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Biomedical subjects

L Gustafsson

Publications and source records attributed to L Gustafsson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Glycerol kinase deficiency in two brothers with and without clinical manifestations.

We report two brothers with glycerol kinase deficiency (GKD). The older brother had serious clinical symptoms, mental and growth retardation, abnormal skeleton, spontaneous fractures and premature loss of abnormal teeth. He and his mother had low serum phosphate levels. He had elevated serum and urine glycerol levels and GKD was found in cultured fibroblasts. Prenatal diagnosis was performed in the second pregnancy. Glycerol kinase activity was considered normal in a chorionic villus sample of the foetus. After birth, it was found that the boy had elevated serum and urine glycerol levels. Enzymatic analysis in cultured fibroblasts revealed that this boy also had GKD, in spite of having no expression of the disease. Chromosomal analyses in the parents and both boys were normal. Major rearrangements or deletions were not detected in molecular studies of DNA from the two brothers. The hybridisation pattern was normal and no allelic loss was observed.

Abnormalities, Multiple↗
PubMed1996

Influence of the nitrogen source on Saccharomyces cerevisiae anaerobic growth and product formation.

To prevent the loss of raw material in ethanol production by anaerobic yeast cultures, glycerol formation has to be reduced. In theory, this may be done by providing the yeast with amino acids, since the de novo cell synthesis of amino acids from glucose and ammonia gives rise to a surplus of NADH, which has to be reoxidized by the formation of glycerol. An industrial strain of Saccharomyces cerevisiae was cultivated in batch cultures with different nitrogen sources, i.e., ammonium salt, glutamic acid, and a mixture of amino acids, with 20 g of glucose per liter as the carbon and energy source. The effects of the nitrogen source on metabolite formation, growth, and cell composition were measured. The glycerol yields obtained with glutamic acid (0.17 mol/mol of glucose) or with the mixture of amino acids (0.10 mol/mol) as a nitrogen source were clearly lower than those for ammonium-grown cultures (0.21 mol/mol). In addition, the ethanol yield increased for growth on both glutamic acid (by 9%) and the mixture of amino acids (by 14%). Glutamic acid has a large influence on the formation of products; the production of, for example, alpha-ketoglutaric acid, succinic acid, and acetic acid, increased compared with their production with the other nitrogen sources. Cultures grown on amino acids have a higher specific growth rate (0.52 h-1) than cultures of both ammonium-grown (0.45 h-1) and glutamic acid-grown (0.33 h-1) cells. Although the product yields differed, similar compositions of the cells were attained. The NADH produced in the amino acid, RNA, and extracellular metabolite syntheses was calculated together with the corresponding glycerol formation. The lower-range values of the theoretically calculated yields of glycerol were in good agreement with the experimental yields, which may indicate that the regulation of metabolism succeeds in the most efficient balancing of the redox potential.

Amino Acids↗
PubMed1995

Low efficiency of cytologic screening for cancer in situ of the cervix in older women.

Cytologic screening for cervical cancer has proven to be beneficial in many countries, although the value of this intervention in women older than 50 years remains controversial. The purpose of this study was to investigate the efficiency of detecting cancer in situ by means of a cytologic smear at different ages, with special emphasis on the benefit of screening in women above the age of 50. We analyzed 466,275 smears taken in an open cohort of 118,890 women in Sweden between 1969 and 1988. The number of cancers in situ detected per 1,000 smears, the detection ratio, was used as an outcome measure in univariate analyses and in multivariate regression models. Cancer in situ was detected in 1,076 women in the study cohort. The detection ratio peaked at ages 30 to 34 and decreased heavily during the next 15 years of age. The efficiency of taking smears at ages above 50 was only 20 per cent (OR, 0.19; 95% CI, 0.14-0.26) of that at ages 30 to 34. These results were not changed when adjusting for time period and time interval since the previous smear. In spite of a high incidence of invasive cervical cancer in older women, the benefit of cytologic screening to detect cancer in situ above the age of 50 is uncertain.

Adult↗
PubMed1995

Energetics and product formation by Saccharomyces cerevisiae grown in anaerobic chemostats under nitrogen limitation.

Anaerobic fermentation of glucose (20 g/l) by Saccharomyces cerevisiae CBS 8066 was studied in a chemostat (dilution rate = 0.05-0.25 h-1) at different concentrations of the nitrogen source (5.00 g/l or 0.36 g/l ammonium sulphate). The ethanol yield (g ethanol produced/g glucose consumed) was found to be higher and the glycerol yield (g glycerol formed/g glucose consumed) lower during nitrogen limitation than under carbon limitation. The biomass yield on ATP (g dry weight biomass produced/mol ATP consumed), was consequently found to be lower during nitrogen-limited conditions.

Adenosine Triphosphate↗
PubMed1995

Efficiency of organised and opportunistic cytological screening for cancer in situ of the cervix.

Cervical cancer incidence and mortality can be reduced by removal of precursor lesions detected at cytological screening. Organised screening, i.e. regular invitation of defined target groups, is generally considered more effective than opportunistic screening. The latter method however, is predominant in most settings. There is no scientific basis for advocating one type of screening or the other. Our aim was to compare the two types and to analyse their efficiency. We analysed 466,275 smears taken in an open cohort of 118,890 women during 1969-88. A computerised database permitted standardised classification of all smears and complete ascertainment of cancer in situ through record linkage. The number of in situ cancers detected per 1000 smears, the detection ratio, was used as an outcome measure both in univariate analyses and in multivariate logistic regression models. Cancer in situ was detected in 1076 women in the study cohort, with a detection ratio of 3.0 at organised and 2.1 at opportunistic screening, yielding an unadjusted odds ratio of 0.69 (95% CI 0.61-0.79). After adjustment for age and time period, the probability of detecting cancer in situ was around 25% higher with opportunistic than with organised screening (OR = 1.26; 95% CI 1.09-1.46). This difference in favour of opportunistic screening was most pronounced in the first 10 year period and disappeared during the last decade. The difference in efficiency between organised and opportunistic screening in the detection of cancer in situ was slight, if any. The dogma that organised screening is significantly more efficient than the opportunistic type needs reconsideration.

Adult↗
PubMed1995

Growth of Escherichia coli K88 in piglet ileal mucus: protein expression as an indicator of type of metabolism.

The physiological and molecular responses of enterotoxigenic Escherichia coli K88 strain Bd 1107/7508 during growth in piglet ileal mucus and lipids extracted from mucus were studied in terms of growth rate, protein expression, and rate of heat production. E. coli K88 multiplied at maximum speed in mucus and in lipids extracted from mucus. By two-dimensional gel electrophoresis of [35S]methionine-labelled cells, it was demonstrated that the synthesis of a subclass of 13 proteins was changed at least fourfold during exponential growth in mucus compared with growth in M9 minimal medium. Ten of these proteins were repressed, while three were induced, and one of the induced proteins was identified as heat shock protein GroEL. Furthermore, two-dimensional analysis of E. coli K88 cells grown on lipids extracted from mucus revealed a set of lipid utilization-associated proteins. None of these was induced fourfold during exponential growth in mucus. Microcalorimetric measurements (monitoring the rate of heat production) of E. coli K88 grown in mucus indicated metabolic shifts in the stationary phase, in which five of the lipid utilization-associated proteins were expressed at a higher level. An isogenic E. coli K88 fadAB mutant deficient in fatty acid degradation genes grew as well as the wild type on mucus and mucus lipids. The heat production rate curve of the mutant grown in mucus differed from that of the wild type only during the stationary phase. From these results it was concluded that protein expression is influenced when E. coli K88 is grown in piglet ileal mucus rather than in M9 minimal medium. Lipids extracted from ileal mucus can serve as a substrate for E. coli K88 but appear not to be utilized during exponential growth in mucus. Stationary-phase cells metabolize fatty acids; however, the functional purpose of this is unclear.

Anaerobiosis↗
PubMed1995

Improved control of invasive cervical cancer in Sweden over six decades by earlier clinical detection and better treatment.

PURPOSE: Cancer of the cervix uteri can be controlled by cytologic screening for the detection of precursor lesions, but such intervention remains unrealistic in many countries in which this cancer is common. The possibility of reducing mortality by earlier clinical detection, followed by basic therapy, has never been properly assessed. PATIENTS AND METHODS: We compiled records of incident cases of invasive cancer of the cervix diagnosed in a defined area of Sweden from 1930 through 1990. In a cohort of 6,044 women, we analyzed temporal trends in incidence and survival by clinical stage and age at diagnosis. Generalized proportional hazards models were used to study several factors simultaneously and quantify the overall reduction in mortality. RESULTS: For each successive stage at diagnosis, the overall risk of dying increased 2.5-fold (95% confidence interval [CI], 2.4 to 2.7). From 1930, a marked improvement in stage distribution was accompanied by increasing survival rates in stages I and II disease. These changes largely took place before the introduction of screening and external-beam radiation. The 10-year relative survival rate increased from 33% in the 1930s to approximately 55% in the 1950s and thereafter. CONCLUSION: Improvements in public and professional awareness of cervical cancer resulted in diagnoses at earlier clinical stages. The rate of cure in early stages improved when basic local treatment was introduced, but only little of the progress was attributable to the introduction of more advanced treatment technologies. These findings offer considerable hope for a substantial reduction in the mortality of cervical cancer without cytologic screening, even in countries with limited resources.

Adult↗
PubMed1994

Infectious diseases, reproductive effort and the cost of reproduction in birds.

Reproductive effort can have profound effects on subsequent performance. Field experiments on the collared flycatcher (Ficedula albicollis) have demonstrated a number of trade-offs between life-history traits at different ages. The mechanism by which reproductive effort is mediated into future reproductive performance remains obscure. Anti-parasite adaptation such as cell-mediated immunity may probably also be costly. Hence the possibility exists of a trade-off between reproductive effort and the ability to resist parasitic infection. Serological tests on unmanipulated collared flycatchers show that pre-breeding nutritional status correlates positively with reproductive success and negatively with susceptibility to parasitism (viruses, bacteria and protozoan parasites). Both immune response and several indicators of infectious disease correlate negatively with reproductive success. Similar relations are found between secondary sexual characters and infection parameters. For brood-size-manipulated birds there was a significant interaction between experimentally increased reproductive effort and parasitic infection rate with regard to both current and future fecundity. It seems possible that the interaction between parasitic infection, nutrition and reproductive effort can be an important mechanism in the ultimate shaping of life-history variation in avian populations.

Animals↗
PubMed1994

Survival trend after invasive cervical cancer diagnosis in Sweden before and after cytologic screening. 1960-1984.

BACKGROUND: Cytologic screening can reduce mortality from cervical cancer by detection and removal of premalignant lesions. Conceivably, mortality is further reduced because more women with invasive disease are diagnosed at an earlier, curable stage. This hypothesis can be assessed in Sweden, where population-based screening programs were introduced successively over about a decade starting in 1964. METHODS: Record linkages permitted complete follow-up through 1986 of all 17,377 patients with invasive cervical cancer diagnosed in Sweden from 1960 through 1984. We analyzed relative survival rates that describe the survival of patients after elimination of the effects of causes of death other than cancer of the cervix. RESULTS: Prognosis improved substantially in patients younger than age 50 years at diagnosis; from 1960-1964 to 1980-1984, the 5-year relative survival rate increased from 69.8% to 88.8% at age 20-29 years, from 71.7% to 85.5% at age 30-39 years, and from 68.6% to 77.9% at age 40-49 years. The excess mortality was thus reduced by more than half in patients diagnosed when younger than 40 years. In contrast, only slight or no improvement was noted in those diagnosed at older ages when screening was less extensive. In all time periods, a strong association was found between older age at diagnosis and poorer prognosis. CONCLUSION: Although alternative explanations for our findings must be seriously considered, the most obvious interpretation is that cytologic screening reduces mortality from cervical cancer by earlier diagnosis of invasive disease.

Adult↗
PubMed1994

Plasticity of NO synthase expression in the nervous and endocrine systems.

Using immunohistochemistry and in situ hybridization the effect of nerve injury and of hormones was analysed in sensory and hypothalamic systems and in the pituitary gland. After peripheral axotomy a marked increase in NOS protein and mRNA levels was observed in dorsal root ganglia, the trigeminal ganglion and a less dramatic effect in the nodose ganglia. This effect lasted in the dorsal root ganglion neurons for at least 10 weeks. In the hypothalamic magnocellular neurons a transient increase was observed in the paraventricular and supraoptic nuclei. A similar effect was also seen after salt loading. In the anterior pituitary gland NOS was expressed in gonadotrophs and folliculo-stellate cells. Castration markedly increased NOS levels in the anterior lobe, and this could be counteracted by steroid hormone replacement. Thus, the present results show that the constitutive, neuronal NOS can be dramatically regulated in response to various manipulations, suggesting an important involvement of NO in these situations.

Amino Acid Oxidoreductases↗
PubMed1993

Nitric oxide synthase in the rat anterior pituitary gland and the role of nitric oxide in regulation of luteinizing hormone secretion.

By using immunohistochemistry and in situ hybridization, we have demonstrated that the nitric oxide (NO)-synthesizing enzyme NO synthase is present in gonadotrophs and in folliculo-stellate cells of the anterior pituitary gland of male and female rats. A marked increase in levels of NO synthase protein and mRNA was observed after gonadectomy. In vitro studies on dispersed anterior pituitary cells suggest that NO inhibits gonadotropin-releasing-hormone-stimulated luteinizing hormone release. An inhibitory effect of NO has also been shown on growth-hormone-releasing-hormone-stimulated release of growth hormone [Kato, M. (1992) Endocrinology 131, 2133-2138]. Thus these findings support a dual mechanism for NO in the control of anterior pituitary hormone secretion, an autocrine mediation of luteinizing hormone release on gonadotrophs, and a paracrine effect on growth hormone secretion involving folliculo-stellate cells closely related to somatotrophs. We speculate that NO may participate in producing the pulsatile secretion patterns of these two pituitary hormones.

Amino Acid Oxidoreductases↗
PubMed1993

Detection of preinvasive cancer of the cervix and the subsequent reduction in invasive cancer.

BACKGROUND: Cytologic screening and follow-up can reduce the incidence of cervical cancer by detection and removal of precursor lesions. It is unknown, however, whether differences in histopathologic criteria for these precursor lesions affect the benefit of screening. These criteria may be difficult to study, but they are likely to be reflected in reported incidence of in situ cancer in small areas of Sweden. PURPOSE: Our purpose was to test the hypothesis that the benefit of screening can be predicted by histopathologic criteria as reflected in the reported incidence of cancer in situ. METHODS: Incidence data were from the Swedish National Cancer Registry. Regression models showing the relationship between in situ and invasive cancer were formulated and estimated. Each county (total, 24) was a unit of measurement, and adjustment was made for the incidence of invasive cancer before screening. RESULTS: During population-based screening in Sweden, the incidence of cancer in situ varied about fourfold among the 24 counties, which indicates that the criteria used to diagnose cancer in situ differed markedly. No statistically significant (P < .05) associations were found between the incidence of cancer in situ in 1965, 1970, or 1975 and the reduction in invasive cancer 5, 10, or 15 years later. According to the best-fitting model, detection of 100 extra cases of cancer in situ per 100,000 women per year in 1975 resulted in a reduction of 1.0 (95% confidence interval [CI] = -1.6-3.7) cases of invasive cancer 10 years later. The corresponding best model estimate implied a reduction of 4.6 cases (95% CI = 1.5-7.7) in a model restricted to cancer in situ in patients aged 20-50 years (when organized screening took place), invasive cancer in patients aged 30-60 years, and cancer in situ measured in 1970. CONCLUSIONS: The absent, or at most weak, association between detection of cancer in situ and subsequent reduction in invasive cancer indicates that relaxed histopathologic criteria for cancer in situ may result in extensive, unnecessary treatment of lesions that would regress spontaneously. IMPLICATION: Further studies are urgently needed to enable identification of neoplasms likely to progress to invasive, fatal disease.

Adult↗
PubMed1993

Growth and metabolism of Saccharomyces cerevisiae in chemostat cultures under carbon-, nitrogen-, or carbon- and nitrogen-limiting conditions.

Aerobic chemostat cultures of Saccharomyces cerevisiae were performed under carbon-, nitrogen-, and dual carbon- and nitrogen-limiting conditions. The glucose concentration was kept constant, whereas the ammonium concentration was varied among different experiments and different dilution rates. It was found that both glucose and ammonium were consumed at the maximal possible rate, i.e., the feed rate, over a range of medium C/N ratios and dilution rates. To a small extent, this was due to a changing biomass composition, but much more important was the ability of uncoupling between anabolic biomass formation and catabolic energy substrate consumption. When ammonium started to limit the amount of biomass formed and hence the anabolic flow of glucose, this was totally or at least partly compensated for by an increased catabolic glucose consumption. The primary response when glucose was present in excess of the minimum requirements for biomass production was an increased rate of respiration. The calculated specific oxygen consumption rate, at D = 0.07 h-1, was more than doubled when an additional nitrogen limitation was imposed on the cells compared with that during single glucose limitation. However, the maximum respiratory capacity decreased with decreasing nitrogen concentration. The saturation level of the specific oxygen consumption rate decreased from 5.5 to 6.0 mmol/g/h under single glucose limitation to about 4.0 mmol/g/h at the lowest nitrogen concentration tested. The combined result of this was that the critical dilution rate, i.e., onset of fermentation, was as low as 0.10 h-1 during growth in a medium with a low nitrogen concentration compared with 0.20 h-1 obtained under single glucose limitation.

Ammonium Sulfate↗
PubMed1993

Energy flux and osmoregulation of Saccharomyces cerevisiae grown in chemostats under NaCl stress.

The energetics and accumulation of solutes in Saccharomyces cerevisiae were investigated for cells grown aerobically in a chemostat under NaCl stress and glucose limitation. Changed energy requirements in relation to external salinity were examined by energy balance determinations performed by substrate and product analyses, with the latter including heat measurements by microcalorimetry. In both 0 and 0.9 M NaCl cultures, the catabolism was entirely respiratory at the lowest dilution rates tested but shifted to a mixed respiratory-fermentative metabolism at higher dilution rates. This shift occurred at a considerably lower dilution rate for salt-grown cells. The intracellular solute concentrations, as calculated on the basis of intracellular soluble space determinations, showed that the internal Na+ concentration increased from about 0.02 molal in basal medium to about 0.18 molal in 0.9 M NaCl medium, while intracellular K+ was maintained around 0.29 molal despite the variation in external salinity. The intracellular glycerol concentration increased from below 0.05 molal at low salinity to about 1.2 molal at 0.9 M NaCl. The concentrations of the internal solutes, however, changed insignificantly with growth rate and energy metabolism. The additional maintenance energy expenditure for growth at 0.9 M NaCl was, depending on the growth rate, 14 to 31% of the total energy requirement for growth at 0 M NaCl. Including the energy conserved in glycerol, the total additional energy demand for growth at 0.9 M NaCl corresponded to 28 to 51% of the energy required for growth at 0 M NaCl.

Adenosine Triphosphate↗
PubMed1993

The expression of potential colonization factors of yeasts isolated from fish during different growth conditions.

Three strains, Rhodotorula rubra, Rhodotorula glutinis, and Candida zeylanoides, isolated from fish, were tested for the expression of putative tissue colonization factors. All strains were able to bind collagen type I, fibronectin, and laminin to various degrees after growing on various solid and broth media, while the binding to collagen type IV was sparse under all conditions tested. For the three strains tested, a very low cell surface hydrophobicity was shown for growth on various solid and broth media. Mostly, the strains also expressed a negatively charged surface. Extracellular protease activity using different substrates was shown for all three strains. Furthermore, two properties related to iron scavenging, i.e., binding of lactoferrin and production of siderophores, were also tested. For the three strains a capacity to bind lactoferrin as well as a capacity to excrete siderophores were demonstrated. Since these different properties have been correlated to virulence and to the capacity of colonization in other organisms, we address the question of whether the expression of these properties in yeasts could contribute to colonization in fish.

Animals↗
PubMed1992

Optimization of cervical cancer screening.

The aim of this study was to investigate how a screening program interacts with the dynamic natural history of cervical neoplasia in order to learn how screening for cervical cancer should be carried out most cost-effectively. For the purpose of optimization, the fundamental quantities of the natural history are the shape of the curve of age-specific prevalence rates of cancer in situ, and the duration of this stage before progression to invasive cancer. Since these quantities seem similar in different populations, the results probably can be generalized. Simulation studies revealed that optimal screening implies a nonperiodic schedule, and that this schedule is dependent not only on the number of screenings, but also on the efficiency of the screening rounds. With lower efficiency, the schedule should be concentrated into a shorter period. The effect of screening is also especially sensitive to the choice of age at the first and--to a smaller extent--last screening. The results concerning three different objectives also were compared, namely reduction of the cumulative number of invasive cancers, reduction of deaths due to cervical cancer, and reduction of years-of-life lost. The choice of objective also plays a role in the design of an optimal screening program. The theoretical approach in this analysis easily can be developed and accommodated to more complex individual situations such as prior screening histories and differing screening schedules in high- and low-risk women.

Adult↗