Serum immunoglobulin G antibody to Porphyromonas gingivalis in rapidly progressive periodontitis: titer, avidity, and subclass distribution.

Porphyromonas gingivalis is a suspected pathogen in rapidly progressive periodontitis (RPP). We have determined the anti-P. gingivalis serum immunoglobulin G (IgG) isotype response and avidity and the subclass titer distributions for 30 RPP patients and 30 age-, sex-, and race-matched healthy subjects by using enzyme-linked immunosorbent assay technology. Patients and control subjects were classified as seropositive if their total IgG response to P. gingivalis was twofold or more than the median response in healthy subjects. The predominant antibody responses for both patients and healthy subjects were IgG2 and IgG3, with a subclass order of IgG2 greater than IgG3 greater than IgG1 greater than IgG4. The avidity of the IgG response was highest for the seropositive healthy subjects and was no different between seronegative and seropositive RPP patients. The subclass antibody responses did not depend on gender, and there were no correlations between titer, avidity, or subclass with disease severity in the RPP patients as measured by pocket depth or bone loss on dental X rays. The seronegative RPP patients exhibited antibody responses that were greater than the responses of seronegative healthy subjects for all four subclasses, while the seropositive RPP patients had higher IgG1 and IgG4 levels than seropositive healthy subjects. These findings are consistent with the hypothesis that both carbohydrate and protein antigens are important in the IgG response to P. gingivalis. The relative predominance of IgG2, a subclass which lacks strong complement fixation and opsonic properties, and the low avidity of patient anti-P. gingivalis IgG antibodies suggest that humoral responsiveness to infection with P. gingivalis may be ineffective in clearing this organism.     

Ependymal changes in experimental hydrocephalus

A morphologic investigation of ependyma over gray matter (caudate nucleus) and over periventricular white matter (tapetum) of the rabbit lateral ventricle was performed four months after the induction of experimental hydrocephalus. Ependymal cells over the caudate nucleus are not modified by hydrocephalus. They remain cuboidal and heavily ciliated. Numerous microvilli cover the cell surface. The extracellular space of the neuropil is not expanded. Ependymal cells over the periventricular white matter are markedly modified. The characteristic response of these ependymal cells is to enlarge and to form lacunae in their apical cytoplasm. Their apical, horizontal cytoplasmic processes elongate as adjacent ependymal cells separate. The ex-tracellular space of the neuropil is expanded. It is proposed that the changes seen in ependymal cells over periventricular white matter are a response to enlargement of the ventricular surface permitted by the orientation of neuronal and glial fibers parallel to the ventricular surface. With expansion of the ventricular surface, overlapping apical processes become elongated and modified, containing a terminal web. With further enlargement, sliding of an overlapping apical process of one cell uncovers the apical process of its neighboring cell. By this mechanism, the ventricular surface area of any ependymal cell whose surface has been partially covered by its neighbor is increased. With further progression, this compensation fails and the neuropil is exposed to the ventricular cavity. Over caudate nucleus, expansion of ventricular surface is hindered by the disposition of fascie adherentes along intercellular clefts oriented perpendicular to the ventricular surface. Lateral sliding of horizontal apical processes does not occur as such processes are not found in ependyma over the caudate nucleus. The differential response of the ventricular surface in these two areas characteristically seen in hydrocephalus is; determined by regional differences in the morphology of their ependymal cells and underlying neuropil.     

Expression of mitoses per thousand cells and cell density in breast carcinomas: a proposal.

A method of standardizing mitotic counts is described. This provisional approach, which expresses mitoses as a percentage of breast cancer cells present, holds the promise of facilitating interlaboratory agreement as well as providing a measure of tumor cellularity, probably an independent prognostic indicator in its own right. We suggest that this approach or one similar to it will maximize the evaluation and quantitation of proliferative activity from routinely available histologic material. Furthermore, the method is accomplished with little added effort beyond the customary histologic evaluation.     

Antigenic and genetic characterization of serotype G2 human rotavirus strains from South Africa from 1984 to 1998

Within South Africa, cyclic peaks of serotype G2P[4] rotavirus infection have been observed and these strains were prevalent in some locations. To examine the cyclic phenomenon of serotype G2 rotaviruses, historical stool collections from South Africa spanning 15 years were screened for G2 strains. Subgroup (VP6) ELISA, polyacrylamide gel electrophoresis (PAGE), and P genotyping were performed on 43 G2 strains to investigate the associated DS-1 genogroup characteristics. Antigenic variation of the gene encoding the major neutralization glycoprotein (VP7) was also investigated using G2-specific monoclonal antibodies. In addition, the VP7 gene of 14 serotype G2 strains was sequenced to examine genetic variation. Serotype G2 strains from South Africa displayed a 10 year cyclic pattern with major epidemics occurring in 1987 and 1997. Serotype G2 strains were also found co-dominant with G(1) strains in 1984, 1990, and 1993. The G2 strains from the major epidemics appeared to have emerged from community strains in a manner similar to that suggested for G(1) strains The serotype G2 strains displayed subgroup I specificity and short electropherotypes characteristic of DS-1 genogroup rotavirus strains but appeared to differ in the VP4 gene. Genetic analyses revealed three major serotype G2 lineages, i.e., strains isolated prior to 1987, strains isolated between 1988 and 1994, and strains isolated from 1995. The use of monoclonal antibodies and PCR primers designed against older G2 strains has resulted in the failure to serotype G2 strains circulating currently.     

Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease.

We have stratified the cancer risk implications of lobular pattern in situ neoplasias of the breast by separating marked examples of this histologic spectrum (lobular carcinoma in situ [LCIS]) from lesser examples (atypical lobular hyperplasia). The lesser-developed examples have been shown previously to have a lower relative risk (RR) of later invasive carcinoma of the breast (IBC). Forty-eight examples of LCIS were found in 10,542 otherwise benign breast biopsies, representing an incidence of 0.5%. Nine patients were excluded from follow-up because of bilateral mastectomy within 6 months of entry biopsy, IBC within 6 months of entry biopsy, or prior IBC. Follow-up of the remaining 39 patients was complete, averaged 18 years, and revealed an RR of subsequent IBC of 6.9 (P less than .00001). Average overall follow-up for LCIS patients was 19 years; it was 25 years for those alive and free of IBC at the time of their follow-up interview. Neither family history of IBC nor postmenopausal estrogen therapy further affected risk. The absolute risk of IBC after LCIS was 17% at 15 years (adjusted for withdrawals), and the RR was 8.0 in the first 15 years of follow-up compared with the general population. An analysis based on a time-dependent hazards model found that during the first 15 years following biopsy women with LCIS had 10.8 times the risk of breast cancer compared with biopsied women of comparable age who lacked proliferative disease. Some previously published articles reporting lobular neoplasia (LN) suggest that those series with the greatest incidences of LN (whether termed LN or LCIS) have the lowest RR of subsequent breast cancer. Those series with higher incidences of LN include less well-developed histologic patterns of LN (atypical lobular hyperplasia). We conclude that our study of LN and studies performed by others support the higher risk of IBC after histologically flagrant examples (LCIS, about nine times higher) and a relatively lower but definable risk after more histologically subtle examples (atypical lobular hyperplasia, four to five times lower). This relative cancer risk is probably not constant over more than 15 years; thus, cancer risk 15 to 25 years after initial diagnosis of LCIS is uncertain.     

Risk factors for breast cancer in women with proliferative breast disease

To assess the importance of various risk factors for breast cancer in women with benign proliferative breast lesions, we reevaluated 10,366 consecutive breast biopsies performed in women who had presented at three Nashville hospitals. The median duration of follow-up was 17 years for 3303 women, 1925 of whom had proliferative disease. This sample contained 84.4 per cent of the patients originally selected for follow-up. Women having proliferative disease without atypical hyperplasia had a risk of cancer that was 1.9 times the risk in women with nonproliferative lesions (95 per cent confidence interval, 1.2 to 2.9). The risk in women with atypical hyperplasia (atypia) was 5.3 times that in women with nonproliferative lesions (95 per cent confidence interval, 3.1 to 8.8). A family history of breast cancer had little effect on the risk in women with nonproliferative lesions. However, the risk in women with atypia and a family history of breast cancer was 11 times that in women who had nonproliferative lesions without a family history (95 per cent confidence interval, 5.5 to 24). Calcification elevated the cancer risk in patients with proliferative disease. Although cysts alone did not substantially elevate the risk, women with both cysts and a family history of breast cancer had a risk 2.7 times higher than that for women without either of these risk factors (95 per cent confidence interval, 1.5 to 4.6). This study demonstrates that the majority of women (70 per cent) who undergo breast biopsy for benign disease are not at increased risk of cancer. However, patients with a clinically meaningful elevation in cancer risk can be identified on the basis of atypical hyperplasia and a family history of breast cancer.