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Biomedical subjects

S J Brown

Publications and source records attributed to S J Brown.

At least 73 records · Page 4Linked to original sources

The beetle Tribolium castaneum has a fushi tarazu homolog expressed in stripes during segmentation.

The genetic control of embryonic organization is far better understood for the fruit fly Drosophila melanogaster than for any other metazoan. A gene hierarchy acts during oogenesis and embryogenesis to regulate the establishment of segmentation along the anterior-posterior axis, and homeotic selector genes define developmental commitments within each parasegmental unit delineated. One of the most intensively studied Drosophila segmentation genes is fushi tarazu (ftz), a pair-rule gene expressed in stripes that is important for the establishment of the parasegmental boundaries. Although ftz is flanked by homeotic selector genes conserved throughout the metazoa, there is no evidence that it was part of the ancestral homeotic complex, and it has been unclear when the gene arose and acquired a role in segmentation. We show here that the beetle Tribolium castaneum has a ftz homolog located in its Homeotic complex and expressed in a pair-rule fashion, albeit in a register differing from that of the fly gene. These and other observations demonstrate that a ftz gene preexisted the radiation of holometabolous insects and suggest that it has a role in beetle embryogenesis which differs somewhat from that described in flies.

Amino Acid Sequence↗

Thallium imaging for brain tumors with results measured by a semiquantitative index and correlated with histopathology.

BACKGROUND: The optimal management of patients with brain tumors requires knowledge of the tumor characteristics upon presentation and the discovery of recurrence after therapy. Thallium-201 (Tl-201) chloride has shown varying uptake in tumors, depending on their viability and the type and degree of malignancy. This study explores the diagnostic potential of thallium imaging in patients with brain tumors. METHODS: Forty-three Tl-201 single photon emission computed tomographic scintigrams were performed on 40 patients with intracranial neoplasms, nearly equally divided between patients with no prior treatment and patients who had prior treatment and were suspected to have recurrent tumor and/or radiation necrosis. A thallium tumor index was calculated as the ratio of counts for a region of interest drawn in the lesion area and its mirror image in normal brain tissue. A two-tailed Student's t test was performed to compare the thallium index and histopathologic findings. RESULTS: A value of 1.5 for the thallium tumor index allowed for the best correlation between the prediction of malignancy and the histopathologic results. In the pretreatment group, a thallium tumor index greater than 1.5 correlated with high grade malignancy, and less than 1.5 correlated with either a well differentiated astrocytoma or benign cyst. In the posttreatment group, a thallium tumor index greater than 1.5 correlated with recurrent and/or residual malignant tumor. CONCLUSIONS: For those patients undergoing initial evaluation, the thallium study can help in the differential diagnosis of an intracranial mass lesion and offers confirmation of results of biopsy. For those patients who already have received treatment, the study can be used to detect recurrent or residual tumor.

Adult↗

Macrothrombocytosis in cavalier King Charles spaniels.

Low platelet counts (< 150 x 10(9)/litre) have been measured by autoanalyser in cavalier King Charles spaniels with a wide range of diseases. However, the direct examination of blood smears revealed adequate numbers of platelets but many abnormally large platelets and it was not clear whether the large platelets were the result of disease or a breed abnormality. The numbers and diameters of the platelets in a group of clinically normal King Charles spaniels and a group of other breeds were measured by autoanalyser and manually. The automated platelet counts were lower in the King Charles spaniels than in the other breeds (P < 0.01), but the manual counts were similar. The platelet diameter was greater in the cavalier King Charles spaniels (median values 2.5 to 3.75 microns, P < 0.001) than the other breeds (median values 1.25 to 2.5 microns) and had a bimodal distribution with peaks at 1.25 to 2.5 microns and 3.75 to 5 microns. No clinical evidence of platelet dysfunction was detected. These findings indicate that cavalier King Charles spaniels may have large platelets which could lead to the erroneous diagnosis of thrombocytopenia by automated haematological analysis.

Animals↗

Indium-111-labeled anti-EGFr-425 scintigraphy in the detection of malignant gliomas.

BACKGROUND: The monoclonal antibody anti-epidermal growth factor receptor (EGFr) antibody-425, against the epidermal growth factor receptor, has the potential to bind specifically to gliomas and not normal brain tissue. A prospective study was conducted (1986-1988) to evaluate the use of Indium-111 (111In)-labeled anti-EGFr-425 in the localization of gliomas before radioimmunotherapy with Iodine-125 (125I)-labeled anti-EGFr-425. METHODS: Twenty-eight patients with intracranial neoplasms were injected intravenously with an average dose of 2.2 mCi 111In-labeled anti-EGFr-425. Planar and single-photon emission computed tomography scans were performed after 48 and 72 hours. Control studies also were performed in two cases with 111In-labeled Co 17-1A (an antibody to colorectal cancer) and in one case with unlabeled 111In chloride. RESULTS: The immunoscintigraphic findings were generally in good agreement with computerized tomographic findings. The definitive diagnosis was established by biopsy findings: 23 gliomas (1 Grade I, 5 Grade II, 6 Grade III, and 11 Grade IV), 1 meningioma, and 4 metastatic lesions. The localization of gliomas with 111In-labeled anti-EGF-425 had a sensitivity of 0.96, a specificity of 0.60 and an accuracy of 0.90. CONCLUSION: Immunoscintigraphy with 111-In labeled anti-EGFr-425 can be useful in the management of malignant gliomas, especially before radioimmunotherapy with 125I-labeled anti-EGFr-425.

Adult↗

Embryonic expression of the single Tribolium engrailed homolog.

We have cloned and sequenced the single Tribolium homolog of the Drosophila engrailed gene. The predicted protein contains a homeobox and several domains conserved among all engrailed genes identified to date. In addition it contains several features specific to the invected homologs of Bombyx and Drosophila, indicating that these features most likely were present in the ancestral gene in the common ancestor of holometobolous insects. We used the cross-reacting monoclonal antibody, 4D9, to follow the expression of the Engrailed protein during segmentation in Tribolium embryos. As in other insects, Engrailed accumulates in the nuclei of cells along the posterior margin of each segment. The first Engrailed stripe appears as the embryonic rudiment condenses. Then as the rudiment elongates into a germ band, Engrailed stripes appear in an anterior to posterior progression, just prior to morphological evidence of the formation of each segment. As in Drosophila (a long germ insect), expression of engrailed in Tribolium (classified as a short germ insect) is preceded by the expression of several homologous segmentation genes, suggesting that similar genetic regulatory mechanisms are shared by diverse developmental types.

Amino Acid Sequence↗

Are there acceptable anterior chamber intraocular lenses for clinical use in the 1990s? An analysis of 4104 explanted anterior chamber intraocular lenses.

PURPOSE: The authors pose the question as to whether there are any anterior chamber intraocular lenses (AC IOLs) acceptable for clinical use in the 1990s. METHODS: Data on the incidence and types of complications of 4104 AC IOLs that were submitted to the Center for IOL Research from 1982 to 1993 were retrieved from the laboratory database and analyzed using cumulative frequency calculations and the chi-square test. Normalized explantation rates were related to implantation rates that were derived from market-share analysis. RESULTS: Of 4104 explanted IOLs, 50% were closed-loop designs (n = 2095/4104); 26% (1100/4104) were miscellaneous, older designs; and 22% (919/4104) were open-loop lenses. The most important complications were corneal pathology (2065/4104) and inflammation (1370/4104). Closed-loop designs were responsible for almost 80% of corneal pathology, with an increasing complication rate with ongoing implant duration (P < 0.0001). Open-loop AC IOLs showed, in relation to their normalized rate of implantation, a significantly lower rate of complications and explantations (P < 0.01). CONCLUSION: Complication rates of flexible, open-loop AC IOLs are much lower than previously assumed. They should be distinguished clearly from most older AC IOL designs. Consideration of these lenses as an alternative to sutured posterior chamber IOLs for secondary or exchange implantation may be warranted for selected clinical indications. They also could provide an alternative to the aphakic spectacle rehabilitation program in developing countries, which will have a positive impact on the overwhelming backlog of patients with cataract in the underprivileged world.

Anterior Chamber↗

Genetic control of early embryogenesis in the red flour beetle, Tribolium castaneum.

The power of genetic analysis possible with the fruit fly, Drosophila melanogaster, has yielded a detailed understanding of pattern formation controlled by homeotic and segmentation genes in early embryogenesis. We are studying the genetic regulation of embryogenesis in the red flour beetle, Tribolium castaneum. The dynamic process of germ rudiment formation and sequential segmentation exhibited by Tribolium provides a context different than Drosophila within which to assess the function of homeotic and segmentation gene homologs. Our analyses of the genes in the HOM-C suggest many similarities in structure and function with the well-characterized Drosophila genes. Abdominal resembles its Drosophila homolog abdominal-A in functioning to establish segmental identities in the abdomen, such that in each case mutations result in homeotic transformations to PS6. Although the anterior functional boundary of abdominal-A homologs is precisely conserved, the domain within which Abdominal is important extends more posterior than that of abdominal-A. The final expression pattern of the segmentation gene engrailed in Tribolium is identical to Drosophila, suggesting that these homologs are involved in a conserved developmental process. However, as expected the development of that pattern is different; engrailed stripes anticipate the formation of each new segment as they appear sequentially in the elongating germ band. Although the grasshopper even-skipped and fushi tarazu homologs are not apparently important in segmentation, the expression patterns of the Tribolium homologs strongly suggest that they have gained a role in segmentation in the lineage leading to beetles and flies. Nevertheless, differences between Tribolium and Drosophila in the dynamics of even-skipped expression and the fushi tarazu mutant phenotype indicate divergence in the regulation and roles of these genes.

Animals↗

Postconcussional disorder: time to acknowledge a common source of neurobehavioral morbidity.

Closed head injuries are common, affecting approximately 2 million people annually in the United States. The majority of these are "mild" in the sense of not being associated with prolonged unconsciousness, intracranial bleeding, skull fracture, or protracted periods of confusion. Yet a proportion of such "mild" injuries are accompanied by persisting cognitive, vegetative, and affective-behavioral sequelae, some of which affect day-to-day life. We argue that there is sufficient research to indicate that postconcussional symptoms occur and that they tend to have a predictable configuration. It is necessary to recognize the existence of "Postconcussional Disorder" in our nosology in order to provide more prompt diagnosis and management and to facilitate scholarly communication and research regarding this important neurobehavioral disorder.

Cognition Disorders↗

Communication strategies used by an expert nurse.

Individualization of care, or tailoring of care, involves taking into account the client's individuality, and allowing that individuality to determine interpersonal approaches and health-illness management actions (Cox, 1982). Cox's definition of tailoring was empirically supported in a study of three naturally occurring clinical encounters (Brown, 1992). The present analysis was conducted using the research methods of discourse analysis to further understand how the expert nurse in Brown's study used speech actions to enact tailoring. The nurse provided clients with explicit opportunities to introduce their issues, elicited descriptions of their daily lives, expressed personal regard for them, yet also assessed their clinical states. This discourse profile is unlike others reported in the literature and may be considered exemplary.

Adult↗

[Reasons for the explantation of posterior chamber lenses].

In this study we analysed the overall incidence and the types of complications seen after cataract surgery and implantation of posterior chamber intraocular lenses (PC-IOLs) based on a review of 1460 explanted PC-IOLs. Of these explanted PC-IOLs, 1072 (73.4%) were three-piece PMMA IOLs with Prolene haptics, 261 (17.9%) were one-piece all-PMMA IOLs, 81 (5.6%) were silicone IOLs and 46 (3.1%) were of various other designs (multifocal IOLs, disc IOLs etc.). The mean implant duration for all IOLs was 25.57 +/- 29.24 months. The two most important reasons for explantation were IOL decentration (622/1460, 42.6%) and inflammation (347/1460, 23.77%). There was no difference in reasons for explantation between one-piece and three-piece IOLs. Operative techniques such as "can opener" capsulotomy and sulcus fixation have more influence on IOL decentration than the IOL design alone. Modern operative techniques such as continuous curvilinear capsulorhexis, phacoemulsification and symmetrical in-the-bag fixation of "capsular IOLs" should decrease the explantation and complication rate in the future.

Follow-Up Studies↗

[Complications after implantation of anterior chamber lenses. An analysis of 4,100 explanted intraocular lenses].

In this study we analyzed the incidence and types of complications seen after cataract surgery and implantation of anterior chamber intraocular lenses (AS-IOLs). This report is based on a review of 4104 explanted AC-IOLs that were submitted to the Center for IOL Research over the past 10 years. The results from pathological examinations were correlated with clinical information. Of the 4104 IOLs, 50% were closed-loop designs (n = 2095/4104), and 22% were open-loop lenses (919/4104). The IOLs most frequently explanted were the closed loop designs Leiske (n = 847) and Stableflex (n = 808). The most important reason for explantation was corneal pathology. Closed-loop IOLs had a much higher complication rate than open-loop lenses. Flexible open-loop AC-IOLs showed the highest explantation rate during the first postoperative year due to surgical problems. The complication rate of closed-loop AC-IOLs increased with implant duration and were responsible for 80% of the corneal pathology. Flexible open-loop AC-IOLs can be an alternative for secondary or exchange implantation. Furthermore, they could also be a viable alternative for cataract surgery in developing countries in order to help catch up with the overwhelming backlog of cases that exist there.

Aged↗

The role of gallium-67-citrate in the detection of phenytoin-induced pneumonitis.

A patient with a history of cardiac transplant presented with a fever of undetermined etiology. The patient had been on multiple medications, including phenytoin, which can occasionally cause allergic or hypersensitivity pneumonitis. A chest x-ray and CT scan of the chest revealed no active disease. A 67Ga study was obtained after intravenous administration of 377.4 MBq (10.2 mCi) of 67Ga-citrate. The images showed diffuse intense lung uptake bilaterally. Bronchoscopic biopsy revealed hypersensitivity pneumonitis. Phenytoin was withdrawn and corticosteroid was started in therapeutic doses. A follow-up gallium study obtained 25 days after the baseline demonstrated marked improvement in the lungs with concurrent clinical recovery. This case illustrates the usefulness of 67Ga in the detection of drug-induced pneumonitis and in the follow-up of response to therapy.

Alveolitis, Extrinsic Allergic↗

Ixr1, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin.

Structure-specific recognition proteins (SSRPs) bind to DNA containing intrastrand cross-links formed by the anticancer drug cisplatin. A yeast gene encoding an SSRP, designated IXR1, was cloned and sequenced. The Ixr1 protein, a member of the high mobility group-box protein family, bound specifically to DNA modified with cisplatin but not inactive platinum compounds. A yeast strain with an inactivated IXR1 gene was half as sensitive to cisplatin and accumulated one-third as many platinum-DNA lesions after treatment with cisplatin as the parental strain. These findings suggest that SSRPs play a role in mediating the cytotoxicity of cisplatin.

Amino Acid Sequence↗

Sequence and structural implications of a bovine corneal keratan sulfate proteoglycan core protein. Protein 37B represents bovine lumican and proteins 37A and 25 are unique.

Amino acid sequence from tryptic peptides of three different bovine corneal keratan sulfate proteoglycan (KSPG) core proteins (designated 37A, 37B, and 25) showed similarities to the sequence of a chicken KSPG core protein lumican. Bovine lumican cDNA was isolated from a bovine corneal expression library by screening with chicken lumican cDNA. The bovine cDNA codes for a 342-amino acid protein, M(r) 38,712, containing amino acid sequences identified in the 37B KSPG core protein. The bovine lumican is 68% identical to chicken lumican, with an 83% identity excluding the N-terminal 40 amino acids. Location of 6 cysteine and 4 consensus N-glycosylation sites in the bovine sequence were identical to those in chicken lumican. Bovine lumican had about 50% identity to bovine fibromodulin and 20% identity to bovine decorin and biglycan. About two-thirds of the lumican protein consists of a series of 10 amino acid leucine-rich repeats that occur in regions of calculated high beta-hydrophobic moment, suggesting that the leucine-rich repeats contribute to beta-sheet formation in these proteins. Sequences obtained from 37A and 25 core proteins were absent in bovine lumican, thus predicting a unique primary structure and separate mRNA for each of the three bovine KSPG core proteins.

Amino Acid Sequence↗

The role of iodine-131 and thallium-201 imaging and serum thyroglobulin in the management of differentiated thyroid carcinoma.

BACKGROUND: A prospective study was conducted to evaluate the use of iodine-131 sodium scintigraphy, thallium-201 chloride scintigraphy, and quantitative serum thyroglobulin estimation in the detection of differentiated thyroid carcinoma after thyroidectomy and iodine-131 sodium ablative therapy. METHODS: Thirty-one patients with a median age of 45.6 years (range, 20-73 years) were included in the study. After optimal endogenous thyroid-stimulating hormone stimulation (> 50 mU/ml), 53 pairs of iodine-131 and thallium-201 scans were performed. Concomitant serum thyroglobulin levels were available for 32 pairs of scans. The presence or absence of thyroid cancer was established by clinical, radiologic, and/or biopsy findings. RESULTS: The concordance between iodine-131 and thallium-201 scan findings in the presence of disease (25 scan sets) was 36%. The concordance in the absence of disease (28 scan sets) was 82%. Iodine-131 scanning was found to be significantly better (P < 0.05) than thallium-201 scanning, in terms of sensitivity (0.8 versus 0.6), specificity (0.96 versus 0.82), accuracy (0.89 versus 0.72), and the predictive value of a positive test (0.95 versus 0.75). The measurement of serum thyroglobulin had a low sensitivity (0.3) in the study but had a specificity of 1.0. CONCLUSION: It was concluded that iodine-131 sodium scintigraphy is superior to thallium-201 scintigraphy and serum thyroglobulin estimation for the detection of residual or metastatic differentiated thyroid carcinoma. However, the use of combined modalities provides a higher diagnostic yield. Thallium-201 scintigraphy was especially useful in cases in which iodine-131 scintigraphy was negative and quantitative thyroglobulin levels were elevated.

Adenocarcinoma↗

Structure and function of the homeotic gene complex (HOM-C) in the beetle, Tribolium castaneum.

The powerful combination of genetic, developmental and molecular approaches possible with the fruit fly, Drosophila melanogaster, has led to a profound understanding of the genetic control of early developmental events. However, Drosophila is a highly specialized long germ insect, and the mechanisms controlling its early development may not be typical of insects or Arthropods in general. The beetle, Tribolium castaneum, offers a similar opportunity to integrate high resolution genetic analysis with the developmental/molecular approaches currently used in other organisms. Early results document significant differences between insect orders in the functions of genes responsible for establishing developmental commitments.

Animals↗