Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of lymphoid cell populations were examined in terms of their ability to replicate vesicular stomatitis virus (VSV), a lytic, RNA-containing virus maturing at the cell surface. The number of cells capable of producing VSV was estimated in terms of infectious centers by the virus plaque assay (VPA), and morphologically by electron microscopy (EM). The lymphoid cells examined in this study included: (a) lymph node cells from delayed hypersensitive guinea pigs stimulated by specific antigen, (b) mouse spleen cells activated by selective bone marrow-derived (B) cell and thymus derived (T) cell mitogens, and (c) cells of human and murine continuous lymphoblastoid or lymphoma lines. In unstimulated cultures of guinea pig lymph node cells there is a background of approximately 1 in 1,000 cells which produces VSV; in purified protein derivative (PPD)-stimulated cultures the number of cells producing virus was 1.6% in the VPA and 1.9% by EM. These cells were large lymphocytes with some morphological features of transformed lymphocytes but were not typical blast cells. A few macrophages were associated with virus in both stimulated and control cultures. These observations indicate that (a) cells responsive to antigens, as detected by a marker virus, were lymphocytes; (b) cells other than lymphocytes (macrophages) were capable of replicating VSV even without antigenic stimulation; and (c) the correlation of results obtained by VPA and morphologic examination was usually quite good. Of the total number of mouse spleen cells stimulated with concanavalin (Con A), a T cell mitogen, 4.5 (EM)-5.7% (VPA) were associated with VSV. These were characteristic transformed lymphocytes, similar to phytohemagglutinin (PHA)-stimulated human lymphocytes. In contrast Escherichia coli lipopolysaccharide (LPS)-treated mouse spleen cultures contained lower numbers of virus plaque-forming cells. The majority of such cells associated with virus displayed extensive rough endoplasmic reticulum. Two cultured murine lymphomas containing lymphocytes with the theta surface marker (L5178Y and EL-4) showed a 15-100-fold higher incidence of virus-producing cells than leukemias (L1210 and C57Bl/6) which did not carry this marker. Similarly, the L2C guinea pig leukemia, a known B cell leukemia, yielded a low percent of virus plaque-forming cells (<2%). However, MOPC-104, a plasma cell tumor presumed to be of B cell origin, was found to be an efficient virus producer. There was a wide variation in the efficiency of VSV replication among human lymphoblastoid lines. One line, Wil-2, produced 80% infectious centers after 24 h of exposure to VSV, and all cells were associated with virus at the EM level. The relationship between the virus-producing cells and different lymphocyte subpopulations as well as the efficiency of the two assays for studying virus-producing lymphocytes is discussed.
 ...
PMID:The production of vesicular stomatitis virus by antigen- or mitogen-stimulated lymphocytes and continuous lymphoblastoid lines. 434 76

The envelope glycoprotein, G, of vesicular stomatitis virus (VSV) is initially glycosylated by the en bloc transfer of Glc3Man9GlcNAc2 oligosaccharides to 2 specific asparagine residues in the nascent polypeptide chain. We carried out in vivo and in vitro studies to determine whether the size of the oligosaccharide chains on two related but different G proteins can affect their ability to fold correctly. For the in vivo studies we used a mutant lymphoma cell line, Thy-1-e, which transfers the truncated oligosaccharide, Glc3Man5GlcNAc2, to nascent polypeptides. The growth of VSV in these cells was temperature-sensitive compared to that in parental Thy-1+ cells, and VSV (San Juan) was more affected than VSV (Orsay). These results are congruous with our previous observation that in the absence of glycosylation virus assembly is temperature-sensitive and VSV (San Juan) is inhibited more than VSV (Orsay). To examine the effect of oligosaccharide size on the properties of the G protein in vitro we treated G proteins containing either Man8GlcNAc2 or Man5GlcNAc2 oligosaccharide chains with guanidine hydrochloride and measured their ability to refold using an in vitro aggregation assay. The San Juan G protein with Man5GlcNAc2 oligosaccharides aggregated at 40 degrees C but not at 30 degrees C. The Orsay G protein with Man5GlcNAc2 oligosaccharides and both proteins containing Man8GlcNAc2 oligosaccharides did not aggregate at either temperature. We conclude that the size of the oligosaccharides present on the folding G protein can be crucial in attaining a proper conformation, and the extent of their effect depends on the primary structure of the polypeptide.
 ...
PMID:The effect of oligosaccharide chains of different sizes on the maturation and physical properties of the G protein of vesicular stomatitis virus. 625 53

Etoposide (VP 16) is a semi-synthetic derivative of 4'- demethylepipodophyllotoxin , a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum ) and the Indian species Podophyllum emodi Wallich . Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose-limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and Gl toxicity (nausea, vomiting, stomatitis) occur in about 20-30% of patients given recommended dosages. Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non-small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front-line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years. Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
 ...
PMID:Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, adverse effects and use as an antineoplastic agent. 632 63

Pseudotypes of vesicular stomatitis virus (VSV) bearing envelope antigens of human T-cell leukemia virus (HTLV) types 1 and 2 were prepared by propagating VSV in cells lines productively infected with HTLV. Plaque assays of VSV (HTLV) pseudotypes were employed to determine the presence of (i) HTLV receptors on cells and (ii) neutralizing antibodies in the serum of patients with adult T-cell leukemia-lymphoma (ATLL). Cell surface receptors for HTLV-1 and HTLV-2 were found on nonlymphoid cells of human and mammalian origin. Neutralizing antibodies specific to VSV(HTLV-1) were found in sera of ATLL patients in titers varying from 1:50 to 1:30,000 and did not correlate closely with antibody titers for internal viral antigens. Sera from ATLL patients in the United Kingdom (Caribbean immigrants), United States, and Japan completely neutralized VSV (HTLV-1), indicating that the HTLV isolates from these distinct geographic regions represent a single envelope serotype. Neutralization of VSV (HTLV-1) was more specific and more sensitive than assays of syncytium inhibition. No cross-neutralization was observed between bovine leukosis virus and HTLV, and only limited cross-reaction was found for envelope antigens of HTLV-1 and HTLV-2. These studies show that VSV (HTLV) pseudotypes can be readily used to screen for neutralizing antibodies in patients' sera and to distinguish HTLV envelope serotypes.
 ...
PMID:Pseudotypes of human T-cell leukemia virus types 1 and 2: neutralization by patients' sera. 632 49

The toxic effects of high-dose busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) with autologous or syngeneic bone marrow rescue were evaluated in 19 patients (11 with acute myelocytic leukemia, one with acute lymphocytic leukemia, one with acute myelofibrosis, two with chronic myelocytic leukemia, one with Hodgkin's disease, and three with non-Hodgkin's lymphoma). Their mean age was 26 years (range, 6-50); nine patients had syngeneic and ten had autologous bone marrow rescue (six of whom had in vitro bone marrow incubation with 4-hydroperoxycyclophosphamide). Severe myelosuppression was expected and was seen in all patients; leukocyte and platelet count recovery occurred at a median of 19 days (range, 11-59) and 30 days (range, 20-89), respectively. Nausea, vomiting, and diarrhea were frequent but readily managed with vigorous medical therapy. Stomatitis was severe in 14 patients. Skin, renal, cardiac, pulmonary, and CNS complications directly attributable to drug-related toxic effects were transient and non-life-threatening. Hepatic function abnormalities were common but tended to be transient. Most patients tolerated high-dose busulfan and cyclophosphamide with manageable side effects. Hepatic veno-occlusive disease was fatal in two patients, while diffuse interstitial pneumonitis with disseminated herpes virus infection was fatal in three patients with lymphoma. All patients treated in relapse or without previous therapy had a complete tumor response. Further studies with this regimen should be pursued.
 ...
PMID:Preliminary results of high-dose busulfan and cyclophosphamide with syngeneic or autologous bone marrow rescue. 637 4

We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt's lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2-16 yr) and 34 young adults 17-35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt's lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:An effective therapy for both undifferentiated (including Burkitt's) lymphomas and lymphoblastic lymphomas in children and young adults. 654 90

This study was designed to evaluate the usefulness of Coenzyme Q10 (CoQ10) in the prevention of side effects due to anthracycline agents-Adriamycin (ADM) and Daunorubicin (DNR)-by comparing the preventive effect between CoQ10-treated and non-treated groups. The subjects were 79 patients, 55 of whom had malignant lymphoma. The age range was from 16 to 77 years with a mean age of 45.4 years. CoQ10 was administered by intravenous drip at 1 mg/kg/day the day before ADM or DNR administration, on the day and for a further 2 days after administration. In mean total dose, complete remission rate and mortality, no significant differences were observed between the 2 groups. Although there were also no significant differences in the degree of alopecia, fever, nausea and vomiting, the incidences of diarrhea and stomatitis were significantly (p less than 0.10 and p less than 0.05, respectively) reduced in the CoQ10-treated group. Depression of ST waves (more than 0.05 mV) and changes in T waves (R/10 greater than T, flat, inversion) on ECG were regarded as a parameter of aggravation. Such ECG aggravation was found in 20 of 40 patients given CoQ10 (50.0%) and in 18 of 25 receiving none (72.0%); a cardiotoxicity-inhibiting tendency was thus evident (p less than 0.10). In heart rate, tachycardia was noted in the nontreated group when the period of use of anthracycline agents exceeded 8 weeks. Twenty nine patients received ADM or DNR for 8 weeks or more, and, of them, 17 were treated with CoQ10; 11 of the 17 (64.7%) showed ECG aggravation, while 11 of 12 patients (91.7%) not treated with CoQ10 showed ECG aggravation. A tendency to depress ECG aggravation was thus observed in the treated group (p less than 0.10).
 ...
PMID:[Investigation of the preventive effect of CoQ10 against the side-effects of anthracycline antineoplastic agents]. 674 67

THP-ADM is a new antitumor antibiotic which belongs to the anthracycline group. This agent was administered to 42 histology proven various malignant disease patients with a schedule of 60-80 mg per body (40-55 mg per m2) iv bolus, every three weeks. THP-ADM administration revealed mild upper GI toxicity (vomiting 19%, stomatitis 21%) and leukopenia (less than 2,000 per mm3) in 80% and thrombocytopenia (less than 60,000 per mm3) in 38% with good rebound. There was no signs or symptoms of cardiac failure including the patient who had received 740 mg per body (500 mg per m2). Definite response (CR, PR) was observed in ovarian carcinoma 4/11, cervix carcinoma 2/7, breast carcinoma 1/6, malignant lymphoma 5/5 and mesothelioma 1/2. Furthermore, some response (MR) was observed in lung metastasis from endometrial carcinoma 2/4, and stomach carcinoma 1/3. The above indicated usefulness of this agent and further study should be continued, especially a controlled study with adriamycin.
 ...
PMID:[Preliminary phase II clinical study of 4'-O-tetrahydropyranyl doxorubicin (THP-ADM)]. 688

To determine if the immunodominant neutralizing epitopes on the external envelope glycoprotein of the recently identified sequence variants of human T cell leukemia/lymphoma virus type I (HTLV-I) from Melanesia are functionally conserved, sera from Japanese patients with adult T cell leukemia and from HTLV-I-infected Melanesians of Papua New Guinea and the Solomon Islands were tested for neutralizing antibodies by use of vesicular stomatitis virus pseudotypes bearing envelope antigens of Japanese and Melanesian HTLV-I strains. Neutralizing antibody titers of the Japanese and Melanesian sera and of monoclonal and polyclonal antibodies directed against a known neutralizing epitope on the external envelope glycoprotein of HTLV-I were equivalent against the Japanese and Melanesian HTLV-I pseudotypes. The demonstrated two-way cross-neutralization between Japanese and Melanesian strains of HTLV-I indicates that their antigenic determinants for neutralization are functionally indistinguishable and that HTLV-I exists as a single serotype worldwide.
 ...
PMID:Functional conservation of the neutralizing domains on the external envelope glycoprotein of cosmopolitan and melanesian strains of human T cell leukemia/lymphoma virus type I. 750 32

We retrospectively reviewed the regimen-related toxicity associated with busulphan (1 mg/kg orally QID days -7 to -4) and cyclophosphamide (60 mg/kg IV days -3 and -2) (Bu/Cy) chemotherapy in 69 consecutive patients who underwent autologous bone marrow transplantation (ABMT). Twenty-four patients received bone marrow (BM) alone, 22 received BM plus post-transplant granulocyte-colony stimulating factor (G-CSF) and 23 received peripheral blood progenitor cells (PBPC) +/- BM plus post-transplant G-CSF. Toxicity was scored using the criteria of Bearman. Grade II and III toxicities included mucosa (38%), liver (8%), central nervous system (5%), kidney (5%), heart (3%), pericardium (2%), bladder (2%) and lung (2%). There were five treatment related deaths (7%) from pneumonitis (2) and veno-occlusive disease, pulmonary hemorrhage and sepsis (1 each). Post-transplant G-CSF (+/- PBPC) resulted in a trend (p = 0.07) towards a reduction in post-transplant stomatitis, but did not impact on the already low incidence of other organ toxicities. As Bu/Cy for ABMT is associated with minimal non-hemopoietic toxicity, the addition of other cytotoxic agents is justified in an attempt to augment the anti-tumour effect of this conditioning regimen.
Leuk Lymphoma 1994 Jul
PMID:High dose busulphan/cyclophosphamide for autologous bone marrow transplantation is associated with minimal non-hemopoietic toxicity. 752 88


<< Previous 1 2 3 4 5 6 7 8 Next >>