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Biomedical subjects

J Russo

Publications and source records attributed to J Russo.

At least 271 records · Page 15Linked to original sources

Influence of differentiation and cell kinetics on the susceptibility of the rat mammary gland to carcinogenesis.

The susceptibility of the rat mammary gland to carcinogenesis decreases with aging and is nullified by pregnancy and lactation. This work was carried out to determine whether these differences in susceptibility to carcinogenesis are the result of variations in cell kinetics induced by both aging and parity. Cell cycle (Tc) and growth fraction (GF) were studied in the mammary gland epithelium of young virgin, old virgin, and parous Sprague-Dawley rats. For the study of Tc, five young virgin, five old virgin, and five parous rats received while in estrus an i.p. injection of 1.7 muCi [3H] thymidine per g body weight. Mammary gland biopsies were taken at 2-hr intervals for the first 24 hr and every 4 hr thereafter up to 72 hr. GF was determined in two young virgin, two old virgin, and two parous rats in which an osmotic minipump releasing 1 microCi [3H]thymidine per hr was implanted i.p. After 5 days, the animals were killed, and the mammary glands were removed. Mammary gland biopsies and whole glands were fixed in Bouin's fluid and embedded in paraffin. Deparaffinized sections were processed for autoradiography. The labeled mitosis wave, labeling index, and GF were determined. The results indicated that, in young virgin rats, mammary gland Tc was 9.9 hr in the most undifferentiated structures (terminal end buds), lengthening to 17.3 hr in terminal ducts (TD) and to 28.2 hr in alveolar buds (AB). In the mammary gland of old virgin rats, Tc was 18.75 hr in terminal ducts in regression, 20.57 hr in TD, and 30.75 hr in AB. In parous rats, mammary gland Tc was 23.9 hr in TD and 49.63 hr in AB. Lengthening of Tc in all of these structures was due to a lengthening of G1, while the duration of the other phases of the cell cycle remained unchanged. GF was 0.55 in terminal end buds of young virgin rats, decreasing to 0.39 and 0.13 in TD and AB, respectively. In terminal ducts in regression of old virgin rats, GF was 0.19, decreasing to 0.054 and 0.030 in TD and AB, respectively. In TD and AB of parous rat, mammary gland GF was 0.009 and 0.004, respectively. These results suggest that the high susceptibility to carcinogenesis that has been demonstrated in young virgin rats is due to the presence of a large proliferative compartment, mainly in terminal end buds and TD, while the low susceptibility of parous animals is due to the formation of a large compartment of nonproliferating cells, and that those cells still proliferating have a longer G1 than do those of young and old virgin rats.

Age Factors↗

Lidocaine anesthesia: comparison of iontophoresis, injection, and swabbing.

The duration and depth of anesthesia produced by lidocaine with three methods of administration were studied. To test duration of anesthesia, either lidocaine or placebo was administered by iontophoresis, subcutaneous infiltration, or swabbing to each of three sites 3 cm apart on the flexor surface of each forearm of 27 subjects. To test for feeling, the tip of a 21-gauge hypodermic needle was pressed on each application site every five minutes until feeling returned. The depth of anesthesia achieved with iontophoresis or infiltration of lidocaine was tested on the flexor surface of each forearm of 12 subjects, with a random assignment of application methods to each arm. Lidocaine iontophoresis produced local anesthesia of significantly longer duration (p less than 0.001) than topical application of lidocaine or placebo by any route of administration, but of significatnly shorter duration (p less tahn 0.001) than lidocaine infiltration. The results showed that lidocaine iontophoresis is an effective method of producing local anesthesia for about five minutes without requiring the use of a hypodermic needle and syringe.

Administration, Topical↗

Susceptibility of the mammary gland to carcinogenesis: I Differentiation of the mammary gland as determinant of tumor incidence and type of lesion.

The influence of age and mammary gland differentiation on the incidence of tumors induced by 7,12-dimethylbenz(a)anthracene (DMBA) was studied by correlating the development of the mammary glands of 20-180-day-old, virgin Sprague-Dawley rats with the number and type of tumors induced by DMBA administered at those various ages. The number of terminal end buds (TEBs), terminal ducts (TDs), and alveolar buds (ABs)/sq mm and their DNA-labeling indices (DNA-LI) were determined. Highest density of TEB occurred when the rats were 20 days old, decreasing thereafter. DNA-LI ranged between 25.2 and 29 in TEB of rats aged 30-55 days, which was coincident with the highest incidence of carcinomas. With aging, the number of TEBs and their DNA-LI decreased and the number of TDs and ABs increased, although with a low DNA-LI, which correlated with a lower incidence of carcinomas and higher incidence of benign lesions.

9,10-Dimethyl-1,2-benzanthracene↗

Decentralization of pharmaceutical services without satellite pharmacies.

The decentralization of pharmaceutical services without the addition of pharmacy satellites is described. Mobile, master medication carts are used by pharmacy personnel in the patient-care areas to fill the unit dose carts used by nurses. A combination medication administration record and patient profile eliminates duplication of effort by pharmacy and nursing. Responsibilities of pharmacists and technicians, the process of hospital-wide implementation of the system, current levels of service, and a clerkship designed to improve staff pharmacists' clinical abilities are described. The ratio of the number of drug doses administered to the number of drug doses handled per patient-day increased after the implementation of the new system. This indicated that individual doses were handled fewer times by pharmacy personnel. This method of decentralization permitted integration of distributive and clinical pharmaceutical services with a minimal personnel cost increase, no additional space requirements nor expenditures for renovation, and only a small cost for master medication carts. Because the pharmacists work in the patient-care areas, they are in more frequent contact with nurses, physicians and patients.

Costs and Cost Analysis↗

Developmental stage of the rat mammary gland as determinant of its susceptibility to 7,12-dimethylbenz[a]anthracene.

Postnatal development of the mammary gland was studied in 80 noninbred Sprague-Dawley virgin rats ranging in age from 2 to 112 days, and the changes induced by 7,12-dimethylbenz[a]anthracene (DMBA) were studied in 60 noninbred Sprague-Dawley virgin rats that, at the age of 55 days, were inoculated intragastrically with 10 mg DMBA/100 g body weight. To correlate the sequential structural changes in the two groups, animals of both groups were killed weekly and their mammary glands removed and processed for wholemount. Terminal endbuds (TEB), terminal ducts (TD), alveolar buds (AB), and lobules per square millimeter were counted in wholemount preparations under a stereomicroscope. During postnatal development, the mammary gland tree grew by sprouting numerous ducts ending in club-shaped TEB. The density of TEB reached a peak when the rats were 21 days old (25 +/- 2 TEB/mm2), decreased sharply until the animals were 63 days old, and then decreased slowly until they were 84 days of age. The number of TEB decreased because of their differentiation mainly into AB or their evolution to TD. AB later differentiated into lobules. AB increased in number steadily to a plateau when the animals were 70--84 days old. After DMBA was administered to the rats at 55 days of age, the number of TEB remained higher than that in the control animals and the TEB became larger and had higher mitotic activities. Such TEB were called intraductal proliferations (IDP); they evolved to adenocarcinomas. DMBA increased the number of TD and decreased the number of AB and lobules in relation to the control animals. These findings led to the conclusion that DMBA administration to 55-day-old rats alters the differentiation of TEB leads to AB leads to lobules, inducing instead the sequence TEB leads to IDP leads to adenocarcinoma.

9,10-Dimethyl-1,2-benzanthracene↗

Ultrastructural localizations of adenosine triphosphatase activity in resting mammary gland.

Adenosine triphosphatase (ATPase) activity was localized at an ultrastructural level in the resting mammary glands of female BALB/c mice. A Mg++ dependent ATPase was localized in the plasma membranes of both the epithelial and myoepithelial cells of the mammary tubules. A second type of ATPase activity that was not Mg++-dependent but that was Na+ and K+ dependent was localized primarily in the plasma membranes of the myoepithelial cells. Preincubation with either ouabain or N-ethylmaleimide decreased the quantity of reaction product, indicating that both types of ATPase activity were sensitive to these inhibitors. Control media, containing adenosine triphosphate and Pb(NO3)2 without cations, demonstrated that the amount of nonezymatic hydrolysis was negligible. These differences in the cationic requirements for plasma membrane ATPase activity can be used to distinguish histochemically the epithelial from myoepithelial cells in mammary tissue.

Adenosine Triphosphatases↗

Adenosine triphosphatases as histochemical markers for the cell of origin in experimental mammary carcinoma.

Different adenosine triphosphatase (ATPase) activities were detected at an ultrastructural level in order to differentiate epithelial and myoepithelial cells in normal and neoplastic mouse mammary tissues. Mg2+ dependent and Na+-K+-dependent ATPase activities were studied in: BALB/c mouse mammary gland; a BALB/c carcinoma from a transplantable D2 hyperplastic nodule; a stable cell line, MCF-8, derived from the BALB/c carcinoma; and a BALB/c scirrhous-like carcinoma induced by MCF-8 cell inoculation. Mg2+-dependent ATPase was detected in the plasma membranes of the normal mouse mammary epithelial cells, the epithelial component of the BALB/c carcinoma, the MCF-8 cells in culture, and the atypical epithelial component of the scirrhous-like carcinoma. Na+-K+-dependent and Mg2+-dependent ATPase were localized in the plasma membranes of the myoepithelial cells of the normal mammary gland and the BALB/c carcinoma. The results from these histochemical studies established that the cell of origin in both the BALB/c carcinoma and the scirrhous-like carcinoma was the mammary epithelial rather than the myoepithelial cells. Furthermore, these results indicated that the MCF-8 cell line was derived from the epithelial component of the primary BALB/c carcinoma. These conclusions, which were based on histochemical study, were supported by the presence of intracisternal type A viral particles in the epithelial cells of the primary BALB/c carcinoma, the MCF-8 cells in culture, and the epithelial cells of the scirrhous-like carcinoma. Thus, the enzymatic markers were specific for cell type and remained unchanged by the process of cell transformation.

Adenocarcinoma, Scirrhous↗

Differentiation of normal human mammary epithelial cells in culture: an ultrastructural study.

An ultrastructural and cytochemical study of normal human mammary epithelial cells cultured from post-weaning breast fluids is described. Cells were examined at the time of plating and at intervals up to 28 days in culture. Three different stages in the morphological differentiation of these cells in vitro were observed: (1) the first stage was the formation of a monolayer of single cells, which occurred between days 1 and 10 in culture. The cells in this stage were not interconnected by junctional complexes and lacked Mg++- dependent ATPase activity in the plasma membranes, but did contain a large quantity of lipid and exhibited some secretory characteristics. (2) The second stage, occurring at 10 to 16 days in culture, was characterized by the formation of junctional complexes, the appearance of Mg++-dependent ATPase in the plasma membrane and a decrease in the number of dense bodies with peroxidase activity. (3) The third stage, occurring at 16 to 28 days in culture, was characterized by the formation of stratified layers of epithelial cells, which were interconnected by a larger number of desmosomes with numerous pleomorphic microfilaments. The Mg++-dependent ATPase activity in the plasma membrane was retained and the dense bodies with peroxidase activity were rarely observed at this stage. During the last seven days were prominent in the cells of the stratified layer. After 28 days in the culture, the cells began to round up and slough off the culture plate.

Adenosine Triphosphatases↗

Fine structure of a murine mammary carcinoma cell line.

A fine structural study was made of cells from the epithelioid MCF-8/5-2A cell line derived from a MuMTV-free D2 transplantable hyperplastic outgrowth. Electron microscopy shows the cells to be truly epithelial with many cell-to-cell junctions and microvilli. The cells are similar in many respects to normal mouse mammary gland and some of the conventional mammary tumor derived cell lines. This study supports previous observations of the absence of MuMTV in MCF-8 within the limits of morphological detection, and demonstrates the presence of numerous virus particles within, or budding into, cisternae of the endoplasmic reticulum and nuclear envelope. These intracisternal A particles have not been previously described in such abundance in mammary tumor tissue culture cells.

Animals↗

Reexpression of the original tumor pattern by a human breast carcinoma cell line (MCF-7) in sponge culture.

A stable cell line (MCF-7), derived from a pleural effusion of a patient with metastatic breast carcinoma, was maintained in these laboratories for more than 3 years in conventional monolayer culture. To further characterize the tumor origin of the MCF-7 line, cells were grown on collagen-coated cellulos sponges. On the three-dimensional sponge matrix, the cells formed clusters, ductlike structures, and lumina similar to the patterns observed in the antecedent primary tumor and in the pleural metastasis. The similarity between the original tumor and the cells grown in sponge suggested that the MCF-7 cells did in fact retain the potential to express the histologic patterns of tumor, even in the absence of stroma support. This study confirmed the utility of sponge culture for the investigation of the retention of tumor characteristics by cultured cells of neoplastic origin.

Adenocarcinoma, Scirrhous↗

An experimental animal model for the study of human scirrhous carcinoma.

Scirrhous-like carcinomas were induced by the inoculation of cloned mouse mammary carcinoma cells into the cleared fat pads of BALB/c mice. The inoculated cells induced palpable tumors in 100% of the animals within 60 days. The epithelial cells in vivo grew in rows and clusters and were attached by short developing desmosomes. Microvilli and organelles were scarce; intracisternal type A particles were observed in all the epithelial cells. Carcinoma cells invaded the dermis and muscle. The stroma was formed by morphologically normal fibroblasts and large masses of collagen. No virus particles were observed budding from the epithelial cell surface or in the stromal fibroblasts. The similarities between the scirrhous-like carcinoma in BLAB/c mice and the juman scirrhous carcinoma suggest this animal system as a model for the study of the human disease.

Adenocarcinoma, Scirrhous↗

Histopathology of spontaneous regression in virus-induced murine leukemia.

The histopathology of the spontaneous regression of murine leukemia induced by a particular strain of Friend leukemia virus was studied in Swiss ICR/Ha mice. Animals inoculated with the regressing strain of Friend virus exhibited an initial pathologic response identical to that induced by conventional strains of Friend virus. Unlike the fatal leukemia produced by conventional Friend virus, the pathology of the disease induced by the regressing strain of Friend virus appeared to be self-limiting. The histopathology of the two diseases is compared in this report.

Animals↗

An ultrastructural study of normal human mammary epithelial cells in culture.

The ultrastructure of normal human mammary cells cultured from post-weaning breast fluids is described. Cells from confluent monolayers in two week old cultures were studied. The epithelial nature of these cells was established by the demonstration of a well developed system of cell-to-cell interdigitation and numerous desmosomes. These cells also share with breast epithelial cells in vivo, polarity, with blunt short microvilli on the apical surface and an oriented arrangement of organelles in the basal and apical portions of the cells. The Golgi apparatus, which is the most highly developed organelle, is localized in the apical pole and contains substantial quantities of secretory material in the cisternae and vesicles. A variegated palisade of finely granular material mixed with tonofilaments is seen in the basal portion of the cells; many of these tonofilaments end in the terminal web of the desmosomes. The regular occurrence of these cells in breast fluids during the terminal phases of lactation suggests that their separation is a part of normal breast involution.

Breast↗