Malignant fibrous histiocytoma: Similarities to the “fibrohistiocytoid cells” in chronic inflammation

Summary Ultrastructural, enzyme histochemical and immunohistochemical studies were performed on tissue obtained from eight cases of malignant fibrous histiocytoma (MFH) and five cases of sacral decubitus ulcer. The MFH was composed of two major tumour cell types: fibroblast-like and histiocyte-like cells. Both cell types demonstrated abundant branching, fragmented rough endoplasmic reticulum (rER), many free ribosomes, occasional small mitochondria, an oval, elliptical or irregularly shaped nucleus with one or two prominent nucleoli and often a few dense bodies. However, pseudopodial projections, multivesicular bodies and phagosomes, common histiocyte organelles, were not seen. With little difference between cases or selection sites, the MFH cells reacted to acid phosphatase (AcP) and -naphtyl butyrate esterase (ANBE) by enzyme histochemistry and with ferritin (Fer), 1-antitrypsin (AT), 1-antichymotrypsin (ACT), fibronectin (FN), HLA-DR, HLA-DP, Leu 10 and OKT 9 in immunohistochemical studies. MFH tumour cells did not immunostain with monocyte/macrophage markers (Leu M1, Leu M3, Mo 1, Mo 2 and Macrophage) although non-neoplastic histiocytes did react to these markers. In addition, granulation tissue, such as that found in sacral decubitus ulcers, was examined and the existence of a specific cell type called the fibrohistiocytoid (FH) cell was documented. The FH cell was short, spindle shaped and elliptical. Ultrastructurally, it had fragmented rER distributed in a branching pattern, dispersed free ribosomes, small mitochondria and a few dense bodies, but lacked diverse fused lysosomes and distinct pseudopodial cytoplasmic extensions. The FH cells reacted with AcP, alkaline phosphatase and ANBE but not with peroxidase using enzyme histochemistry and with Fer, AT, ACT, FN, HLA-DR, HLA-DP, Leu 10 and OKT 9 but not with monocyte/macrophage markers, C3d receptor, C3bi receptor in immunohistochemical studies. The FH cells had morphological, enzyme histochemical and immunohistochemical characteristics intermediate between fibroblasts and histiocytes. Similarities between MFH cells and the FH cells seen in chronic inflammation are discussed.     

Action ofγ-aminobutyric acid and its phenyl derivative on central links of vascular reflexes from aortic-carotid chemo- and mechanoreptors

Experiments on decerebrate cats revealed an inhibitory effect of -aminobutyric acid (GABA; 100–200 g/kg) and its phenyl derivative, phenyl-GABA (20 mg/kg), on depressor responses of the systemic arterial pressure and on inhibition of spontaneous electrical activity in the renal nerve arising in response to excitation of the carotid sinus mechanoreceptors and afferent fibers on the sinus and depressor nerves carrying impulses from mechanoreceptors. Pressor responses of the systemic arterial pressure and electrical activity evoked in the renal nerve by stimulation of the carotid sinus chemoreceptors were intensified after administration of the same doses of GABA and phenyl-GABA. The results are interpreted from the standpoint of the depriming action of GABA and its phenyl derivative on the paramedian reticular nuclei of the medulla.Paper read at the March, 1974 Meeting of the Volgograd Scientific Society of Pharmacologists.Department of Pharmacology, Volgograd Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 79, No. 4, pp. 71–75, April, 1975.     

Induction of lymphokine-activated killer cells with low-dose interleukin 2 and interferon-γ in oral cancer patients

Lymphokine-activated killer (LAK) cells were induced with low-dose recombinant interleukin 2 (rIL-2) and recombinant interferon- (IFN-) in 28 oral carcinoma patients. The patients received daily intravenous injections of rIL-2 (1.2×10⁵ U/m²) and rIFN- (7.0×10⁴ U/m²), and both natural killer (NK) and LAK activities were periodically examined. A significant increase in CD16⁺CD57⁺ and CD16⁺CD57^– NK subsets was observed after the induction. An increase in the T-cell population was also found, with a significant increase in CD3⁺HLA-DR⁺, CD8⁺Leu8^–, and CD4⁺Leu8^– cells. Significant increases in NK activity, from the original level of 32.0±13.7 to 49.9±15.2%, and LAK activity, from 4.8±3.5 to 11.0±6.1%, at Day 7 were observed. Both activities were maintained at high levels during the cytokine injections, but greater enhancement of the killing activities could not be obtained subsequently. When NK and LAK activities were investigated in each subpopulation of CD3^– and CD16^– cells, no remarkable cytotoxic activity could be observed before induction in any subset without NK activity in CD3^– cells (31.1±14.3%). At Day 7, NK activity of CD16^– cells increased up to 21.4±14.9%, accompanied by an increase in CD3^–-cell activity (54.5±20.6%). LAK activities of both subsets were also enhanced, with activity at Day 7 of 6.5±5.6 and 9.4±6.6% in CD16^– and CD3^– cells, respectively. These increased activities were maintained at the same level during the induction. Phorbol myristate acetate-induced polymorphonuclear leukocyte (PMNL) O ₂ ^– generation was significantly increased, from the original 81.1±28.1 to 95.6±34.9 pmol/min/10⁴ cells, after 1 week of treatment. Protein kinase C activity in the cytosol decreased, and the activity in the membrane fraction conversely increased. No remarkable adverse effects except for mild fever were observed. Together with LAK induction ability and PMNL enhancement, with scarce toxicity, a combination of low-dose rIL-2 and rIFN- is thought to be useful in cancer treatments.     

Multicenter Crossover Comparison of the Safety and Efficacy of Intraglobin-F with Gamimune-N, Sandoglobulin, and Gammagard in Patients with Primary Immunodeficiency Diseases

The safety and clinical efficacy of a liquid, -propiolactone-stabilized intravenous -globulin, Intraglobin-F, was evaluated in a multicenter, double-blind study comparing Intraglobin-F to Gamimune-N, Sandoglobulin, or Gammagard. -Propiolactone stabilizes the IgG molecule to decrease aggregate formation and is a potent virucidal agent that reduces the risk of viral transmission by intravenous -globulin (IVIG) preparations. Twenty-seven patients with primary immunodeficiency diseases were enrolled at three centers. Each patient received 6 months of therapy with either Intraglobin-F or the IVIG preparation that they had received during the preceding 3 months, then crossed over to the other preparation. Twenty-three patients completed the study. One patient withdrew because of an adverse event, generalized urticaria. A second patient withdrew because of fatigue and perceived decreased efficacy. Adverse reactions were comparable and occurred in 8.7% of the infusions of Intraglobin-F and 6% of the infusions with Sandoglobulin. None were severe or life-threatening. There was no discernible difference in efficacy between any of the products. The number of days when patients noted symptoms in their diaries was similar for Intraglobin-F and the comparison preparations, 4158 vs 4143. Similarly, there were no differences in the number of physician visits (33 vs 22), days missed from work or school (405 vs 404), days with fever (41 vs 47), or days of prophylactic antibiotics (675 vs 642). There was an increase in the number of days when antibiotics were given therapeutically (578 vs 451); most of the difference was attributable to one patient. There also was a difference in the number of days of hospitalization (21 vs 0), but 19 of the days were accounted for by two patients. When the patients were asked to score their feeling of well-being on a scale of 1 to 5, with 1 being entirely well, the mean score for the patients on Intraglobin-F was 1.86 (range, 1.0 to 3.0), compared to 1.85 (range, 1.0 to 3.2) for patients while on the comparison preparations. Trough IgG levels were slightly lower during the period when patients were treated with Intraglobin-F compared to the other products. There were no abnormalities in blood chemistries or hematologic parameters. Thus, Intraglobin-F is comparable to three of the marketed IVIG preparations in efficacy and safety, as well as patient acceptability, and offers the additional benefit of an extra virucidal step to reduce further the risk of transmitting viral infections.     

Recurrente Hemmung der Extensor-Fusimotoneurone?

Summary The antidromic effect of ventral root or muscle nerve stimulation has been studied on functionally isolated -efferents to the medial gastrocnemius muscle in the intercollicular decerebrate cat. Tetanic stimulation of the ventral root at levels below the threshold for the investigated -efferents decreases the activity of 10 out of 19 -motoneurones. This effect is greater in cats with intact contralateral dorsal roots. Tetanic stimulation of synergic muscular nerves inhibits some of the investigated -motoneurones, whereas tetanic stimulation of antagonistic muscular nerves fails to have any inhibitory effect. It is suggested that the recurrent inhibition of -motoneurones is mediated via at least one additional interneuron between the Renshaw cell and the -motoneuron.

     

Adaptation to stress increases the resistance of the heart to adrenotoxic damage

Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR G. N. Kryzhanovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 4, pp. 411–413, April, 1989.     

Human T-lymphocyte subset production of immune (γ) interferon

Human T, T, and T lymphocyte subpopulations have the capacity to respond to phytohemagglutinin (PHA)in vitro with proliferation and the production of a pH 2 and heat-labile interferon. This occurs both when the subsets are isolated by direct rosetting techniques or by negative selection. Macrophages enhance the production of the interferon by each lymphocyte subset and do not themselves produce interferon in response to products of PHA-activated lymphocyte subsets. Thus our studies indicate that subpopulations of T lymphocytes known to differ with regard to morphology, surface receptors, RNA content, response to corticosteroids and X-irradiation, and other functional capabilities do not differ with regard to their capacity to produce interferon.     

Effect of whole-body γ-ray irradiation on the rate of steroid hormone hydroxylation by rat liver microsomes

The rate of hydroxylation of androgens was shown to be significantly reduced by -ray irradiation in doses of over 600 R. The rate of hydroxylation of estrogens showed little change. During irradiation under these conditions the content of cytochrome P-450 in the rat liver microsomes fell. The decrease in the rate of hydroxylation of steroid hormones by rat liver microsomes under the influence of whole-body -ray irradiation evidently depends on quantitative changes in cytochrome P-450.Department of Molecular Pharmacology and Radiobiology, Medico-Biological Faculty, N. I. Pirogov Second Moscow Medical Institute.(Presented by Academician of the Academy of Medical Sciences of the USSR A. A. Pokrovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 6, pp. 668–670, June, 1976.     

Intravenous γ-globulin in myasthenia gravis: Interaction with anti-acetylcholine receptor autoantibodies

Clinical improvement has been observed in myasthenia gravis patients treated by intravenous immunoglobulin (IVIg). In order to investigate the mechanism of action of these IVIg, we looked for anin vitro interaction between IVIg and the anti-acetylcholine receptor autoantibodies. Significant inhibition by IVIg of anti-acetylcholine receptor autoantibody activity from 30 MG sera was observed and binding of anti-acetylcholine receptor autoantibodies on IVIg was found for four of five myasthenia gravis sera. These observations suggest that IVIg contains Ig directly binding to and inhibiting pathogenic autoantibodies.     

Flow Cytometric Analysis of In Vitro Proinflammatory Cytokine Secretion in Peripheral Blood from Multiple Sclerosis Patients

The cytokines, interferon- (IFN-), tumor necrosis factor- (TNF-rpar;, and interleukin-2 (IL-2) are important endogenous proinflammatory proteins and have been linked to disease activity in multiple sclerosis. In this study, we use flow cytometric methodology to compare the secretion of IFN-, IL-2, and TNF- from peripheral blood-derived T cells of multiple sclerosis patients to the secretion in healthy controls. The percentages of IFN-, IL-2, and TNF- secreting cells are not significantly different between multiple sclerosis patients and controls. However, the TNF- secreting CDS cell percentage is correlated with the IFN- and IL-2 secreting CD3 cell percentages in multiple sclerosis patients. In the controls, only the TNF- secreting CD3 cell percentage is correlated with IFN-. These findings show that correlated secretion of cytokines occurs in multiple sclerosis and suggest that concerted intercytokine interactions may play an important role in the disease.     

Prenatal development of the cat thyroid: immunohistochemical demonstration of calcitonin in the "C" cells

Summary The presence of calcitonin in the cat thyroid was studied immunohistochemically in a series of gland development. the first positive cells are to be found on the 38th day of gestation, i.e. 1–2 days after level nine of ontogenetic development has been reached. The cytoplasm of these cells form only a narrow border round the nucleus. With advancing development the bumber of calcitonin-positive and its amount increases. From approximately the 50th day of prenatal development, the initially diffusely scattered, solitary calcitonin-positive cells are gradually replaced by groups of cells, which begin to occupy a characteristic position in relation to the follicular epithelium. The largest quantity of calcitonin-positive cells is found in foetuses about to be born.In non-pregnant adult cats, the incidence of immunohistochemically calcitonin-reactive cell is more sporadic and their distribution in the lobes of the thyroid is uneven.     

Effect of the gaba antagonist 4-ethylbicyclophosphate on global and synaptic neuronal evoked responses in hippocampal slices

Laboratory of Organic Synthesis, Reception of Physiologically Active Substances Group, Institute of Physiologically Active Substances, Academy of Sciences of the USSR, Chernogolovka, Moscow Region. Laboratory of Functional Synaptology, Brain Institute, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR O. S. Adrianov. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 4, pp. 339–341, April, 1991.     

The effects of the quality and probability of reinforcement on feeder selection by lobectomized dogs

The role of the prefrontal cortex was studied in an active selection situation in which dogs had to choose one of two feeders, with changes in the quality and probability of the reinforcement provided in one of the feeders. The study was performed in two stages. Before surgery, animals were trained to place themselves on a start area during the interstimulus interval. Dogs were presented with a conditioned stimulus for investigation of the sequence of selection of feeders with identical reinforcements. After bilateral extirpation of the prefrontal areas (the proreal gyrus), dogs continuously ran from one feeder to the other during the interstimulus period. In response to the conditioned stimulus, the animals repeated the reaction of selecting the same feeder on many occasions during the first few (7–9) days. When there was a conflict between the probability and quality of reinforcement, the dogs came to prefer the feeder with the greater reinforcement quality despite its lower probability of presentation. In our experiments, operated animals presented with food at probabilities of 30% and 100% performed feeder selections with different probabilities. One of the functions of the prefrontal cortex in intact animals would appear to be to support the reaction of selecting the greater probability of reinforcement.Translated from Zhurnal Vysshei Nervnoi Deyatelnosti, Vol. 54, No. 3, pp. 409–419, May–June, 2004.     

Oligoclonal T-cell populations in an inflammatory pseudotumor of the pancreas possibly related to autoimmune pancreatitis: an immunohistochemical and molecular analysis

Inflammatory pseudotumors (IPT), also known as inflammatory myofibroblastic tumors (IMT), are benign inflammatory processes that may have an infectious etiology and are very rare in the pancreatico-biliary region. Recent studies suggest a biological distinction between IPT and IMT, the latter being a true neoplastic process. We describe a case of pancreatic IPT, originally diagnosed as malignancy, which presumably recurred 4 months after the operation. Histologically, the tumor consisted of a smooth muscle actin and CD68-positive spindle cell population and a more abundant mononuclear inflammatory cell population, primarily composed of macrophages and T-lymphocytes. Inflammatory cells were the source of connective tissue growth factor and transforming growth factor-1 and tended to accumulate around nerves and blood vessels, as well as around residual pancreatic parenchymal elements, where an intense angiogenetic response was detected. Comparative genomic hybridization analysis of the tumor showed no chromosomal imbalances. Polymerase chain reaction-based analysis of T-cell receptor gene rearrangement revealed an oligoclonal pattern. These findings suggest that the pathogenesis of aggressive cases of IPT could be related to the development of an intense and self-maintaining immune response, with the emergence of clonal populations of T-lymphocytes. The relation of the pancreatic IPT to autoimmune pancreatitis is emphasized.     

In vitro contractility of the hypertrophied right ventricle of rats with pulmonary hypertension due to confinement in “hypoxic cages”

Summary Four weeks' confinement of rats in individual airtight cages with walls of defined permeability for respiratory gases induced hypoxic pulmonary hypertension and right ventricular hypertrophy.Parameters of isometric contractility of strips of hypertrophied right myocardium did not show significant changes when compared with the parameters of the inotropic state of slices of normal right ventricle.     

Renal tubular reabsorption of taurine,γ-aminobutyric acid (GABA) andβ-alanine studied by continuous microperfusion

Summary Renal tubular reabsorption of taurine, -aminobutyric acid (GABA), and -alanine was studied in vivo et situ by continuous microperfusion of single proximal tubules of the rat. In each case, reabsorption was much slower than that for other amino acids that have been studied. With a concentration of 0.1 mmol/l in initial perfusate, about 60% of initial load was reabsorbed over perfusion distance of 3 mm. Taurine reabsorption saturated with only 2.17 mmol/l in initial perfusate. Assuming simple two-parameter kinetics, upper limits for K _m of 0.54 mmol/l and forV _max of 0.59 pmol·cm^–1·s^–1 for tubular reabsorption of taurine were estimated. High (20 mmol/l) concentrations of taurine or -alanine in perfusate completely inhibited GABA reabsorption, butl-phenylalanine (20 mmol/l) had no significant effect. The results indicate that the three amino acids are reabsorbed slowly from the proximal tubule by what may be a common transport system. This system appears to have a high affinity but low capacity and to be different from other known renal tubular transport systems for amino acids.Supported by National Science Foundation Research Grant No. PCM 75-09918 and by grant No. 1740 of the Austrian Fonds zur Förderung der Wissenschaftlichen Forschung.     

A murine model of NKT cell-mediated liver injury induced by alpha-galactosylceramide/d-galactosamine

Natural killer-T (NKT) cells are rich in the liver. However, their involvement in liver injury is not fully understood. We developed here a new murine model of NKT-cell-activation-associated liver injury, and investigated a role of tumor necrosis factor alpha (TNF-) and Fas in pathogenesis. We injected intraperitoneally alpha-galactosylceramide (-GalCer), an NKT-cell stimulant, into d-galactosamine (GalN)-sensitized mice. Survival rate, pathological changes of the liver, and plasma concentrations of cytokines were studied. Alpha-GalCer/GalN administration gave a lethal effect within 7 h, making pathological changes such as massive parenchymal hemorrhage, hepatocyte apoptosis, sinusoidal endothelial cell injury, and close apposition of lymphocytes to apoptotic hepatocytes. Anti-NK1.1 mAb-pretreated mice and V14NKT knock out (KO) mice did not develop liver injury. Tumor necrosis factor-alpha (TNF-) and interferon-gamma (IFN-) were elevated at 4 h in the plasma. These cytokines were produced by hepatic lymphocytes as demonstrated by in vitro stimulation with -GalCer. The lethal effect was suppressed in TNF- KO mice, TNF receptor-1 KO mice, and lpr/lpr (Fas deficient) mice, whereas it was not in IFN- KO mice. These results indicate that the present liver injury is characterized by parenchymal hemorrhage and hepatocyte apoptosis, and mediated by TNF- secretion and direct cytotoxicity of -GalCer-activated NKT cells.