secretion triggered by depolarization of nerve terminals by regulating Ca2+ fluxes.
Fifteen patients with colorectal tumours, 15 patients with Crohn's disease (CD) and two groups of normal controls were investigated for the presence of spontaneous suppressor cell activity (SSCA) in peripheral blood mononuclear cells (PBMC). In comparison to the age and sex matched controls patients with colorectal carcinoma exhibited a significant increase in SSCA (P less than 0.01). No evidence could be obtained that the suppressive effect was due to a soluble factor such as prostaglandins. In contrast, patients suffering from CD presented a decreased SSCA. No correlation was obtained between the enhanced SSCA in tumour patients and the clinical stage of the disease, levels of oncofetal antigens or serum immune complexes. Likewise in patients with CD no correlation was found between decreased SSCA and CD index or different serum parameters. When PBMC of the different test groups were incubated with histamine or cimetidine before they were added to the indicator system the suppressive activity remained unchanged. Also pre-incubation of normal PBMC with alpha-fetoprotein or carcinoembryonic antigen did not change the spontaneous suppressor cell activity. Whether the significantly enhanced in vivo activity of spontaneous suppressor cells in patients with colorectal carcinoma is one of the multifactorial mechanisms leading to the establishment of cancer or whether it rather represents a reflection of the immune system on colorectal tumour antigens remains unsolved.
Sixty patients with spinal muscular atrophy (SMA) are presented. Although the life span with Type I SMA (Werdnig-Hoffmann disease) may be short, children with the disease can be made more comfortable with appropriate medical care and parental support. Despite electrodiagnostic findings which are not always pathognomonic and muscle biopsies which can be difficult to interpret, the clinical presentation of these infants is so typical and the natural course of the disease so predictable that management can be telescopically designed. findings and muscle biopsies are more definitive. In these more benign forms of SMA, anticipatory medical management focuses on possible In SMA-II (Childhood) and SMA-III (Kugelberg-Welander), electrodiagnostic findings and muscle biopsies are more definitive. In these more benign forms of SMA, anticipatory medical management focuses on possible dislocating hips, scoliosis, pulmonary compromise, and sudden increase in weakness associated with intercurrent illness or prolonged immobilization due to fractures or surgery. Further considerations include maintenance of strength and endurance, independence in self-care, psychosocial, educational, and vocational endeavors. These more chronically affected children are eminently habilitable.
Peripheral blood mononuclear cells of patients with different tumors of the gastrointestinal tract (esophagus, stomach, colon, rectum), with Crohn's disease and healthy controls were analyzed for their capacity to produce mitogen induced interleukin-2 (I1-2). Tumor patients could be divided into two groups, one group exhibiting a nearly normal and a second group showing a significantly decreased production of I1-2. Most of the patients with a carcinoma of the colon were found in the low-producer group. Patients with Crohn's disease did not significantly differ from the relevant controls. Tumor patients with proven metastasis produced less I1-2 as compared to those with localized disease although the differences are not significant. When I1-2 containing supernatants of patients with tumors were additionally analyzed for the presence of prostaglandin E2, an inverse relationship could be demonstrated. Supernatants showing a suppressed activity of I1-2 exhibited increased amounts of PGE2, indicating a modulation of I1-2 production by prostaglandin E2.
Eleven boys, 8.3 to 15.5 (mean 11.6) years old, with hemophilia, were studied by bicycle ergometry to determine their physical fitness. Parameters analyzed and compared to data for normal children included total work, mean power minutes of exercise, heart rate (HR), and blood pressure (BP), as well as catecholamine levels. The hemophilic child performs significantly less total work (67%), mean power (49%), minutes of exercise, (30%), and HR (8%). There were no differences in BP. Norepinephrine rose from a resting level of 204.5 to 652pg /ml after exercise, and epinephrine rose from 20.5 to 76.6pg/ml, levels comparable to those achieved by normal children during exercise. Children with hemophilia demonstrate poor exercise performance, which we believe is due to a lack of physical conditioning. Recommendations are made for individual exercise prescriptions to improve the fitness of these children.
Cystic dilatations of the biliary tract are rare anomalies. In the individual case, diagnosis may pose great problems. The relevance of the various methods was assessed in eight patients investigated with different diagnostic methods. In all patients the predominant symptom was uncharacteristic upper abdominal complaints. Two patients showed intermittent jaundice. Among non-invasive methods sonography is preeminent and permits precise demonstration of intra- and extrahepatic biliary duct dilatations. It can be complemented by CAT-scanning. Whereas intravenous cholegraphy does not permit sufficient ascertainment of the diagnosis, ERCP and PTC allow precise demonstration of the anomaly. Functional hepatobiliary scanning is indicated where endoscopic methods are not available. Among the eight patients sonography was decisively relevant in five cases and ERCP in all cases. The remaining functional assessments furnished important additional informations.
The effect of somatostatin on lipolysis was investigated utilizing isolated chicken adipocytes. Somatostatin-14 and -28 inhibited basal lipolysis. This ability to suppress glycerol release (used as an index of lipolysis) was emphasized in presence of stimulated lipolysis. Concentration of 1 ng/ml somatostatin-14 (0.625 nM) and somatostatin-28 (0.312 nM) was found to inhibit completely the glycerol release induced by concentrations of glucagon up to 2 ng/ml (0.58 nM). The percentage of inhibition was dose-dependent. The antilipolytic effect of somatostatin-14 was also observed during ACTH and aminophylline-stimulated lipolysis. Among the mechanisms which could account for the inhibition, a possible competitive effect of somatostatin-14 with 125I-labelled glucagon binding to adipocyte membranes was excluded. The small inhibiting effect of somatostatin-14 on glycerol release prompted by dibutyryl cyclic AMP, together with the significant inhibiting effect on aminophylline-stimulated lipolysis argued for a reduction of cyclic AMP accumulation. The increase of cyclic AMP levels induced by glucagon was substantially reduced in presence of somatostatin-14. It was concluded that in chicken adipocytes somatostatin inhibited the rate of lipolysis and that reduction on cyclic AMP could be responsible, at least in part, for the antilipolytic effect.
The present paper reports new findings concerning interaction of [3H]-Arginine-vasopressin with putative receptors in rat anterior pituitary gland. It shows the presence of a single type of receptor sites, with a limited binding capacity and a dissociation constant of nearly 1nM. The parent neurohormone oxytocin revealed weak affinity as compared with vasopressin [Ki = 100nM and Ki = 1nM, respectively]. None of the various peptides tested and, especially corticotropin-releasing factor CRF, competed for binding. Receptor characteristics appeared to be unaffected by lack of circulating vasopressin in Brattleboro rats presenting complete deficiency in synthesis of that peptide.
Previous cytokinetic studies in Moloney-virus (M-MuLV)-induced lymphomas of BALB/c mice showed an intrathymic maturation block of prethymic lymphocytes derived from hematopoietic tissues. Thymus-cell cultures during the latent period of lymphoma development showed a proportion of nonlymphoid cells (NLC) from uninfected mice of 0.1% (3 days) to 0.002% (20 days), rising in infected mice to 1-2% after 5 weeks. Concomitantly, thymic epithelial cells exhibit progressive degenerative changes in vivo in infected mice with virus replication and in vitro a marked cellular polymorphism with nuclear atypia becomes overt. Immunofluorescence studies of thymopoietin II and serum thymus factor in epithelial cells indicate a marked decrease of these hormones in the epithelial cells from infected mice. These results suggest a functional defect of virus-infected thymic epithelial cells which causes a progressive accumulation of nondifferentiating T-cell precursors.