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Biomedical subjects

M E Phillips

Publications and source records attributed to M E Phillips.

At least 19 recordsLinked to original sources
PubMed1992

Effect of colcemid on the water permeability response to vasopressin in isolated perfused rabbit collecting tubules.

1. The effect of the microtubule-disruptive agent, colcemid (N-deacetyl-N-methyl-colchicine), on the water permeability response to vasopressin has been investigated in isolated cortical collecting tubules from the rabbit kidney perfused in vitro. 2. Pretreatment of collecting tubules with colcemid inhibited the increase in water permeability elicited by vasopressin, 50 microU ml-1, in a time- and dose-dependent manner. After 75 min exposure to the drug, inhibition of the response to the hormone averaged 72 +/- 6% (n = 4, P < 0.01) at a colcemid concentration of 7.2 x 10(-5) M. Inhibition was estimated to be half-maximal at a colcemid concentration of 1.9 x 10(-6) M. 3. Colcemid, 2.7 x 10(-7) to 7.2 x 10(-5) M, had no effect on basal water permeability nor on the increase in lumen negative potential difference (PD) induced by the hormone. 4. Lumicolcemid, an isomer of colcemid that does not disrupt microtubules, had no influence on the water permeability response to vasopressin. 5. Pretreatment with colcemid, 2.7 x 10(-5) M, for 45 min inhibited the water permeability response to 8-CPT-cAMP, 1.8 x 10(-5) M, by 38 +/- 4% (n = 5, P < 0.01). 6. When collecting tubules were exposed to colcemid, 5.5 x 10(-5) M, for 45 min after the hydrosmotic response to vasopressin had been established, the drug had no influence on the maintenance of the raised water permeability. 7. The results provide further evidence that cytoplasmic microtubules play a role in the initiation of the hydrosmotic response to vasopressin in the mammalian collecting tubule at a site distal to the generation of cyclic AMP.

Animals↗
PubMed1992

Identification of risk factors for radiographic hyperparathyroidism in 422 patients with end-stage renal disease: development of a clinical predictive index.

The hand radiographs of 422 patients with end-stage renal failure were graded for severity of subperiosteal resorption. Two hundred and seventy-three patients (64.7%) had no evidence of resorption; 114 (27.0%) showed resorption, in 32 of whom it was severe (7.6% of the total). Thirty-five patients (8.3%) were assessed as having doubtful evidence of subperiosteal resorption. Age, gender, race, renal diagnosis, duration of renal failure and vitamin D status were assessed as potential risk factors for the development of subperiosteal resorption. Duration of renal failure, female gender, young age, and certain renal diagnostic groups namely obstructive uropathy, unknown diagnosis, presumed glomerulonephritis and tubulointerstitial disease emerged as independent risk factors. Diabetic patients appeared to be least at risk of developing subperiosteal resorption. Patients whose renal failure was of unknown duration showed a degree of risk similar to those whose duration was < 2 years. In order to identify prospectively patients likely to develop subperiosteal resorption by the time they reach renal replacement therapy, the relative risks were used to create a risk index. Use of such an index might allow prophylactic treatment to be given to those particularly at risk. The concept of a risk index requires testing by a prospective study, which is in progress.

Adolescent↗
PubMed1991

Studies on the cellular origin of neurothekeoma: clinical, light microscopic, immunohistochemical, and ultrastructural observations.

The clinical, histopathologic, and immunohistochemical features of 11 cases of neurothekeoma are reported. One case was examined by electron microscopy. The mean age of the patients was 27.1 years; the study comprised eight female and three male patients. Most lesions were nondescript papules and located on the upper part of the body, seven cases of neurothekeoma on the head. Eight cases were classified as cellular neurothekeoma on the basis of a striking fascicular pattern and three cases as myxomatous neurothekeoma because of prominent myxoid stromal change. All cellular neurothekeomas failed to express S-100 protein, whereas the three myxomatous types were strongly positive for this marker. Other than vimentin, there was no significant immunoreactivity with other immunohistochemical markers. Ultrastructural study of one case of cellular neurothekeoma was inconclusive for cell type although a perineurial origin could not be excluded. On the basis of these results, we conclude that cellular neurothekeoma differs from myxomatous neurothekeoma not only by clinical and histologic findings but also by immunoreactivity with S-100 protein. These findings also suggest the existence of two distinct subtypes of neurothekeoma and possible origin of the two variants of neurothekeoma from different cell types or at least variation in phenotypic expression of a common cell type. On the other hand, it cannot be excluded that these two variants are different stages in the natural history of neurothekeoma.

Adolescent↗
PubMed1991

Racial origin and primary renal diagnosis in 771 patients with end-stage renal disease.

A total of 771 individuals with end-stage renal disease treated at one centre from 1964 to 1990 were studied. Data on racial origin, gender, age, and primary renal diagnosis were analysed. The male: female ratio (468:303) and proportions of individuals in different diagnostic groups (renal diagnosis based on European Dialysis and Transplant Association (EDTA) groups) were similar to EDTA data for the UK as a whole. Racial distribution was Caucasian 79.0%, Indian subcontinent (Is-c) 12.7%, Caribbean, 5.6%, African 1.6% and other Asian 1.2%. In Britain individuals from the Is-c constitute 2.2% of the general population and those from the Caribbean 1.0%. We found differences in the distribution of primary renal disease among patients from different racial groups. Adult polycystic kidney disease was almost entirely confined to Caucasians (75 to 79 patients). Diabetic nephropathy was relatively more common in individuals (especially males) from the Is-c. Hypertensive renal disease was relatively more common in those of Caribbean descent and in Africans, whilst 'Unknown diagnosis' was most common in patients from the Is-c.

Adolescent↗
PubMed1990

Noninvasive monitoring of renal blood flow characteristics during acute renal failure in man.

Duplex Doppler ultrasound (DDU) was used to study the blood flow characteristics of the renal interlobar artery in 20 subjects with acute renal failure (ARF), 14 subjects with transient impairment of renal function and 23 control subjects with normal function. Renovascular resistance was assessed by pulsatility index (PI) and change in flow velocity by change in mean frequency shift (delta f). The 99% confidence intervals for PI in the three groups were 3.32-5.46, 1.58-2.34 and 0.99-1.33 respectively. Values for delta f were 0.2-0.38, 0.5-0.62 and 0.7-1.02 kHz respectively. Ten ARF patients recovered function, 99% confidence intervals for PI just prior to recovery were 0.9-1.48 and for delta f 0.52-1.02 kHz. There was increased renovascular resistance and reduced intrarenal blood flow velocity at the onset of ARF. These changes persisted during ARF; recovery of function occurred after they returned to normal. Similar, but less marked, changes were found in patients with a transient impairment of function.

Acute Kidney Injury↗
PubMed1990

Cutaneous manifestations of the L-tryptophan-associated eosinophilia-myalgia syndrome: a spectrum of sclerodermatous skin disease.

The natural history of the clinical and pathologic features of skin disease was reviewed prospectively in 30 patients with the L-tryptophan-associated eosinophilia-myalgia syndrome. Overall, cutaneous manifestations developed in 26 patients (87%). Early lesions were nonspecific and characterized predominantly by an erythematous macular eruption on the trunk and extremities. The most characteristic abnormality noted was the spectrum of sclerodermatous disease in 15 patients (50%) often after a subacute stage of peripheral or truncal edema. Clinical and/or biopsy evidence of eosinophilic fasciitis was seen in nine patients (30%). Findings consistent with diffuse, limited, or localized scleroderma were subsequently observed in nine patients (33%). Small mucinous papules, similar to those seen in scleromyxedema, were found in five patients (17%). Alopecia, frequently a late sequela, developed in 11 (37%). Common histologic features included papillary dermal fibrosis, dermal and fascial infiltrates consisting of mononuclear cells and eosinophils, deposition of glycosaminoglycans in the dermis, and, in some patients, numerous mast cells.

Adult↗
PubMed1989

The effects of ionophore A23187 on permeability of the frog mesentery microvasculature.

The effects of the divalent cation ionophore A23187, upon microvascular permeability have been investigated in single perfused capillaries and venules in the mesenteries of pithed frogs. In all experiments, the vessels were perfused with Ringer solutions containing the macromolecules Ficoll 70 (40 mg ml-1) and bovine serum albumin (10 mg ml-1). Hydraulic permeability (Lp) of the vessel walls and the effective osmotic pressure (sigma delta pi) exerted across them by the perfusate macromolecules were estimated by the method of Michel (1980). In eleven experiments addition of A23187 to the perfusate raised Lp from a mean value (+/- S.E.M.) of 4.76 (+/- 1.05) x 10(-7) cm s-1 cmH2O-1 to one of 11.97 (+/- 1.96) x 10(-7) cm s-1 cmH2O-1 and reduced sigma delta pi from a mean (+/- S.E.M.) of 16.5 (+/- 2.01) cmH2O to one of 7.6 (+/- 1.93) cmH2O. The effects of A23187 on Lp and sigma delta pi were reversible. A23187 was found to increase Lp and reduce sigma delta pi after the mesentery had been exposed to compound 48/80 to degranulate the mast cells two or more hours previously. A23187 also appeared to be effective in raising Lp and lowering sigma delta pi in the absence of Ca2+ ions from the perfusate and superfusate. The ionophore was found to reduce permeability, however, when Mg2+ ions were removed from the perfusate and superfusate both in the absence and in the presence of Ca2+. This reduction in permeability could be converted into an increase in Lp and fall in sigma delta pi if Mg2+ were restored to the superfusate. It is concluded that A23187 increases vascular permeability in a reversible manner and that Mg2+ ions in the extracellular fluids are necessary for its action.

Animals↗
PubMed1989

Effect of nocodazole on the water permeability response to vasopressin in rabbit collecting tubules perfused in vitro.

1. The effect of the microtubule-disruptive agent, nocodazole (methyl [5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl] carbamate), on the water permeability response to vasopressin or the synthetic cyclic AMP analogue, 8-parachlorophenylthio-cyclic AMP (8-CPT-cAMP), has been investigated in isolated cortical collecting tubules from rabbit kidneys, perfused in vitro. 2. Pre-treatment with nocodazole, 1-4 micrograms ml-1, had no significant effect on basal water permeability, but inhibited the increase in hydraulic conductivity elicited by vasopressin, 50 microU ml-1, in a dose-dependent manner. Inhibition of the response to the hormone averaged 65 +/- 6% (n = 8, P less than 0.001) at a nocodazole concentration of 4 micrograms ml-1. 3. Nocodazole, 1-4 micrograms ml-1, had no effect on the increase in lumen-negative potential difference (PD) induced by the hormone. 4. Pre-treatment with nocodazole, 4 micrograms ml-1, inhibited the development of the water permeability response to 8-CPT-cAMP, 1.8 x 10(-5) M, by 45 +/- 7% (n = 7, P less than 0.001). 5. When collecting tubules were exposed to nocodazole, 4 micrograms ml-1, after the hydrosmotic response to vasopressin had been fully established, the drug had no inhibitory effect on the maintenance of a high water permeability. 6. The results are consistent with the view that cytoplasmic microtubules play a role in the initiation of the water permeability response to vasopressin in the mammalian cortical collecting tubule at a cellular site beyond the generation of cyclic AMP.

Animals↗
PubMed1989

Sonography of acute appendicitis: a critical review.

In 20% of the cases of acute appendicitis, especially in children, the elderly, and ovulating women, the findings are atypical. The radiographic procedures used to aid in the diagnosis have not been proven reliable. Sonography has often been used to diagnose or rule out appendiceal abscesses, or diseases that can mimic acute appendicitis, such as gynecologic, obstetric, or biliary abnormalities. Recently, high-resolution sonography with graded compression has been shown to be very helpful in the diagnosis of acute appendicitis in several studies. High-resolution 5- to 7.5-MHz transducers are used to compress the bowels, displace the interfering gas in the right lower quadrant, and directly visualize the inflamed appendix with a sensitivity that varies from 80 to 95%, a specificity of 95 to 100%, and an accuracy of 91 to 95%. It is also possible to differentiate acute appendicitis from the gangrenous and perforated appendix. High-resolution sonography is currently the diagnostic method of choice for appendicitis, particularly in patients with equivocal clinical findings. The technique, normal and pathologic anatomy values, and limitations of sonography are discussed.

Acute Disease↗
PubMed1988

Growth factor involvement and oncogene expression in prostatic tumours.

The effects of EGF, TGF alpha and 5 alpha-dihydrotestosterone on the growth of a prostatic epithelial cell line have been evaluated in clonal growth assays. Similar bioassay systems have been used to identify tumour-associated growth promoters derived from a human prostatic carcinoma cell line (PC3). Growth factor activity was associated with proteins of Mr 20-30 kDa. In a separate study, EGF receptor concentration and cellular proto-oncogene expression was assessed in prostatic tumour samples. In prostatic carcinoma samples, strong correlation was observed between EGF receptor concentration and c-myc expression. There were no significant correlations between EGF receptor concentration and tumour grade or androgen receptor content in carcinoma samples. EGF receptor concentration was significantly higher in prostatic carcinoma specimens than in BPH.

Animals↗
PubMed1988

Growth factor receptors and oncogene expression in prostate cells.

Specimens of benign prostatic hypertrophy (BPH) and prostate carcinoma and prostate cells in culture were assessed for their capacity to bind androgens, radioiodinated EGF, and IGF-I, and to express certain cellular protooncogenes. Prostate cell lines contained receptors for both EGF and IGF-I. Similarly, clinical samples of human diseased prostate contained receptors for both of these factors. Prostate carcinoma contained higher concentrations of EGF receptors based on DNA than did BPH, although it is accepted that BPH may not be the appropriate comparison for carcinoma. Increased EGF receptors were associated circumstantially with a decline in androgen receptors with deteriorating differentiation status and with an increase in expression of c-myc. Androgen receptor concentration correlated with increased expression of c-fos. Deteriorating differentiation status was associated with the appearance or increase in secondary sites with lower affinity for IGF-I. Whereas c-myc expression was increased in all grades of carcinoma compared to BPH, expression of c-H-ras accompanied loss of differentiation. Although those alterations are hindered by tissue heterogeneity and correlations are essentially circumstantial, they may provide clues to the progression of prostate cancer that can be validated in prostate cell lines with similar growth response capabilities.

Animals↗
PubMed1988

Inflammatory changes in permeability and ultrastructure of single vessels in the frog mesenteric microcirculation.

1. In fifteen experiments, single microvessels in the exposed mesenteries of pithed frogs were perfused with Ringer solutions containing bovine serum albumin (40 mg ml-1). For each vessel, the hydraulic permeability of its walls (Lp) and effective osmotic pressure exerted across them (sigma delta pi) were determined from measurements of fluid filtration rates at two capillary pressures (Michel, Mason, Curry, Tooke & Hunter, 1974) before and at predetermined times after the tissue temperature had been raised abruptly from approximately 15 degrees C to 30-35 degrees C. Temperatures greater than 30 degrees C appear to damage the tissues of frogs acclimatized to temperatures of 5-10 degrees C. 2. In fourteen out of fifteen experiments Lp rose when the temperature was raised to 30-35 degrees C. In twelve of these experiments the increase in Lp was greater than expected from the fall in water viscosity with temperature, and was progressive. In five vessels where measurements were made 1-2 min after tissue temperature was raised, Lp increased from an initial mean value (+/- S.E.M.) of 3.76 (+/- 0.54) x 10(-3) micron s-1 cmH2O-1 to one of 8.72 (+/- 1.68) x 10(-3) micron s-1 cmH2O-1. In nine vessels where measurements were made at 10 min after tissue temperature was raised, Lp increased from an initial mean value of 4.03 (+/- 0.72) x 10(-3) micron s-1 cmH2O-1 to one of 16.9 (+/- 3.5) x 10(-3) micron s-1 cmH2O-1. Further increases in Lp were seen at 15 and 20 min. 3. The changes in the effective osmotic pressure opposing filtration, sigma delta pi, were very variable. Out of the twelve vessels which showed large changes in Lp with tissue heating, four showed no reduction in sigma delta pi after 10 min, though sigma delta pi fell in three of these vessels at 15 min. In the other eight vessels, sigma delta pi fell as Lp rose. A quantitative theory developed in this paper allowed the changes in sigma delta pi to be analysed in terms of a component across the regions of vessel wall of increased permeability (sigma H delta pi H) and a component across regions where Lp was unchanged. In six vessels sigma H delta pi H approximated to zero; in two vessels sigma H delta pi H was 6.2 and 4.5 cmH2O.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

A biologically active parathyroid hormone-like substance secreted by an adenosquamous carcinoma of the transverse colon.

Recently, controversy has emerged as to whether paraneoplastic hypercalcemia in nonparathyroid tumors is due to ectopic production of a parathyroid hormone (PTH)-like substance. A sensitive DNA hybridization technique was unable to reveal PTH mRNA in a collection of such tumors. However, there is growing evidence that squamous differentiation of tumors favors the expression of PTH-like substances. We report the case of a 41-year-old woman with an adenosquamous carcinoma of colonic origin associated with severe hypercalcemia. The squamous component of liver metastases showed immunoreactivity with two different PTH antisera, suggesting the production of a PTH-like substance.

Adenocarcinoma↗
PubMed1987

Effect of albumin on the osmotic pressure exerted by myoglobin across capillary walls in frog mesentery.

1. Individual capillaries in mesenteries of pithed frogs were perfused sequentially with two frog Ringer solutions containing myoglobin at a concentration of 70 mg/ml. The first perfusate solution contained bovine serum albumin at a concentration of 10 mg/ml. The second perfusate contained no albumin. The modified Landis micro-occlusion technique (Michel, Mason, Curry & Tooke, 1974) was used to measure the capillary hydraulic conductivity and the effective osmotic pressure of the myoglobin solution across the capillary wall under conditions where the transcapillary concentration difference was established by steady-state ultrafiltration. 2. In six capillaries the effective osmotic pressure of the myoglobin solution at 20-22 degrees C was 15.9 +/- 2.2 (S.E. of mean) cmH2O when albumin was in the perfusate and 10.1 +/- 1.1 cmH2O after albumin was removed from the perfusate. 3. The hydraulic conductivity of the capillary wall increased from a mean value of 6.5 +/- 1.4 X 10(-7) cm/(s cmH2O) when albumin was in the perfusate to 15.6 +/- 3.8 X 10(-7) cm/(s cmH2O) during perfusion with Ringer solution containing myoglobin alone. 4. Control experiments to measure steady-state filtration rates at pressures 10-30 cmH2O were carried out to check the assumption in the method that the reduction in the measured osmotic pressure of myoglobin was the result of changes in the properties of the molecular sieve within the capillary wall and was not simply the result of solute accumulation on the tissue side of the capillary wall. 5. The measured reduction in the effective osmotic pressure of myoglobin when albumin was removed from the perfusate does not conform to the hypothesis (Crone, 1984) that the tight segment of the intercellular junction is the principal molecular filter for myoglobin in the wall of frog mesenteric capillaries. 6. Our results do conform to the hypothesis that a network of fibrous molecules, reinforced by adsorbed albumin, forms the principal molecular filter at the capillary wall in frog mesenteric capillaries.

Albumins↗
PubMed1987

Steady-state fluid filtration at different capillary pressures in perfused frog mesenteric capillaries.

1. The theory of steady-state filtration through capillary walls (Michel, 1984) has been developed and investigated in experiments on single capillaries of the frog mesentery perfused with Ringer solutions containing bovine serum albumin (BSA) and Ficoll 70. 2. In each experiment, the micro-occlusion technique of Michel, Mason, Curry, Tooke & Hunter (1974) has been used to investigate the relation between fluid movements per unit area of capillary wall (Jv/A) and capillary pressure (Pc) under two sets of conditions in the same vessel. First, the relation has been determined following brief perfusions, where the difference in oncotic pressure across the capillary wall approximated to the perfusate oncotic pressure at all values of Pc. These results are referred to as the transient data. Secondly, the relation was investigated by estimating Jv/A at values of Pc which had been maintained constant during at least 2 min of perfusion prior to the measurement. Under these conditions the concentration of macromolecules in the pericapillary fluid was determined by the steady-state composition of the filtrate passing through the capillary wall, and these results are referred to as steady-state data. 3. In all fifteen capillaries investigated, the relationship between Jv/A and Pc was linear for the transient data and conspicuously non-linear in the steady state. When Pc exceeded the oncotic pressure of the perfusate, steady-state values for Jv/A lay slightly above but parallel to the transient values for the same vessel. At values of Pc less than the perfusate oncotic pressure, the transient data showed reabsorption of fluid from the tissues, but in the steady state either fluid movements were so small as to be undetected or slight filtration was observed. The steady-state data followed the pattern predicted by theory. 4. The transient data were used to estimate the reflection coefficient of the capillary wall (sigma) to the macromolecular solute. In seven vessels, the mean sigma to BSA was 0.76 (S.E. of mean +/- 0.04) and in eight different vessels mean sigma to Ficoll 70 in the presence of BSA (10 mg ml-1) was 0.98 (S.E. of mean +/- 0.05). The steady-state data were consistent with the prediction that the oncotic pressure opposing high filtration rates approximates to sigma 2 pi c in the steady state, where pi c is the perfusate oncotic pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗