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Biomedical subjects

S Lundberg

Publications and source records attributed to S Lundberg.

At least 19 recordsLinked to original sources
PubMed1995

Cloning, expression and characterization of two putative calcium-binding sites in human non-erythroid alpha-spectrin.

The C-terminus of alpha-spectrins contains two putative calcium-binding sites or EF-hands. To characterize the binding, we have isolated clones from a human fetal liver cDNA library and expressed several fragments comprising either one or both of these sites. When the isolated clones were sequenced, we found that three consecutive nucleotides differed compared to the published sequence. The discrepancy affected two codons in the first of the two putative calcium sites. These codons translated into glutamate and phenylalanine, which are identical to the residues present at the same position in other alpha-spectrins. In the presence of magnesium, only recombinant peptides comprising the second putative site bound calcium as determined by a calcium overlay assay. Although the first putative EF-hand appeared to bind some calcium in the absence of magnesium, no binding could be detected under stringent conditions. Therefore, it is likely that the second EF-hand constitutes the only functional calcium-binding site in the C-terminus of human non-erythroid alpha-spectrin. Since peptides comprising the second EF-hand bound calcium nearly as well as intact spectrin, it is also apparent that the second EF-hand constitutes the major binding site for calcium in spectrin. The relative change in negative ellipticity, induced by the binding of calcium, indicates a dissociation constant of approximately 120 microM.

Amino Acid Sequence↗
PubMed1992

Characterization of calcium binding to spectrins.

Calcium binding to brain and erythrocyte spectrins was studied at physiological ionic strength by a calcium overlay assay and aqueous two-phase partitioning. When the spectrins were immobilized on nylon membranes by slot blotting, the overlay assay showed that even though both spectrins bound 45Ca2+, the brain protein displayed much greater affinity for calcium ions than erythrocyte spectrin did. Since the observed binding was weaker than that displayed by calmodulin under similar conditions, the overlay assay results indicated that the binding must be weaker than 1 microM. The phase partition experiments showed that there are at least two sites for calcium on brain spectrin and that calcium binding to one of these sites is reduced significantly by magnesium ions. From the partition isotherm, the dissociation constants were estimated as 50 microM for the Mg(2+)-independent site and 150 microM for the Mg(2+)-dependent site. The phase partition results also showed that erythrocyte spectrin bound calcium ions at least 1 order of magnitude weaker. By examining calcium binding to slot-blotted synthetic peptides, we identified two binding sites in brain spectrin. One mapped to the second putative calcium binding site (EF-hand) in alpha-spectrin and the other to the 36 amino acid residue long insert in domain 11. In addition, a tryptic fragment derived from the C-terminal of erythrocyte alpha-spectrin, which contained the two postulated EF-hands, also bound calcium. These findings suggest that the calcium signal system may also involve direct binding of calcium to spectrin beside known calcium modulators such as calmodulin and calpain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Evolution of increased susceptibility to infectious diseases in age structured populations.

Current theory on the epidemiology of infectious diseases in genetically heterogeneous host populations ignores age structure. Thus, the possibility that microparasites might have negative effects on fitness in different ways during different phases of the lives of their hosts is not accounted for. For example, infections causing mortality and morbidity among juveniles might also have an impairing effect on reproduction among adults, as is the case in many so called childhood diseases. I demonstrate that when this is the case there may be a selective pressure for the host to evolve a higher level of susceptibility to an infection, provided it has the following properties: it should (i) provide life-long immunity, (ii) have a negative effect on reproduction and (iii) not cause too many mortalities.

Adult↗
PubMed1989

Measurement of human cervical compliance.

A critical evaluation of the various methods for the measurement of the compliance of the human cervix uteri was made. The resistance of this tissue to a dilating force was measured by a previously constructed strain gauge instrument equipped with exchangeable Pratt cervical dilators. The dilating resistance offered by the cervical canal was recorded on a polygraph at a constant paper speed. Control experiments in which the dilating instrument was allowed to meet artificial cellulose tissue showed that the peak value recorded was of importance for estimating cellulose tissue resistance. Measurements of the area under the curve were shown to be of minor importance in this system. Using this technique in clinical applications, it was also shown that peak resistance provides the most accurate measurement of human cervical resistance.

Abortion, Induced↗
PubMed1988

Gangrenous dermatitis caused by Corynebacterium ulcerans in Richardson ground squirrels.

Gangrenous dermatitis caused by Corynebacterium ulcerans developed in 63 of 350 wild Richardson ground squirrels (Spermophilus richardsonii). Six squirrels died of toxemia and/or septicemia, but 57 responded to topical and parenteral administration of antibiotics. The epizo-otic was believed to be associated with fighting; infected and carrier ground squirrels most likely transmitted the C ulcerans through bite wounds. Individuals handling ground squirrels should be cautioned that C ulcerans may produce a diphtheria-like disease in human beings.

Animals↗
PubMed1987

DNA flow cytometry and histopathological grading of paraffin-embedded prostate biopsy specimens in a survival study.

Methods to disintegrate old paraffin-embedded tissue blocks for the application of DNA flow cytometry open up new possibilities for retrospective studies on the correlation between tumor cell nuclear DNA pattern and prognosis of the neoplastic disease. In the present work we used such a method to study the relationship between DNA ploidy, histopathological grade, and survival for 50 patients with prostate carcinomas diagnosed 1958-1974. Plugs of histologically identified tissue from benign and tumor areas were sampled from paraffin blocks of prostate biopsy specimens by using a 4-mm skin biopsy punch. Thirty-micron sections were cut from each plug for dewaxing and disintegration. The cell suspensions obtained were stained with 4',6-diamidino-2-phenylindole dihydrochloride and analyzed by flow cytometry. In about one-half of the cases where two or more plugs were analyzed we found a heterogeneous tumor cell nuclear DNA pattern. No apparent correlation was found between the histopathological grade and the DNA ploidy. Using Cox's multiple regression analysis, we found a significant correlation between DNA ploidy and survival of these patients (P = 0.043) when we controlled for histopathological grade (Dhom grade), acid phosphatase level, occurrence of metastases, age, year of diagnosis, and type of biopsy. The correlation between DNA ploidy and survival was just above the level of significance (P = 0.059) when Gleason grade was substituted for Dhom grade in the regression model.

Acid Phosphatase↗
PubMed1987

Isolation and nephrotoxic studies of orellanine from the mushroom Cortinarius speciosissimus.

A nephrotoxic substance has been isolated from Cortinarius speciosissimus. The 1H-NMR and 13C-NMR mass spectra indicated the chemical structure to be 3,3',4,4'-tetrahydroxy-2,2'-bipyridine-N-N'-dioxide. The toxin was quantitated using reversed phase high performance liquid chromatography (HPLC) with electrochemical detection. The detection limit of this method was 500 pg, corresponding to a signal-to-noise ratio of 2.5. The toxin had an LD50 in mice of approximately 20 mg/kg i.p. Light microscopic examination of the kidneys of mice surviving treatment with the toxin showed interstitial nephritis and tubular necrosis.

2,2'-Dipyridyl↗
PubMed1986

Organophosphorus anticholinesterases do not mediate analgesia through inhibition of enkephalin degradation.

The effect on enkephalin degradation of the four highly potent organophosphorus anticholinesterases, soman, sarin, tabun and DFP was studied in synaptosomal fractions of rat brain striata. None of the agents effected any of the enkephalin degrading enzymes, the puromycin sensitive aminopeptidase, the p-hydroxymercurybenzoate (p-HMB) sensitive dipeptidyl aminopeptidase or the phosphoramidon sensitive enkephalinase. Furthermore, no peptidase function of acetylcholinesterase was found, when Leu-enkephalin was used as substrate at low concentrations (27 nM). Supporting the in vitro data, no difference was obtained in the striatal levels of Met- and Leu-enkephalin between rats receiving a high single dose of soman and controls. The results show that the analgesic effect of anticholinesterases are more likely due to mechanisms other than inhibition of enkephalin degradation.

Acetylcholinesterase↗
PubMed1986

Relative hepatotoxicity of some industrial solvents after intraperitoneal injection or inhalation exposure in rats.

Intraperitoneal LD50 (lethal dose 50% kill) values and minimal liver toxic doses in female Sprague-Dawley rats were determined for the following industrial solvents: toluene, methylene chloride, carbon tetrachloride, 1,1,1-trichloroethane, 1,1,2-trichloroethane, trichloroethylene, ethanol, methyl ethyl ketone, and dioxane. For the following solvents LC50 values and minimal liver toxic air concentrations were also determined: xylene, styrene, chloroform, tetrachloroethylene, and dimethylformamide (DMF). The serum activity of the enzyme sorbitol dehydrogenase (SDH) was used as an indicator of liver damage. Carbon tetrachloride, chloroform, and DMF were hepatotoxic in low doses compared to LD50 values (TD50 (toxic dose 50%) values approximately 30, 90, and 50 mg/kg). Chloroform and DMF were hepatotoxic in comparatively low concentrations after a 4-hr inhalation exposure (TC50 (toxic concentration 50%) values approximately 590 and 740 mg/m3). Even relatively high doses of the other solvents did not raise the SDH activity. Significant direct (metabolite-mediated) hepatotoxicity seems to be an uncommon feature among commonly used industrial solvents.

Animals↗
PubMed1985

Partial denervation of the ovaries by transection of the suspensory ligament does not inhibit ovulation in rats treated with pregnant mare serum gonadotropin.

Adrenergic nerves reach the ovary via two routes: along the arteries to the ovary and via the suspensory ligament. Results from earlier investigations suggest that denervation of the nerves along the arteries does not influence the ovulatory process. In the present study we have examined whether denervation by transection of the ovarian suspensory ligament influences the ovulatory process. Partial denervation of the ovary by transection of the ovarian suspensory ligament, sham operation, or only anesthesia were performed on immature 25-day-old rats. To induce ovulation, pregnant mare serum gonadotropin (PMSG) was injected in the morning (0800-0930), when the rats were 26 days old. This PMSG treatment normally induces ovulation around 0200 in the early morning of day 29 with subsequent formation of corpora lutea. Rats were killed 5-8 hr, 3 days, and 5 days after this ovulation time. Ovarian interstitial norepinephrine levels were markedly decreased after transection of the suspensory ligament. Ovulations had occurred in all denervated, as well as sham-operated, and control rats. The various groups did not differ in the number of ovulations per rat. Thus, the adrenergic nerves in the suspensory ligament appear not to be necessary for ovulation. Whether catecholamines themselves play a role in the ovulatory process cannot be elucidated from this experiment, since the norepinephrine content in the ovary was not totally depleted. It seems unlikely that adrenergic nerves reach the corpus luteum via the suspensory ligament, since transection of this structure did not change the luteal content of norepinephrine.

Animals↗
PubMed1985

Coevolution of competing species: ecological character displacement.

Character displacement of competing species is studied. A model, originally developed by MacArthur and Levins (Proc. Natl. Acad. Sci. USA 51 (1964), 1207-1210) and further analyzed by Lawlor and Maynard Smith (Amer. Nat. 110 (1976), 70-99), has been reanalyzed. In the present paper, a more formally correct analysis of the MacArthur-Levins model is provided. A standard population genetics approach to sexually reproducing populations is adopted. The same conclusion as proposed by Lawlor and Maynard Smith emerges; competition can lead only to character divergence. In our analysis we either require that allopatrically evolved consumer populations must be able to coexist at an ecologically stable equilibrium (hence, we require mutual invasibility), or consider the feasibility of allopatric equilibria.

Analysis of Variance↗
PubMed1983

Delayed dimethylformamide biotransformation after high exposures in rats.

Rats were exposed to two dimethylformamide (DMF) air concentrations (2250 and 565 ppm for 4 h). Concentrations of DMF and the biotransformation product monomethylformamide (MMF) were measured in blood and some tissues at different times after the end of exposure. MMF concentrations 0 and 3 h after the end of the high exposure were generally lower than MMF concentrations at the same time after the low exposure. The results suggest that DMF biotransformation to MMF is delayed after the high exposure. As the hepatotoxic effect of DMF has been correlated with MMF, this could contribute to the previously observed slower appearance of hepatotoxicity after a high compared to a low DMF dose.

Adrenal Glands↗