IgE-antigen complexes enhance Fc epsilon R and Ia expression by murine B lymphocytes.

Murine monoclonal IgE interacts with B cells of BALB/c mouse spleen with greater efficiency in the presence of its specific antigen. Complexes of anti-DNP IgE and DNP-OVA not only resist elution from B lymphocytes by acid but have a substantially longer dissociation half-time when compared with monomeric IgE (440 vs. 8 min, respectively). Further, these IgE-antigen complexes induce Fc epsilon R expression in lymphoid cells more efficiently than IgE alone. Maximum levels of B cell Fc epsilon R were observed after a 24 h incubation with 1 microgram/ml IgE in the presence of 1 microgram/ml DNP-OVA, while 30 micrograms/ml monomeric IgE was needed to elicit a similar increase of Fc epsilon R expression. Most importantly, overnight incubation of B cell-enriched BALB/c spleen cells with IgE-antigen complexes resulted in an augmented membrane expression of class II MHC antigens. B cell surface expression of both I-A and I-E antigens responded to a comparable level after incubation with IgE-antigen complexes but did not occur in response to either IgE or antigen alone. The enhanced sIa expression occurred in parallel to IgE-antigen concentrations that gave rise to Fc epsilon R hyperexpression. Moreover, double staining for Fc epsilon R and surface Ia antigen shows that B cells exhibiting the highest density of Fc epsilon R also demonstrated the most surface I-A, suggesting that B lymphocytes are autonomous in their response to IgE-antigen complexes. Changes in class I MHC or sIgM were not observed after overnight incubation with IgE and antigen. These results demonstrate the importance of IgE-antigen complexes for intercellular signaling and further suggest that the IgE system plays a broader role in immune response than it has generally been credited.

Expression of neurotransmitter receptors and myc protooncogenes in subclones of a human neuroblastoma cell line.

Phenotypic variability of the human neuroblastoma cell line SK-N-SH was studied with the use of three subclones that interconvert at a slower rate than the parent cell line, i.e., a neuroblast-type subclone (SH-SY5Y), a nonneuronal, strongly substrate adherent subclone (SH-EP), and an intermediate type subclone (SH-IN). Rhodamine-phalloidin staining of actin fibers revealed differences in the cytoskeleton morphology of the three subclones, while the clathrin subunit proteins (heavy and light chains), components of coated vesicles, were invariant. Dramatic differences were observed for the expression of neurotransmitter systems, i.e., the mu and delta opioid receptor, the muscarinic cholinergic receptor and its effect on phosphatidylinositol turnover, and the uptake1 transporter for catecholamines. While these systems were strongly expressed in the parent line and the neuroblast-like clones SH-SY5Y and SH-IN, they were absent or barely detectable in the nonneuronal EP clone. Furthermore, the protooncogenes N- and c-myc were only expressed in the neuroblast containing lines, consistent with their growth characteristics of fully transformed cells. The strong c-myc expression in the absence of c- or N-myc amplification in SK-N-SH, adds a new form of high protooncogene activity in neuroblastoma cell lines. The remarkable differences of neurotransmitter systems and myc expression among the various phenotypes of human neuroblastoma cells should be considered in the therapy of neuroblastoma.

Biology and chemistry of low affinity IgE receptor (Fc epsilon RII/CD23).

Recent studies have established that the low affinity Fc receptor for IgE (Fc epsilon RII/CD23) is a structurally and functionally unique immunoglobulin receptor. DNA sequence analysis predicts that, in contrast to other FcR, Fc epsilon RII is not a member of the immunoglobulin gene superfamily and, indeed, is inserted into the membrane in opposite orientation from most other membrane proteins. While the Fc epsilon RII of macrophages, eosinophils, and platelets mediate IgE-dependent cytotoxicity and promote phagocytosis of IgE-antigen complexes, the function of Fc epsilon RII on B lymphocytes remains unclear. Much effort has been directed toward establishment of its role in IgE regulation, but the plurality of B cell Fc epsilon RII expression, i.e. greater than 90% of the mu + /delta + B lymphocytes, is incongruous with simply a role in regulating only IgE responses. Hence, the discovery that Fc epsilon RII is identical to the B-cell activation antigen, CD23, together with its novel structural features, suggests an additional more important role for this interesting protein and would explain the disparity between a commonly expressed receptor with apparently limited functions.

Early conversion for gangrenous cholecystitis: impact on outcome.

BACKGROUND: Early conversion from laparoscopic to open cholecystectomy for patients with gangrenous cholecystitis has been advocated. This study investigated the impact of early conversion on patient outcome. METHODS: Data from all patients with gangrenous cholecystitis undergoing laparoscopic cholecystectomy between 1992 and 2002 whose procedure had been converted to open surgery were prospectively collected and analyzed. Morbidity, length of stay, intensive care unit admission, and operative time served as outcome measures. RESULTS: Of the 97 patients in the study, 33 underwent conversion to open cholecystectomy. The conversion was early for 24% of the patients, after the initial dissection, for 33% and after an extended attempt at completion of the laparoscopic cholecystectomy for 37%. There was no difference in the overall morbidity among the groups, whereas the length of hospital stay appeared to be longer in the early conversion group. The operative time was significantly shorter after early conversion (p < 0.01, chi-square test). CONCLUSION: Laparoscopic cholecystectomy is not feasible for all patients with gangrenous cholecystitis. However, a concerted effort to perform the cholecystectomy with the minimally invasive approach does not have an adverse impact on patient outcome and is likely to benefit patients although it poses a moderate risk of conversion.

Open Rives-Stoppa ventral hernia repair made simple and successful but not for everyone.

BACKGROUND: The Rives-Stoppa (RS) repair of ventral incisional hernias (VIHR) is technically difficult. It involves the retromuscular placement of mesh anterior to the posterior fascia and the primary closure of the anterior fascia. Recurrence rates are 0-8%. We proposed that the operation could be done with equal success by placing the mesh in an intraperitoneal position and primarily closing the fascia anterior to the mesh. METHODS: 81 patients who had undergone an open RS-VIHR with intraperitoneal mesh were evaluated for hernia recurrence and factors associated with recurrence. RESULTS: 55 women and 26 men (mean BMI 38+/-9) underwent RS-VIHR (mean age 49+/-11 years). Of these patients, 44 (54%) had a prior VIHR, 30 (37%) had an incarcerated hernia and 34 (42%) had multiple fascial defects. PTFE was used in 83% and Prolene in 12%. Average LOS was 5.8+/-12 days. All received perioperative intravenous antibiotics and 28% were discharged on oral antibiotics. Follow-up averaged 30+/-24 months. Recurrent VIH developed in 12/81 (15%), with three occurring after removal of infected mesh and one after a laparotomy. Excluding these four, the recurrence rate was 10%. There was no correlation between hernia recurrence and age, BMI, hernia size, number of prior repairs, or LOS (t-test p>0.05). Hernia recurrence did not correlate with gender, prior peritoneal contamination, incarceration, multiple defects, adhesions, mesh type, oral antibiotics, cardiac disease, diabetes, tobacco use, or seroma (X(2) p>0.05). Those with a wound infection and/or abscess formation had a significantly higher recurrent hernia rate (60% vs. 8%, X(2) p<0.001). Patients with pulmonary disease had a significantly higher recurrence rate (50% vs. 12%, X(2) p=0.01). CONCLUSIONS: RS-VIHR with intraperitoneal mesh is a successful and less technically challenging method of repair than prior modifications. Aggressive efforts to identify infection and treat early may prevent abscess formation and subsequent recurrent hernia. Patients with chronic pulmonary disease have an unacceptably high recurrence rate and should not be considered as candidates for elective RS-VIHR.

Cigarette smoking and atherosclerosis in autopsied men.

The association of cigarette smoking and atherosclerorosis was investigated in 1320 autopsied men, 25--64 years of age. Aortic and coronary lesions were evaluated visually in coded specimens and objectively by analysis of radiographs. Using schedules that had been tested on pairs of living persons, interviewers obtained estimates of cigarette smoking habits of the deceased men from surviving relatives. Data were analysed for black and white men in the total sample of cases and also in groups according to the presence (selected disease group) or absence (basal group) of diseases thought to be associated with smoking (emphysema, lung cancer, etc.) or with coronary heart disease (myocardial infarction, hypertension, diabetes, stroke, etc.). Atherosclerotic involvement of aorta and coronary arteries was greatest in heavy smokers and least in nonsmokers for both races in the total sample of cases, the basal group and the selected disease group.

Individual cigarette usage: self-reported data as a function of respondent-reported data.

The interview method was used to collect data from living respondent-subject pairs regarding cigarette usage of the subject; the nonsmoker subject was explicitly not studied. Several different measures of usage were tested. The mean correlation coefficient between subject-reported data and the corresponding respondent-reported data was 0.86; that is, at least 70% of the variability in subject-reported data can be accounted for from information obtained from an appropriate living respondent closely associated with the subject. Selected regression equations are presented for estimating cigarette usage of a subject from data provided by a respondent.

Differential expression of VIP/PACAP receptor genes in breast, intestinal, and pancreatic cell lines.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are structurally-related neuropeptides that function as trophic factors in addition to their more classical roles as neurotransmitters. Binding and molecular cloning studies have shown that their actions are mediated by receptors encoded by at least three different genes. VIP binding has been demonstrated on many tumor types, and radiolabeled VIP has recently been used as a novel method to localize intestinal tumors in humans and their sites of metastasis. To determine the receptor subtype and level of gene expression, we screened breast, intestinal, and pancreatic, cell lines by Northern blot analysis. Breast lines expressed VIP/PACAP1 receptor mRNA levels comparable to intestinal lines, in agreement with the studies showing particularly high VIP binding in these tumors and their derived cell lines. Pancreatic cell lines expressed mRNA for several receptor types. This extends the potential utility of VIP and PACAP in the localization of tumors, and because VIP and PACAP may regulate the growth rate of some tumors by autocrine or other mechanisms, the identification of receptor subtypes on these lines sets the stage for studies in which the activity of these individual receptors in growth and other processes can be investigated.

Diabetes mellitus with hyperparathyroidism: another indication for parathyroidectomy?

BACKGROUND: Patients with hyperparathyroidism have alterations in carbohydrate metabolism characterized by insulin resistance, hyperinsulinemia, and glucose intolerance. The clinical significance of these findings in the management of patients with diabetes mellitus (DM) after parathyroidectomy for hyperparathyroidism has been controversial. METHODS: A retrospective review identified 87 patients with DM and hyperparathyroidism who underwent parathyroidectomy. The follow-up documentation of 70 patients who underwent diabetic management was then evaluated to assess the benefit of parathyroidectomy on glucose management. RESULTS: Thirteen patients had type 1 DM, and 74 patients had type 2 DM. Primary hyperparathyroidism was present in 93% of patients with type 2 DM; 64% of patients with type 1 DM had secondary hyperparathyroidism. At follow-up, glucose control was stable in 40% of patients, had improved in 37% of patients, and had deteriorated in 23% of patients (P = .003). Improved glucose control was not dependent on age, duration of DM, duration of hyperparathyroidism, length of follow-up, or calcium levels. The patients with decreased requirements had a significantly lower parathyroid hormone level (P = .05). Improved glucose control was most significant in patients whose condition was managed with oral hypoglycemics (P = .05) or insulin (P = .03). CONCLUSIONS: The clinical and laboratory investigations on the influence of hyperparathyroidism on DM support the benefit of parathyroidectomy in patients with DM. Patients with type 1 and type 2 DM show improvement in glucose control after parathyroidectomy. The presence of DM and hyperparathyroidism is an indication for parathyroidectomy because it results in either stabilization or improved glucose control in 77% of patients.

The rapid low-dose (1 microgram) cosyntropin test in the immediate postoperative period: results in elderly subjects after major abdominal surgery.

BACKGROUND: Recently the rapid low-dose (1 microgram) cosyntropin test has been found to be superior to the standard (250 micrograms) rapid cosyntropin test for evaluating the hypothalamic-pituitary-adrenal axis. Because the 1-microgram test has not been studied in postoperative patients, we evaluated the test after major abdominal surgery. METHODS: We performed rapid 1-microgram cosyntropin tests in 20 patients aged 65 years or older immediately and 24 hours after uncomplicated elective abdominal surgery (group A) and in 10 patients who were suspected of having adrenal insufficiency after abdominal surgery (group B). Subsequently, 250 micrograms of cosyntropin was infused over 8 hours on 2 successive days in group B patients. RESULTS: Ninety-five percent of group A patients had normal rapid 1-microgram cosyntropin test results immediately after surgery and 90% had normal test results 24 hours postoperatively. Six group B patients had abnormal rapid 1-microgram cosyntropin test results. Additional testing indicated primary adrenal insufficiency in 2 patients and central adrenal insufficiency in 1 patient; another patient probably had primary adrenal insufficiency and 2 patients appeared to be euadrenal. Four group B patients had normal rapid 1-microgram cosyntropin test results. After additional testing, 3 of these patients appeared to have normal adrenal function; 1 probably had primary adrenal insufficiency. CONCLUSION: The rapid 1-microgram cosyntropin test accurately evaluated adrenal gland function in selected patients after uncomplicated surgery. The test, however, was difficult to interpret in unselected seriously ill postoperative patients. Therefore we recommend that postoperative patients with unexplained hypotension or other features suggestive of adrenal insufficiency who have random plasma cortisol levels less than 20 micrograms/dL be treated with glucocorticoids and the hypothalamic-pituitary-adrenal axis be studied by standard tests after recovery.