The effect of bilateral thoracoplasty on lung development in fetal sheep

The relationship of breathing movements to lung development in the ovine fetus was investigated by partially removing ribs on each side of the chest and closing the deficiencies with silicone membranes at 114 days of gestation; the increase in compliance of the chest wall that resulted caused blunting of the amplitude of phasic negative pressures recorded in the trachea to less than 10 torr. Compared to sham operated controls (n = 5), the lungs of the thoracoplasty group (n = 5) at term weighed significantly (P less than 0.05) less, both wet (1.5 +/- 0.2 v. 2.3 +/- 0.1% of body weight) and dry (0.14 +/- 0.01 v. 0.18 +/- 0.01% of body weight. In addition, DNA content of the thoracoplasty group was less than that of the control group (0.47 +/- 0.05 mg v. 0.72 +/- 0.20 mg). Distensibility of the left lung with air at 40 cmH20 was less than in the thoracoplasty group than in controls (10.0 +/- 2.0 v. 18.9 +/- 3.0 ml.kg-1 body weight) but no differences were found in the concentrations of saturated phosphatidylcholine in lung tissue and lavage fluid, in DNA concentrations or in the amount of lung water (as % of wet weight of lung). It is concluded that phasic negative pressures of normal intensity are necessary for normal development of the fetal lungs.     

Concanavalin A crossed affinoimmunoelectrophoretic analysis of the major pig serum proteins during fetal development

The interaction between concanavalin A (Con A) and alpha-fetoprotein (AFP), transferrin (TF), fetuin, alpha 1-antitrypsin (AT) and alpha 1-acid glycoprotein (AGP) has been analyzed by crossed affinoimmunoelectrophoresis (CAIE) in fetal extracts or sera, from 26-day-old porcine fetuses to birth, and in adult pigs. Most of the TF and AFP (100 and 85-90%, respectively) reacted with Con A during the entire developmental period. AGP showed both two reactive and one nonreactive Con A isoforms, whose proportions change greatly during development. In younger fetuses 100% of the protein was Con A-nonreactive. This variant represented 64% in 50-day-old fetuses, 80% in newborn pigs and 20% in adult sera. Fetuin and AT showed a maximum of three Con A-reactive microforms and one Con A-nonreactive microform, which was always a minor form. These microforms were detected mainly in young fetuses. Although the proportion of Con A-reactive variants of fetuin and AT changes during fetal development, the predominant microform was always that with intermediate affinity against Con A. The same microform was also predominant in adult AT, whereas the more reactive microform in respect to Con A predominates in adult fetuin.     

Neurotransmitter and amino acid analysis and ultrastructural observations of fetal brain cortex transplantation to adult rat brain under the effect of dexamethasone

OBJECTIVE: To conduct an investigation of fetal cortical tissue graft survival using transmission electron microscopy and analyzing neurotransmitters and amino acids and their function, with special reference to the effect of dexamethasone. METHODS: Transplantation of fetal cortical brain tissue to 100 adult Wistar albino rats weighing 170 to 220 g was performed. The rats were divided into three groups. Only transplantation of fetal cortical brain tissue was performed in the first group (n=36). In the second group (n=48), dexamethasone was administered in addition to fetal cortical tissue transplantation. The third group (n=16) was used as the surgical control group. The rats were allowed to live for 6 weeks and were then decapitated. The grafts were examined by electron microscopy. Additionally, quantitative analyses of the neurotransmitters and amino acids of the grafts were conducted using high-pressure liquid chromatography. RESULTS: Electron microscopic observations revealed that the grafts were still surviving at the end of the 6th week in both groups. However, in the group that received dexamethasone, neurons and their organelles were better developed than in the group that did not receive dexamethasone. Concommitantly, results of quantitative analysis in the dexamethasone group revealed statistically extremely significant higher amino acid values for glutamic acid, aspartic acid, beta-alanine, and lysine and significantly higher values for gamma-aminobutyric acid, glutamine, glycine, and serine when compared to the nondexamethasone group. CONCLUSION: Dexamethasone is effective in increasing the survival and in developing the ultrastructural and functional outcome of transplanted neurons in fetal grafts.     

Development of the human fetal visceral pleura. An ultrastructural study

OBJECTIVE: To develop a method to predict long-term outcome after head injury and determine if outcome can be accurately predicted 24 hours after injury. DESIGN: A retrospective review was performed on a study cohort of 672 head-injured patients admitted in coma (Glascow Coma Scale score < or = 8) who remained comatose for at least 6 hours, survived more than 24 hours, and had 6-month outcome data available. Stepwise logistic regression analysis was used to determine which clinical variables predicted 6-month outcome. Statistically significant clinical predictors were combined into a single examination variable (MPX score), which reflected a rank-ordering of examinations from worst to best, which was then further weighted by patient age. The relation between 6-month outcome and MPX score at admission and 24 hours was plotted and analyzed. MEASUREMENT AND MAIN RESULTS: Age, best motor score, and pupillary reactivity at admission and 24 hours were significant predictors of outcome; extraocular motility was predictive at 24 hours only. Age was the most important independent predictor, followed by best motor score, pupillary reactivity, and extraocular motility. Combining these predictors into MPX score resulted in a set of graphs that reliably predicted long-term outcome. The 24-hour MPX data were better predictors of 6-month outcome and were more specific in predicting negative outcomes than admission data. CONCLUSIONS: The method is simple to use, relying on bedside neurologic examination and a single graph, but appears to predict long-term outcome accurately as early as 24 hours after head injury. If validated on other large series of patients, this method could provide an objective and practical basis for terminating care in patients unlikely to survive a head injury.     

Light microscopic and ultrastructural observations of a metastasizing malignant epithelioid schwannoma

The light microscopy and ultrastructure of a malignant epithelioid schwannoma are described. Characteristic cells resembling perineural elements with various degrees of differentiation were observed. Primitive epithelioid cells contained scant ergastoplasm, and few tubules and filaments, but did have abundant free ribosomes and Golgi membranes. Also noted were junctional complexes and focal fusion of plasma membranes, basal laminae were absent. Better differentiated cells were completely limited by a well-developed basal membrane and had an abundance of intracytoplasmic filaments and multiple pinocytotic vesicles. The intercellular ground substance was composed of numerous fine collagen fibrils and amorphous, basement membrane-like, electron-dense material. A striking ultrastructural similarity of the tumor cells to those encountered in ethylnitrosourea-induced malignant schwannomas in rats was noteworthy.     

Amylase-producing lung cancer: ultrastructural and biochemical studies

A case of lung cancer with elevated amylase activity in serum, urine, and tumor tissue was studied electron microscopically and biochemically. Ultrastructurally, there were numerous electron-dense granules in the cytoplasm of most tumor cells. These granules were located in the apical region of tumor cells and had a single limiting membrane, associated with a clear zone just beneath it. Furthermore, circular, lamellar and annulate structures, which closely resembled those observed within zymogen granules of the salivary glands in postnatal mice and rats, were sometimes recognized within these granules. These observations suggested that these granules were identical to a postnatal or immature form of zymogen granules in salivary glands. Biochemical analysis confirmed that the amylases obtained from the tumor tissue were composed of the sialic acid-containing glycoprotein, which was not found in normal amylases. A possible histogenesis of the amylase-producing lung cancer was briefly discussed.     

Androgen regulation of epidermal growth factor receptor binding activity during fetal rabbit lung development

The luteolytic response to a prostaglandin F2 alpha analogue, cloprostenol, was investigated in vivo and in vitro at defined stages of the luteal phase. In vivo administration of cloprostenol to female marmoset monkeys on day 3 after ovulation had no effect on plasma progesterone concentrations, whereas administration on day 14 after ovulation reduced plasma progesterone to preovulatory concentrations within 4 h. To identify the cellular basis for this luteolytic action, marmoset luteal tissue obtained on days 3, 6 and 14 after ovulation was incubated in vitro and progesterone production, cAMP accumulation and phosphoinositide (PI) turnover measured in response to cloprostenol, human chorionic gonadotrophin (hCG) with or without cloprostenol, or dibutyryl-cAMP with or without cloprostenol. Progesterone production was stimulated by both hCG and dbcAMP at all stages of the luteal phase. Although neither hCG nor dbcAMP had any significant effects on PI turnover, hCG also increased cAMP accumulation. In marmoset luteal tissue obtained on day 3 after ovulation, cloprostenol had no significant effect on basal or hCG/dbcAMP-stimulated progesterone production but significantly stimulated PI turnover. In contrast, on days 6 and 14 after ovulation, cloprostenol significantly inhibited hCG- and dbcAMP-stimulated progesterone production and the cAMP response to hCG, but had no significant effect on PI turnover. Since progesterone production by the marmoset corpus luteum depends on the luteotrophic support of luteinizing hormone (LH), these observations suggest that the luteolytic action of cloprostenol in vivo involves the inhibition of LH/hCG action at sites both prior and subsequent to cAMP accumulation. However, such luteolytic effects do not appear to require the generation of inositol phosphates by increased PI turnover.     

Histological observations on some of the endocrine glands in the ironfish, with special regard to the hypophysis

Endocrine glands of the ironfish were studied light microscopically to elucidate the relationship between the races of the genus Carassius. The rostral pars distalis of the adenohypophysis consists mainly of acidophils corresponding to prolactin cells and lead-hematoxylin positive cells corresponding to corticotrophs (ACTH cells). The prolactin cells are obviously arranged in the form of follicles. The proximal pars distalis contains orangenophils (STH cells) and two types of basophils (TSH and GTH cells). In the pars intermedia, three types of cells are identified: periodic acid Schiff positive cells, lead-hematoxylin stainable cells and orangenophils containing PAS positive coarse granules. In addition, small agranular cells are seldom demonstrated in the entire adenohypophysis. A considerable amount of aldehyde fuchsin positive neurosecretory material is laden in the cells of the nucleus preopticus and in the pars nervosa. The nucleus lateralis tuberis is composed of three portions: pars anterior, pars posterior, and pars lateralis. The thyroid follicles found in the pharyngeal region and head kidney show a mild state of activity. The interrenal cells intermingled with the chromaffin cells have a considerable amount of eosinophil cytoplasm. Judging from the gonadal condition, the breeding season of the ironfish may extend to the end of July.     

Effects of ultraviolet B irradiation on fetal pig islet-like cell clusters

Gut mucosal hypoperfusion plays a major role in the pathogenesis of ongoing sepsis and multiple organ dysfunction syndrome. Traditionally, therapy included increasing systemic flow, thus secondarily augmenting blood flow to the gut. Direct manipulation of the gut mucosal microcirculation avoiding systemic effects, i.e., selective gut microcirculatory control (SGMC), has not been tested with a clinically available vasodilating drug. We hypothesized that a topically applied vasoactive drug would affect gut mucosal microcirculation without systemic effects. Twelve Sprague-Dawley rats were randomly assigned to cecal ligation and perforation (CLP), or sham (SC) laparotomy. Twenty-four hours after surgery, mucosal arterioles of a 3-4 cm exteriorized ileal segment were studied using intravital microscopy while suffused with saline followed by sodium nitroprusside (SNP, 100 microg/mL, 3.4 mM). SNP normalized (to SC saline values, 14.5 +/- .6 microm) the CLP arteriolar diameters, from 11 +/- 6 to 14.6 +/- .3 microm (p < .05), while mean arterial pressure (MAP) was stable. Flowmotion patterns were also normalized by SNP, and intercapillary areas (i.e., diffusion distance) were decreased. We conclude that SNP exerted beneficial effects on gut mucosal microcirculation without affecting MAP; therefore, SGMC may be a novel way to affect the course of sepsis.     

Gonadoblastoma: histologic, ultrastructural, and histochemical observations in five cases

In this series of gonadoblastomas it appeared that the germ cells were the motivating force underlying either tumor proliferation or regression. The ultrastructural morphology confirmed the presence of undifferentiated gonadal cells with active steroid synthesis by the interstitial cells. The Call-Exner-like bodies which showed extensive calcification were composed of basement membrane material containing a sulfated mucosubstance. A histochemical comparison with the noncalcifying Call-Exner bodies of a granulosa-cell tumor differed only in their glycoprotein content. The calcium deposits were identified as oriented hydroxyapatite crystals by electron diffraction, and it is proposed that the basement membrane material serves as a nucleation site for calcification. High serum testosterone levels were correlated with the presence solely of interstitial cells in one case. The finding of a gonadoblastoma without the presence of a Y chromosome contradicts earlier proposals concerning the requirement of a Y chromosome for germ cell proliferation.     

The localization of cholinesterase in the retina of the fetal and newborn guinea pig

Retinae of guinea pigs from the fortieth day of gestation to one day postnatally were processed for the localization of cholinesterases in the electron microscope according to the method of Lewis and Shute ('66). Selective inhibition served to distinguish acetylcholinesterase from non-specific cholinesterase activity. Acetylcholinesterase activity was found initially in small amounts in some regions of the outer plexiform layer at the fortieth day of gestation. At later stages it increased in distribution being observed at some photoreceptor terminals and in non-synaptic regions of the layer. Activity was less intense initially in the inner plexiform layer but increased rapidly so that by birth it encompassed a majority of processes. Perikarya of horizontal and some amacrine and ganglion cells possessed acetylcholinesterase activity in their nuclear envelope and rough endoplasmic reticulum. The possible role of the enzyme in inhibitory circuits of the fetal retina is discussed.     

Observations on early development of the murine fetal oral vestibule

The Spontaneous Selective Attention Task (SSAT) is a visual word-identification task that measures the type of selective attention that occurs spontaneously when there are multiple stimuli, all potentially relevant, and insufficient time to process each of them fully. The present study was designed to examine the sensitivity of the SSAT by comparing the performance of 40 schizophrenic inpatients and 30 schizophrenic outpatients to that of 70 normal controls. The pattern of results reported previously for schizophrenic inpatients versus normals was replicated, and these findings were extended to include schizophrenic outpatients in partial symptom remission. Schizophrenic inpatients and outpatients were just as accurate in identifying words as normals, but spontaneous selective attention under conditions of predictability was abnormal in both patient groups. Furthermore, the ability of the SSAT to discriminate between schizophrenic patients and controls was confirmed. A ratio measure of spontaneous selective attention had a sensitivity of 77% and a base rate of 9% in a normal population (when a cutoff value was set to minimize false positives and false negatives). Thus, the SSAT is a sensitive measure of an attentional phenotype that may be useful in genetic studies of schizophrenia.     

Carbonate dehydratase (carbonic anhydrase) and the fetal lung

Carbonic anhydrase activity (carbonic dehydratase, EC 4.2.1.1) has been detected in the fetal lungs of stillborn human infants and rhesus monkeys, but a role for this enzyme in the fetal lung has not been elucidated. In utero the mammalian lung develops as a liquid-filled structure, the liquid being secreted by the lung. In the fetal lamb this liquid, when compared with plasma, has a high chloride and a low bicarbonate concentration, suggesting a possible role for carbonate dehydratase. Studies on 10 fetal lambs confirmed the presence of carbonate dehydratase in the lung. Levels at 60-66 days were negligible and rose to 0.30 Meldrum Roughton units/mg protein at about 140 days (term 147 days), with little change after birth. In another six fetal lambs at 135-136 days, inhibition of this enzyme with 100 mg acetazolamide suppressed the mean rate of secretion of lung liquid by 64.5% (P less than 0.005), which correlated with a significant drop in chloride concentration (P less than 0.001). This magnitude of changes in secretion after acetazolamide is of the same order as that occurring in the secretion of cerebrospinal fluid when carbonate dehydratase is inhibited. This observation supports the hypothesis that carbonate dehydratase in fetal lung affects the secretion of lung liquid, although its mechanism is as yet unknown.     

Effects of cocaine on fetal and postnatal development in mice

The goal of the current investigation was to study the effect of in utero exposure of cocaine on fetal and postnatal development. 48 adult female NIH Swiss mice were used as experimental animal models. Each of the 24 mice were injected intraperitoneally with cocaine HCl at a daily dose level of 45 mg/kg (body weight). Each of the 24 control animals were daily injected with saline. One week after the treatment started, one male was introduced into each female cage. The day the vaginal plug was found was recorded as day one of pregnancy. Both cocaine treated and saline treated animals were subdivided into three subgroups each with 8 animals in each subgroup. Subgroup one was used to obtain midgestational (11 day) fetuses, subgroup two was used to obtain full term fetuses (18 day) and subgroup three was used to obtain pups. Individual fetal weights were taken and each fetus was examined for developmental anomalies. Midgestational fetuses exposed to cocaine had lower body weights than those of the controls. The full term fetuses, however, had similar weight in both experimental and control groups. The pups were weighed every 2 days from day 2 to day 16. The pups showed a slightly wider range of weights in the cocaine treated group as they matured to 16 days. All fetuses and pups revealed no soft tissue anomaly which, along with the weight data, supported our earlier findings.     

Testosterone secretion by the early fetal pig testes in organ culture

The alkaline phosphatase activity was measured in testicular fluid and in epididymal plasma from caput and cauda epididymidis in boars with normal sperm production and in boars in which the number of spermatozoa passing from the testis to the epididymidis was reduced. The testicular fluid and the epididymal plasma from caput epididymidis contained low amounts of alkaline phosphatase in comparison with epididymal plasma from the cauda. This applies to both groups of boars e.g. boars with normal as well as with totally lacking or lowered sperm production. As no fluid resorption takes place between caput and cauda the distal part of the epididymidis must be the main production site for alkaline phosphatase. The production there is not related to the presence of spermatozoa in the duct. In the caput, on the other hand, it seems that the level of alkaline phosphatase in some way is influenced by the sperm supply to the duct.     

Suppressive effect of fetal testes on development of fetal ovaries transplanted into adult males in the rat

The age-related testicular effect on the ovarian primordia was studied by combined transplantation of fetal testes and ovaries in adult male hosts. First, ovarian primordia of 14-day fetal rats were transplanted into a renal subcapsular position of castrated or intact adult male rats. In both the castrated and the intact hosts, most of the ovarian transplants developed normally with only 3 of them having in part seminiferous tubule-like structures in addition to normal ovarian structure. Second, a 14-day ovary was combined with a fetal testis the age of which varied from 13- to 18-day, and the combination was transplanted. In the combination of a 14-day ovary and a 13-day testis, the results varied in such a way that the ovary or the testis alone developed or otherwise, both gonads developed well. In union with 15- to 18-day testes, the ovaries did not develop, although the testes developed well. These results suggest that the 14-day ovarian primordia have a slight reactiveness to androgens of host rats and that the 13-day fetal testes begin to inhibit the development of the 14-day ovaries co-transplanted with them.     

Immunocytochemical studies on endocrine cells of alimentary tract of the pig in the embryonic and fetal period of life

The study aimed at immunocytochemical analysis of alimentary tract endocrine cells between 20th day of embryonal life and 105th day of fetal life of domestic pig. In the pancreas, presence of endocrine cells was detected already in 20th day and, at the time, the cells comprised around 3/4 all cells in primordia of the organ. Starting at that time, numerous endocrine cells produced insulin and glucagon and individual cells synthesized somatostatin and pancreatic polypeptide. In the 20th day, stomach and duodenum contained single endocrine cells but hormone production was not detected until days 27 and 30. Beginning from this days, both organs manifested rapid increase in the number of gastrin-producing cells. In each of the three organs, the number of somatostatin-producing cells exhibited most extensive changes.