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Biomedical subjects

K Pittman

Publications and source records attributed to K Pittman.

12 recordsLinked to original sources
PubMed1991

Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction.

Only small numbers of cells from solid tumours are needed for haematogenous metastasis. Detection is difficult because existing techniques are not sensitive enough. We have used reverse transcriptase to make complementary DNA from peripheral blood messenger RNA, and the polymerase chain reaction (PCR) to amplify cDNA specific for a gene actively transcribed only in the tumour tissue type. We prepared cDNA from peripheral blood of seven patients with malignant melanoma, four patients with other metastatic cancers, and four healthy subjects, as well as from several melanoma-derived cell lines. PCR was used to amplify the gene for tyrosinase, a tissue-specific gene in melanocytes. Since normal melanocytes are not thought to circulate in peripheral blood, detection of tyrosinase transcription in peripheral blood should indicate the presence of circulating cancer cells. The method was highly sensitive and could detect a single melanoma cell from a cell line in 2 ml normal blood. Blood samples from four of the seven patients with malignant melanoma gave positive results, whereas all eight control subjects gave negative results. This method does not depend on the characterisation of cancer-specific genetic abnormalities and can be applied to any cancer for which tissue-specific genes can be identified, including epithelial cancers. It could prove useful in the diagnosis of primary or metastatic cancers, in assessing prognosis, and in detecting residual disease after treatment.

Amino Acid Sequence↗
PubMed1982

Dissociation of the contributions of the prefrontal cortex and dorsomedial thalamic nucleus to spatially guided behavior in the rat.

Rats with lesions of the medial frontal cortex or dorsomedial nucleus of the thalamus (MD) were studied in two spatial localization tasks: the Morris water task and the 8-arm radial arm maze. Rats with medial frontal lesions failed to learn to swim from different locations to a hidden platform located at a specific place in a large tank (Morris task) and were impaired at learning the location of reward in the radial arm maze. Rats with MD lesions were not impaired at spatial orientation in either task. The results provide the first unequivocal evidence of a spatial orientation deficit following frontal lesions and lend support to the notion that the frontal cortex forms part of a 'spatial mapping system'. The results suggest that although MD is the major afferent to the frontal cortex, it does not provide necessary spatially-relevant input.

Afferent Pathways↗
PubMed1982

A phase I and clinical pharmacology study of intravenously administered carminomycin in cancer patients in the United States.

Carminomycin (CMN) was administered i.v. to 44 patients with a variety of nonhematological cancers every 4 weeks at doses of 15, 20, 22.5, and 25 mg/sq m. Granulocytopenia was the dose-limiting toxicity. The median granulocyte count for previously untreated patients receiving 22.5 mg/sq m was 0.962 cells/microliters, and for previously treated patients receiving 20 mg/sq m it was 0.420 cell/microliters. Moderate to severe phlebitis was associated with drug administration in 50% of cases. Nausea, vomiting, and alopecia were mild. Three of nine patients who received a total CMN dose of greater than or equal to 100 mg/sq m (mean, 132 mg/sq m) developed unexplained decreases in radionuclide cardiac ejection fraction, with one patient developing decreased QRS amplitude and congestive heart failure at a total dose of 160 mg/sq m. CMN is rapidly metabolized to carminomycinol. The elimination half-lives of CMN and carminomycinol are 6 to 10 and 50 hr, respectively. CMN was found to be a more potent inhibitor of human granulocyte-macrophage colony-forming units than was carminomycinol. Objective partial responses were seen in two of seven previously untreated patients with non-small cell lung cancer and one of three patients with squamous cell carcinoma of the head and neck previously untreated with chemotherapy.

Adult↗
PubMed1977

Species differences in the hepatic response to mirex: ultrastructural and histochemical studies.

Mirex was fed at levels of 1, 5, 15, and 30 ppm to mice, 5 and 30 ppm to rats, while monkeys received the chemical by stomach tube at levels of 0.25 and 1 mg/kg (equal to 5 and 20 ppm). Mice were killed and their livers obtained at 2, 4, 6, 9, 10, 15 and 18 months, whereas rats were killed and surgical biopsies were taken at 16, 19, 26, and 36 months. Cytochemical techniques were employed to detect activities of lysosomal beta-glycerol phosphatase (ACpase) and glucose 6-phosphatase (G-6-pase). ACpase and G-6-pase remained unchanged and comparable to controls in livers of mice receiving 1 ppm. G-6-pase decreased in centrilobular areas while ACpase increased with time in the higher groups. At 12 months, liver cells that lost their G-6-pase activity surrounded by Kupffer cells that contained strong ACpase. In contrast, rat livers had no increase in ACpase and little loss in G-6-pase. Surprisingly, and in spite of the high levels of mirex ingested, monkey livers showed no loss of G-6-pase or activation of ACpase. Ultrastructurally, the underlying feature in all livers was proliferation of smooth endoplasmic reticulum (SER) displaying species variation. Thus, in mice, intense proliferation of SER that was both time- and dose-dependent was localized in specific regions of the cytosol. Hepatic cells, damaged and necrotic in mice fed 5, 15, and 30 ppm, were phagocytosed by activated Kupffer cells. SER proliferation in rat and monkey liver cells was less conspicuous than in mice. Except for this change, rat and monkey liver cells were normal. There studies emphasize species and enzyme variations in response to mirex. An interesting aspect observed was the lack of lysosomal catabolism during liver enlargement.

Acid Phosphatase↗