Constitutive secretion of the granule chymase mouse mast cell protease-1 and the chemokine, CCL2, by mucosal mast cell homologues

BACKGROUND: The mucosal mast cell (MMC) granule-specific beta-chymase, mouse mast cell protease-1 (mMCP-1), is released systemically into the bloodstream early in nematode infection before parasite-specific IgE responses develop and TGF-beta1 induces constitutive release of mMCP-1 by homologues of MMC in vitro. Intraepithelial MMC may also express the chemokine CCL2 (monocyte chemotactic protein-1) during nematode infection but the expression of this chemokine by MMC homologues has not been investigated. OBJECTIVE: To investigate the expression and to compare the mechanisms of constitutive release of the chymase, mMCP-1, and the chemokine, CCL2. METHODS: MMC homologues were generated by culturing bone marrow cells in the presence of TGF-beta1, IL-3, IL-9 and stem cell factor (SCF). The intracellular distribution of mMCP-1 and CCL2 was examined by confocal microscopy. The involvement of the Golgi complex and of protein synthesis in the constitutive release of mMCP-1 and CCL2 was investigated using the Golgi-disrupting agent brefeldin A and cycloheximide to block protein synthesis. Secreted analytes were quantified by ELISA. RESULTS: mMCP-1 colocalized with Golgi matrix protein 130 but was most abundant in the granules, whereas CCL2 was not found in the granules but appeared to be located uniquely in the Golgi complex. Extracellular release of mMCP-1 was significantly inhibited ( approximately 40%) by cycloheximide and by the Golgi-disrupting agent brefeldin A, indicating both continuous protein synthesis and transportation via the Golgi complex are required for optimal mMCP-1 secretion. A similar but more marked inhibitory effect with both compounds was demonstrated on the constitutive secretion of CCL2. CONCLUSION: The culture conditions that promote mMCP-1 expression and release by MMC homologues also promote the expression and release of CCL2. Constitutive release involves de novo protein synthesis and requires a functional Golgi complex, suggesting that similar mechanisms of extracellular secretion operate for both mediators.     

A double-blind, placebo-controlled study of the effect of imipramine on TRH-induced urinary urgency in healthy men.

We studied the effect of imipramine (IMI) on thyroid releasing hormone (TRH)-induced urinary urgency as a way of investigating the mechanism of the beneficial effect of IMI on enuresis. In a double-blind study, 12 normal, healthy men between 21 and 39 yr of age ranked their urge to urinate at 30-sec intervals following IV injection of TRH (500 micrograms) or saline. The subjects then were randomly assigned to either IMI (1 mg/kg) or placebo groups for 10 days, and the procedure was repeated. Compared to saline, TRH produced a significant elevation in urinary urgency in all subjects. IMI did not significantly blunt TRH-induced urinary urgency. Thus, the mechanism by which IMI affects enuresis is likely not mediated at the level of the urinary urgency induced by TRH.     

Asymmetrical effects of albumin on transsynovial fluid movement.

The effect of intraarticular infusions of albumin solution on transsynovial flow was studied in healthy rabbit knee joints and compared with the effect of albumin solution perfused through the synovial microcirculation. Increasing intravascular albumin levels enhanced fluid absorption from the joint cavity, whereas increasing intraarticular albumin levels reduced the absorption rate. The slope of intraarticular pressure-versus-absorption rate plots was reduced by albumin in proportion to the reduction in fluidity (1/viscosity). When joint pressure was held constant, the transsynovial absorption rate was reduced by albumin in excess of the fluidity reduction and even reversed to filtration into the joint cavity. Thus intraarticular albumin acts by a dual mechanism, namely by increasing synovial interstitial fluid viscosity and by exerting a peri-capillary oncotic pressure. However, the latter effect was much less than that of intravascular albumin. Reasons for this are discussed.     

Anterior and posterior association cortex contributions to the somatosensory P300

A P300 (P3)-evoked response is generated in a variety of mammalian species upon detection of significant environmental events. The P3 component has been proposed to index a neural system involved in attention and memory capacity. We investigated the contribution of anterior and posterior association cortex to somatosensory P3 generation. Somatosensory event-related potentials (ERPs) were recorded in controls (n = 10) and patients with unilateral lesions in temporal-parietal junction (n = 8), lateral parietal cortex (n = 8), or dorsolateral frontal cortex (n = 10). Subjects pressed a button to mechanical taps of the fifth finger (targets; p = 0.12), randomly interposed in sequences of taps to the second (standards; p = 0.76) and the third or fourth finger (tactile novels; p = 0.06). Occasional shock stimuli were delivered to the wrist (shock novels; p = 0.06). The scalp-recorded P3 was differentially affected by anterior and posterior association cortex lesions. Subjects with temporal-parietal lesions showed markedly reduced P3s to all types of stimuli at all scalp locations. The reductions were largest at the parietal electrode site over the lesioned hemisphere. Parietal patients had normal P3s for all stimulus types except for contralateral shock novels, which generated reduced P3s. Frontal lesions had reductions of the novelty P3 over frontal sites with minimal changes in the target P3. The data support the existence of multiple intracranial P3 sources. The data further indicate that association cortex in the temporal-parietal junction is critical for generating the scalp-recorded target and novelty P3s, whereas dorsolateral frontal cortex contributes preferentially to novelty P3 generation. The N2 component was reduced by parietal and frontal lesions in patients who had intact target P3s, suggesting that different neural systems underlie N2 and P3 generation.     

Thoracoscopic excision of mediastinal parathyroid adenomas: a report of two cases and review of the literature

Background:Most abnormal parathyroid glands can be removed through a standard cervical incision; even those in the superior mediastinum. Those located in certain areas of the mediastinum, for example posteriorly or in the aortopulmonic window, historically have required excision through a median sternotomy or thoracotomy. Angioablation is a nonsurgical alternative to management of these lesions.Study Design:We present two case reports of mediastinal parathyroid adenomas that were excised thoracoscopically, and review the literature regarding the management of mediastinal parathyroid adenomas.Results:Both patients who underwent precise localization and thoracoscopic excision of their mediastinal parathyroid adenomas had resolution of their hypercalcemia with minimal associated morbidity and shortened recovery periods.Conclusions:We suggest that thoracoscopic excision of mediastinal parathyroid adenomas is the better means of controlling hypercalcemia secondary to parathyroid adenoma in those patients considered for either median sternotomy, thoracotomy or angiographic ablation where the exact location of the lesion can be established preoperatively.     

Minimally Invasive Axillary– Coronary Artery Bypass

Axillary artery-to-coronary artery bypass using reversed saphenous vein provides a simple method of applying the minimally invasive coronary bypass grafting procedure when the internal thoracic artery is not an adequate conduit. Although this may allow extended use of the minimally invasive coronary bypass procedure, the long-term patency of this technique is unknown.     

Wound healing response in surgical patients: recent food intake is more important than nutritional status

We have recently found that an impairment of the wound healing response (WHR) occurs in surgical patients with protein-energy malnutrition before there are any measurable changes in body fat and protein stores. The hypothesis of this study was that the patients' recent food intake is more important in determining the WHR than the patients' overall nutritional status. We have measured the recent food intake (by dietary recall), the WHR (by hydroxyproline accumulation in subcutaneous GORE-TEX implants), the pre-operative weight loss (per cent), and body fat and protein stores (by in vivo neutron activation analysis) in 83 patients awaiting a major elective gastrointestinal resection, and divided them into two groups: adequate recent food intake (n = 59) and inadequate recent food intake (n = 24). There was no significant difference between these two groups for age, sex, diagnosis, surgical procedure, weight loss (per cent), or the amount of body fat and protein stores but there was a significant difference in the WHR (1.81 +/- 0.16 s.e.m. versus 1.04 +/- 0.22 s.e.m. nmol hydroxyproline/mg GORE-TEX, P less than 0.005). These results show that pre-operative food intake has a greater influence over the wound healing response than absolute losses of protein and fat from body stores and they suggest that the maintenance of a normal food intake up until the time of surgery is of importance in preventing an impairment of the wound healing response.