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B Berman

Publications and source records attributed to B Berman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Chimeric molecules between keratinocyte growth factor and basic fibroblast growth factor define domains that confer receptor binding specificities.

Basic fibroblast growth factor (FGF) and keratinocyte growth factor (KGF) are structurally related fibroblast growth factors, yet they exhibit distinct receptor binding specificity. Basic FGF binds with high affinity to FGFR1, FGFR2, and FGFR4, whereas KGF does not interact with these receptors and can only bind an isoform of FGFR2 known as the KGFR. Basic GFG binds KGFR but with lower affinity than KGF. In order to identify domains that confer this specificity, four reciprocal chimeras were generated between the two growth factors and were analyzed for receptor recognition and biological activity. The chimeras are designated BK1 (bFGF1-54:KGF91-194), BK2 (bFGF1-74:KGF111-194), KB1 (KGF31-90:bFGF55-155), and KB2 (KGF31-110:bFGF75-155). The two BK chimera similarly interacted with FGFR1 and FGFR4 but differed from each other with respect to KGFR recognition. BK1 displayed a slightly better affinity for KGFR than BK2 and induced a higher level of DNA synthesis in keratinocytes compared with bFGF and BK2. A neutralizing monoclonal antibody directed against bFGF specifically neutralized the biological activity of the BK chimeras. The reciprocal chimeras, KB1 and KB2, exhibited KGF-like receptor binding and activation properties. However, KB2 displayed higher affinity for KGFR and was significantly more potent mitogen that KB1. Altogether, our results suggest that the amino-terminal part of KGF and bFGF plays an important role in determining their receptor binding specificity. In addition, the results point to the contribution of a segment from the middle part of KGF (residues 91-110) for recognition and activation of the KGFR, as the two chimeras containing these residues (BK1 and KB2) displayed an enhanced interaction with the KGFR.

3T3 Cells↗
PubMed1995

Fibroblast growth factor receptors display both common and distinct signaling pathways.

We compared the mitogenic and signaling pathways of three Fibroblast Growth Factor Receptors (FGFRs), FGFR1, KGFR and FGFR4 in the same cell line. Each receptor was expressed in L6E9 rat myoblasts that do not normally express detectable levels of FGFRs and clones that express comparable levels of each receptor were selected. Our results show that FGFs induce an effective survival and growth of FGFR1 and KGFR expressing cells. In addition, these cells exhibit a morphology that is reminiscent of that of malignantly transformed cells and display anchorage independent growth in a ligand dependent manner. Unlike KGFR and FGFR1, FGFR4 mediates a less effective growth, and cells overexpressing this receptor do not undergo any morphological changes nor do they display an anchorage independent growth in response to FGFs. All three receptors exhibit both quantitative and qualitative differences in their ability to induce tyrosine phosphorylation of cellular substrates. Both FGFR1 and KGFR induce strong phosphorylation of phospholipase C-gamma and a 90 kDa protein, while FGFR4 induces a relatively weak phosphorylation of phospholipase C-gamma and completely fails to induce phosphorylation of the 90 kDa. The three receptors also induce phosphorylation of the mitogen activated protein kinases (MAPK) but the effect of FGFR1 is far stronger than that of the other two receptors. Since FGFR4 is expressed in myoblasts in vivo, we examined whether this receptor can function in the differentiation pathway of myoblasts. Contrary to its weak mitogenic activity, FGFR4 effectively mediates the inhibition of myogenic differentiation in L6E9 cells and also suppresses the expression of the myogenic regulatory protein myogenin. Taken together, our results suggest that the signaling mechanism of FGFR4 differs from that of FGFR1 and KGFR, and that the primary role of FGFR4 in myoblasts may be the maintenance of their non differentiated state.

Animals↗
PubMed1995

Keloids.

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Humans↗
PubMed1995

Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions.

OBJECTIVE: To determine the effect of a transfusion program on risk of stroke recurrence in children with sickle cell disease. DESIGN: The clinical course and experience with transfusion therapy at eight centers were reviewed for subjects whose initial stroke occurred after January 1988. RESULTS: Sixty subjects were observed for 191.7 patient-years. Eight had a single recurrent stroke (two intracranial hemorrhages and six infarctions) for a prevalence of 13.3%, or one recurrence for each 24 patient-years of observation. Thirteen subjects had 15 transient neurologic events; two of these had subsequent strokes, but the overall risk was similar for those who did and those did not have transient events. Hemoglobin S levels were greater than the desired maximum of 30% at the time of 7 of 16 transient events and five of six recurrent infarctions. The stroke recurrence rate was similar to those in previous reports of children receiving long-term transfusion therapy but significantly less than that reported for children who did not receive transfusions (p < 0.001). CONCLUSIONS: We conclude that maintenance of hemoglobin S at a level less than 30% appears to be effective in reducing the rate of recurrent infarction but does not prevent transient neurologic events. Transient neurologic events are common but do not appear to be related to recurrent stroke.

Adolescent↗
PubMed1995

Efficacy of Chinese acupuncture on postoperative oral surgery pain.

One of the challenges of acupuncture research is designing appropriate control groups. To address this problem, after surgical third molar extractions 19 patients were randomly assigned to an acupuncture group (n = 11) or a placebo acupuncture group (n = 8). The length of time for reaching moderate pain and pain intensity after oral surgery were recorded by standard patient self-report. The results indicated that subjects treated with acupuncture reported longer pain-free duration times (mean, 181 versus 71 minutes; p < or = 0.046) and experienced less pain intensity than those who received placebo acupuncture. This study provides a model for an acupuncture control that could examine the placebo effect in clinical acupuncture research.

Acupuncture Analgesia↗
PubMed1995

Electroacupuncture reduces morphine-induced emesis in ferrets: a pilot study.

We treated morphine-induced emesis in ferrets with electroacupuncture (EA) for five minutes at the acupuncture point Neiguan (P6) using two different frequencies of stimulation: 1.0 Hz and 5.0 Hz (n = 5 ferrets per group). Both EA treatments reduced the number of emetic episodes (39% reduction of episodes, p < or = 0.05 at 1.0 Hz; 43% reduction of episodes, p < or = 0.05 at 5.0 Hz) and prolonged the onset time of emesis as compared with control receiving no EA. This model demonstrates that under these conditions EA is effective as an antiemetic against morphine in the ferret and may allow for further studies on the mechanisms of acupuncture and emesis.

Analgesics, Opioid↗
PubMed1995

Long-term central venous access in patients with sickle cell disease. Incidence of thrombotic and infectious complications.

PURPOSE: Central venous access devices (CVAD) have been used with increasing frequency in recent years among pediatric patients. We retrospectively reviewed our experience in 25 children and young adults with sickle cell disease (SCD) over a 4 1/2 year period in an attempt to define occurrence rates of perioperative complications, thrombosis requiring catheter removal, and infectious episodes. PATIENTS AND METHODS: The setting was a university-associated tertiary children's hospital. Patients were 25 children and young adults (ages 8 months to 23 years) with SCD who required CVAD placement between February 1987 and April 1992. A total of 31 catheters (totally implantable ports and partially implanted catheters) were placed for 17,444 patient catheter days. RESULTS: Rates of significant perioperative complications, thrombotic events requiring catheter removal, and infectious episodes were recorded. No perioperative complications were noted. Five episodes of catheter occlusion requiring replacement occurred in two patients (0.29 per 1,000 catheter patient days, involving 8% of patients and 16% of catheters). Fifteen episodes of catheter-associated bacteremia occurred in eight patients (0.86 per 1,000 catheter patient days involving 32% of patients and 26% of catheters). Three catheters required removal because of infection unresponsive to antibiotic therapy. CONCLUSION: The occurrence of thrombosis requiring catheter removal and infection in our population of patients with SCD was comparable to that reported in patients with malignant disease, cystic fibrosis and acquired immune deficiency syndrome. CVAD represents an effective, reliable, and reasonably safe means of establishing and maintaining venous access for a selective group of children and young adults with SCD who have limited peripheral venous access and require intravenous therapies.

Adolescent↗
PubMed1995

Pentoxifylline, pentifylline, and interferons decrease type I and III procollagen mRNA levels in dermal fibroblasts: evidence for mediation by nuclear factor 1 down-regulation.

Pentoxifylline (PTX) is a methylxanthine that exhibits multiple biologic activities, including the inhibition of collagen synthesis by dermal fibroblasts. Because some PTX activities have recently been linked to transcription factor-mediated regulation of gene transcription, we have investigated if PTX acts to inhibit collagen synthesis at a transcriptional locus by measuring procollagen mRNA levels by assaying for the presence of an activator of procollagen gene promoters, nuclear factor (NF)-1. The effects of another methylxanthine, pentifylline (PTF), shown herein to be a tenfold more potent inhibitor of collagen synthesis than PTX, and interferon-alpha, -beta, and -gamma were studied in parallel. Analysis of extracellular protein and RNA from 48-h-treated fibroblasts showed that PTX, PTF, and interferons decreased alpha 1(I), alpha 2(I), and alpha 1(III) procollagens by reducing the steady-state levels of the corresponding procollagen mRNA transcripts. Reduction of procollagen mRNA levels appeared to be dependent on new protein synthesis, as it was prevented by treatment with cycloheximide. Assay for the presence of nuclear NF-1 by gel mobility shift analysis showed that extracts from interferon, PTX, and PTF-treated fibroblasts lacked proteins recognizing the consensus DNA binding sequence for NF-1. Taken together, these observations suggest interferons and methylxanthines may inhibit fibroblast collagen synthesis by a common mechanism requiring new protein synthesis that suppresses procollagen gene transcription through down-regulation of NF-1.

Adult↗
PubMed1995

Oncostatin M stimulates collagen and glycosaminoglycan production by cultured normal dermal fibroblasts: insensitivity of sclerodermal and keloidal fibroblasts.

It is thought that normal fibrotic repair progresses to dermal fibrosis when fibroblasts are activated persistently by chronic exposure to cytokines such as transforming growth factor-beta. However, additional cytokines and mechanisms may play a role in the development of fibrosis. Thus, we examined a recently described T-lymphocyte/macrophage-derived cytokine, oncostatin M, for its effect on the production of collagen and glycosaminoglycan by microcultures of normal dermal, sclerodermal, and keloidal fibroblasts. Treatment with oncostatin M for 48 h induced dose-dependent (1-100 ng/ml) increases in the collagen and glycosaminoglycan production of nine normal fibroblast strains, which in the absence of fetal bovine serum at 100 ng/ml averaged 196% and 244%, respectively. Oncostatin M treatment increased both types I and III procollagens and their mRNA transcripts, as well as levels of hyaluronic acid, chondroitin-4/6 sulfates, and dermatan sulfate, but not fibronectin or general noncollagenous protein synthesis. In contrast, the collagen production of six of eight sclerodermal and keloidal fibroblast strains was essentially unresponsive to oncostatin M treatment, with 100 ng/ml inducing an average increase of only 34% for the eight fibrotic strains. Oncostatin M stimulation of fibrotic fibroblast glycosaminoglycan production was also hyporesponsive, as 100 ng/ml of oncostatin M induced an average increase of only 101%. These results indicate that oncostatin M could function as a stimulator of normal fibrotic repair via activation of fibroblast collagen and glycosaminoglycan synthesis and that the persistent activation of sclerodermal and keloidal fibroblasts is accompanied by a loss of sensitivity to oncostatin M stimulation.

Adult↗
PubMed1995

Fulminant head and neck congestion in advanced cutaneous T cell lymphoma: a poor prognostic indicator.

BACKGROUND: Clinical factors associated with a poor prognosis in patients with cutaneous T cell lymphoma (CTCL) include the extent and type of skin involvement and the presence and extent of lymphadenopathy. MATERIALS: We report retrospectively the clinical course and survival time of four patients with advanced CTCL after the development of fulminant head and neck congestion. METHODS: All four patients presented with marked erythema and edema of the head and neck with marked cervical adenopathy. Treatment with multidrug chemotherapy and radiation induced only brief remissions. The clinical picture was felt to be due to extensive tumor infiltration of the skin as well as lymphatic compression due to cervical adenopathy rather than venous compression at the level of the mediastinum. Survival from onset of this fulminant head and neck congestion was 1-5 months. CONCLUSION: Development of this fulminant head and neck congestion in patients with advanced CTCL heralds a progressively deteriorating clinical course with a poor prognosis.

Adult↗
PubMed1995

Mononuclear cells isolated from fibrotic skin lesions in avian scleroderma constitutively produce fibroblast-activating cytokines and immunoglobulin M.

University of California, Davis line 200 and 206 chickens develop an inherited autoimmune fibrotic disease associated with autoantibodies and other features similar to human scleroderma. Early in life, line 200/206 chickens develop mononuclear cell (MNC) infiltrates in the skin, followed by severe dermal fibrosis and vascular occlusions. Cultured fibroblasts derived from fibrotic skin lesions of line 200/206 chickens display an activated phenotype producing elevated quantities of collagen and glycosaminoglycan (GAG) compared to fibroblasts derived from normal chicken skin. To demonstrate a link between skin mononuclear cell infiltration and fibroblast activation, we cultured MNC isolated from developing fibrotic skin lesions, normal appearing skin, and peripheral blood of line 206 chickens for 24-72 h. Subsequent assay of MNC culture supernatants for effect on the collagen and GAG production of normal chicken skin fibroblasts demonstrated that only fibrotic lesion MNC supernatants contained significant collagen and GAG synthesis stimulatory activity. Both stimulatory activities were constitutively produced, undialyzable, heat and protease sensitive, and coeluted on gel filtration with a M(r) of 24-32 kD. Gel filtration also revealed that fibrotic lesion MNC secrete a protein > 250 kD, which we have identified as immunoglobulin (Ig) M by Western blot analysis. These results demonstrate that skin infiltrating MNC secrete both fibroblast-activating cytokines and IgM and thus they likely play an important role as effector cells in the development of dermal fibrosis and autoantibodies in this avian model of scleroderma.

Animals↗
PubMed1995

Dermatologic uses of interferons.

Interferons are members of the cytokine family, with diverse antiviral, antiproliferative, antifibrotic, and immunomodulatory activities. Over the past 10 years, interferon use in clinical dermatology has extended beyond its historical antiviral efficacy. In this article, FDA-approved indications and non-FDA-approved dermatologic uses of interferons are reviewed.

Humans↗
PubMed1994

Transient erythroblastopenia of childhood in infants < 6 months of age.

PURPOSE: During a 6-year period, we identified six infants < 6 months of age with transient erythroblastopenia of childhood (TEC). PATIENTS AND METHODS: All patients presented with moderate to severe anemia, reticulocytopenia, and age-appropriate mean corpuscular volume and fetal hemoglobin level. RESULTS: Severe aregenerative anemia in an infant < 6 months of age often raises the diagnostic possibility of Diamond Blackfan anemia (DBA). Given prognostic and therapeutic implications, distinction between DBA and TEC is of crucial importance. CONCLUSIONS: We suggest that TEC may occur more commonly in infants < 6 months of age than has heretofore been recognized and that it has a clinical and hematologic picture similar to that seen in older children. Recognition of the occurrence of TEC in very young infants may help avoid an inappropriate diagnosis of DBA.

Age Factors↗
PubMed1994

Short versus long echo time for cranial MR angiography in children and adults.

PURPOSE: To evaluate the ability of short-echo-time (TE) versus long-TE three-dimensional time-of-flight MR angiography sequences to decrease phase-related signal loss and refocus signal from blood in intracranial MR angiography of adults and children. METHODS: We evaluated 3-D time-of-flight cranial MR angiography in 33 cases (18 children and 15 adults) using two sequences. The longer-echo reference sequence had a TE of 8.0 milliseconds and a field echo of 6.5 milliseconds; the shorter-echo sequence had a TE of 5.1 and a field echo of 4.2 milliseconds. Repetition time, flip angle, and matrix were constant. The bandwidth for the longer-echo sequence was 130 Hz, 195 Hz for the shorter-echo sequence. RESULTS: The greatest improvement in diagnostic images was for children; significant and mildly improved signal recovery was demonstrated in 15 and 2 cases, respectively, of a total of 18 studies. This allowed improved diagnostic assessment. However, in the adult group significantly and mildly improved signal recovery were present in only 2 and 6 cases, respectively, of a total of 15 studies. In the group of children and adults combined, decreased lumen definition and peripheral vessel visibility were present in 24 and 30 of 33 cases, respectively, because of higher signal from background tissue when the shorter-TE field-echo sequence was used and, hence, reduced vascular contrast. CONCLUSION: The use of a short-field-echo/TE sequence is therefore recommended as the initial study in children but as a secondary examination in areas of abnormality in adults. This study illustrates the improved signal recovery from phase-related sources and improved visibility of intracranial stenosis in children with the use of a short-echo sequence. In adults, the short-echo sequence should not be used for the initial screening but reserved for secondary evaluation.

Adolescent↗