Biomedical subjects

C J Jones

Publications and source records attributed to C J Jones.

304 records · Page 17Linked to original sources

PubMedDate not supplied

Myogenic and flow-dependent control mechanisms in the coronary microcirculation.

We have recently gained evidence that segmental coronary microvascular diameters, and therefore resistances, are controlled by myogenic and endothelial responses to pressure and flow. Furthermore, intact heart studies are demonstrating that these mechanisms may interact importantly with the metabolic mechanisms primarily governing coronary blood flow. Further studies utilizing measurement of segmental coronary microvascular diameters in isolated microvessels and in the beating heart may elucidate the nature of these interactions. Clinical studies may determine whether reversal of endothelial impairment in the diseased coronary microcirculation contributes to autoregulatory vasodilation, increases resting myocardial perfusion, and increases the threshold for myocardial ischemia during exercise.

Animals↗

PubMedDate not supplied

alpha-adrenergic responses of isolated canine coronary microvessels.

Although alpha-adrenergic activation is known to increase coronary microvascular resistance in vivo, the magnitude of its segmental microvascular consequences is not well understood. Quantification of these effects in vivo is hindered by escape mechanisms that minimize the influences of constrictors, and alterations in flow and pressure, which effect microvascular tone by shear stress-dependent and myogenic mechanisms, respectively. To eliminate these confounding influences, we have studied responses in vitro under conditions with these variables controlled. We evaluated the diameter changes of isolated canine coronary arterioles (110 +/- 12 microns, n = 35) response to alpha-adrenergic activation by norepinephrine (10(-10) to 10(-4) M) in the presence of beta-adrenergic blockade by alprenolol (10(-6) M). In contrast to the situation in vivo, alpha-adrenergic activation did not constrict isolated coronary arterioles, but constricted isolated coronary venules in a dose-dependent manner over a range of 10(-10) to 10(-4) M (-27 +/- 3% maximum diameter change). Coronary arteriolar alpha-adrenergic constriction was not promoted by 1) subthreshold or vasoactive doses of the vasoconstrictors KCl, angiotensin II, U46619, endothelin-1, neuropeptide Y or arginine vasopressin, 2) inhibition of the presynaptic uptake of norepinephrine by imipramine (10(-6) M), 3) inhibition of EDRF synthesis by NG-monomethyl-L-arginine (10(-5) M) or 4) inhibition of prostaglandin synthesis by indomethacin (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

PubMedDate not supplied

A simple method for embedding small specimens for photomicrography and sectioning following intracellular microiontophoresis of lucifer yellow CH.

A simple method for the rapid processing of small specimens following intracellular labelling with the fluorescent naphthalimide dye Lucifer Yellow CH is described which involves embedding in glycol methacrylate-based resin on cavity slides. The technique, which may be suitable for other intracellular and extracellular fluorescent markers, permits early fluorescence photomicrography of whole mounts and subsequent recovery of the specimens for serial sectioning and further analysis. In the present study on isolated human eccrine sweat glands, the procedure has facilitated both the identification of cells from which electrical records have been made and the determination of their dye-coupling status.

Eccrine Glands↗

PubMedDate not supplied

Permeability of the near-term rat placenta to hydrophilic solutes.

The permeability of the rat placenta at 21 days' gestation (term is 23 days) has been measured with fetuses intact in situ and by perfusion of the fetal circulation. Intact measurements were made by removal of fetuses at known time intervals after injection of radioisotopes to the anaesthetized mother and measurement of their radioactivity content. Unidirectional clearance (Kmf) was calculated and found to be in proportion to the diffusion coefficient in water (Dw) for [14C]mannitol, [14C]sucrose, [51Cr]EDTA and [3H]inulin but was relatively high for 22Na and low for [125I]albumin. The high value for 22Na is partially explained by transfer across the yolk sac placenta; cautery of the vitelline vessels significantly reduced the Kmf for 22Na but not that for [51Cr]EDTA or [125I]albumin. The low [125I]albumin value is explained on the basis of restricted diffusion of this tracer. Perfused permeability measurements were made by injection of radioisotope into the anaesthetized mother and measurement of the radioactive content of fetal perfusate samples. Although the Kmf for Na+ was significantly (P less than 0.01) reduced by 25 per cent, there was no other significant difference between results with the perfused placentae compared with those from the intact placentae. Comparison of the intact data with similar measurements in guinea pig and human confirms the similar permeability properties of the haemochorial placentae as a whole; the extra trophoblast layers in the rat make no discernible difference.

Animals↗

PubMedDate not supplied

Glycogen distribution in the capillaries of the placental villus in normal, overt and gestational diabetic pregnancy.

Glycogen distribution has been examined in placental capillaries in normal (N; 11), overtly diabetic (OD; 8) and gestational diabetic (GD; 7) pregnancies using light and electron histochemistry. Light microscopy revealed a wide variation in glycogen deposition in all three groups, but the method was too insensitive to visualize deposits in the villous capillaries. An ultrahistochemical technique, however, rendered glycogen detectable. Endothelial cells (EC) and pericytes (PERI) in 100 capillaries per specimen were scored as to whether their glycogen was dispersed (D) or aggregated (A). Again, a large range in the amounts of both types of glycogen was seen. When EC and PERI comprising a capillary cross-section were considered together as 'functional units', a higher (P < 0.11) relative number of cells containing A was found in OD (51 +/- 8 per cent) than in N (41 +/- 17 per cent) or GD (43 +/- 18 per cent). In OD more EC and PERI, considered separately, tended to contain A than those in N and GD, but large variations in the data precluded statistical significance. The proportion of PERI containing aggregated glycogen was higher (P < 0.0002) than that of EC in all groups. We suggest that, on average, placental EC and PERI contain higher glycogen levels in OD than in N or GD. Moreover, these cells might contribute to the high glycogen levels in placentae from diabetic pregnancies.

Capillaries↗

PubMedDate not supplied

Ultrastructure of the human placenta in metabolic storage disease.

Eleven placentae and one fibroblast cell culture from pregnancies complicated by various inherited metabolic disorders, together with five chorionic villus biopsies from pregnancies at risk, were examined for ultrastructural evidence of accumulation of metabolites. Abnormal ultrastructural features were present as early as 10 weeks gestation. Myelin bodies were found in all placental cell types in a case of Niemann-Pick disorder and stromal cells showed marked vacuolation in Hurler's disease. Membranous arrays were occasionally identified in the lysosomes of stromal cells in a case of Sandhoff's disease, together with some myelin body formation in the trophoblast and endothelium. In Pompe's disease, intralysosomal accumulations of glycogen were present in all cell types except syncytiotrophoblast, while in sialic acid storage disorder all placental cells were affected except for the cytotrophoblast. Collagen fibre disorientation and excess associated proteoglycan was seen in a formalin-fixed placenta with Sanfilippo mucopolysaccharidosis, and syncytial vacuolation, caused possibly by delays in fixation, was evident in many specimens. The specimens were collected from different centres and the fixation procedure varied significantly. The most satisfactory results were obtained from chorionic villus sampling in vivo and from pregnancies terminated using aspiration followed by immediate fixation. The importance of liaison with clinicians is stressed in order to obtain optimal preservation of the tissue. This is particularly vital in immature specimens of placenta where abnormal storage product material may not have had time to accumulate.

Amniocentesis↗

PubMedDate not supplied

Preparation of plasma membrane vesicles from the rat placenta at term and measurement of Na+ uptake.

Cytochemistry revealed that alkaline phosphatase was localized predominantly to the maternal facing plasma membrane of syncytiotrophoblast layer II in the haemotrichorial rat placenta at term. Plasma membrane vesicles prepared from term rat placenta by homogenization, treatment with MgCl2, and differential centrifugation were enriched 14-fold in alkaline phosphatase activity as compared to homogenate. These vesicles were mainly oriented right side out, as shown by a lack of effect of saponin treatment on alkaline phosphatase activity. Na+ uptake into the vesicles under equilibrium exchange conditions was significantly stimulated (P less than 0.01) nearly threefold in the presence of an outwardly directed H+ gradient as compared to no gradient. The stimulation by a H+ gradient was abolished in the presence of 0.5 mM amiloride. Measurements with the pH-sensitive dye BCECF in the absence of Na+ showed that 95.2 +/- 0.6 per cent of a 1.2 pH unit H+ gradient was dissipated from the vesicles in 2 min, but the remaining gradient was maintained for up to 15 min. These experiments therefore provide evidence that vesicles derived mainly from the maternal facing plasma membrane of syncytiotrophoblast layer II of the rat placenta possess a Na+/H+ exchanger.

Alkaline Phosphatase↗

PubMedDate not supplied

Paracellular permeability pathways in the human placenta: a quantitative and morphological study of maternal-fetal transfer of horseradish peroxidase.

Physiological data indicate that both a transcellular and a paracellular pathway are available for transfer across the human placenta but the morphological correlate of the latter is uncertain. We measured the permeability of the dually perfused human placental cotyledon to the predominantly cationic protein horseradish peroxidase (MW 40,000), to the neutral polymer 14C-dextran (MW 50-70,000) and to the extracellular space marker creatinine (MW 113). Following fixation and cytochemistry, we used brightfield microscopy to localize peroxidase reaction product within the same tissue. Steady state unidirectional maternofetal clearance (Kmf) for the peroxidase (0.90 +/- 0.27 microliters/min/g, n = 9) was not significantly different from that for 14C-dextran (0.95 +/- 0.07 microliters/min/g, n = 3) suggesting that charge does not markedly influence peroxidase permeability. The Kmf for creatinine was 13.1 +/- 2.5 microliters/min/g (n = 9); these permeability data are similar to those reported for the placenta in vivo. Microscopically, peroxidase reaction product was localized to the microvillous surface of the syncytiotrophoblast of most villi and to the trophoblastic basement membrane and connective tissue cells of the villous core in a few villi. The reaction product was also associated with fibrin-containing deposits attached to the villous core at sites of discontinuity of the syncytial epithelium. The staining pattern within the deposits was consistent with a diffusion gradient of the peroxidase. These fibrin-containing deposits at discontinuities in the syncytiotrophoblast may provide one paracellular route for peroxidase diffusion from the intervillous space into the villous core.

Cell Membrane Permeability↗

PubMedDate not supplied

An ultrastructural and ultrahistochemical study of the human placenta in maternal pre-eclampsia.

At the electronoptical level the placental villi of the pre-eclamptic woman are characterized by focal syncytial necrosis, loss and distortion of microvilli, dilatation of syncytial rough endoplasmic reticulum, decreased syncytial pinocytotic activity, a reduced number of syncytial secretory droplets, cytotrophoblastic hyperplasia, degeneration of occasional cytotrophoblastic cells, thickening of the trophoblastic basement membrane and the presence of small fetal capillaries with bulbous endothelial cells. Ultrahistochemical studies show reduced alkaline phosphatase and dehydrogenase activity in the syncytiotrophoblast but an increased acid phosphatase activity. It is suggested that all the observed morphological abnormalities, with the exception of cytotrophoblast cell degeneration, are explicable solely on the basis of utero-placental ischaemia and that no other aetiological factor need be invoked: the cause of the cytotrophoblast cell degeneration is, however, unknown. The ultrastructural findings indicate that there is a decrease in the transfer and synthetic activity of the trophoblast and that cellular respiration is also probably depressed. Nevertheless, there is some evidence that changes of a compensatory nature, designed to limit the effects of the tissue damage, are brought into play.

Acid Phosphatase↗

PubMedDate not supplied

An ultrastructural and ultrahistochemical study of the human placenta in maternal essential hypertension.

An electron-optical study of the placenta in essential hypertension indicates that the morphological changes seen in this disease are qualitatively very similar to those found in placentae from pre-eclamptic women: these changes are accentuated if pre-eclampsia is superimposed on essential hypertension. It is therefore suggested that the abnormalities seen in placentae from hypertensive women are due solely to ischaemia. The extent and degree of ischaemic damage suffered by the placenta is essential hypertension were, however, much less marked and extensive than in placentae from pre-eclamptic patients whilst in placentae from cases of essential hypertension complicated by pre-eclampsia there was less evidence of ischaemic damage than in placentae from cases of pre-eclampsia or comparable severity developing in previously normotensive women. It is suggested that the placenta is able to adapt to a state of chronic ischaemia in a manner that it is not able to do in late onset ischaemia and that the adaptive mechanisms adopted not only limit ischaemic damage but also afford protection to the placenta against the effects of superimposed pre-eclampsia.

Acid Phosphatase↗

PubMedDate not supplied

Nematosomes in the human placenta.

In this study, the ultrastructure of the human placental 'nematosome' or 'glomerular body' is described. It is usually found as electron-dense aggregates forming an inclusion 0.3 to 0.5 micron in diameter and of variable length, and occurs within cytotrophoblast cells in different configurations which include spirals, concentric rings, parallel arrays, random coils and paracrystalline structures. Analysis of random electron micrographs of placentae from normal and complicated pregnancies showed that the nematosome is present in low frequencies in the first and second trimesters but is more commonly found at full term; their incidence did not differ markedly from normal in any of the pathological conditions studied, ranging from 10.4 to 21.9 per cent, and their frequency suggests that there may be several nematosomes per cell. The relationship of the nematosome to the centriole is discussed, and it is suggested that morphometric analysis may elucidate the three-dimensional structure of nematosomes, their distribution within cells and their relationship to the plasma and other membranes.

Animals↗

PubMedDate not supplied

The Drosophila mutation turnip has pleiotropic behavioral effects and does not specifically affect learning.

The Drosophila mutant turnip (tur) was isolated on the basis of its poor performance in an olfactory learning task, and also has a reduction in protein kinase C (PKC) activity. PKC has been found in the nervous systems of a wide range of organisms and appears to have an important role in learning and memory-related processes. Unfortunately, previous reports documenting the learning defect of tur lacked the controls required to assess the origins of the poor performance of the mutant. We have analyzed the effects of the tur mutation on both associative and nonassociative learning as well as on PKC activity. Additionally, the effects of the mutation on the task-relevant sensorimotor abilities of the flies were assessed. Although we were able to replicate previous behavioral and biochemical results obtained with tur, we discovered that the tur mutation also affected response to electric shock and caused a drastic reduction in the locomotor ability of the flies. Because locomotion is an essential component of the learning assays, this result makes it impossible to conclude that tur specifically affects learning and demonstrates the crucial importance of sensorimotor controls in conditioning experiments.

Animals↗

PubMedDate not supplied

Excision of oral squamous cell carcinoma in a horse.

A large oral squamous cell carcinoma in a 27-year-old Arabian stallion was removed by partial excision of the incisive bone. There was no gross evidence of recurrence or metastasis 5 months later.

Animals↗

PubMedDate not supplied

Ultrastructural localization of insulin receptors in human placenta.

PROBLEM: Investigations to date on localization of placental insulin receptors (IR) at the ultrastructural level focused on the maternal facing side of the placenta but did not allow localization of IRs to intracellular compartments. METHOD: The ultrastructural localization of IR in placentae from early and term gestation was studied using the immunogold technique and a monoclonal antibody against the external domain of the IR (clone MA20). RESULTS: At 10 wk gestation, there were high levels of IR in both cytotrophoblast and syncytiotrophoblast, with sparse microvillous labeling. Fetal vessels contained various amounts of IR while stromal cells were also labeled. By 13 wk, this pattern was unchanged; however, at term, fewer IR were present in the syncytiotrophoblast, with more label on microvilli than before. Fetal vessels were well labeled, while stromal cells appeared unchanged. Intense labeling of fetal erythrocytes provided an internal positive control, while omission of the primary antiserum produced loss of binding. CONCLUSION: The data suggest a spatiotemporal alteration in placental IR distribution during pregnancy, possibly reflecting a shift in control of placental growth and metabolism from mother to fetus.

Chorionic Villi↗

PubMedDate not supplied

The tumour suppressor gene p53 as a regulator of proliferative life-span and tumour progression.

This review develops the concept of p53 as a transcription factor mediating growth arrest or cell death in response to long-term (senescence-related) as well as acute (DNA damage) signals. Evidence is presented to support the importance of both functions in tumour development. The role of p53 in senescence is discussed in the context of the telomere theory and in relation to its more established function as a 'guardian of the genome'. Finally, data indicating important tissue-specific differences in the control of proliferative life-span by p53 are reviewed, together with potential clinical implications.

Cell Division↗

PubMedDate not supplied

An ultrahistochemical study of the placental content of respiratory enzymes in normal and prolonged pregnancies.

The placental content of malate dehydrogenase and lactate dehydrogenase has been studied at the ultrastructural level. In the trophoblast both enzymes have a predominantly mitochondrial localization although occasional membrane-bound extra-mitochondrial activity is also seen. As compared with the first trimester placenta, there is a highly significant decrease in the activity of both enzymes within the trophoblast at term; this may represent an adaptative change to reduce placental oxygen consumption and increase the amount of oxygen available to the fetus. In prolonged pregnancies, there is a continued decline in trophoblastic malate dehydrogenase activity but the lactate dehydrogenase activity tends to increase, these changes suggesting that there is a switch from oxidative pohosphorylation to anaerobic glycolysis. It is not clear whether this change to a less efficient mode of energy generation is due to an intrinsic ageing change within the trophoblast or is secondary to placental ischaemia.

Animals↗