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Biomedical subjects

M Lund

Publications and source records attributed to M Lund.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cardiac allograft vasculopathy: the green lane hospital experience 1987-1998.

AIMS: To determine the prevalence of cardiac allograft vasculopathy in heart transplant recipients at Green Lane Hospital and to examine potential risk factors for vasculopathy. METHODS: We retrospectively reviewed the coronary angiograms of all cardiac transplant recipients. Angiography was usually performed one, two and five years after operation. The diagnosis of allograft vasculopathy was made if there was any evidence of coronary artery disease. Patients' medical records were reviewed for potential risk factors. RESULTS: Ninety-one patients underwent cardiac transplantation between December 1987 and March 1998. One year survival was 87%. Angiographic evidence of coronary disease was present in 30 patients and in three patients coronary lesions were first identified at post mortem. Vasculopathy was present in 25%, 35% and 61% of patients at one two and five years following transplant. Donor-acquired lesions could not be excluded as few patients had immediate postoperative angiograms for comparison. Five late deaths have been due to vasculopathy. Recipient age, race, donor age and ischaemic time were similar for those with and without vasculopathy. Frequency or severity of acute rejection episodes, cytomegalovirus infection, lipid profiles, diabetes and hypertension were not significantly different in patients with vasculopathy. CONCLUSION: Cardiac allograft vasculopathy is a common finding after heart transplantation. No definite risk factors were identified in this patient group.

Adult↗
PubMed1999

Telomerase activity and telomere length in lymphocytes from patients with cutaneous T-cell lymphoma.

BACKGROUND: Telomeres shorten with successive cell divisions in normal somatic cells. Telomerase is a ribonucleoprotein enzyme associated with cellular proliferation and plays an important role in maintaining the stability of chromosomes and the length of DNA telomeres. Telomerase activity has been detected in tissues from many human tumors, but is not present in the majority of normal tissues. Thus, measurement of telomerase activity and telomere length may contribute to understanding the mechanism of tumorigenesis and provide useful diagnostic or prognostic information. The aim of this study was to investigate the telomerase activity and telomere length from patients with cutaneous T-cell lymphoma (CTCL). METHODS: Eighteen skin-homing T-cell lines were established from skin biopsies and 10 peripheral blood mononuclear cells (PBMC) were isolated from patients with various stages of CTCL together with 22 PBMC from healthy donors. For each sample an identical amount of cellular protein was measured quantitatively for telomerase activity using the telomerase polymerase chain reaction-enzyme-linked immunosorbent assay based on the telomeric repeat amplification protocol method. Telomere length was assayed using a commercial kit. RESULTS: Eight of ten PBMC and 16 of 18 skin-homing T-cell lines from patients with CTCL showed moderate to strong telomerase activity. Freshly obtained PBMC from healthy donors showed weak levels of telomerase activity. A shorter telomere length was found in cell lines and PBMC from patients with CTCL compared with healthy controls. Four skin-homing T-cell lines going into growth crisis showed sharply reduced telomerase activity. CONCLUSIONS: The results of the current study indicate that both skin-homing T-cells and PBMC from CTCL have high telomerase activity and short telomere length. These changes are similar to the changes observed in the majority of malignant cells including other types of T-cell lymphoma. It is interesting to note that even in the very early stages of CTCL such as parapsoriasis (which is a clinically benign disease) the changes already are present, indicating that a significantly high level of telomerase activity frequently occurs in CTCL and may be an important event in tumorigenesis. Telomerase activity and telomere length are useful markers for CTCL risk assessment.

Aged↗
PubMed1999

Human serum albumin and immunoglobulin on Dracunculus medinensis.

Dracunculus medinensis recovered from infected humans were examined for the occurrence and localization of human serum albumin and immunoglobulins. Immunoelectrophoretic examination of homogenates prepared from adult female worms (ADGW) and first stage larvae (LVGW) showed that anti-human albumin antibodies reacted to both stages of the parasite. By direct fluorescence antibody technique, antigens resembling human albumin and human immunoglobulins (isotype IgG) were identified on the surface of adult female worms. The occurrence of host-like compounds on the parasites may be an adaptation for survival of the parasites. A possible interference of these compounds should be considered in attempts to develop methods for immunological diagnosis of D. medinensis infections.

Animals↗
PubMed1999

Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure.

OBJECTIVES: The purpose of this study was to assess the tolerability and efficacy of carvedilol in patients with New York Heart Association (NYHA) functional class IV symptoms. BACKGROUND: Carvedilol, a nonselective beta-adrenergic blocking drug with alpha-adrenergic blocking and antioxidant properties, has been shown to improve left ventricular function and clinical outcome in patients with mild to moderate chronic heart failure. METHODS: We retrospectively analyzed the outcomes of 230 patients with heart failure treated with carvedilol who were stratified according to baseline functional class: 63 patients were NYHA class IV and 167 were NYHA class I, II or III. Carvedilol was commenced at 3.125 mg b.i.d. and titrated to 25 mg b.i.d. as tolerated. Patients with class IV symptoms were older (p = 0.03), had lower left ventricular fractional shortening (p < 0.001), had lower six-min walk distance (p < 0.001) and were receiving more heart failure medications at baseline compared with less symptomatic patients. RESULTS: Nonfatal adverse events while taking carvedilol occurred more frequently in class IV patients (43% vs. 24%, p < 0.0001), and more often resulted in permanent withdrawal of the drug (25% vs. 13%, p < 0.01). Thirty-seven (59%) patients who were NYHA class IV at baseline had improved by one or more functional class at 3 months, 8 (13%) were unchanged and 18 (29%) had deteriorated or died. Among the less symptomatic group, 62 (37%) patients had improved their NYHA status at 3 months, 73 (44%) were unchanged and 32 (19%) had deteriorated or died. The differences in symptomatic outcome at three months between the two groups were statistically significant (p = 0.001, chi-square analysis). Both groups demonstrated similar significant improvements in left ventricular dimensions and systolic function. CONCLUSIONS: Patients with chronic NYHA class IV heart failure are more likely to develop adverse events during initiation and dose titration when compared with less symptomatic patients but are more likely to show symptomatic improvement in the long term. We conclude that carvedilol is a useful adjunctive therapy for patients with NYHA class IV heart failure; however, they require close observation during initiation and titration of the drug.

Actuarial Analysis↗
PubMed1999

The protein disulphide isomerase gene of the fungus Trichoderma reesei is induced by endoplasmic reticulum stress and regulated by the carbon source.

The gene pdi1 encoding protein disulphide isomerase was isolated from the filamentous fungus Trichoderma reesei by degenerate PCR based on a consensus PDI active-site sequence. It was shown that the Trichoderma pdi1 cDNA is able to complement a yeast mutant with a disrupted PDI1 gene. The putative T. reesei PD1I protein has a predicted 20-amino acid N-terminal signal sequence and the C-terminal fungal consensus ER retention signal HDEL. The mature protein shows strong conservation relative to other fungal protein disulphide isomerases. The T. reesei pdi1 promoter has two possible unfolded protein response (UPR) elements and it was shown by treatments with dithiothreitol and tunicamycin that the gene is under the control of the UPR pathway. Expression of a heterologous protein, an IgG antibody Fab fragment, in Trichoderma increases pdi1 expression, probably by inducing the UPR. The level of T. reesei pdi1 mRNA is also regulated by the carbon source, being lowest in glucose-containing media and highest on carbon sources that induce the genes encoding extracellular enzymes. The mechanism of this regulation was studied by examining pdi1 mRNA levels under conditions where the extracellular enzymes are induced by sophorose, as well as in the strain RutC-30, which is mutant for the glucose repressor gene cre1. The results suggest that neither sophorose induction nor glucose repression by the CREI protein affect the pdi1 promoter directly.

Amino Acid Sequence↗
PubMed1999

Telomerase activity is spontaneously increased in lymphocytes from patients with atopic dermatitis and correlates with cellular proliferation.

Telomerase is a ribonucleoprotein enzyme involved with cellular proliferation and cellular senescence. The aim of the present study was to investigate telomerase activity in lymphocytes from patients with atopic dermatitis (AD) and to observe its regulation of cellular proliferation. Peripheral blood mononuclear cells (PBMC) were isolated from 15 patients with AD and 13 healthy donors. Cells were stimulated with purified protein derivative (PPD) of tuberculin (10 microg/ml), interleukin 2 (IL-2) (100 U/ml), anti-CD3 monoclonal antibody (anti-CD3) (1 microg/ml), anti-CD3 plus IL-2, and staphylococcal enterotoxin A (SEA) (0.1 microg/ml). Telomerase activity was measured by the telomeric repeat amplification protocol-based telomerase polymerase chain reaction enzyme-linked immunosorbent assay at 0 and 72 h of incubation. In addition, DNA synthesis of the cells was assayed using 3H-thymidine incorporation. We found that telomerase activity in non-stimulated PBMC from patients with AD was significantly up-regulated without any stimulation during the 72 h of in vitro incubation. The most potent stimulator of telomerase activity was SEA, followed by anti-CD3 plus IL-2, anti-CD3 alone, and PPD. IL-2 did stimulate telomerase activity and DNA proliferation with increasing dosage of IL-2. The DNA proliferation was paralleled by increase in telomerase activity. There was no significant difference between telomerase activity in stimulated lymphocytes from AD patients and normal donors, but the relative increase in telomerase activity tended to be less in AD patients. A spontaneously higher telomerase activity in lymphocytes from AD patients could indicate that T lymphocytes are already stimulated in vivo or that a population of T cells in peripheral blood exhibits an increased telomerase activity compatible with cellular immaturity.

Adult↗
PubMed1999

Structural heterogeneity of the binding sites of HSA for phenyl-groups and medium-chain fatty acids. Demonstration of equilibrium between different binding conformations.

A new facet of the very heterogeneous albumin molecule is described. Chromatography at pH 6-9 of human serum albumin (HSA) on a phenyl-sepharose column separates it into two nonconvertible conformations that are, in turn, in equilibrium with its binding and nonbinding forms. The hydrophobic interaction of HSA with phenyl-sepharose depends on ionic strength, pH, and time of contact with the immobilized ligand. Binding as a function of pH shows a minimum at pH 6.5, and the binding profile at pH 7-9 fits the titration of a weak monoprotic acid with a pKa of 7.3. There was no observable difference in the CD spectra or the masses of the two forms. The equilibrium between the albumin forms was examined under defined conditions and cannot be explained by a simple two-state model. Thus rechromatography of the nonbinding fraction derived from a sample in which 50% of the protein was originally retained resulted only in 10-20% bound protein. Correspondingly only 70-80% of the binding form was retained. A model explaining the observations can be derived if two species, I and II, exist in the solution, both being in an equilibrium with a binding and a nonbinding form, but in which I is not in equilibrium with II. The rate of conversion between the binding and nonbinding conformations was determined to be faster than 15 s at room temperature.

Binding Sites↗
PubMed1999

Impact of concurrent amiodarone treatment on the tolerability and efficacy of carvedilol in patients with chronic heart failure.

OBJECTIVE: To assess the safety and efficacy of carvedilol when administered to heart failure patients already receiving amiodarone. DESIGN: Retrospective analysis of the clinical outcome of 230 patients treated with carvedilol for chronic heart failure, stratified according to whether they were already receiving amiodarone (amiodarone group, 80 patients) or not (non-amiodarone group, 130 patients) at baseline. SETTING: Heart failure clinic at a university affiliated public teaching hospital. MAIN OUTCOME MEASURES: Incidence of adverse events; changes in functional status and echocardiographic dimensions at three months. RESULTS: Adverse reactions to carvedilol occurred in 33 (41%) of the amiodarone group and 43 (29%) of the non-amiodarone group (p = 0.049). Carvedilol was discontinued in 21 (26%) of the amiodarone group and 37 (25%) of the non-amiodarone group (NS). The clinical outcome at three months did not differ significantly between the two groups; 31 (39%) of the amiodarone group improved their New York Heart Association status, 28 (35%) were unchanged, and 21 (26%) deteriorated compared with 67 (45%), 51 (34%), and 32 (21%), respectively, for the non-amiodarone group (NS). Both groups had highly significant decreases in heart rate and left ventricular end systolic dimension, and a significant increase in left ventricular ejection fraction after three months of carvedilol treatment, with no significant differences between the groups. CONCLUSIONS: The beneficial effects of carvedilol on left ventricular remodelling, systolic function, and symptomatic status are not affected by concurrent treatment with amiodarone. Adverse reactions necessitating cessation of carvedilol are no more frequent in patients receiving amiodarone.

Adrenergic beta-Antagonists↗
PubMed1999

Effects of LPS on transport of indocyanine green and alanine uptake in perfused rat liver.

Lipopolysaccharide (LPS) initiates cholestasis. Whether this process is mediated by tumor necrosis factor-alpha (TNF-alpha) and whether the cholestatic response to LPS is associated with intrahepatic accumulation of possibly toxic substances are under debate. To study these questions the hepatic uptake and biliary excretion of indocyanine green (ICG) was examined in the isolated perfused rat liver 18 h after intravenous treatment of rats with either saline, 1 mg/kg body wt LPS, or LPS and intraperitoneal pentoxifylline (POF) (n = 6 in each group). POF inhibits TNF-alpha release after LPS administration. LPS induced a typical acute-phase response with increased mRNA for acute-phase proteins, reduced albumin mRNA, and increased hepatic uptake of alanine. Intrinsic hepatic clearance of ICG in controls (1.01 +/- 0.05 ml. min(-1). g liver(-1)) was similarly decreased by LPS alone (0.62 +/- 0.04 ml. min(-1). g(-1); P = 0.002 vs. control) or combined with POF (0.66 +/- 0.06 ml. min(-1). g(-1)). A kinetic analysis indicated that LPS reduced both uptake and excretion processes in a balanced manner, so that intrahepatic ICG content was unaffected or even slightly reduced, as confirmed by measurement of ICG contents in the perfused livers. In livers from parallel-treated nonperfused rats, mRNA for the organic anion transporting protein-1 (Oatp1, which is likely to mediate ICG uptake) was unaffected by LPS, whereas the concentration of Oatp1 protein was reduced. Thus LPS induced an acute-phase response that included downregulation of ICG uptake by reduction of Oatp1 protein concentration, possibly at a posttranscriptional level. TNF-alpha appears not to be the mediator because POF did not modify these LPS effects.

Alanine↗
PubMed1999

The sorting determinant guiding Hsp150 to the COPI-independent transport pathway in yeast.

The COPI coatomer is thought to be required in yeast directly for retrograde transport from the Golgi to the endoplasmic reticulum (ER), and directly or indirectly for ER-to-Golgi transport. Unexpectedly, the secretory glycoproteins Hsp150 and invertase have been found not to require COPI for ER exit. The features according to which cargo proteins are selected for the COPI-independent pathway are not known. The ER form of Hsp150 has three distinct domains: an N-terminal fragment of 54 amino acids (subunit I) is followed by 11 repeats of a 19 amino acid peptide plus a unique C-terminal fragment of 114 amino acids (subunit II). By fusing heterologous proteins to different Hsp150 domains and expressing them in sec21-1 and sec21-3 mutants with temperature-sensitive mutations in the gamma-COPI subunit, we show here that the repeats of subunit II function as sorting determinants for COPI-independent ER exit. The C-terminal fragment of Hsp150 could be replaced by E. coli beta-lactamase or rat nerve growth factor receptor ectodomain (NGFRe), and subunit I could be deleted, without inhibiting COPI-independent transport. However, when the repetitive region was omitted and beta-lactamase was fused directly to the C terminus of subunit I, COPI was required for efficient ER exit. Mass spectroscopic analysis demonstrated that both subunit I and II of Hsp150 were extensively O-glycosylated, suggesting that the O-glycosylation pattern was not decisive for cargo selection.

Amino Acid Sequence↗
PubMed1997

Cardiac transplantation in New Zealand: eight years experience.

Between December 1987 and December 1995, 62 patients underwent orthotopic cardiac transplantation at Green Lane Hospital. Their cardiac dysfunction resulted from dilated cardiomyopathy (32), coronary artery disease (21), rheumatic heart disease (7), congenitally corrected transposition of the great arteries (1) and hypertrophic cardiomyopathy (1). Before transplantation all patients were in New York Heart Association (NYHA) functional class III or IV. Eight patients (13%) died in the perioperative period and a further seven (11%) died 1 to 4 years after transplantation. Actuarial 1 and 3 year survival was 87% and 80% respectively. Forty-five of forty-seven surviving patients were in NYHA functional class I at the time of analysis. The results confirm that cardiac transplantation has a limited but valuable role in the treatment of end stage myocardial dysfunction.

Actuarial Analysis↗
PubMed1997

Enkephalin-like immunoreactivity in human skin is found selectively in a fraction of CD68-positive dermal cells: increase in enkephalin-positive cells in lesional psoriasis.

Opioid peptides are synthesized in neurons, endocrine cells, monocytes/macrophages and B and T lymphocytes. They interact with opioid receptors located on immune cells and nociceptive nerve terminals. Because opioid peptides might be of importance in inflammatory skin diseases, for example psoriasis, sections of skin from psoriatic patients were immunohistochemically stained with antisera against methionine and leucine enkephalin, CD68 (KP1, PG-M1), calprotectin (M747), M130 (Ber-MAC3), CD1a and CD3. Enkephalin-like activity was detected selectively in dermal CD68-positive macrophages/monocytes. The activity showed no association with the activation markers M747 and Ber-MAC3. There was a statistically significant increase in enkephalin-positive cells in involved psoriatic skin compared with uninvolved and normal skin. These results were confirmed by radioimmunoassay which showed elevated levels in extracts from involved psoriatic skin compared with uninvolved skin (81%) and normal skin (204%). Furthermore, preproenkephalin mRNA of an expected size was detected in involved psoriatic skin. If the increased levels of enkephalins present in monocytes/macrophages in psoriatic skin lesions reach the threshold for biological activity, they may play a role in the regulation of the inflammatory processes seen in this skin disease.

Adult↗
PubMed1997

Does bromide cause conversion of epilepsy to psychosis?

The aim of this study is to find out whether bromide was able to cause conversion of epilepsy to psychosis i.e., so-called paradoxical normalization such as has been seen in treatment with modern antiepileptic drugs. Spontaneous conversion has been known for three hundred years. Locock introduced bromide in the treatment of epilepsy in 1857. Belgrave wrote in 1868 on its effect on epileptic attacks and concommitant insanity. In 1868 Holm observed reduction of the frequency of seizures at the same time as psychotic symptoms or just dysphoria. In 1875 Voisin described a dose-dependent intoxication with psychosis and/or neurological signs. Stark in 1875 and Bannister in 1881 were the first to clearly describe the antagonism between epileptic seizures and psychotic symptoms, an antagonism or conversion described by many authors, both in cases with high and low dosage, and with and without intoxication. Thus, the title of this paper should be answered in the affirmative. Bromide has been used as a sedative and has rarely caused intoxication. Thus the presence of epilepsy is not a condition for the development of bromide intoxication. A case with epilepsy and fatal massive bromide intoxication is reported. It is discussed whether the pathological findings give support to Wolf's hypothesis of latent epileptic activity in subcortical pathways during "normalization".

Bromides↗
PubMed1997

Atopic dermatitis may be a genetically determined dysmaturation of ectodermal tissue, resulting in disturbed T-lymphocyte maturation. A hypothesis.

Although atopic dermatitis is a skin disorder, it includes immune deviations such as T-cell accumulation and activation in the skin, resulting in chronic, relapsing eczema. The T-lymphocyte activation in the skin is not accompanied by specific allergies in up to two thirds of the patients. It has been shown that T-cell lines and clones can be established from skin biopsies of patients with atopic dermatitis showing cytokine-dependent, but antigen-independent, continuous growth in vitro. This indicates the existence of skin-homing T-lymphocytes with growth requirements different from those of mature T-lymphocytes in the blood. We suggest that atopic dermatitis is a genetically determined change of ectodermal tissue. The thymic epithelium is derived from the ectoderm, and because of that we hypothesize that the maturation of the T-cell immune system of persons who develop atopic dermatitis is disturbed due to a faulty selection of T-lymphocytes in the thymus. "Dys"-matured T-cells leave the thymus as a consequence of faulty selection and continue their growth in the skin. The cells are eventually eradicated by the immune surveillance conducted by the normal part of the patients' immune system and as a consequence of diminished output of faulty selected T-lymphocytes during maturation. Because of the increased proliferation capacity of the aberrant T-cells, a cytokine imbalance occurs and in some patients this leads to the development of type I allergies due to a skewing of the humoral immune system towards IgE production.

Dermatitis, Atopic↗
PubMed1997

Medications that may contribute to sexual disorders. A guide to assessment and treatment in family practice.

Approximately 15% to 25% of family practice patients have concerns about sexual function and are most comfortable discussing these issues with their family physician. While many physicians have avoided this topic in the past, citing lack of knowledge and skill, the family practice setting is ideal for a preliminary evaluation of sexual dysfunction and treatment for certain etiologies. This especially is true for changes in sexual function secondary to medication effects. This article provides basic guidelines designed to assist physicians in evaluating the effects of medications and other substances on sexual function. Also included are lists of medications known or suspected to have adverse effects on sexual function. Physicians are encouraged to address the sexual concerns of their patients and to incorporate these guidelines and the medication lists into their evaluation.

Antihypertensive Agents↗
PubMed1996

[Visual laser coagulation for benign prostatic hyperplasia. Preliminary experiences].

A total of 28 patients with symptomatic bladder outlet obstruction due to benign prostatic hyperplasia were treated by visual laser coagulation (VLAP) performed with the Myriadlase sidefiring neodymium: YAG laser fibre at 40 Watts power. The treatment was performed as an outpatient procedure using intraurethral gel anaesthesia and light intravenous sedation and analgesia. Prostatic volume was 32 g (18-90 g), and 650 Joule per gram prostatic tissue (516-1000 J/g) was administered. The patients were evaluated at mean 9.2 weeks. The mean operative time was 34 minutes. The procedure was very gentle, all patients tolerated it well and there was no bleeding. Most patients experienced some dysuria for three to four weeks after the procedure, two had severe symptoms. Two patients remained in retention and required transurethral resection. The rest expressed subjective satisfaction with the results. Peak urinary flow increased from mean 9.0 ml/sec preoperatively to 15.4 ml/sec; a mean increase of 78%. One patient developed clinical urinary tract infection. There were no other complications of clinical significance.

Aged↗