Effects of two extracellular matrices on morphologic and biochemical properties of human type II cells in vitro

Previous observations have suggested that differentiated functions of adult rat type II alveolar cells are affected in part by cell-matrix interactions. We examined several aspects of differentiated adult human type II cells cultured on either bovine corneal endothelial cell extracellular matrix (BCECM) or matrix derived from the Englebreth-Holm-Swarm tumor (EHS). Compared to cells cultured on BCECM, adult human type II cells grown on EHS assumed a more cuboidal shape, had a more defined apical-basal polarity, and appeared to contain a greater number of lamellar bodies and neutral lipid inclusions. These cells also incorporated a greater percentage of [14C]acetate into saturated phosphatidylcholine (SPC) than did their counterparts grown on BCECM. In contrast, the relative incorporation of [14C]acetate into phosphatidylglycerol (PG) was lower in cells grown on EHS than cells cultured on BCECM. The histochemical stain for alkaline phosphatase was useful in identification of human type II cells. Alkaline phosphatase expression was elevated in cells cultured on EHS compared to those cultured on BCECM. These results suggest that maintenance of a differentiated morphology, lipid synthesis, and expression of alkaline phosphatase activity by primary cultures of adult human type II cells are also influenced by cell-matrix interactions. All markers of differentiated function of type II cells except synthesis of PG are better maintained on EHS than on BCECM. Under the conditions of these experiments, synthesis of SPC and PG appears to be independently regulated.     

Evidence of persistent viral infection in Menière's disease

Aspects of humoral and cell-mediated immunity that might characterize the continuation of symptoms in 25 patients with chronic Meniere's disease were examined. We found significant elevations of both humoral and cellular immune responses to viral antigens of herpes simplex I, varicella-zoster, rubella, and cytomegalovirus. Serum immunoglobulins were quantitatively abnormal in 24 of 25 patients, without a consistent pattern. These immune responses may be linked to persistent viral infection in chronic Meniere's disease.     

Albumin Adsorption and Retention on C18-Alkyl-Derivatized Polyurethane Vascular Grafts

The short-term albumin affinity and thrombo-resistance of a polyether polyurethane vascular graft have been improved. The method is based on the C18 alkylation of the polymer. Thrombus formation by a planimetric technique and albumin retention on wire-reinforced polyurethane tubes, both C18 alkylated and untreated, were measured in short-term (4-h) exposure at femoral arterial sites in the dog. 125I-Albumin was preabsorbed on tubes and then exposed to blood for successive 2-h periods. Albumin uptake on alkylated tubes prior to blood exposure and retention following 2 h of blood exposure were significantly greater than on controls. Following a fast desorption phase in blood, the remaining albumin was more slowly desorbed from alkylated than from control tubes. Reincubation with albumin and blood reexposure produced a similar tendency, suggesting blood conditioning does not reduce the albumin affinity-enhancing property of C18 alkylation in the short term. Blood-preconditioning experiments suggested endogenous albumin has a high affinity for the C18-alkylated surface. Scanning electron microscopic examination showed thrombus and platelet densities were higher on control than on alkylated surfaces. These results suggest in vivo albumin affinity is increased for C18-alkylated polyurethane, which may be linked to decreased thrombus formation on these surfaces.     

Neuropathological study 16 years after autologous adrenal medullary transplantation in a Parkinson's disease patient.

To date, there is no clinicopathological correlation of adrenal medullary transplant cases in patients with survival beyond a few years. Postmortem examination of a brain from a patient with Parkinson's disease (PD), 16 years after autologous adrenal medullary transplant, was performed using tyrosine hydroxylase (TH) and chromogranin A. The patient experienced a four-year initial improvement in motor function followed by resumption of the progressive nature of her disease that continued until her death. She expired 16 years following grafting. At autopsy, TH stain of the brain revealed severe loss of TH-immunoreactivity in the substantia nigra and Lewy bodies, confirming the diagnosis of PD. The transplant site was identified by the presence of scarring and there was complete absence of any TH staining cells at the site of the transplant. There were few surviving cells staining with chromogranin A. The absence of TH-staining cells in the transplant 16 years after surgery provides further evidence that adrenal medullary transplants do not survive in the long term.     

Sural nerve biopsies in Guillain-Barre syndrome: axonal degeneration and macrophage-associated demyelination and absence of cytomegalovirus genome.

T-cell infiltration was detected by immunohistochemistry in only 2 of 10 sural nerve biopsies from patients with Guillain-Barré syndrome (GBS). The number of endoneurial macrophages, identified by the monoclonal antibody MAC 387, was increased, compared with the number in 10 cases of axonal neuropathy. Macrophage-associated demyelination was identified in 7 and axonal degeneration in 8 cases. Cytomegalovirus (CMV) genome was not detected with the polymerase chain reaction.     

Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of individual follow-up and computerized record linkage using the Canadian Mortality Data Base

We compared two methods of ascertaining mortality in a historical prospective mortality study. Computerized Record Linkage (CRL) with the centralized historical Canadian Mortality Data Base (CMDB) was carried out on 2469 men and an attempt was also made to trace the subjects by individual follow-up (IFU). All but 88 were traced and 60 were reported to be dead. CRL was able to locate the deaths of three men who had been untraced by IFU. Contradictory information on vital status was obtained on 5 subjects--in 4 of them, the discrepancy was resolved in favour of CRL. Overall, CRL using the CMDB performed very well. We also consider factors that affect the relative costs of the two methods, which should be balanced against the accuracy of information obtained.     

Phase I study of epirubicin given on a weekly schedule

Epirubicin was studied in a phase I setting to find the maximum tolerated dose when given weekly for 3 of 4 weeks. Forty-one evaluable patients were treated in groups at doses increasing from 20 to 45 mg/m2. The highest dose level produced the maximum degree of myelosuppression (lowest neutrophil count, 1.9 X 10(9)/L; range, 0-3.7) recorded on Day 22. This was well-tolerated in this group of mainly pretreated patients. Nonhematologic side effects were minimal. This dose schedule allows a greater dose per unit time to be administered than other recommended schedules for epirubicin.