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)

Using single-electrode voltage clamp, heart interneurons of the medicinal leech were shown to possess both a rapidly inactivating outward current, IA, and a more slowly inactivating outward current, IK. IA and IK could be separated by their voltage sensitivity and kinetic properties. FMRF-NH2 (Phe-Met-Arg-Phe-NH2) modulates IK by shifting both steady state activation and inactivation to more hyperpolarized potentials, but it does not affect the time constants. IA and IK appear to use K+ as a charge carrier; a change in the external [K+] produced a shift in the apparent reversal potential in the direction predicted with potassium as the charge carrier. Both IA and IK are sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP), and TEA and 4-AP both interfere with the effects of FMRF-NH2 on IK. The biophysical properties of IA and of IK in the presence and absence of FMRF-NH2 were incorporated into a Hodgkin-Huxley model of these currents that could reproduce voltage-clamp data. FMRF-NH2 produces two apparently dissimilar effects on the heartbeat rhythm--acceleration and disruption. We suggest that both effects could result from the hyperpolarizing shifts in steady state activation and inactivation of IK.
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PMID:Modulatory effects of FMRF-NH2 on outward currents and oscillatory activity in heart interneurons of the medicinal leech. 134 5

1. The putative neurotransmitter FMRFa (Phe-Met-Arg-Phe-amide) caused an inhibitory modulation of the voltage-gated sodium current (INa) in central neurones, the peptidergic caudo dorsal cells (CDCs) of the mollusc Lymnaea stagnalis. FMRFa reduced INa at all command potentials tested (ranging from -35 to +20 mV), but the amplitude of the effect of FMRFa was voltage dependent, inhibition being stronger at more negative potentials (50 +/- 5% reduction at half-maximal INa activation versus 25 +/- 8% at the peak of the I-V curve). 2. INa current traces were well fitted by a Hodgkin & Huxley based model, using m3 activation kinetics and two time constants for inactivation. 3. The steady-state inactivation curve of INa was characterized by half-maximal inactivation at -42.5 +/- 1.81 mV and a slope factor of 4.6 +/- 0.28 mV. The fastest time constant of inactivation ran from 100 +/- 5 to 0.8 +/- 0.32 ms and the slower time constant from 505 +/- 45 to 4.8 +/- 1.40 ms in the range -40 to -5 mV. 4. FMRFa had no significant effect on either component of inactivation, nor on the voltage dependence of steady-state inactivation, nor on the maximal conductance. 5. FMRFa affected the activation of INa. The activation time constant was increased, ranging from 0.75 +/- 0.050 to 0.22 +/- 0.017 ms under control and from 0.91 +/- 0.043 to 0.31 +/- 0.038 ms with FMRFa in the voltage range -25 to +5 mV. The steady-state activation curve was shifted to less negative potentials: half-maximal activation occurred at -26.5 +/- 1.2 mV under control and at 23.6 +/- 1.4 mV with FMRFa; the slope factor (4.6 +/- 1.4 mV in control experiments) was not affected. The combination of slower activation kinetics and a shift in the voltage dependence of activation in the Hodgkin & Huxley based model, adequately explained the reduction of INa by FMRFa. 6. The physiological consequence is that the spiking threshold is increased, causing an arrest of on-going firing activity and a decrease in excitability.
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PMID:Inhibitory modulation by FMRFamide of the voltage-gated sodium current in identified neurones in Lymnaea stagnalis. 168 48

Recombinant granulocyte colony-stimulating factor (rG-CSF) primed the ability of human neutrophils to generate increased levels of reactive oxidants in response to fMet-Leu-Phe, and also resulted in an increased rate of protein biosynthesis which was similar to that induced by granulocyte-macrophage colony-stimulating factor. However, rG-CSF reduced the chemotactic activity of neutrophils in response to endotoxin and did not result in an enhanced rate of killing of Staphylococcus aureus. rG-CSF was administered to patients after high dose chemotherapy and autologous bone marrow transplantation for the treatment of either Hodgkin's disease or multiple myeloma. This cytokine decreased the period of neutropenia following such treatment. Neutrophil function in two patients, measured seven days after the final administration of rG-CSF, was severely impaired as indicated by a greatly decreased ability to generate reactive oxidants. However, seven days later (i.e. 14 days post-therapy), the functional activity of the neutrophils from these patients had returned to normal. These data indicate that assays of neutrophil function together with morphological assessment of neutrophil numbers and maturity should be performed in order to evaluate the immune status of patients undergoing such therapy.
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PMID:Effects of recombinant human granulocyte colony-stimulating factor on neutrophil function in vitro and in vivo following chemotherapy and autologous bone marrow transplantation. 172 83

Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to inhibit the chemotaxis and enhance the oxidative burst response of human neutrophils in vitro. The present study describes the effect of recombinant GM-CSF on the neutrophil and monocyte function in patients with lymphoma undergoing GM-CSF treatment. Patients with either Hodgkin's or non-Hodgkin's lymphoma were treated with various dosages (2-16 micrograms kg-1 body weight per day for 5 days) of rhGM-CSF by intravenous or subcutaneous route. Prior to and on day 5 of rhGM-CSF treatment, neutrophil and monocyte chemotaxis and chemiluminescence responses to f-Met-Leu-Phe, zymosan activated serum (ZAS) and opsonized zymosan (OZ) were determined. It was observed that chemotactic response of neutrophils to f-Met-Leu-Phe and ZAS was reduced, whereas the chemiluminescence response of both cell types to f-Met-Leu-Phe and zymosan was enhanced by up to 43-fold. rhGM-CSF treatment did not affect degranulation of the neutrophils as measured by release of vitamin B12 binding protein. Degree of modulation of neutrophil and monocyte function by rhGM-CSF was independent of rhGM-CSF dosages administered. These data suggest that phagocytic defence system may be enhanced by GM-CSF treatment and that this cytokine may be a useful therapeutic adjunct in compromised patients.
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PMID:Modulation of neutrophil and monocyte function by recombinant human granulocyte macrophage colony-stimulating factor in patients with lymphoma. 190 35

Melphalan (L-phenylalanine mustard) is a bifunctional alkylating agent that is commonly administered orally to treat a wide variety of malignancies, including cancers of the breast and ovary, as well as multiple myeloma. Although commercially available in Europe and Canada, intravenous (IV) melphalan remains investigational in the United States. The role of IV melphalan in cancer chemotherapy is not well defined, despite its manageable toxicity and higher and more predictable blood levels following IV administration compared with oral administration. In addition, unlike oral melphalan, an extensive phase I evaluation of IV melphalan has not been undertaken. At lower doses (eg, 30 to 70 mg/m2), both as a single agent and in combination, the activity of IV melphalan has been evaluated in only a limited number of diseases. However, striking activity has been observed in previously untreated patients with rhabdomyosarcoma, a disease not generally considered responsive to alkylating agents. When administered at high doses (greater than 140 mg/m2) requiring bone marrow reinfusion, melphalan effects a high response rate (but no improvement in survival) in a variety of nonhematologic tumor types, including resistant tumors such as melanoma and colon carcinoma. In contrast, in poor-prognosis patients with non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, or neuroblastoma, high-dose melphalan-containing regimens have yielded both high response rates and improved survival, despite considerable toxicity. Additional clinical trials will be necessary to define the spectrum of activity of lower doses of IV melphalan and to define subgroups of patients most likely to benefit from high-dose melphalan.
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PMID:The systemic administration of intravenous melphalan. 305 5

Between July 1975 and June 1979, 194 patients with State II or III breast carcinoma were randomized to receive either L-phenylalanine mustard (L-PAM), cyclophosphamide and 5-fluorouracil and prednisolone (CFP), or CFP and BCG. Sixty-one patients have recurred despite the adjuvant chemoimmunotherapy trial. Fifty-three are evaluable for survival and 36 for response to chemo-hormonal therapy. Those treated with a chemo-hormonal regimen for their first recurrence exhibited a 53% objective response rate to cytotoxic therapy or a 35% response to hormonal therapy. Prior exposure to L-PAM, cyclophosphamide, or 5-fluorouracil did not preclude response to "salvage" therapy regimens containing those agents. Neither menopausal status, estrogen receptor content, size of the primary tumor, adjuvant treatment, nor extent of the recurrence had any effect on subsequent survival. Overall, the entire group exhibited median survival of 37 months from initial diagnosis and 13 months from recurrence. Unlike recurrent Hodgkin's disease, there was no demonstrable relationship between the length of the disease-free interval and the likelihood of subsequent response to cytotoxic or hormonal treatment. Comparison is made to the results of "salvage" therapy administered after three other large adjuvant treatment series.
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PMID:Treatment of breast carcinoma recurrent after adjuvant chemoimmunotherapy. 638 84

From July 1968 through December 1977, 171 previously untreated patients with pathological stage IIIA Hodgkin's disease were evaluated at Stanford University Medical Center. All patients underwent lymphography, staging laparotomy and splenectomy; 86 patients were treated with total lymphoid irradiation (mantle followed by inverted-Y) to 4400 rad. These patients received prophylactic irradiation to the preauricular region (3600 rad/4-5 wk.) if the high cervical lymph nodes were positive; the lung (1500 rad/4-5 wk.) if the ipsilateral pulmonary hilum was positive; and the liver (2200 rad/5-6 wk.) if the spleen was positive. Eighty-five patients were treated with total lymphoid irradiation followed by adjuvant chemotherapy-either nitrogen mustard, vincristine and procarbazine (MOP) or procarbazine, L-phenylalanine mustard, and vinblastine (PAVe). Five-year survival rates were not significantly different in the two groups (86% vs. 89%, P = .4); however, the five-year freedom from relapse rate was significantly better in the combined modality group (66% vs. 86%, P = .0026). Because of the success of MOP in the treatment of patients who had relapses after treatment with irradiation alone, the five-year freedom from second relapse rates in the two groups were not significantly different (85% vs. 88%, P = .8). Analysis of a large number of possible prognostic factors failed to identify any subgroup of patients whose survival was significantly improved by the use of adjuvant chemotherapy, including patients with "anatomic substage III2" (P = .52), clinical stage III (P = .26), unfavorable histology (P = .78), age greater than 39 yr. (P = .44), males (P = .55), and S- (P = .92). The most important factors indicating a benefit from adjuvant chemotherapy on survival were greater than or equal to 5 sites of involvement, including those above and below the diaphragm (P = .15) and extensive splenic involvement (more than four nodules detected in the splenectomy specimen) (P = .15). Possible explanations for these observations, which differ from those of series reported at other institutions, are discussed.
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PMID:Prognostic factors in pathological stage IIIA Hodgkin's disease. 721 5

Three ribosome-inactivating proteins (RIPs) similar to those already known (Stirpe et al. (1992) Bio/Technology 10, 405-412) were purified from the seeds of Phytolacca dioica. These proteins, called Phytolacca dioica RIPs (PD-S1, PD-S2 and PD-S3 RIPs), are glycoproteins, with M(r) approx. 30,000, inhibit protein synthesis by a rabbit reticulocyte lysate and phenylalanine polymerization by isolated ribosomes, and depurinate rat liver rRNA in an apparently identical manner as the A-chain of ricin and other RIPs (Endo et al. (1987) J. Biol. Chem. 262, 5908-5912). Part of the purified rat liver ribosomes appeared resistant to the action of PD-S RIPs. The most abundant protein, PD-S2 RIP, gave a weak or nil cross-reaction with sera against various other RIPs, including a pokeweed antiviral protein from the roots of Phytolacca americana. PD-S2 RIP was linked to a monoclonal antibody (Ber-H2) against the CD30 human lymphocyte antigen and the resulting immunotoxin was selectively toxic to the CD30 + Hodgkin's lymphoma-derived L540 cell line.
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PMID:Purification and partial characterization of single-chain ribosome-inactivating proteins from the seeds of Phytolacca dioica L. 821 14

The CHK2 gene encodes a protein kinase that is important for the regulation of cell cycle arrest after DNA damage. CHK2 acts downstream of ataxia teleangiecstasia mutated (ATM), modulates the function of p53 and may help mediate cell cycle arrest at G2/M by phosphorylation of Cdc25C. Recently, the human homolog of the checkpoint kinase Cds1 (CHK2) has been suggested to be a tumor suppressor gene. Heterozygous germline mutations have been reported in Li-Fraumeni syndrome (LFS), a highly penetrant familial cancer phenotype, and in sporadic colon cancer. LFS is associated with the development of lymphoid malignancies, especially childhood ALL. Therefore, we analyzed the DNA from 143 lymphoid malignancies to determine whether they had mutations of the CHK2 gene. The 14 exons of CHK2 were studied by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing of aberrantly migrating bands. One missense mutation changing serine to phenylalanine (codon 428) in an evolutionarily highly conserved domain was found in a non-Hodgkin's aggressive lymphoma. Another point mutation in the non-coding region was identified in one of adult T-cell leukemias (ATL) samples. This result suggests that mutation of the CHK2 gene may rarely be involved in the development of selected lymphomas.
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PMID:Analysis of the CHK2 gene in lymphoid malignancies. 1169 18

Somatostatin receptors are widely expressed on cells and tissues throughout the human body. Apart from their expression in the physiological target organs of the peptide, somatostatin receptors are also expressed in various tumours. The expression of somatostatin receptors on neuroendocrine tumours led to the development of somatostatin receptor scintigraphy using [(111)In-DTPA-D-Phe(1)]-octreotide ((111)In-pentetreotide) in order to visualize somatostatin receptor positive tumours and their metastases in vivo. Previous studies reported the expression of somatostatin receptors in both normal and pathological cells and tissues of the human immune system as well. Somatostatin receptors have been demonstrated in Hodgkin's and non-Hodgkin's lymphomas and sst scintigraphy has shown to be a useful tool in diagnosis and staging of these diseases. Moreover, sst expression has also been detected in granulomateus diseases, like sarcoidosis and auto-immune diseases, like rheumatoid arthritis. In this paper we discuss the (possible) role of somatostatin receptor scintigraphy in diagnosis, staging or follow-up of patients suffering from sarcoidosis and rheumatoid arthritis.
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PMID:The role of octreotide scintigraphy in rheumatoid arthritis and sarcoidosis. 1497 19


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