Vasoactive effects of basic and acidic fibroblast growth factors in hamster cheek pouch arterioles

Fibroblasts growth factors (FGFs) exhibit well-known angiogenic actions, but there is some controversy about whether they have vasoactive effects on blood vessels which might contribute to angiogenesis per se. To clarify this, changes in arteriolar diameter were recorded during observation by videomicroscopy of 3rd- and 4th (terminal)-order arterioles (resting diameters 22.5 +/- 0.5 microns and 14.4 +/- 0.3 microns, respectively) in the hamster cheek pouch in response to FGF application. Recombinant human bFGF (basic) and aFGF (acidic) were applied from micropipettes positioned 5-10 microns from the adventitial surface of vessels. Maximum vasodilator effects of adenosine (10(-4) M) applied in a similar way were also observed. Adenosine increased the diameters of 4th-order arterioles by 37.2 +/- 3.8% and those of 3rd-order arterioles by 38.7 +/- 2.7. bFGF produced vasodilatation (threshold dose 0.1 ng ml-1) in both classes of arterioles, while aFGF produced dose-dependent constriction (threshold dose 0.01 ng ml-1). A maximal dilator effect in 4th-order arterioles was obtained with 100 ng ml-1 bFGF, when diameters reached 82.6 +/- 2.4% of those with adenosine. Maximal constrictor effect (-48.2 +/- 5.6% of resting diameter) occurred with a dose of 100 ng ml-1 aFGF. Vehicle alone (MOPS or bicarbonate buffer used as solvents for FGFs) had no effect. As vasoconstrictors are known to stimulate growth of smooth muscle cells while dilators stimulate growth of endothelial cells, it is possible that the opposing vasoactivities demonstrated for aFGF and bFGF are linked with their selective mitogenicity for smooth muscle and endothelial cells, respectively, and contribute to their angiogenic actions.     

Acidic and basic fibroblast growth factors down-regulate collagen gene expression in keloid fibroblasts

The effects of acidic and basic fibroblast growth factors (FGFs) on collagen expression by keloid fibroblasts were examined in the absence and presence of heparin. Collagen biosynthesis and gene expression of type I collagen were down-regulated by the FGFs in the presence of heparin. Acidic FGF, in a concentration range of 0.4 to 50 ng/ml, had little or no effect on collagen synthesis after a 4-day incubation. However, in the presence of heparin (100 micrograms/ml) acidic FGF, in concentrations ranging from 2 to 50 ng/ml, decreased [3H]hydroxyproline synthesis by 44 to 68%, compared with untreated control cultures. Total [3H]hydroxyproline synthesis was similar between control and heparin-treated cultures. Basic FGF (2.0 to 50 ng/ml) was effective in suppressing [3H]hydroxyproline synthesis by 50 to 90% after a 4-day incubation without heparin in keloid and normal fibroblast cultures. The steady-state levels of type I collagen messenger RNA were significantly decreased by acidic FGF in the presence of heparin, as well as by basic FGF without heparin. The data suggest that the FGFs are effective in down-regulating excess collagen production by keloid fibroblasts and that this inhibitory effect is apparently associated with pretranslational events. Moreover, acidic FGF is apparently dependent on heparin, whereas basic FGF is not, for potentiation of the down-regulatory effects of the FGFs.     

前列腺增生危险因素的病例对照研究

目的 研究前列腺增生(BPH)的各种危险因素及其危害程度.方法 以132例病理确诊的前列腺增生患者为病例组,以年龄匹配的132例无前列腺增生患者为对照组进行1:1配对病例对照研究.采集人口学因素、高血压史、糖尿病史、实验检测等临床资料.资料分析采用单因素和多因素条件Logistic回归分析.结果 (1)单因素分析显示:在吸烟、饮酒、糖尿病史、高血压史、慢性支气管炎史、肾囊肿史和慢性前列腺炎史差异统计学意义(P<0.05).(2)多因素分析显示:吸烟(OR=0.530)、糖尿病史(OR=2.227)、高血压史(OR=1.862)、慢性前列腺炎(OR=2.414)是BPH的独立危险因素(P<0.05).结论 前列腺炎史、高血压史、糖尿病史是BPH发病的危险因素,吸烟为保护性因素.良好的血压和血糖控制是预防BPH的重要方法.     

Acidic and basic fibroblast growth factors in human breast tissue

Previously we have reported changes in fibroblast growth factors (FGF) in conditioned medium (CM) derived from rat mammary tumours undergoing remission. We have used a similar approach to assay for the presence of FGFs in human breast tissue and cell lines. The majority of cancer tissues (35/50), benign tissues (8/9) and all cancer adjacent normal tissues (20/20) released heat labile, NR6 transforming activity which coeluted from heparin with acidic FGF (aFGF) at 0.9-1.1 M NaCl and was neutralised by antibodies to aFGF. The conclusion that the majority of breast cancers contain active aFGF was supported by immunoblotting. The CM of a minority (15/50) of cancers and one benign tissue had highly transforming activity for NR6 cells, and was mitogenic for a breast cancer cell line, was heat labile, and strongly heparin binding, eluting at 1.5-2.0 M salt. It was not immunoreactive with antibodies to aFGF, basic FGF (bFGF) or Kaposi's FGF (kFGF) and its activity was reduced by the presence of aFGF, suggesting competition for the same receptor. Very little aFGF was observed in the CM of these tumours, and neither aFGF nor other FGF activity was detected in CM of breast cell lines.     

Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia

Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer, an equal number of cases of benign prostatic hyperplasia (BPH) and an equal number of apparently healthy control subjects. The three groups were matched for age and town of residence in the greater Athens area. Steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1 (IGF-1) were measured in duplicate by radioimmunoassay in a specialized US centre. Statistical analyses were performed using multiple logistical regression. The results for IGF-1 in relation to prostate cancer and BPH were adjusted for demographic and anthropometric factors, as well as for the other measured hormones. There was no relation between IGF-1 and BPH, but increased values of this hormone were associated with increased risk of prostate cancer; an increment of 60 ng ml(-1) corresponded to an odds ratio of 1.91 with a 95% confidence interval of 1.00-3.73. There was also some evidence for an interaction between high levels of testosterone and IGF-1 in relation to prostate cancer. This finding suggests that, in addition to testosterone, IGF-1 may increase the risk of prostate cancer in humans.     

Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma

BACKGROUND: The p27KIP1 gene, whose protein product is a negative regulator of the cell cycle, is a potential tumor suppressor gene; however, no tumor-specific mutations of this gene have been found in humans. This study was undertaken to identify and to assess potential alterations of p27KIP1 gene expression in patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer. METHODS: We analyzed 130 prostate carcinomas from primary and metastatic sites, as well as prostate samples from normal subjects and from patients with BPH. Immunohistochemistry and in situ hybridization were used to determine the levels of expression and the microanatomical localization of p27 protein and messenger RNA (mRNA), respectively. Immunoblotting and immunodepletion assays were performed on a subset of the prostate tumors. Associations between alterations in p27KIP1 expression and clinicopathologic variables were evaluated with a nonparametric test. The Kaplan-Meier method and the logrank test were used to compare disease-relapse-free survival. Prostate tissues of p27Kip1 null (i.e., knock-out) and wild-type mice were also evaluated. RESULTS: Normal human prostate tissue exhibited abundant amounts of p27 protein and high levels of p27KIP1 mRNA in both epithelial cells and stromal cells. However, p27 protein and p27KIP1 mRNA were almost undetectable in epithelial cells and stromal cells of BPH lesions. Furthermore, p27Kip1 null mice developed enlarged (hyperplastic) prostate glands. In contrast to BPH, prostate carcinomas were found to contain abundant p27KIP1 mRNA but either high or low to undetectable levels of p27 protein. Primary prostate carcinomas expressing lower levels of p27 protein appeared to be biologically more aggressive (two-sided P = .019 [Cox regression analysis]). CONCLUSIONS/IMPLICATIONS: On the basis of these results, we infer that loss of p27Kip1 expression in the human prostate may be causally linked to BPH and that BPH is not a precursor to prostate cancer.     

Induction of basic fibroblast growth factor mRNA by basic fibroblast growth factor in Müller cells

PURPOSE: To investigate the induction of basic fibroblast growth factor (bFGF) gene expression in cultured rat Müller cells by bFGF and to study the mechanism of induction. METHODS: Müller cells from 1- to 3-day-old Sprague-Dawley rats were isolated and cultured with Dulbecco's modified Eagle's medium with 10% fetal calf serum. Cultured cells were identified by immunocytochemistry using antibodies against vimentin, carbonic anhydrase II, and glutamine synthetase. Cells of passages 1 through 4 were treated with bFGF, the protein kinase C (PKC) inhibitor, H-7; calphostin C, or the PKC activator, PMA; and protein kinase A (PKA) inhibitor, H-89; as well as the adenylate cylase activator, forskolin; or the adenylate cyclase inhibitor, SQ22536. Northern blot analysis was performed to determine the mRNA expression of bFGF, ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). RESULTS: Addition of bFGF to culture medium induced bFGF gene expression in a dose- and time-dependent manner. Induction of bFCF mRNA started at a bFGF concentration of 0.1 ng/ml. The bFGF mRNA level was elevated by 2-fold at 1 ng/ml of bFGF, 2.8-fold at 5 ng/ml, and reached a peak of 4-fold at 10 ng/ml and 3.7-fold at 50 ng/ml. At 10 ng/ml of bFGF, induction of bFGF mRNA was observed as early as 2 hours (2-fold) after treatment. The bFGF mRNA level continued to increase to 3.7-fold by 4 hours, and reached a maximum of 4.4-fold by 8 hours. A slow decline of the bFGF mRNA level was observed after 8 hours of bFGF treatment (3.5-fold by 12 hours, and 3-fold by 24 hours). This induction of bFGF gene expression was blocked by PKC inhibitors H-7 (30 microM). The PKC activator PMA (0.1 microM) also upregulated bFGF gene expression, but the effects of bFGF and PMA were not additive. An adenylate cyclase inhibitor, SQ22536 (100 microM), did not inhibit bFGF-induced bFGF gene expression. Although forskolin (5 microM), an adenylate cyclase activator, also upregulated the level of bFGF mRNA, the effects of forskolin and bFGF were additive. In addition, no inhibitory effect on bFGF-induced expression of bFGF mRNA was found using H-89 (1 microM). Exogenous bFGF did not alter the mRNA levels of CNTF and BDNF. CONCLUSIONS: These results indicate that bFGF induces bFGF gene expression in cultured rat Müller cells through PKC activation. The authors' findings raise the possibility that Müller cells in vivo also respond to available bFGF (for example, that released from the endogenous reservoirs in the case of injury) or to exogenous bFGF by producing more bFGF, which could in turn promote photoreceptor survival.     

Errors in the diagnosis of benign prostatic hyperplasia

Monitor blood glucose level before, during and for up to 24 hours after exercise. Ensure refined carbohydrate snack is taken prior to exercise. Reduce insulin dosage if possible. Inject insulin away from any exercising muscle. Remember that glycogen stores are replenished in two phases: immediately after the exercise and two to three hours later. These are the key risk times for hypoglycaemia. If blood glucose control is poor (14 mmol/litre or higher) prior to exercise, the 'stress' effect of the exercise may cause further increases in the blood sugar level unless control is achieved.     

Collagen type XVI expression is modulated by basic fibroblast growth factor and transforming growth factor-beta

A new instrument for laparoscopic access consists of a trocarless, reusable, visual-access cannula with an external thread that ends in a blunt tip. The device has no sharp ends or moving parts. The cannula does not transect but radially stretches and elevates vessels, fascia, and muscle fibers, preserving the fascia's natural gridiron shutter mechanism at the access site. The outer thread stabilizes the cannula, and no fascial suture is necessary. In a prospective clinical trial between 1994 and 1997, the instrument was used in 203 patients requiring 234 access ports for diagnostic and operative laparoscopies. No device-related complications or failed attempts were recorded. The cannula caused less tissue trauma at access sites, and may decrease the frequency of hernias and postoperative access site pain.     

Bladder compliance in patients with benign prostatic hyperplasia

Factors influencing bladder compliance were examined in 116 patients with benign prostatic hyperplasia (BPH), by evaluating patients' histories, response of isolated bladder strips to acetylcholine, and the effect of prostatic urethral anesthesia. Patients' age, frequency of micturition, and duration of voiding difficulty were not correlated with bladder compliance. Bladder compliance was significantly low in patients within 30 days after urinary retention, as compared with bladder compliance in patients without an episode of retention. More than 30 days after retention, however, there was a tendency toward increased bladder compliance. Restricted to patients without an episode of retention, bladder compliance in the overactive detrusor group was found to be significantly lower than in the normal group. The responses to acetylcholine of bladder strips were compared between patients with low and normal-compliance bladders. The dose-response curve of patients with low-compliance bladders did not differ from that of those with normal compliance bladders, even when patients with an episode of retention were excluded. After prostatic urethral anesthesia, a significant increase of bladder compliance was observed in patients with an overactive detrusor, while the increase was not significant in patients with a normal detrusor. Our results strongly suggest that easy irritability of the anatomically altered prostatic urethra, as well as bladder over-distension caused by urinary retention, are important factors affecting bladder compliance in BPH patients.     

Ultrasonically determined patterns of enlargement in benign prostatic hyperplasia

A series of 430 men aged 40 to 79 years underwent transrectal ultrasonography (TRUS) as part of a community survey of benign prostatic hyperplasia (BPH). We describe a reproducible method of prostate volume estimation and discuss the implications of prostate dimension changes in BPH. The mean prostate and adenoma volumes for the group were 32 ml (SD 14) and 15 ml (SD 11) respectively. The antero-posterior dimension of the prostate (APD) had the strongest correlation with gland volume compared with the transverse dimension (TD) and length (L). The mean ratio of adenoma volume to prostate volume was 0.45 (SD 0.13) and this increased with increasing gland volume. There was a modest correlation between the ratio and prostate volume. BPH is characterised by a proportionally greater increase in the APD compared with L and TD and by an increasing adenoma/prostate ratio. TRUS is useful in assessing the type and extent of adenoma and prostate enlargement in BPH.     

Transurethral thermotherapy in the management of benign prostatic hyperplasia

To elucidate the intradialytic urea concentration gradients, we examined 26 hemodialysis patients wearing a double-lumen central venous catheter during their first or second fistula-punctured dialysis session. In 17 patients (group A), after 60 and 240 minutes of treatment with a mean blood flow of 196.4 +/- 9.9 mL/min, blood urea nitrogen (BUN) was measured in blood samples taken simultaneously from the central venous catheter, a vein in the arm opposite the access site, and the arterial and venous lines of the dialyzer. In 16 patients (group B), after 60 minutes of treatment with a mean blood flow rate of 197.5 +/- 12.3 mL/min, BUN was measured in blood samples taken from the dialyzer arterial line and then, after decreasing the blood flow to 50 to 60 mL/min for 1 minute, in samples taken from a vein in the arm opposite the access site, the central venous catheter, and the dialyzer arterial line. In group A, the mean BUN values in the dialyzer arterial line at 60 and 240 minutes were found to be 3.7% +/- 3.7% and 3.5% +/- 3.4% higher than the corresponding values in the central veins, respectively (P = NS between 60 and 240 minutes). In group B, after 1 minute of low blood flow, this difference was 1.5% +/- 2.4% (P = 0.06 compared with group A). The peripheral veins in group A patients at 60 and 240 minutes had 9.7% +/- 5.2% and 10.9% +/- 5.3% higher BUN values, respectively, compared with the central veins. This difference in group B patients after 1 minute of low blood flow was 6.8% +/- 4.2%. Urea access recirculation rate in group A, calculated by the classical three-samples method, was found to be 7.6% +/- 5.0% at 60 minutes and 9.9% +/- 5.8% at 240 minutes (P = NS). In group B, BUN values in the dialyzer arterial line after 1 minute of low blood flow increased significantly by 3.4% +/- 4.5% (P < 0.01). Our study shows that during conventional hemodialysis with a blood flow rate of 200 mL/min, urea concentration in the central veins is lower than in the dialyzer arterial line. This gradient after 1 minute of low-flow dialysis had a tendency to decrease. At the same time, however, the urea concentration gradient between the peripheral and central veins remained high, indicating that during conventional hemodialysis, intercompartmental disequilibrium plays a significant role in the arteriovenous gradient.     

Transurethral enzyme injection--future management of benign prostatic hyperplasia

Although benign prostatic hyperplasia, a common condition among elderly men, has been effectively treated with transurethral resection of the prostate, this surgical procedure is associated with many well-recognized risks and complications. Because of this potential morbidity and mortality, various alternative treatment strategies for benign prostatic hyperplasia have been proposed. The use of enzyme solubilization and ablation of prostatic tissue to alleviate urinary outlet obstruction has proved effective in dogs and warrants investigation in human trials. Transurethral enzyme injection of the prostate has the potential for being a treatment modality with minimal invasiveness, limited requirements for anesthesia, and minimal associated toxicity for the management of benign prostatic hyperplasia.     

Differential expression of fibronectin, tenascin-C and NCAMs in cultured hippocampal astrocytes activated by kainate, bacterial lipopolysaccharide or basic fibroblast growth factor

We have cloned a mouse cDNA encoding a Mothers-against-dpp (MAD)-related protein, MADR1. Madr1 is ubiquitously expressed in the mouse embryo, indicating a broad function in a variety of tissue during embryogenesis, potentially relaying signals of numerous BMPs. However, its expression in the testis is strictly germ cell-specific and developmentally regulated. Testicular Madr1 expression starts in some seminiferous tubules at 2 weeks of age. After mid-puberty, a stage-specific Madr1 expression is established. During the cycling of the seminiferous epithelium, Madr1 expression initiates in the pachytene spermatocytes of stage V seminiferous tubules, peaks at stage X, then decreases as pachytene spermatocytes differentiate into secondary spermatocytes and then round spermatids. In the testis of adult Bmp8b homozygous mutant males, the Madr1- expressing pachytene spermatocytes are the first cell population to show increased apoptosis. These data suggest that MADR1 serves as a downstream component of the BMP8 signaling pathway during the differentiation of meiotic male germ cells.     

Studies on the expression of fibroblast growth factors and fibroblast growth factor receptors in human prostate cancer

PURPOSE: We tried to clarify the role of fibroblast growth factors (FGFs) and those receptors (FGF-Rs) in cell proliferation of human prostate cancer. METHODS: The mRNA expression of FGF1, FGF2, FGF7, FGF-R1, FGF-R2 (IIIb), and FGF-R2 (IIIc) was investigated by RT-PCR in androgen sensitive cells (LNCaP), androgen-independent cells (PC3) and primary cultured stromal (PS) and epithelial cells (PE) from benign prostatic hyperplasia (BPH). Expression of the mRNA of FGF-R1, FGF-R2 (IIIb) and FGF-R2 (IIIc) in human prostate cancer tissue was similarly analyzed. Furthermore, the level of FGF-R1 expression in human prostate cancer was measured by semi-quantitative RT-PCR. RESULTS: FGF-R1 mRNA was detected in LNCaP, PC3 and the primary cultured stromal cells of BPH. FGF-R2 (IIIb) was seen in LNCaP cells and the primary cultured epithelial cells of BPH, while FGF-R2 (IIIc) was only observed in PC3. FGF1 mRNA was expressed in LNCaP and PC3, while FGF2 mRNA was in PC3 alone. The expression of FGF7 mRNA was detected only in the primary cultured stromal cells. Of 17 patients with human prostate cancer, FGF-R2 (IIIb) was detected in 2 and FGF-R2 (IIIc) in 15. Histological type of two cases having FGF-R2 (IIIb) were well differentiated adenocarcinoma. The mRNA levels of FGF-R1 in poorly and moderately differentiated types were significantly higher than those in well differentiated ones (p < 0.05). CONCLUSION: These findings suggest that several changes of expression in FGFs and FGF-Rs may correlate with malignant progression of human prostate cancer.     

Regulation of prostate growth by fibroblast growth factors

Growth of the prostate is controlled by androgen. However, there is information indicating that androgen may not act directly, but may act indirectly through polypeptide growth factors, to control prostate growth. This review will focus on the involvement of members of the fibroblast growth factor (FGF) family in this process. The properties of FGFs and FGF-receptors are described that implicate these molecules in growth control. Information is provided that prostate stromal cells synthesize FGF2 and FGF7. FGF2 is a potent mitogen for stromal cells; whereas, FGF7 is exclusively a mitogen for epithelial cells. Transforming growth factor beta (TGF beta), also produced by prostate cells, inhibit cell growth. This suggests that prostate growth is controlled by autocrine and paracrine mechanisms. Evidence is presented that altered FGF expression accompanies benign prostatic hyperplasia and prostate cancer. A model is proposed whereby androgen regulates TGF beta, influencing FGF2 and FGF7 expression, and in turn regulating growth of the prostatic stroma and epithelium. An imbalance in the influence of these growth factors may contribute to prostate disease.     

Disorders of kidney function in patients with benign prostatic hyperplasia

The examination of 648 males aged 50 to 86 to conduct an early outpatient detection of renal dysfunction in the elderly men employed an original technique of renal function assessment based on the kinetics of urinary 5-NOK elimination. Renal dysfunctions were revealed in 165 patients, in 159 of them the underlying cause was benign prostatic hyperplasia. The results were compared with those obtained at radionuclide tracing and Reberg-Tareev test. The correlation found indicated the authors' technique informative value and its compatibility with the above methods. Identification of renal dysfunction at early stages of benign prostatic hyperplasia allowed their timely hospitalization and operative treatment which enables the physicians to prevent progression of chronic renal failure in these patients.     

Economic public health aspects of benign prostatic hyperplasia in Austria

Benign prostatic hyperplasia (BPH) is one of the most frequent diseases in advanced aged men. The introduction of a new coding system (ICD-VESKA) in 1989 made it possible to analyze the number of hospitalized cases and to calculate the costs of inpatient care. In 1990 10,710 BPH cases were treated within Austrian hospitals. Controlling for multiple entries 9,742 individual patients (269.4 per 100,000) were treated 138,761 days. Case fatality was 0.5% (46 deaths). The number of inpatients comprises only the top 1,3% of morbidity, the total number is estimated with 770,000 patients. Based on the official nursing fees total costs in public affiliated hospitals were AS 250 millions. Including private hospitals total costs increase to AS 306 millions. The inpatient care of BPH represents only a small proportion of the total health and economic burden, which obviously mainly occurs in the outpatient system. Therefore BPH is one of the diseases of which social and economic importance is usually underestimated due to a lack of information.