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Biomedical subjects

C Stanton

Publications and source records attributed to C Stanton.

At least 19 recordsLinked to original sources
PubMed1998

Development of a probiotic cheddar cheese containing human-derived Lactobacillus paracasei strains.

Cheddar cheese was manufactured with either Lactobacillus salivarius NFBC 310, NFBC 321, or NFBC 348 or L. paracasei NFBC 338 or NFBC 364 as the dairy starter adjunct. These five strains had previously been isolated from the human small intestine and have been characterized extensively with respect to their probiotic potential. Enumeration of these strains in mature Cheddar cheese, however, was complicated by the presence of high numbers (>10(7) CFU/g of cheese) of nonstarter lactic acid bacteria, principally composed of lactobacilli which proliferate as the cheese ripens. Attempts to differentiate the adjunct lactobacilli from the nonstarter lactobacilli based on bile tolerance and growth temperature were unsuccessful. In contrast, the randomly amplified polymorphic DNA method allowed the generation of discrete DNA fingerprints for each strain which were clearly distinguishable from those generated from the natural flora of the cheeses. Using this approach, it was found that both L. paracasei strains grew and sustained high viability in cheese during ripening, while each of the L. salivarius species declined over the ripening period. These data demonstrate that Cheddar cheese can be an effective vehicle for delivery of some probiotic organisms to the consumer.

Amino Acids↗
PubMed1998

Elevation of conjugated cis-9, trans-11-octadecadienoic acid in bovine milk because of dietary supplementation.

Cows on pasture were fed full fat soybeans (toasted, flaked, and pelleted) or ground full fat rapeseeds to investigate effects on cis-9, trans-11-octadecadienoic acid in milk. Three herds of 16 cows each that were on pasture were fed 3.1 kg/d of unmolassed beet pulp (control), 3.0 kg/d of rapeseed concentrate, or 3.1 kg/d of a soybean supplement. The concentration of cis-9, trans-11-octadecadienoic acid in the milk of cows fed the rapeseed and soybean supplements was significantly higher than in the milk of cows fed the control diet during the feeding trial. Over the trial, the cis-9, trans-11-octadecadienoic acid concentration in the milk of individual cows varied from 6.8 to 25.7 mg/g of fat in the control herd, from 10.6 to 33.5 mg/g of fat in the herd fed the rapeseed concentrate, and from 8.8 to 30.5 mg/g of fat in the herd fed the soybean supplement. The concentration of cis-9, cis-12-octadecadienoic acid, the substrate for cis-9, trans-11-octadecadienoic acid synthesis in the rumen, was 4.9 g/100 g of fatty acid methyl esters in the milk fat of cows fed the soybean supplement, 2.5 g/100 g of fatty acid methyl esters in the milk fat of cows fed the rapeseed concentrate, and 2.3 g/100 g of fatty acid methyl esters in the milk fat of the control cows. Milk yield and milk constituent yields were not affected by supplementation of either full fat soybeans or rapeseeds compared with controls, but milk protein concentration was significantly reduced by both oilseed supplements.

Animals↗
PubMed1996

Processing and expression of rat and human clotting factor-X-encoding cDNAs.

The cDNA encoding clotting factor X, which participates in the middle stage of the blood coagulation cascade was cloned from a rat liver cDNA library. Sequencing of the rat factor-X-encoding cDNA revealed that this vitamin-K-dependent protein has a dibasic Arg-Arg sequence at the propeptide cleavage site, as occurs in other vitamin-K-dependent proteins. Although the human and rat deduced amino acid sequences are remarkably similar (76% identical), they do significantly differ in that human factor-X contains a unique Thr-Arg sequence at the propeptide cleavage site [Fung et al., Proc. Natl. Acad. Sci. USA 82 (1985) 3591-3595], where a dibasic sequence would normally be expected. This specific site is the recognition motif for the endoprotease, furin, which is located in the Golgi apparatus. Both rat and human cDNAs expressed in Cos-1 cells resulted in secretion of a mixture of single- and two-chain forms of factor X. The two-chain forms were devoid of the propeptide and were produced at similar rates by the transfected cells. The efficient processing of human factor X, when compared to rat factor X, may indicate that an additional protease(s), which recognizes the Thr-Arg motif, may be involved in proteolytic processing of the human enzyme.

Amino Acid Sequence↗
PubMed1996

Maternal mortality.

A new approach to measuring maternal mortality indicates that there are some 585,000 maternal deaths, 99% of them in developing countries. This is around 80,000 deaths more than earlier estimates have suggested and indicates a substantial underestimation of maternal mortality in the past. There is a greater disparity in levels of maternal mortality between industrialized and developing countries than in any other public health indicator. While significant progress has been made in reducing infant mortality, the same is not true for maternal mortality. Although the actions needed to reduce maternal mortality have long been known, 1 woman in 50 is still dying as a result of pregnancy-related complications and the figure rises to 1 in 10 in many parts of Africa. By contrast, the figure for developed countries can be as low as 1 in 8,000.

Cause of Death↗
PubMed1995

Evidence for competition between vitamin K-dependent clotting factors for intracellular processing by the vitamin K-dependent gamma-carboxylase.

This study demonstrates an apparent competition between newly synthesized precursors of prothrombin and factor X for binding to and processing by the gamma-carboxylase in the ER membrane of hepatocytes. The precursor of factor X appears to exhibit a strong affinity for the carboxylase than the prothrombin precursor. This conclusion is supported by the findings that 1) in normal hepatocytes, the factor X precursor prevents increased prothrombin precursor binding to the ER membrane, 2) increased prothrombin binding to the ER membrane was measured in H4-II-E-C3 Reuber H-35 cells where factor X synthesis is suppressed. The variations in the concentrations of the prothrombin and the factor X precursors that were as associated with the ER membrane correlated with the available prothrombin and factor X substrate pools for the gamma-carboxylase.

Animals↗
PubMed1995

Langerhans cell histiocytosis involving the corpus callosum and cerebellum: gadolinium-enhanced MRI.

Langerhans cell histiocytosis is a systemic disorder consisting of abnormal histiocyte proliferation, in the form of focal deposits. Central nervous system involvement is most common in the hypothalamus, although other sites have been described, such as the cerebellum and the meninges. We present a case with presumed involvement of the corpus callosum and cerebellum, demonstrating gadolinium enhancement on MRI.

Adolescent↗
PubMed1995

Progressive outer retinal necrosis secondary to varicella zoster virus in acquired immune deficiency syndrome.

BACKGROUND: A syndrome consisting of rapidly progressive outer retinitis in patients with suppressed immune systems has been described. The etiologic agent appears to be a member of the herpes virus family. METHODS: A 41-year-old man with acquired immune deficiency syndrome (AIDS) developed bilateral outer retinitis and choroiditis, which progressed despite antiviral treatment. A transscleral eye wall biopsy specimen and whole globe were submitted for microbiologic and histologic study. RESULTS: Polymerase chain reaction of a transscleral eye wall biopsy specimen and of the enucleated specimen determined the etiologic agent to be varicella zoster virus (VZV). Histologic studies demonstrated intranuclear inclusions consistent with viral particles in choroidal cells. CONCLUSION: Our study revealed intranuclear inclusions in choroidal cells, a previously undocumented finding in progressive outer retinal necrosis. Polymerase chain reaction was very useful in identifying the causative agent.

AIDS-Related Opportunistic Infections↗
PubMed1994

Intracellular proteolytic processing of the two-chain vitamin K-dependent coagulation factor X.

The vitamin K-dependent clotting factors require posttranslational proteolytic processing before they are secreted by the liver into blood as mature zymogens. For most of these proteins, the sequences around the cleavage sites show a common motif (Arg-X-Lys/Arg-Arg) which define the substrate specificity for the endoprotease furin/PACE of the Golgi apparatus. In this paper, we present data which suggest that an additional Ca(++)-dependent endoprotease(s) is located in the endoplasmic reticulum, and may participate in processing of the two-chain vitamin K-dependent coagulation factor X. The single-chain 70 kDa factor X precursor in microsomes from rat liver was labeled by 14C-gamma-carboxylation and its conversion to a two-chain form followed in an incubation system with microsomal membrane fragments. A Ca(++)-dependent endoprotease(s) converted the factor X precursor to a two-chain form with a light-chain of 21 kDa. The endoprotease(s) showed little reactivity towards release of the factor X propeptide. The data provide new information about the endoprotease system in liver which participates in clotting factor proteolytic processing.

Amino Acid Sequence↗
PubMed1994

Intrasacral myxopapillary ependymoma.

Intrasacral ependymomas are rare, accounting for only a small fraction of primary sacral tumors. They are typically large at diagnosis, which is preceded by a long history of pain. We present a case discovered during investigation of infertility. MRI features of the myxopapillary subgroup are described.

Adult↗
PubMed1993

Intracellular maturation of the gamma-carboxyglutamic acid (Gla) region in prothrombin coincides with release of the propeptide.

Vitamin K-dependent coagulation factors undergo several post-translational modifications before the proteins are secreted into the blood as functional zymogens of the coagulation system. The modifications include Asn-linked glycosylation, Asn/Asp hydroxylation, removal of a signal peptide for translocation of the polypeptide into the endoplasmic reticulum and removal of a propeptide which, when attached to the intracellular coagulation factor precursor, directs the protein for vitamin K-dependent gamma-carboxylation. gamma-Carboxylation of targeted Glu residues results in formation of Ca(2+)-binding gamma-carboxyglutamic acid (Gla) residues. Ca2+ binding by these residues induces a conformational change in the protein which is a necessary event for optimal activation or activity of the clotting factor in blood. In the present study we have monitored the intracellular prothrombin precursor in the secretory pathway of liver cells to determine the effect that the propeptide has on Ca(2+)-dependent folding of the protein. The data provide evidence that the Ca(2+)-induced conformational change required for activation of prothrombin coincides with release of the propeptide in the trans-Golgi apparatus of the liver cell and elucidates an important function for the endoproteinase furin in biosynthesis of vitamin K-dependent clotting factors.

1-Carboxyglutamic Acid↗
PubMed1992

Processing and trafficking of clotting factor X in the secretory pathway. Effects of warfarin.

Clotting factor X undergoes several post-translational processing steps in the liver before the protein appears in blood as the mature two-chain zymogen. In this study we have followed the factor X precursor through the secretory pathway in rat liver in order to identify the site for proteolytic processing of the precursor into a two-chain form and the site for warfarin inhibition of precursor trafficking within the pathway. Isolated rat liver Golgi apparatus was shown to harbour two single-chains of factor X precursors of 70 and 74 kDa and the heavy (50 kDa) and light chains of factor X. It was demonstrated that the two-chain factor X form was produced from a late processing form of the factor X precursor, which indicated that the site for proteolytic conversion to a two-chain form was in the trans-Golgi compartment. The 70 and 74 kDa single-chain precursors and also the light chain of the two-chain form were shown to contain the factor X propeptide which is normally removed before the coagulation factor appears in blood. The data demonstrate that intra-chain cleavage of a single chain factor X precursor in the trans-Golgi compartment can precede release of the propeptide. Warfarin was shown to affect trafficking of the factor X precursor between the endoplasmic reticulum (ER) and the Golgi apparatus. The data suggest a link between vitamin K-dependent gamma-carboxylation of the precursor and its exit from the ER. Warfarin administration resulted in accumulation of factor X precursors associated with the ER membrane. These precursors appear to be stabilized from intracellular degradation while in the ER. In contrast to the large increase in the factor X precursor concentration in the ER membrane, there was no change in the prothrombin precursor concentration as a result of warfarin action on the liver. However, intracellular turnover of the microsomal prothrombin precursor pool in warfarin-treated rats resulted in a pool of less negatively charged proteins, indicating ongoing protein synthesis but inhibition of gamma-carboxylation. The data are consistent with previous findings [Wallin & Martin (1988) J. Biol. Chem. 263, 9994-10001] suggesting that prothrombin and factor X are processed differently by the vitamin K-dependent carboxylase in the ER membrane.

Amidohydrolases↗
PubMed1992

Demyelinating polyneuropathy in eosinophilia-myalgia syndrome.

Eosinophilia-myalgia syndrome (EMS) is a newly recognized disorder, characterized by myalgia, weakness, scleroderma-like changes, and eosinophilia. EMS is associated with lots of L-tryptophan allegedly contaminated with byproducts of the manufacturing process. We describe 3 patients with EMS who presented with a severe demyelinating sensorimotor polyneuropathy. Electrodiagnostic studies revealed multifocal conduction block, slowing and temporal dispersion of motor responses, and prolonged or absent F-responses. Despite plasmapheresis; corticosteroids; and, in 1 patient, cyclophosphamide, 2 patients died and the remaining patient experienced minimal recovery. Pathology revealed patchy perivascular infiltrates and fibrosis in the connective tissue of muscle and nerve. Autopsy of the central nervous system in 2 patients did not reveal changes unique to EMS. In addition to other organ involvement, EMS may manifest as a potentially fatal polyneuropathy, which initially appears to have prominent demyelinating features.

Demyelinating Diseases↗
PubMed1992

Autosomal recessive osteopetrosis: bone marrow imaging.

Technetium-99m sulfur colloid scintigraphy was performed prospectively in 12 infants and children with autosomal recessive osteopetrosis, to correlate the appearance of bone marrow stores with advancing age. Baseline images were obtained in all patients, and one to five follow-up images were obtained in eight patients after they began therapy with calcitriol, interferon-gamma, or both. Conventional radiography was performed along with the nuclear studies in all cases. Magnetic resonance (MR) images of the head or lower extremities were also obtained in six patients and were correlated with the scintigraphic findings. Patterns of abnormal distribution of bone marrow appeared to be age-dependent. In patients younger than 1 year, marrow stores were primarily in the skull base and at the ends of the long bones. In patients aged 3-5 years, marrow stores shifted to the diaphyseal regions of long bones and to the calvarium. In the appendicular skeleton, areas of greatest bone marrow activity corresponded to regions of relative decreased opacity on radiographs and areas of intermediate or high signal intensity on T2-weighted MR images. The skull base showed appreciable marrow activity in spite of densely sclerotic bone on radiographs.

Bone Marrow↗
PubMed1991

Processing of prothrombin in the secretory pathway.

Antibodies raised against plasma prothrombin and the prothrombin propeptide were used to identify prothrombin precursors in rough and smooth microsomes and in the Golgi apparatus. The data demonstrate that the propeptide is part of the prothrombin molecule when undergoing a variety of modifications in the Golgi apparatus. It is shown that these modifications result in an increase in the apparent molecular mass of the prothrombin precursor from 78 kDa in early processing to 83 kDa in late processing. The 83 kDa prothrombin precursor was not recognized by the anti-propeptide antiserum and most likely represents the final product of the precursor in the secretory pathway. Evidence is presented that the propeptide is released from the parent molecule in the Golgi apparatus by a membrane-bound Ca(2+)-dependent serine proteinase(s) with characteristics similar to those of the proalbumin-to-albumin-converting enzyme. Vitamin K-dependent carboxylase activity was measured in membrane fragments obtained from the Golgi apparatus preparation. Sucrose-density-gradient centrifugation and the use of marker enzymes showed that carboxylase activity was highest in fractions enriched in cis-Golgi cisternae. Two different synthetic peptides were used as substrates for the carboxylase. These peptides were from the N-terminal and the C-terminal part of the gamma-carboxyglutamic acid (Gla) region of prothrombin. It is shown that the N-terminal and the C-terminal peptides were preferred as substrates for the carboxylase in the microsomal and the Golgi apparatus preparations respectively. It is also shown that the prothrombin precursor acquires negative charges in the Golgi apparatus that do not result from addition of sugars in late processing. These negative charges could be eliminated by thermal decarboxylation, suggesting that Gla residues may also be synthesized in late processing.

Amino Acid Sequence↗
PubMed1991

Cutaneous malignant melanoma metastatic to the choroid.

Cutaneous malignant melanoma metastatic to the eye is a well-documented occurrence in the ophthalmic literature. Typically, ocular metastatic disease occurs concomitantly with or following the documentation of disseminated metastases. We present the clinical and histopathologic findings in a 62-year-old man whose first manifestation of metastatic cutaneous melanoma was his choroidal lesion.

Choroid Neoplasms↗