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Biomedical subjects

S H Smith

Publications and source records attributed to S H Smith.

At least 19 recordsLinked to original sources
PubMed2006

Carcinoma ex pleomorphic adenoma with sebaceous differentiation in the mandibular salivary gland of a dog.

A carcinoma ex pleomorphic adenoma was diagnosed in the left mandibular salivary gland of an 8-year-old female spayed dog. The animal presented with a large nonpainful swelling in the left submandibular region. A computed tomography scan detected an irregularly enhancing soft tissue mass that was closely associated with the left external ear canal and extended to the left wing of the atlas. On surgical exploration, the mass was intimately associated with the left mandibular salivary gland. Both the mass and the adjacent gland were removed, and the diagnosis was determined by histopathology. The tumor was comprised of basaloid and low columnar epithelial cells, many glandular units formed by well-differentiated sebocytes, and multifocal regions of necrosis, mineralization, and hemorrhage. Salivary gland tumors with sebaceous differentiation are very rare in animals, with one previously reported case in a cat.

Adenoma, Pleomorphic↗
PubMed2002

A comparative review of melanocytic neoplasms.

Melanoma is a devastating disease frequently encountered within both veterinary and human medicine. Molecular changes linked with neoplastic transformation of melanocytes include mutations in genes that encode proteins intrinsic to the regulatory pathways of two tumor suppressor proteins (retinoblastoma protein and p53), proto-oncogene mutation to oncogenes, altered expression of epithelial cadherin and CD44 adhesion molecules, and upregulation of angiogenic factors and other growth factors. Histologic evaluation of the primary mass is the most common means of diagnosis, with cytology used more frequently to document metastasis. Melanoma's highly variable histologic and cytologic patterns can make diagnosis by either method problematic. Adherent epithelioid morphology, including signet ring forms, and nonadherent round and spindle forms are recognized, with pigmentation an inconsistent finding. The site of the tumor, the thickness of the primary tumor or depth of invasion, and the number of mitotic figures per high-power field or per millimeter are used histologically to predict biologic behavior, whereas site and degree of pleomorphism are typically used for cytologic preparations. Diagnosis of amelanotic melanoma can be aided by ancillary diagnostic techniques. Tumor cells are usually positive for vimentin, S100, neuron-specific enolase, and Melan-A, and negative for cytokeratin. Melan-A as a positive marker is not as sensitive as the others are but is likely more specific. Monoclonal antibodies to human melanosome-specific antigens 1 and 5 cross-react with canine antigens for a combined sensitivity rate of 83%. Mouse monoclonal antibody IBF9 specifically recognizes canine melanoma antigen and also has good sensitivity. Serologic markers, including cytokines, cell adhesion molecules, and melanoma-inhibitory activity, are being investigated as potential sentinels of melanoma. Currently, there is no single diagnostic technique capable of differentiating benign from malignant melanocytic neoplasms or predicting survival time.

Animals↗
PubMed2001

Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control.

PURPOSE: Progress has been made in the treatment of medulloblastoma, the most common childhood malignant brain tumor: However, many long-term survivors will have posttherapy growth hormone insufficiency with resultant linear growth retardation. Growth hormone replacement therapy (GHRT) may significantly improve growth, but there is often reluctance to initiate GHRT because of concerns of an increased likelihood of tumor relapse. PATIENTS AND METHODS: This study retrospectively reviewed the use of GHRT for survivors of medulloblastoma in 11 neuro-oncology centers in North America who received initial treatment for disease between 1980 and 1993 to determine its impact on disease control. A Landmark analysis was used to evaluate the relative risk of relapse in surviving patients. RESULTS: Five hundred forty-five consecutive patients less than 15 years of age at diagnosis were identified. Six-year progression-free survival (mean +/- SD) was 40% +/- 5% in children less than 3 years of age at diagnosis compared with 59% +/- 3% for older patients. Older patients with total or near-total resections (P = .003) and localized disease at diagnosis (P < .0001) had the highest likelihood of survival. One hundred seventy patients (33% +/- 3% of the cohort) received GHRT. GHRT use varied widely among institutions, ranging from 5% to 73%. GHRT was begun a mean of 3.9 years after diagnosis, later in children younger than 3 years at diagnosis (5.4 years). By Landmark analyses, for those surviving 2, 3, and 5 years after diagnosis, there was no evidence that GHRT increased the rate of disease relapse. CONCLUSION: This large retrospective review demonstrates that GHRT is underutilized in survivors of medulloblastoma and is used relatively late in the course of the illness. GHRT is not associated with an increased likelihood of disease relapse.

Adolescent↗
PubMed2001

Calcium, cross-bridges, and the Frank-Starling relationship.

The steep relationship between active force and length in cardiac muscle is based on a length dependence of myofilament Ca(2+) sensitivity. However, it is not muscle length but the lateral spacing between actin and myosin filaments that sets the level of Ca(2+) sensitivity, mainly through modulation of myosin-mediated activation of the thin filament.

Actin Cytoskeleton↗
PubMed2001

Cerebral vascular hamartomas in five dogs.

Vascular hamartomas are considered developmental lesions rather than true neoplasms. Reports of such anomalies in the canine brain are scarce, and their classification is confusing. This case series of vascular hamartomas from the brains of five dogs was characterized using histochemistry and immunohistochemistry, in addition to gross and microscopic findings. All five hamartomas were located in the telencephalon, three in the pyriform lobe, without any predilection for the left or right side. Each hamartoma consisted of a proliferation of thin-walled vessels which varied in caliber. These vessels were elastin-negative, with varying amounts of collagen and no muscular component. In four of the five hamartomas, lining cells were actin- and factor VIII-positive. All five hamartomas contained glial fibrillary acid protein (GFAP)-positive parenchyma at moderate to high frequency, and four contained neurofilament-positive axons between component vessels. This report shows that vascular hamartomas in the canine brain are structural malformations for which immunohistochemistry is useful for accurate classification.

Animals↗
PubMed2000

Length-dependence of cross-bridge mediated activation of the cardiac thin filament.

Length-dependent Ca(2+)activation of the thin filament plays a critical role in the steep force-length relationship of cardiac muscle (Frank-Starling relation). Recent evidence indicates that the increase in myofilament Ca(2+)sensitivity and Ca(2+)-troponin C affinity that occurs with increase in sarcomere length results from a cooperative activation of the thin filament by attached cross-bridges. At short sarcomere length the Ca(2+)sensitivity is lower because the access of cross-bridges for actin is reduced. The aim of this study was to determine the length-dependence of myosin-mediated thin filament activation in skinned bovine ventricular muscle, as assayed by the generation of force with progressive reduction of MgATP concentration in the absence of Ca(2+). If the interaction between myosin and actin is weaker at short sarcomere length there should be a lower MgATP concentration needed to maintain the relaxed state. Contrary to expectation, the force-pMgATP relationship was not significantly influenced by change in sarcomere length. However this relationship became length-sensitive in the presence of phosphate analogs which stabilize weak-binding cross-bridges. We suggest that sarcomere length modulates Ca(2+)sensitivity by controlling the size of the population of thin filament regulatory units in the weakly-bound state.

Actin Cytoskeleton↗
PubMed2000

Hemihyperaesthesia and hyperresponsiveness resembling central pain syndrome in a dog with a forebrain oligodendroglioma.

A 4-year-old male Boxer was presented with neurological signs referable to a right forebrain lesion that was confirmed with computed tomography. Whilst characteristic signs of a unilateral forebrain lesion were observed, the dominant and striking finding was a right-sided hemisensory disturbance characterised by hyperaesthesia and hyperresponsiveness. Necropsy revealed a gelatinous mass confined to the right forebrain that was identified histologically as an oligodendroglioma. The lesion was centred on the internal capsule and involved ventral frontal and temporal lobes and the ventrolateral thalamus, including lateral and medial parts of the ventrocaudal nuclear region (ventrobasilar complex) of the thalamus. On clinical and neuroanatomical grounds, the case exhibited features in common with central pain syndrome in human patients with thalamic lesions. These included a somatosensory disorder of hyperaesthesia affecting an entire side of the head and body, behavioural manifestations consistent with spontaneous pain and a lesion involving the ventrobasilar complex. Of interest, the hemisensory abnormality was ipsilateral to the lesion, contrasting with central pain in humans, in which clinical signs are contralateral to analogous lesions. It is suggested that species-specific differences in spinal cord organisation of pain pathways, particularly the greater bilateral projection of nociceptive afferents to thalamic relay nuclei in carnivores, may account for this disparity. Notably, central pain is rare in human patients with brain tumours, even those affecting the thalamus, and this may also be the case in dogs.

Animals↗
PubMed1999

Monitored control programme for proliferative enteropathy on British pig farms.

The effect of control programmes on proliferative enteropathy and its causative agent (Lawsonia intracellularis) was investigated on four farrow-to-finish pig farms in Britain. Faeces samples from groups of boars and gilts in breeding programmes, and from preweaning and postweaning pigs were monitored prospectively every month for six months by a L intracellularis-specific polymerase chain reaction (PCR). On one farm with 150 sows, an outbreak of acute proliferative enteropathy in boars and gilts was controlled clinically by the use of tiamulin and chlortetracycline. The percentage of detectable PCR-positive pigs decreased from between 50 to 70 per cent to zero in the treated pigs and their progeny less than 14 weeks old, but clinical signs of the disease and PCR-positive pigs were detected in some 14-week-old pigs derived from the treated groups. On another farm with 160 sows, an outbreak of chronic proliferative enteropathy in six-week-old pigs (23 to 26 per cent PCR-positive) was controlled by the use of oral tylosin phosphate. Faeces samples from the medicated pigs on this farm remained PCR-negative during the study period, whereas samples from unmedicated control pigs showed that the infection persisted in some pigs for at least six weeks. The two other monitored farms remained PCR-negative and clinically negative for the disease during the study period. These farms treated the pigs regularly with oral chlortetracycline.

Animals↗
PubMed1999

Effect of ionic strength on length-dependent Ca(2+) activation in skinned cardiac muscle.

The length-dependence of myofilament Ca(2+) sensitivity is considered to be an important component of the steep force-length relationship in cardiac muscle (Frank-Starling relation). Recent studies suggest that Ca(2+) sensitivity is a function of the number of strong-binding cross-bridge interactions formed at a given sarcomere length. However, the length-dependent step in the thin filament activation process is still unknown. This study was designed to test the hypothesis that sarcomere length influences the transition of the thin filament from the unattached (blocked) state to the weakly bound (closed) state. This hypothesis was tested by determining the length-dependence of Ca(2+) sensitivity as a function of ionic strength in skinned bovine ventricular muscle. Previous studies have shown that reduction in ionic strength below a critical level, in the absence of Ca(2+), shifts the thin filament to the closed state. In this study normal Ca(2+) regulation was maintained at low ionic strength but the length-dependence of Ca(2+) sensitivity and the length-dependence of Ca(2+) binding were eliminated. These results are consistent with the hypothesis that the transition from the blocked to the closed state is a function of filament geometry as well as Ca(2+) and ionic strength.

Animals↗
PubMed1998

Questionnaire survey of proliferative enteropathy on British pig farms.

Risk factors for proliferative enteropathy were investigated by means of a postal questionnaire survey of randomly selected British pig farms. Replies were received from 319 (56 per cent) of the 569 questionnaires posted, representing 1.5 per cent of the total number of pig farms in Britain. Thirty-one per cent of the farms had experienced at least one episode of proliferative enteropathy within the previous three years, usually confirmed by their veterinary surgeon. There was a strong association for the occurrence of proliferative enteropathy in herds of over 500 sows (P < 0.005) and in herds with enzootic pneumonia (P < 0.01). Outbreaks had occurred in five of the six nucleus herds surveyed, the other had only 80 sows. Outbreaks occurred in 32 of 69 herds that had obtained their replacement boars from nucleus herds (P < 0.05), suggesting that infected boars may carry the disease into distant herds. The use of either fully slatted (P < 0.05) or fully meshed floors (P < 0.01) above sunken pits in buildings used to house pigs immediately after weaning, and the use of partially (P < 0.05) or fully slatted floors (P < 0.05) in buildings used to house pigs two to six months old, were risk factors for outbreaks of proliferative enteropathy, compared with the use of straw bedding or solid floors. The destocking of entire buildings containing pigs two to four months old before the introduction of fresh pigs, was associated with a reduced risk (P < 0.05), but the destocking of selected pens rather than the whole building had no such association. The type of diet, or feeding or watering system and the types of buildings used were not identified as risk factors.

Animal Husbandry↗
PubMed1998

Overview of the Diabetes Initiative of South Carolina.

Implementation is underway for many of these programs, and there are descriptions of activities elsewhere in this symposium. The Board recognizes that in dealing with the complications of a chronic disease like diabetes, many years of intense effort will be needed before significant results may be appreciated. Progress will be monitored regularly by the Surveillance Council and SCDCP/DHEC, and modifications of the plan will be made by the Board at intervals after review of the data. We are optimistic that over the next decade, this system will make a significant impact to reduce mortality, morbidity, and costs of diabetes, and the result will be an increased quality of life for people affected by diabetes in South Carolina.

Diabetes Mellitus↗
PubMed1995

CD40 cross-linking inhibits specific antibody production by human B cells.

Ligation of CD40 on B cells is a co-stimulatory signal for proliferation, antibody secretion, heavy chain switching and rescue from apoptosis after somatic mutation in the germinal centre. The importance of these manifold responses to CD40 activation for humoral immunity is exemplified by the inability of boys with X-linked hyper IgM syndrome to make IgG, IgE or IgA due to a mutation in in the gene coding for CD40 ligand (CD40L). In the present study, we have investigated the effect of CD40 ligation on specific antibody production by human B cells to influenza virus. The antibody response was T cell dependent and specific for the strain of influenza virus used as antigen. Addition of either CD40 mAb or recombinant trimeric CD40L profoundly inhibited specific antibody production. Antibody production by unseparated tonsillar mononuclear cells and by T-depleted B cells stimulated with antigen in the presence of T cell replacing factor were equally inhibited with CD40 antibody showing that the effect was due to ligation of CD40 on B cells rather than blocking of T cell help. The specific antibody detected in these experiments was mostly IgG with little or no IgM and was obtained from surface IgM B cells consistent with activation of a secondary (memory) response. Co-stimulation of tonsillar B cells with CD40 antibody and anti-IgG induced proliferation of IgG+ B cells. These results suggest that CD40 ligation can inhibit specific antibody responses and stimulate proliferation in the same IgG+ (memory) B cell subpopulation. Addition of CD40 antibody during the first 24-48 h of the response was required for inhibition, suggesting that the effect was on early B cell activation and/or proliferation required for antibody production. There was no correlation, however, between the ability of CD40 mAb to stimulate proliferation and inhibit antibody production. We suggest that early activation of CD40 in the specific antibody response inhibits the formation of plasma cells and promotes instead the generation of memory cells.

Antibodies, Monoclonal↗