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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 1,045 records · Page 58Linked to original sources
PubMed1984

Nicotine-depressed function in isolated rat heart.

Experiments were conducted to assess the effects of nicotine on the isolated rat heart. Hearts removed from laboratory rats were perfused via the aorta with oxygenated (95% O2-5% CO2) Krebs-Henseleit solution. After 30 min, the hearts were challenged with perfusate containing nicotine. Heart rate and coronary flow decreased in response to nicotine concentrations of 5 micrograms/ml or above. Solutions containing 5, 10 and 20 micrograms/ml nicotine depressed heart rate by 9, 29 and 25%, and coronary flow by 11, 28 and 33%. Pulse pressure was significantly depressed by 20 micrograms/ml nicotine. Perfusion with nicotine-free solution for 10 min completely reversed the decreases in heart rate, coronary flow and pulse pressure. These results indicate that nicotine continuously infused into the isolated rat heart depresses heart rate and coronary flow in a dose-response manner and that these changes are reversible over the range of concentrations used.

Animals↗
PubMed1984

Stability of doxorubicin in relation to chemosensitivity determinations: loss of lethality and retention of antiproliferative activity.

The chemical stability of doxorubicin in a variety of tissue culture media has been studied by thin layer chromatography (TLC). In all the media examined, authentic doxorubicin was converted to a chemically distinct form as evidenced by the failure of this form to migrate on TLC plates. The rates of conversion were rapid enough (t 1/2 approximately equal to 3 hr) to be of consequence in chemosensitivity determinations, especially if working solutions of doxorubicin were to be routinely made and stored in tissue culture media. The addition of certain antioxidants to media did not prevent the conversion of authentic doxorubicin. However, doxorubicin was quite stable in distilled water. No single component of media was found to be responsible for the conversion of authentic doxorubicin, although arginine, histidine, tyrosine, NaHCO3, and Fe(NO3)3 could each generate a form of doxorubicin which did not migrate in TLC analysis. Purification of the nonmigrating form of doxorubicin demonstrated that in vitro conversion resulted in considerable loss of lethality while antiproliferative activity was retained. These observations provide possible explanations for the variability in chemosensitivity determinations and may explain some of the failures to predict clinical responsiveness.

Antioxidants↗
PubMed1984

Radioreceptor assay of neuroleptics in refractory chronic schizophrenic patients.

Radioreceptor assay, a promising new tool for studying serum levels of neuroleptics and their biologically active metabolites, was used to elucidate the role of neuroleptic plasma levels in 24 chronic schizophrenic patients with a poor clinical response to standard treatment. Most of these 24 patients attained serum levels reportedly associated with improvement in more acute patients, suggesting that their lack of response was not due to relative absence of drug in serum. Alternative reasons for lack of response despite adequate plasma levels are discussed.

Adult↗
PubMed1984

Is cerebellar granule cell migration regulated by an internal clock?

We have studied the time course of migratory behavior of cerebellar granule cells in the microwell tissue culture system. [3H]Thymidine served as a marker for particular granule cell generations. When cultured 4 hr after [3H]thymidine injection for 6 days in microwell cultures, labeled granule cells were seen to migrate along fiber bundles expanding between reaggregates called "cables" for 3 to 4 days. After 5 and 6 days in vitro the percentage of labeled non-migrating cells found in clusters in reaggregates and on cables increased considerably. Whereas unlabeled cells continued to migrate. Comparable results were obtained when granule cells developed in vivo for various times after label and their developmental state was determined in vitro. Cells from cerebellar populations labeled 1 to 4 days before culture maintained their ability to migrate in vitro, even after granule cells had entered the internal granule cell layer. In contrast, the percentage of migrating cells labeled 5 and 6 days before culture was reduced significantly. The results suggest that the time span of granule cell migration is predetermined intrinsically rather than by external signals.

Animals↗
PubMed1984

Sequential methotrexate plus 5-FU in advanced breast and colorectal cancers: a phase II study.

Fifty-two patients with advanced breast or colorectal cancer have been treated with methotrexate (MTX) (50 mg/m2) followed 6 hours later by 5-FU (600 mg/m2). The mean serum MTX level immediately prior to 5-FU administration was 1.37 mumols/L (1.37 X 10(-6) M). Of 29 evaluable patients with breast cancer (six of whom had received prior chemotherapy), one achieved a complete response and five achieved a partial response (total response rate, 21%). Among 16 evaluable patients with colorectal cancer (three of whom had received prior chemotherapy), there were no objective responses. Although hematologic toxicity was generally mild, mucositis occurred in 20 patients (severe in three), and at least one early death was attributable to toxicity. These results indicate that at doses of MTX and 5-FU which are in general use in combination chemotherapy for breast cancer, sequential treatment does not have a therapeutic advantage. In colorectal cancer, the same combination is inactive.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Reproducible pneumonia in gnotobiotic piglets induced with broth cultures of Mycoplasma hyopneumoniae and the effect of animal passage on virulence.

The virulence of a laboratory adapted culture of Mycoplasma hyopneumoniae strain NB12 was determined in three- to five-day-old gnotobiotic piglets. Intranasal inoculation or exposure to an aerosol of the culture caused low incidences of pneumonia in the piglets. Passage of M hyopneumoniae strain NB12 in gnotobiotic piglets resulted in a rapid increase in virulence. After only three in vivo passages, severe pneumonia involving most lobes of the lung developed in all inoculated piglets within three and a half weeks. All 49 piglets inoculated with the piglet-passaged NB12 strain in nine subsequent experiments developed pneumonia but the extent of the pneumonic lesions varied considerably from piglet to piglet. The histopathology of the lung lesions was similar to that reported as being induced by other strains of M hyopneumoniae in gnotobiotic piglets and resembled that seen previously in conventionally reared neonatal piglets inoculated with homogenised lung from pigs with enzootic pneumonia. Aspiration pneumonia caused by milk inhalation occurred in some piglets. The pneumonia induced with the piglet-passaged NB12 strain was judged to be suitable for the study of porcine enzootic pneumonia or for the evaluation of chemotherapeutic agents.

Animals↗
PubMed1984

New storage procedure for human tumor biopsies prior to estrogen receptor measurement.

Breast tumor biopsies required for steroid receptor determination are normally frozen in liquid nitrogen and stored until assay. However, some limitations of this type of storage exist. To try to both eliminate the need for liquid nitrogen and as part of a study of serial assays on a single tumor biopsy, alternative storage media were investigated. This study shows that storage of breast tumor biopsies at -20 degrees in sucrose buffer made 50% in glycerol prevented the tissues from freezing, yet retained the specific estrogen receptor content both quantitatively and in terms of molecular form (8S:4S ratio). Receptor was stable for up to 100 days, and individual samples could be successfully reassayed throughout this period. Forty-four biopsies from 40 patients were halved, and one section from each was stored in liquid nitrogen, while the other was stored in sucrose:glycerol. Overall, the correlation of receptor content between the two storage methods was good. Using a clinical cutoff value of 20 fmol/mg cytosol protein, only one sample of the 44 would have been classified differently after storage in the two media. Progesterone receptor in biopsies stored in sucrose:glycerol also appears to be stable for at least a limited period.

Biopsy↗
PubMed1984

Measurement of ferritin-bearing peripheral mononuclear blood cells in cancer patients by radioimmunoassay.

A radioimmunoassay has been developed to measure ferritin bound to the surface of isolated human peripheral blood mononuclear white blood cells (PBMs) in order to investigate the possible relationship of this phenomenon to breast and other forms of cancer. The assay measures the specific binding (%SP) of affinity-purified 125I-labeled rabbit anti-Hodgkin's spleen ferritin antibody to isolated patient PBMs. A preliminary prospective, preclinical trial on 300 patients was run which included: (a) normals, benign breast disease, and medical/surgical patients as non-cancer controls; (b) postoperative primary cancer and advanced cancer in clinical remission as post cancer controls; and (c) both early preoperative breast cancer patients and cancer patients with localized recurrences or active disseminated disease as test groups. The mean %SP for the non-cancer control groups was in the range of 4.3 to 5.1 (n = 187), which was identical to that for inactive cancer or postoperative cancer, which was no evidence of recurrence. Using a %SP normal cutoff level of 6.5, which resulted in a false-positive rate of approximately 10% for both non-cancer and post-cancer control groups, only 27% of early preoperative cancers (n = 22) gave elevated %SP values. These results suggest that measurement of ferritin-PBM is inappropriate for early disease diagnosis. In contrast, 91% of patients with advanced active breast cancer and 73% of those patients with other types of advanced cancers, including tumors of ovarian, lung, colon or esophageal origin, showed elevated %SP values more than double those of post-cancer controls. The mean %SP value in active advanced cancer was 10.8 for breast (n = 12) and 10.6 for all other solid tumors investigated (n = 34). Paired patient comparisons of ferritin-PBM and plasma carcinoembryonic antigen in breast cancer showed elevations in 91% of the patients for ferritin-PBM and 67% for carcinoembryonic antigen. Overall, these results suggest that patients with advanced cancer display elevated levels of ferritin on the surface of their PBMs and that this measurement may be a useful adjunct in monitoring and evaluating the clinical status of cancer patients.

Breast Diseases↗
PubMed1983

Forskolin stimulates the conversion of tyrosine to dopamine in catecholaminergic neural tissue.

Forskolin stimulates the conversion of tyrosine to dopamine in slices and synaptosomes from rat striatum, in synaptosomes from rat hypothalamus, and in slices from bovine retina. In striatal synaptosomes, there is an approximately 80% stimulation of dopamine formation from tyrosine, but no effect with DOPA as substrate, suggesting that the effect is on tyrosine hydroxylase. Stimulation is saturable with a half-maximal effect at under 1 microM forskolin. Forskolin stimulation is additive with, and hence independent of , activation due to KCl, but not that due to dibutyryl-cyclic AMP. Stimulation of dopamine synthesis by forskolin may provide an approach for elucidating the regulation of the adenylate cyclase system associated with catecholaminergic nerve endings.

Animals↗
PubMed1983

Improved procedure for the determination of protein binding by conventional equilibrium dialysis.

The binding of drugs to plasma proteins has been studied extensively using a variety of methods, including equilibrium dialysis. Published information on controls used in these studies is frequently inadequate; in other cases, there are deficiencies in the experimental design for the controls. A method is described that eliminates many of the problems associated with artifactual errors in dialysis studies. Multiple replicated controls are performed at the same time as the test, under identical conditions. The controls are used to correct for concentration-dependent binding of drug to the membrane or other equipment. The method was used to determine the binding of sulfadimethoxine to CF-IV-1 alpha-globulin at therapeutic concentrations. The level of binding was low (9-13%), but the stringent control technique permitted statistical analysis which showed each mean test value to be significantly different from its corresponding control. Furthermore, there was a linear relationship between the control-corrected percentage binding values and total drug concentration, whereas there was no correlation between total drug concentration and the uncorrected percentage binding values.

Blood Proteins↗