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Biomedical subjects

C Little

Publications and source records attributed to C Little.

At least 91 records · Page 5Linked to original sources
PubMed1984

NHL-3 protocol. Six-drug combination chemotherapy for non-Hodgkin's lymphoma.

Combination chemotherapy and radiotherapy (RT) were administered to 73 adults with non-Hodgkin's lymphoma (NHL). Ten cycles of the following drugs were given: intravenous Adriamycin (doxorubicin) (25 mg/m2), cyclophosphamide (700 mg/m2) and vincristine (1.5 mg/m2) on day 1; arabinosylcytosine (100 mg/m2) and methotrexate (10 mg/m2) on days 3 to 5; and oral prednisone (60 mg/m2) on days 1 to 5. Radiotherapy was given to resistant or initially bulky disease (2000 rad). Patients were also randomized to receive pseudomonas vaccine or no immunotherapy. Of 61 evaluable patients, 33 (54%) achieved a complete response (CR) and 18 (30%) a partial response (PR). Among 44 evaluable patients with diffuse histiocytic lymphoma (DHL), 22 (50%) had a CR, and 15 (34%) a PR. For 17 evaluable patients with nodular (4) and diffuse (11) mixed and poorly differentiated lymphocytic and diffuse "undifferentiated" (2) lymphomas, CR and PR rates were 65% and 18%, respectively. No statistically significant differences in response rate or duration and survival have been observed between the patients randomized to receive pseudomonas vaccine or no immunotherapy. Median follow-up time from start of treatment was 47.5 months. Median survival for all 73 patients (including inevaluables ) and for 52 DHL patients was 30.7 months. Poor prognostic features influencing survival included: female sex (P = 0.003), poor response to therapy (CR versus PR; P = 0.001), prior chemotherapy, (P = 0.01) and high levels of lactic dehydrogenase (P = 0.001). It can be concluded that this combination of cycle and phase-active agents is of similar efficacy to other reported regimens in inducing major responses and that it has the potential to prolong disease-free survival. The analysis of prognostic factors has been used to dissect poor prognostic categories that might require different modalities of treatment.

Adult↗
PubMed1984

Treatment of diffuse poorly differentiated lymphocytic lymphoma. An analysis of prognostic variables.

Forty patients with diffuse poorly differentiated lymphocytic lymphoma (DPDL) Stages II-IV were treated with three different and successive combination chemotherapy protocols. Seventeen patients were treated with the cyclophosphamide (CTX) L2 protocol which included maintenance chemotherapy for 3 years. Only three patients were treated with the NHL-3 (non-Hodgkin's lymphoma) protocol, and 20 patients received the NHL-5 program. All protocols included radiotherapy (1500-4800 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system (CNS) prophylaxis with intrathecal methotrexate in patients with bone marrow involvement. Seventy-eight percent of local recurrences occurred in previously irradiated areas. Two-year survival rates were 55% and 70% for the CTX-L2 and NHL-5 protocols, respectively. Median disease-free survival for 24 complete response (CR) patients was 16.5 months. Of the 40 patients, 37 were evaluable for response to therapy. The CTX-L2 produced an 80% total response (TR) rate, a 60% CR, and a 20% partial response (PR). The patients on the NHL-5 achieved a TR rate of 95%, 74% CR, and 21% PR. Differences in TR and CR between the two protocols were not significant. Only 1 of 3 patients on the NHL-3 protocol achieved a CR. There was a trend for age greater than 50 years to lessen the chances of CR (P = 0.091); however, sex, symptoms, stage of disease, and LDH level were not significantly related to CR rate. Response to treatment (CR versus PR versus failure) was the most important factor influencing survival (P less than 0.001); age (greater than 50 years) was also significant (P = 0.008). Lactate dehydrogenase (LDH) was of borderline significance (P = 0.06). Cox regression model showed age (greater than 50 versus less than 50 years, P = 0.001), LDH (greater than 500 versus less than or equal to 500 U/L, P = 0.019) and symptoms (A or B) to be the best predictors of survival.

Adult↗
PubMed1984

Collagen in the egg shell membranes of the hen.

Collagen-like proteins have been found in the egg shell membranes of the hen. Materials similar to types I and V collagens were detected in each of the two layers of this membrane, the thick outer membrane and the thin inner membrane. Collagen was extracted by acid-pepsin digestion and isolated by differential salt precipitation. Identification of type-specific collagen-like material was established by coelectrophoresis on SDS-polyacrylamide gels using known collagen standards. These bands were susceptible to digestion by bacterial collagenase. From differential staining of the gels it was estimated that the ratio of collagen types I:V was approximately 100:1. Further confirmation of these biochemical results was obtained with immunofluorescence microscopy using type-specific antisera against chicken types I and V collagen with the indirect sandwich technique. Both the inner and outer shell membranes contained the two types of collagen. Within each membrane, the large, coarse 2.5-micron fibers contained predominantly type I collagen-like material, while type V collagen was mainly associated with the delicate narrower fibers of approximately 0.6-micron diameter. These tended to be concentrated in the inner membrane. At the electron microscopic level, both types of fibers were coated with glycoproteins that stained positively with ruthenium red. The deposition of these collagen-like substances by the hen oviduct on to the surface of the developing egg is an additional example of interstitial-type collagen synthesis and secretion by epithelial rather than by mesenchymal cells.

Animals↗
PubMed1984

NAD(P)H dehydrogenase from rabbit and rat liver: purification and some properties.

NAD(P)H dehydrogenase from rabbit liver was purified to electrophoretic homogeneity using a procedure also found applicable for the rat liver enzyme. Rabbit and rat liver enzymes showed different behaviour in isoelectric focusing and different Km values and turnover numbers. Both enzymes were inhibited to similar extents by warfarin. The rabbit enzyme is composed of two subunits of mol. wt 27,000 and contained 1 FAD group per subunit. Some absorption and circular dichroism properties of the rat enzyme are shown.

Animals↗
PubMed1984

The binding and hydrolysis of sphingomyelin by phospholipase C (Bacillus cereus) as shown by 31P NMR.

31P nuclear magnetic resonance studies showed that heavily inactivated phospholipase C (Bacillus cereus) initially caused line broadening in the 31P resonance from sphingomyelin thus indicating enzyme-lipid association. Using larger amounts of enzyme or longer preincubation caused a displacement of the 31P resonance to a position suggesting phosphorylcholine formation. Incubation of the heavily inactivated enzyme with a phosphonolipid caused a displacement of the 31P resonance suggesting hydrolysis.

Bacillus cereus↗
PubMed1984

An anion binding site in the active centre of phospholipase C from Bacillus cereus.

The bi-Zn2+-enzyme phospholipase C (Bacillus cereus) is readilly inhibited by univalent anions. N.m.r. studies on the 113Cd-substituted enzyme showed the presence of an inert and a perturbable metal, neither of which seemed affected by I-. X-ray crystallographic analysis showed the binding of one I- to the enzyme 4.8 A from the nearest metal (too far for a metal-halide bond). Phospholipase C contains an arginine residue apparently necessary for substrate binding and I- partially protected against inactivation by an arginine reagent. Thus an arginine residue may represent the binding site for univalent anions in the enzyme active centre.

Anions↗
PubMed1983

Purification and some properties of myeloperoxidase and eosinophil peroxidase from human blood.

Myeloperoxidase and eosinophil peroxidase have been isolated from outdated human blood. Peroxidase activity was extracted from washed leucocytes using 0.5 M-CaCl2 and the extract further purified by chromatography on concanavalin A--Sepharose, phenyl-Sepharose and finally by gel filtration. The final enzyme preparations were highly purified according to spectral and gel-electrophoretic criteria. Under reducing and denaturing conditions on polyacrylamide-gel electrophoresis myeloperoxidase gave rise to bands of Mr 57 000, 39 000 and 15 500, whereas the eosinophil enzyme yielded bands of Mr 50 000 and 15 500. Both enzymes were very resistant to denaturation either by the chaotropic agents urea and guanidinium chloride or by elevated temperatures. Spectral properties of the native and reduced forms of the enzymes are reported.

Chromatography, Affinity↗
PubMed1983

Monoclonal antibodies that distinguish non-small cell from small cell lung cancer.

Two murine IgG2Ak monoclonal antibodies (703D4, 704A 1) were produced and characterized after immunization with a human large cell lung cancer line (NCI-H 157). These antibodies detect different epitopes on 31 kilodalton [35S]methionine incorporating protein(s). Radiobinding and immunohistochemical studies show these antibodies bind to most (11/13) human non-small cell lung cancer (adenocarcinoma, epidermoid, and large cell), but not to small cell lung cancer (0/11) tumors tested. The epitopes these antibodies recognized are also expressed on human melanomas (7/8), two other tumors (osteogenic sarcoma, renal cell carcinoma), but not on many other human tumors (breast, colon, neuroblastoma, lymphoid), and not on a panel of normal adult human tissues. Because the antigen(s) are preserved after fixation and because of their ability to distinguish lung cancer types from each other and normal tissues, they should be of clinical, as well as of biologic interest.

Animals↗
PubMed1982

Comparative studies on oestrogen-induced rat uterus peroxidase and rat eosinophil peroxidase.

Rat eosinophil peroxidase and rat uterine peroxidase II showed similar electrophoretic mobilities, molecular weights, specific activities and spectral properties and could be purified by essentially identical techniques. Antibodies raised against the uterine enzyme strongly inhibited the eosinophil enzyme. It is suggested that rat eosinophil peroxidase and rat uterine peroxidase II may well be one and the same enzyme.

Animals↗
PubMed1982

Effect of Co2+-substitution on the substrate specificity of phospholipase C from Bacillus cereus during attack on two membrane systems.

Phospholipid degradation by native phospholipase C from Bacillus cereus and enzyme forms where one or both of the Zn2+ prosthetic groups had been replaced with Co2+ was studied in human erythrocyte membranes (ghosts) and resuspended freeze-dried bovine brain myelin. The rate of total phospholipid degradation was 2-9-fold more rapid with erythrocytes than with myelin. With both membrane systems the activity decreased in the order ZnZn-enzyme greater than ZnCo-enzyme greater than CoCo-enzyme. For all three enzyme forms with either membrane system, phosphatidylethanolamine (or the ethanolamine-containing phosphoglycerides) and phosphatidylcholine were hydrolysed most rapidly and sphingomyelin least. The relative rate of sphingomyelin degradation was highest with the ZnCo-enzyme. In myelin at low ionic strength there seemed to be a core of phospholipid that was very resistant to degradation by native phospholipase C but which was much more accessible to the Co2+-substituted forms. It is suggested that ZnCo-phospholipase C has potential applications in membrane studies.

Animals↗
PubMed1982

Inhibition of Bacillus cereus phospholipase C by univalent anions.

The rate of phospholipid hydrolysis in erythrocyte ghosts by Bacillus cereus phospholipase C was markedly decreased by the presence of NaCl at concentrations between 25 and 200 mM. The inhibition seemed to be due to Cl- and was unaffected by the type of cation present. The larger univalent anions such as HCO3-, Br-, Cl-, NO3-, CNO- and I- seemed most effective, whereas the bivalent anion SO42- was relatively ineffective at 0.1 M, as were acetate and formate. Tris buffers at 0.1 M caused marked inhibition. With bovine brain myelin, phospholipid hydrolysis by phospholipase C was also much more strongly inhibited by I- and Cl- than by SO42- or acetate. NaCl inhibited the hydrolysis by the enzyme of the soluble substrate dihexanoylglycerophosphocholine, thereby suggesting that the inhibiton did not arise simply from substrate effects.

Anions↗
PubMed1982

Treatment of advanced diffuse histiocytic lymphoma: an analysis of prognostic variables.

Sixty-five patients with Stages III and IV diffuse histiocytic lymphoma (DHL) were treated with two different and successive combination chemotherapy protocols. Twenty-seven patients were treated with the cyclophosphamide (CTX) L2 protocol, which included maintenance chemotherapy for three years. Thirty-eight patients received the NHL-3 program. Both protocols included radiotherapy (1350--4000 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system prophylaxis with intrathecal methotrexate or cytosine arabinoside in patients with bone marrow involvement. Two-year survival rates were 44 and 56%, respectively, for the CTX-L2 and NHL-3 protocols. Of the 65 patients, 59 were evaluable for response to therapy. The CTX-L2 produced a 58% total response (TR) rate, 39% complete (CR), and 19% partial (PR). The patients on NHL-3 achieved a TR rate of 82%, 33% CR, and 48% PR. The difference in TR was significant (P = 0.05), but in CR was not. Prior chemotherapy (P = 0.077) and serum lactic dehydrogenase (LDH) level above 500 U/liter (P = 0.01) significantly lessened the chances for achievement of a CR. However, sex, age, the presence of systemic symptoms, stage (III vs. IV), and prior RT were not found to be significantly related to CR rate. This analysis suggests that a high level of serum LDH characterizes a subgroup of patients with particularly aggressive DHL that requires a more intensive modality of treatment.

Adolescent↗
PubMed1982

Spectral properties of the oestrogen-induced rat uterus peroxidase II and some of its derivatives.

1. The visible absorption spectrum of peroxidase II, isolated from the uterine tissue of oestradiol-treated rats, and some of its derivatives were recorded. The spectral properties of this enzyme are very similar to eosinophile peroxidase and lactoperoxidase, suggesting that these enzymes may have a similar form of haem as prosthetic group. 2. The uterine peroxidase is modified upon interaction with H2O2 and the difference spectrum of this modified enzyme is similar to that of complex II of lactoperoxidase. The modified enzyme was found to revert spontaneously to the native enzyme at rates which depended on the concentration of free enzyme and H2O2.

Animals↗
PubMed1982

Combination chemotherapy of advanced chronic lymphocytic leukemia: the M-2 protocol (vincristine, BCNU, cyclophosphamide, melphalan, and prednisone).

The M-2 protocol (vincristine, cyclophosphamide, BCNU, melphalan, and prednisone) was administered monthly to 63 evaluable patients with advanced chronic lymphocytic leukemia. Complete remission (absence of all clinical and bone marrow evidence of leukemia) and partial response (greater than 50% decrease in organ enlargement and reduction of WBC count to below 15,000 x 10(6)/liter) were achieved in 17% and 44%, respectively, for a total response rate of 61%. The median survivals from therapy of patients achieving a CR, RR, or no response were 73+, 40, and 14 mo respectively. The median survival time from onset of treatment for stages II, III, and IV disease were 47, 20 and 19 mo, respectively, which was not statistically different from historical controls. However, when untreated patients are compared to this latter group, a significant survival advantage from diagnosis was found (p = 0.01), stressing the importance of prior therapy as the only unfavorable prognostic factor. Although complete remissions in CLL, as reflected in apparently normal bone marrow B-lymphocyte markers, can be induced wih acceptable morbidity, the majority of patients relapse after cessation of therapy. An alternative approach to the M-2 protocol will be needed to eradicate the disease.

Antineoplastic Agents↗
PubMed1981

Identification of the apparently essential lysine residues in phospholipase C (Bacillus cereus).

Phospholipase C (Bacillus cereus) contains two apparently essential and very reactive lysine residues that may be labelled selectively by pyridoxal 5'-phosphate [Aurebekk & Little (1977) Biochem, J. 161, 159--165]. One of these lysine residues was found in the 25-amino acid N-terminal fragment liberated by CNBr digestion of the pyridoxal-labelled enzyme and identified as lysine-6. Two of the labelled peptides isolated from the chymotryptic digest of pyridoxal-labelled enzyme contained proline, suggesting that the other labelled lysine residue is situated in the same region of the primary structure as the single proline residue of the enzyme.

Amino Acids↗