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Biomedical subjects

W A Bye

Publications and source records attributed to W A Bye.

7 recordsLinked to original sources

Randomised controlled trial of recombinant human interferon -alpha A for chronic active hepatitis B.

The efficacy of interferon treatment for Australian patients with chronic active hepatitis B (CAH-B) was assessed by a three-centre randomised controlled trial in Sydney and Brisbane. Thirty patients (29 with histologically-proven CAH-B with and without cirrhosis and one with chronic persistent hepatitis) were allocated to receive either thrice weekly intramuscular injections of recombinant human leucocyte interferon -alpha A (either 2.5, 5.0 or 10.0 million units/m2) for six months followed by 12 months of observation, or to be observed for 18 months without active treatment. Three of 23 treated patients but none of seven controls underwent clinical, biochemical and histological resolution of their disease with loss of HBsAg, HBeAg and HBV-DNA from serum. An additional six treated and two control patients underwent a sustained partial remission of their disease. This was characterised by resolution of symptoms and serum aminotransferase abnormalities in association with seroconversion from HBeAg positive to negative, loss of HBV-DNA from serum but persistent hepatitis B surface antigenaemia. In such patients, there was significant improvement in histological appearances but some necroinflammatory activity remained and fibrosis was unchanged. Although total response rates were similar in treated and control subjects, they appeared to occur earlier after interferon treatment. Treatment with interferon was associated with predictable but minor side effects that usually did not necessitate dose reduction and rarely compromised the patient's life style. Interferon is thus a feasible treatment for CAH-B. Complete responses occurred only in treated patients and partial responses appeared to occur earlier in treated than in untreated patients. However, differences in the partial response rate at 18 months were not significant and seroconversion from HBeAg positive to negative was not associated with complete histological resolution of disease activity. Hence, while interferon is a promising agent for treatment of CAH-B, efforts must continue to define more optimal treatment regimes and to identify those patients most likely to respond to this agent.

Adult↗

Acute diarrhoea in adults: a prospective study.

A prospective study of 74 adults with acute diarrhoea was carried out in Sydney in 1984-1985 to determine the infective agents that were involved and their relationship to clinical, epidemiological and laboratory features. Thirty-four potential pathogens were identified in 32 (43.2%) patients. These included, in order of frequency: Campylobacter spp., rotavirus, Clostridium difficile, Salmonella enteritidis, Aeromonas hydrophila, Vibrio parahaemolyticus, adenovirus, a small round virus and Giardia lamblia. A seasonal trend was noted; the majority of Campylobacter isolations occurred in summer. The patients with Cl. difficile infection formed a distinct group, and experienced a subacute onset of diarrhoea after antibiotic administration, with few systemic symptoms. Except in these patients, the clinical and epidemiological features, together with results of faecal microscopy, were not a reliable predictor of the nature of the pathogens that were identified. While most patients with diarrhoea can be treated supportively, stool culture is an important procedure in patients with severe or protracted illness when specific antimicrobial therapy is contemplated.

Acute Disease↗

The membranous epithelial (M) cell and the mucosal immune system.

Membranous epithelial (M) cells are specialized epithelial cells overlying the subepithelial lymphoid follicles in the gastrointestinal and respiratory tracts. Antigens, including some viruses and bacteria, penetrate the mucosal barrier via the M cell, which endocytoses and transports antigens and microorganisms into the Peyer's patch or bronchial-associated lymphoid tissue. Here antigens may initiate an immune response and/or disseminate and induce disease. This review discusses the structure and function of the M cell, its role in macromolecular uptake, and its interaction with the immune system.

Animals↗

Structural features of and cholesterol distribution in M-cell membranes in guinea pig, rat, and mouse Peyer's patches.

Evidence suggests that M cells, which are antigen-sampling epithelial cells that overlie the domes of Peyer's patches, have an apical plasma membrane that differs from that of absorptive cells. We examined the structural features of rat, mouse, and guinea pig M-cell apical membranes and compared them with those of dome and villus absorptive cell apical membranes using electron microscopy of thin sections and freeze-fracture replicas. We also determined the distribution of morphologically detectable cholesterol in M-cell plasma and intracellular membranes in dome epithelium exposed to the polyene antibiotic, filipin. The areal density of P-face intramembrane particles was significantly less on M-cell microvilli than on microvilli of dome absorptive cells and villus absorptive cells. Areal densities of E-face intramembrane particles were similar on M-cell and absorptive-cell microvilli. M-cell apical plasma membranes were rich in cholesterol, displaying numerous filipin-induced membrane lesions in thin sections and freeze-fracture replicas. In contrast, apical membrane endocytic pits and coated vesicles in M cells failed to show filipin-induced membrane lesions. These findings suggest that, compared with the apical membranes of absorptive cells, those of M cells have a low protein to lipid ratio and an abundance of morphologically detectable cholesterol except in domains involved in endocytosis. Additionally, a subpopulation of dome epithelial cells displayed distinctive tight junctions with high strand counts and unusual depth. Although the cell type associated with these modified tight junctions could not be identified with certainty, their interspecies frequency paralleled the interspecies frequency of M cells in dome epithelium. These expanded tight junctions may result from physical tension caused by epithelial shape changes induced by intraepithelial lymphoid trafficking or, alternatively, may help buttress M cells that have attenuated cytoplasmic processes due to the presence of central hollows.

Animals↗

Structure, distribution, and origin of M cells in Peyer's patches of mouse ileum.

The derivation of membranous epithelial (M) cells, which are specialized antigen sampling cells overlying the lymphoid follicles of Peyer's patches, is unknown; it has been suggested recently, however, that M cells differentiate from absorptive cells on the follicular epithelium. To examine whether M cells, like other intestinal epithelial cells, derive directly from undifferentiated crypt cells, we studied the structure, selected functional features, proliferation, and distribution of Peyer's patch M cells in the ileum of adult mice. We observed a spectrum of M-cell structure ranging from mature to immature-appearing M cells. Most immature-appearing M cells lacked the central cytoplasmic hollow found in those mature M cells that contained lymphoid cells. The microvilli of immature-appearing M cells were more numerous and regular appearing than those of mature M cells, but they were sparser and shorter, and some were wider than those of absorptive cells. Many immature-appearing M cells contained more free ribosomes than did mature M cells. Both mature and immature-appearing M cells were observed on all regions of follicular domes, including the base near the mouths of surrounding crypts. Type 1 reovirions adhered with considerable selectivity to the apical membrane of mature and immature-appearing M cells but were observed in endocytic vesicles only in mature M cells. Neither mature nor immature-appearing M cells showed evidence of lipid absorption, in contrast to adjacent absorptive cells. Both mature and immature-appearing M cells internalized more bound cationized ferritin than did absorptive cells. Only mature M cells transported cationized ferritin to the intercellular spaces. Nuclei of a few immature-appearing M cells were labeled 24 h after injection of [3H]thymidine in concert with the appearance of labeled absorptive cell nuclei. These observations strongly suggest that many, if not all, M cells derive directly from undifferentiated crypt cells.

Animals↗