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D C Herbert

Publications and source records attributed to D C Herbert.

At least 55 records · Page 3Linked to original sources

Intercellular communication within the rat anterior pituitary gland: IV. Changes in cell-to-cell communications during pregnancy.

Cell-to-cell communication by gap junctions was investigated in the female rat anterior pituitary gland from 9 through 21 days of pregnancy and subsequently on days 2 and 20 of the lactational period. Compared with intact estrus females, the major morphological characteristics of the pituitary gland during pregnancy were remarkably developed prolactin cells and gonadotrophs. A close relationship of both cell types was clearly evident. Gap junctions were present at each of the time intervals studied; however, they were noted only between adjacent folliculo-stellate cells. No remarkable changes were noted in the number of gap junctions during the middle stage of pregnancy (day 9 through day 15), with the relative number resembling that found in intact, 90-day-old controls during estrus (0.47 +/- .01 junctions/follicle-control vs. 0.50 +/- 0.08--day 15 of pregnancy). In the later stages of pregnancy (day 17 through day 21), a demonstrable increase was observed (0.64 +/- 0.10--day 17, 0.79 +/- 0.11--day 19 and 0.72 +/- 0.12--day 21), whereas during the lactation, this pattern returned to that seen at midpregnancy. Since both prolactin and the gonadal steroid hormones dramatically fluctuate during pregnancy and lactation, it is postulated that they may have an active role in gap junction formation during these two phases of reproductive life.

Animals↗

Evidence that hepatocytes can phagocytize exogenous substances.

Although the phagocytic action of Kupffer cells is well known, such a phenomenon has not been well documented for hepatocytes. Following the injection of a suspension of egg lecithin-coated silicon particles (0.5-1.5 microns in diameter) into the portal vein of rats, Kupffer cells showed minimal phagocytotic action, which was in contrast to the hepatocytes which displayed numerous phagocytized silicon particles. By comparison, when noncoated silicon particles of the same diameter as those that were coated were injected into the portal vein, the opposite observation was made. There was no uniformity in the ability of the hepatocytes to phagocytize either coated or noncoated particles from one lobule to another. Some showed active phagocytosis, while in others no evidence of such a process was observed. These data provide strong evidence for the selective phagocytic action of liver hepatocytes.

Animals↗

Effects of aging and food restriction on the trigeminal ganglion: a morphometric study.

A quantitative morphometric study of the rat trigeminal ganglion was conducted to determine the changes that occur with aging. All measurements were tracked from young to old age in two rat groups simultaneously. One group was fed ad libitum, the other was maintained on restricted food intake from 6 weeks on. Immunocytochemical and radioimmunoassay techniques were used to study the neuron group that produces the peptide, CGRP and to compare it with the CGRP-negative neuron group. We observed that in the trigeminal ganglion, soma diameters and nucleus diameters of all neurons, whether CGRP positive or negative, increased modestly with age; so did total ganglion weight. Food restriction delayed, but did not prevent the increases in neuron diameters. No significant changes occurred as a function of age in the total number of neurons per ganglion, the ratio of CGRP positive to CGRP negative neurons and ganglion content of CGRP. Food restriction did not affect the parameters that remained constant with age. These findings are in contrast to the marked inhibitory effect of food restriction on age-related increase in thyroid calcitonin, a hormone that is encoded by the same gene as CGRP.

Aging↗

Intercellular communication within the rat anterior pituitary gland. III. Postnatal development and periodic changes of cell-to-cell communications in female rats.

Cell-to-cell communication by gap junctions was investigated in the female rat anterior pituitary gland from 10 through 45 days of postnatal development and in 60-day-old animals. Gap junctions initially appeared between adjacent folliculo-stellate cells on day 25. Their appearance in female rats was 5 days later than that observed in males (Soji et al., 1990). Gap junction number increased until the animals became 40 days of age, when they reached a level that resembled that found in adults. In addition, a correlation was evident between the frequency of gap junctions and stages of the estrous cycle, where they were most numerous during either proestrus or estrus. These results along with those previously published suggest that gap junction formation within the female rat hypophysis is in part modulated by both gonadal steroid hormones as well as prolactin.

Animals↗

Cytochemistry of Ca(++)-dependent adenosine triphosphatase (Ca-ATPase) in rat anterior pituitary cells.

In the present study, we demonstrate the localization of Ca(++)-ATPase in the anterior pituitary of the male rat. Ca(++)-ATPase was mainly distributed on the membrane system of the granular cells, which included the plasma membrane, the outer mitochondrial membrane, the enveloping membrane of secretory granules, the smooth endoplasmic reticulum and some components of the Golgi complex. No reaction product was detected on the membrane of the rough endoplasmic reticulum or that surrounding the lysosomes. A positive reaction was clearly observed on the membranes surrounding 'large' secretory granules, while that present on the membranes of the 'small' granules was comparatively weak. The cells which contained the 'large' granules were interpreted as growth hormone-secreting cells and those in which the 'small' granules were located as gonadotrophs. There were either no reaction or one that was barely detectable on the plasma membrane of the folliculo-stellate cells. These data along with our previous findings (Soji, 1982, 1984) suggest that the membranous enzymes are not uniformly distributed over all pituitary cells but rather are specific for a given cell population(s).

Animals↗

Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice.

Transferrin (TF) is a plasma protein that transports and is regulated by iron. The aim of this study was to characterize human TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration. Chimeric genes were constructed containing 152, 622, and 1152 base pairs (bp) of the human TF5'-flanking region with the coding region of a reporter gene, CAT (chloramphenicol acetyltransferase), and introduced into the germ line of mice. Transgenes containing TF 5'-flanking sequences to -152 bp were expressed poorly in all tissues examined. In contrast, transgenes containing TF sequences to -622 or -1152 bp were expressed at high levels in brain and liver, greater than or equal to 1000-fold higher than tissues such as heart and testes. Liver and brain are major sites of endogenous TF mRNA synthesis, but liver mRNA levels are 10-fold higher than brain. A significant diminution of CAT enzymatic activity in liver accompanied iron administration in both TF(0.67) and TF(1.2)CAT transgenic mice, mimicking the decrease of transferrin in humans following iron overload. Levels of endogenous plasma transferrin also decreased in iron-treated transgenic mice. Transgenic mouse lines carrying human TF chimeric genes will be useful models for analyzing the regulation of human transferrin by iron and for determining the molecular basis of transferrin regulation throughout mammalian development into the aging process.

Animals↗

Intercellular communication within the rat anterior pituitary gland. I. Postnatal development and changes after injection of luteinizing hormone-releasing hormone (LH-RH) or testosterone.

The postnatal development of gap junction formation and cell-to-cell communication were investigated in male rats from 10 through 40 days of age. These junctions initially appeared between adjacent folliculo-stellate cells on day 20. Their numbers increased until the animals reached the age of 40 days, when their frequency reached a level that resembled that found in adults. The ontogeny of these junctions was examined in rats treated with luteinizing hormone releasing hormone (LH-RH) or testosterone. The two hormones were injected for 1 week into rats aged 3, 13, 23, or 33 days. The appearance of gap junctions was accelerated in a similar fashion by LH-RH and testosterone, with their formation and numbers being advanced by 10 days over that observed in the untreated controls. The results suggest a role for the gonadal steroid hormones in the formation of gap junctions in the rat hypophysis.

Animals↗

Intercellular communication within the rat anterior pituitary gland. II. Castration effects and changes after injection of luteinizing hormone-releasing hormone (LH-RH) or testosterone.

This study investigated the relationship between gap junction formation and sex steroids in the male rat anterior pituitary gland. Animals were castrated at 5 days of age and separated into the following three groups: 1) oil-treated controls, 2) those injected with LH-RH, and 3) those given testosterone. On days 10, 20, 30, and 40, five rats in each group were sacrificed and their hypophyses removed for ultrastructural examination. When compared with age-matched, intact animals, there was a marked suppression in follicular development and in the number of gap junctions present in the pituitary glands of both the castrated controls as well as the castrates given luteinizing hormone releasing hormone (LH-RH). In contrast, the morphology of these structures in the animals given testosterone was indistinguishable from that observed in the intact controls. These observations provide more definitive evidence that in the male rat pituitary gland maturation of the structural organization of the follicles, including gap junction formation, requires an intact hypophyseal-gonadal axis and is highly dependent on the hormone testosterone.

Animals↗

Tissue specific expression of mouse transferrin during development and aging.

Transferrin (TF) is a major plasma protein that binds ferric iron and transports it to all target tissues of the body. This study is the first step to identify the tissue specific expression of the transferrin gene in mice during development, into maturity and throughout the aging process. The transferrin gene expresses mainly in mouse liver, the cerebral hemispheres and cerebellum. In mouse, transferrin is expressed in peritoneal macrophages and in mouse macrophage cell line MO59. At 19 days of gestation, transferrin mRNA is detected in the fetal lung, heart, stomach and kidney. TF mRNA levels increase in liver throughout gestation with maximum expression occurring at 19 days. Transferrin mRNA was detected in placentas of pregnant mice, with levels progressively increasing throughout the term of pregnancy. The levels of liver TF mRNA in mouse vary in a cyclic manner during the development increasing with the aging processes. Because of the dynamic nature of tissue requirements for transferrin during homeostasis the TF gene serves as a promising system for analyzing tissue-specific regulation in vivo during development and aging. Results from this study designate periods in the life-span of the mouse where regulatory mechanisms interacting with the TF gene appear to dynamically alter its expression.

Aging↗

Intercellular communication between rat anterior pituitary cells.

Cell-to-cell communication within the rat anterior pituitary was investigated in 60-day-old male rats with immunohistochemistry, scanning electron microscopy, freeze-fracture electron microscopy, and conventional transmission electron microscopy. A dense cytoreticular network of cytoplasmic processes from the folliculostellate cells was found to contain immunoreactive S-100 protein and was observed throughout the anterior pituitary. Nonimmunoreactive cells, which were granular, were situated in the center of each network. Almost all of the granulated cells were situated in close proximity to the folliculostellate cells. Scanning electron microscopy revealed that the gland consisted of microlobules enclosed by a basal lamina. On the surface of the microlobules were blood vessels whose branches invaded its internal structures. Cytoplasmic processes from folliculostellate cells projected outside the microlobule. Freeze-fracture electron microscopy demonstrated the presence of numerous intramembranous particles on the P-face of the plasma membrane. Scattered on the cell surface were groups of particles forming gap junctions. Meshworks of ridges which were representations of tight junctions were also observed near clusters of microvillous fragments. Clusters of particles forming small gap junctions were located between the meshworks of tight junctions. Small gap junctions were clearly observed by conventional electron microscopy between junctional complexes in a manner similar to that seen by freeze-fracture electron microscopy. Slender cytoplasmic processes of folliculostellate cells came in contact near the basal lamina and were adjoined by small gap junctions. The ratio of nongranular cells which contained gap junctions to those in which the junctions were absent was about 1:1. The size of the gap junctions ranged from 50 nm to 3 microns. No gap junctions were observed along the plasma membranes of the granular cells. The significance of an intercellular communication system within the anterior pituitary gland of the rat is to establish a mechanism for rapid transmission of information in an organ which lacks direct innervation.

Animals↗

Granulated 'marginal cell layer' in the rat anterior pituitary gland.

A granulated 'marginal layer cell' was observed in the lining of Rathke's residual pouch of 5 and 10 day-old rat anterior pituitary glands. Immunohistochemistry was not employed to identify the precise function of these cells. However, the cytological characteristics of nearly all of the cells indicated that they resembled GH-secreting cells, with a few displaying morphological features of corticotrophs. In pituitary glands of 5-20 day-old rats, both ends of Rathke's residual pouch extended into the pars distalis at the site of transitional zone of this lobe and of the pars intermedia. The cells within the 'invading' residual pouch contained numerous microvilli. In the middle portion of the residual pouch, cavities lined by 'marginal layer cells' had numerous microvilli and were adjoined by junctional complexes. In the adult rat pituitary gland, there were no granulated cells in the 'marginal cell layer' and no invasion of the residual pouch into the anterior lobe. From these data the possible source of the follicle and of the folliculo-stellate cells in the anterior pituitary of the rat is proposed.

Animals↗

The depression in rat pineal melatonin production after saline injection at night may be elicited by corticosterone.

A hind-leg subcutaneous saline injection into rats at night elicits a decrease in N-acetyltransferase (NAT) activity and melatonin content of the pineal gland. The decrement in pineal melatonin production after saline injection is prevented by adrenalectomy. The present studies were undertaken to determine what factor(s) from the adrenal gland cause(s) the drop in pineal melatonin production after saline injection at night. In the first study, groups of intact and adrenal-demedullated male rats were given a saline injection at 23.10 h (3 h, 10 min after lights off) and their pineals were collected 15 or 30 min later. Pineal NAT activity was depressed in both intact and adrenal-demedullated rats at 15 min postinjection as compared to their respective control animals. Pineal melatonin levels exhibited a drop in intact animals at 15 min and in adrenal-demedullated rats at 30 min. In a second study, hypophysectomy was found to prevent the drop in nocturnal pineal NAT activity and melatonin levels normally associated with a hind leg injection of saline. Finally, in a third experiment, groups of hypophysectomized rats were injected i.p. with corticosterone at 23.10 h and killed 10, 25 or 40 min postinjection. Corticosterone injection in hypophysectomized rats produced a response similar to that caused by saline injection in intact animals: NAT activity was depressed at 10 min and melatonin content was lowered at 25 min. These results suggest that the adrenal-mediated depression in melatonin synthesis after saline injection at night in rats may be elicited by an adrenal cortical hormone (corticosterone) and apparently does not involve the release of factors from the adrenal medulla.

Adrenalectomy↗

Mechanism of dietary modulation of calcitonin levels in Fischer rats.

Aging caused an increase in serum calcitonin that was markedly suppressed by food restriction. Food restriction had no significant effect on gut calcium absorption, urinary calcium excretion, serum 1,25(OH)2 vitamin D, blood ionized calcium, the clearance of calcitonin from plasma, and its rate of inactivation in vitro by the kidney and liver. In contrast, food restriction modulated an increase with age in calcitonin secreting C-cells, thyroidal calcitonin and thyroidal calcitonin mRNA pools. We conclude that the lowering of age-related increase in serum calcitonin levels by food restriction is likely because of lowered thyroid calcitonin pools rather than changes in the metabolism of calcium, which is the primary stimulus for calcitonin secretion. Our findings also suggest that food restriction decreases age-related increase in calcitonin levels, at least in part, by modulating the expression of the calcitonin gene.

Aging↗

Pituitary and testicular function in the restricted (Hre) rat.

A systematic morphological and biochemical examination of the pituitary-testicular axis in the male restricted (Hre) rat was undertaken in order to understand the possible site(s) and mechanism(s) responsible for their infertility. The adult Hre rat had increased plasma levels of LH and FSH but normal levels of prolactin and testosterone, and normal weights of the sex accessory glands. The increased plasma levels of LH and FSH correlated with hypertrophy and vacuolation of the gonadotrophs in Hre rats. Leydig cells from adult Hre rats exhibited an enhanced testosterone response to LH and hCG in vitro but not in vivo. There was a shift in the normal age-related decline in the response of cultured Sertoli cells to FSH in Hre rats, which was evident as early as 25 days of age, and which corresponded to a delay of 10-14 days in the pubertal increase in testicular weight. The search for the mechanism of the suppression of spermatogenesis in the Hre rat should take into account two events, which may or may not be related: (i) the delay in the onset of spermatogenesis during puberty and (ii) inhibition of spermatogenesis in the adult, which may result from abnormal function of both the Sertoli and Leydig cells.

Animals↗

Expression of three viral oncogenes (v-sis, v-myc, v-fos) in primary human brain tumors of neuroectodermal origin.

We determined which viral oncogenes (v-sis, v-myc, and v-fos) were expressed in five primary human brain tumors of neuroectodermal origin (two glioblastomas multiforme, one medulloblastoma, one cystic cerebellar astrocytoma, and one ganglioglioma) and which of these oncogenes is correlated with malignancy. Using the dot hybridization technique, we determined the relative amounts of mRNA coded by these genes using the same nitrocellulose filter. The v-myc probe showed a 4- to 12-fold greater hybridization to the mRNA from two glioblastomas and the medulloblastoma (malignant group) than the mRNA from the cystic cerebellar astrocytoma or the ganglioglioma (benign group). In contrast, RNA hybridizing to v-sis and v-fos were accumulated to a greater extent in the benign tumors. These data suggest that the amount of myc expression may be correlated with the degree of malignancy of brain tumors of neuroectodermal origin.

Brain Neoplasms↗

Nyctohemeral rhythms of gonadal, thyroid and pineal function in the hyperprolactinemic male rat.

In young adult male rats bearing a donor anterior pituitary gland grafted for 3 weeks under a kidney capsule, serum prolactin (PRL) concentrations were elevated and exhibited a rhythm with the highest values in the light phase. Serum PRL in control animals did not exhibit a significant rhythm. Eutopic pituitary PRL content, manifesting a biphasic (12-hr) rhythm with crests during the day and night in controls, exhibited a similar pattern in grafted rats though an overall reduction in pituitary PRL content was seen in the grafted animals. Neither the normal biphasic serum testosterone rhythm nor the normal 24-hr rhythm (nocturnal surge) of pineal N-acetyltransferase activity and melatonin content were altered in the hyperprolactinemic rats. Serum thyroxine (T4) and triiodothyronine (T3) and their free indices (FT4I, FT3I) and serum thyrotropin (TSH) were highest during the day in controls and grafted rats and a 12-hr rhythmic component was detected in data for these variables. In the grafted animals, the 12-hr component was reflected in an additional peak at night detectable by testing of means. The overall serum T4, FT4I, and TSH levels were lower in grafted rats though overall T3 and FT3I levels did not differ between grafted and controls. T3 uptake (T3U) values were similar between controls and grafted rats, in both cases exhibiting a fall during the night. Changes in serum thyronines could not be explained by changes in serum binding as assessed by the T3U, and thus may represent changes in thyroidal secretion of T4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Adult-onset Still's disease. Clinical course and outcome.

We reviewed the long-term natural history of 21 adult-onset Still's disease patients. Patient subsets were identified according to clinical course patterns. These included monocyclic systemic disease in 4, polycyclic systemic disease in 2, chronic articular monocyclic systemic disease in 10, and chronic articular polycyclic systemic disease in the remaining 5 patients. Functional outcome differed according to course patterns and the extent of articular involvement. Systemic manifestations, per se, did not contribute to poor functional prognosis. Chronic articular disease had the worst outcome: 27% evolved to functional class III status, compared with none in the cyclic systemic groups. Those patients who had a chronic articular pattern or a polyarticular onset and course were at higher risk to develop disabling arthritis. An aggressive approach to therapy, including the early use of remittive agents, should be considered in these patient subsets.

Adolescent↗