PubMed Health⌕ Search

Biomedical subjects

J S Hyams

Publications and source records attributed to J S Hyams.

At least 19 recordsLinked to original sources
PubMed2001

Myosin V-mediated vacuole distribution and fusion in fission yeast.

The class V myosins are actin-based motors that move a variety of cellular cargoes [1]. In budding yeast, their activity includes the relocation of a portion of the vacuole from the mother cell to the bud [2, 3]. Fission yeast cells contain numerous (approximately 80) small vacuoles. When S. pombe cells are placed in water, vacuoles fuse in response to osmotic stress [4]. Fission yeast possess two type V myosin genes, myo51(+) and myo52(+) [5]. In a myo51Delta strain, vacuoles were distributed throughout the cell, and mean vacuole diameter was identical to that seen in wild-type cells. When myo51Delta and wild-type cells were placed in water, vacuoles enlarged by fusion. In myo52Delta cells, by contrast, vacuoles were smaller and mostly clustered around the nucleus, and fusion in water was largely inhibited. When cells containing GFP-Myo52 were placed in water, Myo52 was seen to redistribute from the cell poles to the surface of the fusing vacuoles. Vacuole fusion in fission yeast was inhibited by the microtubule drug thiabendazole (TBZ) but not by the actin inhibitor latrunculin B. This is the first demonstration of the involvement of a type V myosin, possibly via an interaction with microtubules, in homotypic membrane fusion.

Calmodulin-Binding Proteins↗
PubMed2001

A MAP kinase-dependent actin checkpoint ensures proper spindle orientation in fission yeast.

The accurate segregation of chromosomes at mitosis depends on a correctly assembled bipolar spindle that exerts balanced forces on each sister chromatid. The integrity of mitotic chromosome segregation is ensured by the spindle assembly checkpoint (SAC) that delays mitosis in response to defective spindle organisation or failure of chromosome attachment. Here we describe a distinct mitotic checkpoint in the fission yeast, Schizosaccharomyces pombe, that monitors the integrity of the actin cytoskeleton and delays sister chromatid separation, spindle elongation and cytokinesis until spindle poles have been properly oriented. This mitotic delay is imposed by a stress-activated mitogen-activated protein (MAP) kinase pathway but is independent of the anaphase-promoting complex (APC).

Actins↗
PubMed2001

Shedding a little light on light chains.

Myosin II regulatory light chains have an important role in the organization and function of the contractile machinery at cytokinesis. Two recent reports provide new insights into these important proteins.

Amino Acid Motifs↗
PubMed2001

Localization of fission yeast type II myosin, Myo2, to the cytokinetic actin ring is regulated by phosphorylation of a C-terminal coiled-coil domain and requires a functional septation initiation network.

Myo2 truncations fused to green fluorescent protein (GFP) defined a C-terminal domain essential for the localization of Myo2 to the cytokinetic actin ring (CAR). The localization domain contained two predicted phosphorylation sites. Mutation of serine 1518 to alanine (S(1518)A) abolished Myo2 localization, whereas Myo2 with a glutamic acid at this position (S(1518)E) localized to the CAR. GFP-Myo2 formed rings in the septation initiation kinase (SIN) mutant cdc7-24 at 25 degrees C but not at 36 degrees C. GFP-Myo2S(1518)E rings persisted at 36 degrees C in cdc7-24 but not in another SIN kinase mutant, sid2-250. To further examine the relationship between Myo2 and the SIN pathway, the chromosomal copy of myo2(+) was fused to GFP (strain myo2-gc). Myo2 ring formation was abolished in the double mutants myo2-gc cdc7.24 and myo2-gc sid2-250 at the restrictive temperature. In contrast, activation of the SIN pathway in the double mutant myo2-gc cdc16-116 resulted in the formation of Myo2 rings which subsequently collapsed at 36 degrees C. We conclude that the SIN pathway that controls septation in fission yeast also regulates Myo2 ring formation and contraction. Cdc7 and Sid2 are involved in ring formation, in the case of Cdc7 by phosphorylation of a single serine residue in the Myo2 tail. Other kinases and/or phosphatases may control ring contraction.

Actins↗
PubMed2001

Two type V myosins with non-overlapping functions in the fission yeast Schizosaccharomyces pombe: Myo52 is concerned with growth polarity and cytokinesis, Myo51 is a component of the cytokinetic actin ring.

The fission yeast genome project has identified five myosin genes: one type I myosin, myo1(+), two type II myosins, myo2(+) and myp2(+), and two type V myosins, myo51(+) and myo52(+). Cells deleted for myo51(+) show normal morphology and growth rates whereas deletion of myo52(+) results in a partial loss of cell polarity, slow growth and cytokinetic defects. Combining both deletions in a single strain is phenotypically non-additive, myo52(delta) being epistatic to myo51(delta). Overproduction of Myo51 gives rise to elongated cells which fail to form functional septa whereas overproduction of Myo52 results in branched cells with aberrant septa that fail to cleave. Myo52 localises to the poles of growing cells but during cell division it relocalises to the cell equator as a bar that is bisected by the cytokinetic septum. Myo51 shows no obvious localisation during interphase but at cytokinesis it is associated with the contractile cytokinetic actin ring (CAR). Both myosins are dependent upon an intact actin cytoskeleton for localisation. Myo52 partially colocalises with the (alpha)-glucan synthase Mok1 at the cell tips and to a lesser extent at the septum. Mok1 is delocalised and upregulated in myo52(delta) and myo52(delta) cell walls are resistant to digestion by the cell wall degrading enzyme zymolyase. Thus myo52(+) appears to be involved in the local delivery or positioning of vesicles containing cell wall precursors at the cell tips and has a role in the maturation or cleavage of the septum. Myo51 has a non-essential role in cytokinesis as a component of the cytokinetic actin ring.

Actins↗
PubMed2000

Cytokinesis in fission yeast: a myosin pas de deux.

Cytokinesis in the fission yeast, Schizosaccharomyces pombe consists of two distinct but overlapping events: the assembly and constriction of a cytokinetic actomyosin ring (CAR) and the formation of a cross wall or septum. These two processes must be spatially and temporally coordinated both with each other and with other cell cycle events, most notably spindle formation and anaphase chromosome segregation. In fission yeast, the CAR contains two unusual type II myosins, Myo2, encoded by the gene myo2(+), and Myp2, encoded by myp2(+). The relationship of these two proteins to each other and their relative contribution to CAR assembly and contraction is largely unknown. Here we review what is known about the role of each myosin in cytokinesis and present some new information concerning their regulation and possible physical interaction.

Actins↗
PubMed2000

Use of infliximab in the treatment of Crohn's disease in children and adolescents.

BACKGROUND: Crohn's disease is often poorly responsive to conventional therapy with corticosteroids and immunomodulators. A novel chimeric antibody to tumor necrosis factor-alpha, infliximab, has shown utility in the treatment of refractory Crohn's disease in adults. PURPOSE: To evaluate the efficacy of open-label administration of infliximab in children and adolescents with active intestinal Crohn's disease. METHODS: Chart review of the experience with 19 subjects (mean age 14.4 years, range 9 to 19 years) receiving 1 to 3 infusions of infliximab (5 mg/kg/dose) over a 12-week period for corticosteroid-resistant disease (n = 7) or corticosteroid dependence (n = 12). Disease activity was monitored by physician global assessment and the Pediatric Crohn's Disease Activity Index. RESULTS: Significant initial improvement (first 4 weeks after infusion) was noted in all subjects, with Pediatric Crohn's Disease Activity Index values decreasing significantly (mean +/- SD, 42.1 +/- 13.7 to 10.0 +/- 5.6, P <.0001). Over the subsequent 8-week period, 8 of 19 treated subjects had worsening of symptoms, although none deteriorated to severe activity. The mean Pediatric Crohn's Disease Activity Index at 12 weeks was 26.8 +/- 16. 4. The mean daily prednisone dosages at baseline, 4 weeks, and 12 weeks were 28 +/- 14 mg, 20 +/- 12 mg, and 8 +/- 12 mg, respectively (P <.01). Adverse effects were noted in 3 patients during infusion (dyspnea, rash) and were self-limited. CONCLUSIONS: Infliximab is associated with short-term clinical improvement in children and adolescents with severe Crohn's disease. The rapid return of disease activity in some patients suggests that additional dosing strategies may be required. Long-term safety necessitates close monitoring.

Adolescent↗
PubMed2000

Allergic gastroenteropathy in preterm infants.

OBJECTIVES: To determine the clinical presentation, histopathologic features, and outcome of biopsy-proven allergic gastroenteropathy (AGE) in preterm infants. We hypothesized that AGE is a more frequent cause of gastrointestinal disease in this population than previously suspected. STUDY DESIGN: The retrospective portion of the study, from 1992 to 1997, included preterm infants <37 weeks' gestation who underwent biopsy because of suspected AGE. The prospective portion, from January to December 1998, included 20 infants undergoing endoscopy and biopsy because of suspected AGE. RESULTS: Twenty-five infants (12 retrospective/13 prospective) with mean gestational age of 29 weeks at birth and mean postnatal age at diagnosis of 78 days were diagnosed with AGE. Three clinical patterns of presentation were noted: group 1, gastroesophageal reflux disease (n = 5); group 2, non-specific feeding intolerance (n = 8); and group 3, lower gastrointestinal bleeding (n = 12). Ten patients had negative biopsy findings (3 retrospective/7 prospective) and had clinical features indistinguishable from those of groups 1 and 2. Patients in group 3 were most likely to have positive biopsy findings (12 of 12). Fifteen patients responded to a casein hydrolysate formula, and 10 patients required an amino acid-based formula. Patients with AGE who had eosinophilic infiltration and villous atrophy took longer to recover than those with eosinophilic infiltration alone (P <.03). Subsequently, most have tolerated formula challenges and are currently tolerating cow's milk. CONCLUSIONS: AGE may be an under-recognized cause of gastrointestinal symptoms in preterm infants. Confirmation with endoscopy and biopsy can be done safely and provides the basis for appropriate dietary management.

Follow-Up Studies↗
PubMed2000

Dyspepsia in children and adolescents: a prospective study.

BACKGROUND: Dyspepsia is poorly characterized in the pediatric population. The goal of the current study was to describe the clinical constellation and natural history of dyspepsia in children and adolescents seen in a pediatric gastroenterology practice. METHODS: A standardized questionnaire was administered by a pediatric gastroenterologist to all subjects 5 or more years of age (and their parents or guardians) treated in a referral pediatric gastroenterology practice for 1 month or more of abdominal pain or discomfort, nausea, or vomiting. Subjects with dyspepsia and dyspepsia subtypes (ulcer-like, dysmotility-like) were identified by using previously defined adult criteria. Evaluation and treatment were performed at the discretion of the attending pediatric gastroenterologist. RESULTS: During a 1-year period, 257 patients were screened with 127 subjects fulfilling criteria for dyspepsia (59% girls, 85% white; median age, 11.7 years; median duration of symptoms, 8 months). Symptoms were ulcer-like in 26% and dysmotility-like (nausea predominance) in 15% of subjects. In those with dyspepsia, irritable bowel syndrome and gastroesophageal reflux were noted in 24% and 43%, respectively. Esophagogastroduodenoscopy and biopsy were performed in 56 subjects with 21 (38%) having mucosal inflammation (Helicobacter pylori in 5). The remaining 35 subjects (62%) were considered to have functional dyspepsia. Duration of symptoms less than 1 year and vomiting were risk factors for mucosal inflammation. Follow-up at 6 months to 2 years revealed 70% of subjects were either asymptomatic or much improved regardless of the cause of dyspepsia. CONCLUSION: Most children and adolescents with dyspepsia do not have serious disease. In our referral population H. pylori infection was unusual, and no peptic ulceration was found. Most subjects with functional dyspepsia have improvement of symptoms over time.

Adolescent↗
PubMed2000

Corticosteroids in the treatment of gastrointestinal disease.

Corticosteroids remain the mainstay of anti-inflammatory and immunosuppressive therapy for many gastrointestinal conditions. We are now starting to understand their mechanism of action and the phenomenon of corticosteroid resistance. Because of the ubiquity of corticosteroid receptors in virtually all cells of the body, side effects of therapy are common and may affect multiple body sites. Newer corticosteroid analogues are being developed to minimize these complications, and concomitant use of other immunomodulatory drugs often facilitates corticosteroid dosage reduction or even withdrawal in chronic inflammatory states.

Adrenal Cortex Hormones↗
PubMed1999

Infliximab: a novel chimeric monoclonal antibody for the treatment of Crohn's disease.

Crohn's disease (CD) is characterized by transmural inflammatory disease involving any portion of the gastrointestinal tract. Patients with CD have increased mucosal concentrations of the cytokine tumor necrosis factor-alpha (TNF-alpha), a key mediator of mucosal inflammation. In addition, TNF-alpha has multiple biologic activities involved in apoptosis, metabolism, and activation of granulocytes, lymphocytes, eosinophils, fibroblasts, chondrocytes, and endothelial cells. Recently, infliximab has emerged as a novel chimeric monoclonal antibody that inhibits TNF-alpha. Infliximab is indicated for the treatment of moderately to severely active CD in patients having an inadequate response to conventional therapy. To date, a small number of clinical trials with infliximab have demonstrated efficacy and tolerability when the agent is initiated as a 5-mg/kg single intravenous infusion. In patients with fistulizing CD, administration of 2 subsequent 5-mg/kg doses 2 and 6 weeks after the initial dose appears to be efficacious. Infliximab seems to be a promising therapeutic strategy for patients with refractory CD.

Antibodies, Monoclonal↗