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Biomedical subjects

N R Saunders

Publications and source records attributed to N R Saunders.

At least 109 records · Page 6Linked to original sources
PubMed1988

Complement-mediated pulmonary edema in sheep.

Incubation of plasma with zymosan results in complement activation. Infusion of zymosan-activated plasma (ZAP) into the pulmonary circulation in sheep results in a transient rise in pulmonary vascular resistance, accompanied by hypoxemia. This is associated with production of the vasoactive prostaglandin metabolite, thromboxane. We hypothesized that ZAP infusion caused pulmonary edema and may transiently alter pulmonary permeability to protein. Two sets of experiments were conducted involving six sheep. Three sheep underwent open lung biopsies during ZAP infusion, and electron microscopy documented early reversible interstitial pulmonary edema in response to ZAP infusion. Three other sheep were prepared with lung lymph fistulae and subjected to a similar infusion of ZAP. These studies documented a rapid rise in lymph flow and lymph protein clearance, occurring immediately upon infusion of ZAP. These experiments demonstrate a rapid reversible interstitial edema in sheep lung in response to ZAP infusion and suggest that permeability to protein may be transiently altered as a result of this injury.

Animals↗
PubMed1988

Blood-brain, blood-cerebrospinal fluid and cerebrospinal fluid-brain barriers in a marsupial (Macropus eugenii) during development.

1. The blood-brain, blood-CSF and CSF-brain barriers to protein have been studied in post-natal tammar wallabies (newborn to 70 days) using morphological and physiological techniques. 2. Endogenous and exogenous plasma proteins, and in some experiments horseradish peroxidase, were used as indicators of barrier integrity or permeability. 3. Immunocytochemical studies of endogenous tammar proteins showed that these (e.g. albumin) were present in the lumen of vessels in the brain, in cerebrospinal fluid (CSF) and within some cells in the choroid plexus and brain. No staining of the brain extracellular space was obtained; in particular there was no perivascular staining. Possible artifacts that could account for this lack of staining are discussed. 4. Ultrastructural studies showed the presence of well-formed tight junctions between cerebral endothelial cells and between choroid plexus epithelial cells, even as early as the day of birth. A membrane specialization between adjacent neuropendymal cells that had the same ultrastructural appearance as the 'strap junction' previously described in human and sheep fetuses was observed. These junctions may act as a barrier (CSF-brain barrier) to the passage of protein from CSF into brain in these immature animals, as has previously been described in eutherian fetuses. 5. In experiments in which exogenous plasma proteins or horseradish peroxidase were injected intravenously, care was taken to limit both the volume and protein load injected. These proteins penetrated into CSF. The naturally occurring steady-state CSF/plasma ratio for several proteins was approached by several of the injected (human) proteins within a few hours of I.V. injection, suggesting that much of the protein in CSF, at least when sampled from the hindbrain, originates from plasma in this species. No penetration across cerebral vessels was observed. Uptake of some proteins (e.g. albumin), occurred into neuroependymal cells at some ages. 6. These results suggest that the very immature brain of the newborn tammar is protected from protein present in the circulating plasma even at an embryonic stage of development by a combination of a well-formed blood-brain barrier to protein in the cerebral vessels and a CSF-brain barrier to protein at the level of the neuroependyma. The adult-type blood-CSF barrier to protein (tight junctions between adjacent choroid plexus epithelial cells) is present but appears to be bypassed in the immature brain, probably by a transcellular route across the choroid plexus.

Animals↗
PubMed1987

Cellular distribution of transferrin immunoreactivity in the developing rat brain.

The cellular distribution of immunoreactive transferrin has previously been studied in adult rat brain with the conclusion that transferrin is largely confined to oligodendrocytes, although studies in the developing rodent brain indicated some staining of neurons. Detailed investigations of a wider range of ages than studied earlier have shown that in the developing rat brain, transferrin is not only present in oligodendrocytes but also in other glial cell types and in neurons and endothelial cells. The preponderant cell type which is positive for transferrin and its regional distribution are, however, related to the age of the animal except in most circumventricular organs in which strong transferrin immunoreactivity was seen throughout the developmental period studied.

Animals↗
PubMed1987

Fetuin: the bovine homologue of human alpha 2HS glycoprotein.

The fetal protein fetuin has previously been considered to be confined to species of the order Artiodactyla (cattle, sheep, etc.) in spite of demonstrable biological in vitro effects in tissues of other species [(1983) Comp. Biochem. Physiol. 76A, 241-245]. We have determined the partial amino acid sequence of bovine fetuin and compared it with the published sequence of human alpha 2HS glycoprotein. The N-terminal 105 residues and a segment aligned with residues 170-225 of alpha 2HS glycoprotein revealed 109 of 161 residues to be identical between the two proteins (68% homology). Mouse polyclonal antibodies to fetuin, and trypsin digest fragments of this protein have been prepared and used for a comparison of native and digested proteins. Polyclonal antibodies to native protein showed little if any cross reactivity. However, antibodies to trypsin digest fragments of fetuin showed obvious cross reactivity with alpha 2HS.

Amino Acid Sequence↗
PubMed1987

Fetuin as a marker of cortical plate cells in the fetal cow neocortex: a comparison of the distribution of fetuin, alpha 2HS-glycoprotein, alpha-fetoprotein and albumin during early development.

Fetuin, alpha 2HS-glycoprotein (alpha 2HS), alpha-fetoprotein (AFP) and albumin have been shown to be present in some regions of the neocortex in two early stages of development of the cow brain using PAP immunocytochemistry. In the pre-cortical plate stage fibres of the primordial plexiform layer stained positively for fetuin. No staining was seen for albumin but plasma and cerebrospinal fluid (CSF) were positive for alpha 2HS and AFP. In the early cortical plate stage the strongest fetuin positive staining was seen in the earliest formed cells of the plate. alpha 2HS staining was much less intense but similar in distribution. The possible role of fetuin, or related glycoproteins, in cortical plate differentiation is discussed. Staining for AFP and for albumin was seen mainly in the ventricular zone and marginal zone fibres, and had a similar distribution and intensity for both proteins. Plasma and CSF stained for all four proteins. Tests showed some cross-reactivity between fetuin and anti-alpha 2HS and, to a much lesser extent, between antisera to AFP and albumin and antigens denatured by fixation.

Animals↗
PubMed1987

A fetuin-related glycoprotein (alpha 2HS) in human embryonic and fetal development.

The human plasma protein, alpha 2HS glycoprotein, has an amino acid composition very similar to that of fetuin, the major protein in fetal calf and lamb serum. Immunohistochemical studies of human fetuses (6-33 weeks gestation) showed that alpha 2HS glycoprotein and fetuin have similar distributions in developing brain and several other tissues, e.g., bone, kidney, gonads, gastrointestinal tract, respiratory and cardiovascular systems. There were notable differences in the liver and thymus in the distribution of the two proteins. Fetuin and alpha 2HS glycoprotein are present in plasma and cerebrospinal fluid of both human and sheep fetuses; their concentrations are reciprocally related: in human plasma and cerebrospinal fluid alpha 2HS glycoprotein concentration is high and fetuin low; the reverse is the case in sheep fetuses. Estimates of the concentration of alpha 2HS glycoprotein in human fetal cerebrospinal fluid and plasma were obtained. It is suggested that alpha 2HS glycoprotein may play a role in developing tissues, especially in the human fetus, similar to that of fetuin in other species.

Blood Proteins↗
PubMed1987

Cell junctions and membrane specializations in the ventricular zone (germinal matrix) of the developing sheep brain: a CSF-brain barrier.

Cell junctions in the ventricular zone (germinal matrix) of the embryonic and foetal sheep brain were examined with thin-section and freeze-fracture electron microscopy. Neuroependymal cells in the early ventricular zone (days 19-40 of embryonic development, gestation period 147 days) exhibit a novel arrangement of cell junctions that connect adjacent neuroependymal cells at their lateral cell membranes next to the ventricular system. Small but typical gap junctions were also identified from the earliest stages examined. In serial thin sections and using a goniometer with a tilting device, the cell contacts showed a tight junction-like appearance of close and continuous fusion between neighbouring cell membranes. However, they were not arranged in a belt-like fashion close to the ventricular surface, but spiralled from the ventricular pole of the cells along the lateral cell membrane towards the deeper parts of the ventricular zone. Their freeze fracture appearance was different from that of single-stranded tight junctions in that the dimensions of their ridges and grooves were generally greater and the E-face grooves contained many particles. The junctions were especially prominent where more than two cells made contact. At mid-gestation they were less prominent than earlier and at 125 days gestation the neuroependymal layer was replaced by a mature-looking normal ependymal layer in which individual ependymal cells were connected by zonulae adherentes and large gap junctions; orthogonal arrays were also prominent. The close contact between gap junctions and single-stranded junctions found early in gestation suggests that there may be some developmental relation between these two membrane specializations. The transient single-strand junctions presumably form the morphological basis for a recently described CSF-brain barrier in the early foetal sheep brain. They may also have some mechanical function in anchoring neighbouring cells together in the region of the developing brain where cells are continuously dividing and migrating.

Animals↗
PubMed1987

Right lower lobe consolidation: an unusual complication of the modified Blalock-Taussig operation.

Persistent right lower lobe consolidation in a 5-year-old girl is described. In infancy she had been diagnosed to have tricuspid atresia and pulmonary stenosis, and she had undergone a modified Blalock-Taussig shunt using a polytetrafluoroethylene tube graft at the age of 1 year. The shunt had parasitized and then occluded the right main bronchus. At bronchoscopy, the shunt was removed. The pneumonia resolved, and the child remains well 10 months later. This complication of the modified Blalock-Taussig shunt, which does not appear to have been reported previously, demonstrates the need for bronchoscopy in unresolving pneumonia in childhood.

Arteriovenous Shunt, Surgical↗
PubMed1986

An immunocytochemical demonstration of alpha 2HS-glycoprotein in the developing neocortex of the rat.

The presence of the plasma protein alpha 2HS-glycoprotein (alpha 2HS) has been demonstrated in the developing rat neocortex, using biotin-streptavidin immunocytochemistry. alpha 2HS was observed in the neocortex on embryonic day 20 but not earlier. At this age it was present in cells of the subplate and of the intermediate layer and in layer I anteriorly. Between postnatal day 5 and day 10 alpha 2HS-positive cells were found in greater number in various cortical layers and in fibres in layer I. At postnatal day 28 no alpha 2HS-positive cells or fibres could be found in the neocortex. alpha 2HS has been reported to be very closely related to fetuin which is a fetal plasma protein found in cells of the developing cortex in the sheep and the pig. It is suggested that these glycoproteins may be important in some aspects of early neocortical differentiation.

Aging↗
PubMed1986

Synthesis of plasma proteins in fetal, adult, and neoplastic human brain tissue.

The synthesis of plasma proteins directed by mRNA from human brain tissues was studied by combining in vitro or in ovo translation of mRNAs with crossed immunoelectrophoresis of the mRNA-directed labeled polypeptides, followed by autoradiography of the washed plates. Poly(A)-containing mRNA was prepared from different developmental stages of fetal and postnatal human brain and also from primary glioblastomas and meningiomas. Several plasma protein-like polypeptides were identified in the autoradiographs by their migration coordinates in the two-dimensional gels, compared with immunoprecipitates formed by mature, unlabeled, stainable proteins. These included polypeptides migrating like Gc globulin, haptoglobin, fibrinogen, alpha-fetoprotein, transferrin, cholinesterase, and alpha 2-macroglobulin; other, yet unidentified plasma proteins, were also observed. In general, the synthesis of these plasma proteins appeared to be more pronounced in fetal and neoplastic brain tissues than in postnatal tissues. However, clear immunoprecipitates for some of these plasma proteins could also be detected in products directed by mRNA from particular regions of mature, normal brains, indicating that some synthesis of plasma proteins takes place in the human brain even as late as 40 years of age. mRNAs for several proteins were also identified in samples of neoplastic brain. mRNA for transferrin was identified in normal fetal and adult brain but not in either the glioblastomas or meningiomas studied. Microinjected Xenopus oocytes, in which post-translational processing occurs as well, were also used to translate fetal brain mRNA. Several plasma proteins could be detected in the translation products which were induced and stored in the oocytes. These included hemopexin, which could not be detected in the in vitro system. Others, such as cholinesterase, were found to be secreted by the oocytes. These findings indicate that different cell types in the human brain may produce and either store or secrete particular plasma proteins at defined stages in their development.

Animals↗
PubMed1986

Proteins in cerebrospinal fluid and plasma of the pouch young tammar wallaby (Macropus eugenii) during development.

The concentrations of total protein and albumin in cerebrospinal fluid (CSF) and plasma of tammar wallaby pouch young (Macropus eugenii) from birth until leaving the pouch have been measured. Total protein in CSF increased from birth (about 240 mg/100 ml) to 15-20 days postnatal (about 400 mg/100 ml) after which it declined. Albumin showed a proportionately greater increase from around 40 mg/100 ml to over 130 mg/100 ml, followed by decline after 75 days. Total protein and albumin in plasma increased throughout the period studied. Other proteins identified in CSF and plasma were: fetuin, alpha 2-macroglobulin, transferrin, alpha-lipoprotein, beta-lipoprotein, immunoglobin G and fibrinogen. One protein was only present in early pouch young (up to about 40 days) and was presumed to be the tammar equivalent of alpha-fetoprotein.

Aging↗
PubMed1986

Surgical treatment of idiopathic mediastinal fibrosis: report of five cases.

Idiopathic mediastinal fibrosis is a rare disease of unknown aetiology. It is a benign condition in which abnormal proliferation of fibrous tissue occurs within the mediastinum, leading to constriction and obliteration of local structures, particularly the great veins. It is a rare cause of superior vena caval obstruction (1-2%) but one that is potentially amenable to surgical palliation. The results of venous reconstruction in five patients with superior vena caval obstruction secondary to idiopathic mediastinal fibrosis are reported. Reversed autogenous saphenous vein grafts were used in two patients, woven silicone rubber prostheses in two, and bovine pericardial conduits in one patient. Useful long term results were obtained in three patients, but the bovine pericardial graft and one of the vein grafts failed within a few weeks.

Adult↗
PubMed1985

Postnatal development of the telencephalon of the tammar wallaby (Macropus eugenii). An accessible model of neocortical differentiation.

The sequence of development of cell layers in the neocortex of the tammar has been followed from 24 days gestation to 213 days postnatal. The tammar is born at 27 days gestation and the major period of its development occurs during the subsequent 250 days, most of this time being spent within the pouch. Although the pattern of differentiation of the cell layers appears to resemble that described for many Eutherian mammals, the neocortex is at an embryonic 2 layered stage at birth and a cortical plate is not present throughout the telencephalon until 10-15 days postnatal. A transient subplate zone, presenting a characteristic appearance with widely spaced rows of cells aligned parallel to the cortical surface, develops between 20 and 70 days postnatal, but no secondary proliferative region is seen in the subventricular zone of the dorso-lateral wall. Preliminary experiments with (3H)-thymidine injections indicate that the cortical plate follows the "inside-out" pattern of development described in many Eutherian mammals and that the oldest neurons are found in the parallel cell rows of the subplate zone. The importance of the late differentiation of the neocortex in relation to the time of birth and the resulting usefulness of the tammar as an experimental model of cortical development is discussed.

Aging↗
PubMed1985

Messenger ribonucleic acid (mRNA) from developing rat cerebellum directs in vitro synthesis of plasma proteins.

Poly(A)-containing messenger RNA from different ages of postnatal rat cerebellum was translated in the reticulocyte lysate system, using [35S]methionine to label newly synthesized polypeptides. Translation products were identified using crossed immunoelectrophoresis and antisera against whole rat plasma and/or specific plasma proteins, followed by autoradiography. It was found that postnatal cerebellar mRNA directs the synthesis of low density lipoprotein (LDL), fibrinogen, transferrin, alpha 1-macroglobulin, alpha 2-macroglobulin and probably also alpha-fetoprotein, albumin and alpha 1-lipoprotein. mRNAs for several other yet undefined plasma proteins were also detected. In general, the synthesis of plasma proteins appeared to decline with cerebellar maturation. X-irradiation or hypothyroidism resulted in selective changes in the levels of mRNA-directed plasma proteins. In the X-irradiated cerebellum these included an increase in the level of mRNA for alpha-fetoprotein and a decrease in the level of mRNA for fibrinogen. In contrast, hypothyroidism decreased cerebellar plasma protein synthesis in general. These observations indicate that plasma proteins are actively produced within the developing rat cerebellum, and that the rate of their synthesis depends on the developmental stage and is influenced by the types of cells present.

Age Factors↗
PubMed1985

CSF-brain permeability in the immature sheep fetus: a CSF-brain barrier.

The permeability of the neuroependyma between CSF and brain extracellular space has been studied in fetal sheep of 60 and 125 days gestation. Both radioactive ([3H]inulin, [14C]sucrose, [125I]albumin) and visible (horseradish peroxidase) markers have been perfused through the ventricular system for periods of up to 5 h in anaesthetized exteriorized fetal sheep whose physiological condition was monitored continuously. A previously undescribed barrier between CSF and brain extracellular fluid has been discovered in the immature (60-day) fetal sheep. Horseradish peroxidase penetration was confined to a limited depth of the neuroependyma and was mainly into the cells lining the cerebral ventricles; in older fetuses there was extracellular penetration to a distance of several millimetres from the ventricular surface, as previously described in adult animals. The volumes of distribution of sucrose and insulin were less in the immature brain than in the more mature brain, which may be a reflection of restricted diffusion across the neuroependyma in the younger brains. The morphological nature of the barrier in fetuses of 60 days and younger appears to be a membrane specialization between the cells of the neuroependyma. It is of a type not previously described; it seems to have the effect of narrowing rather than obliterating the extracellular pathway between CSF and brain. The possible functional significance of this observation is discussed.

Animals↗
PubMed1985

Contribution of circulating formed elements to prostanoid production in complement-mediated lung injury in sheep.

Incubation of plasma with zymosan results in complement activation. Infusion of this "zymosan-activated plasma" (ZAP) into the superior vena cava in sheep results in pulmonary leukostasis, pulmonary hypertension with generation of thromboxane (TXB), and hypoxemia. To examine the contribution of circulating formed elements to TXB generated when ZAP is infused, we studied four pairs of sheep in a cross-circulation model. Acetylsalicylic acid (ASA) irreversibly acetylates cyclooxygenase and blocks TXB production. Four hours after an intravenous dose of ASA (10 mg/kg), no circulating ASA was detectable by high-pressure liquid chromatography. Infusion of ZAP in ASA-treated animals resulted in no pulmonary hypertension and no rise in serum TXB levels. Treated animals were then cross-circulated with untreated sheep through cannulas that attached a carotid artery of each animal to a jugular vein of the other, creating simultaneous arteriovenous fistulas between the animals. A roller pump maintained cross-circulation flow at 450 ml/min for 15 minutes. This resulted in greater than 80% mixing of the circulating blood volumes of each pair of animals, verified by measurement of an intravascular marker. After cross-circulation the ASA-treated animals were still unable to generate TXB in response to ZAP infusion. Untreated animals had a typical response when infused with ZAP after cross-circulation, with elaboration of large amounts of TXB. Since the treated animals with circulating, nonaspirinated formed elements showed no response and the untreated animals with similar blood composition had a normal response, we conclude that circulating formed elements do not contribute significantly to the TXB recovered from sheep infused with activated complement components.

Animals↗
PubMed1984

Differential immunocytochemical staining for fetuin and transferrin in the developing cortical plate.

The distribution of the plasma proteins fetuin and transferrin in fetal sheep neocortex has been studied using the indirect immunoperoxidase method. Most of the cells (presumed to be neurons) in the early cortical plate (35 days gestation) were positive for fetuin. In contrast the fibre systems on either side of the cortical plate were positive for transferrin; some fibres were weakly positive for fetuin. It is proposed that these fibres may originate from brainstem and perhaps from some thalamic nuclei and that the plasma proteins are probably transferred from the neuronal cell bodies to their peripheral processes. It is further suggested that plasma proteins such as fetuin and transferrin may have a role in neuronal differentiation and synaptogenesis.

Animals↗