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Biomedical subjects

U Berg

Publications and source records attributed to U Berg.

At least 19 recordsLinked to original sources
PubMed2000

Development of renal cell carcinoma in living donor kidney grafts.

BACKGROUND: Although development of malignancies after transplantation is well recognized, de novo development of cancer in renal transplants is a rare phenomenon. We describe two cases of de novo development of renal cell carcinoma in two living donor grafts. MATERIALS AND RESULTS: The recipients were 45 and 4 years, respectively, at transplantation and their fathers were donors. Because of failure to grow, they were both treated with human growth hormone. Over the years a number of cysts developed in the grafts and after 8 and 7 years the echogenecity of some of the cysts changed. Biopsy confirmed the diagnosis renal cell carcinoma 9 and 11 years after transplantation. The grafts were removed and the immunosuppressive therapy discontinued. The two fathers are well with normal function of the native kidney and no signs of cyst formation or cancer. CONCLUSION: Two cases of de novo development of cancer in living donor kidney transplants are described. Because a stimulatory effect of growth hormone on tumor genesis has been described, this treatment may have been of importance in the tumor development. The findings emphasize the importance of annual ultrasonographic surveillance of renal grafts, especially in the pediatric population.

Carcinoma, Renal Cell↗
PubMed2000

Renal response to a protein load persists during long-term follow-up of children after renal transplantation.

BACKGROUND: Kidney donors and transplant recipients may be at risk of complications from glomerular hyperfiltration of the single kidney. It has been assumed that tests of the existence of renal functional reserve [delta glomerular filtration rate (deltaGFR), delta effective renal plasma flow (deltaERPF)] can be used to demonstrate hyperfiltration. It would therefore be of interest to evaluate the response of the kidney graft to a protein load. i.e., testing the renal reserve and to find out whether a reduction in baseline GFR is preceded by a loss of deltaGFR. METHODS: We repeatedly studied the change in GFR and renal plasma flow (ERPF) after an oral protein load in 30 children after renal transplantation (Tx). Follow-up time was 1.0-8.0 years. Renal function was evaluated with the clearances of inulin and para-aminohippuric acid (PAH). Seven recipient/donor pairs were examined twice (median 0.3 and 4 years, after Tx). RESULTS: The baseline GFR and ERPF remained stable throughout the follow-up and the increase after stimulation (deltaGFR and deltaERPF) did not change in the whole group of Tx children over the years. However, a reduction in the baseline GFR from the first to the last investigation occurred in 23 of 30 children. In the 23 patients whose baseline GFR decreased, deltaGFR was still preserved. In the recipient/donor pairs, the baseline GFR and ERPF were the same, but on the second investigation, donors showed higher deltaGFR. CONCLUSION: Despite fairly low baseline GFR and ERPF values in the Tx children, no change occurs in the capacity to increase GFR and ERPF after a protein load during follow-up, which suggests that they are not maximally hyperfiltrating.

Child↗
PubMed2000

Synthesis and chiroptical properties of Methanocycloocta

The synthesis of chiral methanocyclocta[b]indoles, the fused structures obtained from enantiomeric bicyclo[3.3.1]nonanones via Fisher indolization reaction, is reported. The starting optically active bicyclo[3.3.1]nonane-2,6-dione (1) was obtained by a chiral HPLC enantiomer separation on a swollen microcrystalline triacetylcellulose column and by the enzymatic resolution of the racemic dione. The circular dichroism (CD) spectra of the chiral structures 4, 5, and 7 were recorded, and the absolute configuration for the indole compounds was assigned. The theoretical calculations of the CD spectrum of diindole 4 reproduce the (1)B(b) couplet at 229 nm but predict wrong signs for the (1)L(a) and (1)L(b) bands using standard polarization directions. The CD spectrum of indole ketone 5 is reproduced correctly.

Journal Article↗
PubMed2000

Synaptosome-associated protein of 25 kilodaltons in oocytes and steroid-producing cells of rat and human ovary: molecular analysis and regulation by gonadotropins.

The synaptosome-associated protein of 25 kDa (SNAP-25) is crucially involved in exocytosis in neurons. The aim of this study was to investigate whether it is present in the ovary. We found SNAP-25 to be expressed in nonneuronal cells of the rat and human ovary, namely in all oocytes and in steroidogenic cells, including granulosa cells (GC) of large antral follicles and luteal cells. Both isoforms, SNAP-25a and b, were found in the ovary. Oocytes obtained by laser capture microdissection were shown to express SNAP-25b, whereas SNAP-25a was found in rat GC and human luteinized GC. Immunohistochemical observations of strong SNAP-25 staining in GC of large growing antral follicles compared with absent or weak staining in small follicles suggested a role in folliculogenesis. To study a presumed regulation of SNAP-25, we used a rat GC line (GFSHR-17), which expresses FSH receptors, and luteinizing human GC, which express LH receptors. FSH elevated SNAP-25 mRNA and protein levels about fivefold within 24 h in GFSHR-17 cells. The cAMP analogue dibutyryl-cAMP (db-cAMP) mimicked this action of FSH. The effects of both db-cAMP and FSH were inhibited by the protein kinase A (PKA) inhibitor H89. In contrast, SNAP-25 protein and mRNA-levels were not altered by LH/hCG in luteinized human GC. Our results for the first time identify SNAP-25b in oocytes and SNAP-25a in steroidogenic cells of the mammalian ovary. SNAP-25a and b may be involved in different exocytotic processes in these cell types.

Animals↗
PubMed2000

Identification of an ovarian voltage-activated Na+-channel type: hints to involvement in luteolysis.

An endocrine type of voltage-activated sodium channel (eNaCh) was identified in the human ovary and human luteinized granulosa cells (GC). Whole-cell patch-clamp studies showed that the eNaCh in GC is functional and tetrodotoxin (TTX) sensitive. The luteotrophic hormone human CG (hCG) was found to decrease the peak amplitude of the sodium current within seconds. Treatment with hCG for 24-48 h suppressed not only eNaCh mRNA levels, but also mean Na+ peak currents and resting membrane potentials. An unexpected role for eNaChs in regulating cell morphology and function was indicated after pharmacological modulation of presumed eNaCh steady-state activity in GC cultures for 24-48 h using TTX (NaCh blocker) and veratridine (NaCh activator). TTX preserved a highly differentiated cellular phenotype. Veratridine not only increased the number of secondary lysosomes but also led to a significantly reduced progesterone production. Importantly, endocrine cells of the nonhuman primate corpus luteum (CL), which represent in vivo counterparts of luteinized GC, also contain eNaCh mRNA. Although the mechanism of channel activity under physiological conditions is not clear, it may include persistent Na+ currents. As observed in GC in culture, abundant secondary lysosomes were particularly evident in the regressing CL, suggesting a functional link between eNaCh activity and this form of cellular regression in vivo. Our results identify eNaCh in ovarian endocrine cells and demonstrate that their expression is under the inhibitory control of hCG. Activation of eNaChs in luteal cells, due to loss of gonadotropin support, may initiate a cascade of events leading to decreased CL function, a process that involves lysosomal activation and autophagy. These results imply that ovarian eNaChs are involved in the physiological demise of the temporary endocrine organ CL in the primate ovary during the menstrual cycle. Because commonly used drugs, including phenytoin, target NaChs, these results may be of clinical relevance.

Animals↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗