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Biomedical subjects

S J Miller

Publications and source records attributed to S J Miller.

At least 91 records · Page 5Linked to original sources

Stroke following rottweiler attack.

A previously healthy 50-year-old man suffered a major right cerebral infarction shortly after receiving head and neck bites in an attack by two rottweilers. Arteriography revealed occlusion of the right middle cerebral artery, an intimal flap and pseudoaneurysm in the high right internal carotid artery just proximal to the skull base, and an obstructed right vertebral artery. The powerful jaw mechanism of rottweilers and other large mastiff-type dogs makes their bites particularly destructive. The predilection of these animals for attacking the head and upper body makes occult crush injury to the extracranial cerebral vessels an important diagnostic consideration following such attacks.

Animals↗

Mouse skin is particularly susceptible to tumor initiation during early anagen of the hair cycle: possible involvement of hair follicle stem cells.

Stem cells are believed to be a necessary target of chemical carcinogens. Based on autoradiographic, ultrastructural, and biologic criteria, we have recently proposed that hair follicle stem cells reside not in the bulb, but in the upper outer root sheath in an area called the bulge. Proliferating cells have been shown to be more susceptible to tumor initiation, and we have recently demonstrated that cells in the bulge undergo transient proliferation during early anagen. Therefore, we theorized that mouse skin should be particularly susceptible to carcinogen application during early anagen phase. In this paper, we show that early anagen Swiss and Sencar mouse skin is indeed particularly susceptible to one- and two-stage chemical carcinogenesis, resulting in tumor yields one to five times those obtained with telogen-timed carcinogen application. Our findings implicate a possible involvement of the bulge cells as precursors to some of the skin cancers, and support the concept that these are stem cells. These observations also raise important questions about the cellular origins and biologic behavior of chemically induced murine skin tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Visual fields with protective eyewear.

Sports-related eye injuries are quite common, yet the number of athletes who utilize protective eyewear is extremely low. The purpose of this study was to determine if there is a significant visual field loss associated with wearing eye protection. One of the authors was subjected to standard kinetic visual field testing with and without eye goggles. No significant difference was revealed. Physicians, physical therapists, and trainers should promote the use of protective eyewear and reassure athletes that they will not lose visual field.

Athletic Injuries↗

Measuring service quality and its relationship to future consumer behavior.

The authors adapt the SERVQUAL scale for medical care services and examine it for reliability, dimensionality, and validity in a primary care clinic setting. In addition, they explore the possibility of a link between perceived service quality--and its various dimensions--and a patient's future intent to complain, compliment, repeat purchase, and switch providers. Findings from 159 matched-pair responses indicate that the SERVQUAL scale can be adapted reliably to a clinic setting and that the dimensions of reliability, dependability, and empathy are most predictive of a patient's intent to complain, compliment, repeat purchase, and switch providers.

Ambulatory Care Facilities↗

Murine teratology and pharmacokinetics of the enantiomers of sodium 2-ethylhexanoate.

A mouse model for the induction of exencephaly with sodium (+/-)-2-ethylhexanoate has been developed using multiple administration regimes. With three consecutive administrations at one-half-day intervals, the most sensitive time to induce exencephaly was Gestational Days 8-9. Using the racemic substance it was determined that the SWV strain was more sensitive to the induction of exencephaly than the C57BL/6NCrlBR strain. The enantiomers of 2-ethylhexanoic acid were separated via preparative HPLC to greater than 99.8% optical purity, and greater than 99% purity according to a gas chromatographic analysis. It was demonstrated that the (R)-enantiomer is a more potent teratogen than the (S)-enantiomer for the induction of exencephaly as well as malformations of other organ systems. Pharmacokinetic analyses for each of the enantiomers were performed in maternal plasma, maternal muscle, and embryo. The pharmacokinetics showed that the peak concentration (Cmax) for both enantiomers in the three compartments was approximately equivalent and was attained within 15 min following the third administration. The area under the concentration versus time curve values for the two enantiomers were approximately 10% higher for the (R)-antipode because of a slightly slower elimination of this compound. There was negligible (or no) racemization of the two enantiomers in the biological samples. The results suggest that teratologic differences in the enantiomers of sodium 2-ethylhexanoate are not due to differences in the concentrations of these antipodes in the embryo, but more likely result from the specific interaction of the enantiomers with chiral molecules in the embryo.

Abnormalities, Drug-Induced↗

Urokinase plasminogen activator is immunocytochemically detectable in squamous cell but not basal cell carcinomas.

The presence of plasminogen activators (PA) in a variety of solid tumors appears to correlate, in a number of instances, with enhanced invasive or metastatic capabilities. In the present study, we have immunocytochemically examined basal cell (BCC) and squamous cell carcinomas (SCC) comprising a spectrum of histologic subtypes for the presence of urokinase-type (uPA) and tissue-type (tPA) PA. Neither uPA nor tPA was noted in any BCC, whether of the nodular, infiltrative, morpheaform, or basosquamous variety. uPA but not tPA was seen in 12 of 16 SCC examined; the tumors lacking uPA were all histologically well differentiated. No relationship between uPA expression and depth of invasion was noted, and uPA was not preferentially expressed at tumor borders. We conclude that uPA presence in SCC may relate to the degree of differentiation.

Animals↗

Eccrine syringofibroadenoma (Mascaro): an ultrastructural study.

To confirm the eccrine acrosyringeal differentiation of eccrine syringofibroadenoma (ESFA) and to elucidate the histogenesis of its angiofibrotic stroma, a case of ESFA from a 45-year-old man was examined by light and electron microscopy. Histologically, the parenchyma featured anastomosing, slender epithelial cords containing small cuboidal cells and occasional duct-like structures. The stroma had increased numbers of mast cells, increased capillaries with swollen endothelial cells, and prominent fibrosis. Ultrastructurally, the following findings were characteristic of ESFA: a) abundant glycogen particles in epithelial cells, b) numerous intracytoplasmic and extracellular spaces lined with microvilli, c) intraepithelial duct formation, consisting of microvilli, vesicles, rod-shaped dense bodies, multivesicular dense bodies, and peripheral network of tonofilaments, and d) large numbers of mast cells, closely associated with fibroblasts, surrounding increased numbers of capillaries containing swollen endothelial cells. These ultrastructural features support the acrosyringeal differentiation of ESFA. We hypothesize that mast cell hyperplasia and degranulation may play an important role in the formation of the angiofibrotic stroma.

Adenofibroma↗

Measurement of free desipramine in serum by ultrafiltration with immunoassay.

We developed an ultrafiltration method for assaying free desipramine (DMI) in serum. An ultrafiltrate of DMI-containing serum was prepared by centrifugation through an Amicon Centrifree micropartition filter. Syva DMI solid-phase extraction (SPE) columns were used to extract the DMI from the serum and ultrafiltrate. The Syva monoclonal EMIT assay was used to quantify the DMI in the extract. In some experiments, the percent free DMI was quantified with radioactivity. Nonspecific losses of DMI in serum to the ultrafilter system were low (recoveries > 91%). Extraction of [3H]DMI from phosphate-buffered saline (to mimic serum ultrafiltrate) with the Syva SPE system was quantitative (recoveries of 98.4% +/- 4.6%). Free DMI concentrations, derived from serum containing 2.5-2500 micrograms/L DMI, were determined by ultrafiltration; results agreed well with values determined by equilibrium dialysis, the average percent of free DMI being 18.4% +/- 0.25% and 15.9% +/- 0.51%, respectively. To increase the sensitivity of the free DMI assay in the therapeutic range (total DMI 125-300 micrograms/L), we increased fourfold the ultrafiltrate volume applied to the SPE column. For free DMI at 11-130 micrograms/L, the within-run and between-run CVs for the ultrafiltration method were < 9% and < 15%, respectively. Binding of DMI to serum proteins decreased over the pH range 6.0-8.0, although temperatures between 20 and 28 degrees C did not affect binding. The ultrafiltration assay is fast, accurate, simple, and adaptable to standard laboratory instrumentation.

Desipramine↗

Biology of basal cell carcinoma (Part I).

Basal cell carcinoma is the most common malignancy in humans. Although rarely metastatic, it is capable of significant local destruction and disfigurement. This two-part article reviews the current understanding of basal cell carcinoma biology. Part I examines significant clinical, histologic, and ultrastructural features that relate to invasive potential. Genetic characteristics, including tumor growth rate, chromosomal abnormalities, and oncogene presence, are discussed, and expression of important cell and matrix proteins, including keratin, fibronectin, and HLA antigens, are reviewed. Further topics to be explored in Part II include host immunologic responses, theories of pathogenesis, and valuable second-line therapeutic regimens for treatment of multiple cancers.

Basal Cell Carcinoma↗

Biology of basal cell carcinoma (Part II).

Host-tumor relationships involve several factors that can enhance or suppress neoplastic growth. This second part of a review of basal cell carcinoma biology examines the role that hormones, cytokines, local and systemic immunity, congenital and genetic syndromes, and environmental factors play in the development of this neoplasm. Theories of etiology and pathogenesis are discussed, and transplantation and cell culture techniques used to study this cancer are explored. Valuable second-line therapies for treatment of multiple tumors are reviewed, and important areas of present and future research are emphasized.

Animals↗

Nucleotide sequence of RNA 2 of a Czechoslovakian isolate of red clover necrotic mosaic virus.

The complete nucleotide sequence (1448 nucleotides) of RNA 2 of a Czechoslovakian isolate TpM-34 of red clover necrotic mosaic virus (RCNMV-TpM-34) has been determined. The sequence contained one major open reading frame (ORF) with the potential to encode a protein of 326 amino acids (Mr 35755), designated P2. The nucleotide sequence of RNA 2 of RCNMV-TpM-34 and the previously published sequence of RNA 2 of an Australian isolate of the virus (RCNMV-Aus) were 83% identical and there was 80% amino acid sequence identity between the P2 proteins of these isolates. However the N-terminal two-thirds of the P2 proteins shared a higher degree of similarity than the C-terminal regions which were predicted to have a more flexible structure. An ORF in the 3' portion of RNA 2 of RCNMV-Aus, which could encode a protein of Mr 5000, was not present in RNA 2 of RCNMV-TpM-34. RNAs 1 and 2 of RCNMV-TpM-34 and RCNMV-Aus are bilaterally compatible.

Amino Acid Sequence↗

A spontaneous red clover necrotic mosaic virus mutant with a truncated movement protein.

A spontaneous red clover necrotic mosaic virus mutant, TpM-341, was isolated by multiple passage of Czechoslovakian isolate TpM-34 in beans, followed by three cycles of single lesion isolation in cowpea and in Chenopodium quinoa. The symptoms induced in cowpea by TpM-34 and TpM-341 differed. TpM-34 gave rise to chlorotic lesions which expanded with time, often becoming confluent with adjacent lesions, and developed necrotic margins; the plants became systemically infected. TpM-341 induced necrotic lesions which, once developed, did not expand further; plants did not become systemically infected. Analysis of pseudorecombinants formed between the RNAs of TpM-34 and TpM-341 showed that RNA 2 determined the difference in symptoms. Comparison of the nucleotide sequence of the open reading frames (ORFs) encoding the P2 movement proteins of the two isolates revealed only one difference, a deletion of an A residue in a sequence of four A residues (nucleotides 790 to 793). Construction of full-length TpM-34 and TpM-341 RNA 2 cDNA clones, from which infectious RNA 2 could be transcribed in vitro, and in vitro mutagenesis of a cDNA clone of TpM-341, confirmed that the difference in the symptoms induced by TpM-341 was caused by the loss of this A residue. This single base deletion was predicted to cause a translational frame-shift in the P2 ORF causing the loss of 88 amino acids at the C terminus which were replaced by a sequence of 34 different amino acids, producing a truncated P2 protein. In vitro translation of RNA 2 transcribed from cDNA clones showed that RNA with four or three A residues starting at nucleotide 790 produced proteins of Mr 36K and 30K respectively, in agreement with the predictions based on the nucleotide sequence.

Base Sequence↗

Medication-nutrient interactions: hypophosphatemia associated with sucralfate in the intensive care unit.

Clinically significant medication-nutrient interactions are of concern to the nutritional support practitioner. To emphasize the possible effect of the aluminum-containing medication sucralfate on serum phosphorus levels, patients admitted to the intensive care unit of a small private hospital were monitored for a 4-week period. Sixteen patients demonstrated low serum phosphorus levels; eight (50%) of these were receiving sucralfate. Eighteen patients had no low phosphorus levels measured; five (28%) patients in this group were receiving sucralfate. The hypophosphatemia observed in these patients was probably multifactorial; respiratory alkalosis and dextrose feeding as well as sucralfate use are consistent with hypophosphatemia.

Adult↗

Antibacterials. Synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 2. The "A" group.

The synthesis and structure-activity relationship (SAR) studies of the effect of varying the "A" group in a series of 5-(acetamidomethyl)oxazolidonone antibacterials (2) are described. Compounds 2 were principally prepared either by the six-step synthesis described previously (J. Med. Chem. 1989, 32, 1673) or by elaboration of the synthetic intermediate 2 (A = H) via electrophilic aromatic substitution or elaboration of the intermediate 2 (A = I) by transition metal catalyzed carbon-carbon bond-forming reactions. Antibacterial evaluation of compounds 2 with A = alkyl, ethenyl, ethynyl, hydroxyalkyl, aldo and keto, oximinoakyl, carboalkoxy, nitro, amino, halo and psi-halo, alkylthio, alkylsulfinyl, and alkysulfonyl against Staphylococcus aureus and Enterococcus faecalis led to the identification of several SAR trends. In several series of homologues (alkyl, ketyl, aximinoalkyl, amino, halo and psi-halo, and alkythio), antibacterial activity increased with increasing lipophilicity. But in series with where A is a substituent with a trior tetrasubstituted (substituent larger than H) quaternary atom attached directly to the aromatic ring (hydroxyalkyl, alkylsulfinyl, alkylsufonyl), the activity peaked at the member of the series with the "tert-butyl" connectivity pattern. Conjugated electron-withdrawing substituents also had increased activity relative to nonconjugated analogues of comparable lipophilicity.

Anti-Bacterial Agents↗

Phosphorylation of native 97-kDa 3-hydroxy-3-methylglutaryl-coenzyme A reductase from rat liver. Impact on activity and degradation of the enzyme.

Immunoprecipitation of native rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, phosphorylated by [gamma-32P]ATP in the presence of reductase kinase, revealed a major 97-kDa 32P band which disappeared upon competition with pure unlabeled 53-kDa HMG-CoA reductase. A linear correlation between the expressed/total HMG-CoA reductase activity ratio (E/T) and the fraction of 32P released from the 97-kDa enzyme established the validity of the E/T ratio as an index of HMG-CoA reductase phosphorylation state in isolated microsomes. Incubation of rat hepatocytes with mevalonolactone resulted in a rapid increase in phosphorylation of microsomal reductase (decrease in E/T) followed by an enhanced rate of decay of total reductase activity which was proportional to the loss of 97-kDa enzyme mass determined by immunoblots. Inhibitors of lysosome function dampened both basal and mevalonate-induced reductase degradation in hepatocytes. In an in vitro system using the calcium-dependent protease calpain-2, up to 5-fold greater yields of soluble 52-56-kDa fragments of reductase (immunoblot and total activity) were obtained when the substrate 97-kDa reductase was phosphorylated before proteolysis. Immunoblots of unlabeled phosphorylated reductase compared with gels of immunoprecipitated 32P-labeled reductase resolved a 52-56-kDa doublet which contained 32P solely in the upper band. These data suggest that a major phosphorylation site of HMG-CoA reductase lies within the "linker" segment joining the membrane spanning and cytoplasmic domains of the native 97-kDa protein.

Animals↗