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Biomedical subjects

C Stanton

Publications and source records attributed to C Stanton.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

The effect of alcohol in isolated blunt splenic trauma.

The effect of alcohol on trauma patients is controversial, with numerous authors citing no difference in mortality in acutely intoxicated patients. The purpose of our study was to retrospectively investigate the effect of alcohol in adult patients with isolated blunt splenic injury. From 1980 through 1989, 47 adult patients with splenic trauma as the only major injury were admitted to the Trauma Service. There were 37 males and ten females with a mean age of 29 years (range, 15 to 61). Motor vehicle accidents were responsible for 44 (94%) of the injuries. Group 1 consisted of 24 patients with a mean blood alcohol level of 185 mg/dl (range, 15 to 380). In Group 2 there were 23 patients without detectable blood alcohol. There were no statistically significant differences between the two groups in age, Abbreviated Injury Severity Score, initial hematocrit, and grade of splenic injury. Hypotension was present in 13 patients (55%) in Group 1 versus six patients (26%) in Group 2 (p less than 0.05). Significant abnormalities in clotting studies were present on admission in six patients (25%) in the alcohol-detected group versus one in the other group (p less than 0.05). Blood transfusion requirements in the first 24 hours were significantly greater in Group 1 (mean, 3.9 units) versus Group 2 (mean, 0.5 units) (p less than 0.001). If alcohol was present, there was much less chance for splenic conservation, as 18 patients (75%) underwent splenectomy versus seven patients (30%) in the nonalcohol group (p less than 0.05). There was one death and this occurred in a patient acutely intoxicated who suffered a cerebral infarct.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Screening for congenital dislocation of the hip by child-health nurses in Western Australia.

The child-health nurse screening programme for the presence of congenital dislocation of the hip in Western Australia was evaluated by the use of data that were collected as a routine from the Congenital Malformations Registry, the records of child-health nurses and the Hospital Morbidity System. The programme performed well operationally, with a sensitivity of 68.5%, a specificity of 98.8%, and a positive predictive value of 15.1%. Of the children who were born in the study period (1981-1983), 450 children were diagnosed with congenital dislocation of the hip, and 46 (10.2%) of these children required 104 hospital admissions for the treatment of their dislocation. Of the children whose hips were found to be dislocated in screening (those who were screened as "true-positive" cases), 10.1% were hospitalized, whereas 16.1% of those children who were missed by screening (who screened as "false negative") required hospitalization (95% confidence interval [CI] for the difference in proportions, -7.8% to 19.9%). A comparison of the measures of hospitalization was made between the children who were found to be "true positive" on screening and the children whose dislocation was diagnosed in the hospitals of their birth--a group that generally is considered to show the best outcome. A somewhat-higher proportion of children who were screened as "true positive" required an open surgical procedure (5.0% of children compared with 2.8% of children; 95% CI for the difference, -2.1% to 6.5%). The differences in the other measures of hospitalization between the two groups were small.

Child↗

Neuronal antinuclear antibodies in a patient with Lambert-Eaton myasthenic syndrome and small-cell lung carcinoma.

A patient with small-cell lung carcinoma and the Lambert-Eaton myasthenic syndrome had circulating neuronal antinuclear antibodies. Serum stained the nuclei of all neurons in sections of human brain and identified a closely spaced group of 33-39 kDa proteins in immunoblots of human neuronal nuclei. These autoantibodies are indistinguishable from those recently identified in patients with paraneoplastic subacute sensory neuronopathy.

Antibodies, Antinuclear↗

A controlled study of efficacy of interstitial or external irradiation in a virus-induced brain-tumor model in rats.

In a controlled study of interstitial radiotherapy in the avian sarcoma virus (ASV)-induced glioma model in rats, prolongation of survival was demonstrated (p = 0.08 in Experiment 1 and p = 0.03 in Experiment 2) following mean dosages of 7582 to 9902 cGy 125I, when compared to nontreatment or to control studies with implantation of nonradioactive seeds. More significant (p = 0.02) prolongation of survival was demonstrated following external beam whole-head radiotherapy with nine fractions of 333 cGy, three times weekly over 3 weeks (total dose 3000 cGy). Survival was more prolonged when whole-head radiotherapy was begun 35 days following virus inoculation rather than at 71 days, probably reflecting a greater efficacy with smaller tumor targets.

Animals↗

Factors responsible for the high perforation rate seen in early childhood appendicitis.

The incidence of perforated appendicitis has remained high in the infant and young child resulting in substantial morbidity. The purpose of the present study was to investigate the factors contributing to the high perforation rate seen in this age group. A retrospective analysis was done on 77 patients under the age of seven who underwent appendectomy for appendicitis. The perforation rate was 72.7 per cent. Duration of pain correlated with patient age and perforation rate. Under the age of five, only 17 per cent had symptoms for less than 36 hours. Children with symptoms that lasted longer than 48 hours had a perforation rate of 98 per cent. Associated illnesses including respiratory infections, otitis media, and gastroenteritis were common in both simple and perforated appendicitis, often leading to a delay in diagnosis. Of patients with perforation, 36 per cent were seen at least once by the primary physician and discharged. The keys to the diagnosis of appendicitis in this young age group were history and physical exam. Right lower quadrant findings were present in 95 per cent of patients with simple appendicitis and 71 per cent of patients with perforation. The primary-care physician and consulting surgeon have crucial roles in diagnosing the disease early in its course.

Appendicitis↗

The immunohistochemical demonstration of early perineurial change in the development of localized hypertrophic neuropathy.

A case of localized hypertrophic mononeuropathy was studied by electron microscopy and immunohistochemistry for S100 protein, epitopes recognized by the Leu-7 monoclonal antibody, 200 kD neurofilament polypeptide, and the epithelial membrane antigen (EMA). The primary role of perineurial cell proliferation without the participation of Schwann cells in this process was directly demonstrated by EMA immunohistochemistry. Focal delamination of the EMA-positive perineurium, increased fibrosis between its layers, and compartmentalization of the fascicles by EMA-positive septae were the first recognizable changes. In practice, recognition of these early changes by EMA immunocytochemistry may be important for the clear definition of functionally unimpaired segmental margins for excision and graft implantation, and also for the future study of the process responsible for aberrant perineurial proliferation.

Adolescent↗

Graft appendiceal fistulas.

We report the fifth case of a graft appendiceal fistula. The four previously reported cases are reviewed. This is the first report of the utility of the tagged red blood cell study in the evaluation of a patient with a graft appendiceal fistula.

Aged↗

Late multifocal gliomas in adolescents previously treated for acute lymphoblastic leukemia.

Three of 37 adolescents in long-term remission from childhood acute lymphoblastic leukemia (ALL) developed malignant multifocal gliomas several years after completing treatment that included central nervous system (CNS) prophylaxis with radiation (RT) and intrathecal methotrexate (IT-MTX). No recurrence of the leukemia was evident when the CNS tumors were discovered. Seventeen other similar cases have been recorded. The occurrence of second malignancies is reviewed in the context of this development and of the oncogenic effects of radiation. It is probable that prolonged exposure to IT-MTX may have had a synergistic effect with radiation in contributing to the unusual incidence of glial tumors in these patients.

Adolescent↗

Expression of epithelial membrane antigen in perineurial cells and their derivatives. An immunohistochemical study with multiple markers.

Paraffin-embedded surgical pathology specimens from skin (5) and muscle (2) biopsies, from Morton's neuromas (3), traumatic neuromas (8), schwannomas (21), neurofibromas (12), and from one perineurioma and one neurothekeoma were studied by immunoperoxidase histochemistry and antibodies against epithelial membrane antigen (EMA), Leu 7 epitopes (Leu 7), S-100 protein (S-100) and cytokeratins. Normal, reactive and neoplastic perineurial cells stain consistently for EMA, whereas Schwann cells express Leu 7 and/or S-100 positivity. None of the immunoreactive cells stained for cytokeratin. Our findings indicate that perineurial and Schwann cells can easily be distinguished by their different patterns of immunoreactivity with the above markers.

Cell Line↗

GFA protein reactivity in nerve sheath tumors: a polyvalent and monoclonal antibody study.

We studied glial fibrillary acidic (GFA) protein immunoreactivity in 30 schwannomas, including two intracerebral examples, 26 neurofibromas and 12 neuromas using the immunoperoxidase method with a polyvalent antiserum (PVAS) and three well-characterized monoclonal antibody (MAb) preparations. Twelve of the schwannomas, including both intracerebral tumors, two of the neurofibromas and none of the neuromas immunostained with PVAS. Except for one schwannoma, all the PVAS-positive tumors were positive with two of the MAb preparations. While both of the intracerebral schwannomas were positive with the third MAb, none of the extracerebral tumors were. Our results suggest that: 1) human nerve sheath tumors contain cells having polypeptides that share epitopes with GFA protein, but 2) these polypeptides differ from astrocytic GFA protein by at least one epitope, and 3) the location of the tumors in relation to the central nervous system may influence GFA protein immunoreactivity.

Antibodies↗

Antioxidant enzyme defence responses of human MCF-7 and SW480 cancer cells to conjugated linoleic acid.

The relationship between antioxidant-enzyme defence responses and cellular growth suppression in human MCF-7 (breast) and SW480 (colon) cancer cells, exposed to CLA in culture was studied. MCF-7 and SW480 cells (1 x 10(6)/flask) were cultured in appropriate medium for 4, 8 and 12 days with varying levels of CLA (0-30 ppm). A dose-dependent decrease in cell numbers and increase in lipid peroxidation, as determined by thiobarbituric acid reactive substances (TBARS) was observed in both cell lines following incubation with CLA. Exposure of both cell lines to 20 ppm CLA for 2-6 days produced a reduction (83-91%) in 3H-leucine incorporation into protein while 3H-uridine and 3H-thymidine incorporation into RNA and DNA were reduced by 49-91% and 86-98%, respectively, compared with untreated control cells. The activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were induced in both cell lines exposed to CLA (20 ppm) over a period of 12 days, although to a greater extent in MCF-7 cells than in SW480 cells. The data indicate that CLA-induced cytotoxicity against MCF-7 and SW480 cancer cell lines is related to the extent of lipid peroxidation of CLA treated cells and affirm that the CLA- induced antioxidant enzymes failed to protect these cells from cytotoxic lipid peroxidation products.

Adenocarcinoma↗

Milk fat conjugated linoleic acid (CLA) inhibits growth of human mammary MCF-7 cancer cells.

The relationship between growth and the antioxidant enzyme defence system in human MCF-7 (breast) cancer cells treated with bovine milk fat enriched with conjugated linoleic acid (CLA) was studied. Milk enriched in CLA was obtained from cows on pasture supplemented with full fat rapeseeds and full fat soyabeans (1). Cell number decreased up to 90% (p < 0.05) and lipid peroxidation increased 15-fold (p < 0.05) following incubation of MCF-7 cells for 8 days with increasing levels of milk fat yielding CLA concentrations between 16.9 and 22.6 ppm. Growth suppression and prooxidant effects of milk fat CLA were independent of the variable composition of the milk fat samples, suggesting that CLA was the active ingredient in milk fat responsible for the cytotoxic effect. Mixtures containing isomers of CLA (c9, t11-, t10, c12-, c11, t13- and minor amounts of other isomers) and linoleic acid (LA) at similar concentrations to the milk fat samples were as effective at inhibiting growth and stimulating peroxidation of MCF-7 cells as the milk fatty acids. Incubation of the cells with the c9, t11 CLA isomer (20 ppm) or the mixture of CLA isomers (20 ppm) for 8 days resulted in a 60% decrease (p < 0.05) in viability compared with untreated controls and was significantly (p < 0.05) more effective than incubation with the t10, c12 CLA isomer (20 ppm), which caused only a 15% decrease in cell numbers under similar conditions. A 25% increase (p < 0.05) in cell proliferation occurred when LA (20 ppm) alone was incubated with MCF-7 cells for 8 days. 14C-CLA was preferentially incorporated into the phospholipid fraction of the MCF-7 cell lipids in a dose-dependent manner and CLA accumulated in cell membranes more efficiently when the cells were incubated in the presence of milk fat than the c9, t11 synthetic CLA isomer. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities were induced in MCF-7 cells exposed to milk fat (containing 16.9-22.6 ppm CLA) over 8 days. The data indicate that milk fat triglyceride-bound CLA, consisting primarily of the c9, t11 isomer, was cytotoxic towards MCF-7 cells.

Animals↗

Recurrent Lhermitte-Duclos disease: report of two cases and association with Cowden's disease.

Two cases of Lhermitte-Duclos disease (LDD), one associated with Cowden's disease, are reported. Both demonstrated recurrence long after initial surgical resection. There is a propensity for occurrence in the left cerebellar hemisphere. On MR there is hypointensity on T1-weighted images and moderately high signal on T2-weighted images, with parallel linear striations on the surface of the lesion felt to represent dysplastic cerebellar folia. LDD is felt to be a low-grade neoplasm and potential component of Cowden's phakomatosis.

Adult↗