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Biomedical subjects

H Andersson

Publications and source records attributed to H Andersson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Oat beta-glucan increases bile acid excretion and a fiber-rich barley fraction increases cholesterol excretion in ileostomy subjects.

The purpose of this study was to investigate whether oat beta-glucan is responsible for the increased bile acid excretion previously observed with oat-fiber diets. The excretion patterns in ileostomy subjects given diets containing oat-bran bread with and without added beta-glucanase, a beta-glucan-degrading enzyme, were compared. The effect of a beta-glucan-rich barley fraction on sterol excretion was also investigated. Nine ileostomy subjects were served four diets in random order, each diet for 2 consecutive days. Four different kinds of bread, mainly made from oat bran (OB diet, 12.5 g beta-glucan/d), oat bran with beta-glucanase (OBE diet, 3.8 g beta-glucan/d), barley (B diet, 13.0 g beta-glucan/d), or wheat flour (W diet, 1.2 g beta-glucan/d) were added to a basal diet. The 24-h excretion of bile acids was 53% higher in the OB diet period than in the OBE diet period (P < 0.05) and also was significantly higher than in the B and W diet periods (P < 0.05). Median (range) bile acid excretion was 851 (232-1550), 463 (123-1414), 755 (133-1187), and 606 (101-980) mg/d in the OB, OBE, B, and W diet periods, respectively. The excretion of cholesterol was significantly higher in the B diet period than in the OBE and W diet periods (P < 0.05), but the mechanism behind this effect of barley fiber is unknown. In oat bran, however, beta-glucan mediates an increase in bile acid excretion, which most probably explains the effect of oat fiber in lowering serum lipids.

Adult↗
PubMed1995

Prostaglandins reduce hydrochloric acid-induced increase in duodenal mucosal permeability by a mechanism not related to stimulation of alkaline secretion.

The aim was to investigate whether prostaglandins affect HCl-induced mucosal permeability and to elucidate the role of mucosal bicarbonate secretion in protection. Proximal duodenum of anaesthetized rats were perfused with hydrochloric acid and the effects on luminal alkalinization, mucosal permeability and morphology examined in the absence and in the presence of prostaglandin E2 and/or indomethacin. Luminal alkalinization was determined by back titration of the perfusate and mucosal permeability assessed by measuring the clearance of 51Cr-labelled ethylenediaminetetraacetat ([51Cr]EDTA) from blood-to-intestinal lumen. Perfusion with 100 mM HCl for 5 min increased mucosal permeability sixfold and caused villus tip damage. Luminal administration of PGE2 at a concentration of 10(-6) M had no effect whereas 10(-4) M increased alkalinization by 100% but neither concentration affected the HCl-induced increase in mucosal permeability. PGE2 (10(-4) M), however, improved the ability of the duodenal mucosa to recover from the HCl-induced increase in mucosal permeability. Indomethacin (5 mg kg-1, i.v.) increased alkalinization, augmented HCl-induced mucosal permeability and aggravated mucosal injury. In animals pre-treated with PGE2 plus indomethacin, the HCl-induced increases in mucosal permeability were lower and injury less pronounced than in animals treated with indomethacin alone. No correlation was found between the rate of alkalinization and the HCl-induced increase in mucosal permeability. It is concluded that endogenous prostaglandins reduced the extent of 100 mM HCl-induced duodenal mucosal damage by a mechanism other than the stimulation of alkaline secretion.

Animals↗
PubMed1995

Carboplatin in combination with epirubicin and cyclophosphamide in patients with advanced ovarian cancer. A phase II study.

Seventy-one patients with epithelial ovarian cancer stage III (n = 56) or IV (n = 15) were treated with carboplatin 300 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 400 mg/m2 every fourth week. Patients clinically free of tumour after six courses (n = 58) underwent a second-look laparotomy. Seventeen patients were microscopically tumour-free (24% of all) and an additional 10 (14%) had only microscopic cancer. Median time to progression was 19 months. The median survival was 33 months and the estimated 5-year survival 27%. The toxicity was mainly haematological, with leukopenia WHO grade 3-4 seen in 88% and thrombocytopenia grade 3-4 in 42% of the patients. The gastrointestinal toxicity was mild and no renal toxicity was seen. This chemotherapy regimen was effective with acceptable toxicity and could be given on an out-patient basis. The possibility of increasing the efficacy and decreasing the toxicity was discussed.

Adult↗
PubMed1995

Time-course of trimethyltin effects on the monoaminergic systems of the rat brain.

The normalization of certain behavioral functions after a trimethyltin (TMT) insult indicates that compensatory processes may occur (Paule and McMillan, 1986; Bushnell and Angell, 1992). The monoamine (MA) neurons are known to be sensitive to TMT, however, a detailed temporal description of the effects is lacking. One week after TMT exposure, 8 mg/kg i.p. to adult male Sprague-Dawley rats, the levels of serotonin (5-HT) and noradrenaline (NA) were decreased in several brain regions, whereas the levels of dopamine were unaltered. In addition, a reduced density of 5-HT immunoreactive fibers was seen in hippocampus and cortex. The lesion in the serotonergic and noradrenergic systems was followed by a recovery. Twelve weeks after TMT treatment, 5-HT and NA levels were increased in hippocampus, and 5-HT levels in striatum. In cerebellum, NA, 5-HT and 5-HIAA levels were decreased at 12 weeks. Compensatory processes led to recovered levels of 5-HT and NA in all regions but cerebellum, although regionally specific increases developed with time possibly due to hyperinnervation. Inhibition of the aromatic amino acid decarboxylase with NSD1015 yields accumulation of catecholamine and 5-HT precursors. Two weeks after TMT, levels of 5-HTP and L-dopa were not different in the TMT-treated rats as compared to controls, indicating that TMT does not affect MA synthesis.

Animals↗
PubMed1995

Navoban (tropisetron) alone and in combination with dexamethasone in the prevention of chemotherapy-induced nausea and vomiting: the Nordic experience. The Nordic Antiemetic Trial Group.

To evaluate the efficacy and safety of Navoban (tropisetron) three different Nordic multicentre trials were conducted during the period 1988-92. In all, 1050 patients were recruited from 15 centres. In the first study, Navoban monotherapy was compared with a high-dose metoclopramide cocktail. In the second, Navoban +/- dexamethasone was evaluated for those patients not fully protected by Navoban alone. In the third trial, Navoban was evaluated for various chemotherapy regimens, for long-term efficacy, and for various risk groups of patients. Spontaneous intercycle variations were also evaluated. Navoban was found to be as effective as the antiemetic cocktail but with a more favourable spectrum of side effects and a simpler schedule of administration. Navoban was more effective during the acute than the delayed phase. Addition of dexamethasone significantly improved prevention of both acute and delayed emesis. Long term efficacy seemed to be stable up to 10 cycles of chemotherapy. Patients treated with noncisplatin regimens showed significantly higher protection rates than patients treated with cisplatin. Various cancer diagnoses and cytostatic agents were also evaluated. Gender and age were important risk factors. Navoban was found to be an efficacious antiemetic agent, especially regarding acute nausea and vomiting. Addition of a corticosteroid significantly improved the effect during highly emetogenic chemotherapy. The role of Navoban for delayed emesis must be evaluated in future trials. The two most common side effects were headache and constipation. Overall, Navoban was well tolerated and patient compliance with the drug was high.

Antiemetics↗
PubMed1995

Effects of low-fat milk and fermented low-fat milk on cholesterol absorption and excretion in ileostomy subjects.

OBJECTIVE: To study small bowel cholesterol absorption and sterol excretion in order to explain possible serum cholesterol-lowering mechanisms of low-fat milk products. DESIGN: Two 24-h sterol balance studies with 1 litre of low-fat milk or one litre of fermented milk, in random order, added to a controlled diet. [3H]Cholesterol absorption was measured during each period. The results were compared to those on two 24-h periods with isocaloric amounts of lemonade given to the same basic diet, before and after the study. One litre of the two milk products was also consumed in addition to their normal diets in a cross-over design of 3 weeks and with run-in and run-out periods of 2 weeks each with 1000 ml of lemonade preceding the balance studies: SETTING: Outpatient clinic, where the subjects were eating their meals during the day and ileostomy bags collected. SUBJECTS: Nine ileostomy subjects, who have earlier participated in similar studies, volunteered for the study. All subjects completed the study. RESULTS: Cholesterol absorption was highest (66%) in the lemonade period, intermediate in the low-fat milk period (61%) and lowest in the fermented low-fat period (55%) (P < 0.05 for differences). Net cholesterol excretion (excretion minus intake) and calculated endogenous cholesterol excretion were significantly (P < 0.05 for differences) higher in the low-fat milk period than in the lemonade period and the fermented low-fat milk period. No significant change in serum cholesterol was, however, seen after 3 weeks on each milk regimen. CONCLUSION: Assimilation of cholesterol by microorganisms could possibly explain the reduced uptake of cholesterol with fermented milk. The mechanism behind the increased endogenous cholesterol excretion, induced by low-fat milk, is unclear.

Adult↗
PubMed1994

Positively charged residues influence the degree of SecA dependence in protein translocation across the E. coli inner membrane.

The sec machinery catalyzes the translocation of nascent polypeptide chains across the inner membrane of E. coli, yet some inner membrane proteins depend only weakly or not at all on an intact sec function for membrane insertion even though they have stretches of chain protruding into the periplasmic space. Earlier work has demonstrated that the length of a periplasmic loop correlates with its degree of sec-dependence. We now show that the content of positively charged residues in a translocated loop also correlates with the degree of dependence on SecA function, suggesting that arginines and lysines may be inherently difficult to move across the membrane during sec-dependent translocation.

Adenosine Triphosphatases↗
PubMed1994

Membrane protein topology: effects of delta mu H+ on the translocation of charged residues explain the 'positive inside' rule.

The membrane electrochemical potential is critical for the export of most periplasmic proteins in Escherichia coli. Its exact role during insertion of integral inner membrane proteins, however, remains obscure. Using derivatives of the inner membrane protein leader peptidase (Lep), we now show that the membrane potential appears to stimulate the membrane translocation of chain segments containing negatively charged residues, that positively charged regions appear to be more easily translocated in the absence of a potential, and that certain Lep constructs insert with different topologies in the presence and absence of a membrane potential, suggesting that the electrochemical potential introduces an asymmetry between the topological effects of positively and negatively charged amino acids during the process of membrane protein insertion in E. coli.

Amino Acid Sequence↗
PubMed1994

Trimethyltin-induced expression of GABA and vimentin immunoreactivities in astrocytes of the rat brain.

Adult Sprague-Dawley rats were given a single dose of trimethyltin chloride (TMT). Three days following treatment, a neuronal alteration was observed in the CA3c pyramidal cell layer of hippocampus which was not accompanied by any apparent astrocyte reaction. At 1 as well as 2 weeks after treatment, a gliosis in hippocampus, piriform, and entorhinal cortices was detected by glial fibrillary acidic protein (GFAP) immunohistochemistry. Concomitant with the enhanced astrocytic GFAP, astrocytes were swollen and expressed immunoreactivity to vimentin and gamma-aminobutyric acid (GABA). The astrocytic GABA immunoreactivity may reflect a trimethyltin-induced alteration in astrocyte phenotype, or alterations in compartmentalization and/or metabolism of GABA.

Animals↗
PubMed1994

Tropisetron (Navoban) in the prevention of chemotherapy-induced nausea and vomiting--the Nordic experience.

An open, noncomparative, Nordic multicenter study was carried out during 1991-1992 to evaluate the 5-HT3 receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1-19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%-73% (days 2-6) in the complete series. Treatment efficacy remained stable (60%-79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P < 0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course, but not later on. There were no differences in delayed nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effect of rye bran on excretion of bile acids, cholesterol, nitrogen, and fat in human subjects with ileostomies.

The excretion of bile acids, cholesterol, dry matter, nitrogen, fat, and energy in ileostomy effluent, and plasma lipid concentrations were studied in eight subjects with ileostomies. The subjects consumed a wheat bread-based, low-fiber diet (LFD) for 3 wk and a rye bran bread-based, high-fiber diet (HFD) for 3 wk. The ileal excretion of dry matter, nitrogen, fat, and energy was higher during the HFD period. The daily excretion and the percentage of conjugated bile acids were significantly higher and the percentage of free bile acids lower in the ileostomy effluents during the HFD as compared with the LFD period. No significant difference in the excretion of cholesterol, net cholesterol, sterol, or net sterol was noted between the HFD and LFD periods. No significant differences in plasma concentrations of HDL-, LDL-, and total cholesterol, and apolipoprotein A-I and B were observed between the two 3-wk dietary periods.

Adult↗
PubMed1994

Alginate, small bowel sterol excretion, and absorption of nutrients in ileostomy subjects.

The effect of alginate on ileostomy excretion of sterols and nutrients was investigated in six ileostomy subjects fed a constant low-fiber diet with or without supplementation with 7.5 g sodium alginate. A mean of 95% of uronic acids derived from the sodium alginate was recovered in the ileostomy contents. Supplementation with alginate increased fat excretion by 140% and decreased bile acids excretion by 12%. Sodium and potassium excretion were significantly increased whereas starch and nitrogen excretion were unchanged. Five of six subjects showed a decreased apparent absorption of iron and manganese with alginate, which, however, was not statistically significant. Absorption of phosphorus, calcium, magnesium, and zinc were unchanged. Almost no digestion of sodium alginate occurs in the stomach and small intestine. The increased fatty acids excretion may be explained by the binding or trapping of fatty acids in the gel matrix formed by alginate, which may also cause a reduced bile flow.

Adolescent↗
PubMed1994

Ileostomy output and bile acid excretion after intraduodenal administration of oleic acid.

BACKGROUND: Ileostomy output and small-intestinal transport are regulated by complex mechanisms, which the present study aimed to further elucidate. METHODS: The time-related ileostomy output and bile acid excretion after intraduodenal administration of a fat solution (oleic acid, 3.5 g) was studied in 29 ileostomy patients. Eighteen patients had the entire small bowel preserved (group I), whereas 11 had various lengths of the ileum resected or bypassed (group II). RESULTS: Intraduodenal fat administration resulted in a prompt and significant increase in ileostomy output in both groups. The accumulated 2-h output after fat administration amounted to 60% of the normal 24-h output in group I and 30% in group II. A marked increase in bile acid excretion preceded the flow response. The fat-induced response was abolished by administration of cholestyramine. CONCLUSIONS: Bile acids seem to have important regulatory effects with regard to secretion/absorption and transport of small-bowel contents, affecting ileostomy output, with clinical implications in many patients.

Bile Acids and Salts↗
PubMed1994

Digestion and absorption of sorbitol, maltitol and isomalt from the small bowel. A study in ileostomy subjects.

OBJECTIVE: To quantify small bowel digestion and absorption of sorbitol, isomalt and maltitol in ileostomy patients and estimate the metabolizable energy. SUBJECTS: Study A: Nine ileostomy patients, under a constant controlled diet, ate during three consecutive days 2 milk chocolate bars per day, containing 2 x 15 g of polyol, each day with another polyol in random order. The first bar was taken 30 min after breakfast, and the second bar, 7 h after breakfast. Effluents were recovered during the whole study. Study B: 5, 10 or 20 g of sorbitol or isomalt were consumed each day in a drink during two 3-day periods by two ileostomy subjects. The recovery in the ileal effluent was measured over 24 h. RESULTS: Study A: Carbohydrate recovery in ileostomy effluent was 26.8 +/- 2.8% (mean+SEM) for sorbitol, 24.8 + 5.7% for maltitol (2/3 as sorbitol) and 40.0 +/- 0.7% for isomalt (1/3 being sorbitol and mannitol). Ileal excretion, compared with a day without polyol, was compared in 4 subjects. The total volume excreted, as well as dry matter increased after polyol consumption. When taking this extra loss into account, the metabolizable energy value of the polyols for 2 x 15 g intake were: sorbitol, 12 kJ/g (2.8 kcal/g); maltitol, 13 kJ/g (3.1 kcal/g); isomalt, 9 kJ/g (2.1 kcal/g). Study B: The level of digestion and absorption of both sugar alcohols was dose dependent. CONCLUSIONS: These results indicate that sorbitol, maltitol and isomalt are rather extensively absorbed, but the digestibility of the other nutrients is also reduced, due to the osmotic load caused by the polyols in the small intestine. There are evidences of a dose dependency of the energy value of the polyols.

Adult↗
PubMed1993

Position-specific Asp-Lys pairing can affect signal sequence function and membrane protein topology.

Positively charged amino acids are major determinants of the topology of bacterial inner membrane proteins, whereas negatively charged residues by themselves have little or no influence on the transmembrane orientation. Further, positively charged amino acids can very efficiently block the function of signal sequences when placed immediately downstream, while negatively charged residues are much less potent also in this regard. Here, we show that a negatively charged aspartic acid situated close to a positively charged lysine can attenuate both of these effects in a position-specific manner, suggesting that intra- or intermolecular charge pairing can modulate the interactions between positively charged residues in the nascent chain and parts of the secretory machinery or membrane phospholipids. These observations further underscore the importance of charged amino acids during protein translocation and membrane protein assembly.

Amino Acid Sequence↗
PubMed1993

Population-based cohort investigations of the risk for malignant tumors in first-degree relatives and wives of men with breast cancer.

BACKGROUND: Retrospective studies of familial cancer risks could be subjected to bias and should be supplemented with prospective studies if possible. Few such studies exist, and no prospective population-based study has addressed the risk for malignant tumors among relatives or wives of men with breast cancer. METHODS: All first-degree relatives and wives of 153 men whose conditions were diagnosed as male breast cancer from 1965 to 1989 in the southern health-care region of Sweden were identified through parish data. Relatives and wives alive January 1, 1958, were included in two cohorts. Their vital status and cancer morbidity were studied in the Swedish Cancer Registry, Cause of Death Registry, and Census Registry. RESULTS: The incidence for malignant tumors was significantly increased among female first-degree relatives (standardized morbidity ratio [SMR], 1.36). Significantly elevated SMR were seen for breast carcinoma (SMR, 1.80), ovarian carcinoma (SMR, 2.27), and cancer of the parotid gland (SMR, 5.58). Elevated nonsignificant SMR were seen for cancer of the cervix uteri and for bone and soft tissue sarcoma. An almost significant decreased overall cancer incidence was seen for male first-degree relatives (SMR, 0.75). The most pronounced decrease was seen for cancer of the prostate. The increased breast cancer incidence in female relatives were present in mothers, sisters, and daughters. The overall tumor incidence was not increased (SMR, 0.98) in wives of men with breast cancer. There was no significant increase in breast cancer incidence (SMR, 0.97). CONCLUSIONS: Female first-degree relatives of men with breast cancer have an elevated incidence of breast cancer and other female genital tumors, whereas male first-degree relatives have a reduced cancer incidence. Wives of men with breast cancer have a similar cancer incidence as the general population.

Bone Neoplasms↗
PubMed1993

Sec dependent and sec independent assembly of E. coli inner membrane proteins: the topological rules depend on chain length.

Translocation of proteins across the inner membrane of Escherichia coli normally requires the participation of the sec machinery. A number of proteins are known, however, where translocation can proceed unhindered even when the function of either SecA or SecY, central components of the sec machinery, is blocked. We now show that there is a linear correlation between the length of a translocated region and its degree of dependence on SecA and SecY for lengths between 25 and 55 residues. We also find that positively charged residues have distinctly different topological effects during SecA dependent and SecA independent membrane protein insertion, and that a short cytoplasmic segment in Lep can be converted to a translocated segment (with a concomitant inversion of the original topology of the whole molecule) by increasing its length into the SecA/Y dependent realm.

Adenosine Triphosphatases↗