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Biomedical subjects

N Russell

Publications and source records attributed to N Russell.

72 records · Page 4Linked to original sources
PubMed1985

Spreading and enhanced motility of human keratinocytes on fibronectin.

Soluble human plasma fibronectin or collagen types I or IV, when preincubated with tissue culture plastic dishes, were effective spreading agents for cultured human keratinocytes and increased spreading in a time-and concentration-dependent manner. Spreading on fibronectin, but not on type IV collagen, was inhibited by antifibronectin; therefore, the contribution of fibronectin to the spreading activity of the natural matrix produced by keratinocytes could not be determined using antifibronectin. Fibronectin mediated spreading at both high (1.1 mM) and low (0.1 mM) Ca++ concentrations, and spreading was not altered by cycloheximide. Insoluble fibronectin deposited by keratinocytes correlated with phagokinetic tracks on particulate gold salts, and added fibronectin, as well as type I collagen and type IV collagen, enhanced motility of keratinocytes. These studies show that production of fibronectin and responsiveness to it are similar in fibroblasts and keratinocytes and demonstrate that fibronectin can act as a matrix factor for keratinocytes.

Cell Movement↗
PubMed1984

Cisplatin plus cytosine arabinoside in adults with malignant gliomas.

A combination of cisplatin and cytosine arabinoside was used to treat 21 patients with glioblastomas and 5 patients with recurrent grade II gliomas. Cisplatin 60-100 mg/m2 was given I.V. in 250 ml 0.45% saline and preceded by 500 ml dextrose 5% in 0.45% saline. Mannitol 50 g was given I.V. concurrently with the cisplatin. Cytosine arabinoside 500-1000 mg/m2 was given by rapid I.V. infusion immediately after the cisplatin. Of 25 evaluable patients, 10 (40%) experienced objective tumor shrinkage on CT scan, and 6 (24%) stabilized. There were 2 complete remissions. Patients who had had no prior treatment had a higher response rate (58%) than those previously treated (23%). Myelosuppression occurred in some patients 2-3 weeks after treatment. Gastrointestinal toxicity (vomiting and diarrhea) was dose-limiting. Two patients had possible neurological toxicity. Recommended doses for further studies are cisplatin 90 mg/m2 and cytosine arabinoside 900 mg/m2.

Adult↗
PubMed1984

Treatment of malignant gliomas in adults with BCNU plus metronidazole.

Twenty-six adult patients with astrocytomas were treated with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) 180-240 mg/m2 I.V. every 6-9 weeks, with metronidazole 1.5 g/m2 p.o. 12 h and 1 h before BCNU and again 6 h and 24 h after BCNU. Of twenty-two evaluable patients, 9 (41%) responded with evidence of reduced tumor size on CT scan, 3 (14%) stabilized and 10 (45%) failed. Patients with no prior chemotherapy or radiotherapy, good performance status, low grade tumors, and age less than or equal to 50 years had the highest response rates, although differences were not statistically significant. Median survival and duration of response have not been reached with a median follow-up time of ten months. Hematological toxicity was dose-limiting and was probably not augmented by the metronidazole. There was one death from infection that was possibly drug-related. Gastrointestinal toxicity was substantial, and was probably increased by the metronidazole. While the combination of BCNU and metronidazole were tolerable, the response rate seen was no higher than that noted for BCNU alone, and further studies using this dose-schedule are not recommended in astrocytomas.

Adult↗
PubMed1984

Production of soluble and cell-associated fibronectin by cultured keratinocytes.

Fibronectin has been demonstrated in epithelial cell types in culture, but published studies of keratinocytes have shown patterns of fibronectin produced by cells grown in medium with serum, which contains fibronectin. Since plasma fibronectin can bind to cells in vitro, cells grown in serum-supplemented media could show artifactual patterns of cell-associated fibronectin. To study insoluble fibronectin produced by keratinocytes, we plated cells in the absence of feeder layers in medium lacking fibronectin. Medium conditioned by metabolically labeled keratinocytes was studied by immunoprecipitation and by extraction with gelatin-Sepharose. Cells grown in fibronectin-free medium were labeled using affinity-purified anti-fibronectin antibody and fluorescein-conjugated antirabbit IgG. Keratinocytes produced soluble fibronectin, since both immunoprecipitation and adsorption to gelatin-Sepharose detected 35S-methionine-labeled material which comigrated with human plasma fibronectin on sodium dodecyl sulfate polyacrylamide gels. Demonstration of insoluble, cell-associated fibronectin was enhanced in Triton X-100-extracted cells and was seen in subcellular fibrillar arrays at both physiologic and reduced Ca++ concentrations, but in intracellular locations only at physiologic Ca++ concentrations. When cells grown in 1.1 mM Ca++ were removed with Triton X-100, diffusely distributed fibrillar fibronectin remained on the surface of the coverslip. Asymmetric "tracks" of fibronectin left by sparsely plated cells suggested movement. Fibronectin is deposited by keratinocytes on the culture surface and may be modulated by culture conditions.

Animals↗
PubMed1984

Mechanisms of deoxyadenosine toxicity in human lymphoid cells in vitro: relevance to the therapeutic use of inhibitors of adenosine deaminase.

Deoxyadenosine (AdR) appears to be central to the molecular events mediating immunodeficiency in children born with adenosine deaminase (ADA) deficiency but it is still uncertain whether lymphotoxicity is due to AdR directly inhibiting transmethylation reactions in which S-adenosylmethionine is the methyl group donor, or is due to phosphorylation of AdR to deoxyadenosine triphosphate (dATP) which then inhibits ribonucleotide reductase or is due to other mechanisms. Using AdR and the ADA inhibitor deoxycoformycin (dCF) and assessing cell viability, nucleoside incorporation into RNA and DNA, as well as measuring deoxyribonucleoside triphosphate (dNTP) concentrations and S-adenosylhomocysteine (SAH) hydrolase activity, we have studied various types of human lymphoid cells and demonstrated in them the relative importance of the above two mechanisms of AdR toxicity. Treatment of normal resting peripheral blood lymphocytes in culture with AdR and dCF resulted in impaired viability. Although elevated dATP levels as well as decreased SAH hydrolase activities were both observed, the failure of a known inhibitor of ribonucleotide reductase (hydroxyurea) to produce toxicity, and the inability of deoxycytidine (CdR) to achieve a rescue effect, point to another mechanism, possibly inhibition of trans-methylation or ATP depletion being the more likely causes of toxicity in resting lymphocytes. The same mechanism may well account for the rapid and severe lymphopenia in patients treated with dCF. On the other hand, in cultured lymphoblasts in the exponential phase of growth. AdR and dCF produced marked inhibition of growth and cell death both in a Thy-ALL line and in a c-ALL line, in the absence of significant inhibition of SAH hydrolase, but with a substantial elevation in dATP concentrations and depressed levels of the other dNTP. Minor toxicity occurred in a proliferating B lymphoblast line despite almost complete inactivation of SAH hydrolase. These observations indicate inhibition of ribonucleotide reductase as the more likely mechanism of toxicity in rapidly proliferating lymphocytes. Other T-cells actively synthesizing DNA, such as PHA-stimulated or MLC activated lymphocytes and T-lymphoid colony forming cells, are also likely to be affected by the same mechanism. Indeed in PHA-stimulated lymphocytes, deoxycytidine caused significant although incomplete rescue from toxicity due to dCF and AdR. In patients with ADA deficiency or treated with ADA inhibitors, both mechanisms could be operative. These observations are also relevant to the possible use of dCF and AdR as immunosuppressive agents and for the removal of T-cells or residual Thy-ALL blasts from bone marr

Adenosine Deaminase Inhibitors↗
PubMed1984

Intracarotid chemotherapy with a combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cis-diaminedichloroplatinum (cisplatin), and 4'-O-demethyl-1-O-(4,6-O-2-thenylidene-beta-D-glucopyranosyl) epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors.

Thirty-seven patients with intracranial primary or metastatic tumors were treated with an intraarterial combination of BCNU, cisplatin, and VM-26 to determine the efficacy, toxicity, and maximal tolerated doses for the combination. A transfemoral fluoroscopic approach was used to catheterize temporarily the internal carotid or vertebral artery. Thirteen of 19 (68%) evaluable primary brain tumors and 9 of 16 (56%) evaluable brain metastases responded. The response rate was lower in patients previously treated with both cranial irradiation and i.v. chemotherapy than in patients less heavily pretreated (54% vs. 82%), although even patients previously treated i.v. with all three of the study drugs responded. All five patients with both extracranial and intracranial evaluable tumor deposits experienced a greater response of their intracranial than of their extracranial tumor. Ipsilateral retinal and neurological toxicity were dose-limiting, with major toxicity (permanent decreased vision or hemiparesis) occurring in five of nine (56%) patients receiving doses of BCNU greater than or equal to 100 mg/m2 plus cisplatin, 60 mg/m2 plus cisplatin, 60 mg/m2, plus VM-26, 175 mg/m2. Only 9% of the patients treated with a lower VM-26 dose developed permanent severe toxicity, and the doses that we now recommend are: BCNU, 100 mg/m2; cisplatin, 60 mg/m2; and VM-26, 150 mg/m2. The response rate was also dose-related (100% at the highest doses tested vs. 57% at the lower doses).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

Hormonal status of patients with primary malignant melanoma: a review of 313 cases.

We studied 313 patients with a confirmed diagnosis of primary malignant melanoma who presented to The University of Texas System Cancer Center between 1976 and 1980, to determine the relationship of endocrine status to the presentation of this tumor. There were 171 women and 142 men, a ratio of 1.20:1. Age, age range, race, and residence distribution were comparable for both sexes. The women married and had their first pregnancy at ages at least comparable to the population in general. They tended to have multiple pregnancies (average, 2.64), to nurse their children, to have an aggregate 32 years of menstrual activity, and to use exogenous hormones (73%). The female patients in this study had more favorable lesions than their male counterparts in all five microstaging categories: type of melanoma, location, level of invasion, thickness, and stage. Analysis of the hormonal subgroups among the women revealed the morphology of the primary tumor to be independent of menopausal status, parity, or the use of exogenous hormones. These findings suggest that hormonal background does not effect the acquisition of malignant melanoma, but may influence its subsequent spread.

Adult↗
PubMed1982

A double-blind comparison of fluspirilene and fluphenazine decanoate in schizophrenia.

A double-blind comparison of fluspirilene and fluphenazine decanoate in 28 schizophrenic patients over six months showed equal improvement and the same incidence of side-effects in each group of patients. It would be expected from the literature that a better ratio of therapeutic to side-effects would appear with fluspirilene than with fluphenazine. The absence of such an effect in this study may be attributable to an initial lack of familiarity by the investigators with the use of fluspirilene, indicating an important potential variable in the comparison of a new drug with an established one.

Adult↗
PubMed1981

Results of treatment for squamous carcinoma of the lower gum.

The records of 61 patients with a diagnosis of squamous carcinoma of the lower alveolar ridge were reviewed. The overall two-year survival was 67% with a local or regional failure of 5%. The majority of patients were treated with surgery initially with an excellent local control of 98%, if the patient who died in the postoperative period and the patient lost to follow-up are excluded. Radiation therapy should be used postoperatively for those patients whose cancer exhibits some of the adverse findings such as extensive nodal metastasis, perineural invasion, or inadequate margins of surgical resection.

Adult↗
PubMed1981

Spinal subdural hematoma in association with anticoagulant therapy.

A case of spinal subdural hematoma occurring in association with anticoagulant therapy is reported. Seven similar cases from the literature are reviewed the emphasis on the clinical features, investigation, and the results of treatment. The prognosis for recovery is good, only if the condition is diagnosed and the clot evacuated before severe spinal cord compression and subsequent ischemic necrosis has occurred.

Aged↗
PubMed1981

Further studies of the human platelet receptor for quinine- and quinine-dependent antibodies.

Previous studies have shown that the receptor for quinine- and quinidine-dependent antibodies is not expressed on the surface of platelets from patients with the Bernard-Soulier (B-S) syndrome. We now report data to suggest that these platelets lack the receptor for these antibodies. Since B-S platelets are also missing 2 related components of the GP I complex, GP lb and glycocalicin, our findings suggest that the receptor for quinine- and quinidine-dependent antibodies may be associated with this complex on normal platelets. An antibody previously shown to be directed against a surface antigen that migrated in the GP I position on SDS-polyacrylamide gel electrophoresis specifically blocked the reaction of the receptor with quinine- or quinidine-dependent antibodies. Purified glycocalicin, however, lacked detectable receptor activity. In contrast, a mixture of GP lb and a putative structural analog of this glycoprotein (Mr 210,000) eluted from wheat germ affinity columns after chromatography of Triton X soluble preparations of platelets or membranes was shown to contain at least 80% of the total receptor activity. Our results strongly suggest that the receptor is associated with GP lb and/or its high m.w. structural analog(s).

Antibodies↗
PubMed1980

Malignant melanoma of the external ear. Review of 102 cases.

The medical records of 102 patients with a diagnosis of melanoma of the external ear seen at The M.D. Anderson Hospital over approximately a 30 year period were reviewed. Survival was correlated with the sex, the clinical appearance of the lesion, the anatomic site of origin, the microscopic thickness and level of invasion, the absence or presence of clinical and pathologic nodal metastasis, the type of neck dissection and the type of definitive surgical treatment to the ear. The thickness and nodal metastasis adversely affected prognosis. Proper surgical treatment usually involves less than total amputation of the ear. A randomized prospective study should answer the question of whether elective neck dissection of the periauricular, parotid and upper posterior cervical and jugulodigastric nodes is justified. The use of chemoimmunotherapy offers a negligible therapeutic benefits for disseminated disease but may be of prophylactic value in a planned, adjunctive protocol for poor risk patients.

Adolescent↗
PubMedDate not supplied

A cranio-cervical malformation presenting as acute respiratory failure.

An 18-year-old, previously healthy male presented with bilateral pneumonia and acute respiratory failure with severe carbon dioxide retention. The presence of mild brainstem signs and hypoventilation led to the discovery of a platybasia, basilar invagination, and kinking of the medulla oblongata with early syrinx. He was operated upon but postoperatively was noted to have a mixed type of sleep apnea. This case illustrates the diagnostic challenge in acute respiratory failure in a previously healthy young person and the possible pathogenic mechanisms underlying it.

Adolescent↗
PubMedDate not supplied

Current trends in the management of chronic myeloid leukaemia.

Conventional or alkylating treatment for chronic myeloid leukaemia has little impact on overall survival. Recent treatments, however, are encouraging. Alpha interferon may prolong the chronic phase in some patients, while allogeneic bone marrow transplantation is curative in over 50% of patients with HLA-compatible donors.

Antineoplastic Agents↗