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Biomedical subjects

M Holm

Publications and source records attributed to M Holm.

At least 19 recordsLinked to original sources
PubMed2006

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in cancer patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards, are based on all relevant publications since 1985 and were discussed and accepted in a consensus conference. Undernutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis. EN should be started if undernutrition already exists or if food intake is markedly reduced for more than 7-10 days. Standard formulae are recommended for EN. Nutritional needs generally are comparable to non-cancer subjects. In cachectic patients metabolic modulators such as progestins, steroids and possibly eicosapentaenoic acid may help to improve nutritional status. EN is indicated preoperatively for 5-7 days in cancer patients undergoing major abdominal surgery. During radiotherapy of head/neck and gastrointestinal regions dietary counselling and ONS prevent weight loss and interruption of radiotherapy. Routine EN is not indicated during (high-dose) chemotherapy.

Cachexia↗
PubMed2006

Modulation of chemokine gene expression in CD133+ cord blood-derived human mast cells by cyclosporin A and dexamethasone.

We have recently developed a protocol for generating huge numbers of mature and functional mast cells from in vitro differentiated umbilical cord blood cells. Using CD133 as a positive selection marker to isolate haematopoietic progenitors we routinely expand the number of recovered cells at least 150-fold, which vastly exceeds the yields of conventional protocols using CD34+ cells as a source of progenitors. Taking advantage of the large quantities of in vitro differentiated mast cells, here we assess at the levels of transcription and translation the kinetics of chemokine gene induction following receptor mediated mast cell activation or following pharmacological activation of specific signal transduction cascades that become activated upon classical FcepsilonRI receptor crosslinking. We demonstrate that chemokine genes encoding IL-8, MCP-1, MIP-1alpha, and MIP-1beta are induced with different kinetics and with different amplitudes in a receptor activation dependent manner, and that these events can be mimicked using pharmacological agents which activate distinct signal transduction pathways. These findings were corroborated by adding immunomodulators such as cyclosporin A and dexamethasone prior to mast cell activation. Finally, we demonstrate that the same modulators added after mast cell activation can differentially quench ongoing chemokine gene induction. Thus, considering the vast yields of mast cells, our protocol is valuable not only for studying regulation of gene expression in mast cells in general, but also as an experimental tool to develop better and more balanced treatments of mast cell related disorders.

AC133 Antigen↗
PubMed2005

Dynamic expression of the angiotensin II type 2 receptor and duodenal mucosal alkaline secretion in the Sprague-Dawley rat.

Activation of angiotensin II type 2 receptors (AT2R) has been shown to stimulate duodenal mucosal alkaline secretion (DMAS) in Sprague-Dawley rats (S-D). This finding could not be confirmed in another line of S-D, and the present study investigates whether the level of AT2R expression determines the response to the AT2R agonist CGP42112A. DMAS was measured in anaesthetized rats using in situ pH-stat titration. Real-time PCR and Western blot were used to assess AT1R and AT2R RNA and protein expression, respectively. CGP42112A (0.1 microg kg(-1)min(-1) I.V.) elicited a 45% net increase in DMAS in the previous S-D line studied, whereas no change occurred in the new S-D line. Luminal administration of prostaglandin E2 (10(-5) M) increased DMAS similarly in both S-D lines. AT2R protein expression was significantly higher in tissue from the previous line compared to the new line. Individual AT1R to AT2R ratios (RNA and protein) were significantly higher in the new line compared to the previous S-D line. In the new S-D line intravenous infusion of angiotensin II (Ang II; 10 microg kg(-1) h(-1)) over 120 min significantly lowered the duodenal AT1aR to AT2R RNA ratio. Prolonged Ang II infusion over 240 min increased AT2R protein expression and evoked a 42% stimulatory response in DMAS to CGP42112A. The level of local AT2R expression determines the effect of the AT2R agonist CGP42112A on rat duodenal mucosal alkaline secretion. AT2R expression should be confirmed before interpreting the experimental effects of pharmacological interferences with this receptor.

Angiotensin II↗
PubMed2005

A study of finger lengths, semen quality and sex hormones in 360 young men from the general Danish population.

BACKGROUND: It has been suggested that finger length may correlate with function or disorders of the male reproductive system. This is based on the HOXA and HOXD genes' common embryological control of finger development and differentiation of the genital bud. The objective of this study was to explore the association between the ratio of 2nd to 4th finger length (2D:4D ratio) and testis function in a sample of young Danish men from the general population. METHODS: Semen samples and finger measurements were obtained from a total of 360 young Danish men in addition to blood samples for sex hormone analysis to describe the possible association between 2D:4D and semen and sex-hormone parameters. RESULTS: A statistically significant inverse association with the 2D:4D was found only in relation to hormone levels of FSH in the group of young men with a 2D:4D >1 (P = 0.036) and a direct association with the total sperm count in the group of young men with a 2D:4D < or = 1 (P = 0.045). CONCLUSION: The statistically significant results may be 'false positives' (type I error) rather than representing true associations. This relatively large study of young, normal Danish men shows no reliable association between 2D:4D finger ratio and testicular function. Measurements of finger lengths do not have the power to predict the testicular function of adult men.

Adolescent↗
PubMed2005

Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis.

Insulin-like factor 3 (INSL3) serum levels were measured in 135 andrologically well-characterized normal men and 85 patients with testicular disorders to investigate how the hormone, which is a major secretory product of human Leydig cells, is related to testosterone (T), LH, and semen quality. INSL3 was measured by using a newly developed fluorescence immunoassay. Median (2.5-97.5 percentiles) INSL3 serum levels were as follows: normal men (n = 135), 0.99 (0.55-1.73) ng/ml; infertile men (n = 23), 1.11 (0.60-2.07) ng/ml; anorchid men (n = 21), nondetectable (ND); patients with 47, XXY, Klinefelter syndrome (n = 21), 0.12 (ND-0.78) ng/ml; men with hypogonadotropic hypogonadism and T substitution (n = 11), ND; and men with hypogonadotropic hypogonadism and human chorionic gonadotropin (hCG) treatment (n = 5), 0.36 (0.13-0.73) ng/ml. Before testicular biopsy, two infertile men had blood samples drawn directly from vena spermatica. Here, the serum INSL3 levels were 15-fold higher than in serum from peripheral blood samples (13.84 and 14.00 ng/ml, respectively). In two unilaterally orchiectomized former testis cancer patients, who underwent hCG stimulation test, INSL3 serum levels were unchanged 72 and 96 h after hCG stimulation. In conclusion, we provide a normal range for INSL3 serum levels in adult men and show that the majority, if not all, circulating INSL3 derives from the testes. Furthermore, our data strongly indicate that INSL3 secretion is dependent on the differentiating effect of LH on Leydig cells but independent of the steroidogenic LH-mediated action. Thus, even though T and INSL3 are both dependent on LH, these two Leydig cell hormones are regulated differently.

Adolescent↗
PubMed2004

EHEC outbreak among staff at a children's hospital--use of PCR for verocytotoxin detection and PFGE for epidemiological investigation.

This is the first report of a major foodborne outbreak of enterohaemorrhagic Escherichia coli (EHEC) in Sweden. It occurred among the nursing staff at a children's hospital with approximately 1600 employees. Contaminated lettuce was the most likely source of infection. Nine persons were culture-positive for Escherichia coli (E. coli) O157 and verocytotoxin-positive by PCR and a further two were verocytotoxin-positive by PCR only. All 11 EHEC-positive individuals had attended a party for approximately 250 staff members, which was held at the hospital. In a questionnaire 37 persons stated that they had symptoms consistent with EHEC infection during the weeks after the party. There was no evidence of secondary transmission from staff to patients. The value of PCR as a sensitive and fast method for diagnosis is discussed in this paper. Pulsed-field gel electrophoresis (PFGE) was used to ascertain that staff members were infected by the same clone, and that two patients with E. coli O157 infection were not.

DNA, Bacterial↗
PubMed2004

Cytogenetic and molecular analysis of a family with three brothers afflicted with germ-cell cancer.

A thorough cytogenetic investigation and an analysis of detailed questionnaires were performed in a family with three brothers afflicted with germ-cell tumors (GCTs), in an attempt to detect a congenital factor related either to a hereditary genetic background or an environmental/lifestyle influence. One brother had an intracranial tumor in the pineal region and the two others had testicular tumors. Peripheral blood was studied by traditional karyotyping, multicolor-FISH, high-resolution comparative genomic hybridization (HR-CGH), and molecular analysis of selected loci on sex chromosomes (Yq11 region, TSPY, and the androgen receptor gene); however, no abnormalities were detected. The HR-CGH analysis of microdissected histological components of the overt tumors and the adjacent carcinoma in situ demonstrated a pattern of genomic imbalances characteristic for sporadic GCTs, including gain of 12p. The questionnaire and interview revealed a history of different cancers in the extended family, and a possible in utero and/or infantile exposure of the three brothers with GCTs to compounds suspected of endocrine-disrupting properties. Although no genetic aberration was detected in this family, we suspect the presence of a recessive hereditary factor pre-disposing to cancer, which probably was manifested as GCTs in the three brothers because of an adverse effect of an environmental factor on the early germ-cell differentiation.

Adult↗
PubMed2003

Stenting and extracorporeal shock wave lithotripsy in chronic pancreatitis.

BACKGROUND: Early observational studies of endoscopic treatment and extracorporeal shock wave lithotripsy (ESWL) reported considerable or complete relief of pain in 50%-80% of patients with chronic pancreatitis. There is no consensus on the measurement of pain, making comparison of observational studies difficult, and little attention has been paid to the type and amount of analgesics used by patients before and after decompressive treatment. METHODS: We performed a retrospective study of all patients with chronic pancreatitis and large-duct disease and receiving decompressing treatment between 1 November 1994 and 31 July 1999. Primary parameters were type and amount of analgesics used. RESULTS: Forty-nine patients with chronic pancreatitis and large-duct disease received stenting of the pancreatic duct (28 patients), ESWL (6 patients) or both (15 patients). After a median follow-up of 21 months, 35% of all patients were pain-free and a further 6% were not using analgesics. Seven patients no longer needed opioids during follow-up, but five other patients needed addition of opioids to treatment. The median opioid dose among opioid-dependent patients rose slightly (9%). The median increase of weight after treatment was 1 kg per year. CONCLUSION: After decompressive treatment of patients with chronic pancreatitis and large-duct disease, we observed a small increase in weight and a small reduction in the number of opioid users. The changes may not be different from the natural course of the disease.

Adult↗
PubMed2001

Jejunal luminal nitric oxide during severe hypovolemia and sepsis in anesthetized pigs.

OBJECTIVE: Lowered gut blood perfusion and the associated intestinal mucosal barrier dysfunction is considered important in the pathophysiology leading to critical illness. Intestinal mucosal nitric oxide formation has been attributed a key role in the regulation of epithelial permeability and other properties of the intestinal mucosal barrier. This study was performed to delineate intestinal mucosal NO formation during hypovolemia or sepsis, both of which are associated with intestinal hypoperfusion. MATERIALS AND METHODS: Seventeen pigs were subjected to 2 h of severe hypovolemia (bleeding induced) or sepsis (systemic infusion of live Escherichia coli) or no treatment (controls). Jejunal mucosal NO production was monitored by a tonometer. Mesenteric blood flow was measured as portal venous blood flow by an ultrasonic transit time flowmeter probe, and oxygen delivery and consumption were calculated from regional blood samples. RESULTS: Intestinal perfusion and oxygen delivery were reduced by the same order of magnitude in both groups. Jejunal mucosal NO production and oxygen consumption decreased markedly in the hypovolemia group but remained stable in the group subjected to septic shock. CONCLUSIONS: These data suggest that blood loss inhibits jejunal mucosal NO production as part of a general downregulation of nonvital organs. Sepsis represents a more complex stress condition with activation/maintenance of host defense mechanisms as reflected by maintained jejunal mucosal NO production despite reduced gut blood perfusion.

Analysis of Variance↗
PubMed2001

Identification of a structural motif that confers specific interaction with the WD40 repeat domain of Arabidopsis COP1.

Arabidopsis COP1 is a photomorphogenesis repressor capable of directly interacting with the photomorphogenesis-promoting factor HY5. This interaction between HY5 and COP1 results in targeted deg radation of HY5 by the 26S proteasome. Here we characterized the WD40 repeat domain-mediated interactions of COP1 with HY5 and two new proteins. Mutational analysis of those interactive partners revealed a conserved motif responsible for the interaction with the WD40 domain. This novel motif, with the core sequence V-P-E/D-&phi;-G (&phi; = hydrophobic residue) in conjunction with an upstream stretch of 4-5 negatively charged residues, interacts with a defined surface area of the ss-propeller assembly of the COP1 WD40 repeat domain through both hydrophobic and ionic interactions. Several residues in the COP1 WD40 domain that are critical for the interaction with this motif have been revealed. The fact that point mutations either in the COP1 WD40 domain or in the HY5 motif that abolish the interaction between COP1 and HY5 in yeast result in a dramatic reduction of HY5 degradation in transgenic plants validates the biological significance of this defined interaction.

Amino Acid Sequence↗
PubMed2001

PEBP2 and c-myb sites crucial for lambda5 core enhancer activity in pre-B cells.

The lambda5 gene is expressed exclusively in precursor (pre-) B cells where its gene product, as part of the pre-B cell receptor, is crucial for the proliferation of these cells. Several DNA regions regulate the activity and expression pattern of the lambda5 gene. Amongst these is an enhancer, B(lambda5), located 5' of the gene. Here we analyze the lambda5 enhancer core, b(lambda5), which in earlier experiments was demonstrated to retain 50% of the enhancer activity, and show that this activity is restricted to pre-B cells. We identify a DNA element within b(lambda5), PEBP2(lambda5), which is essential for enhancer activity: mutation within this site dramatically reduces core enhancer activity in pre-B cells. The PEBP2(lambda5) site binds bacterially produced polyoma enhancer binding proteins (PEBP) (Runx/AML/CBFA). Furthermore, PEBP2 proteins present in nuclear extracts from murine pre-B cells bind to the PEBP2(lambda5) element. PEBP2 proteins in mature B cells also bind to the PEBP2(lambda5 )element, implying that if PEBP2 proteins are responsible for the stage-specific expression, they have to be non-activating or inhibiting in mature B cells. We also demonstrate that a described partner of PEBP2, c-myb, binds to a sequence termed myb(lambda5) located just upstream of the PEBP2(lambda5) site in the core enhancer. The myb(lambda5) element is also crucial for enhancer activity, since mutating the myb site reduces core enhancer activity to the same extent as mutating the PEBP2 site. Earlier reports have shown that c-myb is expressed at high levels in pre-B cell lines whereas its expression is down-regulated in more mature B cell lines. Thus, c-myb may be involved in determining the stage-specific expression of the lambda5 gene.

Animals↗
PubMed2001

Dynamic involvement of the inducible type of nitric oxide synthase in acid-induced duodenal mucosal alkaline secretion in the rat.

It has previously been shown that mucosal nitric oxide synthase (NOS) is involved in acid-induced duodenal mucosal alkaline secretion. The primary aim of the present study was to elucidate which isoform of NOS is responsible in rats. Immunohistochemistry showed that inducible NOS (iNOS) was constitutively expressed in villous epithelial cells. Exposing the duodenal mucosa to 10 mM HCl resulted in an increased duodenal mucosal alkaline secretion. This response was totally inhibited by intraluminal administration of a selective inhibitor of iNOS (L-N6-1-iminoethyl-lysine). One hour after the acid exposure, western blot technique showed a marked increase in mucosal iNOS expression. A second acid exposure resulted in a further stimulation of alkaline secretion. These data suggest that exposure of the duodenal mucosa to HCI initiates an increased mucosal alkaline secretion, via NO synthesis mediated by iNOS located in the epithelial cells of the villi. In addition, luminal acid stimulates expression of iNOS.

Animals↗
PubMed2001

Calreticulin is an interleukin-3-sensitive calcium-binding protein in human basophil leukocytes.

BACKGROUND: IL-3 enhances basophil histamine release upon stimulation with any known secretagogue. The molecular mechanism behind this regulation is not known, although some observations suggest that IL-3 modulates the calcium part of the signal transduction mechanism. The inhibitory action of glucocorticoids on basophils can be reversed by stimulation with IL-3. METHODS: Calcium-binding proteins in the basophil cell line KU812 were identified by two-dimensional gel electrophoresis, Calcium-overlay assay, N-terminal sequence analysis, and mass spectometry. The presence of the same proteins in purified human basophil leukocytes was established by comigration of KU812 and human basophil proteins on the two-dimensional gels. The expression of the calcium-binding proteins in the absence and presence of IL-3 and/or anti-IgE was determined by densitometric measurement of the spots on the two-dimensional gels. RESULTS: Calreticulin was identified on the two-dimensional gel of KU812 proteins. A protein with exactly the same migration pattern was found on the gels of proteins from purified human basophils. Immunoblotting with a specific antihuman calreticulin antibody confirmed that this protein was calreticulin. Subsequent analysis showed that the expression of calreticulin in the basophils is upregulated twofold upon stimulation with rhIL-3, even in doses below those needed for enhancement of histamine release. CONCLUSIONS: The expression of calreticulin in human basophil leukocytes is regulated by IL-3. Calreticulin is known to modulate IP3-dependent Ca2+ influx in different cell systems, and calreticulin overexpression inhibits steroid-induced transcriptional activation. Therefore, modulation of calreticulin expression may be one mechanism by which IL-3 exerts its effects on human basophils.

Basophils↗
PubMed2001

Effects of hypovolaemia on acid-induced duodenal mucosal damage in the rat.

Modest acute hypovolaemia in rats markedly decreases the duodenal mucosal alkaline secretion via neurohumoral links. The present study was undertaken to investigate if such a procedure influences the morphological changes observed following an acid challenge of the duodenal mucosa. Experiments were performed on anaesthetized male Sprague-Dawley rats. HCl (10 or 100 mM) was infused during 15 min into the duodenum via a luminally situated catheter. Time controls were compared with animals bled 10% of total blood volume. Mucosal damage was evaluated by light microscopic morphometry on transverse sections and by scanning electron microscopy of the luminal surface. Perfusion with either 10 mM or 100 mM HCl reduced villus length by about 30%. The villus area was unaffected by 10 mM HCl, but was reduced significantly by 10% by 100 mM HCl as compared with NaCl time controls. Hypovolaemia did not influence the morphometrical changes induced by 10 mM HCl but reduced significantly both villus length (-28%) and villus area (-10%) as compared with the unbled 100 mM HCl group. Scanning electrone microscopy (SEM)-based visual damage score was not influenced by the hypovolaemia procedure in any of the acidities. Morphological changes of the duodenal mucosa, induced by moderate intra-luminal acidity (10 mM HCl), is not influenced by hypovolaemia. However, at higher acidities (100 mM HCl) the hypovolaemia contributes to more severe mucosal damage.

Animals↗
PubMed2001

Global repolarization sequence of the ventricular endocardium: monophasic action potential mapping in swine and humans.

The aim of this study was to evaluate the global sequence of repolarization over the ventricular endocardium. Disturbances in myocardial repolarization are associated with the genesis of arrhythmias. However, little is known about the global sequence of repolarization. Monophasic action potentials (MAPs) were recordedfrom 61 +/- 18 LV and/or RV sites in ten healthy pigs and from 43 +/- 15 LV or RV sites in eight patients using the CARTO system. Local activation time (AT), end-of-repolarization (EOR) time, and MAP duration were calculated and three-dimensional global maps of AT, EOR, and MAP duration constructed. LV maps were obtained from all ten pigs and RV maps from three pigs. Five RV maps and five LV maps were obtained from the eight patients. (1) EOR sequence was recognizable in 12 of 13 pig maps and in all the patient maps. (2) EOR followed the sequence of activation in 12 of 13 pig maps and 8 of 10 patient maps. (3) The longest MAPs were recorded in or near the earliest activation area, and the shortest ones in or near the latest activation area in all the pig maps and in nine often and eight often patient maps, respectively. (4) In all maps, MAP duration and AT were negatively correlated, and EOR and AT positively correlated. In conclusion, repolarization gradients exist over the pig and the human ventricular endocardium. The activation sequence is a determinant for the repolarization sequence. The magnitude of the progressive MAP shortening with progressively later activation, relative to local AT, is a critical factor governing the direction and pattern of the EOR.

Action Potentials↗
PubMed2001

Angiotensin II type 2 receptor-mediated duodenal mucosal alkaline secretion in the rat.

The aims of this study were to elucidate the distribution of angiotensin receptors (AT(1) and AT(2)) in the duodenal wall and to investigate whether AT(2) receptors are involved in the regulation of duodenal mucosal alkaline secretion, which is of importance for the mucosal defense against gastric acid. Immunohistochemistry was used to locate AT(1) and AT(2) receptors in chloralose-anesthetized rats. Duodenal mucosal alkaline output was measured by use of in situ pH-stat titration. Immunohistochemistry demonstrated a distinct staining for both AT(1) and AT(2) receptors in the lamina propria of the villi and also for AT(1) receptors in the muscularis interna. When angiotensin II was infused in the presence of the AT(1) receptor antagonist losartan, mucosal alkaline secretion increased by ~50%. This response was inhibited by the AT(2) receptor antagonist PD-123319. The AT(2) receptor agonist CGP-42112A increased mucosal alkaline secretion by ~50%. This increase was absent in the presence of PD-123319 but not in the presence of losartan or the local anesthetic lidocaine. We conclude that angiotensin II stimulates duodenal mucosal alkaline secretion by activation of AT(2) receptors located in the duodenal mucosa/submucosa.

Anesthetics, Local↗