Secretory Cell Proliferation Research Articles

Expansion of secretory cells in the fallopian tubal epithelium in the early stages of the pathogenesis of ovarian serous carcinomas

to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC). The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test. The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (p<0.01); when comparing the same patient groups, that of SCO was 3.4 times higher (p<0.05). The immunohistochemical characteristics of the investigated lesions (in scores) were as follows: PAX2 was expressed in the intact epithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), β-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (p<0.05) for: 1) PAX2 between the intact epithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 4) ALDH1 between the intact epithelium and SCE, between and SCE and STIC, and between STIC and HGOSC. SCE was shown to be an independent intraepithelial lesion. The incidence of this abnormality increased with age and significantly differed in the patients with fallopian tubal lesions in extraovarian diseases from that in those with malignant ovarian serous tumors (by 5.3 times), while these groups showed a three-fold difference in SCO. Thus, SCP may serve as a more sensitive marker for the early stages of the pathogenesis of ovarian serous carcinoma. The studied types of SCE demonstrated multiple molecular events (loss of PAX2 expression and increased Bcl-2, beta-catenin, and ALDH1 expressions), some of which underwent considerable changes, by increasing the severity of a pathological process (loss of ALDH1, and beta-catenin, and bcl-2 expressions). Thus, therapeutic exposure in the early stages of pathogenesis may have a few points of application and just several molecules can serve as independent markers for early pathological changes in the fallopian tubal epithelium.

CFTR gene therapy, a method to rescue lung hypoplasia in congenital diaphragmatic hernia?

despite progress in neonatal care and despite changing concepts in treatment in the recent years, the mortality rate of infants with congenital diaphragmatic hernia (CDH) remains high ([20][1]). Pulmonary hypoplasia and vascular alterations associated with CDH have tremendous postnatal functional

Study of the Lactation Curve in Dairy Cattle on Farms in Central Mexico

Accurate knowledge of lactation curves has an important relevance to management and research of dairy production systems. A number of equations have been proposed to describe the lactation curve, the most widely applied being the gamma equation. The objective of this work was to compare and evaluate candidate functions for their predictive ability in describing lactation curves from central Mexican dairy cows reared under 2 contrasting management systems. Five equations were considered: Gaines (exponential decay), Wood (gamma equation), Rook (Michaelis-Menten ×exponential), and 2 more mechanistic ones (Dijkstra and Pollott). A database consisting of 701 and 1283 records of cows in small-scale and intensive systems, respectively, was used in the analysis. Before analysis, the database was divided into 6 groups representing first, second, and third and higher parity cows in both systems. In all cases except second and above parity cows in small-scale systems, all models improved on the Gaines equation. The Wood equation explained much of the variation, but its parameters do not have direct biological interpretation. Although the Rook equation fitted the data well, some of the parameter estimates were not significant. The Dijkstra equation consistently gave better predictions, and its parameters were usually statistically significant and lend themselves to physiological interpretation. As such, the differences between systems and parity could be explained due to variations in theoretical initial milk production at parturition, specific rates of secretory cell proliferation and death, and rate of decay, all of which are parameters in the model. The Pollott equation, although containing the most biology, was found to be over-parameterized and resulted in nonsignificant parameter estimates. For central Mexican dairy cows, the Dijkstra equation was the best option to use in describing the lactation curve.

CFTR modulates lung secretory cell proliferation and differentiation.

We have permanently reversed the lethal phenotype in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR)-deficient (knockout) mouse after in utero gene therapy with an adenovirus containing the cftr gene. The gene transfer targeted somatic stem cells in the developing lung and intestine, and these epithelial surfaces demonstrated permanent developmental changes after treatment. The survival statistics from the progeny of heterozygote-heterozygote matings after in utero cftr gene treatment demonstrated an increased mortality in the homozygous normal pups, indicating that overexpression during development was detrimental. The lungs of these pups revealed accelerated secretory cell proliferation and differentiation. The extent of proliferation and differentiation in the secretory cells of the lung parenchyma after in utero transfer of the cftr gene was evaluated with morphometric and biochemical analyses. These studies provide further support of the regulatory role of the cftr gene in the development of the secretory epithelium.

Sensitivity of mammary secretory cell turnover to protein restriction and re-alimentation during early lactation

Milk production depends on both the number and activity of secretory cells within the mammary gland. Our earlier work showed the sensitivity of lactational performance to changes in diet during lactation (Goodwill et al, 1996). This study investigated the influence of protein undernutrition and re-alimentation on secretory cell proliferation and death in the mammary gland of rats during early lactation.

Cell proliferation studies in the rat prostate: II. The effects of castration and androgen-induced regeneration upon basal and secretory cell proliferation.

The changes over short and prolonged periods (up to three months) after castration on the proliferative activity of basal and secretory epithelial cells in the rat prostate were studied. Although castration induced widespread apoptosis of the secretory cells, no compensatory hyperplasia of the basal cells in response to this was noted. Instead, observations of the cell kinetics and ultrastructure suggested that both the basal and secretory cells entered a quiescent state as a result of castration. The proliferative potential of secretory cells was not diminished up to three months after castration. During androgen-induced regeneration of the prostate the pattern of basal and secretory cell proliferation was found to be similar to that observed during normal growth, although it was more rapid and of shorter duration.

Histopathology of otitis media with effusion. An electron microscopic study of human temporal bones.

Ultrastructural studies of the middle ear mucosa appear to be of significant value in better understanding the pathology of otitis media with effusion (OME). Our present study was undertaken in order to take advantage of the use of electron microscopy in investigating all areas of the middle ear mucosa. Tissues studied were obtained from the fresh postmortem temporal bones of three patients with OME and terminal head and neck malignancies. In the mucoid type of effusion (cases 1 and 2), goblet cells were seen to proliferate and secretory activity was greatly enhanced. In contrast, there was no evidence of secretory cell proliferation in the serous type of effusion. It was noteworthy that accumulated fluid was not homogeneous in the same ear, as exemplified by case 1, in which both mucoid and serous effusions were present. This occurrence was possibly the result of topographic diversity involving the secretory activity of the middle ear.

Morphological basis of alveolar-capillary gas exchange.

Morphological basis of alveolar-capillary gas exchange.

Effects of adrenalectomy, adrenalectomy--ovariectomy, and cortisol and estrogen therapies upon enzyme activities in lactating rat mammary glands.

The effects of adrenalectomy and adrenalectomy–ovariectomy on the 5th day of lactation followed by cortisol and estrogen therapies on enzyme activities in rat mammary glands were investigated. This stage of lactation was selected because mammary secretory cell proliferation is essentially complete at this time thereby enabling study of the effects of cortisol and estrogen on enzyme levels in a nonproliferating secretory cell population. Eighteen enzymes were selected for study on the bases of their respective roles in milk biosynthesis and carbohydrate and energy metabolism and/or on the basis of previous studies indicating that their activities increase during midlactation or are regulated, in part, by steroid hormones. After adrenalectomy on the 5th day of lactation, cortisol therapy was required for normal increases in the activities of succinic dehydrogenase, citrate cleavage enzyme, malic enzyme, UDPglucose pyrophosphorylase, UDPglucose 4-epimerase, and glucose-6-phosphate dehydrogenase. The activities of UDPglucose pyrophosphorylase and glucose-6-phosphate dehydrogenase were higher than normal in cortisol-treated animals. Cortisol therapy during the last 2 days of the experiment increased the activity of UDPglucose pyrophosphorylase and possibly citrate cleavage enzyme. The activities of α-glycerolphosphate dehydrogenase, phosphoglucomutase, 6-phosphogluconate dehydrogenase, pentose phosphate metabolizing ability, hexokinase, phosphofructokinase, fructose-1,6-diphosphate aldolase, pyruvate kinase, lactic dehydrogenase, aspartate aminotransferase, isocitrate dehydrogenase, and extramitochondrial malate dehydrogenase were not notably affected by adrenalectomy or cortisol therapy. The activities of 6-phosphogluconate dehydrogenase, pentose phosphate metabolizing ability, phosphofructokinase, and pyruvate kinase may have increased after the 5th day of lactation in adrenalectomized as well as in normal animals. Combining ovariectomy with adrenalectomy reduced pup weight gains more than adrenalectomy alone, but did not further decrease significantly the activities of any of the enzymes measured. Ovariectomy had no effect when cortisol was administered. Cortisol therapy completely reversed adverse effects of estrogen given to adrenalectomized–ovariectomized animals. On the bases of these and previous data, it was concluded that cortisol regulates the rates of synthesis of several mammary gland enzymes during midlactation.

Enzymatic Activities in Mammary Glands of Several Species

The activities of a number of enzymes in the pathways of energy metabolism and lactose, fat and protein biosynthesis, and DNA levels in guinea pig and cow mammary glands at various stages of pregnancy and lactation, and in sow, mouse, and rabbit mammary glands at full lactation were determined. Large increases in enzyme activities and in DNA levels occurred during early lactation in guinea pig mammary glands but not in cow mammary glands. The significant apparent species differences in enzyme activities observed may have been due to interspecies differences in rates of secretory cell proliferation, in the compositions of the mammary gland samples, or in the inherent nature of the regulatory mechanisms associated with the initiation of lactation. Enzyme levels did not appear to be related to interspecies differences in milk composition.