Biomedical subjects

M M Smith

Publications and source records attributed to M M Smith.

At least 55 records · Page 3Linked to original sources

PubMed1998

Quantification of insulin in dried blood spots.

A method has been developed in which the concentrations of insulin in dried blood spots on filter paper can be estimated. The technique involves elution of blood from the paper, evaporation, and rehydration in assay buffer. The resuspended samples are then assayed by radioimmunoassay. The ratio of control plasma to control dried blood spot insulin values is used as a conversion factor for unknown samples on paper to express the dried blood spot insulin concentration in plasma equivalents. Intra-assay variability was 14%, and interassay variability was 25%, but the elution conversion factor had a variability of about 40% among individuals. This technique has substantial advantages for field studies, but elevated values should be confirmed by a venous plasma sample measurement in a conventional radioimmunoassay.

Blood Proteins↗

PubMed1998

Exodontics.

Exodontic therapy may be challenging and difficult especially if the involved tooth has minimal or no periodontal disease. Surgical methods aid the clinician's ability to perform exodontic therapy for the maxillary fourth premolar, mandibular first molar, maxillary canine, and mandibular canine. Complications of exodontic therapy may include fracture, ocular trauma, and infection.

Animals↗

PubMed1998

Substrate specificity of prostate-specific antigen (PSA).

BACKGROUND: The serine protease prostate-specific antigen (PSA) is a useful clinical marker for prostatic malignancy. PSA is a member of the kallikrein subgroup of the (chymo)trypsin serine protease family, but differs from the prototypical member of this subgroup, tissue kallikrein, in possessing a specificity more similar to that of chymotrypsin than trypsin. We report the use of two strategies, substrate phage display and iterative optimization of natural cleavage sites, to identify labile sequences for PSA cleavage. RESULTS: Iterative optimization and substrate phage display converged on the amino-acid sequence SS(Y/F)Y decreases S(G/S) as preferred subsite occupancy for PSA. These sequences were cleaved by PSA with catalytic efficiencies as high as 2200-3100 M-1 s-1, compared with values of 2-46 M-1 s-1 for peptides containing likely physiological target sequences of PSA from the protein semenogelin. Substrate residues that bind to secondary (non-S1) subsites have a critical role in defining labile substrates and can even cause otherwise disfavored amino acids to bind in the primary specificity (S1) pocket. CONCLUSION: The importance of secondary subsites in defining both the specificity and efficiency of cleavage suggests that substrate recognition by PSA is mediated by an extended binding site. Elucidation of preferred subsite occupancy allowed refinement of the structural model of PSA and should facilitate the development of more sensitive activity-based assays and the design of potent inhibitors.

Amino Acid Sequence↗

PubMed1998

Copper, iron, zinc, and manganese in dietary supplements, infant formulas, and ready-to-eat breakfast cereals.

High intakes of iron, zinc, or manganese can interfere with copper absorption. Thus, the purpose of this study was to determine whether the amounts and chemical forms of iron, zinc, manganese, and copper added to food products and nutritional supplements might pose a threat to copper status. More than 25% of the vitamin and mineral supplements examined contained no copper, 40% contained the poorly absorbed cupric oxide, and < 30% contained a highly bioavailable form of copper such as cupric sulfate or cupric chloride. Nearly 40% of the prenatal supplements examined contained both iron and zinc without a nutritionally significant amount of copper. More than 80% of the infant formulas examined had ratios of iron to copper exceeding 20:1, which is higher than the recommended ratios of 10-17:1. None of the 40 ready-to-eat breakfast cereals examined were fortified with copper or manganese although 50% of these cereals contained > or = 25% of the reference daily intake for both iron and zinc. Copper availability could be improved by reformulation of several food products and supplements.

Biological Availability↗

PubMed1998

Management of substernal goiter.

OBJECTIVE: To analyze the presentation, evaluation and treatment of patients with large substernal goiters, with emphasis on the radiographic evaluation and the results of treatment. STUDY DESIGN: A retrospective chart review of 150 patients undergoing thyroidectomy at the Vanderbilt University Department of Otolaryngology-Head and Neck Surgery. METHODS: Charts of patients undergoing thyroidectomy were reviewed. Those with substernal goiter, defined as a major portion of the goiter within the mediastinum, were included in the study. When available, the radiographic studies were reviewed by a staff neuroradiologist. RESULTS: Twenty-three patients (15.3%) presented with substernal extension of the goiter. Characteristics of these patients included mean age of 59 years, 78% female, symptoms of compression such as dyspnea, choking, and dysphagia (65%), hoarseness (43%), and previous thyroid surgery (30%). Seventeen percent were asymptomatic. Preoperative radiographs demonstrated tracheal compression (73%), tracheal deviation (77%), esophageal compression (27%), and major vessel displacement (50%). Histology revealed multinodular goiter (16/23, 70%), thyroiditis (3/23, 13%), and malignancy (4/23, 17%). The average size of the resected specimen in greatest dimension was 8.0 cm (range, 3.0-14.0 cm) and weighed 148 g (range, 39-426 g). All were successfully approached through a transcervical incision without the need for sternotomy, and total thyroidectomy was performed in 83% of the cases. No major complications have been documented, and no evidence of tracheomalacia was encountered. CONCLUSION: Despite the large size of these goiters and the significant involvement of the major mediastinal structures, all were approached through the transcervical incision. Further, despite significant tracheal involvement, there were no cases of tracheomalacia or major complications. For intraoperative planning, the authors advocate the routine use of preoperative computed tomography scanning.

Adult↗

PubMed1998

Regional peripheral vascular supply based on the superficial temporal artery in dogs and cats.

Cutaneous arterial blood supply to the temporal region was evaluated in 8 dogs and 8 cats. Subtraction radiography and angiography of the carotid and superficial temporal arteries were used in 4 dogs and 4 cats to determine arterial blood supply to the temporal region and frontalis muscle. A myocutaneous axial pattern flap based on the superficial temporal artery and frontalis muscle may be indicated for cosmetic reconstruction in dogs and cats following surgical resection of neoplastic lesions or traumatic wounds in the maxillofacial region. The frontalis muscle was identified as the thin subcutaneous continuation of the platysma muscle extending cranially and rostrally. Dissection of the temporal region in 4 dogs and 4 cats revealed the subcutaneous location of the superficial temporal artery as it continues rostrally from the caudal aspect of the zygomatic arch.

Angiography↗

PubMed1998

Evolutionary origins of the vertebrate dentition: phylogenetic patterns and developmental evolution.

The theory that teeth evolved from dermal denticles linked with the origin of jaws no longer accounts for the diversity of new data emerging from the fossil record. We have reviewed oropharyngeal dental patterns in all fossil groups of early vertebrates to establish the primitive condition, in order to understand the polarity of change. The evolutionary precedence of dermal denticles before teeth now seems less likely; both may be alternative manifestations of a common morphogenetic system. This developmental system involves regulatory changes affecting the odontode, a fundamental exoskeletal unit, and can explain skeletal diversity. However, tooth and denticle differences may have diverged at loci deep within vertebrate phylogeny, as real differences exist between them. Teeth were conceived as evolving from non-growing odontodes with regulation of precise increase in size, position, sequence of time of development, and polarity of shape. A characteristic feature of teeth is the ability to replace from a developing sequence, programmed with these parameters, prior to demand. Tooth whorls, a feature of denticles in the oropharyngeal region, may be regarded as a preadaptation of this tooth replacement mechanism. The new fossil evidence suggests that teeth may have evolved from these more specialised oropharyngeal denticles in agnathan vertebrates.

Animals↗

PubMed1998

Acanthosis nigricans as a risk factor for non-insulin dependent diabetes mellitus.

The prevalences of obesity and of non-insulin dependent diabetes mellitus (NIDDM) have increased in the United States population over the past two decades, and thus diabetes prevention has become a major concern of public health agencies such as the National Institutes of Health. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of NIDDM. Subjects with hyperinsulinemia, impaired glucose tolerance, or gestational diabetes are well accepted as being at high risk for diabetes. We propose that the easily identifiable skin lesion, acanthosis nigricans, is common in the major minority groups in the United States and that its presence is a surrogate for laboratory-determined hyperinsulinemia.

Acanthosis Nigricans↗

PubMed1998

The Drosophila gene Medea demonstrates the requirement for different classes of Smads in dpp signaling.

Signals from transforming growth factor-beta (TGF-beta) ligands are transmitted within the cell by members of the Smad family, which can be grouped into three classes based on sequence similarities. Our previous identification of both class I and II Smads functioning in a single pathway in C. elegans, raised the issue of whether the requirement for Smads derived from different classes is a general feature of TGF-beta signaling. We report here the identification of a new Drosophila class II Smad, Medea, a close homolog of the human tumor-suppressor gene DPC4. Embryos from germline clones of both Medea and Mad (a class I Smad) are ventralized, as are embryos null for the TGF-beta-like ligand decapentaplegic (dpp). Loss of Medea also blocks dpp signaling during later development, suggesting that Medea, like Mad, is universally required for dpp signaling. Furthermore, we show that the necessity for these two closely related, non-redundant Smads, is due to their different signaling properties - upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus. These results provide a paradigm for, and distinguish between, the requirement for class I and II Smads in Dpp/BMP signaling.

Amino Acid Sequence↗

PubMed1998

Acanthosis nigricans.

Acanthosis nigricans is a lesion affecting localized areas of the skin in persons with obesity and/or hyperinsulinemia. Roughening of the skin correlates with histological papilomatosis and the apparent darkening is due to hyperkeratosis. Biochemical mechanisms for developing this hyperplastic lesion are unclear, but likely involve local cutaneous growth factors. Cross sectional surveys of unselected populations have demonstrated that young children have low prevalences of obesity and acanthosis nigricans, but the prevalences of both increase with increasing age until plateaus are reached after the age of ten. Nearly 40% of Native American teenagers have acanthosis nigricans, whereas about 13% of African American, 6% of Hispanic, and less than 1% of white, non-Hispanic children aged 10-19 have clinically apparent acanthosis nigricans. We conclude that the presence of this skin lesion is a clinical surrogate of laboratory-documented hyperinsulinemia. Acanthosis nigricans identifies a subgroup within an ethnic group who have the highest insulin concentration, the most severe insulin resistance, and thus the highest risk for the development of type 2 diabetes.

Acanthosis Nigricans↗

PubMed1998

Pulp remains viable following vital amputation of the mesio-buccal root of the maxillary fourth premolar in dogs.

Vital amputation of the mesio-buccal root of the maxillary fourth premolar (P4) was performed bilaterally in 8 dogs. Histopathologic evaluation of the tooth structure revealed normal pulp in the remaining mesio-buccal, mesio-palatal, and distal roots and crown during a mean follow-up period of 3.5 +/- 1.9 months. Amputation site healing was characterized by a reparative dentin bridge produced by odontoid cells. Tunnel defects were observed in 13 of 16 (81%) dentin bridges. It is concluded that the pulp of a tri-rooted, periodontal disease-free tooth remains viable during a 6-month period following vital root amputation. These results point to the intriguing possibility that this may also occur in humans, however, this needs to be directly tested in man.

Animals↗

PubMed1998

Imaging of Bezold's abscess.

OBJECTIVE: Our purpose was to describe the CT findings in patients with Bezold's abscesses. CONCLUSION: Bezold's abscesses are rare complications of mastoiditis. In our series most were seen in adults and were associated with a history of cholesteatoma and mastoidectomy. CT of the neck and temporal bone can help the surgeon determine appropriate treatment.

Abscess↗

PubMed1998

Periodontal healing of canine experimental grade-III furcation defects treated with autologous fibrinogen and absorbable barrier membrane.

OBJECTIVE: To determine the effects of autologous fibrinogen (AF) and absorbable barrier membrane (ABM) on periodontal healing of canine experimental grade-III furcation defects. ANIMALS: 18 conditioned, laboratory-source, adult Beagles. PROCEDURE: Defects were developed bilaterally at the second and fourth premolars and maintained for 12 weeks. Defects were treated with AF, ABM, AF and ABM, or debridement. Digital subtraction radiography, histologic evaluation, and histomorphometric analysis of defect healing was done at 1, 3, and 6 months after treatment to determine percentage increases in bone volume, height, area, and length of periodontal regeneration along the perimeter of the defect. RESULTS: Comparison of defects at post-treatment intervals indicated significantly greater healing of debridement and AF-treated defects, compared with ABM-treated defects at 3 months; however, by 6 months, there were no significant differences in defect healing for all histomorphometric variables. Defects treated with ABM were associated with significantly less root ankylosis than other treatments. Defects treated with debridement had significantly greater increases in bone volume at 6 months after treatment, compared with groups treated with ABM. There was a significant correlation between regenerated bone area, bone volume, and periodontal regeneration for all treatments at 3 and 6 months after treatment. CONCLUSION AND CLINICAL RELEVANCE: Use of AF and ABM did not enhance the amount of periodontal healing, compared with debridement only. The ABM-treated defects were essentially devoid of root ankylosis. Grade-III furcation defects may respond equally well to conservative periodontal surgery or guided tissue regenerative techniques. The prevention of root ankylosis is a substantial benefit favoring this latter method of treatment.

Absorption↗

PubMed1997

Neural crest potential for tooth development in a urodele amphibian: developmental and evolutionary significance.

Tooth development in urodele amphibians occurs from a restricted region of anterior cranial neural crest. An in vitro culture system was used to test the odontogenic potential of more caudal regions of neural crest, including an "intermediate region" of neural folds which has never previously been tested for either fate or potential. Explants of different axial levels of neural crest with stomodaeal ectoderm and endoderm demonstrated that odontogenic potential extends not only further caudally than the axial level fated to produce teeth, but also beyond that with potential to produce cartilage. Our results show that chondrogenic potential is found only within the most rostral portion of the intermediate region, but that odontogenic potential extends to its most caudal limit. This separation of skeletogenic cell lineages in the neural crest necessitates a reevaluation of the designations of "cranial" and "trunk" and a reconsideration of the evolutionary implications of developmentally distinct crest-derived mesenchyme populations. The proposal that odontogenic potential extends into the trunk neural crest may be explained as conserved from a phylogenetically older, more extensive skeletogenic ability which produced the exoskeleton of more basal vertebrates.

Ambystoma mexicanum↗

PubMed1997

Histone octamer function in vivo: mutations in the dimer-tetramer interfaces disrupt both gene activation and repression.

Within the core histone octamer each histone H4 interacts with each H2A-H2B dimer subunit through two binding surfaces. Tyrosines play a central role in these interactions with H4 tyrosines 72 and 88 contacting one H2A-H2B dimer subunit, and tyrosine 98 contacting the other. To investigate the roles of these interactions in vivo, we made site-directed amino acid substitutions at each of these tyrosine residues. Elimination of either set of interactions is lethal, suggesting that binding of the tetramer to both dimers is essential. Temperature-sensitive mutants were obtained through single amino acid substitutions at each of the tyrosines. The mutants show both strong positive and negative effects on transcription. Positive effects include Spt- and Sin-phenotypes resulting from mutations at each of the three tyrosines. One allele has a strong negative effect on the expression of genes essential for the G1 cell cycle transition. At restrictive temperature, mutant cells fail to express the CLN1, CLN2, SWI4 and SWI6 genes, and have reduced levels of CLN3 mRNA. These results demonstrate the critical role of histone dimer-tetramer interactions in vivo, and define their essential role in the expression of genes regulating G1 cell cycle progression.

Chromatin↗

PubMed1997

Absorption, retention and urinary excretion of chromium-51 in rats pretreated with indomethacin and dosed with dimethylprostaglandin E2, misoprostol or prostacyclin.

Drug-nutrient interactions affecting chromium were investigated in this study. Rats were injected with indomethacin to reduce endogenous prostaglandin synthesis and dosed with prostaglandin analogues or prostacyclin. Effects on absorption, tissue distribution and urinary excretion of 51Cr from 51CrCl3 were evaluated using a 2 x 4 factorial experimental design. Forty-eight adult male rats were food deprived for 12 h and then injected intraperitoneally with indomethacin (5 mg/kg body wt) or placebo. Thirty minutes later, rats were intubated and dosed with one of four treatments: a prostaglandin E1 analogue (misoprostol) at 50 microg/kg body wt; a prostaglandin E2 analogue (16,16-dimethylprostaglandin E2) at 7.5 microg/kg body wt; prostacyclin at 20 microg/kg body wt; or control (7.64 mmol/L Tween-80 suspended in 0.15 mol/L NaCl containing 0.48 mol/L ethanol). Immediately after intubation, rats were dosed with 3.7 mBq of 51CrCl3 by micropipette. Blood was collected from the tail at intervals after 51Cr dosing. Six hours after dosing, 51Cr rats were exsanguinated by cardiac puncture. Indomethacin, an inhibitor of prostaglandin synthesis, significantly increased (P < 0.05) 51Cr in blood at all time periods tested except at 15 min. In tissues, indomethacin significantly increased 51Cr retention. Urinary 51Cr excretion at 6 h was higher (P < 0.05) in indomethacin-pretreated rats than in control rats. Administration of indomethacin, which blocks prostaglandin synthesis, enhanced 51Cr absorption, whereas dosing with 16,16-dimethylprostaglandin E2 decreased 51Cr absorption.

16,16-Dimethylprostaglandin E2↗

PubMed1997

Measurement of airborne flour exposure with a monoclonal antibody-based immunoassay.

BACKGROUND: The development of simple and standardised methods to measure airborne levels of workplace biological allergens is an important step in reducing the incidence of occupational asthma. Such a method would be useful for measuring wheat flour allergens which cause asthma in bakers. Measurement of allergen per se rather than total dust enables exposure to be better defined. METHODS: Monoclonal antibodies were produced, their specificity analysed by immunoblotting and then used to affinity-purify a putative flour allergen. The importance of this protein as an allergen was tested by RAST using sera from allergic bakers and it was identified by N-terminal sequencing. Suitable monoclonal antibodies were chosen to develop an enzyme-linked immunosorbent assay. Commercial baking flours and personal airborne dust samples were analysed using the immunoassay. RESULTS: A sensitive and specific monoclonal antibody-based enzyme-linked immunosorbent assay was developed to measure a wheat alpha-amylase inhibitor. The wheat alpha-amylase inhibitor content of bulk wheat flours was 0.124% (95% confidence limits 0.083-0.164%) and airborne levels in bakeries had a geometric mean of 744 ng/m3 (95% confidence limits 371-1,496 ng/m3). CONCLUSION: This assay is suitable for widespread use as the monoclonal antibodies and standards are well defined and potentially infinitely available. The assay therefore offers distinct advantages over those exposure assessment methods currently in use. Comparable results would be obtained by different investigators over a prolonged time period. The assessment of flour allergen exposure and the relationship with clinical response could then be investigated using a multi-centered approach.

Air Pollutants, Occupational↗

PubMed1997

Hyperactive pectoralis reflex as an indicator of upper cervical spinal cord compression. Report of 15 cases.

Myelopathy from cervical spondylosis is often accompanied by hyperreflexia of the upper-extremity deep tendon reflexes (DTRs). Reflexes such as the pectoralis jerk and the deltoid jerk may only be apparent in the context of hyperreflexia. Although the nerve roots involved in the reflex arcs are well described, levels of cervical spinal cord compression that lead to the hyperreflexia are not as clear. This is of particular significance for patients with multilevel cervical spondylosis in determining the levels responsible for their symptoms. The authors examined 15 consecutive patients who presented for treatment of cervical myelopathy. The clinical examination was then correlated with levels of cervical spinal cord compression by cervical magnetic resonance imaging or computerized tomography with intrathecal contrast enhancement. The presence of a prominent pectoralis jerk was seen only in patients with spinal cord compression at the C2-3 and/or C3-4 levels (nine patients). No patient with compression at or below the C4-5 disc space without coexisting compression at a higher level had hyperactive pectoralis reflexes. This association between the C3-4 level and a hyperactive pectoralis reflex was significant (p < 0.004, Fisher's exact test). The deltoid reflex was tested in the last nine consecutive patients. It was present in patients with compression of the upper spinal cord at levels C3-4 and C4-5 (four of five patients) but appeared in only one of four patients with compression below C4-5. This association did not attain statistical significance. The presence of a hyperactive pectoralis reflex is specific for lesions of the upper cervical spinal cord. Examination of upper-extremity DTRs may be helpful in planning the appropriate levels for surgical decompression in patients with multilevel spondylosis and myelopathy.

Humans↗