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Biomedical subjects

S M Brown

Publications and source records attributed to S M Brown.

At least 19 recordsLinked to original sources
PubMed2002

Scaling laws in NMR scattering via dipolar fields.

Breaking translational symmetry in magnetostatics imparts a scale dependence that is commonly investigated in physics (W. Warren et al., 1993, Science 262, 2005-2008). An interesting and important example arises in nuclear magnetic resonance studies involving the dipolar mean field of adjacent nuclear spins where the scattering (transfer of spatial spin gratings) via intermolecular macroscopic fields carries a signature of the local spatial distribution of the spin density. For arbitrary geometry, the inverse problem of extracting this spin distribution from experiments is intractable. Here we point out a simple, universal crossover in the scaling behavior at the sample's characteristic length scale, xi, of the species fluctuations in the sample along the measurement direction. This behavior is observed experimentally in an oil-water emulsion, an important representation of complex, heterogeneous, soft matter.

Emulsions↗
PubMed2001

Cutting edge: positive selection induced by a self-peptide with TCR antagonist activity.

Antagonist-like engagement of the TCR has been proposed to induce T cell selection in the thymus. However, no natural TCR ligand with TCR antagonist activity is presently known. Using a combination of bioinformatics and functional testing we identified the first self-peptide that can both deliver antagonist-like signals and promote T cell selection in the thymus. The peptide is presented by appropriate MHC class I molecules in vivo. Thus, endogenous antagonist peptides exist and may be involved in TCR repertoire selection.

Animals↗
PubMed2001

Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1.

Purification from calf thymus of a DNA N-glycosylase activity (HMUDG) that released 5-hydroxymethyluracil (5hmUra) from the DNA of Bacillus subtilis phage SPO1 was undertaken. Analysis of the most purified fraction by SDS-polyacrylamide gel electrophoresis revealed a multiplicity of protein species making it impossible to identify HMUDG by inspection. Therefore, we renatured the enzyme after SDS-polyacrylamide gel electrophoresis and assayed slices of the gel for DNA N-glycosylase activity directed against 5hmUra. Maximum enzymatic activity was identified between molecular mass markers 30 and 34 kDa. Protein was extracted from gel slices and subjected to tryptic digestion and analysis by mass spectrometry. Analysis revealed the presence of 11 peptides that were homologous or identical to the sequence of the recently characterized human single-stranded monofunctional uracil DNA N-glycosylase (hSMUG1). The cDNA of hSMUG1 was isolated and expressed as a recombinant glutathione S-transferase fusion protein that was shown to release 5hmUra with 20x the specific activity of the most purified bovine fraction. We conclude that hSMUG1 and HMUDG are the same protein.

Amino Acid Sequence↗
PubMed2001

Exploring the transcriptome of the malaria sporozoite stage.

Most studies of gene expression in Plasmodium have been concerned with asexual and/or sexual erythrocytic stages. Identification and cloning of genes expressed in the preerythrocytic stages lag far behind. We have constructed a high quality cDNA library of the Plasmodium sporozoite stage by using the rodent malaria parasite P. yoelii, an important model for malaria vaccine development. The technical obstacles associated with limited amounts of RNA material were overcome by PCR-amplifying the transcriptome before cloning. Contamination with mosquito RNA was negligible. Generation of 1,972 expressed sequence tags (EST) resulted in a total of 1,547 unique sequences, allowing insight into sporozoite gene expression. The circumsporozoite protein (CS) and the sporozoite surface protein 2 (SSP2) are well represented in the data set. A BLASTX search with all tags of the nonredundant protein database gave only 161 unique significant matches (P(N) < or = 10(-4)), whereas 1,386 of the unique sequences represented novel sporozoite-expressed genes. We identified ESTs for three proteins that may be involved in host cell invasion and documented their expression in sporozoites. These data should facilitate our understanding of the preerythrocytic Plasmodium life cycle stages and the development of preerythrocytic vaccines.

Amino Acid Motifs↗
PubMed2001

Intralesional injection of herpes simplex virus 1716 in metastatic melanoma.

We have previously shown that avirulent but replication-competent herpes simplex virus (HSV) 1716 causes cell death in human melanoma cell lines in vitro and selectively replicates in melanoma tissue in nude mice. We now present a pilot study of intratumoral injection of HSV1716 into subcutaneous nodules of metastatic melanoma in five patients with stage 4 melanoma. Two patients each received one injection, two received two injections, and one received four injections of 10(3) plaque-forming units HSV1716. In one patient, flattening of previously palpable tumour nodules was seen 21 days after two direct injections of HSV1716, and in injected nodules from all three patients who received two or more injections there was microscopic evidence of tumour necrosis. Immunohistochemical staining of injected nodules revealed evidence of virus replication confined to tumour cells. These findings suggest that HSV1716 is non-toxic and could be of therapeutic benefit in patients with metastatic melanoma.

Biological Therapy↗
PubMed2001

Herpes simplex virus dermatitis in patients using latanoprost.

PURPOSE: To describe the possible association of latanoprost with herpetic dermatitis of the periocular skin. METHOD: Interventional case reports. A 79-year-old woman with open-angle glaucoma developed a vesicular dermatitis of the left lower eyelid 14 months after starting latanoprost therapy. An 84-year-old man with pigmentary glaucoma developed a vesicular dermatitis of the right upper lid after 2 months of treatment with latanoprost and 8 days of treatment with tobramycin/dexamethasone for presumed bacterial conjunctivitis. In both cases, the dermatitis was characteristic of a herpetic infection. RESULTS: Latanoprost was discontinued in both cases. The woman was treated with vidarabine 3% ointment, and the man was not treated with antiviral agents. In both patients, the dermatitis healed uneventfully. The lesions of the man were cultured, and a biopsy was performed; herpes simplex virus type 1 was recovered from the culture and confirmed by immunofluorescence testing. CONCLUSION: Latanoprost, which has been associated with reactivation of herpetic keratitis, may also cause reactivation of herpetic dermatitis of the periocular skin.

Aged↗
PubMed2001

The feasibility of short automated static perimetry in children.

OBJECTIVE: To evaluate the feasibility of short automated static perimetry using tendency-oriented perimetry in the pediatric population. DESIGN: Prospective observational case series. PARTICIPANTS: Fifty normal children age 6 through 12 years. TESTING: Subjects underwent testing with the Octopus TOP-32 program on the Octopus 1-2-3 automated perimeter. Testing was performed in a typical clinical setting without adaptations to the perimeter, prolonged training, or the use of custom seating. Each eye was tested twice. MAIN OUTCOME MEASURES: Ability to complete automated static perimetry tests with both eyes. Mean sensitivity, mean defect, and loss of variance; gray scale and numeric representations of the field; duration of each test and of the entire session; subjective assessment of each test as normal or abnormal; calculation of test specificity. Comparisons by age and test number were performed. RESULTS: All subjects successfully completed all four tests. The mean duration for each test was 2:30+/- 0.23 minutes. The average time for the whole session, including training, testing both eyes twice, and rest periods, was 25.8+/-4.87 minutes. Improvement in the specificity of the test (fewer abnormal tests in normal children) occurred in direct relation to subject age (R = 0.5). CONCLUSIONS: Automated static perimetry using short, tendency-oriented programs can be successfully performed in normal children age 6 through 12 years in a typical clinical setting. Age was the best predictor of the mean sensitivity, reproducibility, and accuracy of the test, with the most reliable results obtained after 7 years of age. In children 6 to 7 years old, significant interindividual variability was present, and testing success was more dependent on the child's maturity and ability to concentrate. Short automated perimetry seems to be a promising tool for the evaluation of peripheral vision in pediatric patients.

Automation↗
PubMed2001

Relaxation of postoperative astigmatism after lens implantation through a 6.25 mm scleral wound in children.

PURPOSE: To investigate the evolution of postoperative astigmatism in children having cataract extraction with intraocular lens (IOL) implantation through a 6.25 mm superior scleral tunnel wound. SETTING: A university clinical practice. METHODS: A retrospective chart review of all pediatric patients having cataract extraction and IOL implantation in the practice of 1 surgeon from 1995 to 2000 was performed. Statistical comparisons were performed using the Student t test for nonpaired data. RESULTS: Ten eyes of 9 children were included. Six cataracts were due to corneal or corneoscleral lacerations, 3 were idiopathic, and 1 occurred after blunt trauma. Eight eyes could not be refracted preoperatively because of mature cataract. The mean cylindrical correction of all refractions performed 1 to 15 days after surgery (n = 6) was 6.71 diopters (D) +/- 1.63 (SD); of those performed at 16 to 30 days (n = 6), 2.71 +/- 2.09 D; and of those performed at 31 to 45 days (n = 7), 1.93 +/- 1.48 D. The mean spherical equivalent of the final (dispensed) refraction was -0.21 +/- 1.79 D; the mean cylindrical correction of this refraction was 1.13 +/- 0.79 D. The difference between the cylindrical correction of the final prescription and the corneal astigmatism in fellow eyes was not statistically significant (P =.29). CONCLUSIONS: Relaxation of large amounts of suture-induced astigmatism occurs in children having cataract extraction. Surgeons should not hesitate to secure scleral wounds meticulously in children for fear of a permanent undesirable refractive outcome.

Adolescent↗
PubMed2001

Second cluster of strabismus cases after periocular anesthesia without hyaluronidase.

We describe a second cluster of cases of iatrogenic strabismus that occurred in clinical practices following cataract surgeries that occurred in 2000 when hyaluronidase was once again unavailable for use in periocular anesthetic regimens. Twelve cases of transient or permanent strabismus were referred by 4 anterior segment surgeons who had no previous cases of postcataract strabismus when performing periocular injections with hyaluronidase. The charts of the patients were reviewed retrospectively. Recurrence of an increase in postoperative strabismus when hyaluronidase became unavailable for a second time supports the concept that this enzyme may be more important than previously suspected in preventing damage to the extraocular muscles after periocular anesthetic injections.

Aged↗
PubMed2001

Gene isolation and characterization of two acyl CoA oxidases from soybean with broad substrate specificities and enhanced expression in the growing seedling axis.

The first committed step in the beta-oxidation of fatty acids is catalyzed by the enzyme acyl-CoA oxidase (ACOX), which oxidizes a fatty acyl-CoA to a 2-trans-enoyl-CoA. To understand the role of beta-oxidation during seedling growth in soybean, two ACOX cDNAs were isolated by screening a seedling library with a DNA fragment obtained by RT-PCR by using degenerate oligonucleotides. The two cDNAs (ACX1;1 and ACX1;2) are 86% identical to each other at the nucleotide and the amino acid level. Their deduced amino acid sequences share significant homology with known acyl-CoA oxidases, including the conserved CGGHGY motif, a putative flavin mononucleotide binding site. In both sequences, the last three amino acids, ARL, represent a putative peroxisome targeting signal. The mRNA and protein of both cDNAs accumulated in all seedling tissues, with relatively stronger expression in the growing seedling axis and hypocotyl, and weaker expression in the cotyledon. Immunolocalization studies indicated that the two proteins were localized in the phloem cells of hypocotyl tissue. The two cDNAs were expressed in Escherichia coli and shown to possess acyl-CoA oxidase activity. With fatty acyl-CoA substrates of varying chain lengths, it was demonstrated that both ACX1;1 and ACX1;2 have broad substrate specificities (C8-C18). The stronger expression of ACX1;1 and ACX 1;2 in the axis and hypocotyl tissue, the weaker expression in the oil-rich cotyledon tissue, and the broad substrate specificities suggest that the two acyl-CoA oxidases might play a general house-keeping role during soybean seedling growth, such as the turnover of membrane lipids.

Acyl-CoA Oxidase↗
PubMed2001

Cloning of an Arabidopsis patatin-like gene, STURDY, by activation T-DNA tagging.

Activation T-DNA tagging can generate dominant gain-of-function mutants by overexpression of a particular endogenous gene. We identified an activation-tagged mutant, sturdy, exhibiting a stiff inflorescence stem, thicker leaves, shorter siliques, larger seeds, round-shaped flowers, and delayed growth. It is most important that unlike its wild-type counterpart, this mutant is less prone to lodging. Cloning of STURDY revealed that in sturdy, there is an open reading frame containing a single intron encoding a patatin-like homolog. The T-DNA is inserted into the 3' region of the second exon. The mutant phenotype was shown to be the result of overexpression of STURDY by mRNA analysis and transgenic studies. Preliminary histological studies have revealed an increase in cell number in the inflorescence stem of mutant plants; however, additional studies are needed to better understand the overexpression phenotype.

3' Untranslated Regions↗
PubMed2001

Squamous cell carcinoma of the nail bed: is finger predominance another clue to etiology? A report of 5 cases.

Although squamous cell carcinoma (SCC) is commonly found on sun-exposed skin, the occurrence of this malignancy in the nail bed is rare. We report 5 cases of SCC of the nail bed and suggest that the disproportionate number of neoplasms of this type on the second, third, and fourth fingers, combined with the known relationship of SCC and human papillomavirus (HPV), is evidence that most SCC of the nail bed result from contact with HPV. Moreover, we suggest that patients who present with new, verrucous lesions of the nail bed and have a history of cervical dysplasia, cervical carcinoma, or condyloma acuminata undergo diagnostic biopsy as opposed to traditional destructive therapy for a lesion presumed benign.

Aged↗
PubMed2000

A review of the developmental and reproductive toxicity of styrene.

The reproductive and developmental toxicity of styrene has been studied in animals and humans. The animal studies on styrene have diverse study designs and conclusions. Developmental or reproductive toxicity studies have been conducted in rats, mice, rabbits, and hamsters. In most cases, high doses are required to elicit effects, and the effects are not unique to reproduction or development. In a number of the reports, either the experimental designs are limited or the descriptions of the designs and the endpoints measured are insufficient to draw conclusions about the toxicity of styrene. The more complete and better-reported studies show that styrene does not cause developmental toxicity at dose levels that are not maternally toxic. Some neurochemical or neurobehavioral effects have been reported at high exposures. Styrene does not affect fertility or reproductive function. Considerable animal toxicity data on styrene support the conclusion that styrene is neither an endocrine-active substance nor an endocrine disrupter. Human studies often suffer from either inadequate exposure data or exposure to a wide variety of materials, so that attribution of effects to styrene exposure is impossible. Furthermore, investigators often have failed to account for other exposures in the workplace or for other potentially confounding factors in their studies. Menstrual cycle irregularities and congenital abnormalities were initially reported; however, the better and more recent reports do not show that styrene causes developmental or reproductive effects in humans. Human studies also support the conclusion that styrene is not an endocrine disrupter. Although some study authors have concluded that styrene is either a human or an animal reproductive or developmental toxicant, careful review demonstrates that such conclusions are not justified.

Abnormalities, Drug-Induced↗
PubMed2000

Ocular effects of apraclonidine in Horner syndrome.

OBJECTIVE: To determine the location of action of apraclonidine, an alpha-adrenergic receptor agonist that reduces aqueous production and lowers intraocular pressure (IOP). METHODS: The study cohort consisted of 6 patients with Horner syndrome (decreased or absent sympathetic innervation of 1 eye). We instilled 1% apraclonidine into the affected eye, and the changes in IOP and pupil diameter (PD) of both eyes were measured over 4 hours. In a separate session, apraclonidine was instilled into the normal eye and the measurements were repeated. RESULTS: The average baseline IOP was 16.3 mm Hg for affected eyes and 16.7 mm Hg for normal eyes. The average maximum ipsilateral reduction in IOP was 5.8 mm Hg in affected eyes and 5.2 mm Hg in normal eyes; this difference was not statistically significant. The average baseline PDs for affected and normal eyes were 3.2 mm and 4.2 mm, respectively. Instillation of apraclonidine into affected eyes produced mydriasis of 1.0 to 4.5 mm; baseline anisocoria reversed in all patients. There was no significant change in the PD of normal eyes after ipsilateral instillation of apraclonidine. CONCLUSIONS: Apraclonidine's major site of pharmacologic action for reduction of aqueous production is on postjunctional alpha(2) receptors in the ciliary body. The up-regulation of alpha receptors that occurs with sympathetic denervation unmasks apraclonidine's alpha(1) effect, which clinically causes pupil dilation. Apraclonidine may be a useful medication for the diagnosis of Horner syndrome. Arch Ophthalmol. 2000;118:951-954

Adrenergic alpha-Agonists↗
PubMed1999

The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position.

The aim of the investigation was to determine the effect of age, gender, viral upper respiratory tract infection (URTI), season and sleeping position on the composition of the nasopharyngeal bacterial flora in infancy. Seventy-two babies, 38 male and 34 female, whose birthdates were evenly spread throughout the year were followed from birth to 18 months of age. From 0 to 6 months nasopharyngeal swabs were obtained once a month in periods without URTI and daily for 3 days during episodes of URTI. From 12 to 18 months of age nasopharyngeal swabs were obtained in the early morning alter an overnight sleep and later in the day after the baby had been up for over 2 h. Swabs were obtained in prone and supine sleepers with and without infection. In infants aged 0-6 months URTI had little effect on the nasopharyngeal bacterial flora, but there was a marked effect of age and less marked effect of season and gender. In particular Staphylococcus aureus carriage decreased with age, was most common in the winter months and the density of colonisation was greater in males than females. In infants aged 12-18 months the combination of prone sleeping with URTI and an early morning swab led to increased carriage of staphylococci, streptococci. Haemophilus influenzae and Gram-negative bacilli which are not normally part of the nasopharyngeal flora. These results are relevant to sudden infant death syndrome (SIDS). The combination of prone sleeping and URTI reproduces the nasopharyngeal flora seen in SIDS. Gram-negative bacilli isolated from SIDS cases should not be dismissed as post-mortem contaminants. The features of S. aureus make it a prime candidate for a pathogenic role in SIDS.

Aging↗
PubMed1999

Sleeping position in infants over 6 months of age: implications for theories of sudden infant death syndrome.

The aim of this study was to determine the prevalence of prone and supine sleeping in infants aged 0-12 months and relate this to changes in the number of cases of sudden infant death syndrome (SIDS) since 1985. Seventy-two babies, 38 male and 34 female, were followed for the first 18 months of life with regular home visits and sleeping position was recorded. In addition, data on the number of cases of SIDS in England and Wales between 1985 and 1995 were analysed. All babies slept supine for the first 5 months of life, but once they could turn over in their cots (mean age 7.34 months, range 5-11 months) the majority slept prone. By 11 months of age, 53 regularly slept prone (73%), 95% CI +/- 19.8%), while 11 slept supine, three adopted the side position and five varied from night to night. The number of cases of SIDS in infants aged 7-11 months has fallen significantly (P<0.0001) in a period in which the prevalence of prone sleeping, in that age group, has not changed. The most plausible explanation for this paradoxical result is that supine sleeping in the first 5 months of life reduces the absolute risk of SIDS in the second 6 months of life even though most babies are then sleeping prone. It is suggested that reduced exposure to nasopharyngeal bacterial superantigens in babies sleeping prone might explain this effect.

Adult↗