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Biomedical subjects

L Nilsson

Publications and source records attributed to L Nilsson.

At least 199 records · Page 11Linked to original sources
PubMed1994

Hydrosalpinx reduces in-vitro fertilization/embryo transfer pregnancy rates.

A retrospective study was designed to examine whether the presence of a hydrosalpinx influenced pregnancy outcome following in-vitro fertilization (IVF) treatment in stimulated cycles. A total of 254 women with tubal lesions were included. Patients with one or two hydrosalpinges were compared with patients having other tubal lesions and pregnancy outcome was analysed. Both pregnancy and delivery rates were significantly higher in the patient group without a hydrosalpinx. The results after frozen embryo transfer showed the same tendency. These findings strongly indicate that a permanent hydrosalpinx has a negative influence on implantation, as well as on pregnancy, and suggest that a more active approach against large hydrosalpinges should be undertaken before IVF treatment, in order to improve the pregnancy rates.

Embryo Transfer↗
PubMed1994

Lipoamidase and biotinidase activities in the rat: tissue distribution and intracellular localization.

Lipoamidase (not yet given an EC number) activity was measured in various rat tissues using two different substrates, one natural, lipoyllysine (epsilon-N-(D,L-lipoyl)L-lysine) and one artificial, lipoyl-p-aminobenzoic acid (N-D,L-lipoyl-p-aminobenzoic acid). Biotinidase, EC 3.5.1.12, was measured in the same tissue with the artificial substrate, biotinyl-p-aminobenzoic acid (N-D-biotinyl-p-aminobenzoic acid). Lipoamidase measured as lipoyl-p-aminobenzoic acid hydrolase activity had two pH optima, at pH 6.0 and pH 9.5, in liver homogenate, but only one pH optimum at pH 6.0 in rat plasma. Lipoamidase measured as lipoyllysine hydrolase activity had a pH optimum at pH 5.5 both in liver homogenate and plasma. Similarly, biotinidase shows a single pH optimum at pH 6.0 in liver homogenate and plasma. The properties of lipoyllysine hydrolase and biotinidase were similar with respect to thermostability, pH stability and inhibition pattern, and their properties differed from those of lipoyl-p-aminobenzoic acid hydrolase. Lipoyllysine hydrolase and biotinidase activities were highest in kidney, liver and blood plasma, whereas lipoyl-p-aminobenzoic acid hydrolase activities were highest in liver, brain and kidney. Lipoyllysine hydrolase and biotinidase activities were found mainly in the liver microsomal fraction, and lipoyl-p-aminobenzoic acid hydrolase was recovered from the microsomal fraction and to a small extent from the mitochondrial fraction. These results indicate that liver lipoyl-p-aminobenzoic acid hydrolase is an enzyme protein which differs from lipoyllysine hydrolase, and the data also indicate that liver lipoyllysine hydrolase and biotinidase are the same enzyme protein.

Amidohydrolases↗
PubMed1994

Adjuvant growth hormone treatment during in vitro fertilization: a randomized, placebo-controlled study.

OBJECTIVES: To explore the effect of recombinant, human GH on follicular development and oocyte retrieval after gonadotropin stimulation with the addition of GH or placebo to a standard IVF treatment regimen. Further, to investigate whether GH is a more effective adjuvant if the standard treatment regimen is preceded by GH injections. DESIGN: A randomized, double-blind, parallel, placebo-controlled study. SETTING: The IVF unit at university hospital. PATIENTS: Forty normally ovulating women, age 25 to 38 years, with infertility because of tubal factors and being classified as "poor responders" with at least two previously performed and failed IVF attempts. INTERVENTIONS: Human, recombinant GH (Genotropin, Kabi Pharmacia, Uppsala, Sweden) or placebo (0.1 IU/kg body weight per day) was given SC as pretreatment during down regulation with GnRH and during stimulation with hMG according to the randomized protocol. MAIN OUTCOME MEASURES: Number of oocytes retrieved after stimulation, total amount of gonadotropin used, time required for stimulation, number of follicles developing, rate of fertilization, and cleavage in vitro. Further, the quality of embryos, development of the endometrium, rate of clinical pregnancy, and serum and follicular fluid (FF) concentrations of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 were estimated. RESULTS: The number of oocytes retrieved did not differ significantly between the groups, nor did the amount of hMG required for stimulation. The fertilization rate increased in patients who had received GH. Growth hormone caused a significant increase in serum and FF levels of IGF-I. An increase in serum IGFBP-3 could also be recorded in patients who had received GH. CONCLUSION: Although certain beneficial effects were noted in GH-treated patients, the overall results did not support GH as a clinically useful adjuvant treatment.

Adjuvants, Pharmaceutic↗
PubMed1994

Renal arteriovenous shunting in rejecting allograft, hydronephrosis, or haemorrhagic hypotension in the rat.

We studied the occurrence of arteriovenous (A-V) shunting in three experimental rat models, namely in rejecting allograft kidney, in uni- or bilateral ureteral obstruction, and in haemorrhagic hypotension. Isografted or sham-operated rats served as controls. Radiolabelled microspheres were injected into the renal artery and the increase in the amount of radioactivity in the lungs was considered to reflect A-V shunting in the kidney. In animals exposed to haemorrhage, with a blood pressure not less than 70% of the initial blood pressure, practically no shunting was seen. When animals were bled to a hypotension beyond the autoregulation, A-V shunting occurred inversely correlated to the degree of hypotension. In ureteral obstruction, a less marked but significant increase in shunting of microspheres to the lungs was found after 24 h of unilateral obstruction, irrespective of whether the spheres were injected into the obstructed or the contralateral kidney. Significant A-V shunting during the allograft rejection process was also demonstrated. Histologically, microspheres were found in afferent arterioles less frequently in kidneys with A-V shunting than in controls. These results indicate that A-V shunting is involved in haemorrhagic hypotension, renal graft rejection, and hydronephrosis. In the latter situation A-V shunting is probably regulated by a humoral factor.

Animals↗
PubMed1994

Contrasting roles of rivers and wells as sources of drinking water on attack and fatality rates in a hepatitis E epidemic in Somalia.

In early 1988, an increased incidence of acute hepatitis was observed in villages along the Shebeli River in the Lower Shebeli region of Somalia. This was followed by a large epidemic that lasted until late 1989. In a survey of 142 villages with a population of 245,312 individuals, 11,413 icteric cases were recorded, of which 346 died, corresponding to an attack rate and a case fatality rate of 4.6% and 3.0%, respectively. The etiologic role of hepatitis E virus (HEV) in this epidemic was proven by demonstrating anti-HEV in 128 of 145 sampled cases as a sign of recent infection with HEV. In three villages, where a special study protocol was implemented, the attack rate was found to increase significantly with age from 5% in the group 1-4 years of age to 13% in the group 5-15 years of age and to 20% for persons older than 15 years of age. Among cases 20-39 years of age, the female-to-male ratio was 1.5:1, which was a significant predominance of females. As in other hepatitis E outbreaks, there was a high fatality rate in pregnant females, estimated to be 13.8%. The epidemic peaked with the rise in the level of the river during rainfall, suggesting that the disease was waterborne. The attack rate was higher (6.0%) in villages supplied with river water, while fewer cases were recorded in those relying on wells or ponds for their water supply, 1.7% and 1.2%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Fertilization and pregnancy after intracytoplasmic microinjection of acrosomeless spermatozoa.

Spermatozoa lacking acrosomes were injected into the cytoplasm of mature human oocytes. In two subsequent cycles, 12 of 28 (43%) oocytes were fertilized, and the ET of the second cycle resulted in a twin pregnancy. This report describes, to the best of our knowledge, the first case of successful fertilization and delivery after using acrosomeless spermatozoa. Our hope is that with increasing experience with microinjection, in the near future, this type of infertility will not remain a serious problem.

Acrosome↗
PubMed1993

Decrease of somatostatin receptor binding in the rat cerebral cortex after ibotenic acid lesion of the nucleus basalis magnocellularis: a quantitative autoradiographic study.

The specific binding of 125I-Tyr11-somatostatin-14 (125I-Tyr11-SS-14) was measured in different cortical regions after unilateral ibotenic acid lesion of the rat nucleus basalis magnocellularis (NBM). A marked loss of acetylcholinesterase-positive fibers was observed in the frontal, parietal, temporal and occipital cortices ipsilateral to the lesion. The loss of cholinergic cell bodies in the NBM was further investigated with choline-acetyltransferase (ChAT) immunohistochemistry which indeed demonstrated a loss of ChAT-positive magnocellular perikarya. Autoradiographic analyses of specific binding of 125I-Tyr11-SS-14 demonstrated a significant reduction in binding density in the denervated parts of the neocortex. The decrease in specific binding was most pronounced (40-50%) in the superficial layers (I-III) of the frontal, parietal and temporal cortices 2 and 4 weeks after lesion. A significant loss in 125I-Tyr11-SS-14 binding in the deeper layers was only observed in the frontal cortex after 2 and 4 weeks. In the occipital cortex a significant decrease was measured in the superficial layers only after 4 weeks. The specific binding in all cortical regions returned to normal after 6 weeks. The results suggested that 125I-Tyr11-SS-14 binding sites are localized on cholinergic afferents in the rat neocortex and that an up-regulation of number of binding sites, alternatively an increased binding affinity occurred with time after lesion.

Animals↗
PubMed1993

Environmental influence on somatostatin levels and gene expression in the rat brain.

In the present study we have quantified preprosomatostatin-mRNA and somatostatin levels in rat brain following environmental stimulation. Animals were housed for 30 days in an enriched or impoverished environment prior to analysis. After 30 days of housing half of the rats from each environment were behaviourally tested for 3 days. Housing in enriched environment improved performance in a spatial learning situation. The open-field behaviour of these animals was characterized by initially higher rearing scores and a more rapid habituation to novel environment as measured by spontaneous locomotor activity. We found significantly elevated somatostatin levels in the cortex following enriched environment, compared with impoverished environment. Exposure to behavioural testing of impoverished animals led to increased cortical somatostatin levels. Hypothalamic somatostatin levels increased significantly after housing in enriched environment, while the testing procedure had no influence. Our data shows that the somatostatin system in the rat brain was activated in association with cognitive changes, that were induced by housing in an enriched environment.

Animals↗
PubMed1993

How consistent are molecular dynamics simulations? Comparing structure and dynamics in reduced and oxidized Escherichia coli thioredoxin.

In this study we have examined several parameters that can be used for checking the consistency and accuracy of protein structures and molecular dynamics simulations. This is done by comparing: (1) three X-ray structures of oxidized Escherichia coli thioredoxin (Trx-S2); (2) 14 NMR structures of reduced E. coli thioredoxin (Trx-(SH)2); and (3) 30 different simulations, 15 of Trx-S2 and 15 of Trx-(SH)2. The energy, the agreement with NOE data, the root-mean-square deviation between structures, and the surface characteristics of all these structures are analyzed. The 30 simulations, four water simulations, 20 standard vacuum simulations and six alternative vacuum simulations, are examined with respect to mobility, temperature factors and aromatic side-chain mobility. It is shown that although vacuum simulations may reproduce some parameters, all the features of a water simulation cannot be reproduced in any of these simulations. Several of the parameters described above are shown to be good for discriminating between an accurate and an inaccurate simulation. It is also shown that 100 ps is too short a time to obtain statistically certain temperature factors and correlation functions of aromatic side-chain motions. The results also suggest that performing ten 100 ps simulations spans the conformation space better than one 1 ns simulation.

Computer Simulation↗
PubMed1993

Three-dimensional model for the membrane domain of Escherichia coli leader peptidase based on disulfide mapping.

We have mapped the interface between the two transmembrane alpha-helices in the membrane domain of the Escherichia coli enzyme leader peptidase by analyzing disulfides formed between pairs of cysteine residues introduced near their respective periplasmic ends. The interface is formed primarily from aliphatic amino acids, and the two helices appear to pack against each other in a left-handed supercoil. We suggest that disulfide mapping may be a generally applicable approach for the construction of models of helix-helix interfaces in membrane proteins.

Amino Acid Sequence↗
PubMed1993

Fluorometric determination of cyanate in plasma by conversion to 2,4(1H,3H)-quinazolinedione and separation by high-performance liquid chromatography.

A fluorometric high-performance liquid-chromatographic method is described for the determination of cyanate in human plasma. The method is based on the derivatization of cyanate with 2-aminobenzoic acid (anthranilic acid), leading to a stable cyclic fluorescent product, 2,4(1H,3H)-quinazolinedione. The fluorescent product was extracted with ethyl acetate, passed through a cation-exchange resin to eliminate the excess of derivatization reagent, and then concentrated on a Sep-Pak C-18 cartridge before reversed-phase chromatography and fluorometric detection. The precision of the method was satisfactory (coefficient of variation 2.3%) and the analytical recovery was quantitative (103%). Detection limit was found to be 8 nmol/liter from a 1-ml plasma sample. Cyanate in plasma was stable for 3 months when stored in liquid nitrogen. The mean and SD cyanate level in human plasma from 17 healthy nonsmoking subjects was 45 +/- 21 nmol/liter.

Adult↗
PubMed1993

Co-purification of human serum lipoamidase and biotinidase: evidence that the two enzyme activities are due to the same enzyme protein.

A more than 20000-fold purification of human serum lipoamidase is described. This was accomplished by (NH4)2SO4 precipitation and chromatography on DEAE-Sepharose, Blue Sepharose CL-6B and phenyl-Sepharose CL-4B, followed by preparative isoelectric focusing (IEF) and finally by gel-permeation chromatography. Co-precipitation and co-chromatography of lipoamidase and biotinidase activities with equal yields and purification were obtained in all the purification steps, indicating that lipoamidase and biotinidase activities in human serum are due to the same enzyme protein. After preparative IEF, two fractions with both lipoamidase activity and biotinidase activity were found at pI 4.0 and pI 4.4 respectively. The molecular mass of the enzyme was found to be 76 kDa. When 2-mercaptoethanol was used instead of cysteine as stabilizer during the purification procedure, only one major form (pI 4.0) of the enzyme was obtained after preparative IEF. By addition of cysteine, this form was transformed to an enzyme with pI 4.4, indicating that this latter form is a cysteine adduct, produced during the IEF procedure.

Amidohydrolases↗
PubMed1993

Structural fluctuations between two conformational states of a transmembrane helical peptide are related to its channel-forming properties in planar lipid membranes.

Putative transmembrane helices of membrane proteins in general and channel proteins in particular often contain proline residues which may induce a bend into an otherwise regular helical structure. Here we show by fluorescence-energy-transfer measurements and molecular-dynamics calculations that, in the case of synthetic bilayer-spanning helical polypeptides, a proline-induced bend in a helix acts as a flexible element mediating rigid body motions of the helical segments. Most important, such structural fluctuations in the transmembrane helices seem to play a functional role in the formation of ionic channels in planar lipid bilayers and biological membranes.

Amino Acid Sequence↗
PubMed1993

A population-based study of dementia in 85-year-olds.

BACKGROUND: The aim of this study was to investigate the causes, severity, and prevalence of dementia in a representative sample of 494 85-year-olds living in Gothenburg, Sweden. METHODS: The study included a psychiatric interview, neuropsychological and physical examinations, comprehensive laboratory tests, electrocardiography, chest radiography, computed tomography (CT) of the head, and analysis of cerebrospinal fluid. A person close to each subject was also interviewed. Dementia was defined according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised), Alzheimer's disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and vascular dementia according to recently proposed criteria that incorporate information from CT scanning and the patient's neurologic history. RESULTS: The prevalence of dementia was 29.8 percent (147 subjects). The condition was mild in 8.3 percent, moderate in 10.3 percent, and severe in 11.1 percent. There were no significant sex-related differences in prevalence or severity. Of the subjects with dementia, 43.5 percent had Alzheimer's disease, 46.9 percent had vascular dementia (multi-infarct dementia in 34.6 percent, dementia related to cerebral hypoperfusion in 4.1 percent, and mixed dementia in 8.2 percent), and 9.5 percent had dementia due to other causes. The three-year mortality rate was 23.1 percent in the subjects without dementia, 42.2 percent in the patients with Alzheimer's disease, and 66.7 percent in the patients with vascular dementia. Infarcts detected by CT scanning were significantly more common in the subjects with dementia than in those without it (27.9 percent vs. 12.6 percent). CONCLUSIONS: Dementia was present in nearly a third of unselected 85-year-olds in Sweden. Almost half these subjects appeared to have vascular dementia, which may currently be more amenable to prevention or treatment than Alzheimer's disease.

Aged↗
PubMed1993

Site specific point mutation changes specificity: a molecular modeling study by free energy simulations and enzyme kinetics of the thermodynamics in ribonuclease T1 substrate interactions.

We have theoretically and experimentally studied the binding of two different ligands to wild-type ribonuclease T1 (RNT1) and to a mutant of RNT1 with Glu-46 replaced by Gln. The binding of the natural substrate 3'-GMP has been compared with the binding of a fluorescent probe, 2-aminopurine 3'-monophosphate (2AP), and relative free energies of binding of these ligands to the mutant and the wild-type (wt) enzyme have been calculated by free energy perturbation methods. The free energy perturbations predict that the mutant RNT1-Gln-46 binds 2AP better than 3'GMP, in agreement with experiments on dinucleotides. Four free energy perturbations, forming a closed loop, have been performed to allow the detection of systematic errors in the simulation procedure. Because of the larger number of atoms involved, it was necessary to use a much longer simulation time for the change in the protein, i,e., the perturbation from Glu to Gln, than in the perturbation from 3'-GMP to 2AP. Finally the structure of the binding site is analyzed for understanding differences in catalytic speed and binding strength.

2-Aminopurine↗