Characterization and distribution of basic fibroblast growth factor-containing cells in the rat hippocampus

Basic fibroblast growth factor (bFGF), a member of the heparin-binding growth factor family, is present in relatively high levels in the brain where it may play an important role in the maintenance, repair, and reorganization of the tissue. Although bFGF is associated mainly with astrocytes throughout most of the central nervous system (CNS), a narrow but prominent band of pyramidal neurons, which coincides with the CA2 subregion of Ammon's horn in the hippocampus, stains intensely for bFGF. In order to gain an understanding of which cells express bFGF and whether or not BFGF is a good marker for CA2 neurons, we have used a mouse monoclonal antibody directed against recombinant human bFGF to characterize the distribution and localization of bFGF expression in the hippocampus. We find that about one-quarter of the neurons in CA2 are bFGF positive, and they appear smaller and have more irregular-shaped nuclei than their unstained counterparts. In addition, all glial fibrilary acidic protein (GFAP)-positive astrocytes in the hippocampus stain for bFGF, and the distribution of these astrocytes is heterogeneous in the hippocampus. Finally, in both astrocytes and CA2 pyramidal neurons, bFGF immunoreactivity is localized primarily in the nucleus and to a lesser extent in the cytoplasm and processes of stained cells.     

Serotonin reuptake inhibitor withdrawal

We studied reported withdrawal symptoms in a retrospective chart review of 352 patients treated in an outpatient clinic with the nonselective serotonin reuptake inhibitor clomipramine or with one of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine, paroxetine, or sertraline. In 171 patients who were supervised during medication tapering and discontinuation, the most common symptoms were dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood. When patients with at least one qualitatively new symptom were defined as cases, these symptoms occurred significantly more frequently in patients who had been treated either with one of the shorter half-life SSRIs, fluvoxamine or paroxetine (17.2%), or with clomipramine (30.8%), than in patients taking one of the SSRIs with longer half-life metabolites, sertraline or fluoxetine (1.5%). The rate was not significantly different between the different shorter half-life treatments. Cases treated with fluvoxamine or paroxetine had received a significantly longer period of treatment (median 28 weeks) than noncases (16 weeks), but there were no significant associations with age or with diagnostic grouping. There was a trend toward an association with male sex. The majority of cases occurred despite slowly tapered withdrawal. Symptoms persisted for up to 21 days (mean = 11.8 days) after onset. These symptoms were relieved within 24 hours by restarting the medication, but were not relieved by benzodiazepines or by moclobemide. A role has been suggested for serotonin in coordinating sensory and autonomic function with motor activity. We suggest that this may lead to useful hypotheses about the pathophysiology of withdrawal symptoms from serotonin reuptake inhibitors.     

Establishment of a hereditary nonpolyposis colorectal cancer registry

INTRODUCTION: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition characterized by early age of onset colorectal cancer, right-sided predominance, excess of synchronous and metachronous colonic neoplasms, and extracolonic cancers. The purpose of this study is to report clinical characteristics of HNPCC families in our registry. METHODS: This is a retrospective review of medical records of patients with a significant history of colorectal cancer and interviews with their families. RESULTS: Three hundred one people with cancer in 40 HNPCC families were identified. In 284 of 301 (94 percent) people, 363 cancers were identified. Colorectal cancer only was identified in 182 people (64 percent) and, in conjunction with extracolonic tumors, in another 31 people (11 percent). Extracolonic cancer alone was noted in 71 people (25 percent). Median age at diagnosis of colorectal cancer was 48 (range, 17-92) years. In patients with documented pathology, right-sided tumors predominated (55 percent), synchronous and metachronous tumors were noted in 53 percent, and synchronous of metachronous adenomas were documented in 51 percent of people. Generational anticipation was also noted. CONCLUSION: This study demonstrates and confirms characteristics that have been described in HNPCC. Namely, early age of onset of colorectal cancer, right-sided predominance, multiple synchronous and metachronous neoplasms, increased extracolonic cancers, and generational anticipation.     

Gaucher disease: recommendations on diagnosis, evaluation, and monitoring

BACKGROUND: Timely diagnosis and continued monitoring of patients with type I Gaucher disease is critical because skeletal involvement can permanently disable patients and visceral organ involvement can lead to abdominal pain and secondary hematologic and biochemical complications. OBJECTIVE: To seek clinical consensus for minimum recommendations for effective diagnosis and monitoring of patients with type I Gaucher disease. PARTICIPANTS, EVIDENCE, AND CONSENSUS PROCESS: Contributing authors collaborated in quarterly meetings over a 2-year period to synthesize recommendations from peer-reviewed publications and their own medical experiences. These physicians care for most patients with Gaucher disease in the United States and serve as the US Regional Coordinators for the International Collaborative Gaucher Group Registry, the world's largest database for this disorder. CONCLUSIONS: The definitive method of diagnosis is enzyme assay of beta-glucocerebrosidase activity. Schedules differ for monitoring complications of type I Gaucher disease, depending on symptoms and whether enzyme replacement therapy is used. Hematologic and biochemical involvement should be assessed by complete blood cell count, including platelets, acid phosphatase, and liver enzymes, at baseline and every 12 months in untreated patients and every 3 months and at enzyme replacement therapy changes in treated patients. Visceral involvement should be assessed at diagnosis using magnetic resonance imaging or computed tomographic scans. Skeletal involvement should be assessed at diagnosis using T1- and T2-weighted magnetic resonance imaging of the entire femora and plain radiography of the femora, spine, and symptomatic sites. Follow-up skeletal and visceral assessments are recommended every 12 to 24 months in untreated patients, and every 12 months and at enzyme replacement therapy changes in treated patients.     

Persistent membrane translocation of protein kinase C alpha during 12-0-tetradecanoylphorbol-13-acetate-induced apoptosis of LNCaP human prostate cancer cells

Others have reported that the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA), an activator and down-regulator of most protein kinase C (PKC) isozymes, can induce apoptotic cell death of androgen-sensitive LNCaP but not androgen-insensitive PC-3 or DU 145 human prostate cancer cells. As a first step toward uncovering the mechanism by which TPA induces apoptosis of LNCaP cells, we quantified expression of PKC isozyme mRNAs in unmodified and TPA-resistant LNCaP cells and in naturally TPA-resistant PC-3, PC-3M, and DU 145 cells. All of the cell lines and normal prostate expressed RNAs for PKC alpha, delta, epsilon, eta, and mu; only DU 145 cells and normal prostate expressed PKC beta and theta RNAs, and none expressed PKC gamma. The amount of PKC alpha RNA and protein was 6- to 38-fold lower, and PKC mu RNA was 4.5- to 16.5-fold higher in unmodified and TPA-resistant LNCaP cells than in the androgen-independent cells. We examined the effects of TPA on PKC alpha and mu mRNA levels and on membrane translocation of PKC alpha. Incubation with TPA for 6 h or more induced 95% inhibition of cell growth, a transient 12-fold increase and 5-fold decrease in PKC alpha and mu mRNA levels, respectively, and prolonged translocation of PKC alpha to non-nuclear membranes in unmodified LNCaP cells and in TPA-resistant LNCaP cells from which TPA had been removed for 10 days. TPA-resistant LNCaP cells in the continuous presence of TPA, or 24 h after removal of TPA, had down-regulated PKC alpha and remained resistant to re-addition of TPA. These data demonstrate a strong correlation of the presence and absence of membrane PKC alpha with apoptosis and resistance to apoptosis, respectively.     

Efficiency of lysine or threonine retention in growing rats fed diets limiting in either lysine or threonine

Over a 21-d experiment, the efficiency of lysine and threonine retention was determined in 80 male Sprague-Dawley rats (65.9 +/- 0.3 g, means +/- SE) fed purified diets containing an amino acid mix limiting in either lysine or threonine. With additional increments of the first limiting amino acid, lysine concentration in total body protein (g/16 g N) increased (P < 0.01) in rats fed lysine-limiting diets but, when fed threonine-limiting diets, lysine concentration in body protein first increased and then decreased (P < 0.01). As increments of the first limiting amino acid were added, the threonine concentration in total body protein increased then decreased when both lysine- (P < 0.01) and threonine- (P < 0.06) limiting diets were fed. Lysine and threonine retention were calculated based on comparative slaughter. Sixteen rats were killed on d 0 to estimate the grams of amino acid in the body. Retention responses were analyzed using a logistic equation in which lysine or threonine intake was used to predict retention. The maximum marginal efficiency (dr/dI, retention/intake) was observed at <40% of maximum retention. For lysine retention, it was 81% when lysine was limiting and 70% when threonine was limiting. For threonine retention, it was 58% when threonine was limiting and 49% when lysine was limiting. The maximum cumulative efficiency (retention adjusted for maintenance relative to cumulative intake) for lysine retention was 62% when lysine was limiting or 58% when threonine was limiting. For threonine retention, it was 51% when threonine was limiting and 35% when lysine was limiting. Thus, amino acid concentration in body protein is not constant, and amino acids are used with higher efficiency when first limiting.