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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 307 records · Page 17Linked to original sources
PubMed1994

A contribution to the differential diagnosis of the "group of schizophrenias": structural abnormality of chromosome 4.

A structural abnormality of chromosome 4 [inv 4 (p15.2; q21.3)] is reported in a male presenting with DSM-III-R schizophrenia, undifferentiated type (295.94) and in his mother, who displayed symptoms associated with schizotypal personality disorder (DSM-III-R 301.22). The proband had a performance IQ of 91, poor motor coordination, stature in the lowest quartile and an impaired sense of time. There were no diagnostic physical or neurological abnormalities. Mild ventricular enlargement and prominent sulci were found on computed tomography. Both he and his chromosomally normal father had strabismus which required surgical correction. This case joins the long list of chromosomal abnormalities previously reported to confer an increased risk of mental illness and emphasizes the importance of a sophisticated differential diagnosis in evaluating patients who present with symptoms of schizophrenia. The implications for recent initiatives which attempt to localize genes conferring susceptibility to schizophrenia and other major mental illnesses are discussed.

Chromosome Aberrations↗
PubMed1994

Recent advances in stannous fluoride technology: antibacterial efficacy and mechanism of action towards hypersensitivity.

Stannous fluoride (SnF2) is highly susceptible to oxidation and hydrolysis but both anhydrous and aqueous preparations can be well established by proper formulation. When stability in aqueous preparations is achieved by the use of certain strong complexing agents, reduced antibacterial activity is observed which may be attributed to reduced bioavailability of the stannous ion. In contrast, an anhydrous SnF2 preparation maintains stannous ion in a stable but, uncomplexed form. This preparation displays antibacterial activity in saliva and delivers stannous ion which is absorbed onto surfaces making them less susceptible to plaque formation for an extended period of time (hours). When this anhydrous preparation is brushed onto dentine in vitro or in situ, one observes a nearly complete coverage of the dentine surface and occlusion of tubules by a tin-rich surface deposit. This finding indicates that the observed clinical efficacy of this preparation at relieving hypersensitivity is due to occlusion of tubules by a mixture of low solubility complexes of tin. A water-based SnF2 preparation containing strongly complexed stannous ions does not form a surface coating on dentine in vitro suggesting that this preparation may not be optimal for treating hypersensitivity. Overall, the findings indicate that the stannous ions in a SnF2 preparation must be maintained in a stable, bioavailable form for optimal efficacy against plaque and hypersensitivity to be obtained. The results suggest that these properties are provided by stable anhydrous preparations but are difficult to achieve simultaneously in aqueous preparations. When properly formulated, stannous fluoride preparations can provide multiple oral therapeutic benefits.

Bacteria↗
PubMed1994

Gleason histologic grading in prostatic carcinoma. Correlation of 18-gauge core biopsy with prostatectomy.

Histologic grading of adenocarcinoma of the prostate gland is a reliable predictor of extension and metastasis. Studies involving correlation of grade between biopsy and prostatectomy specimens have traditionally involved biopsies using a large-bore (14-gauge) cutting needle. However, common practice has shifted to the use of biopsy cores with a smaller caliber (18 gauge). This study was undertaken to determine the degree of correlation of tumor grade between 18-gauge core biopsy samples and excised glands. Sixty-seven patients with stage A or B adenocarcinoma of the prostate gland who had previously undergone 18-gauge core biopsy, who underwent radical prostatectomies, were studied. The Gleason score was determined by referred consensus among three pathologists. There was exact agreement between biopsy and excision in 39 cases (58%), whereas 24 cases (36%) differed by one digit. Three cases (4.5%) were undergraded, and one case (1.5%) was overgraded by two or more points. Only six tumors (8.9%) would have been incorrectly specified by the degree of differentiation. Discrepancies in grade of two points or more were not more frequent in cases with a small tumor volume (< or = 10%) in the biopsy specimens. We concluded that with careful histologic evaluation, the grade of tumor identified in these smaller biopsy cores correlates well with that seen at prostatectomy.

Adenocarcinoma↗
PubMed1994

Surgical trainees as anatomy demonstrators.

The aim was to determine whether anatomy demonstrators had increased first-time pass rates in the ABS part of FRCS compared with other candidates and to determine what anatomy departments will do if changes resulting from the Calman/Bottomley report on medical training lead to a decrease in the number of surgical trainees who wish to work as anatomy demonstrators. A questionnaire was sent to departments of anatomy in the UK and Ireland regarding: numbers of demonstrators, career background, funding, employment terms, training and first-time pass rate in ABS. Twenty-six of 32 departments responded, 89 per cent of 206 anatomy demonstrators were surgical trainees. Full-time posts were largely funded by universities and part-time posts largely by private hospitals. Nine departments had a total of 40 posts integrated with local surgical rotations, but only five provided ABS courses in all subjects. For the period 1990-1993 the first-time pass rate of demonstrators in ABS was 75 per cent, compared with the overall pass rate of 37 per cent for UK candidates at The Royal College of Surgeons of candidates at The Royal College of Surgeons of England. Changes brought in by the Calman/Bottomley report may result in fewer surgical trainees working as anatomy demonstrators. This will have major consequences for undergraduate anatomy courses. Anatomy departments will have to develop innovative methods of teaching which do not rely on surgical trainees. We believe that surgical trainees require and desire training in the basic sciences, which include anatomy, physiology, biochemistry and pathology. These objectives could be met by medical schools offering comprehensive taught courses in basic sciences in conjunction with four-month contracts as anatomy demonstrators.

Anatomy↗
PubMed1994

Hereditary nonpolyposis colon cancer: analysis of linkage to 2p15-16 places the COCA1 locus telomeric to D2S123 and reveals genetic heterogeneity in seven Canadian families.

Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominant trait responsible for approximately 6% of colorectal cancers. Linkage of the HNPCC trait to the D2S123 locus on 2p15-16 has previously been reported in two families. This HNPCC locus is now designated "COCA1." We have tested seven Canadian HNPCC families, who have a variety of clinical presentations, for linkage to a panel of microsatellite polymorphisms in the vicinity of D2S123. One family was clearly linked to the COCA1 locus (LOD = 4.21), and a second family is likely to be linked (LOD = 0.92). In three families linkage was excluded. In the remaining two families the data were inconclusive. In the linked family, individuals with cancer of the endometrium or ureter share a common haplotype with 12 family members with colorectal cancer. This supports the suspected association between these extracolonic neoplasms and the HNPCC syndrome. In addition, five of the six individuals with adenomatous polyps (but no colorectal cancer) have the same haplotype as the affected individuals, while the sixth carries a recombination. One individual with colorectal cancer carries a recombination that places the COCA1 locus telomeric to D2S123. This study localizes the COCA1 gene to an 8-cM region that is consistent with the location of the hMSH2 gene. We also confirm that families presently classified as HNPCC are genetically heterogeneous.

Adenomatous Polyps↗
PubMed1994

Echinococcus granulosus (Taeniidae) and autochthonous echinococcosis in a North American horse.

We report the first documented case of autochthonous echinococcosis in a horse of North American origin. Three fully mature and viable unilocular hydatid cysts of Echinococcus granulosus (Batsch, 1786) were an incidental finding at necropsy in the liver of a 14-yr-old gelding thoroughbred that had been foaled in Virginia and raised in Maryland. Protoscolices were armed with 2 rows of 28-37 rostellar hooks; small hooks measured 23-30 microns; large hooks measured 26-33 microns. Morphologically, these were compatible with rostellar armature considered typical for the equine strain of E. granulosus currently known primarily from the United Kingdom. This horse had a history of fox hunting, and huntsman at some premises in the region are known to feed uncooked viscera from horse carcasses to their dogs. These factors would support maintenance of infection by E. granulosus in equine hosts. The putative introduction and establishment of the equine strain of E. granulosus and recognition of endemic equine hydatid disease in the eastern U.S.A. warrants monitoring and additional investigation.

Animals↗
PubMed1994

Evaluation of a new dentifrice for the treatment of sensitive teeth.

A dentifrice containing 5% potassium nitrate, 1.3% soluble pyrophosphate, 1.5% polyvinylmethyl ether and maleic acid (PVM/MA) copolymer and 0.243% sodium fluoride in a silica base (Sensitive/Tartar Control) has been developed to concomitantly control tartar, caries and dentinal hypersensitivity. In vitro and animal studies show that the fluoride in this product effectively inhibits formation of enamel and dentine caries. In vitro studies also demonstrate that this dentifrice effectively reduces hydraulic conductance by occluding dentine tubules with a mixed surface deposit of copolymer and silica. Using an in vitro model that simulates in vivo conditions, this dentifrice also allows a rapid penetration of potassium nitrate through the dentine matrix. These findings demonstrate a correlation under in vivo conditions between the occlusion of dentine and the ability to deliver topically applied agents to target sites within or below dentine. The results indicate that this new dentifrice should provide multiple clinical therapeutic benefits including controlling tooth decay and tartar formation, and reducing and preventing dentinal hypersensitivity.

Animals↗
PubMed1994

Thermodontic stimulator--a new technology for assessment of thermal dentinal hypersensitivity.

A clinical investigation of the reproducibility of threshold and pain temperature scores obtained from use of the Thermodontic Stimulator (TDS) is reported. The TDS is designed for accurate clinical testing of thermal dentinal hypersensitivity. This instrument employs a variable stimulus/fixed response approach to clinical testing of thermal dentinal hypersensitivity. The TDS consists of a probe in a handpiece, a patient signaling device (joystick), a computer, and interface electronics. The TDS provides a precise means of assessing and recording the temperature which elicits a response to thermal stimulation from the subject being evaluated. Two temperatures are recorded. The threshold temperature is recorded when the patient is first able to sense that a cold stimulus has been applied to the tooth. The second score, pain temperature, is recorded when the subject first notices discomfort. Twenty-two subjects participated in this study. Results obtained from the 21 subjects who completed this study (one subject dropped out for non-compliance) demonstrated a reproducibility standard deviation of 1.1 degrees C for the threshold temperature, and 2.8 degrees C for the pain temperature for the duration of the study. There was a good degree of correlation between the measurements of any two test days (Pearson's correlation coefficient). There was no significant difference between the mean pain temperature scores of any two testing days.

Cold Temperature↗
PubMed1993

Peptide-induced changes in class I heavy chains alter allorecognition.

Class I molecules of the MHC are intimately involved in the development and function of CD8+ T cells. Small peptides, derived from endogenous proteins, bind within the Ag binding groove created by the beta-pleated sheets and alpha-helices of the alpha 1 and alpha 2 domains of the class I molecule. This peptide-MHC complex has been shown to influence allorecognition by CD8+ T cells. However, the precise role of peptide in alloantigen recognition remains unclear. We have previously shown that conformational changes induced in the class I molecules can be identified as specific alterations in serologic epitopes. These results suggested that alloreactive T cells may detect structural changes in MHC based on the nature of the peptide binding to the class I protein. Here, we have shown that, in at least some instances, alloreactivity may not depend on the recognition of a precise self-peptide but on an epitope on the class I molecule influenced by the peptide. The nature of specific peptides expressed by class I-bearing cells may, therefore, have a dramatic effect on T cell development, self-tolerance, and alloreactivity.

Amino Acid Sequence↗
PubMed1993

Folding and assembly of phage P22 tailspike endorhamnosidase lacking the N-terminal, head-binding domain.

Tryptic digestion of a thermal unfolding intermediate of the phage P22 tailspike endorhamnosidase produces an N-terminally shortened protein fragment comprising amino-acid residues 108-666 [Chen, B.-L. & King, J. (1991) Biochemistry 30, 6260-6269]. In the present work, the 60-kDa C-terminal fragment was purified to homogeneity from the tryptic digest by gel-fitration chromatography. As in the case for the whole tailspike protein (72 kDa), the purified fragment was found to remain stably folded as a highly soluble, SDS-resistant, enzymatically active trimer. However, its unfolding in the presence of guanidinium chloride was accelerated at least 10-fold compared to the complete, native tailspike protein. Shortened tailspike trimers reconstituted spontaneously and with high yield after diluting a solution containing acid-urea-unfolded fragment polypeptides with neutral buffer. Upon recombinant expression of the 60-kDa polypeptide in Escherichia coli, it also assembled efficiently and formed SDS-resistant trimers. The refolding and assembly pathway of the N-terminally shortened tailspike paralleled that of the complete protein with slightly, but significantly, accelerated folding reactions, at both the subunit and the trimer levels. As found for the complete tailspike protein, yields of refolding and assembly of the 60-kDa fragments into SDS-resistant trimers decreased with increasing temperature. The refolding yield of fragments derived from a temperature-sensitive mutant (Gly244-->Arg) tailspike protein was affected in similar fashion as shown for the whole protein. We conclude that the N-terminal domain (residues 1-107) is dispensable for folding and assembly of the P22 tailspike endorhamnosidase both in vitro and in vivo.

Amino Acid Sequence↗
PubMed1993

Stimulation of phosphoinositide hydrolysis by trans-(+/-)-ACPD is greatly enhanced when astrocytes are cultured in a serum-free defined medium.

Recent studies have demonstrated that astrocytes have much greater abilities to produce and respond to signalling molecules in the CNS than had been previously estimated. We now report a dramatic enhancement in the ability of a glutamate metabotropic receptor agonist, 1-aminocyclopentane-trans-(+/-)-1,3-dicarboxylic acid (trans-(+/-)-ACPD, to stimulate phosphoinositide hydrolysis in astrocytes cultured in a serum-free defined medium compared with astrocytes cultured in conventional serum-containing medium (43.2 +/- 3.6 vs. 3.2 +/- 0.48-fold of basal, respectively). This enhancement was selective to trans-(+/-)-ACPD as little or no difference in the response to carbachol or norepinephrine was seen between the two culture conditions. These results indicate a great potential for the phosphoinositide pathway in astrocyte glutamatergic signal transduction.

Animals↗
PubMed1993

Artificial disc replacement. Preliminary report with a 3-year minimum follow-up.

Artificial disc replacement was performed in six patients with an average age of 55 years and average follow-up of 3.4 years. Four of the six patients had juxtafusion degeneration, one had multilevel disc degeneration, and one patient had isolated disc resorption. The Acroflex disc (Acromed Corporation, Cleveland, OH), which was used in the replacement, is composed of a rubber core vulcanized to two titanium end plates. The latter have superior posts to provide for initial mechanical fixation and porous in-growth surfaces for long-term fixation. Satisfactory results occurred in four of six patients. Poor results occurred in the presence of deformity that resulted in prosthetic failure and isolated disc resorption. There was an average 8 degrees angular and 2.3-mm translational movement and satisfactory in-growth at all interfaces. Design objectives of endurance, biocompatibility, geometry, kinematics, constraint, dynamics, stability, and fail-safe were met; however, this study is preliminary in nature.

Biocompatible Materials↗
PubMed1993

Doctors under the knife.

With Bill Clinton's new reforms only a month away, the health-care system is on the operating table--and the doctors are under the knife. Americans have a love-hate relationship with physicians: they like the care that doctors provide but hold them to blame for the nation's health-care mess. NEWSWEEK looks at how the culture of medicine may change, assesses doctors' fears--and examines the brave new world of HMOs.

American Medical Association↗
PubMed1993

Immunofluorescent evaluation of DNA repair synthesis using interactive laser cytometry.

An improved differential fluorescence analysis technique which employs scanning laser cytometry for the detection of two DNA binding fluorochromes was used to quantitate both total DNA and cellular incorporation of the base analogue, bromodeoxyuridine (BrdUrd), into UV- or methyl methane sulphonate (MMS)-treated DNA. In this procedure DNA containing BrdUrd was partially denatured and immunolabeled by binding anti-BrdUrd monoclonal IgG to incorporated BrdUrd. Anti-BrdUrd was detected with a secondary fluorochrome-labeled polyclonal anti-IgG. Cells were counterstained with propidium iodide to allow the determination of total DNA. Fluorescence was determined using the Meridian ACAS 570 Scanning Laser Cytometer. The computer-analyzed images were generated from monodisperse populations of UV- or MMS-treated cells, allowing the evaluation of DNA synthesis associated with excision repair and of total DNA content in single cells. These data were compared with 3H-thymidine incorporation occurring as a function of excision repair. The analysis of DNA synthesis with this technique is consistent, relatively simple, and rapid with excellent sensitivity and provides a viable method for determining cycling vs. non-cycling cells, total cellular DNA, and excision repair-associated DNA synthesis of individual cells within heterogeneous cell populations.

Bromodeoxyuridine↗
PubMed1993

Induction of astrocyte glutamine synthetase activity by the Lathyrus toxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (beta-L-ODAP).

beta-N-Oxalyl-L-alpha,beta-diaminopropionic acid (beta-L-ODAP) is thought to be the causative agent in lathyrism due to its neuroexcitatory and neurotoxic properties. We have recently reported that beta-L-ODAP is also gliotoxic at high concentrations (Bridges et al.: Brain Res 561:262, 1991). Evidence is now presented that low, subgliotoxic concentrations of beta-L-ODAP may alter the ability of astrocytes to regulate glutamate concentrations in the CNS by increasing astrocyte glutamine synthetase activity. When astrocytes cultured from rat cortex were exposed to 100 microM beta-L-ODAP for 24 h, the resulting glutamine synthetase activity was 155% of control levels. This effect was enantiomer- and isomer-specific, dose-dependent, and required protein translation as the induction was blocked with cycloheximide. The effect of beta-L-ODAP on glutamine synthetase was not mimicked by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) or kainate, suggesting that the induction was not transduced solely through activation of cell surface non-N-methyl-D-aspartate (NMDA) glutamate receptors. An intracellular site of action of beta-L-ODAP is proposed because its effect on glutamine synthetase activity could be blocked by the amino acid uptake blocker dihydrokainate.

Amino Acids, Diamino↗