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Biomedical subjects

T H Smith

Publications and source records attributed to T H Smith.

At least 19 recordsLinked to original sources
PubMed2005

HIV seropositive in pregnant South African women who initially refuse routine antenatal HIV screening.

This study was instituted primarily to determine the HIV seroprevalence of pregnant South African women who refused routine HIV testing at the antenatal clinic of the Johannesburg Hospital, South Africa. Fifty such patients were identified, who, after being fully counselled and informed, agreed to participate in the study, provided total anonymity was adhered to: they did not want to know their results, irrespective of outcome. Blood specimens were given a laboratory reference number only, with no other reference to the patient and analysed utilising the ELISA immunoassay. Twenty-two of the 50 blood specimens, or 44% of patients analysed, tested positive for HIV. This is an alarming statistic, as the HIV prevalence in the general antenatal population at the Johannesburg Hospital is 29.4%.

AIDS Serodiagnosis↗
PubMed2001

Management strategies to decrease the prevalence of mastitis caused by one strain of Staphylococcus aureus in a dairy herd.

The dairy herd at Washington State University had an outbreak of mastitis caused by a single strain of Staphylococcus aureus. The outbreak strain, termed novel, could not be controlled with routine contagious mastitis pathogen control procedures (incidence, 3.4 infections/100 cow months; peak prevalence > 22%). Our objective was to implement mastitis control measures that would decrease the incidence and prevalence of intramammary infection (IMI) caused by S aureus in the herd. The following intervention strategies were successfully implemented: strict segregation of cattle with IMI caused by S aureus, intensified culling of cattle with multiple-quarter IMI caused by S aureus, and inducing cessation of lactation of infected quarters in single-mammary-quarter infected cattle. One year after implementation of these control measures, incidence of IMI caused by S aureus was 0.35 infections/100 cow months, and prevalence had decreased from 20 to 8%.

Animals↗
PubMed2001

Primary mucinous adenocarcinoma of the vagina.

OBJECTIVE: Our goal was to report the management and symptoms of a patient who presented with primary mucinous adenocarcinoma of the vagina with an unusual histologic pattern. METHODS: Our methods included a retrospective description of the management, a review of the literature, and critical evaluation of the treatment modalities available for this very uncommon tumor. RESULTS: Initially posterior partial vaginectomy and abdominoperineal resection was performed with the creation of a permanent colostomy. A bilateral inguinal lymphadenopathy was performed 6 months later on the basis of a palpable enlarged lymph node. Radiotherapy was instituted thereafter. The patient remains disease-free 48 months after initial surgery and is satisfied with her quality of life. CONCLUSIONS: Primary mucinous adenocarcinoma of the vagina is a very rare tumor. Therefore individualized treatment is justified until larger series have been published.

Adenocarcinoma, Mucinous↗
PubMed2001

A review of subtyping in autism and proposed dimensional classification model.

Autism has been divided into subtypes based on social interaction/communication, developmental level, or both. The validity of subtyping systems and the extent to which they overlap were examined. According to this review, a single subtyping system capable of accounting for the symptom heterogeneity in autism has not yet been proposed; however, evidence supports the presence of a three-factor continuum containing at least four subgroups. Foremost among directions for future research is the need for comprehensive studies in which medical screening, careful selection of measures, and longitudinal data collection are included.

Autistic Disorder↗
PubMed2001

Tubular carcinoma of the breast: prognosis and response to adjuvant systemic therapy.

BACKGROUND: Tubular carcinoma of the breast is an uncommon and usually small tumour, and is thought to have a favourable prognosis. The present study examined the long-term prognosis of patients with tubular breast carcinoma and the roles of axillary dissection and adjuvant therapy. METHODS: Eighty-six tubular cases were identified from a large worldwide database of 9520 breast carcinoma patients entered into randomized adjuvant therapy trials run by the International Breast Cancer Study Group from 1978 to 1999. These patients were followed for a median of 12 years. RESULTS: Forty-two (49%) cases were node-positive, of which 33 (79%) had 1-3 nodes involved. Ten (32%) of the 31 smaller tumours (< or = 1 cm in size) were node-positive. Patients with node-positive tubular carcinoma had a significantly better 10-year relapse-free survival (P = 0.006) and survival (P < 0.0001) compared with non-tubular node-positive cases. Overall survival was similar for node-positive and node-negative tubular carcinoma. Overall, 71 patients (83%) received some form of adjuvant systemic therapy. Of the 86 cases, 43 (50%) received more than one course of chemotherapy. There was an 85% decrease in the risk of death for patients who received more than one course of chemotherapy compared to those who did not (hazard ratio 0.15, 95% confidence interval (CI): 0.03-0.82; P = 0.03). CONCLUSIONS: Compared to other histological types of breast cancer, tubular carcinoma has a better long-term prognosis. Adjuvant chemotherapy may further improve prognosis and involvement of axillary nodes may not be an indicator for early death due to breast carcinoma.

Adenocarcinoma↗
PubMed2001

HC-Pro suppression of transgene silencing eliminates the small RNAs but not transgene methylation or the mobile signal.

Post-transcriptional gene silencing (PTGS) is a sequence-specific RNA degradation mechanism that is widespread in eukaryotic organisms. It is often associated with methylation of the transcribed region of the silenced gene and with accumulation of small RNAs (21 to 25 nucleotides) homologous to the silenced gene. In plants, PTGS can be triggered locally and then spread throughout the organism via a mobile signal that can cross a graft junction. Previously, we showed that the helper component-proteinase (HC-Pro) of plant potyviruses suppresses PTGS. Here, we report that plants in which PTGS has been suppressed by HC-Pro fail to accumulate the small RNAs associated with silencing. However, the transgene locus of these plants remains methylated. Grafting experiments indicate that HC-Pro prevents the plant from responding to the mobile silencing signal but does not eliminate its ability to produce or send the signal. These results demonstrate that HC-Pro functions downstream of transgene methylation and the mobile signal at a step preceding accumulation of the small RNAs.

Algorithms↗
PubMed2000

RNA viruses as inducers, suppressors and targets of post-transcriptional gene silencing.

Post-transcriptional gene silencing (PTGS) is a fundamental regulatory mechanism operating in diverse types of organisms, but the cellular components of the gene silencing machinery and the regulation of the process are not understood. Recent findings that cytoplasmically replicating RNA viruses act as both targets and inducers of PTGS has led to the idea that PTGS may have evolved as an anti-viral defense mechanism in plants. Consistent with this hypothesis, it has been found that certain plant viruses encode proteins that suppress PTGS. From a practical standpoint, an understanding of the mechanisms by which viruses regulate PTGS may well lead to better ways to control gene expression in plants. It is often desirable to overexpress selected beneficial genes or to silence detrimental ones in order to confer a particular phenotype. Induction of PTGS using RNA viruses as vectors or as transgenes provides a reliable and efficient way to interfere with the expression of a specific gene or with a family of genes. Conversely, expression of viral suppressors has significant potential to improve yields in technologies that use plants to express beneficial gene products. Given the antiviral nature of gene silencing in plants and the indications that PTGS is an ancient mechanism in eukaryotic organisms, understanding the phenomenon in plants could well lead to the development of anti-viral strategies in both plants and animals.

Gene Silencing↗
PubMed2000

Plant viral suppressors of post-transcriptional silencing do not suppress transcriptional silencing.

Homology-dependent gene silencing is a regulatory mechanism that limits RNA accumulation from affected loci either by suppression of transcription (transcriptional gene silencing, TGS) or by activation of a sequence-specific RNA degradation process (post-transcriptional gene silencing, PTGS). The P1/HC-Pro sequence of plant potyviruses and the 2b gene of the cucumber mosaic virus have been shown to interfere with PTGS. The ability of these viral suppressors of PTGS to interfere with TGS was tested using the 271 locus which imposes TGS on transgenes under 35S or 19S promoters and PTGS on the endogenous nitrite reductase gene (Nii). Both P1/HC-Pro and 2b reversed PTGS of Nii genes in 271-containing tobacco plants, but failed to reverse TGS of 35S-GUS transgenes in the same plant. P1/HC-Pro expression from a transgene also failed to suppress either the initiation or maintenance of TGS imposed by the NOSpro-silencing locus, H2. These results indicate that PTGS and TGS operate through unlinked pathways or that P1/HC-Pro and 2b interfere at step(s) in PTGS that are downstream of any common components in the two pathways. The data suggest a simple assay to identify post-transcriptionally silenced transgenic lines with the potential to be stably converted to high expressing lines.

Cucumovirus↗
PubMed1999

A left atrial myxoma presenting as a cerebrovascular accident.

A 14-year-old female presented with common clinical findings for a rare primary intracardiac tumor. Primary cardiac tumors are rare in all age groups, occurring in 0.05% of routine postmortem examinations. Pediatric primary cardiac tumors are likewise uncommon, with the most common being a rhabdomyoma. Atrial myxomas occur infrequently in the pediatric age group. They occur primarily between the third and sixth decade, making them the most common adult primary cardiac tumor. The following case presentation demonstrates a common clinical presentation for an intracardiac mass rarely diagnosed in the pediatric population. This patient's acute neurologic symptoms required prompt recognition of an intracardiac etiology. This recognition proved critical for the acute and long-term medical and surgical management of this patient.

Adolescent↗
PubMed1998

A viral suppressor of gene silencing in plants.

Gene silencing is an important but little understood regulatory mechanism in plants. Here we report that a viral sequence, initially identified as a mediator of synergistic viral disease, acts to suppress the establishment of both transgene-induced and virus-induced posttranscriptional gene silencing. The viral suppressor of silencing comprises the 5'-proximal region of the tobacco etch potyviral genomic RNA encoding P1, helper component-proteinase (HC-Pro) and a small part of P3, and is termed the P1/HC-Pro sequence. A reversal of silencing assay was used to assess the effect of the P1/HC-Pro sequence on transgenic tobacco plants (line T4) that are posttranscriptionally silenced for the uidA reporter gene. Silencing was lifted in offspring of T4 crosses with four independent transgenic lines expressing P1/HC-Pro, but not in offspring of control crosses. Viral vectors were used to assess the effect of P1/HC-Pro expression on virus-induced gene silencing (VIGS). The ability of a potato virus X vector expressing green fluorescent protein to induce silencing of a green fluorescent protein transgene was eliminated or greatly reduced when P1/HC-Pro was expressed from the same vector or from coinfecting potato virus X vectors. Expression of the HC-Pro coding sequence alone was sufficient to suppress virus-induced gene silencing, and the HC-Pro protein product was required for the suppression. This discovery points to the role of gene silencing as a natural antiviral defense system in plants and offers different approaches to elucidate the molecular basis of gene silencing.

Journal Article↗
PubMed1998

Outbreak of mastitis caused by one strain of Staphylococcus aureus in a closed dairy herd.

The Washington State University dairy experienced an outbreak of intramammary infections (IMI) caused by Staphylococcus aureus during autumn 1993 through summer 1995. The outbreak was believed to be a result of transmission of 1 strain of S aureus in a herd that historically had excellent control of contagious mastitis. Control practices included strict hygiene at time of milking and preferential culling of cows infected with S aureus. Mastitis caused by Streptococcus agalactiae was not found in this herd. Despite excellent control practices, the strain of S aureus caused a new infection rate of approximately 3% of the herd per month. Moreover, a second strain of S aureus, isolated from a cow with mastitis, was introduced into the herd experimentally, and it failed to transmit disease. The outbreak of S aureus mastitis in this herd was eventually controlled by maintaining a program of strict milking time hygiene, by intensifying the program of preferentially culling infected cows, and by segregating cows with S aureus IMI in a separate pen and milking these infected cows last.

Animals↗
PubMed1998

Cleavage susceptibility of reovirus attachment protein sigma1 during proteolytic disassembly of virions is determined by a sequence polymorphism in the sigma1 neck.

A requisite step in reovirus infection of the murine intestine is proteolysis of outer-capsid proteins to yield infectious subvirion particles (ISVPs). When converted to ISVPs by intestinal proteases, virions of reovirus strain type 3 Dearing (T3D) lose 90% of their original infectivity due to cleavage of viral attachment protein sigma1. In an analysis of eight field isolate strains of type 3 reovirus, we identified one additional strain, type 3 clone 31 (T3C31), that loses infectivity and undergoes sigma1 cleavage upon conversion of virions to ISVPs. We examined the sigma1 deduced amino acid sequences of T3D and the eight field isolate strains for a correlation between sequence variability and sigma1 cleavage. The sigma1 proteins of T3D and T3C31 contain a threonine at amino acid position 249, whereas an isoleucine occurs at this position in the sigma1 proteins of the remaining strains. Thr249 occupies the d position of a heptad repeat motif predicted to stabilize sigma1 oligomers through alpha-helical coiled-coil interactions. This region of sequence comprises a portion of the fibrous tail domain of sigma1 known as the neck. Substitution of Thr249 with isoleucine or leucine resulted in resistance to cleavage by trypsin, whereas replacement with asparagine did not affect cleavage susceptibility. These results demonstrate that amino acid position 249 is an independent determinant of T3D sigma1 cleavage susceptibility and that an intact heptad repeat is required to confer cleavage resistance. We performed amino-terminal sequence analysis on the sigma1 cleavage product released during trypsin treatment of T3D virions to generate ISVPs and found that trypsin cleaves sigma1 after Arg245. Thus, the sequence polymorphism at position 249 controls cleavage at a nearby site in the neck region. The relevance of these results to reovirus infection in vivo was assessed by treating virions with the contents of a murine intestinal wash under conditions that result in generation of ISVPs. The pattern of sigma1 cleavage susceptibility generated by using purified protease was reproduced in assays using the intestinal wash. These results provide a mechanistic explanation for sigma1 cleavage during exposure of virions to intestinal proteases and may account for certain strain-dependent patterns of reovirus pathogenesis.

Base Sequence↗
PubMed1997

A cationic lipid for rapid and efficient delivery of plasmid DNA into mammalian cells.

Cationic lipids are widely used for gene transfer into cultured eukaryotic cells. However, lipids with potent transfection activity are often associated with high levels of cytotoxicity, and also require serum-free conditions for optimal performance. These characteristics in many cases result in unsatisfactory transfection efficiency. In this report, we describe a new cationic amphiphile, N-t-butyl-N'-tetradecyl-3-tetradecylaminopropionamidine (Amidine). Amidine requires only 1-2 hour incubation intervals to produce maximal transfection efficiency, and can transfect cells in the presence of serum. Such characteristics significantly minimize cytotoxicity, and also provide time flexibility for researchers. We routinely obtain over 80% transfection efficiency as evidenced by use of an enhanced green fluorescence protein (EGFP) as the reporter. These studies demonstrate the utility of Amidine for rapid and efficient transfection of mammalian cells.

Animals↗
PubMed1997

Rainbow Universal CPG: a versatile solid support for oligonucleotide synthesis.

We have developed a universal solid support, termed Rainbow Universal CPG, for use in automated oligonucleotide synthesis. The universal solid support allows any oligodeoxyribonucleotide sequence to be synthesized from a single type of controlled pore glass (CPG) support. Deprotection of oligodeoxyribonucleotides was optimized using 0.5 M LiCl in concentrated ammonium hydroxide. PCR experiments using three different sets of primers proved that the 3'-hydroxyl function of oligodeoxyribonucleotides synthesized from Rainbow Universal CPG was retained. This universal solid support shows promise for replacing the standard nucleoside CPG supports.

Automation↗
PubMed1994

Somite subdomains, muscle cell origins, and the four muscle regulatory factor proteins.

We show by immunohistology that distinct expression patterns of the four muscle regulatory factor (MRF) proteins identify subdomains of mouse somites. Myf-5 and MyoD are, at specific stages, each expressed in both myotome and dermatome cells. Myf-5 expression is initially restricted to dorsal cells in all somites, as is MyoD expression in neck somites. In trunk somites, however, MyoD is initially expressed in ventral cells. Myogenin and MRF4 are restricted to myotome cells, though the MRF4-expressing cells are initially less widely distributed than the myogenin-expressing cells, which are at all stages found throughout the myotome. All somitic myocytes express one or more MRFs. The transiently distinct expression patterns of the four MRF proteins identify dorsal and ventral subdomains of somites, and suggest that skeletal muscle cells in somites originate at multiple sites and via multiple molecular pathways.

Animals↗
PubMed1993

Pulmonary metastases in children and young adults with differentiated thyroid cancer.

BACKGROUND: The prognostic significance and optimal care of children with differentiated thyroid cancer and pulmonary metastases are not well established. METHODS: Of 209 patients younger than 25 years of age who were treated at University of Texas M. D. Anderson Cancer Center between 1960 and 1990 and for whom there was sufficient information, 19 (9%) had pulmonary metastases at presentation. RESULTS: All of these patients had regional lymphadenopathy at the time of diagnosis. All but two had intense, diffuse radioiodine uptake in the lungs; there were two false-negative scans immediately after surgical procedure caused by competing thyroid residual. The chest radiograph (CXR) was normal in 8 of 17 (42%) patients with abnormal radioiodine scans. After therapy with radioiodine (100-499 mCi), CXR appeared normal in 7 of 9 patients with initial abnormal radiographs (within 6-75 months). Radioiodine uptake by the lungs normalized in 3 of 8 patients with initially normal radiographs, and in 3 of 9 patients with initially abnormal radiographs. There have been no deaths in these 19 patients. CONCLUSION: Pulmonary metastases are not uncommon in children and young adults with differentiated thyroid cancer, especially those who have regional lymphadenopathy. The lung metastases almost always concentrate radioiodine diffusely and may be associated with a normal CXR in almost half of the patients. Pulmonary metastases may be overlooked unless near total thyroidectomy is followed by total body radioiodine scan (TBS) in all children and young adults who have regional lymphadenopathy of the neck.

Adenocarcinoma↗
PubMed1993

Hidden sugars.

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Acids↗