Intracerebral bacillary angiomatosis in HIV.
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Biomedical subjects
Publications and source records attributed to P J Harris.
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The adsorption of mutagens by some dietary fibres has been suggested as one mechanism by which dietary fibres protect against colorectal cancer. It is thought that these dietary fibres carry the mutagen out of the digestive tract, decreasing the effective mutagen concentration to which epithelial cells are exposed. The ability of gastrointestinal mucin to alter the extent to which the hydrophobic mutagen 1,8-dinitropyrene (DNP) adsorbs in vitro onto the insoluble dietary fibre alpha-cellulose, was investigated. It was found that crude and purified human ileal mucins themselves adsorbed DNP and decreased the adsorption of DNP onto alpha-cellulose. Purified mucin which had been treated with trypsin also adsorbed DNP. These studies suggest that in the digestive tract there would be competition for the adsorption of DNP between mucin and insoluble dietary fibres, such as alpha-cellulose. This factor must be considered in predictions about the distribution of hydrophobic, mutagenic carcinogens in the digestive tract and their role in the etiology of colorectal cancer.
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BACKGROUND: Sequential visual field testing is an extremely helpful adjunct to ophthalmoscopy and fundus photography in the management of cytomegalovirus (CMV) retinitis with the antiviral agents ganciclovir or foscarnet in patients with the acquired immune deficiency syndrome (AIDS). The authors studied the visual field defects found in a series of 110 patients with AIDS and CMV retinitis. METHODS: Ophthalmoscopy and fundus photography were performed on all patients. Visual field analysis was performed with either tangent screen, Goldmann kinetic, or Humphrey automated static perimetry. RESULTS: Of 166 eyes in 110 patients with CMV retinitis, visual field defects were present initially in 92 (55%) eyes of 78 (70%) patients, and ultimately in 97 (53%) eyes of 90 patients in whom follow-up was available. Stabilization of visual field defects was indicative of controlled retinitis. CONCLUSION: Sequential visual field testing will confirm ophthalmoscopic evidence of successful antiviral treatment of CMV retinitis and will corroborate very early progression of previously controlled retinitis.
The incidence of colorectal cancer is lower in Polynesian populations of the South Pacific than in European populations. This difference in incidence of the disease may be, at least partly, related to diet. Dietary fiber is believed to protect against colorectal cancer, and one of the ways it may act is by adsorbing mutagens that are carcinogenic. Very little is known about the chemical composition or the ability to adsorb mutagens of these dietary fibers from South Pacific food plants. In contrast to European food plants, which are mostly dicotyledons, South Pacific food plants are mainly monocotyledons. We isolated cell walls (dietary fiber) from the three edible parts of taro (Colocasia esculenta), which is a monocotyledon and a major South Pacific food plant. The ability of these three unlignified cell-wall preparations to adsorb the hydrophobic environmental mutagen 1,8-dinitropyrene was studied. The greatest adsorption occurred with walls from leaf blade, followed by petiole and corm walls, although the differences were not major. The amount of adsorption was intermediate between the low adsorption previously found with unlignified dicotyledon walls (from the flesh of potato tubers and immature cabbage leaves) and the much higher adsorption found with unlignified walls from monocotyledons of the grass and cereal family (Poaceae) (from leaves of seedling Italian ryegrass). These data are consistent with the monosaccharide compositions of the taro wall preparations, which were more similar to those of unlignified walls of dicotyledons than to unlignified walls of the Poaceae. These findings are consistent with the hypothesis that the composition of the dietary fiber determines its adsorptive properties and that there may be important differences between the major dietary fibers of South Pacific and European food plants.
1. Independent of its effects on renal haemodynamics and glomerular filtration, angiotensin II (AII) has direct actions on the proximal tubule involving transepithelial Na+, H+, HCO3-, and water reabsorption, ammoniagenesis, gluconeogenesis and renal growth. 2. The effects of AII on water and electrolyte transport are biphasic and dose-dependent, such that low concentrations (10(-12)-10(-9) mol/L) stimulate reabsorption whereas high concentrations (10(-7)-10(-6) mol/L) inhibit reabsorption. Similar dose-response relations have been obtained for luminal and peritubular addition of AII. 3. The cellular responses to AII are mediated via an AT-1 receptor coupled via G-regulatory proteins to several parallel signal transduction pathways. Low doses inhibit the basolateral adenylate cyclase, lower intracellular cAMP and withdraw the inhibitory effect of protein kinase A on the luminal Na/H exchanger. Stimulation of this exchanger may also occur due to AII-receptor activation of phospholipase C to release diacyl glycerol, or by local transduction in the brush-border membrane involving phospholipase A2. 4. Inhibition of proximal fluid reabsorption is associated with increased intracellular Ca2+ released from intracellular stores, or entering via voltage-sensitive channels in response to the release of inositol-1,4,5-trisphosphate, or following Ca2+ channel opening induced by the arachidonic acid metabolite 5,6-epoxy-eicosatrienoic acid. 5. The stimulatory actions of peritubular AII on proximal transport are inhibited by physiological concentrations of atrial natriuretic factor (ANF) and by parathyroid hormone (PTH). 6. It is concluded that intrarenal AII acts to maintain optimal matching of fluid reabsorption and filtered load in response to changes in sodium balance, as well as to promote acidification of the urine during acidosis and perhaps to potentiate tubular growth following renal injury.
1. The influence of endogenous angiotensin II (AII) on renal haemodynamics and tubular function was examined by clearance and micropuncture methods in anaesthetized rats during AII receptor blockade with the non-peptide antagonist DuP 753 (50 micrograms kg-1 min-1 i.v.). 2. Mean arterial pressure was reduced slightly (-5 +/- 2 mmHg) while filtration fraction and glomerular filtration rate rose by 30% without changes in renal plasma flow (RPF) or renal vascular resistance (RVR). 3. Fractional proximal fluid reabsorption (calculated from lithium clearance) fell from 73 to 64% (P < 0.01) and fractional distal sodium reabsorption decreased from 98 to 94% (P < 0.01). 4. Urine flow rate more than doubled, sodium output increased 4-fold and plasma renin concentration rose 8-fold while potassium excretion remained unchanged. 5. Proximal tubular fluid reabsorption (Jv) as measured by shrinking split-droplet micropuncture decreased by 21% (P < 0.01) during infusion of DuP 753 compared with 22.5% (P < 0.01) during converting enzyme inhibition by enalaprilat (MK422). 6. Responses to DuP 753 were similar to those previously documented with converting enzyme inhibitors except that DuP 753 failed to raise RPF. It is concluded that generation of intrarenal vasodilator paracrines has confounded conclusions about the renal action of converting enzyme inhibitors and we propose that in anaesthetized rats, endogenous angiotensin II (AII) has its major renal influences on glomerular filtration and proximal fluid reabsorption with little effect on renal vascular resistance.
Laser scanning confocal microscopy of the Ca(2+)-sensitive fluorophore fluo-3 has been used to investigate spontaneous and propagated calcium release at high temporal and spatial resolution in enzymatically dispersed rat cardiomyocytes. Waves of fluorescence which propagated throughout the cytosol were evident in spontaneously contracting cardiac cells containing fluo-3, but not in cells containing Ca(2+)-insensitive fluorophores [2',7'-bis (carboxyethyl)-5,6-carboxyfluorescein, SNARF-1, rhodamine-123, or tetramethylrhodamine-labeled dextran]. These waves represent localized areas of elevated [Ca2+] [975 +/- 13 (SE) nM, range 800-1,500 nM; n = 16 cells]. Ca2+ waves were initiated by the spontaneous release of Ca2+ from the sarcoplasmic reticulum (SR) and propagated through cells at rates of 50-150 microns/s. Ca2+ waves were usually initiated at the cell ends, but multiple and variable initiation foci were observed in some cells. Where waves intersected within a single cell there was extinction of wave propagation, confirming the SR as the direct source of Ca2+ and revealing a refractory period in SR Ca2+ release. In some cells high-frequency Ca2+ waves lead to synchronized elevation of [Ca2+] throughout the entire cytosol and within the time period associated with cell depolarization. These observations support the hypothesis that some cardiac arrhythmias are initiated by spontaneous and propagated Ca2+ release and involve subsequent depolarization, global elevation of intracellular [Ca2+], and cell contraction.
Cytasters were induced in the unfertilized eggs of the sea urchin Lytechinus pictus by two different methods: (1) treatment with hexylene glycol or taxol, which are known to lower the tubulin critical concentration in vitro, but do not activate the nuclear cycle, and (2) by raising the cytoplasmic pH from that of unfertilized cytoplasm to that of fertilized, which activated the nuclear cycle and initiated tubulin polymerization. In the unactivated eggs, with increasing concentrations of the inducing agents, temperature and duration of treatment, microtubule structures that formed showed a progression from loose microtubule networks and spiral arrays to tightly organized cytasters. In eggs incubated in sea water containing 2.5 or 10 mM ammonium acetate titrated with HCl or NaOH in steps from pH 5.0 to pH 9.0, the nuclear cycle and tubulin polymerization were initiated at about pH 7.0. The degree of development attainable after three hours was dependent on the pH, with spirals forming at the threshold level of pH 7.0, monasters at pH 7.5, and at pH 8.5 cells formed cytasters, multipolar spindles and even completed multipolar divisions. In unactivated eggs, tubulin was made available by lowering of the tubulin critical concentration; in activated eggs it was made available from some previously unavailable store. The evidence suggests that the amount of assembly-competent tubulin available, regardless of how it is made available, determines the type of structure that is formed, with microtubule bundles and spirals at the lower concentrations and functional cytasters at the upper. We also describe some details of cytaster formation, including the role of microtubule interactions and the movement of dense granules to the aster centers in hexylene glycol-treated eggs.
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Using computerised densitometry to measure immunocytochemical reaction product in a model system, we established conditions that produced a linear relationship between the logarithm of antigen concentration and the measured intensity of staining. We then applied the densitometric technique to assess the changes in tyrosine hydroxylase (TH) and neuropeptide tyrosine (NPY) within sympathetic neurons of rat superior cervical ganglion following chronic decentralization and following reserpine treatment. One week after surgical or pharmacological decentralization, there was appreciable reduction of neuronal levels of both TH and NPY. However, there remained considerable variation in the immunoreactivities of individual cells. Three days of treatment with reserpine elevated TH levels but substantially reduced NPY. Both these effects were prevented by prior decentralization of the ganglia. No differences were seen between normotensive and the Otago strain of genetically hypertensive rats, either in basal TH or NPY immunoreactivities or in responses to the maneuvers performed. Comparison of our findings with previous biochemical data indicate that densitometric immunocytochemistry provides an accurate index of neuronally localised antigen concentrations but also allows analysis of interneuronal differences that are not otherwise apparent.
One of the theories to explain the protective action of some dietary fibres against colon cancer is that certain mutagens and/or cancer promoters are adsorbed to these dietary fibres making the mutagens and/or cancer promoters less available to gut mucosal cells. The abilities of 2 contrasting cell wall preparations (dietary fibre preparations) from potato tubers to adsorb in vitro the hydrophobic mutagen, 1,8-dinitropyrene (DNP), were studied using an incubation mixture containing DNP in phosphate-buffered saline (PBS). Walls from potato skins strongly adsorbed DNP and, at the highest wall concentration tested, only a small porportion of the DNP remained in solution. In marked contrast to the skin walls, potato flesh walls adsorbed only a small proportion of the DNP. Unexpectedly, the flesh walls also caused a large increase in the proportion of DNP found in solution. When flesh walls were pre-extracted with PBS, the ability of the extracted walls to bind DNP increased. The material extracted from the flesh walls was able to maintain DNP in solution, when added to the incubation medium in the absence of cell walls. Pectic polysaccharides appear to be the soluble component responsible for maintaining the DNP in solution. Competition between soluble and insoluble fibre components may have major implications for the availability and distribution of hydrophobic mutagens in the alimentary tract.
The effects of angiotensin II (ANG II) or angiotensin III (ANG III) on renal cortical blood flow (CBF) or papillary blood flow (PBF) were investigated in Inactin-anesthetized young rats with the use of laser-Doppler flowmetry. Infusion of equimolar pressor doses of ANG II (300 ng.kg-1.min-1 iv) or ANG III (267 ng.kg-1.min-1) decreased CBF by 31 +/- 2.6% (P less than 0.001) and 20.3 +/- 3.2% (P less than 0.01), respectively but increased PBF by 19 +/- 6.1% (P less than 0.05) and 14.6 +/- 4.4% (P less than 0.05). The ANG II-induced increase in PBF was not prevented by aortic clamping to maintain constant renal perfusion pressure or pretreatment with the prostaglandin synthase inhibitor, indomethacin. The nonpeptide ANG II receptor antagonist, DuP 753 completely abolished the systemic and intrarenal effects of ANG II. After pretreatment with a kallikrein inhibitor, aprotinin, ANG II infusion increased mean arterial pressure but did not affect PBF, suggesting that kinins, but not prostaglandins, modulate the action of systemic ANG II on PBF. We conclude that circulating ANG II induces vasoconstriction in the cortex and also promotes the intrarenal production of kinins, which act to enhance papillary blood flow.
In-vivo microperfusion was used to localize the reabsorptive defect responsible for the hypercalciuria of diabetes mellitus and to investigate possible causative factors. Unidirectional proximal calcium absorption was not significantly different in rats made diabetic with streptozotocin compared with controls, providing evidence against the involvement of this nephron segment in the phenomenon. Calcium absorption by the loop of Henle, was however, significantly (P less than 0.01) lower in diabetic animals (32.1 +/- 1.2 vs 40.4 +/- 0.6 pmol/min). Based on our knowledge of calcium movements within the loop, it is likely that the reabsorptive defect residues within the thick ascending limb. The calcium lesion was found to be independent of acute changes in intraluminal glucose concentration and could not be corrected by acute insulin treatment. The study also provides new information on the relationship between intratubular glucose and fluid movements in the rat nephron. In diabetic rats a proximal perfusate containing 30 mmol glucose/l resulted in fluid absorption comparable with that seen in control rats perfused with 5 mmol glucose/l. However, intraluminal glucose had a stimulatory effect on fluid absorption in the loop of Henle of diabetic rats (10.7 +/- 0.5 vs 7.9 +/- 0.4 nl/min; P less than 0.01).
We have studied the relationship between the early morphological changes and arterial responsiveness to vasoactive agents in a new animal model that is proposed to mimic the events of early human atherosclerosis. Atheroma-like lesions were produced by positioning a hollow Silastic collar (referred to as a cuff) around the common carotid arteries of rabbits. Following a period of either 48 h or 1, 2, or 4 weeks after surgery, vessels from both cuffed and sham-operated animals were removed, and vascular reactivity to cumulative concentrations of agonists were studied in isolated rings in organ baths. The contralateral arteries were perfused and fixed, studied by light microscopy, and the degree of intimal thickening was quantified by computer-assisted morphometric analysis and expressed as changes in the ratios of the cross-sectional areas of the intima and media in each artery. At 48 h, rings prepared from cuffed arteries were sixfold more sensitive to the contractile effects of serotonin (5-HT) than the corresponding controls. Histologically, such vessels showed some perivascular inflammation but no other morphological abnormality. At 7 days, cuffed vessels were again sixfold more sensitive to 5-HT than controls, and showed a thickened intima with marked smooth muscle proliferation and some infiltration by monocytes. Intimal/medial cross-sectional area ratios remained elevated at 2 and 4 weeks, but the supersensitivity to 5-HT diminished by 2 weeks to threefold and was absent at 4 weeks. The augmented reactivity to 5-HT at 48 h was specific, in that it did not occur for the alpha-adrenoceptor agonist, phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
To date, the prevalence and nature of the late toxicity of cisplatin-based combination chemotherapy for advanced testicular cancer has been poorly documented. Thirty men with a median age of 35 years (range, 23 to 63), who had undergone such treatment were assessed with detailed investigation to determine the type and frequency of chronic toxicity. The median follow-up from the time of commencement of chemotherapy was 75 months (range, 48 to 126). The most common late toxic effects were high tone hearing loss in 23 men (77%) and electrophysiological evidence of peripheral nerve damage in 15 (50%). Both the hearing and nerve abnormalities were predominantly asymptomatic. In addition, elevation of serum cholesterol, noted in 20 patients (67%), was significant (P = .014) when compared with a control population. Hyperuricemia was present in nine patients (30%). Only one patient, with other risk factors (smoking, family history), had evidence of ischaemic heart disease while 20% (all with a smoking history) had a diminished single breath diffusing capacity for carbon monoxide (DLCO). Cisplatin-based chemotherapy is relatively free of major long-term side effects and should not be withheld for fear of late toxicity.
A direct dose-dependent stimulation or inhibition by val5-angiotensin II of sodium reabsorption in the rat proximal nephron has been shown using stationary microperfusion combined with perfusion of the peritubular capilaries. Since the circulating form of the hormone in the rat has been suggested to be the ile5-analogue these experiments have been repeated using the ile5-peptide at peritubular concentrations covering the normal physiological range (10-10 -10-13M). Comparison of the results with the previously published data shows no significant difference between the actions of these two analogues. At the concentrations tested both caused significant stimulation of sodium reabsorption with a maximum effect at 10(-11)M.