The novel carbohydrate tumor antigen C2-O-sLe x is upregulated in canine gastric carcinomas.

Sialyl Lewis x-modified core 2 branched O-glycans (C2-O-sLe(x)) on human leukocytes mediate much higher-affinity adhesion to selectins on activated vascular endothelium than does sialyl Lewis x on other structures. In some canine and human carcinomas, high expression of sLe(x)-decorated carbohydrates has been associated with metastasis and, in humans, a poor prognosis, but detection in canine gastric carcinomas is unreported. The authors hypothesized that these carbohydrates are highly expressed in more malignant types of canine gastric carcinomas, they promote metastasis, and they are associated with a poorer prognosis for dogs. The objectives were to determine the presence and importance of C2-O-sLe(x) expression in canine gastric carcinomas. Routine histological sections of 16 canine gastric carcinomas were categorized on the basis of 3 classification schemes: World Health Organization, Lauren, and Goseki. Serial sections were stained with antibodies directed against C2-O-sLe(x) (CHO-131 monoclonal antibody), cytokeratin (Lu-5 monoclonal antibody), and stains to detect neutral and acid mucins (periodic acid-Schiff and alcian blue). Whereas normal gastric mucosal epithelial cells were negative for C2-O-sLe(x), 56% of the tumors examined were positive for C2-O-sLe(x). Importantly, the majority of more poorly differentiated tumor types had more numerous and larger intensely stained areas of C2-O-sLe(x) expression compared with moderate to well-differentiated tumor types. Signet ring-type carcinomas had markedly higher distribution and intensity of periodic acid-Schiff and alcian blue staining than did tubular carcinomas. These findings suggest that C2-O-sLe(x) is a tumor-associated antigen that may play a role in the invasiveness and metastatic potential of certain types of canine gastric carcinomas.

Viral pathogenesis in chicken embryos and tumor induction in chickens after in ovo exposure to serotype 1 Marek's disease virus.

We examined the susceptibility of late-stage chicken embryos to infection with oncogenic serotype 1 Marek's disease virus (MDV 1). Intravenous inoculation of MDV 1 at embryonic day (ED) 16 resulted in significant replication of the virus in embryonic tissues. Within 5 days of virus exposure, pp38 viral antigen (pp38) was detected in embryonic bursae and MDV 1 was isolated by plaque assay from the spleens, thymuses, and bursae of embryos. The pathogenesis of MDV 1 after intravenous inoculation at ED 16 was similar to that in chicks exposed to MDV 1 after hatching. In contrast to the response of the embryo to intravenous inoculation, embryos exposed to MDV 1 by the amniotic route did not develop detectable pp38, nor could the virus be isolated from the embryonic tissues by plaque assay. These results show that the route of inoculation of MDV 1 in the embryos is critical for allowing the virus to come in contact with target cells.

Response of embryonic chicken lymphocytes to in ovo exposure to lymphotropic viruses.

OBJECTIVE: To examine effects of virus exposure on embryonic lymphoid organ structure, apoptosis, and lymphoid cell subpopulations. ANIMALS: Eggs of specific pathogen free (SPF) White Leghorn chickens at embryonation day (ED) 17. PROCEDURES: Eggs were inoculated with 2,000 plaque-forming units (PFU) of serotype 1 herpesvirus (Marek's disease virus [MDV 1]), 2,000 PFU of herpesvirus of turkeys (MDV 3), or 1,000 embryo infectious doses (EID50) of infectious bursal disease virus (IBDV). On post-inoculation days (PID) 3 and 5, lymphoid organ to body weight ratios were determined, and bursa of Fabricius, thymus, and spleen were evaluated for lesions and apoptosis. Proportions of lymphoid cell subpopulations of PID-3 chicken embryos and 7- to 10-day-old chicks were quantitated by flow cytometry. RESULTS: Lymphoid organ weights were similar in virus-free, MDV1, and IBDV groups. Embryos inoculated with 2,000 PFU MDV 3/egg had lower bursal weights than virus-free controls. In a repeated trial, MDV 3 (1,000 PFU to 4,000 PFU) did not reduce bursal weights among groups. Histologic changes were seen in bursae after MDV 1 and IBDV inoculation. Apoptosis was greater in bursae of MDV 1-infected embryos than controls. Lymphoid cell subpopulations were similar among all groups with the exception of CD8+ and IgM+ cells in spleens of IBDV-infected 10-day-old chicks. CONCLUSIONS AND CLINICAL RELEVANCE: Infection with pathogenic strains of MDV 1 and IBDV did not alter lymphocyte subpopulations in embryos or cause complete destruction of lymphoid organs. Changes in lymphoid cell subpopulations exposed as embryos to IBDV were seen only after hatching.

In ovo vaccination of specific-pathogen-free chickens with vaccines containing multiple agents.

We used in ovo technology to protect chickens against multiple diseases by inoculating vaccines containing mixtures of live viral agents. A single in ovo injection of a vaccine containing serotypes 1, 2, and 3 of Marek's disease virus (MDV), a vaccine strain of serotype 1 infectious bursal disease virus (IBDV), and recombinant fowl pox vaccine with HN and F genes of Newcastle disease virus (rFP-NDV) induced protection against virulent MDV, IBDV, Newcastle disease virus, and fowl poxvirus. The multiple-agent vaccine induced specific antibodies against the viral agents present in the mixture and did not adversely affect the survival of hatched chickens. Inoculation of a vaccine containing serotypes 1, 2, and 3 of MDV and IBDV did not affect hatchability of eggs, although the addition of rFP-NDV to the mixture reduced hatchability by 23%-26%. In ovo vaccination with a vaccine containing MDV and IBDV vaccine viruses did not exacerbate the inhibitory effect of individual viral agents on humoral and cellular immune competence.

A histological analysis of the early effects of alcohol and tobacco usage on human lingual epithelium.

Macroscopically normal tongues were examined from 161 necropsies. Two types of lingual epithelium were investigated by morphometry and the results were statistically analysed in relation to known levels of alcohol and tobacco usage in each case. Alcohol and tobacco were each associated with a reduction in epithelial thickness brought about by a reduction in the maturation layer due mainly to cell shrinkage. By contrast, the progenitor layer increased in size, due to hypertrophy rather than hyperplasia. Changes occurred in each type of epithelium and were more severe with alcohol. There was no significant interaction between alcohol and tobacco. The structural changes appeared to be non-specific reactions to local toxic effects of alcohol and tobacco. They could, if accompanied by equivalent functional decrements, indicate an increased vulnerability to carcinogens, whether or not these derive from alcoholic drinks or tobacco smoke.

Morphometric analysis of atrophic changes in human lingual epithelium in iron deficiency anaemia.

A stereological analysis of epithelial structure at the lateral surface of the tongue showed that iron deficiency anaemia was associated with reduced epithelial thickness despite the absence of overt mucosal abnormalities. The epithelial atrophy was entirely due to a reduction in the size and number of cells in the maturation compartment. By contrast, the progenitor cell compartment was increased in thickness due to an increase in the number of cells. This hyperplastic reaction may be a trophic response to the overall loss of epithelium in this condition.

The biochemistry of vitreous humour. A comparative study of the potassium, sodium and urate concentrations in the eyes at identical time intervals after death.

Analysis of the vitreous humour from an individual's eyes collected at the same time since death showed variation between the eyes in the concentration of potassium, sodium and/or urate. This previously unreported finding would limit the use of measuring these electrolytes in determining the time of death.

The biochemical changes in pericardial fluid after death. An investigation of the relationship between the time since death and the rise or fall in electrolyte and enzyme concentrations and their possible usefulness in determining the time of death.

This paper reports the biochemical changes that occur in pericardial fluid after death. Significant changes in relation to the time since death occurred in potassium, sodium, phosphate, protein and several commonly measured enzymes. The variation in individual results at similar times since death would limit the use of pericardial fluid biochemistry in determining the time of death.

A quantitative histological analysis of the effects of age and sex on human lingual epithelium.

After exclusion criteria had eliminated changes of pathological origin, tongues were obtained from 86 necropsies evenly divided by sex and age from 16-98 years. Epithelium was examined from two precisely defined sites on the lateral and dorsal lingual surfaces. Morphometric techniques were employed to determine various epithelial parameters. The epithelium was thicker in males but rates of ageing change between the sexes were similar. Generally, age changes were similar at each site: the mean epithelial thickness underwent a 30% reduction over the age range studied; the progenitor cell layer remained of constant thickness but its nuclear/cytoplasm ratio reduced significantly; significant reductions also occurred in the rete surface area of the lateral epithelium and in the papillary surface area of the dorsal epithelium. Although some of the parameters showed steeper rates of change in the younger half of the age range, the overall pattern of ageing in the lingual epithelium suggested a continuous trend towards atrophy and simplification of structure occurring evenly throughout the entire adult life span.

Do plasma glycoproteins induce lymphocyte hyporesponsiveness and insulin resistance?

Depression of lymphocyte transformation and an increase in insulin resistance are common to pregnancy, oral contraceptive use, widespread malignancy, infection, and tissue destruction. We suggest that these abnormalities are caused by a rise in the plasma-glycoprotein level which is also common to these clinical states. There is evidence that glycoproteins can inhibit cell division, lymphocyte transformation, and the action of hormones on target cells. Because of the increase in plasma glycoprotein the cells in many organs and their hormone receptors may have a thicker coating of glycoproteins which blunts their response to variuos stimuli.

New approach to organ transplantation based on the fetal allograft.

A new approach to organ transplantation that may be particularly applicable to kidney transplantation is suggested by analogy with the immunological mechanism responsible for the survival of the fetal allograft. The method concerns identifying donor-recipient tissue compatibility by use of the two-way mixed lymphocyte reaction (MLR), in which reacting cells from patients awaiting transplants are primed with phytohaemagglutinin (PHA) and stored. When a donor becomes available, these PHA-primed cells may then be tested against donor lymphocytes, possibly giving a result within 36 hours. Immunosuppressive agents occurring naturally in pregnancy, such as alpha-fetoprotein and chorionic gonadotrophin, may eventually replace standard immunosuppressive treatment with potentially toxic regimens in transplant recipients. If the results of the two-way MLR using PHA-primed cells are shown to be comparable to those of the standard two-way MLR graft survival may be successful in 80% of cases.

Feto-maternal bidirectional mixed lymphocyte reaction and survival of fetal allograft.

Maternal and fetal lymphocytes were tolerant of each other in the bidirectional mixed lymphocyte reaction. This seems to be the principal reason why the mother does not reject the fetal allograft. Tolerance between maternal and fetal cells must be largely due to a genetic mechanism, because the bidirectional mixed lymphocyte reaction between parents and older children was much reduced compared with that between randomly selected pairs of controls. This weak reaction disappeared when immunosuppressive agents were given to one member of the parent/child pair, whereas the mixed lymphocyte reaction between unrelated individuals was not abolished by similar immunosuppression. It is suggested that this genetic mechanism is distinct from the HLA system. Tolerance between maternal and fetal cells was not demonstrated in the unidirectional mixed lymphocyte reaction, suggesting that this tolerance requires the viability of the two cell populations.

Immunological responses in pregnancy and survival of fetal homograft.

Immunological responses were studied in pregnant women and controls using as tests phytohaemagglutinin-induced lymphocyte transformation and the tuberculin reaction. Significantly reduced responses were found to both tests in the pregnant women. These results suggest that a reduction in T-cell activity during pregnancy may help protect the fetus from rejection by its mother's immunological mechanisms.