Biomedical subjects

J C Wu

Publications and source records attributed to J C Wu.

At least 37 records · Page 2Linked to original sources

PubMed2001

Dysfunction of oesophageal motility in Helicobacter pylori-infected patients with reflux oesophagitis.

BACKGROUND: Helicobacter pylori infection has been suggested to be protective against gastro-oesophageal reflux disease. However, a significant proportion of patients with gastro-oesophageal reflux disease are infected by H. pylori. AIM: To study oesophageal motor function in H. pylori-infected patients with reflux oesophagitis. METHODS: Patients with erosive reflux oesophagitis were recruited prospectively for stationary oesophageal manometry and 24-h ambulatory oesophageal pH monitoring. H. pylori status was determined by biopsy urease test. Non-reflux volunteers were recruited as controls. RESULTS: Seventy-four patients with erosive oesophagitis (34 H. pylori-positive, 40 H. pylori-negative) and 48 non-reflux patient controls (22 H. pylori-positive, 26 H. pylori-negative) were recruited. There was no difference in severity of oesophagitis (median grade, 1; P=0.53) or oesophageal acid exposure (total percentage time oesophageal pH < 4, 7.6% vs. 6.8%; P=0.57) between H. pylori-positive and H. pylori-negative groups. Compared to H. pylori-negative patients, H. pylori-positive patients had significantly lower basal lower oesophageal sphincter pressure (12.2 mmHg vs. 15.3 mmHg; P=0.03) and amplitude of distal peristalsis (56.9 mmHg vs. 68.4 mmHg; P=0.03). Ineffective oesophageal motility (14% vs. 7%; P=0.02) and failed oesophageal peristalsis were also significantly more prevalent in H. pylori-positive patients. CONCLUSIONS: Among patients with a similar degree of reflux oesophagitis, H. pylori-infected patients have more severe oesophageal dysmotility and lower oesophageal sphincter dysfunction. Oesophageal motor dysfunction probably plays a dominant role in the development of gastro-oesophageal reflux disease in patients with H. pylori infection.

Adult↗

PubMed2001

Long-term evaluation of recombinant interferon alpha2b in the treatment of patients with hepatitis B e antigen-negative chronic hepatitis B in Taiwan.

The effect of interferon (IFN) on hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) has not been fully investigated in Chinese patients. We enrolled 58 HBeAg-negative CHB Chinese patients with hepatitis B viremia in Taiwan to evaluate the response to IFN. 30 patients received recombinant IFN 5 million units 3 times weekly for 6-10 months, and 28 patients who refused IFN treatment served as controls. Rates of virological response and biochemical response were higher in the treated group at the end of treatment (57% vs 18%, P = 0.006, and 73% vs 29%, P = 0.002, respectively). Both effects were superior in the treated group at 6 months after IFN withdrawal (virological: 30% vs 7%, P = 0.06; biochemical: 47% vs 7%, P = 0.002). Improvement of liver histological activities with persistently biochemical response was found in 65% of the treated patients. After a mean of 32 months' follow-up, virological response was rarely maintained (17% vs 4%, P = 0.228) but biochemical response was better in the treated group (27% vs 4%, P = 0.039). None of the treated patients but five controls developed severe complications of CHB during the follow-up period. A larger total IFN dosage or a younger age (< or = 40 years) were associated with 'sustained' virological response. Younger age and higher baseline alanine transaminase values (> or = 120 Ul(-1)) were related to 'sustained' biochemical response.

Adult↗

PubMed2001

Ranitidine-related Stevens-Johnson syndrome in patients with severe liver diseases: a report of two cases.

Ranitidine is widely used and well tolerated. Ranitidine-related skin eruption is rare and usually mild. We presented two patients who developed Stevens-Johnson syndrome after ranitidine therapy. Before therapy, both patients had severe liver disease and jaundice. The first was a case of ketoconazole-induced hepatitis, and the second was a case of hepatitis C-related liver cirrhosis with hepatocellular carcinoma. Ranitidine was the most likely drug responsible for causing Stevens-Johnson syndrome in these two patients.

Antifungal Agents↗

PubMed2001

Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation.

BACKGROUND AND AIMS: Hepatic steatosis is a histological characteristic in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to evaluate the prevalence of hepatic steatosis in Chinese patients with chronic hepatitis C, and to look for possible correlation with various histopathological changes and to look for possible correlation with various clinical and pathologic variables. METHODS: One hundred and six patients were enrolled, and patients with alcoholism or diabetes mellitus were excluded. Clinical, biochemical and virologic data, including HCV genotype and serum HCV-RNA titer and histological findings, were compared between patients with and without hepatic steatosis. RESULTS: Fifty-five (52%) of the 106 patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis had significantly higher mean serum levels of triglyceride and gamma-glutamyl transpeptidase, higher body mass index, and a higher incidence of obesity compared with patients without hepatic steatosis. No significant differences in serum HCV-RNA titer and HCV genotype or the response to interferon therapy were noted between the two groups. Histological analysis showed patients with hepatic steatosis had a significantly higher mean fibrotic score than patients without hepatic steatosis (1.9 +/- 1.2 vs 1.3 +/- 1.0; P = 0.016). There were no significant differences in the severity of necroinflammation, the presence of lymphoid aggregation/follicle or bile duct damage between the two groups. Multivariate logistic regression analysis showed that independent predictors associated with hepatic steatosis were obesity or a histology fibrotic score of > or = 2. CONCLUSION: It was found that 52% of Chinese patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis were more frequently obese and had more severe hepatic fibrosis.

Adult↗

PubMed2001

Comparison of clinical, virologic and pathologic features in patients with acute hepatitis B and C.

BACKGROUND AND AIMS: The clinical outcomes of adult-acquired acute infection of hepatitis C virus (HCV) and hepatitis B virus (HBV) are quite different. In order to compare the clinical, biochemical, virologic and pathologic pictures in these two groups of patients, we enrolled 22 adult patients with acute hepatitis C and 16 adult patients with acute hepatitis B, on whom liver biopsies were performed within 3 months of acute onset of the illness. RESULTS: The results showed that a significantly younger age, a higher ratio of the clinical symptoms of jaundice, nausea, vomiting, and poor appetite, a higher mean serum level of alanine transaminase, aspartate transaminase, and total bilirubin were present in patients with acute hepatitis B patients than in those with acute hepatitis C (P < 0.05). There was a significantly higher degree of periportal inflammation and total necro-inflammatory activity in the acute hepatitis B patients (P = 0.002 and 0.049, respectively). Fifteen (68.2%) of the 22 patients with acute hepatitis C had detectable serum HCV-RNA, but only two (14.3%) of the 14 tested patients with acute hepatitis B had detectable serum HBV-DNA, detected by using the branched DNA signal amplification assay. Eighteen (82%) of the 22 acute hepatitis C patients and none of the 16 acute hepatitis B patients progressed into a chronic hepatitis stage (P < 0.001). CONCLUSION: The manifestations of mild clinical symptoms, lower mean serum transaminases and bilirubin levels, a lesser degree of histological periportal necroinflammation, and more patients with a high circulatory viral load among the acute hepatitis C patients, may lead to more of that group developing chronicity than patients with acute hepatitis B.

Acute Disease↗

PubMed2001

Seasonal variability of the QT dispersion in healthy subjects.

We studied the seasonal variability of QT dispersion in 25 healthy subjects, aged 36 +/- 5 (25 to 46) years. Four seasonal 12-lead rest electrocardiograms (ECGs) recorded at a double amplitude were performed at 25 mm/s at intervals of roughly 3 months. To avoid possible confusion from the circadian rhythm of QT dispersion, subsequent ECGs were recorded within 30 minutes of the reference summer one. The QT dispersion was calculated as the difference between the longest and the shortest mean QT intervals. There was a seasonal variability in the QT dispersion (P =.001), with the largest QT dispersion occurring in winter (66 +/- 21 ms) and the smallest one in spring (48 +/- 18 ms). In conclusion, there exists a seasonal variability of QT dispersion in healthy subjects and such variability should be taken into consideration in comparison of the QT dispersion.

Adult↗

PubMed2001

Is non-Helicobacter pylori, non-NSAID peptic ulcer a common cause of upper GI bleeding? A prospective study of 977 patients.

BACKGROUND: Non-Helicobacter pylori, non-NSAID ulcer is relatively common in Western countries. Whether it is a significant problem in the Orient is unclear. The aim of this study was to investigate the incidence of non-H pylori, non-NSAID ulcers presenting with GI bleeding. METHODS: A prospective study was done of 1675 consecutive patients presenting with upper GI bleeding over a period of 12 months. Upper endoscopy was performed with biopsy specimens taken from the antrum and body of the stomach for a biopsy urease test (BUT) and histology for detection of H pylori. Exposure to nonsteroidal anti-inflammatory drugs (NSAID) or aspirin within 4 weeks of hospitalization was carefully scrutinized. A 6-week course of treatment with an H2-receptor antagonist was prescribed for patients who did not use an NSAID and had a negative BUT result. Follow-up endoscopy was performed to confirm H pylori status with a BUT and histology. Positive histology at either initial or follow-up endoscopy was used as the standard for diagnosing H pylori infection. RESULTS: Among 977 patients who were found to have ulcer bleeding, 434 (44%) had exposure to aspirin or an NSAID. Of the 543 non-NSAID users, 431 (79.4%) had a positive BUT and 112 (20.6%) were BUT negative on initial endoscopy. Eighty-nine of 112 patients who were NSAID negative, BUT negative returned for follow-up endoscopy. Forty-nine of 89 (55.1%) were found to have a positive BUT and positive histology at follow-up endoscopy. Only 40 of 977 (4.1%) patients admitted with ulcer bleeding were confirmed to have non-H pylori, non-NSAID ulcers. CONCLUSIONS: Non-H pylori, non-NSAID bleeding ulcer is uncommon. A negative BUT is unreliable for exclusion of H pylori infection during the acute phase of ulcer bleeding.

Adolescent↗

PubMed2001

Incidence of gastroesophageal malignancy in patients with dyspepsia in Hong Kong: implications for screening strategies.

BACKGROUND: A "test-and-treat" strategy for H pylori infection has been recommended in Europe and North America as safe and cost-effective for management of patients with dyspepsia. The primary aim of this study was to determine the frequency of gastroesophageal cancer in 2 groups of patients with dyspepsia: those 45 years of age or younger without "alarm" symptoms (low-risk group) and patients over 45 years of age or any patient with "alarm" symptoms (high-risk group). A secondary aim was to determine the frequency of gastric cancer among patients in the low-risk group with or without a positive serology for H pylori. METHODS: Patients with persistent dyspepsia were recruited from 4 regional hospitals in Hong Kong. Those in the low-risk group were evaluated for H pylori by using a whole blood serology test; they underwent endoscopy within 1 week. Those in the high-risk group and those taking nonsteroidal anti-inflammatory drugs (NSAIDs) underwent endoscopy promptly. Alarm symptoms were as follows: weight loss (10 or more pounds over 8 weeks), recurrent vomiting, dysphagia, bleeding, or anemia. RESULTS: Of 2627 patients enrolled, 1017 were in the low-risk group and 1610 in the high-risk group. Twenty-three patients (0.9%) had gastroesophageal cancers (20 gastric, 3 esophageal). Four patients with cancer (17.4%) were in the low-risk group (3 gastric, 1 esophageal); all except the patient with esophageal cancer had a positive serology test. In the high-risk group, 19 patients had cancer (17 gastric, 2 esophageal). CONCLUSION: Gastric cancer is relatively frequent among young patients with dyspepsia who have no alarm features in Hong Kong. This finding raises concerns as to the safety of the "test-and-treat" strategy for the management of patients with dyspepsia in Asia.

Adult↗

PubMed2001

The spatial distribution of macular pigment in humans.

PURPOSE: To estimate the distributions in width as well as in density of macular pigment (MP) in humans at different ages, imaging fundus reflectometry was employed as a tool to reach our aim. METHODS: Imaging fundus reflectometry was used to measure the macular pigment distribution in human eyes with a modified fundus camera to which a cooled CCD camera was attached. The fundus images were taken at 460 nm and 560 nm after the retina was light-adapted to completely bleach rhodopsin. The density of macular pigment was estimated using a model described in the text. The variation in density with retinal eccentricity was fit to Gaussian distribution. The width of MP in retinal eccentricity was estimated by 95% covering area of the distribution profile. A total of 54 normal people served as subjects. They were divided into three groups with ages of 24.8 +/- 2.6 years (N = 24), 40.2 +/- 8.3 years (N = 13) and 67.5 +/- 7.1 years (N = 17) respectively. Statistical t-tests were employed to evaluate the differences in MP density, the half width of MP distributed (HWMPD) in retina with respect to age between the groups. Linear regression was also applied to reveal the relationships of HWMPD distribution with respect to age. RESULTS: The results indicate that the average MP densities are 0.23 +/- 0.08, 0.22 +/- 0.06 and 0.23 +/- 0.06 density unit (DU) for the young to old age groups. The average MP density is 0.23 +/- 0.07. No statistical significant difference is found in the peak MP density between the groups (all p > 0.05). This result pretty agrees with the data that obtained from others by using optical methods. For the young to old age groups, the average estimated HWMPD are 2.6 degrees +/- 0.5 degrees, 3.1 degrees +/- 0.5 degrees and 4.1 degrees +/- 0.6 degrees respectively. The differences between loci of HWMPD in the three groups are statistically significant with p = 0.0059, p < 0.0001 and p = 0.0001 for young vs. mid-age, young vs. old and mid-age vs. old respectively. Linear regressions for the HWMPD vs. age (r = 0.734, p < 0.001) implies that the macular pigment can gradually accumulate and spread out to the periphery of retina through our life span with an increase rate of approximately 0.03 degrees /year. CONCLUSIONS: The accumulation of MP is reflected by the broader area in the macula lutea due to age, but no significant change is observed in peak density. The cause of the extension in the macular area with respect to age is unknown.

Adult↗

PubMed2001

The massively parallel genetic algorithm for RNA folding: MIMD implementation and population variation.

A massively parallel Genetic Algorithm (GA) has been applied to RNA sequence folding on three different computer architectures. The GA, an evolution-like algorithm that is applied to a large population of RNA structures based on a pool of helical stems derived from an RNA sequence, evolves this population in parallel. The algorithm was originally designed and developed for a 16384 processor SIMD (Single Instruction Multiple Data) MasPar MP-2. More recently it has been adapted to a 64 processor MIMD (Multiple Instruction Multiple Data) SGI ORIGIN 2000, and a 512 processor MIMD CRAY T3E. The MIMD version of the algorithm raises issues concerning RNA structure data-layout and processor communication. In addition, the effects of population variation on the predicted results are discussed. Also presented are the scaling properties of the algorithm from the perspective of the number of physical processors utilized and the number of virtual processors (RNA structures) operated upon.

Algorithms↗

PubMed2001

Trauma inhibits erythroid burst-forming unit and granulocyte-monocyte colony-forming unit growth through the production of TGF-beta1 by bone marrow stroma.

OBJECTIVE: To examine the effect of trauma plasma on clonogenic progenitor cultures. SUMMARY BACKGROUND DATA: Severely injured trauma patients often experience altered hematopoietic functions, manifested by an increased susceptibility to infection and the development of a persistent anemia. Experimental and clinical data suggest that trauma results in the release of cytokines into the plasma that have hematopoietic regulatory function, but few studies have examined human bone marrow. METHODS: Plasma was obtained from 42 severely injured patients admitted to the surgical intensive care unit from days 1 to 15 after injury. Bone marrow and normal plasma were obtained from volunteers. Bone marrow mononuclear cells were isolated and plated for granulocyte-monocyte colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth. Parallel cultures were incubated with 2% (v/v) trauma or normal plasma. Additional cultures were plated with neutralizing concentrations of antibodies to transforming growth factor (TGF)-beta1 and MIP-1alpha. Circulating plasma TGF-beta1 was determined by bioassay. mRNA from bone marrow stromal cultures was extracted and probed for TGF-beta1 and macrophage inflammatory protein (MIP)-1alpha. RESULTS: Trauma plasma suppressed CFU-GM and BFU-E colony growth by 40% to 60% at all time periods after injury compared with cultures incubated with normal plasma. Using a noncontact culture system, the authors showed that this inhibition of BFU-E and CFU-GM colony growth was mediated by bone marrow stroma. The inhibition appeared to be due to soluble plasma-induced bone marrow stromal products that did not require direct cell-cell contact. The addition of anti-TGF-beta1 antibodies reversed the suppressive effect of trauma plasma on CFU-GM and BFU-E colony growth during the early but not late time points after injury. Trauma but not normal plasma induced TGF-beta1 mRNA in bone marrow stroma. CONCLUSIONS: Trauma plasma inhibits bone marrow BFU-E and CFU-GM colony growth for up to 2 weeks after injury. This inhibition is mediated through the interaction of trauma plasma with bone marrow stroma. TGF-beta1 production by bone marrow stroma appears to plays an important role in the early but not late bone marrow suppression after injury.

Adolescent↗

PubMed2001

Quantitative PET findings in patients with posttraumatic anosmia.

OBJECTIVE: To investigate quantitative positron emission tomography (PET) findings, particularly from orbitofrontal cortex, in patients with posttraumatic anosmia. SETTING: Neuropsychology outpatient clinic and university brain imaging center. SUBJECTS: Eleven patients with head injury resulting in severe anosmia and 11 controls matched for age. All 11 head-injured patients had their head injuries at least 2 years before involvement in the study. MEASURES: Regional cerebral glucose metabolism was measured with PET. RESULTS: Quantitative evaluation of PET findings for anosmic patients as a group showed orbitofrontal hypometabolism compared with controls. Decreased activity was also noted in mesial temporal lobe. Activity in subcortical white matter was essentially identical between groups. CONCLUSIONS: Findings strongly suggest that posttraumatic anosmia is closely associated with hypometabolism in the orbitofrontal cortex and the medial prefrontal cortex. The results also underscore the importance of posttraumatic anosmia as a clinical sign of orbitofrontal damage, as has been shown previously with neuroSPECT (single photon emission computed tomography).

Adult↗

PubMed2001

Clinical, virologic, and pathologic significance of elevated serum alpha-fetoprotein levels in patients with chronic hepatitis C.

Elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C is not uncommonly seen, but the pathogenesis of this phenomenon remains unclear. The aims of this study were to assess the prevalence of elevated serum AFP in patients with chronic hepatitis C and to evaluate the clinical, virologic, and histopathologic significance of this phenomenon. One hundred and fifteen Chinese patients with a histologic diagnosis of chronic hepatitis C were enrolled. None had evidence of hepatocellular carcinoma by image study at enrollment and for at least 2 years' follow-up. Of the 115 patients, 33 (29%) had elevated serum AFP (more than 12 ng/mL). There was a significantly lower mean serum albumin (4.0 +/- 0.1 vs. 4.3 +/- 0.1 gm/dL, p <0.001) and higher mean scores for periportal necroinflammation (3.3 +/- 0.3 vs. 2.3 +/- 0.2, p = 0.007) and fibrosis (2.3 +/- 0.2 vs. 1.1 +/- 0.1, p < 0.001) in patients with elevated serum AFP when compared with patients without elevated serum AFP. Patients with elevated serum AFP had significantly more incidences of genotype 1b infection when compared with patients without elevated serum AFP (77% vs. 51%, p = 0.021). Mean serum hepatitis C virus (HCV) RNA titer showed no significant difference between the two groups. Multivariate logistic regression analysis showed that as serum albumin of less than 4.2 gm/dL, a histology fibrotic score of more than 3, and HCV genotype 1b infection were significantly independent predictors associated with elevated serum AFP. In conclusion, elevated serum AFP levels were significantly correlated with lower serum albumin levels, advanced fibrosis/cirrhosis, and genotype 1b infection in patients with chronic hepatitis C.

Hepatitis C, Chronic↗

PubMed2001

Deep subcortical (including limbic) hypermetabolism in patients with chemical intolerance: human PET studies.

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Adult↗

PubMed2001

A novel role for bone morphogenetic proteins in the synthesis of follicle-stimulating hormone.

FSH is produced in pituitary gonadotropes as an alpha/beta heterodimer, and synthesis of the beta-subunit is the rate-limiting step in overall FSH production. Synthesis of FSHbeta can be regulated by activin and inhibin, both of which are members of the transforming growth factor-beta superfamily. Bone morphogenetic proteins (BMPs) also belong to the transforming growth factor-beta family and are multifunctional growth factors involved in many aspects of tissue development and morphogenesis, including regulation of FSH action in the ovary. Here we report a novel function for BMP-7 and BMP-6 in regulating FSH synthesis in the pituitary. Using primary pituitary cell cultures derived from transgenic mice that carry the ovine FSHbeta promoter linked to a luciferase reporter gene (oFSHbetaLuc), BMP-7 or BMP-6 was found to stimulate oFSHbetaLuc expression by 6-fold. Transient expression of the oFSHbetaLuc in a transformed gonadotrope cell line, LbetaT2, was induced 4-fold by BMP-7 or BMP-6 treatment. More importantly, BMP-7 and BMP-6 increased endogenous FSH secretion by 10- and 14-fold, respectively, from LbetaT2 cells, demonstrating for the first time that a functional signaling BMP system is present in gonadotropes. Two bioneutralizing antibodies to BMP-7, which cross-react with BMP-6, but not with activin A, decreased basal oFSHbetaLuc expression and FSH secretion from transgenic mouse pituitary cultures by 83-88% and 47-48%, respectively, suggesting an autocrine or paracrine role for BMP-7 or BMP-6 in FSH synthesis. Neither bioneutralizing antibody to activin A or activin B decreased basal oFSHbetaLuc expression or mouse FSH secretion significantly. Dose-dependent inhibition of FSH synthesis by anti-BMP7 was also observed in rat and sheep pituitary cultures. These results combined with the fact that the messenger RNAs for BMP-7 and BMP-6 were detected in mouse pituitaries and LbetaT2 cells indicate that BMP-7 and/or BMP-6 can function as FSH stimulators and may be significant physiological factors maintaining basal FSH expression in vivo.

Animals↗

PubMed2001

The promoter for the ovine follicle-stimulating hormone-beta gene (FSHbeta) confers FSHbeta-like expression on luciferase in transgenic mice: regulatory studies in vivo and in vitro.

Transgenic mice harboring the ovine FSHbeta (oFSHbeta) promoter plus first intron (from -4741 to +759 bp) linked to a luciferase reporter gene (oFSHbetaLuc) were generated to determine whether this promoter can direct tissue-specific expression in vivo and serve as a model for studying hormonal regulation of the FSHbeta gene. Of six lines of transgenic mice analyzed, luciferase was detected uniquely in the pituitaries of five of them. Pituitary luciferase activity was decreased 51-99% by chronic GnRH treatment (Lupron depot). Orchidectomy caused a 2- to 8-fold increase, and ovariectomy caused a 2- to 27-fold increase in pituitary luciferase activity. Furthermore, pituitary luciferase expression was consistently higher on estrus than on diestrus (3- to 20-fold). These data strongly suggested that the transgene was expressed specifically in pituitary gonadotropes and regulated in the same way as the endogenous mouse FSHbeta gene. Using primary pituitary cell cultures prepared from these transgenic mice, basal luciferase expression was maximal on day 3 and then decreased by day 6 of culture, a pattern reflected by endogenous mouse FSH secretion. In these pituitary cultures, basal oFSHbetaLuc expression was decreased 61-82% by follistatin or 59-79% by inhibin. Similarly, mouse FSH secretion was decreased 71% by follistatin or 65% by inhibin. Progesterone inhibited oFSHbetaLuc expression by 44-51%, but it had no effect on endogenous mouse FSH secretion. Estradiol lowered FSH secretion by 21%, but did not decrease oFSHbetaLuc expression significantly. In conclusion, these data demonstrated the ability of the oFSHbeta promoter to direct expression of a reporter gene specifically to pituitary gonadotropes in transgenic mice. Studying oFSHbetaLuc expression in vivo and in cell cultures derived from pituitaries of these transgenic mice should prove useful for understanding many features of FSHbeta regulation.

Animals↗

PubMed2001

Transcriptional regulation of the ovine follicle-stimulating hormone-beta gene by activin and gonadotropin-releasing hormone (GnRH): involvement of two proximal activator protein-1 sites for GnRH stimulation.

Previous studies from our laboratory demonstrated that a transgene consisting of the promoter for the ovine FSH beta-subunit gene and a luciferase reporter (wt-oFSHbetaLuc) was expressed and regulated like the FSHbeta gene in vivo and in vitro. In the present study pituitary cultures were prepared from these transgenic mice as well as mice carrying mutated oFSHbetaLuc lacking two functional activator protein-1 (AP-1) sites at -120 and -83 bp (mut-oFSHbetaLuc). These AP-1 sites were reported necessary for induction of oFSHbetaLuc by GnRH in a HeLa cell system. To examine the importance of the two AP-1 sites in mediating GnRH and activin effects in primary gonadotropes, pituitary cultures derived from transgenic mice were pretreated with follistatin to remove activin or activin-like factors present in the cultures. Follistatin lowered luciferase expression in cultures carrying both wt-oFSHbetaLuc and mut-oFSHbetaLuc transgenes by 74-86%, and subsequent addition of activin induced luciferase expression of both wt- and mut-transgenes by 4- to 14-fold within 4 h, suggesting that these AP-1 sites are not involved in activin stimulation of FSHbeta gene transcription. When GnRH was added along with activin, the wt-oFSHbetaLuc transgene was induced 200% compared with activin alone, but this effect was not observed with the mut-oFSHbetaLuc transgene. These data confirmed the HeLa cell studies showing that GnRH signals through two AP-1 sites to increase oFSHbeta transcription in gonadotropes. However, as the mutation of both AP-1 sites had no apparent effect on the expression and regulation of the transgene in vivo (basal, castration, GnRH down-regulation, cycle stage, and GnRH immunoneutralization), it appears that these AP-1 sites have little influence over the major effect of GnRH observed in vivo. These data also showed that activin plays a major role in transcriptional regulation of the FSHbeta gene, and the oFSHbeta promoter contains the activin response element(s) that is as yet undefined.

Activins↗

PubMed2001

An unusual cutaneous metastasis from hepatocellular carcinoma.

Cutaneous metastases from hepatocellular carcinoma are rare. In this report we detail a case of hepatocellular carcinoma with the unusual manifestations of multiple skin metastases. A 49-year-old male, who had received surgical resection of hepatocellular carcinoma one year prior, presented with multiple reddish-blue, firm, painless and nonulcerative cutaneous papules and nodules over the fingers, palms, toes, soles and back. Pathology of the cutaneous nodules showed characteristic hepatocellular carcinoma with trabecular gland formation. These lesions grew very rapidly and developed to cauliflower appearances which had not been described previously in the literature. The patient died of respiratory failure secondary to lung metastasis two months after the first appearance of the skin lesions.

Carcinoma, Hepatocellular↗