Differential distribution of pepsinogen II between the zones of the human prostate and the seminal vesicle

Pepsinogen II (PG II) is a gastric proenzyme which has previously been found in both human seminal fluid and the prostate gland. However, no regional distribution of PG II has been noted within the prostate nor has it been found in the seminal vesicle. Bouins-fixed sections of central zone, peripheral zone and seminal vesicle, taken from 10 prostates removed at radical prostatectomy or cystectomy, were exposed to antibody against PG II and stained using the A-B-C immunoperoxidase technique. Formalin-fixed tissue from autopsy prostates of four men in the third decade, and six cases with BPH nodules, were also examined for PG II activity. In nine of 10 seminal vesicles, and seven of 10 central zone samples, more than 50 per cent of the cells stained positive for PG II. By contrast, in nine of 10 peripheral zone samples staining was present in five per cent or less of the epithelial cells. Similarly, PG II activity in the four autopsy prostates occurred almost entirely within the central zone and ended abruptly at the boundary between the peripheral and central zones. BPH nodules contained no PG II activity. These findings provide the first evidence that the central and peripheral zones may serve different biological functions. Embryologically it is currently thought that the prostate is of endodermal origin and the seminal vesicle of mesodermal origin. The presence of large amounts of PG II in both the seminal vesicle and central zone lends support to the hypothesis of a common mesodermal origin for these two structures.     

Pathogenesis and biological significance of seminal vesicle invasion in prostatic adenocarcinoma

Seminal vesicle invasion and the percentage involvement by cancer of each seminal vesicle were related to cancer volume, quantitative histological grade and presence or absence of lymph node metastases in 243 radical prostatectomy specimens. There were 47 prostates with seminal vesicle invasion. Frequency and extent of seminal vesicle invasion were strongly correlated with cancer volume, with minimal invasion noted in only 6% of the cases less than 4 cc. The relationship of seminal vesicle invasion to lymph node metastasis was statistically significant but cancer volume and histological grade were much stronger predictors of lymph node metastasis. The route of invasion from the prostate in 46 cases involved direct tumor spread into the midbase region near the ejaculatory ducts. Seminal vesicle invasion often may not be identified if the tissue nearest the ejaculatory ducts at the prostate base is not sampled.     

Pathology of benign prostatic hyperplasia. Insight into etiology.

Morphometric studies of prostates with benign hyperplasia (BPH) have revealed features that may help clarify the disease's natural history and biologic behavior. Hyperplasia arises within a small anatomic region having precise boundaries and containing an unusual juxtaposition of glandular and stromal elements. Diffuse non-nodular enlargement of the transition zone is the commonest morphologic feature of BPH, but nodules show a greater potential for growth and comprise most of the tissue in large (more than 50-gm) resection specimens. Most nodules are predominantly glandular, with features that suggest a pathogenetic role of induction of embryonic-type stroma.     

Differential cytokeratin expression in normal, hyperplastic and malignant epithelial cells from human prostate.

Studies were undertaken to define the expression of cytokeratins in normal, hyperplastic and malignant epithelial cells from human prostate. Cytokeratin (CK) polypeptides, separated by two-dimensional electrophoresis, were identified by immunoblotting with CK-specific monoclonal antibodies. CK polypeptides 5, 7, 8, 15, 18 and 19 were identified in fresh normal and hyperplastic prostate. Expression of CK 15 has not been previously reported in human prostate. Analysis of central and peripheral zone tissues from human prostate did not reveal qualitative differences in CK expression between these areas. Epithelial cells harvested from fresh BPH tissue by percoll gradient centrifugation and propagated in vitro using selective culture techniques showed alterations in CK expression compared to intact human prostate. Specifically, CKs 6, 14, 16 and 17 were noted in cultured BPH epithelial cells but not fresh normal prostate or BPH tissue. Immunoblot analysis of the established prostate cancer cell lines PC3, DU145 and LNCAP showed expression of CKs 8 and 18 but not CKs 5, 7 and 15 which were observed in benign prostate. These studies further characterize CK expression in benign and malignant human prostate and provide insights which may be useful in differentiating normal, hyperplastic and malignant epithelial cells in the human prostate gland.     

Multiple cancers in the prostate. Morphologic features of clinically recognized versus incidental tumors.

Multiple independent tumors were identified in specimens from 117 of 234 prostatectomies for clinical adenocarcinoma; there were 266 incidental cancers in these 117 prostates. The clinically detected carcinoma was the largest (or only) tumor in all 202 Stage B cases. However, among 32 Stage A cases (detection by transurethral resection), there were 8 prostates in which an incidental tumor was larger than the clinically manifest cancer. These were all small tumors except for two incidental cancers with a volume greater than 2cm3; roughly 80% of incidental carcinomas were smaller than 0.5 cm3, whereas fewer than 20% of manifest tumors were smaller than 0.5 cm3. Comparison with a series of cancers found incidentally at cystoprostatectomy for bladder cancer showed the same volume distribution as incidental (smaller) carcinomas in patients with prostate cancer. This distribution was thought to reflect the volume distribution of prostate cancer in the general population older than 50 years of age. It was concluded that additional incidental tumors are common in patients with prostate cancer, but their sum of volumes is seldom as large as the clinical cancer volume.     

Distribution of lactoferrin in the normal and inflamed human prostate: an immunohistochemical study.

A polyclonal rabbit antibody to lactoferrin was used to localize the distribution of lactoferrin within the different zones of the normal human prostate as well as within the inflamed human prostate. Cases of normal central zone, peripheral zone, periurethral glandular tissue, as well as cases in which foci of moderate to severe inflammation, along with varying degrees of inflammation-related atrophy, were studied. In cases with inflammation, the staining pattern of lactoferrin was compared to the staining pattern of prostate-specific antigen. Within the central zone, lactoferrin staining occurred in numerous individual cells peppered throughout the epithelium as well as within multiple intraepithelial lumens (lacunae). These lacunae were often numerous enough to give the central zone epithelium a fenestrated appearance; they were not seen in any of the other regions of the prostate. With the exception of an occasional individual cell or isolated positive gland, normal peripheral zone exhibited very little lactoferrin activity. Staining within the transition zone was similar to that seen in the peripheral zone. Staining within the urethral lining of the epithelium in the periurethral glands showed a distinct pattern of frequent intense staining involving the entire gland; frequent individual positive cells were also often seen. Three patterns of staining were identified in prostatic inflammation. Mild periglandular chronic inflammation produced foci of epithelial lactoferrin positivity that coincided precisely with the areas of inflammation. Severe acute inflammation produced strong staining within luminal secretions while cytoplasmic staining was limited to the luminal surface of the epithelium. Post-inflammatory atrophy showed intense diffuse lactoferrin staining in the scant cytoplasm of the atrophic epithelium. In 12 of the 17 cases of inflammation that were studied, areas of post-inflammatory atrophy or severe inflammation commonly showed absence of prostate specific antigen staining and epithelium that was strongly lactoferrin-positive. Within the normal human prostate, lactoferrin appears to be produced primarily within the epithelium of the central zone, periurethral glands, and lining epithelium of the prostatic urethra. Lactoferrin-filled central zone lacunae appear to be structures unique to the central zone. The distribution of lactoferrin in the periurethral glands and urethral lining epithelium, along with the intense production of lactoferrin in the presence of inflammation, and the preservation of lactoferrin production in severe inflammation or atrophy suggest that lactoferrin may be a key component of the inflammatory response within the human prostate.     

Positive surgical margins at radical prostatectomy: importance of the apical dissection

Positive margins were analyzed in 189 clinical stage B radical retropubic prostatectomies. Margins were identified by serially blocking the entire specimens in planes selected for optimum demonstration of capsule surface. Positive margins were divided into 2 categories: 1) those associated with capsular penetration of cancer and 2) those caused by inadvertent surgical incisions through the capsule into intracapsular cancer. Data were analyzed separately at each of 6 anatomical sites. Frequency of positive margins was related to the volume of cancer. Cancer of greater than 12 cc constituted a distinctive category in which seminal vesicle invasion, lymph node metastases and multiple positive margins were found in the majority of cases, signifying minimal possibility of cure. However, 31 positive margins occurred among 136 patients (23%) who were potentially curable by the criteria of normal seminal vesicles and absence of pelvic lymph node metastases; 17, of these 31 surgically positive margins (55%) occurred at the apex. Positive capsular penetration margins at the apex were volume-related, while negative margins were not. Site specific recommendations for avoiding positive and negative capsular penetration margins are suggested. The prostate apex, rectal and lateral surfaces, bladder neck and superior pedicles accounted for 48, 24, 16 and 10% of all positive margins, respectively. Dissection of the apical prostate and Denonvilliers' fascia require modifications of current surgical techniques if positive margins are to be avoided. Serum levels of prostate specific antigen may require as long as 5 years to become detectable when only 1 positive margin is the only evidence of nonorgan-confined disease.     

Induction and persistence of local rotavirus antibodies in relation to serum antibodies

The induction and persistence of local rotavirus antibodies, including stool IgA, jejunal IgA, and jejunal neutralizing antibody, were evaluated in 14 adult volunteers infected with the CJN strain of human rotavirus. In addition, the relationships between local rotavirus IgA and serum rotavirus IgA, IgG, and neutralizing antibody were determined. Both stool and serum rotavirus IgA appeared to have similar kinetics. Both antibodies peaked by days 14-17 after inoculation in all subjects, then decreased rapidly. By days 26-28, titers had fallen to 13% and 30% of their respective peaks. Serum rotavirus IgG peaked somewhat later, occurring in five subjects on days 26-28. Serum neutralizing antibody peaked on days 26-28 in all but three subjects. Both serum IgG and neutralizing antibodies also declined more slowly than rotavirus IgA. Although all antibody concentrations had decreased to only a fraction of their peak responses by days 270-365 after rotavirus inoculation they remained higher than baseline levels. For example, stool rotavirus IgA concentrations were 13.5-fold higher than baseline, while jejunal rotavirus IgA and neutralizing antibody were 8.9- and 4.3-fold above baseline, respectively. Similarly, serum antibodies remained 3.7- to 11.2-fold higher than baseline at 270-365 days after rotavirus inoculation. These studies imply that serum rotavirus IgA is a good indicator of local antibody responses. Furthermore, although both serum and local antibody titers peaked within 2-4 weeks after infection, these antibodies persisted at above baseline concentrations for at least 9-12 months after infection.     

Low Prenatal Weight Gain Among Adult WIC Participants Delivering Term Singleton Infants: Variation by Maternal and Program Participation Characteristics

Objective: To determine the association of maternal and prenatal WIC program participation characteristics with low prenatal weight gain among adult women delivering liveborn, singleton infants at term. Methods: WIC program data for 19,017 Black and White Alabama women delivering in 1994 were linked with birth certificate files to examine the association of anthropometric, demographic, reproductive, hematologic, behavioral and program participation characteristics with low prenatal weight gain. Results: One third (31.0%) had low prenatal weight gain as defined by the Institute of Medicine. The incidence of low weight gain was increased among women who had < 12 years of education, were single, Black, anemic, had low or normal pre-pregnancy body mass index (BMI), increased parity, interpregnancy intervals 24 months, used tobacco or alcohol, or entered prenatal care or WIC programs after the first trimester. After adjusting for selected maternal characteristics, the adjusted odds ratios (AOR) for low weight gain were increased with short interpregnancy intervals (AOR 1.21 to 2.20); tobacco use (AOR 1.16 to 1.40), anemia (AOR 1.20 to 1.25), and second trimester entry into prenatal care (AOR 1.14 to 1.20); the size of the AORs and 95% confidence intervals varied by BMI and racial subgroup. Conclusions: The results of this study suggest that WIC interventions targeting low prenatal weight gain be focused on risk factors present not only during pregnancy, but during the pre- and interconceptional periods as well. Interventions should target low BMI, tobacco use, and anemia, and include attention to nutrition screening and risk reduction among women in postpartum and family planning clinic settings.     

Drug education practice: results of an observational study.

Understanding normative practice in drug education is a key to identifying means of improving preventive intervention outcomes. In this paper, we report findings of an observational study in which drug education in multiple periods of 146 middle school classes was categorized minute-by-minute according to the type of instruction provided to students. Results indicate that nearly half of all drug education focused on providing students with knowledge. Alternative methods, particularly those that have shown programmatic effectiveness, and those that address risk and protective factors known to be highly predictive of drug use onset, were relatively ignored. Further, teachers showed relatively low consistency in understanding concepts other than knowledge based on comparisons of their ratings of intended instructions with those of trained observers. Nonetheless, there is evidence that some teachers systematically attempted to address drug prevention from either a social influence or an affective education perspective. These findings suggest that if improvements in the effectiveness of drug education are to be seen in the future, a relatively radical transformation of approaches to teaching will be needed.