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Biomedical subjects

A Bergh

Publications and source records attributed to A Bergh.

At least 37 records · Page 2Linked to original sources
PubMed2001

Didecyl squarate--a practical amino-reactive cross-linking reagent for neoglycoconjugate synthesis.

The present paper describes the synthesis and use of the hydrophobic squaric decyl ester glycosides in neoglycoconjugate chemistry. The 2-aminoethyl glycosides of alpha-D-mannopyranose, lactose, globotriose, globotetraose, GM3, and sialyl Lewis(x), as well as the 2-(2-aminoethylthio)ethyl glycoside of alpha-D-mannopyranose, beta-D-glucopyranose, and galabiose were reacted with squaric acid didecyl ester to afford the hydrophobic squaric decyl ester glycosides. These glycosides were efficient reagents for the conjugation to amino-functional microtiter plates, BSA and aminated Sepharose EAH 4B. The decyl ester moiety of the squaric decyl ester glycosides constitutes a traceless hydrophobic tag, which has the major advantage, as compared to the corresponding ethyl esters, that it enables easy purification of the glycosides with silica chromatography and that unreacted excesses glycosides from conjugation reaction mixtures can easily be recovered by means of C18 solid phase extraction.

Amines↗
PubMed2001

Low frequency of microsatellite instability in hereditary prostate cancer.

OBJECTIVE: To investigate whether there is widespread microsatellite instability (MSI) in families with hereditary prostate cancer (HPC). PATIENTS AND METHODS: Eighty-four prostate tumours from 80 Swedish men in 35 families with HPC were screened for genetic instability at microsatellite marker loci BAT-25, BAT-26, BAT-34C4, D2S123 and D17S250. RESULTS: MSI was detected in only five individuals from different families. Three tumours (4%) were unstable at more than two MSI loci and hence classified as high-frequency MSI (MSI-H) according to a previous definition. Interestingly, two of the MSI-H tumours were from patients in families with both HPC and familial colon cancer. CONCLUSIONS: Widespread MSI is a rare event in hereditary prostate cancer, indicating that defective DNA mismatch repair is not an important element in the genesis of HPC.

Adult↗
PubMed2001

Castration-induced reduction of vascular endothelial growth factor expression in benign human prostate tissue is lost in advanced prostate cancer.

OBJECTIVE: To determine the role of vascular response in the castration-induced regression of benign and malignant human prostate tissue, as recent studies show that castration rapidly decreases blood flow and induces endothelial cell death, which may be important for subsequent epithelial cell death and involution of the glandular tissue of the prostate. MATERIALS AND METHODS: The expression of vascular endothelial growth factor (VEGF) and its receptors was analysed using the quantitative reverse transcriptase-polymerase chain reaction, in benign and tumour areas of core biopsies taken before, and approximately 1 week after castration therapy. The castration-induced VEGF response was related to therapy-induced changes in tumour cell apoptotic index and subsequent response in serum prostate-specific antigen (PSA). In another set of patients, serum VEGF was quantified by enzyme-linked immunosorbent assay before, and at 3--6 months after castration therapy. RESULTS: VEGF mRNA was down-regulated after castration in benign prostate tissue (P < or = 0.05), whereas in tumour tissue, VEGF levels were reduced in some of the patients but unchanged or increased in others. In most patients whose tumour tissue responded with VEGF reduction, there was a corresponding increase in tumour cell apoptosis. Serum VEGF levels were not significantly changed after castration. Almost all patients responded with a substantial reduction in serum PSA after castration. CONCLUSION: Castration reduces VEGF mRNA expression in benign prostate tissue and generally in those prostate tumours where castration also induces tumour cell apoptosis. This suggests that a therapy-induced down-regulation of VEGF could be important for tumour cell death.

Apoptosis↗
PubMed2001

Blood vessels are regulators of growth, diagnostic markers and therapeutic targets in prostate cancer.

The vasculature plays an important role in the normal and malignant prostate. Under basal conditions both glandular epithelial and stromal prostate cells produce an abundance of blood flow and angiogenesis regulating substances and the expression of these is generally increased in prostate tumors. The proportion of proliferating endothelial cells is high in the normal prostate compared to other tissues in the body. After castration effects on the vasculature, such as decreased blood flow and vascular regression, precede effects on the glandular compartment. Correspondingly, hormone induced prostate growth is characterized by early effects on the vasculature such as increased blood flow and endothelial cell proliferation, thus indicating that the vasculature may be involved in the androgenic regulation of the prostate. Prostatic intraepithelial neoplasia (PIN) and prostate cancer are associated with increased vascular density and in experimental models prostate cancer growth is apparently angiogenesis-dependent since tumor growth and progression can be inhibited by antiangiogenic treatment. Moreover, vascular density has been related to prognosis in prostate cancer patients. A better understanding of the pathways regulating angiogenesis in the normal prostate and how these pathways change during malignant transformation can hopefully lead to better prognostic markers and therapies for the large group of patients with prostate cancer. The purpose of this review is therefore to summarize the current knowledge on the role and regulation of the vasculature in the prostate and its potential clinical applications.

Humans↗
PubMed2001

Effects of acute graded reductions in testicular blood flow on testicular morphology in the adult rat.

The effect of moderate reductions in testicular blood flow has not been studied systematically. The aim of this study was, therefore, to examine the effects of different degrees of blood flow reduction on testicular morphology and to determine how much flow can be reduced before damage occurs. The subcapsular testicular artery was partially ligated in the left testes of adult rats. Testicular blood flow was measured before, immediately after, and 5 h after the ligation using laser Doppler flowmetry. After 5 h of partial ligation, the testes were removed, and their morphology was examined and related to the degree of blood flow reduction. The number of in situ end-labeled- or TUNEL-positive (i.e., dying) germ cells and the volume density of intravascular polymorphonuclear (PMN) leukocytes were measured. When flow was reduced to approximately 70% or less of its pretreatment value, a dose-related increase in the number of dying spermatogonia and early spermatocytes was seen. The PMN leukocytes accumulated in testicular blood vessels after partial ligation, and the maximum number was observed in testes where flow was reduced by approximately 50% of the pretreatment value. In conclusion, early stages of spermatogenesis are sensitive to a moderate, acute reduction in blood flow. Discrete reductions in flow may, therefore, have a large impact on sperm production.

Animals↗
PubMed2001

Leptin is associated with increased prostate cancer risk: a nested case-referent study.

A Western lifestyle has been implicated in the pathogenesis of prostate cancer. However, no clear association between obesity and prostate cancer has been shown. Leptin may stimulate prostate growth and angiogenesis, and receptors for leptin are present in the prostate. Leptin may, thus, be associated with increased risk of prostate cancer. One hundred forty-nine men with prostate cancer were identified (together with 298 matched referents) who, before diagnosis, had participated in population-based health surveys in Northern Sweden. Blood pressure, body mass index, and use of tobacco were recorded. Leptin, insulin, insulin-like growth factor I (IGF-I), IGF-I-binding proteins 1-3, testosterone, and sex hormone-binding globulin were analyzed in stored samples. Their influences on prostate cancer were estimated by conditional logistic regression analysis. Prostate cancer specimens were investigated for immunoreactivity for the leptin receptor. Relative risk (95% confidence intervals) estimates of prostate cancer over the quintiles of leptin were 1.0, 2.1 (1.1-4.1), 2.6 (1.4-4.8), 1.4 (0.7-2.7), and 1.6 (0.8-3.2). Adjustments for metabolic variables, testosterone, and IGF-I and its binding proteins did not attenuate this increased risk. Immunoreactivity for the leptin receptor was detected in normal, high-grade prostatic intraepithelial neoplasia lesions and malignant prostatic epithelium. Moderately elevated plasma leptin concentrations are associated with later development of prostate cancer. This may be due to direct effects of leptin on prostatic intraepithelial neoplasia lesions, or to indirect actions through other mechanisms. A critical fat mass related to an interior milieu favorable for prostate cancer development seems to exist, because intermediate but not high leptin levels are related to prostate cancer risk.

Adult↗
PubMed2001

BRCA2 mutation in a family with hereditary prostate cancer.

Hereditary prostate cancer is a genetically heterogeneous disease, and so far four different susceptibility loci have been identified. Reports of associated cancers are few, and it is generally considered a site-specific disease. However, some reports have shown an elevated risk for prostate cancer among BRCA2 mutation carriers. In this report, we present a family in which the father and four of his sons were diagnosed with prostate cancer at exceptionally early ages (51, 52, 56, 58, and 63 years, respectively). In addition, three daughters were diagnosed with breast cancer between the ages of 47 and 61. In this family, a truncating mutation in exon 11, 6051delA of the BRCA2 gene, leading to an early termination of the protein (codon 1962), was identified. Although BRCA2 is probably responsible only for a very small fraction of hereditary prostate cancers, this finding supports previous reports of an increased risk of prostate cancer in BRCA2 mutation carriers.

Aged↗
PubMed2000

Vascular endothelial growth factor content in metastasizing and nonmetastasizing Dunning prostatic adenocarcinoma.

BACKGROUND: Tumor angiogenesis is important in progressive tumor growth and metastasis. In the normal rat prostate and in androgen-sensitive prostate tumors androgen ablation causes an involution of the vasculature and a decrease in the vascular endothelial growth factor (VEGF) levels before regression of the prostate gland. To examine whether angiogenesis and metastasis are regulated by VEGF in androgen-insensitive and metastasizing prostate tumors, five Dunning rat prostate cancer sublines were tested; the androgen-sensitive, nonmetastasizing R3327 PAP, and the androgen-insensitive, low metastasizing AT-1, and the three androgen-insensitive, metastasizing AT-2, AT-3, and MatLyLu Dunning prostatic adenocarcinomas. METHODS: VEGF levels were quantified in the rat dorsolateral prostate and in the five Dunning sublines using competitive RT-PCR, Western blot, and Elisa. Vascular density was determined by factor VIII staining. RESULTS: VEGF mRNA was increased in all tumors compared with normal prostates. The two metastatic sublines AT-3 and MatLyLu and the nonmetastatic subline AT-1 showed the highest VEGF mRNA expression. VEGF protein levels in the prostate gland showed increased expression in the metastatic sublines, AT-2, AT-3, and MatLyLu, compared with the nonmetastatic AT-1 subline and the ventral prostate. VEGF proteins in serum were highest in the metastatic AT-3 subline. The vessel density was highest in the two highly metastatic sublines AT-3 and MatLyLu. CONCLUSIONS: Our results suggest that VEGF levels are associated with microvessel density and the previously established metastatic pattern of these rat prostate tumor systems.

Adenocarcinoma↗
PubMed2000

Cancer risk in families with hereditary prostate carcinoma.

BACKGROUND: Little is known regarding the clinical features of hereditary prostate carcinoma (HPC) and whether other malignancies are associated with this disease. The aim of this study was to investigate whether tumors other than prostate carcinoma aggregate in families with HPC or whether this disease can be considered site specific. METHODS: From 62 Swedish families with HPC, a cohort was constructed of 1364 first-degree relatives of the men with prostate carcinoma in these families. Through linkage to the Swedish Cancer Register, all reported cancer between 1958 and 1996 was identified. The expected number of cases was calculated by using the population rates in Sweden. RESULTS: A standardized incidence ratio (SIR) of 1. 16 (95% confidence interval [95% CI], 0.97-1.38) for the overall cancer risk was observed among the 1364 first-degree relatives. However, significant increased risks were noticed for gastric carcinoma (SIR, 2.78; 95% CI, 1.59-4.52), for breast carcinoma in women (SIR, 1.58; 95% CI, 1.01-2.35), and for kidney carcinoma (SIR, 2.51; 95% CI, 1.15-4.77).The excess risk for breast carcinoma was even more pronounced among women before the age of 65 years in families with earlier onset prostate carcinoma (SIR, 3.64; 95% CI, 1. 66-6.91). Seven families with at least two or more relatives with breast, gastric, or kidney carcinoma were identified, and, in one family, four relatives with early onset gastric carcinoma were observed. CONCLUSIONS: In most of the families with HPC, the disease appears to be "site specific," with no excess of other malignancies. However, in a subset of families, a significant aggregation of prostate carcinoma together with breast carcinoma and/or gastric carcinoma was observed that may have been caused by a common germline mutation in a cancer susceptibility gene.

Adult↗
PubMed2000

Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice.

BACKGROUND: In this study, we investigated whether dietary intervention could inhibit tumor growth of an androgen-sensitive human prostatic cancer. METHODS: LNCaP cells were transplanted subcutaneously in nude-mice. The animals were then put on different diets and tumor take, tumor growth and prostate specific antigen (PSA) secretion were studied during 9 weeks. RESULTS: Palpable tumors developed in 75% of the tumor-cell injected sites in animals fed a control diet (corn starch, sucrose, etc.) whereas, for animals given rye bran (RB), ethyl acetate extraction from rye bran supplemented cellulose based diets (CCEE), palpable tumors were seen in only 30% and for soy protein based diets (SCC) 50% of the transplantation sites, respectively. The tumors that grew to palpable size in the rye (RB) and soy (SCC) groups were smaller and secreted less PSA than those in the control group. In the rye and soy groups tumor cell apoptosis was increased, but cell proliferation was unaffected. Addition of fat to the rye diet reduced its effect on prostate cancer growth. CONCLUSIONS: Factors in rye bran and soy protein may inhibit prostate cancer growth. The effect is more apparent for rye than for soy. Further studies are needed to identify the effective substances and to explore the mechanism of action.

Adenocarcinoma↗
PubMed2000

Low frequency of allelic imbalance at the prostate cancer susceptibility loci HPC1 and 1p36 in Swedish men with hereditary prostate cancer.

The aim of this study was to investigate allelic imbalance at the major human prostate cancer susceptibility locus HPC1 at 1q24-25 and the recently reported, putative, susceptibility locus at 1p36 in prostate tumors from Swedish families with hereditary prostate cancer. We analyzed 31 prostate tumors and two lymph node metastases from 33 Swedish men in 22 families with hereditary prostate cancer for the presence of allelic imbalance using microsatellite markers D1S158, D1S422, and D1S238 for the HPC1 locus and D1S1597, D1S407, and D1S489 for the 1p36 locus. Frequencies of allelic imbalance at the two investigated loci were quite low, 3 of 27 informative tumors at the 1p36 locus and 3 of 27 informative tumors at the HPC1 locus. Interestingly, two tumors showed allelic imbalance at both loci investigated, suggesting that they may have lost a great part of chromosome 1. Taking this possibility into consideration, the specific loss of the two investigated loci may be even lower (1 of 27 informative tumors for either locus). The very low level of allelic imbalance found at HPC1 and 1p36 makes it unlikely that these loci encode genes that are acting as classic tumor suppressor genes in the initiation or progression of hereditary prostate cancer. Of the eight tumors from HPC1-linked families, only two showed AI at the HPC1 locus, one of which had lost the wild-type allele.

Allelic Imbalance↗
PubMed2000

Toxaphene levels in salmon (Salmo salar) from the Baltic Sea.

Three toxaphene congeners have been determined in salmon from the Swedish coastal environment using both supercritical fluid (SFE) and the traditional liquid/liquid extractions. The levels obtained using a modifier-free SFE technique, followed by group separation on a silica gel column, were by far much lower than concentrations obtained by SFE with a modifier or liquid/liquid extraction. The mean concentrations on fresh weight basis using a liquid/liquid extraction technique were 5.87, 8.70 and 1.59 microg/kg for CHBs 26, 50 and 62, respectively. There was a plausible relationship between the various fishing sites and the toxaphene levels.

Animals↗
PubMed2000

Effects of finasteride and bicalutamide on prostatic blood flow in the rat.

OBJECTIVE: To determine whether finasteride and bicalutamide, both currently used in the clinical management of patients with prostate diseases because they have anti-androgenic properties, have any effects on prostatic blood flow in a rat prostate model, as androgens are known to be involved in the regulation of prostatic blood flow and angiogenesis. MATERIALS AND METHODS: Both finasteride and bicalutamide were supplied as oral suspensions in water and given daily to rats for 7 days by tube feeding. Blood flows to the ventral and dorsal prostates, and to the kidneys, were measured using the radioactive microsphere technique. In the bicalutamide experiments, some rats were treated with the Leydig cell toxin ethane dimethane sulphonate (EDS), to obtain a castration-like effect, and one group of these rats received testosterone. RESULTS: Finasteride induced a clear decrease in blood flow to the ventral and dorsal prostates after 7 days of treatment, with no significant changes in blood pressure or kidney blood flow. Bicalutamide inhibited the testosterone-induced increment of prostatic blood flow observed in EDS-treated animals. CONCLUSIONS: Finasteride, a blocker of 5alpha-reductase, decreases prostate blood flow after 7 days of administration. The response was slower than that after castration, but was of similar magnitude. Blood flow was also decreased after treatment with the androgen-receptor inhibitor bicalutamide. These observations suggest that prostatic blood flow is increased by dihydrotestosterone, and that the androgen receptor is responsible for mediating this effect.

Androgen Antagonists↗
PubMed2000

Transforming growth factor-beta1 and prostate cancer.

Transforming growth factor-beta1 (TGF-beta1) is an important regulator of the normal and malignant prostate. In the non-malignant prostate, TGF-beta1 stimulates cell differentiation, inhibits epithelial cell proliferation and induces epithelial cell death. TGF-beta1 is secreted into semen and here it is an important immunosuppressive factor. Prostate cancer cells express high levels of TGF-beta1 and it seems to enhance prostate cancer growth and metastasis by stimulating angiogenesis and by inhibiting immune responses directed against tumour cells. Prostate cancer cells frequently lose their TGF-beta receptors and acquire resistance to the anti-proliferative and pro-apoptotic effects of TGF-beta1. Accordingly, high expression of TGF-beta1 and loss of TGF-beta receptor expression have been associated with a particularly bad prognosis in human prostate cancer patients. TGF-beta1 also seems to be a mediator of castration-induced apoptosis in androgen dependent normal and malignant prostate epithelial cells. The ability of some prostate tumours to avoid castration-induced apoptosis is however not simply due to loss of TGF-beta receptor type I or II expression in the tumour cells, but may also be related to an inability of these cells to up-regulate TGF-beta receptor levels in response to castration or possibly due to defects downstream of the receptors. Short-term therapy-induced changes in the TGF-beta system in prostate tumours can probably be used to predict the long-term response to androgen ablation treatment. Further investigations into the TGF-beta system in the prostate are, however, needed to elucidate how alterations in this system affect the behaviour of prostate tumours, and if this system can be manipulated for therapeutical purposes.

Disease Progression↗
PubMed2000

Evaluation of prognostic factors in prostate cancer with partial least squares analysis.

OBJECTIVE: This study was carried out to explore the capability of partial least squares (PLS) analysis, a multivariate projection method, in the evaluation of investigative prognostic biomarkers. MATERIAL AND METHODS: Using PLS analysis, survival and life expectancy were prognosticated in 53 patients with prostate cancer treated with transurethral resection. The age of the patient, stage and grade of the tumours, and immunoreactivity in the tumours for p53, Bcl-2, and TGF-beta1 and its receptors type I and type II (TGFbeta-RI and TGFalpha-RII), and markers for proliferation, vascular density, and macrophage density were included as prognostic factors in the analysis. RESULTS: The prognostic impact of the factors, in decreasing order, was tumour grade, proliferation, stage, vascular density, TGFbeta-RI, metastasis, TGF-beta1, and TGFbeta-RII. Macrophage staining, p53, Bcl-2, and patient age did not contribute to the model. The model explained 62% of the total variance in survival, and the standard deviation of error of prediction was 29 months. CONCLUSIONS: PLS analysis may become a useful tool for evaluation of putative prognostic factors.

Biomarkers↗
PubMed2000

A putative stimulatory role of progesterone acting via progesterone receptors in the steroidogenic cells of the human corpus luteum.

To further explore the proposed auto-regulatory role of progesterone action in the human corpus luteum (CL), the expression and functional roles of progesterone receptor (PR) isoforms A and B during the luteal phase (LP) of the menstrual cycle were investigated. A total of 27 otherwise healthy patients previously scheduled for surgery were recruited after informed consent. An LH rise was detected, and CL were grouped according to age (Days 2-5 post-LH-rise, early LP; Days 6-10, mid LP; Days 11-14, late LP). Using a semiquantitative reverse transcription-polymerase chain reaction assay, the PR-B mRNA levels, which were 100- to 1000-fold lower than PR-A/B mRNA, were 46% lower (P < 0.05, n = 24) in mid LP, compared to early and late LP. CL tissue levels of progesterone and PR-A/B protein levels were inversely correlated to increasing CL age; i.e., significantly reduced levels were observed in the late LP (r(2) = 0.34, P < 0.01, n = 23). Expression of PR-A/B mRNA as well as PR-A/B protein were detected by in situ hybridization and immunohistochemistry, respectively. Both methods revealed a clear and distinct localization to cells in the steroidogenic layer of the CL. Freshly obtained mid-luteal CL cells were cultured in vitro, and media were analyzed for progesterone concentrations after treatment by incremental doses of hCG and the stable PR antagonist mifepristone, alone or in combination. Mifepristone did not per se alter progesterone synthesis, but when it was added in conjunction with hCG, a dose-related inhibitory response was seen, with a maximal 47% reduction in progesterone output at a 10 microM addition (P < 0.05, n = 3). Collectively, these data implicate a stimulatory role of progesterone receptor-mediated action in the steroidogenic cells of the human CL, which may serve as an important pathway for maintaining functional homeostasis during early pregnancy.

Adult↗
PubMed2000

Thoracic paravertebral block for breast surgery.

UNLABELLED: Cosmetic and reconstructive breast augmentation is a frequently performed surgical procedure. Despite advances in medical treatment, surgical intervention is often associated with postoperative pain, nausea, and vomiting. Paravertebral nerve block (PVB) has the potential to offer long-lasting pain relief and fewer postoperative side effects when used for breast surgery. We compared thoracic PVB with general anesthesia for cosmetic breast surgery in a single-blinded, prospective, randomized study of 60 women scheduled for unilateral or bilateral breast augmentation or reconstruction. Patients were assigned (n = 30 per group) to receive a standardized general anesthetic (GA) or thoracic PVB (levels T1-7). Procedural data were collected, as well as verbal and visual analog pain and nausea scores. Verbal postoperative pain scores were significantly lower in the PVB group at 30 min (P = 0.0005), 1 h (P = 0.0001), and 24 h (P = 0.04) when compared with GA. Nausea was less severe in the PVB group at 24 h (P = 0.04), but not at 30 min or 1 h. We conclude that PVB is an alternative technique for cosmetic breast surgery that may offer superior pain relief and decreased nausea to GA alone. IMPLICATIONS: Paravertebral nerve block has the potential to offer long-lasting pain relief and few postoperative side effects when used for breast surgery. We demonstrated that paravertebral nerve block, when compared with general anesthesia, is an alternative technique for breast surgery that may offer pain relief superior to general anesthesia alone.

Adult↗