Does adult T-cell leukemia/lymphoma belong to the cutaneous T-cell lymphoma category?
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Biomedical subjects
Publications and source records attributed to K Iwatsuki.
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We examined the effects of atrial natriuretic polypeptide (hANP) on exocrine function in the isolated and blood-perfused dog pancreas in situ. Intra-arterial injection of hANP (1-10 micrograms) resulted in the dose-dependent increases of the pancreatic juice secretion. The secretory activity of 3 micrograms of hANP was approximately equal to one third of the secretory activity of 0.1 units of secretin. The use of hANP increased the concentration of bicarbonate but not that of sodium and protein in the pancreatic juice as compared with the basal values. These secretory responses to hANP were not inhibited by treatment with haloperidol, sulpiride, phentolamine, propranolol, atropine, cimetidine or ethacrynic acid. These results suggest that hANP acts directly on the pancreatic exocrine gland to stimulate pancreatic secretion; without, however, increasing sodium excretion. The mechanism of this effect remains to be elucidated.
We report three patients with peculiar nodules of the earlobes that developed a few months after the wearing of pierced-type gold earrings. Biopsy specimens showed dense infiltration of lymphoid cells in the dermis and subcutaneous tissue associated with the formation of lymphoid follicles. The clinical and histologic pictures were similar to those of lymphocytoma cutis. Immunohistologically, the nodular lesions were characterized by the proliferation of T cells, mainly suppressor/cytotoxic T cells, and the presence of histiocytic cells displaying Leu-3a antigens on the surface. Patch tests of aqueous gold compound induced a strong skin reaction. A histologic study of the patch test reaction sites revealed a picture of ordinary allergic contact dermatitis showing that T cells, including both helper and suppressor T cells, invaded the spongiotic epidermis and the papillary dermis. Eosinophils and a few Langerhans cells were also present in the dermal infiltrates. These findings suggest that pierced-type gold earrings induced a long-term dermal response that resulted in producing benign lymphoplasia in the sensitized individuals.
Effects of yohimbine on the secretion of pancreatic juice in anesthetized dogs were investigated. Intravenous yohimbine (0.1-1 mg/kg) caused dose-dependent increases in the secretion of pancreatic juice and vasodilation. However, intra-arterial yohimbine (0.3-1 mg) did not cause any secretory responses. The secretory activity of 0.3 mg/kg of yohimbine was approximately equal to that of 0.04 U/kg of secretin and 40 mg/kg of 2-deoxy-D-glucose (2-DG). Secretory responses to yohimbine were inhibited by pretreatment with clonidine or atropine and abolished by vagotomy. The concentration of protein in the pancreatic juice induced by yohimbine was increased, but the bicarbonate concentration was scarcely changed. These results indicate that yohimbine stimulates, at least in part, pancreatic exocrine secretion by acting on the central alpha 2 adrenoceptor in the dog.
Transepidermal migration of leukocytes, with resultant formation of microscopic or macroscopic sterile subcorneal pustules is a phenomenon characteristically noted in psoriasis and related sterile pustular dermatoses. It is natural to assume the presence of potent neutrophil chemotactic substances in the subcorneal portion of the lesional epidermis, because this location is the target of the in vivo leukocyte chemotaxis. In fact, crude psoriasis scale extracts show remarkably high neutrophil chemotactic and activating properties as compared with those of other non-psoriatic inflammatory dermatoses. We isolated a psoriatic leukotactic factor (PLF) having a molecular mass of around 12 kD, distinct from those common to other inflammatory changes involving the skin or those released by bacteria. Further analysis of PLF identified C5 cleavage fragments, together with other chemotactic peptides, such as those derived from monocytes. Likewise, potent low-molecular-mass chemotactic factors, including cell membrane lipid derived chemotactic factor, e.g. leukotriene B4, are also increased in psoriatic lesions, as in other nonpsoriatic inflammatory dermatoses. However, their activity to stimulate the generation of oxygen radicals in neutrophils was found to be much weaker than that of PLF. The peripheral blood leukocytes from active psoriatic patients show enhanced function in chemotaxis, phagocytosis, active oxygen production, and enzyme release; patients' sera contain substances such as anaphylatoxins that activate leukocyte function. Further research is required for clearer understanding of the series of events resulting in the leukocyte chemotaxis, as well as for the elucidation of the background immunoregulatory mechanisms.
In the vascularly isolated and self-hemoperfused dog pancreas, secretin (0.025 clinical units) and adenosine (1.0 mg) administered intra-arterially (i.a.) increased tissue cyclic AMP level by about 46% and 37%, respectively. Although the increases in the nucleotide were not statistically different, only secretin stimulated exocrine secretion. The increase in cyclic AMP induced by adenosine was significantly reversed by pretreatment with theophylline (0.3 mg, i.a.). These results suggest that the effect of adenosine on cyclic AMP formation occurs mainly in the non-exocrine system of the dog pancreas through A2/Ra-receptors.
The effects of forskolin on the secretion of pancreatic juice and on the intracellular levels of cyclic nucleotides were investigated in preparations of the isolated and blood-perfused dog pancreas. Forskolin (3-100 micrograms) injected intra-arterially caused a dose-dependent increase in the secretion of pancreatic juice. The concentration of bicarbonate in the pancreatic juice induced by forskolin was increased. However, protein concentration was decreased. Forskolin-induced secretion was not modified by pretreatment with atropine, phentolamine, propranolol, cimetidine, sulpiride and verapamil. Forskolin (10-30 micrograms) significantly increased cyclic AMP concentration in the pancreatic tissue before the onset of the pancreatic secretion. On the other hand, cyclic GMP concentration was not influenced significantly throughout 30 min after the administration of forskolin. From these results, it is concluded that forskolin may produce an increase in pancreatic secretion mediated through an increase of intracellular cyclic AMP concentration.
The effect of therapeutic ultraviolet light (UV) radiation on the skin lesions of histiocytosis X (HX) was studied in two old patients. Histiocytosis X cells in the biopsy specimens were strongly reactive with OKT-6, OK-Ia1, an anti-S-100 protein antibody, and were weakly stained with Leu-3a. Some HX cells outgrown from the explants bore immunoglobulin G receptors (Fc-IgG) and C3 receptors. In accordance with clinical improvement after repeated topical 8-methoxypsolaren (8-MOP) plus UV-A (PUVA) or UV-B radiation, the density of infiltrating HX cells gradually was decreased. The PUVA therapy seemed to be more effective than UV-B radiation in our treatment schedule. Even after repeated phototherapies, however, the reactivity of surface and cytoplasmic antigens related to OKT-6, OK-Ia1, and S-100 protein in the remaining HX cells were the same as in untreated HX cells. Although the exact mechanism remains obscure, satisfactory therapeutic results were obtained in response to the phototherapies. New skin lesions eventually recurred after cessation of the treatments, but such eruptions resolved when additional PUVA was resumed. These studies confirm that HX cells share a battery of cytologic characteristics with epidermal Langerhans' cells (LC) and that repeated phototherapies provide a beneficial effect for skin lesions of HX without adverse reactions.
The effects of intravenous injection of nitroprusside on pancreatic exocrine secretion and on pancreatic cyclic AMP and cyclic GMP concentrations of mongrel dogs were investigated. Nitroprusside (10-100 micrograms/kg) increased the exocrine secretion together with the increase in cyclic GMP concentration dose dependently but did not affect the cyclic AMP concentration. These results suggest that nitroprusside causes exocrine secretion from the dog pancreas mediated through an increase of intracellular cyclic GMP concentration.
Immunohistologically, cellular infiltrates in regressing plane warts were mainly composed of lymphocytes and mononuclear phagocytes. There were many infiltrating T lymphocytes. Immunoelectron microscopic observation demonstrated that both helper/inducer and suppressor/cytotoxic phenotypes of T lymphocytes infiltrated in the lesions. OKT6-positive cells were observed in the dermis as well as in the epidermis. Moreover, as noted in allergic contact dermatitis, the apposition of T lymphocytes to Langerhans' cell-like cells could be seen. Lymphocytes and a small number of mononuclear phagocytes were found adjacent to damaged keratinocytes in the epidermis, the picture of which has been described as satellite cell necrosis, a hallmark of cytotoxic reaction by aggressors. These findings suggest that specific cell-mediated immunity against virus-infected keratinocytes takes place in the process of regressing plane warts.
Human cell lines obtained after Epstein-Barr virus transformation of lymphocytes from seven patients with bullous diseases (Bullous pemphigoid, Pemphigus) and five controls were screened for the production of autoantibodies against skin antigens. In five out of seven patients, the culture supernatants tested by indirect immunofluorescence on frozen sections of normal human skin and rabbit lip showed the production of autoantibodies with different specificities: basal epidermal cells, whole epidermis, Merkel cells, fibroblasts endothelial cells, etc. All autoantibodies were of IgM class and reacted with intracellular structures. Some of them were further tested by immunoblotting against epidermal keratins and were found to react with the main human epidermal keratins (56 to 67 kDa). In contrast, even when patients had circulating autoantibodies, no supernatant showed any reactivity against the antigens usually involved in these diseases, i.e., the dermoepidermal junction or the intercellular spaces of epidermis. Supernatants from controls did not show any reactivity by immunofluorescence. The results demonstrated that human lymphoid cell lines obtained from patients with bullous diseases elicited the production of anti-intermediate filament autoantibodies known to occur spontaneously in normal patients. It is suggested that this phenomenon may be linked to the blistering conditions that provoke tissue destruction.
Comparative studies on the specificity of the so-called antiepidermal antibodies (Abs) found in human sera were performed by immunoblotting, enzyme-linked immunosorbent assay (ELISA), and immunoelectron microscopy (IEM). After a screening test by indirect immunofluorescence (IF), sera obtained from patients with various diseases and controls could be classified in 5 different groups according to the IF patterns on the epidermis: sera reactive with: (1) the stratum corneum (SC); (2) the upper layer (U-Cyt); (3) the whole epidermis (G-Cyt); (4) basal cells (B-Cyt); and (5) negative ones. By immunoblotting, all the 23 IF-positive sera were found to bind to one or more keratin bands, and did not show any reactivity with epidermal Nonidet P-40 soluble proteins. SC-Abs were mainly directed against a 67 kD Keratin band, whereas U-Cyt- and G-Cyt-Abs bound to both 58-56 kD and 67-63 kD keratins. B-Cyt-Abs reacted strongly with 63 kD Keratins and slightly with a 50 kD band. Antikeratin Abs were detected by immunoblotting even in the IF-negative sera. The ELISA study showed that sera with high IF titers contained high levels of antikeratin Abs. In the IEM study using sera containing U-Cyt- or B-Cyt-Abs, 2 distinct reaction patterns were demonstrated: U-Cyt-Abs stained tonofilaments of suprabasal keratinocytes, while B-Cyt-Abs characteristically reacted with those of basal cells. Moreover, SC-, U-Cyt-, and G-Cyt-Abs were absorbed out by insoluble epidermal proteins, and B-Cyt-Abs were decreased in titer after the absorption test. The present study provides strong evidence that most, though not all, human antiepidermal Abs are directed against different keratin polypeptides, and that antikeratin Abs commonly occur in almost all human sera.
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The effects of adenosine, adenosine 5'-triphosphate (ATP) and inosine on pancreatic exocrine secretion were investigated in the vascularly isolated and self-haemoperfused dog pancreas. Drugs were injected close-arterially (i.a.) in a single bolus. These three purine-related compounds per se did not affect resting rate of pancreatic secretion and the concentrations of protein and bicarbonate in the resting juice. Graded doses of adenosine (0.1-1.0 mg, i.a.) and ATP (0.1-1.0 mg i.a.) administered 1 min prior to secretin (0.025 clinical units, i.a.) increased a secretin-stimulated secretory volume dose-dependently, and the effects of adenosine and ATP were reversed by pretreatments with theophylline (0.3 mg, i.a.). Inosine (1.0 mg, i.a.) affected neither secretin- nor dopamine-stimulated (3 micrograms, i.a.) pancreatic secretion. Adenosine and ATP did not affect dopamine-stimulated pancreatic secretion. These results suggest that adenosine and ATP (or terminal phosphate hydrolyzed derivatives) enhance secretin-stimulated pancreatic exocrine secretion through 'P1' purine receptors in the exocrine cells, without conversion to inosine.
The effects of a synthesized phosphodiesterase inhibitor, ZSY-27, on the secretion of pancreatic juice were investigated in dog isolated and blood-perfused pancreas, and compared with those of secretin and dopamine. Intravenous administration of ZSY-27 (0.3-1 mg/kg) elicited increases in pancreatic secretion. Intra-arterial (i.a.) administration of ZSY-27 (0.1-1 mg) also elicited increased secretion. The secretory activity of ZSY-27 (1 mg) was approximately equal to that of 0.1 units of secretin and 2.5 micrograms of dopamine. The concentration of bicarbonate in the pancreatic juice induced by ZSY-27 i.a. was increased, but the protein concentration was not increased significantly. These effects are analogous to those of secretin and dopamine. ZSY-27-induced pancreatic secretion was not modified by pretreatment with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin-induced secretion was significantly potentiated by infusion of ZSY-27 (25 micrograms/min) but dopamine-induced one was not. These results suggest that ZSY-27 increases pancreatic secretion acting directly on the ductular cells of the dog pancreas, at least in part, through the increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.
The effect of substance P (SP) on pancreatic exocrine responses to exogenous cholecystokinin, secretin, and dopamine, were studied in the isolated and blood-perfused pancreas of dogs. Intra-arterial injection of SP had a significant biphasic effect on pancreatic secretion: an initial transient inhibition, followed by an increase in the secretion stimulated by the infusion of cholecystokinin. However, SP caused only an inhibition of secretion stimulated by the infusion of secretin and dopamine. SP increased protein concentration but not bicarbonate concentration in juice stimulated by cholecystokinin, but SP did not affect significantly either protein or bicarbonate concentrations in juice stimulated by secretin and dopamine. These results suggest that SP has greater effects on the pancreatic secretion stimulated by cholecystokinin than that stimulated by secretin and dopamine.
We examined the hypersecretory function of the isolated, blood-perfused pancreas of dogs with experimentally obstructive jaundice. There was no difference in basal pancreatic secretion between control dogs and obstructively jaundiced dogs. Secretin- or pancreozymin-stimulated increase in total values for pancreatic juice flow, bicarbonate, protein and amylase were greater in dogs with obstructive jaundice than in control dogs; however, concentrations of bicarbonate, protein and amylase were unchanged in each group. Acetylcholine-stimulated increase in total values and concentrations of these factors were the same in dogs with obstructive jaundice and controls. These data suggest that hypersensitivity of the pancreas to secretin and pancreozymin may be one of the main mechanisms of pancreatic hypersecretion.