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Biomedical subjects

C Schultz

Publications and source records attributed to C Schultz.

At least 19 recordsLinked to original sources

The critical region in the cytoplasmic domain of human IL-4 receptor for induction of IgE synthesis.

To examine the region critical for differentiation in the human IL-4 receptor (hIL-4R), we transfected the Abelson murine leukemia virus (A-MuLV)-transformed murine pre-B cell line A20 with plasmid DNA encoding the hIL-4R. Transfectants expressed high affinity hIL-4Rs on the cell surface. Treatment with LPS and hIL-4 induced germline C epsilon transcripts in hIL-4R expressing A20 cells. Several hIL-4R mutant plasmids were then transfected into A20 cells and the transfectants were examined for hIL-4R expression and the ability to induce germline C epsilon transcripts upon stimulation with LPS and hIL-4. Although all A20 transfectants tested expressed the high-affinity hIL-4R, A20 transfectants expressing the mutant hIL-4R, which contains only 8 amino acids in the cytoplasmic domain, did not respond to LPS and hIL-4 with germline C epsilon transcripts. In addition, A20 transfectants expressing an internally deleted hIL-4R, in which the deleted region has been identified as the critical region for growth signal transduction in the previous study, failed to induce germline C epsilon transcripts with LPS and hIL-4. These results indicate that the critical region for the differentiation signal in the hIL-4R is identical to that for the growth signal, suggesting that IL-4 may share, at least partly, a common signal pathway for both growth and differentiation.

Animals

Cross-talk between calcium and cAMP-dependent intracellular signaling pathways. Implications for synergistic secretion in T84 colonic epithelial cells and rat pancreatic acinar cells.

Treatment of various cells with combinations of agents that increase either cAMP or cytosolic calcium can lead to synergistic responses. This study examined interactions, or cross-talk, between these two intracellular messengers and its implication for signaling in two secretory cell types, T84 human colonic epithelial cells and rat pancreatic acinar cells. T84 cell chloride secretion was measured in Ussing chambers. Acinar cell activation was monitored as amylase secretion. Cytosolic calcium was assessed via fura-2 microfluorimetry. A cell-permeant analogue of cAMP synergistically enhanced secretory responses to calcium-mobilizing hormones in both cell types, but paradoxically reduced overall calcium mobilization. The reduction in calcium mobilization could be attributed to an inhibition of calcium influx in T84 cells, although a different mechanism likely operates in acinar cells. The effects of the cAMP analogue were reproduced by other agents that increase cAMP. Furthermore, econazole, an inhibitor of calcium influx, potentiated secretory responses to calcium-dependent stimulation in T84 cells without itself inducing secretion. We conclude that there is cross-talk between calcium and cAMP-dependent signaling pathways at the level of second messenger generation in two secretory cell types. This cross-talk appears to regulate the extent of secretory responses.

Amylases

[Laparoscopic interventions in acute and chronic diverticulitis].

UNLABELLED: Since the beginning of 1993 until May 1994 in our hospital 25 patients were operated upon for diverticular disease. 16 patients required a laparoscopic assisted elective one-stage resection. One laparoscopic Hartmann's procedure was performed on account of a free perforation. 4 patients underwent laparoscopic reconstruction of the intestinal continuity after an Hartmann's resection. In 4 cases it was necessary to change to the conventional procedure. TECHNIQUE: the patient is placed in dorso-sacral position (modified lithotomy position) in order to allow transanal colonic access. 4 trocars are necessary. The linear stapler is used to transsect the sigmoid colon and to dissect the entire mesentery. The left lateral trocar incision is enlarged to remove the specimen. The intracorporeal double staple anastomosis is created by a circular stapler. RESULTS: there were two wound infections, one postoperative bleeding and one small anastomotic leak. After the operation we observed all advantages of the laparoscopic procedure in form of less pain, earlier beginning of bowel movements, faster return to full diet and earlier hospital discharge. These positive results combined with the possibility of a standardized procedure encourage us to continue laparoscopic sigmoidectomy.

Acute Disease

Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4.

Osmoregulation, inhibitory neurotransmission and pH balance depend on chloride ion (Cl-) flux. In intestinal epithelial cells, apical Cl- channels control salt and fluid secretion and are, in turn, regulated by agonists acting through cyclic nucleotides and internal calcium ion concentration ([Ca2+]i). Recently, we found that muscarinic pretreatment prevents [Ca2+]i increases from eliciting Cl- secretion in T84 colonic epithelial cells. By studying concomitant inositol phosphate metabolism, we have now identified D-myo-inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4), as the inositol phosphate most likely to mediate this uncoupling. A novel, membrane-permeant ester prepared by total synthesis delivers Ins(3,4,5,6)P4 intracellularly and confirms that this emerging messenger does inhibit Cl- flux resulting from thapsigargin- or histamine-induced [Ca2+]i elevations.

Atropine

Inositol polyanions. Noncarbohydrate inhibitors of L- and P-selectin that block inflammation.

Selectins are cell adhesion molecules known to support the initial attachment of leukocytes to inflamed vascular endothelium through their recognition of carbohydrate ligands such as the tetrasaccharide sialyl Lewisx (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-). In the present study, we describe the inhibition of L- and P-selectin function by inositol polyanions, simple 6-carbon ring structures that have multiple ester-linked phosphate or sulfate groups. In a purified component competition assay, binding of L- and P-selectin-Ig fusion proteins to immobilized bovine serum albumin-sialyl Lewisx neoglycoprotein was inhibited by inositol hexakisphosphate (InsP6, IC50 = 2.1 +/- 1.4 microM and 160 +/- 40 microM), by inositol pentakisphosphate (InsP5, IC50 = 1.4 +/- 0.2 and 260 +/- 40 microM), and by inositol hexakissulfate (InsS6, IC50 = 210 +/- 80 microM and 2.8 +/- 0.9 mM); E-selectin-Ig binding was unaffected. Inositol polyanions diminished the adhesion of LS180 colon carcinoma cells to plates coated with L- and P-selectin-Ig but not with E-selectin-Ig. Inositol polyanions blocked polymorphonuclear leukocyte (PMN) adhesion to COS cells expressing recombinant transmembrane P-selectin but not to those expressing E-selectin. In addition, inositol polyanions diminished PMN adhesion to activated endothelial cells under rotation-induced shear stress, a process known to require L-selectin function. In vivo, the effects of inositol polyanions were studied in two murine models of acute inflammation. Intravenously administered InsP6 (two doses of 40 mumol/kg) inhibited PMN accumulation in thioglycolate-induced inflammation (55 +/- 10% inhibition) and in zymosan-induced inflammation (61 +/- 4% inhibition). InsP5 and InsS6 also inhibited inflammation in these models, although higher doses were required for InsS6. In conclusion, inositol polyanions are noncarbohydrate small molecules that inhibit L- and P-selectin function in vitro and inflammation in vivo.

Animals

Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation.

Several lines of evidence suggest that cyclic GMP might be involved in long-term potentiation (LTP) in the hippocampus. Arachidonic acid, nitric oxide and carbon monoxide, three molecules that have been proposed to act as retrograde messengers in LTP, all activate soluble guanylyl cyclase. We report here that an inhibitor of guanylyl cyclase blocks the induction of LTP in the CA1 region of hippocampal slices. Conversely, cGMP analogues produce long-lasting enhancement of the excitatory postsynaptic potential if they are applied at the same time as weak tetanic stimulation of the presynaptic fibres. The enhancement is spatially restricted, is not blocked by valeric acid (APV), nifedipine, or picrotoxin, and partially occludes LTP. This synaptic enhancement may be mediated by the cGMP-dependent protein kinase (PKG). Inhibitors of PKG block the induction of LTP, and activators of PKG produce activity-dependent long-lasting enhancement. These results suggest that guanylyl cyclase and PKG contribute to LTP, possibly as activity-dependent presynaptic effectors of retrograde messengers.

Action Potentials

[Cysts of second branchial cleft: review of 32 operated cases].

The aim of this work was to analyze retrospectively the clinical features of 32 patients aged 23.9 years (21 female) with the histological diagnosis of second branchial cleft cyst. In 28 patients, the cyst was localized below the mandibular angle. The presenting symptom was a cervical tumor in 30 patients and pain in eight. Fourteen aspiration punctures was performed obtaining 8 purulent and 6 straw colored aspirates. The preoperative diagnosis was correctly made in only 19 patients; the principal confounding diagnosis was tuberculous adenitis. All patients were operated performing a complete cystectomy in 30 and partial cystectomy in two. Three patients had a surgical wound infection and the cysts recurred 5 months and 4 years after operation in the two patients subjected to partial cystectomy. The histological study revealed squamous epithelial with underlying lymphoid tissue. It is concluded that aspiration puncture is useful for the correct diagnosis and that the cyst must be completely eradicated to avoid recurrences.

Adolescent

Academic emergency medicine: a national profile with and without emergency medicine residency programs.

STUDY OBJECTIVE: Formal data are lacking regarding emergency departments in academic medical centers, particularly those without an emergency medicine residency program. The Education Committee of the Society for Academic Emergency Medicine conducted a survey to define a national profile of academic emergency medicine. DESIGN: Prospective survey with telephone follow-up. SETTING: Academic medical centers. PARTICIPANTS: One hundred twenty-three academic medical centers as defined by the Association of American Medical Colleges. RESULTS: Results were obtained from 94 (78%) institutions: 27 (29%) had an emergency medicine residency program and 67 (71%) had no emergency medicine residency program. Significant differences were found between those with and without emergency medicine residency programs regarding 24-hour attending coverage (96% versus 73%), mean weekly clinical faculty hours (26 versus 33), the number of emergency medicine board-certified faculty, faculty recruitment difficulties (25% versus 75%), and the presence of a curriculum for housestaff (96% versus 38%). No significant differences were noted regarding the presence of a curriculum for medical students (78% versus 64%). Of the 67 institutions with no emergency medicine residency programs, 42% were actively planning a program, and 42% would consider future development of a program. CONCLUSION: This article provides the first comprehensive profile of emergency medicine in the Association of American Medical Colleges academic medical centers. Programs with emergency medicine residency programs provided more 24-hour attending coverage, had more emergency medicine board-certified faculty, and reported less difficulty recruiting additional faculty than institutions with no emergency medicine residency program. Both need to expand their undergraduate educational activities. Many institutions with no emergency medicine residency program are attempting to develop emergency medicine residency programs.

Academic Medical Centers

[Histologic reactions of the bone-implant zone and cortical bone area after long-term hip replacement].

29 femora with cemented hip endoprostheses and 17 age related controls were analyzed regarding different histological criteria. All specimens were processed to undecalcified ultra thin grindings and in addition a few to surface stained block-grindings. The reactions at the bone implant interface in cases without loosening of the implant are: accumulation of macrophages and multinucleated giant cells, fibrous tissue membranes with a mean thickness of 103 microns and mineralization defects near the cement. The mean rate of direct bone/bone-cement contact is 2.7% of the whole cement surface. The phenomenons at the interface were explained as being the result of micromovement and resulting from wear and tear. The cortical bone demonstrates a remarkable loss of bone (up to 60% after 12 years) following an increase of osteoclastic resorption with no change of osteoblast activity. The localization of the bone loss indicates a relation to the new load situation after implantation.

Aged

In vivo study of the state of order of the membranes of gram-negative bacteria by Fourier-transform infrared spectroscopy (FT-IR).

Temperature-induced order/disorder transition profiles were obtained from the membranes of intact Gram-negative bacterial cells by FT-IR analysis of the frequency shifts of the acyl chain methylene symmetric stretching band as a monitor. Cells grown at different temperatures yielded distinct transition profiles. At the individual growth temperatures, however, the nearly alike frequency values indicated a very similar 'state of order' of the bacterial membranes. The FT-IR data were complemented by GC analysis of whole cell fatty acid composition. The FT-IR data obtained in vivo gave direct evidence of the adaptation of the 'state of order' and 'fluidity' of bacterial membranes to varying growth temperatures.

Cell Membrane

cis,cis-cyclohexane 1,3,5-triol polyphosphates release calcium from Neurospora crassa via an unspecific Ins 1,4,5-P3 receptor.

We investigated the effects of new inositol 1,4,5-trisphosphate analogues on the release of Ca2+ from isolated vacuoles of Neurospora crassa. Tri-O-butyryl-inositol 1,4,5-trisphosphate and a set of cis,cis-cyclohexane 1,3,5-triol bis-(CHT-P2) and trisphosphates (CHT-P3) gave an increase in free Ca2+ as measured directly with fura-2, a Ca2(+)-chelator. However, inositol 1,4-bisphosphate, 6-O-palmitoyl-inositol 4,5-bisphosphate and trans-cyclohexane 1,2-diol bisphosphate (trans CHD-P2) did not induce Ca2(+)-release. These results suggest that the 1,5-bisphosphate position in inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) is the only essential arrangement for receptor binding to vacuoles of Neurospora crassa. The structures of these analogues are discussed on the basis of a general concept for the design of new Ins 1,4,5-P3 analogues.

Benzofurans

Patterns and extent of isotype-specificity in the murine H chain switch DNA rearrangement.

We have analyzed the configuration of the H chain locus of 41 hybridomas by Southern blot analysis. Each H chain switch region was determined to be germ line, rearranged, or deleted. Including 13 previously analyzed hybridomas, 60% of those with rearrangements on both alleles showed a correlation of the two alleles, i.e., both the expressed and the nonexpressed alleles have rearranged to the same H chain constant region gene segment. When the two H chain alleles did not rearrange to the same gene, they often rearranged to neighboring H chain genes. These results support a role for isotype-specific factors in H chain switch recombination. The action of these isotype-specific factors may be propagated to some extent along the chromosome, which would lead to rearrangements to neighboring genes.

Alleles

Chloroquine poisoning in a child.

Chloroquine poisoning in children, although infrequent, is extremely dangerous because of the narrow margin between therapeutic and toxic doses. Children clinically present with apnea, seizures, and cardiac arrhythmias. We present the case of a 12-month-old infant, the second-youngest patient reported in the US literature to die from chloroquine poisoning. A serum level of 4.4 mg/L (13.64 mumol/L) was obtained after the infant ingested only one tablet (300 mg). This establishes a new minimal lethal dose/blood level for children. Although some pediatric and adult pharmacokinetic and clinical similarities exist, the outcome is different. Pediatric mortality is 80%, whereas adult mortality is only 10%. Pediatric ingestion cases are primarily unintentional, and most adult cases are suicide attempts. Current treatment in adults includes a protocol of diazepam and epinephrine. Further studies involving children and these medications and other modalities are needed to improve survival.

Apnea