Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphometric studies were conducted to distinguish reactive and malignant lymphoid processes and to obtain a more objective and reproducible grading system for non-Hodgkin's lymphomas (NHL). Twenty-three untreated patients (3 with reactive lymphadenitis, 2 with diffuse lymphomas, 18 with lymphosarcomas) were studied. The sections of lymph nodes were stained with 50% aqueous silver nitrate solution and then counter-stained with methylene blue. MOP-Videoplan (Reichert, Austria) image analyzer was used for morphometry. The size and shape of nucleus, number and position of nucleoli and the number of silver grains (K1) and relative size (K2) of each grain were investigated. The computer classification of lymphoid cells based on a stepwise linear discriminant analysis resulted in 63% correctly classified cells. Among seven most discriminating parameters, the nucleoli area and the number and size of silver grains demonstrated the highest correlation with malignancy. The data obtained have evidenced that nucleolar parameters can be applied to computer classification of lymphoid neoplastic cells and for objective grading of NHL.
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PMID:[Morphometric parameters of malignant cells in non-leukemic hemoblastosis with primary lymph node involvement]. 151 2

We have investigated the basic properties of a predominantly anion-selective channel derived from highly purified human platelet surface membrane. Single channels have been reconstituted into planar phospholipid bilayers by fusion of membrane vesicles and recorded under voltage-clamp conditions. The channel is found to have the following properties: (i) Channel activity occurs in bursts of openings separated by long closed periods. (ii) The current-voltage relationship is nonlinear. Channel current is seen to rectify, with less current flowing at positive than at negative voltages. Rectification may be due to asymmetric block by HEPES/Tris buffers. In 450 mM KCl, 5 mM HEPES/Tris, pH 7.2, the single channel conductance at -40 mV is approximately 160 pS and at +40 mV is approximately 90 pS. (iii) The conductance-concentration relationship follows a simple saturation curve. Half maximal conductance is achieved at a concentration of approximately 1000 mM KCl, and the curve saturates at a conductance of approximately 500 pS. (iv) Reversal potentials interpreted in terms of the Goldman-Hodgkin-Katz equation indicate a Cl: K permeability ratio of 4:1. (v) The channel accepts all of the halides as well as a number of other anions. The following sequence of relative anion permeabilities (in the presence of K+) is obtained: F- less than acetate- less than gluconate- less than Cl- less than Br- less than I- less than NO3- less tha SCN-.(vi) Cations as large as TEA+ are permeant. (vii) Current through the channel is blocked in the presence of DIDS, SITS and ATP, but not by Zn2+.
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PMID:Conduction and blocking properties of a predominantly anion-selective channel from human platelet surface membrane reconstituted into planar phospholipid bilayers. 247 33

Patients with advanced lymphoma who relapse from intensive first-line combination chemotherapy generally have a very poor prognosis. The use of investigational drugs which lack cross-resistance to agents commonly used for initial therapy represents an important approach to the management of such patients. Based upon our prior experience, we developed a protocol which employed a combination of three new agents. Mitoguazone (600 mg/m2) was administered on Days 1 and 10; etoposide (100-125 mg/m2) was administered on Days 2, 3, and 4; and gallium nitrate (300 mg/m2/day) was administered as a continuous iv infusion over 24 hours on Days 1-7. Treatment cycles were repeated every 3-4 weeks pending tolerance to toxic reactions. Forty-two patients are evaluable for response (35 with non-Hodgkin's lymphoma and seven with Hodgkin's disease). All patients had received extensive prior treatment (median of two previous chemotherapy regimens). Less than one-half of patients had achieved complete remission (CR) with previous therapy. Twenty-two patients (52%) showed major antitumor responses (five CR, 17 partial). All patients who achieved CR had diffuse large cell lymphoma. Two patients in CR relapsed in the CNS. The median duration of response for patients who achieved partial response was 4 months (range, 1-11+). Major toxic reactions included myelosuppression, optic neuritis, mucositis, and corneal keratitis or conjunctivitis. This combination of experimental agents has major therapeutic activity in patients with advanced, resistant lymphoma. Optimal application of these drugs may be obtained by use as one arm of an intensive program of alternating non-cross-resistant regimens.
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PMID:Salvage chemotherapy of advanced lymphoma with investigational drugs: mitoguazone, gallium nitrate, and etoposide. 379 Dec 68

Previous trials of gallium nitrate (NSC-15200) showed that bolus administration produced dose-limiting nephrotoxicity without substantial antitumor activity. As an effort to increase the therapeutic index of this compound and to establish a satisfactory out-patient schedule, the authors evaluated the effects of gallium nitrate administered as a continuous infusion in patients with advanced malignant lymphoma. In an initial Phase I trial, four dose levels which ranged from 200 to 400 mg/m2/day in 27 patients were studied. Nausea which impaired oral hydration was found to be dose-limiting. A dose of 300 mg/m2/day was chosen for extended Phase II evaluation and 37 additional patients were entered into the study at that dose level. Overall, 16 of 47 patients (34%) who had bi-dimensionally measurable parameters of disease achieved major antitumor responses (six of 15 with diffuse "histiocytic" lymphoma, five of ten with diffuse poorly-differentiated lymphocytic lymphoma, two of five with nodular poorly-differentiated lymphocytic lymphoma, and three of 17 with Hodgkin's disease). The median duration of response was 2.5 months. Only 8% of patients who received 300 mg/m2/day developed an increase in serum creatinine concentration greater than 1.1 mg/dl over baseline values. Hypocalcemia occurred in two-thirds of patients. Other toxic effects, including paresthesiae, diarrhea, and hearing loss, were noted in less than 5% of patients. There was minimal myelosuppression. The authors conclude that gallium nitrate administered as a continuous infusion for seven days at 300 mg/m2/day is well-tolerated and effective treatment for patients with advanced malignant lymphoma. Outpatient administration using portable infusion pumps is safe and practical. Further evaluation of the drug administered as a constant infusion is indicated in patients with other neoplastic diseases.
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PMID:Treatment of patients with advanced malignant lymphoma using gallium nitrate administered as a seven-day continuous infusion. 683 91

Dysphagia or odynophagia occurs in an estimated 21% of patients with human immunodeficiency virus infection. A causal agent can be identified in 60-90% of the cases and generally can be successfully eradicated. Oesophageal candidosis, the predominant disorder, usually responds to nitrate derivatives and amphotericine B after a 10 to 15 day cure. Ulcerations of the oesophagus is the second major cause of dysphagia in these patients and result from cytomegalovirus and herpes simplex infections or unknown causes. Epstein-Barr virus infection has been suggested but is rarely demonstrated in clinical situations. Similar to other localizations in HIV-infected patients, Kaposi sarcoma and non-Hodgkin malignant lymphomas are the predominant tumours in the bowel. Infections are essentially revealed by sometimes very severe diarrhoea. Infective agents include Cryptosporidium parvum, microsporidiosae, cytomegalovirus, adenovirus, Isospora belli, Clostridium difficile, Salmonellae and non-tuberculous mycobacteria among others. When the search for an infective agent is negative, the diarrhoea is usually considered to be the expression of HIV infection itself. The clinical approach to HIV-related diarrhoea can be based on decision making management scheme according to the results of stool cultures or on complete exploration protocols. Whatever the diagnostic procedure, symptomatic treatment is of major importance because of the severe nutritional impact of HIV-related diarrhoea.
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PMID:[Digestive involvements in human immunodeficiency virus infection]. 789 94

Transepithelial and cell membrane potential measurements have suggested that the basolateral membrane of gerbil vestibular dark cells contains Cl- conductive pathways. We used the patch clamp technique to search this membrane for Cl- conductive channels which could account for the macroscopic observations. Two types of Cl- channel were found in both cell-attached and excised membrane patches. One type was found with an incidence of 19% and had a single-channel conductance of 95 +/- 1 pS (N = 20) in symmetrical Cl- solutions. The other type was found with an incidence of 3% and had a large single-channel conductance of 360 +/- 11 pS (N = 12) in symmetrical Cl- solutions (LC-type Cl- channel). Both types of Cl- channel had linear current-voltage relations and at least 2 substates. In asymmetrical Cl- solutions (gluconate substitution) the current-voltage relations fit the Goldman-Hodgkin-Katz current equation for Cl-. Neither channel was blocked by Zn2+, NPPB, DIDS, DNDS or quinine. The 95 pS channel exhibited a spontaneous 'rundown' of its activity within 1 to 10 min after being excised. This rundown was not reversed by the catalytic subunit of protein kinase A. Channel activity was not dependent on the presence of cytosolic Ca2+ nor markedly altered by variations in cytosolic pH between 6.5 and 8.0. The two Cl- channels were distinguished by the membrane voltage ranges in which they were active and by their anion selectivity. The open probability of the 95 pS channel was insensitive to voltage and the anions NO3-, I- and Br- were only half as permeable as Cl-. By contrast, the LC-type Cl- channel was mostly active between about +/- 30 mV and equally permeable to NO3-, I-, Br- and Cl-. The 95 pS Cl- channel may account for the observed transepithelial and intracellular voltage responses to Cl- concentration steps and provide the path for the recirculation of Cl- across the basolateral membrane. The LC-type Cl- channel shows the same lack of anion discrimination as the anion pathway activated during hyposmotic challenge.
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PMID:Two types of chloride channel in the basolateral membrane of vestibular dark cells. 822 32

The whole cell configuration of the patch clamp technique was used to investigate the mechanism underlying rectification of the isoproterenol-activated chloride (Cl-) current in isolated guinea pig ventricular myocytes. When extracellular Cl- was replaced with either bromide (Br-), glutamate (Glut), iodide (I-), isethionate (Iseth), or nitrate (NO3-), the magnitude of the shift in reversal potential of the macroscopic current suggested the following selectivity sequence: NO3- > Br- > or = Cl- > or = I- > Iseth > or = Glut. This information was used to investigate the role of permeant ions in rectification of this current. Consistent with previous observations, when the concentration of intracellular Cl- (Cli-) was less than the concentration of extracellular Cl- (Clo-) (40 mM Cli-/150 mM Clo-) the current exhibited outward rectification, but when Cli- was increased to equal that outside (150 Cli-/150 Clo-), the current no longer rectified. Rectification in the presence of asymmetrical concentrations of permeant ions on either side of the membrane is predicted by constant field theory, as described by the Goldman-Hodgkin-Katz current equation. However, when the Cl- gradient was reversed (150 Cli-/40 Clo-) the current did not rectify in the opposite direction, and in the presence of lower symmetrical concentrations of Cl- inside and out (40 Cli-/40 Clo-), outward rectification did not disappear. Reducing Cli- by equimolar replacement with glutamate caused a concentration dependent increase in the degree of rectification. However, when Cli- was replaced with more permeant anions (NO3- and Br-), rectification was not observed. These results can be explained by a single binding site model based on Eyring rate theory, indicating that rectification is a function of the concentration and the permeability of the anions in the intracellular solution.
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PMID:On the mechanism of rectification of the isoproterenol-activated chloride current in guinea-pig ventricular myocytes. 830 Dec 61

Muscle fibres of crustaceans represent an useful model for studying the mode of action of substances influencing calcium channels as the membrane generates the active responses on a pure calcium principle and the excitation-contraction link is dependent on external calcium. We followed the effect of Pb2+ ions (1-300 mumol/l) on contractile responses in single muscle fibres of the crayfish evoked by massive or intracellular electrical stimulation, by potassium depolarization and caffeine application, as well as on action potential in single intact muscle fibres and on calcium currents in voltage clamp conditions (vaseline gap) in internally perfused muscle fibre segments. All types of contractile responses, single twitches, tetanus, potassium and caffeine contractures were blocked. The strontium action potential was blocked very effectively by Pb2+ ions. The total calcium currents which can be split by means of Hodgkin-Huxley equations into two components (fast and slow respectively) differing in the rate of activation and inactivation were suppressed after addition of Pb(NO3)2 (50-300 mumol/l). The effect of Pb2+ was concentration and time dependent. At lower concentrations (100 mumol/l) the blocking effect was more pronounced on the fast inactivating Ca current component. The Pb2+ ions prolonged the time constant of inactivation tau h of the slow channel, while leaving that of the fast channel intact.
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PMID:The effect of Pb2+ ions on calcium currents and contractility in single muscle fibres of the crayfish. 840 21

A method is described for the determination of reversal potentials (EREV) from variance of single-channel currents vs. membrane potential in ramp pulse mode. The variance-voltage relationship is represented by a parabola with a minimum of the best fit curve corresponding to the value of EREV. The reversal potential of the maxi-Cl channels changes according to the activity of Cl ions at the internal side of the excised (inside-out) patch membrane as expressed by the Goldman-Hodgkin-Katz equation with PA/PCl = 0.15, indicating the anion nature of the channel. The relative permeabilities (PA/PCl found for halide anions, were 1.15 for iodide and 1.18 for bromide. The relative permeabilities measured (PA/PCl) for other anions were 1.13 for nitrate, 0.59 for bicarbonate, 0.60 for methanesulfonate, 0.40 for SO42-, 0.44 for propionate, and 0.10 for glutamate. No significant differences in PA/PCl of the investigated anions were observed between proliferating myoballs and quiescent myoblasts. This may mean that the newly formed channels possess full-grown selective filters. A close correlation (r = 0.89) was found between the calculated Stokes diameters of the anions under investigation and their relative permeabilities (PA/PCl). The intercept of the best fit line with the abscissa is 7.2 A (7.2 x 10(-10)m), which may correspond to the diameter of the selectivity filter of the maxi-chloride channel in L6 myoblasts. A similar value of the channel size was obtained from the relationship between the minimum cross-sectional areas of the anions and their relative permeabilities, PA/PCl. The best fit line intercepts the abscissa at 27.5 A2, indicating a pore size approximately 6 A. The minimum areas were obtained by computer from molecular models of the anions.
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PMID:Selectivity of maxi chloride channels in the L6 rat muscle cell line. 884 86

Anions and cations have long been recognized to be capable of modifying the functioning of various membrane-related physiological processes. Here, a fluorescent ratio method using the styrylpyridinium dyes, RH421 and di-8-ANEPPS, was applied to determine the effect of a range of anions and cations on the intramembrane dipole potential of dimyristoylphosphatidylcholine vesicles. It was found that certain anions cause a decrease in the dipole potential. This could be explained by binding within the membrane, in support of a hypothesis originally put forward by A. L. Hodgkin and P. Horowicz [1960, J. Physiol. (Lond.) 153:404-412.] The effectiveness of the anions in reducing the dipole potential was found to be ClO4- > SCN- > I- > NO3- > Br- > Cl- > F- > SO42-. This order could be modeled by a partitioning of ions between the membrane and the aqueous phase, which is controlled predominantly by the Gibbs free energy of hydration. Cations were also found to be capable of reducing the dipole potential, although much less efficiently than can anions. The effects of the cations was found to be trivalent > divalent > monovalent. The cation effects were attributed to binding to a specific polar site on the surface of the membrane. The results presented provide a molecular basis for the interpretation of the Hofmeister effect of lyotropic anions on ion transport proteins.
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PMID:Influence of anions and cations on the dipole potential of phosphatidylcholine vesicles: a basis for the Hofmeister effect. 1023 76


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