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Biomedical subjects

M E Phillips

Publications and source records attributed to M E Phillips.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1987

Prostatic disorders: MR imaging at 1.5 T.

Pelvic magnetic resonance (MR) images obtained at 1.5 T of 31 men with known genitourinary disease were reviewed retrospectively. In most, peripheral and central prostatic zones could be seen on axial images obtained with long repetition times/echo times (TRs/TEs). The prostate had no specific signal intensity that enabled differentiation between benign and malignant changes. Each patient with known extracapsular prostatic carcinoma had a peripheral zone defect--1 cm or greater in diameter with ill-defined borders and relatively lower signal intensity than that of the remainder of the peripheral zone--that correlated with the site of clinical-pathologic involvement. Correlation of a peripheral zone defect on long TR/TE images as a sign for extracapsular spread of prostatic cancer was 100% sensitive, yet 54% specific, with excellent interobserver agreement. Stage A2 and B1 prostatic carcinoma was not detected. Benign prostatic hyperplasia was seen as centrally located proliferation and nodularity, usually with discrete margins and a wide spectrum of low- to high-signal-intensity features. MR imaging may have a role in differentiating between intracapsular and extracapsular prostatic carcinoma.

Adult↗
PubMed1987

Normal prostate and adjacent structures: MR imaging at 1.5 T.

Pelvic magnetic resonance images obtained at 1.5 T of 29 male patients with no known genitourinary tract disease were retrospectively reviewed. Normal anatomic features of the prostate and its adjacent structures were studied with spin echo techniques with short and long repetition times/echo times (TR/TE). Long TR/TE (T2-weighted) images routinely showed differentiation of peripheral and central prostatic zones, as well as a separate periprostatic venous plexus. Guidelines were developed to optimize imaging of the relationship of the prostate to adjacent structures.

Adult↗
PubMed1987

Intranuclear androgen receptor deployment and protooncogene expression in human diseased prostate.

Androgen receptors were quantified in nuclei from human prostate tissue and in nuclear fractions derived by exhaustive digestion with micrococcal nuclease. In nuclei from benign hypertrophic prostate (BPH), the population of androgen receptors solubilized during nucleolysis predominated whereas in carcinoma nuclei the nuclease-resistant population was in excess. This phenomenon was restricted to intranuclear deployment and could not be attributed to recompartmentalization within the cell. Receptor content could not be correlated to the expression of the cellular protooncogenes myc, H-ras, K-ras or sis, in either BPH or carcinoma. However, in both BPH and carcinoma, significant correlation was observed between nuclear androgen receptor content and expression of c-fos. Expression of c-fos was not elevated in carcinoma compared to BPH, whereas expression of c-myc was elevated in carcinoma specimens of all grades of glandular differentiation, and expression of H-ras became increasingly elevated as differentiation was lost.

Cell Nucleus↗
PubMed1986

The spectrum of minimal deviation melanoma: a clinicopathologic study of 21 cases.

A retrospective study of 21 patients with the histopathologic diagnosis of minimal deviation melanoma (MDM; n = 18) and borderline melanoma (BM; n = 3) was undertaken to determine the prognosis for these patients compared with that for patients with other types of malignant melanoma. The findings indicate that the prognosis for these uncommon nevomelanocytic tumors is somewhat better than that for other malignant melanomas. Follow-up periods in this series ranged from 18 to 96 months (mean, 57 months). Primary lesions ranged in thickness from 1.6 to 10.4 mm. The histopathologic subtypes included the Spitz variant (nine patients), the spindle cell variant (six patients), the combined spindle and epithelioid cell type (three patients), and the small epithelioid cell type (three patients). Only two of the patients died of widespread metastatic disease. Comparison of the histologic and clinical prognostic indicators of mortality in patients who have malignant melanoma with the clinical and pathologic features seen in this series of 21 patients would appear to indicate a diminished tendency toward metastatic or recurrent disease in patients with MDM and BM.

Adolescent↗
PubMed1985

The effects of bovine serum albumin and a form of cationised ferritin upon the molecular selectivity of the walls of single frog capillaries.

Single frog mesenteric capillaries have been perfused with Ringer solutions containing the neutral macromolecule Ficoll 70 at a concentration of 40 mg ml-1, while the tissues have been washed with Ringer solution containing no macromolecules but otherwise of similar composition. The effective osmotic pressures (sigma delta II) set up across the capillary wall by the Ficoll 70 were used to assess the wall's molecular selectivity. The hydraulic conductivities, Lp, of the capillary walls were also measured. In seven capillaries the addition of bovine serum albumin (BSA) to the perfusate at concentrations of 1 and 10 mg ml-1 increased sigma delta II from a mean value of 7.14 +/- 1.81 cm H2O to one of 18.71 +/- 2.33 cm H2O and at the same time halved Lp. In another eight capillaries, the addition of a form of cationised ferritin (CF) to the perfusate at a concentration of 1 mg ml-1 increased sigma delta II from a mean value of 5.69 +/- 0.87 cm H2O to one of 16.69 +/- 0.262 cm H2O and reduced Lp to between a third and a half of its original value. In a further seven capillaries, the addition of native ferritin at a concentration of 1 mg ml-1 to the perfusate had no effect on either sigma delta II or Lp. It is suggested that both CF and BSA increase the reflection coefficients of capillary walls to Ficoll 70 by binding to the surface coat of the endothelium. The results are discussed in terms of a development of the fiber matrix theory of Curry and Michel (1980).

Animals↗
PubMed1985

The effects of native and modified bovine serum albumin on the permeability of frog mesenteric capillaries.

Single capillaries in the mesenteries of pithed frogs were perfused sequentially with two frog Ringer solutions. The first solution contained no protein; the second solution contained either native or chemically modified bovine serum albumin (BSA) at a concentration of 3-5 mg ml-1. During each perfusion capillary permeability was assessed from the hydraulic conductivity of the capillary wall (Lp) which was determined from measurements of fluid filtration rate at two or more different capillary pressures (Michel, Mason, Curry, Tooke & Hunter, 1974). Lp measured during perfusion with protein-free Ringer solution was on average three times greater than its value for the same vessel perfused with Ringer solution containing native BSA. This confirms the findings of Mason, Curry & Michel (1977). BSA, which had been succinylated to modify the free amino groups of its lysine residues, appeared to be as effective as native BSA in reducing Lp. After modification of its arginine side chains by exposure to 1,2-cyclohexanedione (CHD) in the presence of 0.2 M-NaOH, BSA lost its property of reducing Lp in capillaries perfused with Ringer solution. Exposure of BSA to 0.2 M-NaOH followed by dialysis against normal Ringer solution did not affect its property of reducing Lp. CHD-treated BSA at a concentration of 2.5 mg ml-1 had no effect upon the effective osmotic pressure exerted across capillary walls by Ringer perfusates containing the neutral polymer Ficoll 70 at a concentration of 40 mg ml-1. Native BSA raised the effective osmotic pressure from 7.07 +/- 1.93 cmH2O to 20.50 +/- 2.37 cmH2O (n = 7; P less than 0.001). It is concluded that the effects of BSA on permeability depend upon specific sites in the BSA molecule. It is suggested that these sites involve positively charged arginine side chains of the albumin molecule. The results are discussed in terms of the fibre-matrix hypothesis of capillary permeability and in terms of Brown's (1976) theory for the structure of albumin.

Animals↗
PubMed1984

Rhabdomyolysis and acute renal failure in chronic alcoholics with myopathy, unrelated to acute alcohol ingestion.

Rhabdomyolysis leading to acute renal failure necessitating hemodialysis is described in three chronic alcoholics. In each case an acute medical or surgical event, but not alcoholic intoxication, was implicated. Renal biopsies demonstrated acute tubular necrosis with intraluminal deposits consisting of Tamm-Horsfall protein and myoglobin. After recovery all three patients were demonstrated to have proximal muscle weakness with similar electromyographic abnormalities but nerve-conduction was impaired in only two. Muscle biopsies showed mixed, but predominantly type II fiber atrophy and reduced muscle phosphorylase levels. In the one patient tested the lactate response to forearm muscle ischemia was abnormal. It is postulated that chronic alcoholics may be predisposed to rhabdomyolysis and acute renal failure following acute medical and surgical stress as well as acute alcohol abuse. The muscle damage in these patients may be due to impaired intra cellular glycogen metabolism.

Acute Kidney Injury↗
PubMed1983

Histologic studies of chronic idiopathic urticaria.

Skin biopsy specimens were obtained from 43 consecutive patients with chronic idiopathic urticaria and from seven normal controls. Of 43 patients, 42 had a non-necrotizing perivascular infiltrate composed primarily of mononuclear cells. There was no evidence of damage to vessel walls, of nuclear debris, or of extravasation of red blood cells, and most cells were seen around vessels rather than within the vessel wall. One patient had vasculitis with a neutrophilic infiltrate, nuclear debris, and positive immunofluorescence. Quantitative cell counts revealed four times the number of mononuclear cells and 10 times the number of mast cells in urticaria biopsy sites vs normal skin. Thus chronic urticaria is characterized by an accumulation of mononuclear cells and mast cells with mast cell degranulation presumably associated with hive formation. In our series, the characteristic lesion is not vasculitic. The stimulus responsible for the infiltration of skin with these cells is unknown.

Adolescent↗