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Biomedical subjects

M Sandberg

Publications and source records attributed to M Sandberg.

At least 55 records · Page 3Linked to original sources
PubMed1997

Thyroid carcinoma found at parathyroidectomy: association with primary, secondary, and tertiary hyperparathyroidism.

BACKGROUND: Frequent reports of an association between primary hyperparathyroidism (HPT) and well differentiated thyroid carcinoma, compared with the few reports of associated secondary HPT and thyroid carcinoma, may have implications for different etiologic relationships between the conditions. METHODS: A retrospective review was performed of patients who underwent surgery for HPT between 1975 and 1996 in a single institution. The prevalence of well differentiated thyroid carcinoma diagnosed at the time of parathyroidectomy (PTX) was compared for patients with primary, secondary, or tertiary HPT. RESULTS: There were 845 operations for HPT in 824 patients. Twenty-two patients were found to have thyroid carcinoma at the time of PTX. Thyroid carcinoma was found in 2.6% of the patients with primary and 3.2% of the patients with either secondary or tertiary HPT (P = 0.550). Twenty-one of the patients had papillary carcinoma and 1 had a follicular carcinoma. Eighteen of the carcinomas were < 1 cm in size. A prior history of head and neck irradiation was associated with the diagnosis of thyroid carcinoma at the time of PTX (P < 0.001). Neither renal failure, organ transplantation, female gender, lymphocytic infiltration, nor follicular adenoma of the adjacent thyroid were significant in the association between HPT and thyroid carcinoma. CONCLUSIONS: These data suggest that the association between thyroid carcinoma and HPT is coincidental and possibly related to the closer surveillance of the thyroid gland due to PTX and often concomitant removal of thyroid tissue. Patients with HPT and a history of head and neck irradiation are at increased risk of thyroid carcinoma.

Adolescent↗
PubMed1997

Brain injury after hypoxia-ischemia in newborn rats: relationship to extracellular levels of excitatory amino acids and cysteine.

The aim of this study was to follow extracellular concentrations of excitatory amino acids (EAAs) and cysteine during neonatal hypoxia-ischemia (HI) and reflow and to relate these events to the extent of brain damage evaluated 6 h after the insult. Rat pups (PND 7-10) were subjected to unilateral ligation of the common carotid artery and exposed to hypoxia (7.7% O2). Extracellular amino acids were sampled during HI and for 6 h of reperfusion with microdialysis and the levels were correlated with the extent of brain damage at the site of probe placement. The concentrations of glutamate, aspartate and cysteine increased transiently during HI (15 x, 6 x and 3 x, respectively) in the extracellular space and returned to normal or remained slightly elevated during reperfusion. Changes of EAAs and cysteine were similar during HI in the infarcted, undamaged and border-zone regions. During reperfusion the concentrations of glutamate, aspartate and cysteine were higher in infarcted and border-zone areas compared to undamaged tissue. In neonatal rats, the extracellular levels of EAAs during HI do not correspond to the extent of brain injury whereas the EAA concentrations during reflow are related to the extent of infarction.

Analysis of Variance↗
PubMed1997

Bicarbonate-sensitive cysteine induced elevation of extracellular aspartate and glutamate in rat hippocampus in vitro.

The effect of different concentrations of cysteine (0.125, 0.25, 0.5 and 1 mM) on the net efflux of endogenous amino acids was studied by the incubation of rat hippocampal slices. Addition of cysteine (1 mM) in bicarbonate containing low K+ medium (5 min) selectively increased the basal net efflux of glutamate and aspartate by 370% and 396%, respectively. High K+ media (50 mM) containing cysteine (1 mM) evoked the net efflux of glutamate and aspartate by 1454% and 1019%, respectively. The corresponding effects in control slices without cysteine were 669% and 404%, respectively. No changes were observed on the concentrations of GABA, glutamine and taurine. The cysteine oxidation products, cysteine sulfinate (0.5 microM) and cystine (0.25 mM) were without effects. The effect of cysteine (0.5 mM) was dramatically reduced in media with no added bicarbonate/CO2. Thus, cysteine in a bicarbonate-sensitive manner selectively increases the extracellular concentration of excitotoxic amino acids in adult rat brain in vitro, possibly by interfering with the carrier-mediated glutamate uptake/release.

Animals↗
PubMed1997

Structure, function, and regulation of human cAMP-dependent protein kinases.

A large number of hormones, neurotransmitters, and other signaling substances that bind to G-protein-coupled cell-surface receptors have their signals converge at one sole second messenger, cAMP. The question of how specificity can be maintained in a signal-transduction system in which many extracellular signals leading to a vast array of intracellular responses are all mediated through one second-messenger system has been the subject of thorough investigation and a great deal of speculation. An increasing number of cAK isozymes, consisting of homo- or heterodimers of R subunits (RIalpha, RIbeta, RIIalpha, RIIbeta) with associated catalytic subunits (C alpha, Cbeta, Cgamma), may, at least in part, explain this specificity. The various cAK isozymes display distinct biochemical properties, and the heterogeneous subunits of cAK reveal cell-specific expression and differential regulation at the level of gene transcription, mRNA stability, and protein stability in response to a wide range of hormones and other signaling substances. The existence of a number of anchoring proteins specific to either RIIalpha or RIIbeta, and which localize cAKII isozymes toward distinct substrates at defined subcellular loci, strongly supports the idea that specific functions can be assigned to the various cAK isozymes. The demonstration that selective activation of cAKI is necessary and sufficient for cAMP-mediated inhibition of T-cell proliferation, and the observation that T-cell activation is associated with redistribution and colocalization of cAKI to the TCR, is also compatible with the notion of isozyme-specific effects.

Cloning, Molecular↗
PubMed1997

Characterization of LMP-1's association with TRAF1, TRAF2, and TRAF3.

The latent membrane protein 1 (LMP-1) of Epstein-Barr virus (EBV) contributes to the immortalizing activity of EBV in primary, human B lymphocytes. LMP-1 is targeted to the plasma membrane, where it influences signaling pathways of infected cells. LMP-1 has been found to associate with members of the tumor necrosis factor receptor-associated factor (TRAF) family of proteins. As with LMP-1, the TRAF molecules have been shown to participate in cell signaling pathways. We have characterized and mapped in detail a region of LMP-1 that associates with TRAF1, TRAF2, and TRAF3. TRAF3 alone associates with LMP-1 in a yeast two-hybrid assay, whereas all three TRAF molecules associate with LMP-1 under various conditions when they are assayed in extracts of human cells. TRAF1, TRAF2, and TRAF3 appear to associate independently with LMP-1 but bind an overlapping target site. TRAF3 associates with LMP-1 most avidly and can compete with TRAF1 and TRAF2 for binding to LMP-1. TRAF2 associates with truncated derivatives of the carboxy terminus of LMP-1 more efficiently than with the intact terminus, indicating that LMP-1's conformation may regulate its association with TRAF2. Finally, point mutations that decrease LMP-1's association with the three TRAF molecules to 3 to 20% of wild-type levels do not detectably affect otherwise intact LMP-1's induction of NF-kappaB activity. Therefore, these associations are not necessary for the majority of intact LMP-1's induction of this signaling pathway.

Amino Acid Sequence↗
PubMed1997

The human gene for the regulatory subunit RI alpha of cyclic adenosine 3', 5'-monophosphate-dependent protein kinase: two distinct promoters provide differential regulation of alternately spliced messenger ribonucleic acids.

The present study reports the exon-intron organization of the human RI alpha gene of cAMP-dependent protein kinase and approximately kilobases (kb) of the 5'-flanking region obtained by isolation and sequencing of several phage clones from human genomic libraries. The RI alpha gene is composed of nine coding exons of varying lengths, separated by introns, giving the gene a total length of at least 21 kb. our recent cloning of a processed RI alpha pseudogene with a 5'-noncoding region different from the previously reported RI alpha complementary RNA indicated that the RI alpha gene may have multiple leader exons giving rise to alternately spliced messenger RNAs (mRNAs). Reverse transcription of human testis RNA followed by PCR identified two different RI alpha mRNA species (RI alpha 1a and RI alpha 1b) containing distinct sequences due to alternately splicing the gene. The previously known RI alpha 1b mRNA revealed low constitutive expression in a human B lymphoid cell line (Reh) and was stimulated only 4- to 6-fold by treatment with cAMP. In contrast, very low levels of the novel RI alpha 1a mRNA were present in untreated Reh cells, but were stimulated 40-to 50-fold by cAMP. The 5'-flanking sequence of the RI alpha gene was G/C rich and did not contain any TATA box. Several putative transcription initiation sites were identified in front of each leader exon (exons 1a and 1b) by the 5'-rapid amplification of complementary DNA ends technique. To determine whether the sequences 5' of both leader exons had promoter activities, the 5'-flanking sequences of exons 1a and 1b were inserted in front of a chloramphenicol acetyltransferase reporter gene, and their ability to direct transcription were examined. Transfection of these constructs into rat GH4C1 cells demonstrated that both constructs had promoter activities, as evidenced by high levels of chloramphenicol acetyltransferase activity.

Aged↗
PubMed1996

Fast and slow cyclic nucleotide-dissociation sites in cAMP-dependent protein kinase are transposed in type Ibeta cGMP-dependent protein kinase.

Both cyclic GMP-dependent protein kinase (cGK) and cyclic AMP-dependent protein kinase (cAK) contain two distinct cyclic nucleotide-binding sites referred to as fast and slow sites based on cyclic nucleotide dissociation behavior. In cAK, the fast site lies amino-terminal to the slow site, and sequence homologies between cAK and cGK have suggested similar positioning for the sites in cGK. Recombinant human type Ibeta cGK (wild type (WT) cGK) was overexpressed, and the properties of purified WT cGK and native type Ibeta cGK were similar. cGK was mutated singly at Thr-193 (T193A, T193V, and T193S) and Thr-317 (T317A, T317V, and T317S), which have been predicted to provide cGMP specificity in the cGMP-binding sites of cGK; a double mutant (T193A/T317A) was produced also. Compared with WT cGK, half-maximal activation (Ka) of mutant cGKs by cGMP was increased 2- (T317A), 27- (T193A), or 63-fold (T193A/T317A), but the Ka for cAMP of these mutants was essentially unchanged. The T193A and T193V mutants had a large increase in the rate of the slow component of [3H]cGMP dissociation, but in the T317A and T317V mutants, there was no change in the slow component. The T193S and T317S mutants had only minor effects on [3H]cGMP dissociation, thus establishing the importance of the hydroxyl group of Thr-193 and -317 for cGMP binding to cGK. Thus, in type Ibeta cGK, the slow cGMP-binding site is identified as the amino-terminal site in contrast to the order assigned to the fast and slow cAMP-binding sites of cAK.

Amino Acid Sequence↗
PubMed1996

Structural characterization of the human soluble epoxide hydrolase gene (EPHX2).

The structural organization of the human gene encoding soluble epoxide hydrolase (EPHX2) was determined. Cosmid clones containing the EPHX2 gene were identified by hybridization of a human genomic library with PCR amplified cDNA to the mouse or human soluble epoxide hydrolase as probes. The gene consists of 19 exons and is approximately 45 kb of which more than 15 kb were sequenced. The coding sequence corresponds to 555 amino acid residues, i.e., one additional residue to those in the reported cDNA sequence. The sized of the introns were defined by sequencing or PCR analysis and they contained various repetitive structure elements as expected.

Amino Acid Sequence↗
PubMed1996

Molecular cloning, cDNA structure, and chromosomal localization of the human type II cGMP-dependent protein kinase.

The type II cGMP-dependent protein kinase is an enzyme originally isolated from the small intestine, and is thought to be involved in the regulation of intestinal ion transport and fluid secretion. A complementary DNA clone encoding a part of the human type II cGMP-dependent protein kinase was isolated from a cerebellum library. Based on sequence information from this complementary DNA, the 5'-end of the type II cGMP-dependent protein kinase was amplified from human brain messenger RNA using polymerase chain reaction. The composite complementary DNA encoded a 762 amino acid protein with a calculated molecular mass of 87.4 kDa. Messenger RNAs encoding the type II cGMP-dependent protein kinase were detected in small intestine, colon and prostate. By using polymerase chain reaction and Southern blotting on somatic cell hybrids, the gene encoding, the type II cGMP-dependent protein kinase was mapped to human chromosome 4q13.1-q21.1.

Amino Acid Sequence↗
PubMed1996

Studies on the identity of the rat optic nerve transmitter.

The possible role of glutamate, aspartate, sulfur-containing excitatory amino acids and gamma-glutamyl peptides as major transmitters in the rat optic nerve was evaluated. Four days following optic nerve lesion the K(+)-evoked Ca(2+)-dependent glutamate release was reduced to 31 +/- 16% (+/- S.D., n = 9) comparing release from slices of the denervated (contralateral to the lesion) and non-denervated (ipsilateral) superior colliculus, indicative of a major transmitter function for glutamate. However, significant decreases in glutamate release could not be detected seven days following the lesion (n = 5). Other studies have shown that optic nerve denervation induce formation of synapses of non-retinal origin and cause other cellular changes which may reduce the effect of deafferentation on glutamate release after 7 days. No significant change was observed in aspartate release following the lesion. The concentrations of cysteine sulfinate, cysteate, homocysteine sulfinate, homocysteate and O-sulfo-serine in the optic layers of the superior colliculus were below 1 nmol/g tissue (n = 6). Theoretical considerations indicate that this level is too low for a function of any of these as a major optic nerve transmitter. All postsynaptic components in the rat superior colliculus response, evoked by electrical optic nerve stimulation, were reduced by kynurenate (1-10 mM), a broad spectrum glutamate-receptor antagonist. The study gives further support for the view that glutamate is a major transmitter in the rat optic nerve.

Amino Acids, Sulfur↗
PubMed1996

Development of brain damage after neonatal hypoxia-ischemia: excitatory amino acids and cysteine.

The aim of this study was to investigate the possible role of excitatory amino acids (EAAs) and cysteine in the development of brain damage after hypoxia-ischemia (HI) in neonates. In a rat model of neonatal HI, changes in extracellular (ec) amino acids in cerebral cortex were measured with microdialysis and correlated with the extent of brain damage at the site of probe placement. Extracellular concentrations of glutamate, aspartate and cysteine increased during HI and remained elevated during reperfusion. During HI the pattern of EAA changes was the same in the infarcted, undamaged and border zone regions. During reperfusion, however, the ec concentrations of glutamate, aspartate and cysteine were higher in infarcted and border zone areas compared to undamaged tissue. HI also produced a slight increase of tissue concentration of cysteine and decrease of tissue concentration of glutamate in parietal cortex of the HI hemisphere. The effect of cysteine on brain damage induced by HI and glutamate was also investigated. A subtoxic dose of cysteine potentiated glutamate toxicity in the arcuate nucleus and enhanced brain infarction after HI in neonatal rats. The results show that in neonatal HI the extracellular levels of EAAs during HI are not directly related to brain injury but the EAA levels during reflow predict the extent of infarction. Cysteine increases HI-induced brain injury and potentiates glutamate toxicity in neonatal rats. Speculatively, elevated level of cysteine during reperfusion may participate in the excitotoxic cascade leading to brain injury.

Animals↗
PubMed1996

Gamma-glutamyl peptides and related amino acids in rat hippocampus in vitro: effect of depolarization and gamma-glutamyl transpeptidase inhibition.

The concentrations of gamma-glutamylglutamate, gamma-glutamylglutamine, gamma-glutamylcysteine, glutamate, aspartate, glutamine, cyst(e)ine and glutathione (including disulfides) were determined by HPLC analysis of both the tissue and the surrounding medium of incubated rat hippocampal slices. High potassium concentrations (50 mM; 2 x 4 min) increased the medium concentration of gamma-glutamylglutamate (maximal net efflux 0.07 +/- 0.06 pmol/mg protein/min; n = 8 +/- SD) with a relative time delay compared to the increase in glutamate (maximal net efflux 264 +/- 88 pmol/mg protein/min). Release of gamma-glutamylcysteine, the glutathione precursor, demonstrated an immediate response and gradually approached prestimulus levels (maximal net efflux 0.36 +/- 0.13 pmol/mg protein/min). Addition of acivicin (0.2 mM), a gamma-glutamyl transpeptidase (EC 2.3.2.2.) blocker, during preincubation for 45 min reduced the tissue concentrations (pmol/mg protein) of gamma-glutamylglutamate (19.4 +/- 8.2 (control) vs. 5.8 +/- 3.6 (+ acivicin)), gamma-glutamylglutamine (40.3 +/- 6.7 vs. 25.7 +/- 4.2 pmol/mg protein), glutamine (9.9 +/- 2.0 vs. 4.6 +/- 1.2 nmol/mg protein) and cysteine (1.0 +/- 0.2 vs. 0.56 +/- 0.18 nmol/mg protein). Incubation with acivicin (0.2 mM) reduced the net efflux of gamma-glutamylglutamine (0.79 +/- 0.19 vs. 0.21 +/- 0.07 pmol/mg protein/min) whereas that of the glutathione was increased (4.7 +/- 1.0 vs. 20 +/- 3 pmol/mg protein/min). The medium concentrations of glutamate in both low and high potassium were unaffected by acivicin, while the high potassium induced increase in gamma-glutamylglutamate was blocked. The results demonstrate differential efflux patterns of gamma-glutamyl dipeptides from brain slices and show that in vitro the activity of gamma-glutamyl transpeptidase regulates extracellular concentrations of glutathione, gamma-glutamylglutamine and gamma-glutamylglutamate.

Amino Acids↗
PubMed1996

Expression of type I and III collagen and laminin beta1 after rat sciatic nerve crush injury.

Extracellular matrix changes are thought to be essential to the regeneration of peripheral nerves. The production of this matrix is believed to be regulated by interactions between axons and their supporting cells. In this study matrix production and cell proliferation were studied during rat sciatic nerve regeneration after a crush injury, and compared to that after rat sciatic nerve transection. Expression of proalpha1(I) and proalpha1(III) collagen and laminin beta1 mRNAs was followed in isolated endoneuria by Northern and in situ hybridization both proximally and distally to the site of either a crush injury or transection of rat sciatic nerve up to 18 weeks. Changes in the Schwann cell and fibroblast populations were monitored by morphometric analysis of endoneurial cross-sections immunostained for S-100 protein. The process of axonal regeneration was followed by Bielschowsky's silver staining. A crush injury initially resulted in increased expression of all mRNAs studied in the endoneurial cells. However, with progressing axonal regeneration the amount of collagen mRNAs returned to control levels, whereas the amount of laminin beta1 mRNA in the distal site of the crush remained elevated throughout the study period. The expression of type I collagen mRNA was enhanced after nerve transection injury compared to that after the crush injury. The epineurial fibroblasts actively expressed both type I and III collagen mRNAs after the injury. The proliferation of Schwann cells and the expression of collagen mRNAs are not, at least directly, related to the axonal regeneration. However, the long-lasting and strong expression of laminin beta1 mRNA after a nerve crush injury may be related to good axonal regeneration. The expression of type I collagen in the epineurium may lead to clinically well-recognized epineurial scarring and thus impede axonal regeneration.

Animals↗
PubMed1995

Neurotoxicity of cysteine: interaction with glutamate.

L-Cysteine produces excitotoxic brain damage but its chemical structure differs from that of other excitotoxins. Although it is an NMDAmimetic, its mode of action is complex and may encompass antiexcitotoxic components. The purpose of the present study was to investigate whether cysteine kills neurons by potentiating the effects of glutamate and/or by releasing glutamate. In primary cultures of cortical neurons, 24 h of exposure to glutamate caused a concentration-dependent, dizocilpine-sensitive cell death as measured by release of lactate dehydrogenase. Cysteine was also toxic but higher concentrations were required. In addition, N-acetylcysteine produced mild toxicity at 1 mM. There was no general potentiation between either glutamate and cysteine or glutamate and N-acetylcysteine although some combinations acted synergistically. In no case did the thiols inhibit glutamate toxicity. The interaction between glutamate and cysteine toxicity was also assessed in the immature rat arcuate nucleus in vivo. When given at a dose (0.5 mg/g) that did not cause any toxicity per se, cysteine enhanced the toxicity of glutamate (0.3-0.8 mg/g). Cortical microdialysis was carried out in anesthetized rats (8-10 days old) administered a toxic dose of cysteine (1 mg/g). The levels of taurine were elevated 15-fold, phosphoethanolamine 3-fold and alanine 2-fold. Despite the observation that glutamine decreased markedly and rapidly, there was only a delayed doubling of glutamate concentrations. It is therefore unlikely that cysteine induces neurotoxicity by releasing glutamate. Taken together, the results suggest that there is a synergistic effect between cysteine and glutamate. Speculatively, this potentiation may be produced by reduction by cysteine of the redox site of the glutamate-activated NMDA receptor-ionophore complex.

Animals↗
PubMed1995

Fluorescence, photodestruction, photoionization and thermal degradation of o-phthalaldehyde/beta-mercaptoethanol-labelled aliphatic alpha-oligopeptides.

Photophysical and photochemical properties of o-phthalaldehyde/beta-mercaptoethanol-labelled aliphatic alpha-peptides were investigated. It is found that alpha-peptide derivatives have lower fluorescence quantum yields, higher photodestruction quantum yields and lower yields for formation of solvated electrons as compared to amino acid and simple alkylamine derivatives in aqueous alkaline solution. These properties of the alpha-peptide derivatives sets narrow limits for their utilization in laser-based (high light intensity) detector systems. In contrast, the thermal stability of the peptide derivatives was found to be severalfold higher than for the parent amino acid derivatives. The differential rates of thermal derivative degradation could be utilized in a new approach towards selective determination of peptides. determination of peptides. determination of peptides.

Mercaptoethanol↗
PubMed1995

Morphometry of rat germ cells during spermatogenesis.

BACKGROUND: There has never been a study of the components of germ cells as they progress through spermatogenesis. METHODS: The structural changes taking place in rat germ cells, from spermatogonia to late spermatids, were studied utilizing morphometric techniques conducted largely at the ultrastructural level. RESULTS: Volume and surface area parameters for virtually all cellular and subcellular features were obtained for nine periods during the spermatogenic cycle. Virtually all germ cell components show dynamic properties associated with specific phases of their development. CONCLUSIONS: The data provided can be used in an objective way to characterize structural changes taking place during spermatogenesis and to relate those structural changes to functional properties of germ cells.

Acrosome↗
PubMed1995

Tissue specific basal expression of soluble murine epoxide hydrolase and effects of clofibrate on the mRNA levels in extrahepatic tissues and liver.

The soluble epoxide hydrolase mRNA level in liver was increased eight-fold upon administration of the hypolipidemic drug and peroxisome proliferator clofibrate for 7 days to mice. The soluble epoxide hydrolase mRNA was back at control levels within 1-2 days after clofibrate withdrawal. The highest expression was in liver, intestine and kidney. Lower levels were found in heart and muscle and very low levels were found in testes, lung, brain and spleen. The mRNA levels were increased in liver, kidney and heart by clofibrate.

Animal Feed↗