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Biomedical subjects

N Murray

Publications and source records attributed to N Murray.

At least 127 records · Page 7Linked to original sources
PubMed1986

The use of VP-16 plus cisplatin during induction chemotherapy for small-cell lung cancer.

In an attempt to circumvent innate or acquired tumor-cell resistance to chemotherapy, patients with small-cell lung cancer (SCLC) were treated with induction therapy that incorporated two active and potentially non-cross-resistant chemotherapy regimens on two National Cancer Institute of Canada (NCI-C) trials. Patients with limited disease (LD) SCLC were treated with cyclophosphamide, doxorubicin (Adriamycin [Adria Laboratories, Columbus, Ohio]) and vincristine (CAV) and VP-16 plus cisplatin in two different sequences. One arm was randomized to receive CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles, and the other arm received three courses of CAV followed by three courses of VP-16 plus cisplatin. Both treatment strategies produced similar response rates and survival curves, and each treatment group has a projected 2-year survival of 20%. Patients with extensive disease (ED) were treated with either six cycles of CAV (standard regimen) or CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles. In this study, the alternating regimen produced a higher complete response (CR) rate (40% v 27%) and overall response rate (61% v 39%; P less than .01). The progression-free survival was also superior for the alternating arm (P = .001), as was overall survival (P less than .05). The frequency of thrombocytopenia and severe gastrointestinal toxicity was slightly greater in the alternating arm, but the frequency of neutropenia and infection was less. The alternation of CAV and VP-16 plus cisplatin during induction therapy is an effective treatment strategy in the management of SCLC and superior to CAV alone in extensive SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Alternating chemotherapy and thoracic radiotherapy with concurrent cisplatin-etoposide for limited-stage small-cell carcinoma of the lung.

Seventy patients with limited-stage small-cell lung cancer (SCLC) were given six courses of chemotherapy alternating two drug combinations: a combination of cyclophosphamide, doxorubicin (Adriamycin [Adria Laboratories, Columbus OH]) and vincristine (CAV) was alternated with cisplatin and etoposide at 3-week intervals. Thoracic radiotherapy was administered concurrently with the first cisplatin-etoposide chemotherapy. Prophylactic cranial irradiation (PCI) was administered after the completion of all chemotherapy. No maintenance treatment was used. Seventy-six percent of patients achieved a complete clinical response. The median survival was 78 weeks and the 2-year survival rate was 32% with an average follow-up of 3 1/2 years. Seventeen percent are currently alive and disease free. Cisplatin and etoposide can be administered concurrently with thoracic irradiation with acceptable toxicity. Our results justify further clinical research using alternating chemotherapy and concurrent thoracic irradiation and cisplatin-etoposide chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Carcinoma of the lung in patients under 40 years of age.

Bronchogenic carcinoma in the young population (40 years of age or less) is reported to present in an advanced stage and to have a virulent course. Between 1969 and 1979, 101 patients (65 men and 36 women) presented with cancer of the lung. Their mean age was 36.2 +/- 3.9 years (range 18 to 40 years). Eighty-seven percent had a history of cigarette smoking. Fifty percent of the patients had a strong familial history of malignancy of several organs. The interval between onset of symptoms and diagnosis was 4.01 +/- 3.48 months (3.56 +/- 3.34 for the surgically treated group and 4.16 +/- 3.53 for the nonoperated or unresectable group). Diagnosis was made at bronchoscopy in 32 patients, during thoracotomy in 30 patients, during nodal biopsy in 28 patients, and on cytologic examination of the sputum in 9 patients. The most common cell types were adenocarcinoma in 39 patients, squamous carcinoma in 29 patients, and oat cell carcinoma in 18 patients. Eighty-six patients (the majority) presented in stage III, whereas 9 were in stage I and 6 were in stage II. Twenty-seven patients (26.7 percent) underwent resection for cure, whereas 18 patients were inoperable at surgery. Eighteen of the surgical patients had adjuvant radiotherapy, and chemotherapy, immunotherapy, or both. The average length of survival for the nonresected patients was 7.12 +/- 5.9 months (range 1 to 36 months) and the actuarial survival was 1.5 percent at 36 months. The survival for the surgically managed patients was 56.1 +/- 52.6 months (range 3 to 168 months) or 48 percent at 36 months. At 46 to 168 months after treatment, the only survivors were 13 patients who were surgically managed. Stage III patients had longer survival after surgery (24.1 +/- 24.6 months to 7.09 +/- 5.90 months; range 3 to 74 months and 1 to 36 months, respectively). The survival at 5 years for patients with stage I disease was 78.8 percent, stage II disease 66.6 percent, and stage III disease, 3.6 percent. Early diagnosis and aggressive surgical management are necessary to improve the survival of patients with bronchogenic carcinoma under 40 years of age.

Adolescent↗
PubMed1985

Passive transfer studies in demyelinating neuropathy with IgM monoclonal antibodies to myelin-associated glycoprotein.

Serum or IgM fraction from two patients with a demyelinating neuropathy and IgM monoclonal antibodies to myelin-associated glycoprotein were injected in three different animal species. There were no clinical, electrophysiological or morphological signs of demyelination in either chronic or acute passive transfer experiments. These results suggest that the pathogenesis of this human demyelinating neuropathy may be more complex than has been assumed.

Animals↗
PubMed1985

A monoclonal anti-idiotypic antibody against a human monoclonal IgM with specificity for myelin-associated glycoprotein.

A human monoclonal IgM lambda antibody, directed against MAG, obtained from a patient with polyneuropathy associated with a gammopathy, was used as an immunogen to generate mouse monoclonal anti-idiotype antibodies. One hybridoma antibody, designated A8F2, reacts uniquely with the M-IgM of the patient, shows high affinity binding to the patient's M-IgM, and dose-dependently inhibits binding of the patient's M-IgM to its specific antigen MAG. Thus, A8F2 is a monoclonal anti-idiotype antibody that recognizes a region of the MAG binding site of the patient's IgM. Use of this anti-idiotype antibody in a competition RIA revealed the presence of naturally occurring anti-idiotype in the patient's serum. Because anti-idiotype antibodies may be part of a mechanism for down-regulation of antibody production, the use of A8F2 to induce a specific immunosuppression should be considered.

Animals↗
PubMed1985

Cyclic alternating chemotherapy for small cell carcinoma of the lung.

Eighty-two previously untreated patients with small cell cancer of the lung were treated with six cycles of two alternating drug regimens: a new combination of mitomycin, methotrexate, and etoposide; and cyclophosphamide, doxorubicin, and vincristine. No maintenance chemotherapy was used. Consolidative thoracic irradiation and prophylactic cranial irradiation were employed. The median survival time for 32 limited-disease patients was 59 weeks, and for 50 extensive-disease patients was 35 weeks. Four-year survival was 12% for limited-disease patients and 2% for extensive-disease patients. These results were not superior to conventional combination chemotherapy regimens.

Adult↗
PubMed1984

Indication of a possible role in a demyelinating neuropathy for an antigen shared between myelin and NK cells.

In three patients with monoclonal IgM antibodies to myelin-associated glycoprotein and a demyelinating neuropathy, the human monoclonal antibodies and HNK1, a mouse monoclonal antibody against human natural killer cells, reacted with the same region of myelin-associated glycoprotein. In these three patients there was a pronounced decrease in the number of circulating HNK1-positive cells. Taken together, these findings provide evidence that a cross-reactive cell surface antigen may be involved in an autoimmune response directed simultaneously against the nervous system and the immune system.

Aged↗
PubMed1984

Human monoclonal antibodies to myelin-associated glycoprotein are directed against the polypeptide and not the carbohydrate moiety.

We have used an approach which combines the technique of electrophoretic blotting of polyacrylamide gels with methods for the degradation of carbohydrates, to study the myelin-associated glycoprotein (MAG)-specific antibodies found in 5 patients with demyelinating neuropathy. Our results show that it is possible to deglycosylate proteins on nitrocellulose blots and then to examine their antigenicity and lectin-binding properties. With MAG, our findings suggest that the monoclonal IgM antibodies from all the patients studied have specificity for the polypeptide and not the carbohydrate moiety.

Antibodies, Anti-Idiotypic↗
PubMed1984

Impulse conduction regulates myelin basic protein phosphorylation in rat optic nerve.

The influence of action potential conduction in myelinated axons on the state of phosphorylation of myelin basic protein was studied in rat optic nerve incubated in vitro. For this purpose we used a technique that permits continuous recording of the responses of nerves to electrical stimulation together with the "back-phosphorylation" assay. Our results indicate that action potential conduction, but not electrical stimulation, increased the state of phosphorylation of myelin basic protein. The increment in basic protein phosphorylation was related to the number of impulses conducted, up to a maximal change which occurred after 12 X 10(3) impulses. Also, the effect of action potential conduction was reversible, since the state of myelin basic protein phosphorylation returned to control levels within 5 min of stopping stimulation. These findings raise the interesting possibility that myelin basic protein phosphorylation plays a role in some dynamic function of myelin, perhaps related to ion transport or to the process of recovery of ionic gradients.

Action Potentials↗
PubMed1983

Lambda replacement vectors carrying polylinker sequences.

To simplify the construction and screening of genomic libraries, we have made a new family of lambda replacement vectors (EMBL1, EMBL2, EMBL3, EMBL4) and derivatives containing amber mutations (EMBL3 Sam, EMBL3 AamBam, EMBL3 AamSam). These vectors have a large capacity and polylinker sequences flanking the middle fragment. The polylinkers allow a choice of cloning enzymes and, especially useful in the case of cloning of Sau3A partial digests, the excision of the entire insert by flanking SalI (EMBL3) or EcoRI (EMBL4) sites. Phages with inserts can be selected either biochemically (particularly EMBL3) or genetically by their Spi- phenotype. Amber derivatives of the EMBL3 vector allow the application of genetic screening procedures based on selection for the products of homologous recombination events, and for the selective cloning of DNA sequences linked to supF genes.

Animals↗
PubMed1983

Human monoclonal antibodies to myelin-associated glycoprotein. Comparison of specificity and use for immunocytochemical localisation of the antigen.

Recent reports demonstrate that a population of patients with gammopathy and demyelinating neuropathy have monoclonal antibodies to myelin-associated glycoprotein. Using the immunoblotting technique we compared the species specificity: human monoclonal antibodies to myelin-associated glycoprotein reacted with human, monkey, calf, dog, rabbit and guinea pig myelin, but not with rat or mouse. On the immunoblot myelin-associated glycoprotein consistently stained as a diffuse band with an apparent molecular weight ranging from 90-100 X 10(3) dalton. Experiments showed that when human CNS myelin had been incubated at 37 degrees C before gel electrophoresis, there was a general shift of staining towards the lower end of the molecular weight range. This low molecular weight myelin-associated glycoprotein, when released from the membrane, contains the antigenic determinant. Peptide mapping by limited proteolysis reveals that the antigenic determinants for 4 different monoclonal antibodies appear to lie very close together in the molecule. The distribution of the antigen was studied in nervous tissue with the unlabelled peroxidase-antiperoxidase method. The results obtained are in close agreement with the localization reported with polyclonal antisera to myelin-associated glycoprotein.

Animals↗
PubMed1983

The influence of age on lithium efficacy and side-effects in out-patients.

One hundred and sixty-six unipolar and bipolar out-patients (21-78 years) on long-term lithium treatment were studied on a prospective basis. Although there was a possible tendency for manic attacks to increase in prevalence and severity with age, it was difficult to demonstrate a general age-related decline in lithium efficacy. There was a tendency for the prevalence and severity of fine hand tremor to increase with age. This was not seen with polydipsia/polyuria, the other typical lithium side-effect.

Adult↗
PubMed1983

Depolarizing agents regulate the phosphorylation of myelin basic protein in rat optic nerves.

The regulation of the state of phosphorylation of myelin basic protein has been studied in intact rat optic nerves incubated in vitro. For this purpose the endogenous state of phosphorylation was preserved and the "back-phosphorylation" technique was used to determine the amount of dephosphorylated protein present in extracts of the nerves. Our results indicate that when nerves were incubated in the presence of depolarizing agents, the state of phosphorylation of myelin basic protein was increased. This effect was calcium-dependent and was partly inhibited by chlorpromazine.

Adenosine Triphosphate↗
PubMed1983

Reversal of dexamethasone suppression test nonsuppression in alcohol abusers.

Of 75 detoxified alcohol-abusing inpatients given the dexamethasone suppression test (DST), 13 demonstrated nonsuppression and returned to normal suppression after 4 more weeks of abstinence. The authors question interpreting nonsuppression in alcohol abusers as indicating major depression without a significant period of abstinence.

Adolescent↗