Clear cell adenocarcinoma of the vagina and cervix: incidence, undetected disease, and diethylstilbestrol

We conducted an incidence study to determine the occurrence rates of clear cell adenocarcinoma (CCAC) of the vagina and cervix in young women (born in 1940 and thereafter), and a case-series analysis, focusing on the maternal history of pregnancy and delivery and in-utero exposure to diethylstilbestrol (DES). Overall, 10 cases of CCAC had been listed in the files of the Connecticut State Tumor Registry prior to the study, and each of the 10 cases were confirmed as valid. In addition, another 10 cases, all previously undetected, were found after the tissue slides of young women listed as having other cancers of the vagina and cervix were reviewed by expert pathologists, suggesting that prior estimates of the incidence rate for CCAC must be misleading unless special efforts are taken to identify undetected cases. The incidence rates of vaginal CCAC (11 cases total) were highest in 1975-1979, and decreased slightly during 1980-1982. In the cervix (nine cases total), the rate increased consistently since 1970. History of in-utero exposure to diethylstilbestrol was obtained for five of eight vaginal cases and four of eight cervical cases of CCAC. In all nine cases, exposure to diethylstilbestrol was associated with a history of bleeding during the pregnancy or prior miscarriage. We conclude that the finding of stable (or rising) incidence rates for CCAC occurring nearly 30 years after the marked decrease in diethylstilbestrol sales emphasizes the need for continued clinical and epidemiologic studies of the etiology and clinical course of CCAC.     

Self-limited autoimmune disease related to transient donor B cell activation in mice neonatally injected with semi-allogeneic F1 cells.

BALB/c mice injected at birth with 10(8) semi-allogeneic (C57BL/6 x BALB.IgHb)F1 spleen cells develop a lupus-like syndrome in which autoantibodies bear exclusively the donor allotype. We have analyzed the evolution of donor B cell chimerism and the autoimmune manifestations during the first year of life in these mice. Anti-DNA, -histone, and -cardiolipin IgG antibodies as well as circulating immune complexes appeared in the second week of life, reached the highest values around the sixth week, and then progressively dropped to normal values after the sixth month in most mice. The kinetics of the evolution of the autoimmune manifestations, as well as the kinetics of serum donor Ig allotype, were parallel to the kinetics of donor B cell chimerism, which was particularly prominent in the spleens in early weeks of life, and progressively decreased after remission of the autoimmune syndrome. Membrane-proliferative glomerulonephritis, which was followed as the more representative histological abnormality in this model, was particularly evident after 10 weeks of life, but disappeared by the end of the follow-up. Interestingly, when mice with a self-limited disease were re-injected with 10(8) F1 spleen cells i.v., a flare in the serological manifestations was observed. In these re-injected mice a predominance of anti-DNA, IgG1 antibodies bearing exclusively the donor allotype was also observed, as in the early weeks of life.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-grade angiosarcoma of the skin of the breast: a complication of lumpectomy and radiation therapy for breast carcinoma.

A case of low-grade angiosarcoma arising in the skin of a breast previously irradiated for breast carcinoma is reported. Initially, an asymptomatic breast mass was detected. Excisional biopsy and axillary lymph node dissection revealed a 1.5-cm infiltrating ductal carcinoma with 21 negative lymph nodes. The neoplasm was staged as T1, N0, M0. The patient was entered in a research protocol and was treated with high-dose external beam (4,860 rad) and iridium implant (1,860 rad) irradiation. Seven years later the patient developed low-grade angiosarcoma of the breast skin. The lesion recurred following excision and eventually was treated by simple mastectomy. The patient never had evidence of lymphedema. Cutaneous angiosarcomas occurring as a complication of lumpectomy and radiation therapy for breast carcinoma are rare. In some reported cases the patients have had lymphedema, a known factor predisposing to angiosarcoma. Furthermore, almost all cases previously reported have been high grade. This case suggests that radiation therapy for breast carcinoma may also be complicated by low-grade angiosarcoma.     

HLA-B44 subtyping in a Spanish population: further evidence of Caucasian population diversity

HLA-B44 is the most frequent HLA-B allele in Caucasian populations. Several B44 subtypes, B*4402-B*4406, have been identified in individuals with this ethnic origin. Mismatches among B44 subtypes have been described as major targets for allogeneic responses in bone marrow transplantation. We have developed a PCR-SSO method, based on a B12- specific DNA amplification of exon 2 through exon 3 and subsequent non radioactive hybridization with eight probes, which allow us to discriminate all B12 homozygous combinations. We applied this method to determine the frequency of B44 subtypes in a Spanish population, as well as their HLA-A.-C.-DRB1,-DRB3/DRB4/DRB5.-DQA1 and -DQB1 associated haplotypes. A total of 141 healthy unrelated Spanish individuals and 31 B44-bearing haplotypes were investigated. Four B44 alleles were identified, B*4402 (33%), B*4403 (66%), B*4404 (0.7%), and B*4405 (0.7%). Haplotype analysis showed a clear differentiated distribution pattern for the two major B44 subtypes. B*4402 is associated with Cw5 (11/13) and A2 antigens (10/13). In contrast, B*4403 is mainly found together with DRB1*0701 (14/16). An inverted B*4402/B*4403 frequency in comparison with other European and North American Caucasian populations, revealed the existence of an extended haplotype diversity between populations of the same ethnic origin. Apart from anthropological studies, high resolution typing for HLA class I antigens presenting molecular polymorphism will be of great relevance in unrelated bone marrow transplantation.     

Lymph node infarction – a rare complication associated with disseminated intra vascular coagulation in a case of dengue fever

Background  

Lymph node infarction is known to occur in association with many non-neoplastic and neoplastic conditions however its occurrence in association with DIC is not reported hitherto in the literature.     

Differential effect of the autoimmune Yaa and lpr genes on the acceleration of lupus-like syndrome in MRL/MpJ mice

The Yaa gene (Y chromosome-linked autoimmune acceleration), linked to the BXSB/MpJ Y chromosome, and the autosomal recessive lpr (lymphoproliferation) gene have been shown to accelerate the progression of the lupus-like autoimmune syndrome in the BXSB and MRL strains, respectively. To compare more directly the role of the Yaa and lpr genes in the development of the autoimmune syndrome, the Y chromosome of BXSB mice was transferred to MRL mice by backcross procedures, and the effect of the Yaa gene on the autoantibody formation and the development of lupus-like nephritis in MRL mice was investigated in comparison with those bearing the lpr mutation. The Yaa gene as well as the lpr gene were able to shorten the life span of MRL mice as a result of the accelerated development of lethal lupus-like nephritis. However, the acceleration promoted by the Yaa gene (50% mortality rate: 12 months) was less severe than that induced by the lpr gene (50% mortality rate: 7 months). This may be related to the finding that the lpr gene enhanced the production of a large spectrum of autoantibodies, including anti-DNA, rheumatoid factors and anti-gp70, and of cryoglobulins, whereas only anti-gp70 production among the autoantibodies studies was markedly enhanced by the Yaa gene. The selective autoimmune accelerating effect of the Yaa gene was similarly observed in (NZW X MRL)F1 hybrid mice. Our results suggest that the Yaa gene, unlike the lpr gene, exhibits selective autoimmune accelerating activity, but as a result of increased formation of certain nephritogenic autoantibodies such as anti-gp70 antibodies, the Yaa gene is able to accelerate the progression of lupus-like nephritis in lupus-prone mice.     

A type III secretion system is required for Aeromonas hydrophila AH-1 pathogenesis

Aeromonas hydrophila is a gram-negative opportunistic pathogen in fish and humans. Many bacterial pathogens of animals and plants have been shown to inject anti-host virulence determinants into the hosts via a type III secretion system (TTSS). Degenerate primers based on lcrD family genes that are present in every known TTSS allowed us to locate the TTSS gene cluster in A. hydrophila AH-1. A series of genome walking steps helped in the identification of 25 open reading frames that encode proteins homologous to those in TTSSs in other bacteria. PCR-based analysis showed the presence of lcrD homologs (ascV) in all of the 33 strains of A. hydrophila isolated from various sources. Insertional inactivation of two of the TTSS genes (aopB and aopD) led to decreased cytotoxicity in carp epithelial cells, increased phagocytosis, and reduced virulence in blue gourami. These results show that a TTSS is required for A. hydrophila pathogenesis. This is the first report of sequencing and characterization of TTSS gene clusters from A. hydrophila. The TTSS identified here may help in developing suitable vaccines as well as in further understanding of the pathogenesis of A. hydrophila.     

CD4+ T cells determine the ability of spleen cells from F1 hybrid mice to induce neonatal tolerance to alloantigens and autoimmunity in parental mice

Spleen cells from F₁ hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding alloantigens. However, these mice develop a transient autoimmune syndrome characterized by the production of multiple autoantibodies and glomerulonephritis. Previous reports indicated that the depletion of F₁ donor T cells, shortly prior the injection into parental mice, does not interfere with any of these events. Here, we have explored whether the continuous absence of T cells in F₁ mice influences the ability of their spleen cells to induce neonatal tolerance to alloantigens and the associated autoimmune manifestations. Our results revealed that spleen cells from athymic (BALB/c × C57BL/6) F₁ hybrid (CB6F₁) nulnu mice or from euthymic CB6F₁ mice depleted from birth of CD4⁺ T cells, but not of CD8⁺ T cells, are unable to induce neonatal tolerance to alloantigens and autoimmune manifestations. By contrast, the partial reconstitution of T cells in CB6F¹ nulnu mice, after the neonatal graft of a syngeneic thymus, restored the capacity of spleen cells from these mice to induce tolerance and autoimmunity when injected into newborn BALB/c mice. These results demonstrate that the functional defect of spleen cells from athymic CB6F₁ nulnu mice to induce neonatal tolerance to alloantigens is directly related to the long-term absence of mature CD4⁺ T cells. Interestingly, a new increase in the titers of anti-DNA Ab was observed when spleen cells from athymic CB6F₁ nulnu mice were injected into adult BALB/c mice that had been tolerized at birth with normal CB6F₁ spleen cells. This finding indicates that B cells from CB6F₁ nulnu mice recover their capacity to interact with alloreactive Th2 cells when they are placed into mice having functional CD4⁺ T cells. These data indicate that the continuous absence of CD4⁺ T cells causes a reversible functional defect in F₁ spleen cells that determines their inability to induce neonatal tolerance and autoimmunity.