Plasma membranes purified 32- to 45-fold were isolated from leukaemic T-lymphoblasts, both sensitive and resistant to the Vinca alkaloid vinblastine. On development of drug resistance there was a very significant elevation of ether lipid content. 1-0-alkyl phospholipid increased by 200% with a smaller 30% increase in 1-0-alkenyl phospholipid. Cholesterol and phospholipid levels were also found to increase by 50% and 30% respectively, while the lipid to protein ratio increased by 60%. More modest changes were observed in the fatty acid composition of the membranes, with an alteration in the double bond index from 35.3 to 41.2. These lipid changes may have important implications in the changes to membrane permeability that develop with drug resistance.
Biopsy specimens of the uterine cervix, including colposcopically directed punch biopsy specimens of females with atypical Papanicolaou smear tests, are suitable for analysis by magnetic resonance (MR) spectroscopy. A narrow lined lipid MR spectrum, characteristic of malignant tissue, is obtained from a 6-mm3 biopsy specimen of histologically confirmed squamous carcinoma of the cervix. In contrast, specimens containing inflammatory cells generate a broad component only centered at 1.3 ppm with a T2 relaxation value of less than 350 ms. Most biopsy specimens which contain dysplastic cells or evidence of human papilloma virus (HPV) infection have a discernible lipid spectrum similar to that of the malignant tissue specimen. Long T2 relaxation values found in malignant tissue specimens at 1.3 and 1.2 ppm are observed in some but not all of the biopsies which show evidence of HPV infection. The suitability of small tissue samples, such as punch biopsy specimens, for study by MR illustrates the sensitivity of this technique and its potential as an aid to histopathological discrimination between the various precursor states of cervical cancer.
Tubular sodium handling and tubuloglomerular feedback (TGF) activity were assessed in established compensatory renal hypertrophy in Sprague Dawley rats. Hyperfiltration at the level of the single nephron was confirmed 4-6 weeks following a reduction in renal mass. TGF activity, determined as the difference between late proximal and early distal measurements of single-nephron glomerular filtration rate (SNGFR), was significantly increased in compensatory renal hypertrophy, being 7.8 +/- 1.0 vs 23.3 +/- 1.9 vs 25.5 +/- 2.6 nl/min (P for analysis of variance less than 0.05) following sham operation, unilateral nephrectomy, and 1 1/3 nephrectomy, respectively. Enhanced net tubular Na transport was also observed, with total Na reabsorption up to the late proximal site being 1.8 +/- 0.2 vs 2.7 +/- 0.1 vs 3.1 +/- 0.3 nmol/min (P less than 0.05), and to the early distal site being 3.4 +/- 0.5 vs 5.8 +/- 0.6 vs 7.9 +/- 0.8 nmol/min (P less than 0.05) in the three animal groups respectively. Comparison of proximal tubular length demonstrated a 71.9 +/- 8.1% increase in uninephrectomised vs sham-operated animals. This increase was proportionately greater than the increase in proximal Na reabsorption (50.0 +/- 4.0%) observed in the corresponding animal groups. Concurrent electron microprobe experiments in uninephrectomised and sham-operated animals demonstrated that the proximal tubular intracellular Na concentration was significantly lower following uninephrectomy (16.8 +/- 0.6 vs 18.9 +/- 0.5 mmol/kg wet weight, P less than 0.01), in association with evidence of reduced basolateral Na/K-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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