B lymphoblastoid cell lines with normal and defective O-glycosylation established from an individual with blood group Tn

Individuals with the Tn blood group contain terminal serine/threonine- linked N-acetylgalactosamine residues in their blood cells. This is due to lack of UDP-D-galactose: D-N-acetyl galactosamine beta-D-galactosyl transferase from part of their red cells and probably from their leukocytes. We have established B lymphoblastoid cell lines from such an individual by in vitro infection of his lymphocytes with Epstein- Barr virus. The original line contained a mixture of cells reactive and nonreactive with Helix pomatia lectin (Hp). These cells were subcloned after staining with fluorescent Hp by a fluorescence-activated cell sorter (FACS) into homogeneous, phenotypically stable lines of Hp- positive (Hp+) and Hp-negative (Hp-) cells. The molecular differences between the membrane glycoproteins were characterized by carbohydrate- specific surface labeling techniques, Hp affinity chromatography, polyacrylamide slab gel electrophoresis and glycopeptide/oligosaccharide analysis. The major O-glycosidic membrane glycoprotein (GP105) was retained on Hp-Sepharose columns only from Hp+ cells, whereas the common leukocyte antigen (GP160-200) was partially retained on Hp columns from both lines. These proteins were isolated by immune precipitation with monoclonal antibodies and characterized. The results show that the GP105 glycoprotein from Hp+ cells contains terminal N-acetylgalactosamine residues but also more complex oligosaccharides. The common leukocyte antigen showed different electrophoretic mobilities in Hp+ and Hp- cells. UDP-galactose D-N- acetyl galactosamine beta-galactosyl transferase was almost absent in the Hp+ cells. These cell lines are useful for studies on the functional role and regulation of the biosynthesis of O-glycosidic carbohydrates.     

Unplanned admission after day surgery: A historical cohort study in patients with obstructive sleep apnea

Purpose

Practice guidelines suggest that patients with obstructive sleep apnea (OSA) should be monitored postoperatively to reduce adverse events. This study evaluated outcomes following ambulatory surgery in patients who had previously undergone polysomnography (PSG), and compared unplanned admissions in patients diagnosed with OSA with those in patients without OSA.

Methods

A historical cohort study (July 2003 to March 2009) was conducted using administrative data and supplemented by selective chart review. Patients undergoing ambulatory surgery at the Ottawa Hospital who had a previously documented PSG were identified. The PSG reports were reviewed, and the presence and severity of OSA was determined. Unplanned admissions to hospital within seven days of surgery were identified using administrative data. Using a nested case-control design, three charts were randomly selected for each patient admitted for a focussed health records review. Event rates in patients with OSA and treated with continuous airway pressure were compared with event rates in patients without OSA. An exploratory multivariable analysis was conducted to identify predictors of admission.

Results

There were 77,809 ambulatory surgical procedures in the period studied. A PSG test could be analyzed in 1,547 patients, and OSA was diagnosed in 674 (44%) of those analyzed. The rate of unplanned admission was 7.0% (95% confidence interval [CI] 5.1 to 8.9) in OSA patients compared with 5.6% (95% CI 4.1 to 7.1) in patients without OSA (odds ratio 1.26; 95% CI 0.83 to 1.91; P = 0.246). Median [interquartile range; IQR] hospital length of stay was 7 hr [IQR 5, 8] with OSA and 6 hr [IQR 5, 8] without OSA (P = 0.058). Severity of OSA was not associated with unplanned admission.

Conclusions

We did not identify a clinically important increased rate of unplanned admission associated with a prior diagnosis of OSA.     

Beta-adrenoceptors on lymphocytes of patients with major depressive disorder

3H-Dihydroalprenolol binding to lymphocyte membranes of patients with primary, unipolar major depressive disorder was compared to that of a normal, healthy control population. No significant difference could be demonstrated between the Kd values of the two different groups, but the Bmax values of the depressed patients were significantly lower than those of the controls. Positive correlations were observed between the lymphocyte beta-adrenoceptor Bmax values of the patients and their Beck self-evaluation and Hamilton depression ratings. We propose that decreased lymphocyte beta-adrenoceptor Bmax values may be used as a biological marker for major depressive disorder.     

Imipramine binding sites on platelets of patients with major depressive disorder

3H-Imipramine binding to platelets of patients with primary, unipolar major depressive disorder was investigated and compared to that of a normal, healthy control population. No significant differences could be demonstrated between either the Kd or the Bmax values of the two groups. A negative correlation was observed between imipramine Bmax values and the Hamilton anxiety ratings of the depressed patients. Patients who displayed psychomotor retardation tended to have lower platelet imipramine Bmax values than patients with psychomotor agitation. It is suggested that platelet imipramine Bmax values may be a biological marker for subtypes of depression.     

Alpha 2-adrenoceptor levels on platelets of patients with major depressive disorders

3H-p-Aminoclonidine binding to platelets of patients with primary, unipolar major depressive disorder was compared to that of a normal healthy control population. The variances of platelet alpha 2-adrenoceptor Kd and Bmax values in patients were significantly greater than in the control group. No significant difference could be demonstrated between the Kd values of the two different groups, but the Bmax value of the depressed group was significantly lower than that of controls. We propose that an abnormal platelet alpha 2-adrenoceptor density may be used as a biological marker for major depressive disorder.     

Genetic differences in the endocrine responses to the thyrotrophin-releasing hormone stimulation test in patients with a major depressive episode

The thyrotrophin-releasing hormone (TRH) stimulation test is becoming useful in the diagnosis of depression, but the optimum concentration of TRH required remains uncertain. The test was performed on a carefully selected group of patients with primary unipolar major depressive episodes with melancholia, who were severely depressed, using TRH 200 micrograms and 500 micrograms (groups 1 and 2). The thyroid-stimulating hormone (TSH), growth hormone (GH) and prolactin (PRL) levels were measured in response to TRH. Responses obtained were compared with respect to hormonal and genetic subgroups. Comparing groups 1 and 2 revealed significant differences in the GH responses (P = 0,0059). A similar significant difference was found in the GH response (P = 0,0102) elicited by the women in each group. Comparison of the genetic subgroups of groups 1 and 2 revealed a significant difference in the PRL response of both the genetic spectrum (P = 0,0258) and the group without a genetic history (P = 0,0259) of alcoholism or depression. The TSH response in the genetic spectrum group was also significantly higher (P = 0,0008) in group 2. Further investigations of the responses elicited in the different genetic subgroups may reveal important variables for the investigation of the pathogenesis of depression.     

Heterogeneity of glomerular size in normal donor kidneys: impact of race

Glomerular size has been the subject of many studies and, in a number of settings, has a direct association with the development of glomerular sclerosis. However, the normal distribution of glomerular size has not been thoroughly evaluated in the general population in the United States. To address this issue, we analyzed the baseline biopsy specimens of 103 human donor kidneys to determine the maximal planar area (MPA) of the glomerular tuft in a heterogeneous human population. The MPA of each glomerulus was determined by measurement of sections through the vascular pole and/or origin of the proximal tubule, and was determined on each section by two methods: point counting and computer planimetry. There was very high agreement between these two methods. Multivariate analysis was used to identify significant correlates with MPA. Overall, younger donors had smaller glomeruli (P < 0.0001). Black donors had a larger MPA (23.4+/-8.6 mm2 x 10(-3)) than white donors (17.9+/-6.7 mm2 x 10(-3); P < 0.001), independent of donor age. MPA was not significantly different between genders. This heterogeneity in glomerular size may confound clinical studies if not recognized and may help explain differences in glomerular structure and function in response to injurious processes.     

Aetiology of pulmonary dysfunction in total hip replacement operations. The influence of nifedipine on the factors involved

Patients undergoing total hip replacement surgery who developed pulmonary dysfunction (PD) demonstrated evidence of complement activation and increased thromboxane A2 (TXA2) synthesis. In a double-blind study nifedipine (Adalat; Bayer-Miles) was shown to inhibit complement activation and TXA2 synthesis and thus appears to offer protection against PD.