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Biomedical subjects

L Maxwell

Publications and source records attributed to L Maxwell.

At least 37 records · Page 2Linked to original sources
PubMed1998

Microvascular involvement in cardiac pathology.

Abnormalities of the microvasculature are centrally involved in the pathogenesis of some forms of heart disease, but in others are consequences of it. Microvascular abnormalities may contribute to the progression of viral myocarditis and Chagas' disease. Focal abnormalities may occur early in some cardiomyopathies and do occur later in most types of myocarditis. The thickening of arteriolar walls in chronic hypertension is likely to contribute significantly to the impairment of coronary haemodynamics associated with adaptive ventricular hypertrophy and the consequent diminution of coronary reserve, increasing diffusion distances and failure of angiogenesis to compensate. However, the resulting myocyte necrosis stimulates inflammatory angiogenesis. When ischemic myocyte injury becomes irreversible there is a concomitant loss of capacity for reperfusion, the no-reflow phenomenon. Less severe temporary ischemia reduces the proportion of functional capillaries. Multiple mechanisms are involved in this microvascular stunning, including: reperfusion injury; leukocyte activation; adhesion and accumulation; and impaired endothelium-dependent vasodilation. Many of the microvascular changes are those of the inflammatory response to cell death and form part of a final common pathway in myocarditis, cardiomyopathy, cardiac hypertrophy and failure, and ischemic heart disease. Stimulation of angiogenesis prior to myocyte necrosis in hypertrophy and control of leukocyte activity in ischemic heart disease could minimize myocyte loss.

Cardiomyopathies↗
PubMed1997

Gene therapy of diabetes: glucose-stimulated insulin secretion in a human hepatoma cell line (HEP G2ins/g).

In order to design a feasible somatic cell gene delivery system for the treatment of type I diabetes, a suitable cell type needs to be determined. We have previously shown that the stable transfection of the full-length insulin cDNA into the human liver cell line, (HEP G2ins) resulted in synthesis, storage and acute regulated release of insulin to analogues of cAMP, but not to the physiological stimulus glucose. In attempting to explain the lack of glucose responsiveness of the HEP G2ins cells we have stably transfected these cells with the human islet glucose transporter GLUT 2 (HEP, G2ins/g cells). The HEP G2ins/g cell clones exhibit glucose-stimulated insulin secretion and glucose potentiation of the secretory response to nonglucose secretagogues. While glucose responsiveness commenced at a lower concentration than normal islets, a secretion curve approaching normal physiological conditions was generated. Immunoelectron microscopy revealed the presence of insulin-containing granules, similar in size and appearance to those of the normal beta cell. These results demonstrate that while it is most likely that the HEP G2ins/g cell line predominantly secretes insulin via the constitutive pathway, significant acute regulated release was seen in response to glucose, and thus represents significant progress in the creation of a genetically engineered 'artificial beta cell' from a human hepatocyte cell line.

Blotting, Northern↗
PubMed1996

A confocal microscopic survey of serotoninergic axons in the lumbar spinal cord of the rat: co-localization with glutamate decarboxylase and neuropeptides.

Patterns of co-localization of serotonin with glutamate decarboxylase (the synthetic enzyme for GABA) or each one of eight neuropeptides (calcitonin gene-related peptide, dynorphin, enkephalin, galanin, neuropeptide Y, neurotensin, substance P and somatostatin) were investigated with dual-colour confocal laser scanning microscopy in the lumbar spinal cords of three adult rats. Four regions of the gray matter were studied (laminae I-II, V, IX and X). The extent of co-localization was estimated by direct assessment of merged pairs of optical sections and by automated image analysis. Co-localization of serotonin and glutamate decarboxylase was found only in a few axons of laminae I-II but was not detected in other laminae. Peptides were not co-localized with serotonin in the superficial dorsal horn but considerable co-localization was found in motor nuclei and sparse co-localization was found in laminae V and X. Galanin and substance P frequently co-existed with serotonin in lamina IX but some co-localization with dynorphin, somatostatin, [Met]enkephalin and neuropeptide Y was also detected. Galanin, substance P and dynorphin were also co-localized with serotonin in a few axons of the deep dorsal horn and in the gray matter around the central canal. Neurotensin and calcitonin gene-related compound did not co-exist with serotonin in any of the laminae investigated. This evidence suggests that different populations of serotoninergic axons project to different regions of the spinal gray matter. Those containing glutamate decarboxylase terminate in the superficial dorsal horn and are likely to be involved in antinociception, whereas those containing peptides terminate principally in motor nuclei and are likely to modulate motor activity.

Animals↗
PubMed1996

Distribution of human colonic dendritic cells and macrophages.

To define the phenotype of intestinal dendritic cells and macrophages, resected colonic specimens were used to obtain lamina propria cell suspensions by EDTA treatment, then enzymatic digestion. The phenotype of dendritic cell-enriched suspensions was compared with that of macrophage-enriched populations by immunocytochemistry using the avidin-biotin-peroxidase (ABC) system and immunoelectron microscopy. Dendritic cells expressed HLA-DR (L243) and HLA-DQ-associated (RFD) antigens and CD68 in a perinuclear distribution. Staining for S100 was weak or absent. Macrophages also expressed HLA markers (L243 and RFD1) and CD68. The 25F9 antigen was expressed strongly, whilst CD14 was absent from cells isolated from noninflamed tissues. To determine their anatomic distribution, immunohistochemistry was performed using single- and double-labelling techniques (ABC +or- alkaline phosphatase anti-alkaline phosphatase method). Mutually exclusive subsets of 25F9+ and S100+ cells were seen: 25F9+ macrophages were concentrated in a band immediately beneath the luminal epithelium; S100+/HLA-DR+ dendritic cells formed a reticular network throughout the lamina propria and beneath the basement membrane of the crypts. This distribution suggests that macrophages may help regulate intestinal responses by acting as the first line of defence against the entry of luminal antigens. A breach of the macrophage 'barrier' by invading antigens may necessitate the recruitment of T cell responses by immunostimulatory dendritic cells.

Cell Adhesion↗
PubMed1996

Invasive intestinal spirochetosis: a report of three cases.

We here report on three patients with gastrointestinal symptoms in whom spirochetes were found in colonic biopsies. The patients, heterosexual adults, were not immunocompromised. Electron microscopy was performed on colonic biopsies from each of the three patients. Apart from the basophilic band consisting of spirochetes, the mucosa was normal in two patients on light microscopy and showed mild inflammation in the other one. However on electron microscopy there was invasion of the colonic epithelial cells, macrophages, goblet cells and Schwann cells by spirochetes, and stunting of the microvilli. The spirochetes conformed to the morphology of Brachyspira aalborgi, and no other infective etiology or pathology could be identified in these patients to account for their symptoms. Since the clinical significance of intestinal spirochetosis is uncertain, antibiotics were not administered to any of the three patients and all three improved symptomatically with non-specific treatment. Intestinal spirochetosis, previously thought to be non-invasive and non-pathogenic in humans, may be invasive and may be the cause of gastrointestinal symptoms in some patients.

Adult↗
PubMed1995

Harlequin ichthyosis--a case report.

The Harlequin infant represents the most severe form of nonbullous ichthyosis. Although the clinical features of infants with Harlequin ichthyosis are generally similar, histological, ultrastructural, and biochemical analyses have not shown consistent findings. An unexpected case of Harlequin ichthyosis in a female infant born at 35 wks gestation is presented. Light microscopic and ultrastructural investigations of skin biopsies are detailed. The presence of extracellular lipid material in the stratum corneum has not been described in the previously reported cases of Harlequin ichthyosis.

Fatal Outcome↗
PubMed1995

Hospital nurses and health promotion.

This study examined the role of acute-care nurses in health promotion (HP), using a survey designed to measure the knowledge, attitudes, and practices of nurses in relation to HP. Staff nurses in eight British Columbia hospitals surveyed in 1992 responded that HP is an integral part of nursing care, yet several barriers in the hospital environment inhibit their efforts in this domain. The perceived barriers are lack of time, insufficient resources for patient teaching, and lack of continuity of care. Respondents identified positive features as the attitudes of patients and families, supportive colleagues, and hospital support for HP activities. The study concludes that acute-care nurses are an underutilized resource for HP. The challenge is to make more effective use of nurses' knowledge, attitudes, and skills in promoting health in the hospital setting.

Acute Disease↗
PubMed1994

A new ureteral anastomotic device: the Unilink system. A pilot study using the porcine model.

OBJECTIVE: Ureteral injury is a complication of gynecologic surgery in approximately 1% of all cases. The anatomic site of the injury determines the type of operative repair. When an end-to-end ureteral anastomosis is required, interrupted sutures are usually used. A prospective, randomized animal study was performed to determine the efficacy of a new microvascular anastomotic device, the Unilink system, in repairing transected ureters. STUDY DESIGN: Nineteen pigs underwent randomized anastomosis with the Unilink system on one side and traditional anastomosis with suture on the contralateral side. A postoperative intravenous pyelogram was performed immediately and 2 weeks later, before the anastomotic site at a second laparotomy was harvested. Patency rates for each type of anastomosis were compared microscopically, and the degree of hydronephrosis was compared grossly and radiographically. RESULTS AND CONCLUSION: The anastomotic repair with the Unilink system did not significantly differ structurally or functionally from traditional suture repair.

Anastomosis, Surgical↗
PubMed1994

The augmentation of leucocyte adhesion to endothelium by therapeutic ultrasound.

To determine the effects of exposure of endothelial cells to therapeutic ultrasound on leucocyte adhesion to these cells, confluent cultures of bovine aortic endothelial cells in tissue culture flasks and on collagen coated coverslips were exposed to a maximum of 1.6 W/cm2 1 MHz continuous ultrasound for 15 min, then incubated with neutrophil-rich suspensions containing a known number of viable human leucocytes for intervals from 1 to 240 min. After incubation, nonadherent cells were decanted, the number of leucocytes in the eluted suspension determined and the percentage of adhered cells calculated. Endothelial cell viability was not significantly reduced by ultrasound or by incubation with leucocytes. Whereas untreated endothelial cells were flattened and had surface microvilli, those exposed to ultrasound were plump, rounded and more widely separated along their borders. The percentage of leucocytes that adhered to sonicated endothelium was significantly higher, and this proportion increased with the duration of incubation. Thus, exposure of endothelial cells to ultrasound in vitro can cause intercellular separation and increase the adhesion to leucocytes. If such changes were also to occur in vivo, therapeutic ultrasound would potentiate the inflammatory response.

Animals↗
PubMed1993

The myocardial vasculature during ischemia and reperfusion: a target for injury and protection.

Ischemia and reperfusion may result in injury to one or more of the cellular components of the heart. In addition to damaging myocytes and their contractile capability, ischemia and reperfusion may inflict early and severe injury on the vasculature which, in turn, may further jeopardize the survival of the myocytes. While ischemia is known to cause progressive injury to endothelium and vascular smooth muscle it now appears that reperfusion can inflict additional, possibly severe, injury on the microcirculation which may compromise the return of normal coronary perfusion. This post-ischemic/reperfusion microvascular incompetence ranges from a transient exacerbation of the increase in vascular resistance initiated during ischemia, to a sustained loss of competent capillaries and eventually to the "no reflow" phenomenon which is characterized by the total inability of the affected tissue to be reperfused. Whereas "no reflow" may be of little importance if it occurs in already infarcted tissue, post-ischemic microvascular incompetence in potentially salvable myocardium could be of considerable significance. Evidence is presented that the vascular endothelium, and its ability to regulate coronary vascular tone, play a central and early role in the pathogenesis of myocardial injury. Mechanisms underlying microvascular injury have been identified and pharmacological strategies now exist for the effective manipulation of this injury--a prospect that is of considerable importance in the light of the widespread use of thrombolytic procedures for the reperfusion of the human myocardium.

Animals↗
PubMed1993

Improvement of doxorubicin induced cardiomyopathy in rats treated with insulin-like growth factor I.

OBJECTIVES: This study was designed to assess the effects of treatment with insulin-like growth factor-I (IGF-I) on cardiac function and structure in rats with an established cardiomyopathy. METHODS: Adult male Wistar rats were injected with doxorubicin (2 mg.kg-1 subcutaneously) weekly for 12 weeks and either rhIGF-I (0.8 mg.kg-1.day-1; n = 16, D-I group) or saline (n = 25, D-S group) subcutaneously via an osmotic pump from weeks 9 to 12. A non-doxorubicin injected control group was also studied. After 12 weeks survivors were anaesthetised and cardiac output determined with radiolabelled microspheres. At postmortem pleural effusion and ascitic volumes were measured and the heart was removed for histological examination by light and transmission electron microscopy. RESULTS: Doxorubicin treated animals showed less mean weight gain from week 2 than the untreated control group. Animals treated with IGF-I from week 9 showed a significant (p < 0.05) but non-sustained increase in weight. Survival to 12 weeks was 56% in the D-I group and 44% in the D-S group (p = 0.2). Evidence of cardiac failure was seen in the D-I and the D-S groups, but there was a tendency (p = 0.06) for less ascites in the D-I group (21 (SEM 8) ml) than in the D-S group (46 (10) ml). Cardiac output was significantly higher in the D-I than in the D-S group (132 (7.2) v 91.4 (6.4) ml.min-1, p < 0.01), as was stroke volume (0.323 (0.03) v 0.226 (0.02) ml, p < 0.01). There was focal cardiac damage in both D-I and D-S animals. Scattered groups of myocytes showed prominent vacuolation of the nuclear envelope, sarcoplasmic reticulum, and t tubular system, mild to severe mitochondrial swelling, and loss of orientation and definition of myofibrils. No clear morphological differences were evident between the two groups. CONCLUSIONS: Administration of IGF-I may improve the function of damaged myocardium, although the mechanisms are unclear. Further studies with earlier coadministration of IGF-I, quantitative histological analysis, and with other models of cardiac injury are indicated.

Animals↗
PubMed1992

Anti-oxidant therapy improves microvascular ultrastructure and perfusion in postischemic myocardium.

To determine the contribution of oxygen-derived free radicals to the changes in microvascular structure and function which follow reperfusion of ischemic myocardium, isolated perfused rat hearts were subjected to 15 or 45 min of global ischemia followed by 5 min of oxygenated reperfusion. Hearts were then fixed by perfusion with glutaraldehyde and perfused with nuclear track photographic emulsion to identify competent capillaries in scanning and transmission electron micrographs. Reperfusion after 15 min caused a significant reduction in the density of competent capillaries in the subendocardial third of the left ventricle, but this reduction was lessened but not eliminated by the addition of 0.61 mmole/liter desferrioxamine, but not by 60,000 U/liter superoxide dismutase plus 60,000 U/liter catalase, to the perfusate. After 45 min of ischemia both interventions prevented the myocyte swelling, endothelial cell changes, bleb formation, and reduction in microvascular lumina characteristic of unprotected reperfusion, but only desferrioxamine significantly improved microvascular competence. This suggests that the hydroxyl radical rather than superoxide and/or hydrogen peroxide has a pathogenic role, although desferrioxamine may have other effects as nonspecific chelator. Postischemic reductions in capillary function also occur in reversibly injured myocardium in the absence of structural abnormality. Preventing postischemic microvascular incompetence has the potential to minimize ischemic cell injury and to enhance repair following myocardial infarction, but it also may increase the risk of hemorrhage from venules.

Animals↗
PubMed1992

Endothelin-3-induced microvascular incompetence and mitochondrial damage in rat myocardium.

1. To determine the possible role of an endothelin in the development of postischaemic microvascular incompetence, isolated buffer-perfused rat hearts were perfused with endothelin-3 (ET-3) in phosphate buffer. 2. ET-3 produced a reduction in coronary flow rate, heart rate and arrhythmia. There was a marked reduction in the density of competent capillaries, and the myocytes showed vacuolation and mitochondrial damage in regions where microvascular incompetence was most severe. 3. These results indicate that ET-3 can substantially reduce microvascular perfusion in the heart and can also cause damage to the myocyte.

Animals↗