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Biomedical subjects

U Berg

Publications and source records attributed to U Berg.

At least 37 records · Page 2Linked to original sources

1-(o-aryl)barbituric and 1-(o-aryl)-2-thiobarbituric acid derivatives: chiral atropisomers.

Several 1-(o-aryl)barbituric and -2-thiobarbituric acid derivatives were proven to be chiral in their conformational ground states due to the hindered rotation about the C(aryl)-N(1) bond, by observation of diastereotopic groups (H or CH3) at 5-position of the heteroring by 1H and 13C NMR. Some of the enantiomers were semipreparatively enriched by liquid chromatography on triacetylcellulose or on cellulose tris-(3,5-dimethyl)-phenylcarbamate (chiralcel OD-H). Circular dichroism spectra of the enriched enantiomers have been examined with reference to their stereostructures.

Journal Article↗

Renal function during and after childhood acute poststreptococcal glomerulonephritis.

It is still debatable whether acute poststreptococcal glomerulonephritis (APSGN) can lead to permanent renal impairment. The clinical, immunological, and histological findings during the acute disease have been described thoroughly, however, the hemodynamic events are still poorly understood. In this retrospective study, the inulin and p-aminohippurate clearances were measured to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) within a month of onset of the disease (acute stage) in 26 children, and 2-12 months after onset (follow-up) in 22 children with APSGN. During the acute stage, the mean GFR was 77+/-23 (SD) ml/min per 1.73 m(2), the mean ERPF 537+/-138 ml/min per 1.73 m(2), and the filtration fraction (FF) 14%+/-3%, compared with values for controls of 115+/-11 ml/min per 1. 73 m(2), 607+/-72 ml/min per 1.73 m(2), and 19%+/-2%, respectively (n=42). At follow-up, GFR was 114+/-15 ml/min per 1.73 m(2), ERPF 600+/-68 ml/min per 1.73 m(2), and FF 19%+/-3%. Thus, during the disease both GFR and ERPF fell below values for controls, but later were restored. The GFR, however, was more reduced than the ERPF, as indicated by the reduced FF. This might reflect a relative hyperperfusion of individual nephrons, which might start processes later deleterious to the nephrons. This finding, however, needs to be further investigated and we have therefore started a long-term follow-up of these patients.

Adolescent↗

Functional dopamine-1 receptors and DARPP-32 are expressed in human ovary and granulosa luteal cells in vitro.

The catecholamines norepinephrine and dopamine (DA) are present in the human ovary; in particular, in follicular fluid. Norepinephrine activates ovarian alpha- and beta-adrenergic receptors and modulates ovarian steroidogenesis, but the significance of ovarian DA is unclear. We examined whether a DA receptor of the D1-subtype (D1-R) is present in human ovary and in cultured human granulosa luteal cells (GC). Using RT-PCR, we cloned complementary DNAs from adult human ovarian and GC messenger RNAs, which are identical to the human D1-R sequence. In ovarian sections, D1-R protein was identified (by immunohistochemistry) in granulosa cells of large antral follicles, cells of the corpus luteum, as well as in cultured GC. An immunoreactive band of approximately Mr 50,000 was found in cultured luteinized GC using the same antiserum in Western blots. The D1-R in these cells was functional, because DA, alone or in the presence of the beta-receptor antagonist propranolol, caused cellular contraction. The selective D1-R agonist SKF-38393 induced a similar change in cytomorphology and increased the levels of media cAMP. SKF-38393 failed, however, to significantly affect basal and hCG-stimulated progesterone release in vitro, indicating that the activation of the D1-R was not directly linked to synthesis of progesterone, the major steroid of human GC. Estradiol synthesis likewise was not affected. Using RT-PCR and immunohistochemistry, we found that GC express DA- and cAMP-regulated phosphoprotein of Mr 32,000 (DARPP-32), a protein typically associated with neurons bearing the D1-R. In cultured GC, DA and SKF-38393 induced increased threonine-phosphorylation of DARPP-32, even in the presence of propranolol but not in the presence of D1-R antagonist SCH-23390. Taken together, the presence of DA and a functional DA receptor and DARPP-32 indicate that a novel, physiological regulatory pathway involving DA exists in the human ovary.

Adult↗

Functional and molecular characterization of a muscarinic receptor type and evidence for expression of choline-acetyltransferase and vesicular acetylcholine transporter in human granulosa-luteal cells.

Previously, we provided evidence for the presence of a class of muscarinic receptors on human luteinized granulosa cells (human GC) that is linked to transient increases in intracellular free calcium levels, but not to steroid production. The precise nature of the receptor is not known, and neither its function nor the source of its natural ligand acetylcholine (ACh) is clear. To address these issues we used RT-PCR approaches and isolated complementary DNAs corresponding to the M1 receptor subtype from reverse transcribed human GC messenger ribonucleic acids. M1 receptors were further shown by immunocytochemistry, using a M1 receptor antiserum. Single cell calcium measurements showed that the M1 receptor was functionally active and linked to acute increases in intracellular free calcium, as the M1 receptor specific antagonist pirenzepine blocked the Ca2+-mobilizing effect of oxotremorine M (a muscarinic agonist). An unexpected consequence of M1 receptor activation was evidenced by the ability of muscarinic agonists to stimulate the proliferation of human GC within 24 h. In vivo, ACh, the natural ligand of these receptors is thought to be contained in cholinergic nerve fibers innervating the ovary. Surprisingly, the prerequisite for the synthesis of ACh, the enzyme choline-acetyltransferase (ChAT), is also expressed by human GC, as shown by Western blotting and immunocytochemistry. In addition, these cells express another marker for ACh synthesis, namely the gene for the vesicular acetylcholine transporter, as evidenced by RT-PCR cloning, Western blotting, and immunocytochemistry. In conclusion, our data identify the M1 receptor in human GC and point to a novel, trophic role of the neurotransmitter ACh. Furthermore, the presence of the prerequisites of ACh synthesis in human GC indicate that an autocrine/paracrine regulatory loop also exists in the in vivo counterparts of these cells in the ovary, i.e. in the cells of the preovulatory follicle and/or of the young corpus luteum.

Acetylcholine↗

Stereochemical variations on the colchicine motif. Part 4. A remote metalation approach toward a colchicine analog with a five-membered B-ring.

Attempts to prepare a colchicine analog with a 5-membered B-ring by remote metalation of N,N-diethyl-3,4,5-trimethoxy-2-(5'-methoxy-4'-oxo-2', 5',7'-cycloheptatrienyl)-benzamide (2) led to ring contraction of the methoxytropone ring to the p-methoxycarbonylphenyl derivative (3). Dynamic 1H NMR investigations showed that the biaryl amide 2 exists as a mixture of diastereomers due to hindered rotation around both aryl-aryl and aryl-amide bonds, with rotational barriers of ca. 63 kJ mol-1. The colchicine and allocolchicine analogs 2 and 3 do not notably affect tubulin polymerization, despite the structural similarities with active analogs. The reduced tubulin binding activity of 2 and 3 may be a result of increasing steric bulk.

Colchicine↗

Pediatric renal transplantation in the Nordic countries: a report of the Nordic Pediatric Renal Transplant Study Group.

The Nordic Pediatric Renal Transplant Study Group was organized in 1994 to register and follow children under 16 years of age who receive renal allografts in the Nordic countries. It comprises all transplant centers in Scandinavia, four in Sweden, three in Denmark and one each in Norway and Finland. The following report is based on 430 transplantations performed in 1982-1996. 343 were first transplants and 57 were retransplants. The mean annual incidence of renal transplantations per million children below 16 years of age was 7.4. The mean incidence of retransplantations was 1.0 and therefore the mean incidence of primary transplantations was 6.5 per million children below 16 years of age. 12% of the children were less than 2 years of age, 20% 2-5 years of age and 68% 6-15 years of age. 231 (54%) of the transplants were performed with grafts from living-related donors (LD) and 199 (46%) with cadaveric grafts (CD). 72% of the children had congenital renal disorders and 28% acquired diseases. Cyclosporine-based immunosuppressive protocols were used in all centers. Antibody induction therapy (polyclonal or monoclonal) was used by only three of the nine participating centers. The mean 1-year graft survival rate for all age groups was 88% for recipients of living-donor grafts and 78% for recipients of cadaveric donor grafts.

Adolescent↗

Renal function in cyclosporine-treated pediatric renal transplant recipients in relation to gingival overgrowth.

BACKGROUND: Transplant immunosuppression using cyclosporine (CsA) leads to renal dysfunction as well as gingival overgrowth. The underlying alteration in both these lesions is characterized by an excessive accumulation of extracellular matrix components (fibrosis). To investigate the relationship between CsA-induced nephrotoxicity and gingival overgrowth, the renal function as well as the occurrence of gingival overgrowth was evaluated in pediatric renal transplant recipients: 38 boys and 30 girls, ranging in age from 2 to 20 years, who had been on a CsA-based immunosuppressive regimen for at least 12 months. METHODS: Gingival overgrowth was determined on the basis of measurements of sulcus depth and was diagnosed as positive when the probing depth was > or = 4 mm without exhibiting a loss of periodontal attachment. Renal function tests were performed using inulin and para-aminohippuric acid clearances for evaluating glomerular filtration rate, effective renal plasma flow (ERPF), and filtration fraction (FF). RESULTS: Nineteen percent of the children exhibited gingival overgrowth. The occurrence of gingival overgrowth was positively related (P<0.05) to the mean oral daily dose of CsA, the mean CsA trough blood level, and concomitant administration of nifedipine. The children who were on antihypertensive treatment exhibited lower ERPF and significantly higher FF than the normotensive children. The mean FF value was significantly higher (P<0.05) in the children with gingival overgrowth than in those without gingival overgrowth, whereas glomerular filtration rate and ERPF did not differ between the two groups. CONCLUSIONS: The study suggests that there is a positive correlation between the degree of gingival enlargement and changes in renal function expressed as filtration fraction.

Adolescent↗

Renal transplantation in children less than two years old.

Twenty-one infants, 2 years old or younger, received 21 renal transplants between 1983 and 1995. Six of the transplantations were performed from 1983 to 1989, and the remaining 15 were performed from 1990 to 1995. The median age at transplantation was 16.0 months and the median body weight was 9.0 kg. Living-related donor kidneys were used in 15 cases, an adult cadaveric donor kidney was used in one case, and pediatric cadaveric donor kidneys were used in five cases. All grafts were placed intra-abdominally. The immunosuppressive therapy consisted of cyclosporine, azathioprine, and prednisolone. No prophylactic antithymocyte globulins were used. Five infants have died, one with a functioning graft and four after loss of graft function. All graft losses and deaths occurred during the first 6 months after transplantation. The 5-year patient survival and graft survival rates were 87% for recipients of living donor grafts and 44% for recipients of cadaveric grafts. The median height SD score increased from -3.7 before operation to -1.9 at 1 year, -0.7 at 3 years, and -1.1 at 5 years. The glomerular filtration rate in absolute values remained stable in all infants, whereas a reduction in glomerular filtration rate related to body surface area was seen at follow-up, 5 years after transplantation. We conclude that renal transplantation can be performed with good long-term results in children less than 2 years old.

Adult↗

Epidemiology of chronic renal failure in children: a report from Sweden 1986-1994. Swedish Pediatric Nephrology Association.

In a national survey, chronic renal failure (CRF) in Swedish children was studied during the period 1986-1994; 118 children (72 boys, 46 girls) with CRF, defined as a glomerular filtration rate below 30 ml/min per 1.73 m2 body surface area, were identified. The median annual incidence of CRF was 7.7 and that of terminal renal failure (TRF) 6.4 per million children. The prevalence of preterminal renal failure decreased from 29 to 21 per million children over the study period, while the prevalence of TRF increased from 17.8 in 1986 to 38 per million children in 1994. The increase in TRF prevalence was due to a lower incidence of deaths due to uremia and a slightly increased incidence of TRF compared with an earlier study period, 1978-1985. The results point to a more active treatment of uremia in Sweden now than during the period 1978-1985. The congenital causes of CRF (renal malformations, obstructive conditions, and hereditary disorders) accounted for 67.5% of all cases, which is high compared with data from other countries. No child with non-obstructive pyelonephritis as a cause of CRF was identified. Age at detection of CRF and time from detection of CRF to TRF were studied. As a high proportion of children, 42%, reached 16 years of age without entering TRF, the value of presenting time from CRF to TRF for the remaining individuals is questionable. There were only minor differences in primary renal disease, age at presentation, and time from CRF to TRF when the study results were compared with those from 1978-1985.

Adolescent↗

Effect of motile sperm count after swim-up on outcome of intrauterine insemination.

OBJECTIVE: To analyze the prognostic value of motile sperm count after swim-up in IUI with husband's sperm in a large group of subfertile couples. DESIGN: Retrospective study. SETTING: University hospital. PATIENT(S): Nine hundred two couples undergoing 3,037 treatment cycles. INTERVENTION(S): Intrauterine insemination with husband's sperm after swim-up was performed after mild ovarian stimulation with clomiphene citrate and hCG under hormonal and ultrasonographic control of follicle development. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) in correlation to motile sperm count after swim-up. RESULT(S): A nonlinear increase in PR per treatment cycle was observed with increasing numbers of motile sperm used for IUI. Insemination with < 0.8 x 10(6) motile sperm after swim-up resulted in a PR of < 1% per treatment cycle. When the motile sperm count was above this level, the PR per cycle reached a plateau of 6.9% to 10.2%, with a minor tendency for increase with higher sperm numbers. CONCLUSION(S): Strict analysis of motile sperm count after swim-up is a useful prognostic factor for PRs after IUI. There is a good chance for conception if > or = 0.8 x 10(6) motile sperm are available after appropriate selection methods. Intrauterine insemination performed with considerably higher numbers of motile sperm does not lead to a significant increase in PRs.

Adolescent↗

Hyperacute rejections of two consecutive renal allografts and early loss of the third transplant caused by non-HLA antibodies specific for endothelial cells.

The immunological rejection of HLA-identical kidney transplants indicates that non-HLA antigens may also be targets for transplant rejection. Interest in the possible role of endothelial specific antigens has grown steadily over the years. Most of the studies published, regarding the association of such antibodies with rejection, have demonstrated the reactivity of endothelial antibodies also with monocytes and keratinocytes, but not with lymphocytes. Such antibodies escape detection in conventional crossmatch tests. In this paper, we present a case report of a 10-year-old girl, whose two consecutive kidney allografts, (one living and one cadaveric donor) were hyperacutely rejected in spite of the fact that she had neither been alloimmunized, nor had any HLA-specific antibodies. Endothelial cell specific antibodies were detected in vivo and in vitro after transplantation only 11 days apart, which were considered to be responsible for rejection. The third cadaveric kidney was lost within 1 week post-transplant. Immunopathological investigation of the three rejected grafts revealed deposition of IgM in the endothelium of arteries and in some glomeruli. No deposition of IgG antibodies was found. Antibodies from this patient did not react with lymphocytes, monocytes or keratinocytes. Patient serum had IgM antibodies that were specifically reactive with cultured endothelial cells, demonstrated by binding in vitro and by complement-dependent cytotoxicity of IL-beta stimulated endothelial cells. No HLA antibodies were found following the first two transplantations, but were demonstrated 1 week after the third transplantation, at the time of an acute irreversible rejection. Western blots of proteins solubilized from endothelial cell membranes, indicated that the antibodies reacted with a 97-110 kD protein. Endothelial cell antigen preparations were made from several different umbilical cord veins. Some primary cell cultures, but not all, reacted with the patient's serum. Therefore, we suggest that the target determinant might be polymorphic. These findings imply that the non-HLA endothelial cell specific molecules may function as target(s) for hyperacute antibody-mediated destruction of kidney allografts.

Antibody Specificity↗

Effect of acute endurance and strength exercise on circulating calcium-regulating hormones and bone markers in young healthy males.

Physical activity plays a role in the maintenance of the skeleton but the mechanical, metabolic and hormonal mechanisms involved are largely unknown. The influence of acute endurance and strength exercise on circulating levels of calcitonin, parathyroid hormone (PTH), PTH-related peptide (PTHrP), osteocalcin, carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and ionized calcium (Ca2+) was therefore evaluated. Eight healthy young males performed three exercise bouts on separate occasions: endurance exercise, i.e. cycling on a cycle ergometer for 45 min at 55% of Vo2max (E55%) and 15 min at 85% of Vo2max (E85%) and strength exercise at 85% of three repetitions maximum using a leg-press device (STR). Control experiments included the same subjects with the same time schedule but without exercise. Blood samples were taken before, immediately after exercise and during the recovery period. Hormones and bone markers were measured by use of various immunoassays. There was no obvious influence on calcitonin and PTHrP levels, whereas PTH was increased after strength exercise. ICTP and osteocalcin levels correlated positively at all times and showed regular variations. In comparison with the controls, ICTP levels showed a more pronounced decrease following physical activity whereas osteocalcin followed the same pattern as the controls except for after prolonged endurance exercise when a decrease was abolished. In conclusion, an increase in PTH after strength exercise and a pronounced decrease in ICTP after all exercise together with a relative increase in osteocalcin after prolonged endurance exercise might reflect some mechanisms involved in the positive effect of physical activity on bone mass.

Adult↗

Nerve conduction and autonomic nerve function in diabetic children. A 10-year follow-up study.

In order to study the long-term development of diabetic neuropathy in children with newly diagnosed diabetes mellitus, 144 children were entered in a prospective study of nerve conduction and autonomic nervous function. Neurophysiological recordings of nerve conduction and parasympathetic function (R-R variations) were made at onset of diabetes and after 2, 5 and 10 years. Low sensory nerve conduction and autonomic dysfunction were found in approximately 25% of the children at onset of diabetes when the patients were not yet in complete remission. During years 0-2, an initial improvement of sensory conduction velocities was found. After 2 years, deteriorations in sensory and motor nerve conduction and autonomic nerve function were common and further deterioration was seen over time. A correlation was found between nerve conduction and glycaemic control.

Adolescent↗

Three year results of in vitro production of bovine embryos in serum-poor bovine oviduct conditioned medium. An overview.

This paper presents a synthesis of 3 year results of in vitro production of bovine embryos in medium previously conditioned by bovine oviduct epithelial cells. In Louvain-la-Neuve, Belgium, a total of 18356 oocytes were matured and inseminated in vitro: 13967 (76%) had cleaved at 3 days post-insemination and 3593 (26%) became blastocysts using this culture system. Our data show that conditioned medium can be stored frozen for up to 3 years without significant loss of activity and is resistant to lyophilization. One single batch of conditioned medium was tested within the same period in four different laboratories and yielded variable results: 27 and 37% blastocysts/cleaved embryos in two of them and only 7 and 0% in the two others whereas in each case more than 30% blastocysts were obtained with the local reference co-culture system. In one laboratory, the batch of oil used to overlay the culture drops had a detrimental effect on the blastocyst rate in conditioned medium but not in co-culture.

Animals↗

Secretion of biologically active interferon tau by in vitro-derived bovine trophoblastic tissue.

Secretion of interferon tau (IFN tau) by trophoblastic tissue has been shown to be the first embryonic signal for pregnancy recognition. Therefore we tried to derive biologically active trophoblastic tissue by in vitro techniques. Since conventional in vitro conditions for bovine embryo development were not sufficient for long-term culture, we tested more complex culture conditions, including Ménézo B2 or Buffalo rat liver (BRL) cell-conditioned medium, for their ability to support proliferation and IFN tau secretion by in vitro-derived trophoblastic tissue. IFN tau activity was determined by using a biological assay based on the inhibition of the cytopathic effect of vesicular stomatitis virus on Madin-Darby bovine kidney cells. When cultures of individual hatched blastocysts were started in 60-microliters drops of BRL cell-conditioned medium, mean IFN tau secretion (antiviral units/ml/48 h) corresponded to 1200 on Day 11 and to 5000 on Day 13 (p < 0.01). To characterize trophoblast cell-specific secretions, the inner cell mass was removed from all embryos by microsurgery on Day 13. IFN tau secretion by trophoblastic tissue increased to mean levels of > 10(5) antiviral units/ml/48 h on Day 23m, stayed high for about 1 wk, and then slowly declined to levels below 10(3) antiviral U/ml/48 h. The specificity of the cytoprotective effect of IFN tau was tested by Western blot analysis and by immunoneutralization with use of a polyclonal antiserum specific to IFN tau. Our results demonstrate that viable trophoblastic tissue can be maintained entirely in vitro and secretes high amounts of IFN tau.

Animals↗

Neonatal herpes simplex: clinical findings and outcome in relation to type of maternal infection.

In 39 mothers of children with neonatal herpes simplex virus infection, maternal infection was serologically characterized retrospectively and was related to maternal clinical symptoms and to the clinical findings and outcome in the child. Thirteen mothers had a primary infection (six type 1, seven type 2), mostly with clinical symptoms. The mean age of onset of the disease of the infants was 7 days and a disseminated disease was most commonly found. Most of the type 1-infected children recovered completely, whereas all but one of the type 2-infected children died. Twenty mothers had a recurrent (2 type 1, 18 type 2) and 4 an intermediate infection (primary type 2, prior infection with type 1), mostly asymptomatic. Their children had a localized disease (of the skin-eye-mouth or the central nervous system) with onset at a mean age of 14 or 13 days, respectively. The frequency of neurological sequelae was high. Two mothers had no serological signs of herpes infection.

Age Factors↗