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Biomedical subjects

M M Smith

Publications and source records attributed to M M Smith.

At least 163 records · Page 9Linked to original sources

Predictors of recidivism in DUIIs.

The prior driving records of 397 drivers arrested for drinking and driving in the year 1983 were examined with the purpose of comparing biographical factors and variables relating to driving history and arrest circumstance between recidivist and nonrecidivist drinking drivers. Of these drivers, 174 (44%) had more than one arrest within a 12-year study period, while 223 (56%) had only one. Significant differences were found among drivers with different numbers of drinking and driving offenses. Drivers with one or two DUII arrests had more non-moving traffic violations than drivers with three or more DUII arrests. Drinking and driving offenders with higher levels of arrests were more likely to be unemployed, to have a past criminal record, to be arrested for drinking and driving on a weekday during afternoon and early evening hours, to drive with a suspended or revoked license and to refuse a blood alcohol level determination test. In this study DUII offenders with four or more arrests fit the descriptive model of alcoholism.

Accidents, Traffic↗

Evaluation of a stented laryngoplasty for correction of cranial glottic stenosis in four dogs.

After laryngeal surgery, cranial glottic stenosis secondary to laryngeal web formation was diagnosed as the cause of upper airway obstruction in 4 dogs. Initial treatment of 3 dogs by peroral laryngeal web excision resulted in rapid recurrence of clinical signs. Subsequently, these 3 and the fourth dog were treated by scar excision, mucosal flap coverage, and placement of a silicone intraluminal laryngeal stent for 14 days. By 5 months (average) after surgery, on the basis of clinical evaluation of exercise intolerance, respiratory distress, and stridor, all dogs had alleviation of upper airway obstruction.

Animals↗

The relationships of Uronemus: a carboniferous dipnoan with highly modified tooth plates.

Previous accounts of the dentition of the Carboniferous dipnoan Uronemus have stressed the significance of the scattered small denticles. These, together with the marginal teeth and ridges, have been interpreted as primitive characters of the dipnoan dentition shared with three other genera: the Devonian Uranlophus and Griphognathus and the Carboniferous to Permian Conchopoma. Genera with tooth plates have been considered to be a monophyletic group in which tooth plates are a derived character; Uronemus has been excluded from this group in all previous investigations dealing with the significance of the dentition for determining relationships among dipnoans. The macromorphology of the dentition of Uronemus has been re-examined and correlated with the histology of all the dental tissues. Optical study of thin sections and scanning electron microscope study of the adjacent cut surfaces has shown that the hard, wear-resistant dentine of the teeth and ridges is petrodentine. The arrangement, growth, wear and histology of the dental tissues have been compared with those of denticulated and tooth-plated genera. The arrangement of new teeth relative to the tooth ridge, the pattern of wear along the ridge, and the type of dentine and its growth indicate that the dentition of Uronemus is best interpreted as a tooth plate with one long lingual tooth ridge and reduced lateral tooth rows. Therefore the marginal tooth ridges are not considered to be homologous with those of denticulate dipnoans such as Uranolophus. The presence of petrodentine, a tissue type only found in forms with tooth plates, is consistent with the view that the dentition is derived by modification of a radiate tooth plate. The denticles covering restricted regions of the palate and lower jaw are considered to have been a secondary acquisition. The suggestion that Conchopoma is a close relative of Uronemus is not accepted, and possible new relationships have been proposed. New data on Scaumenacia and Phaneropleuron, two other genera previously compared with Uronemus, are presented. Rhinodipterus, a form with elongate lingual ridges, is also discussed. Phaneropleuron is shown to have radiate tooth plates and not a marginal row of conical teeth as previously described. It is proposed that the tooth plate of Uronemus is derived from a dipterid type of plate. A discussion of some of the other factors involved in determining the relationships of the genus is given.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Comparative morphology, histology and growth of the dental plates of the Devonian dipnoan Chirodipterus.

The dental plates of the Devonian lungfish Chirodipterus australis Miles (Osteichthyes; Dipnoi) are shown to have achieved their characteristic morphology by a growth process different from that assumed for the plates of genera such as Dipterus. Each plate was thickened by the addition of layers of bone that also extended the plate labially, thus providing the base on which and into which dentine grew. Distinctive features of the dentition are: (a) labial increase of the dentine mass by the addition of blister-like denticles of simple enamel-covered dentine, which is initially ingrown by pleromic dentine and subsequently resorbed and replaced by petrodentine; (b) increase in the midline by a similar process that results in the addition of one (or possibly two) new ridges; (c) resorption of the posterior edge of the pterygoid plates and the posterior and posteromedial edges of the prearticular plates, with subsequent development over the resorbed surfaces of several generations of simple regenerative dentine; (d) resorption and redeposition of pleromic dentine and bone in a triangular region posteromedially on the pterygoid plates; (e) the formation of tuberosities that simulate teeth at a short distance in from the labial edge, by four processes: formation of an undulating plate margin, differential growth of petrodentine (hard compact dentine) within the pulp cavity, differential wear of the petrodentine and the adjacent bone plus pleromic dentine, and slightly greater growth of the petrodentine towards the occlusal surface relative to the adjacent bone and dentine; (f) expansion of the large flat surfaces of the plates by gradual replacement of the bone and dentine at the proximal ends of the furrows and also by the development of linkages of petrodentine across the furrows; (g) development of isolated tuberosities on the flat posterolateral parts of the plates. The petrodentine of the ridges, tuberosities and plateaus of the plates is indistinguishable structurally and in its mode of growth from the petrodentine in extant species of dipnoans. Plates similar to those of C. australis have been observed in Stomiahykus, Archaeonectes, Conchodus, Palaedaphus and Sunwapta, as well as several species usually referred to as Dipterus. Sunwapta may be congeneric with C. australis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Sedimentation characteristics of vesicles associated with insulin-sensitive intracellular glucose transporter from rat adipocytes.

The sedimentation characteristics of vesicles associated with the insulin-sensitive intracellular glucose transporter from rat adipocytes were studied. The method used was sucrose density gradient centrifugation, which was carried out under non-equilibrium and equilibrium (isopycnic) conditions. The glucose transport activity was determined by the reconstitution method. As reported previously, the sedimentation velocity of the intracellular glucose-transport activity was considerably slower than that of the counterpart in the plasma membrane. It was found, however, that the specific gravity of the slow-sedimenting glucose-transport activity was almost identical to that of the activity in the plasma membrane (d = 1.118-1.122). It is concluded that the intracellular glucose transport activity is associated not with low-density microsomal vesicles, but with unidentified slow-sedimenting vesicles that have a specific gravity similar to that of the plasma membrane.

Adipose Tissue↗

Formation of the alpha-bungarotoxin binding site and assembly of the nicotinic acetylcholine receptor subunits occur in the endoplasmic reticulum.

During the process by which newly synthesized subunits of the nicotinic acetylcholine receptor (stoichiometry = alpha 2 beta gamma delta) mature and acquire the properties of the fully functional cell surface receptor, they undergo numerous covalent and noncovalent modifications. Using ligand-mediated and subunit-specific immunoprecipitation, four forms in the maturation of the alpha subunit can be detected: the primary translation product; alpha subunit that can bind alpha-bungarotoxin; alpha subunit assembled with the other subunits; and surface receptor. The alpha subunit acquires the ability to bind alpha-bungarotoxin with a t1/2 of approximately 40 min after translation and becomes assembled with a t1/2 of 80 min after translation. Using metabolic labeling and sucrose gradient fractionation, we have determined the subcellular location of alpha subunit when it acquires the ability to bind alpha-bungarotoxin and when it is assembled. Golgi membranes were identified across the gradient by the enzymatic activities UDP-galactose:N-acetylglucosamine galactosyltransferase and alpha-mannosidase. Endoplasmic reticulum membranes were identified by the enzymatic activity glucose-6-phosphatase and by the presence of newly synthesized alpha and beta subunits. Pulse-labeled alpha subunit that bound alpha-bungarotoxin was first detected co-migrating in the gradient with the glucose-6-phosphatase activity. Therefore, the capacity to bind alpha-bungarotoxin was acquired while the alpha subunit was in the endoplasmic reticulum. Assembled alpha subunit was detected by immunoprecipitating with an anti-beta subunit-specific monoclonal antibody. By this method, assembled receptor was first detected 15 min after translation in both the endoplasmic and Golgi portions of the gradient. To validate this method of detecting assembled receptor, we determined the sedimentation coefficient of the receptor subunits in the endoplasmic reticulum. Both unassembled subunits with sedimentation coefficients of 5 S and assembled receptor with a sedimentation coefficient of 9 S were recovered from the endoplasmic reticulum portion of the gradient. Thus, our data concerning the subcellular site of assembly are consistent with assembly occurring in the endoplasmic reticulum followed by rapid transport to the Golgi.

Binding Sites↗

Analysis of DNA sequences homologous with the ARS core consensus in Saccharomyces cerevisiae.

We have previously identified an autonomously replicating segment (ARS) near the 3' end of the histone H4 gene at the copy-I H3-H4 locus. We have now searched for additional autonomously replicating segments and sequences homologous with the ARS core consensus sequence near the copy-II histone H4 gene and both of the histone H3 genes. No new ARS elements were identified by functional cloning assays. However, several matches to the ARS core consensus element were found within the DNA sequences of the copy-I and copy-II genes. An exact match to the ARS core consensus was identified in the region downstream from the copy-I histone H3 gene and a set of sequences with weak homology was also located within the copy-II region. However, restriction fragments including these sequences did not demonstrate ARS activity on a plasmid in transformed cells.

Base Sequence↗

The synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment.

Various cell lines of human synovial fibroblasts derived from synovium obtained at the time of biopsy or total joint-replacement surgery have been established. The synthesis of 3H-labelled hyaluronic acid (HA) in these cells has been determined, and the effects of adding HA of varying molecular size to the cultured cells examined. The results obtained clearly show that the in vitro synthesis of HA by these cells is influenced by the concentration and molecular weight (MW) of the HA in their extracellular environment. Synovial fibroblasts derived from an osteoarthritic joint demonstrated the most marked response on exposure to exogenous HA, showing a stimulation of HA synthesis with preparations of weight-average molecular weight (Mw) greater than 5 X 10(5) in a concentration dependent manner. HA preparations with Mw less than 5 X 10(5) showed little or no effect except at high concentrations where a suppression of biosynthesis was observed. A model to explain these findings is proposed.

Adult↗

Molecular evolution of the Saccharomyces cerevisiae histone gene loci.

The core histone genes of Saccharomyces cerevisiae are arranged as duplicate nonallelic sets of specifically paired genes. The identity of structural organization between the duplicated gene pairs would have its simplest evolutionary origin in the duplication of a complete locus in a single event. In such a case, the time since the duplication of one of the genes should be identical to that since duplication of the gene adjacent to it on the chromosome. A calculation of the evolutionary distances between the coding DNA sequences of the histone genes leads to a duplication paradox: The extents of sequence divergence in the silent component of third-base positions for adjacent pairs of genes are not identical. Estimates of the evolutionary distance between the two H3-H4 noncoding intergene DNA sequences are large; the divergence between the two separate sequences is indistinguishable from the divergence between either of the regions and a randomly generated permutation of itself. These results suggest that the duplication event may have occurred much earlier than previously estimated. The potential age of the duplication, and the attractive simplicity of the duplication of both the H3-H4 and the H2A-H2B gene pairs having taken place in a single event, leads to the hypothesis that modern haploid S. cerevisiae may have evolved by diploidization or fusion of two ancient fungi.

Base Sequence↗

Regulation of phosphorylation of nicotinic acetylcholine receptors in mouse BC3H1 myocytes.

By using 32P-labeling methods and performing immunoprecipitations with specific antibodies, we have found that three subunits of the nicotinic acetylcholine receptor are phosphorylated in mouse skeletal muscle cells. In nonstimulated cells, the molar ratios of phosphate estimated in alpha, beta, and delta subunits were 0.02, 0.05, and 0.5, respectively. All three subunits contained predominantly phosphoserine with some phosphothreonine; the beta subunit also contained phosphotyrosine. Incubating cells with agents that stimulate cAMP-dependent pathways (isoproterenol, forskolin, 8-Br-cAMP) increased the phosphorylation of the delta subunit by 50%, but phosphate labeling of the beta subunit was depressed by a third. In contrast, when cells were incubated with the divalent cation ionophores A-23187 or ionomycin, phosphorylation of both the delta and beta subunits increased. The results indicate that acetylcholine receptors are phosphorylated to significant levels in skeletal muscle cells and that cAMP-dependent and Ca2+-dependent pathways exist for controlling the phosphorylation state of the receptor subunits.

Animals↗

Developmental expression of the myelin proteolipid protein and basic protein mRNAs in normal and dysmyelinating mutant mice.

Expression of the myelin proteolipid protein (PLP) was examined in the nuclei and polysomes of 12-27-day-old quaking, jimpy, and shiverer mouse brains and in 2-27-day-old normal brains and compared with expression of the myelin basic proteins (MBPs). Northern blots showed the presence of multiple mouse PLP RNAs, the developmental expression of which coincided with myelination. Two major mouse PLP RNAs, 3.5 and 2.6 kilobases in length, were observed in both cytoplasmic polyribosomes and nuclei, and, in addition, a larger 4.6-kilobase PLP RNA was observed in nuclei. Quantitative measurements with slot blot analyses showed that the levels of PLP and MBP RNAs peaked simultaneously at 18 days in nuclei but that maximal levels of PLP RNA lagged behind MBP RNA by several days in the polysomes. The developmental expression of both major classes of myelin protein mRNAs was affected in all three mutants. In shiverer brains, the levels of PLP mRNA in polysomes and nuclei were only 30-55% of control levels after 15 days. Thus, the deletion of a portion of the MBP gene appeared to have a major effect on the expression of the PLP gene in this mutant. In jimpy mice, where the mutation has been shown to involve the PLP gene, expression of MBP mRNA was also severely reduced, to less than 25% of control values. In quaking brains, the expression of each gene followed its own developmental course, different from each other and different from the normal mouse. The extent to which the expression of PLP and MBP was affected by the quaking mutation depended on the age at which it was examined.

Animals↗

Influence of simultaneous gonadotropin-releasing hormone agonist and testosterone treatment on spermatogenesis and potential fertilizing capacity in male monkeys.

We examined the effect of continuous sc infusion of a GnRH agonist (Ag) and testosterone (T) supplementation on spermatogenesis and the potential fertilizing capacity of sperm in 15 rhesus monkeys. The monkeys were divided into 3 groups of 5 animals each. Groups 1 and 2 received 25 micrograms/day Ag for 44 weeks. Group 2 also received T replacement therapy [sufficient to maintain serum T values within the normal range; 4-5 ng/mL (13.9-17.3 nmol/L)]. Group 3 received a low dose of the Ag (5 micrograms/day for 24 weeks and then 10 micrograms/day for 20 weeks) to prolong the oligospermic phase before the onset of azoospermia. In groups 1 and 3, there was an initial transient (1 week) rise in serum LH and T levels which then fell below pretreatment value where they remained throughout the treatment period. The serum LH and T levels were lower in the group treated with 25 micrograms/day Ag. Similar changes in serum LH levels occurred in group 2, but T supplementation maintained serum T in the physiological range. The decline in serum LH levels was associated with reduced sensitivity to GnRH, since the responses of serum LH and T to GnRH were either abolished or greatly reduced in the 2 groups treated with 25 micrograms/day Ag and were less than 50% of the pre-Ag responses in monkeys treated with 5-10 micrograms/day Ag. Four of five monkeys treated with 25 micrograms/day Ag alone became azoospermic within 21 weeks. All five animals receiving Ag and T supplementation became azoospermic (mean time to onset, 12.6 weeks). Four of five monkeys treated with 5-10 micrograms/day Ag also had azoospermic ejaculates during the late treatment and early recovery period. Sperm counts recovered to the pretreatment levels in most monkeys by 10 weeks of the recovery period. The quality of semen samples taken from oligospermic monkeys was greatly reduced. The percentage of motile and percentage of live sperm per ejaculate, the net negative surface charge on sperm, and the scores of sperm in the hamster oocyte penetration test were subnormal. T supplementation did not improve these measures of semen quality. Testicular biopsies taken at the end of the Ag administration period from monkeys given 25 micrograms/day Ag showed diffuse atrophy of the seminiferous tubules, which contained primarily Sertoli cells and a few spermatogonia and spermatocytes, but no spermatids. The tubular atrophy and the suppression of spermatogenesis did not appear to be influenced by T replacement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of continuous infusion of a low dose of GnRH antagonist on serum LH and testosterone concentrations, spermatogenesis and semen quality in the rhesus monkey (Macaca mulatta).

Treatment of 4 adult male rhesus monkeys for 8-12 months with 100-400 micrograms of a GnRH antagonist/day by means of using osmotic minipumps led to suppressed serum concentrations of LH and testosterone followed by various degrees of recovery toward pretreatment values. The serum LH response to a challenge of native GnRH was reduced by 30-75% during antagonist treatment. The serum testosterone response to GnRH was exaggerated above the response in the pretreatment period, suggesting hypersensitivity of the testis to gonadotrophin. Antagonist administration under these conditions did not alter body weight or abolish ejaculatory response. Antagonist infusion caused a 96% decrease in sperm counts. Spermatozoa recovered during the final month of antagonist treatment showed a reduced ability to penetrate denuded hamster ova. Testicular biopsies performed at the end of antagonist treatment revealed persistent spermatogenesis. However, the cellularity of the seminiferous tubules was decreased below that of pretreatment biopsies. The results of this study suggest that the amount of testosterone needed to maintain normal spermatogenesis is greater than that needed to maintain electroejaculatory response in monkeys.

Animals↗

High-frequency Bekesy audiometry: VI. Pulsed vs. continuous signals.

Carefully screened normal-hearing young adults (5M, 25 F) performed a fixed-frequency version of high-frequency Bekesy audiometry (HFBA) with pure tones ranging from 2-16 kc/s, using the SHF E-800 unit (Gauz and Smith, J. Aud. Res., 1985, 25, 101-122). Pulsed (P) and Continuous (C) traces were recorded for 1 and 2 min, respectively. Data were described in types of response, amount of threshold decrement of the C trace re P traces, and rate of threshold decrement. P traces showed stability, while the majority (about 70-95%) of C traces overlapped P traces for 2-12 kc/s (our Type I). Some C traces (about 3-25% indicated adaptation followed by stabilization (Type II), while others (about 3-20% showed adaptation without stabilization (Type II/III), without regard for frequency. Rapid adaptation to the limits of the audiometer (Type III) was infrequently encountered below 14 kc/s, but showed an accelerated increase from 14-16 kc/s. During Min 2, a slight decrease in Type I responses and a corresponding increase in Type II responses were obtained. The rate of adaptation (in db/sec) increased with frequency and decreased with duration. This slope was relatively slight at 2-8 kc/s, increased at 10-12 kc/s, and increased notably at higher frequencies. Total amount of adaptation in db (P-C) increased with frequency, although mean values were rather small, most less than 5 db and none exceeding 10 db by the end of Min 2. Excluding Type III responses, no C-mode adaptation exceeded 24 db for any individual. The potential utility of HFBA and implications for future research were discussed.

Acoustic Stimulation↗