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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 145 records · Page 8Linked to original sources
PubMed2001

CYP2D6 polymorphism in a Mexican American population.

BACKGROUND: Pharmacogenetic data are largely unavailable for Mexican Americans, despite being one of the largest populations in America. METHODS: The CYP2D6 genotype (n = 349) and dextromethorphan hydroxylation phenotype (n = 285) were studied in 380 Mexican American subjects from Los Angeles County. RESULTS: The allelic frequency was 22.8% for CYP2D6*2, 10.3% for CYP2D6*4, 7.4% for CYP2D6*10, 2.3% for CYP2D6*5, 1% for CYP2D6*XN (duplication), and <1% for CYP2D6*3 and CYP2D6*17. By using the published antimode for Caucasians, we identified nine subjects as poor metabolizers, an incidence of 3.2%. Of the eight poor metabolizers who were also genotyped, five either were homozygous for the CYP2D6*4 allele (4 cases) or had a combination of CYP2D6*4 and CYP2D6*5 alleles. The mean log(10) dextromethorphan/dextrorphan ratio was -2.47 for those classified as extensive metabolizers. The number of functional alleles among the extensive metabolizers correlated strongly with the phenotype, suggesting a gene-dose effect. CONCLUSION: Compared with previous reports on Caucasian populations, studies show that Mexican Americans appear to possess a lower rate of CYP2D6*4. Frequencies for the other alleles appear to be less divergent between the two groups. This genotypic pattern might be responsible for the lower rate for the poor metabolizer status, as well as for the faster enzyme activity in the extensive metabolizer subjects that was also reflected in our data.

Adolescent↗
PubMed2001

Subdural haematoma after dural puncture headache treated by epidural blood patch.

Subdural haematoma is a well-documented complication of accidental dural puncture, and is thought to be preventable by prompt treatment with an epidural blood patch. An accidental dural puncture occurred in a 39-yr-old primagravida during the siting of an epidural catheter for pain relief in labour. Twenty hours after the puncture, the mother developed a typical postdural puncture headache, which increased in severity over the subsequent 24 h. An epidural blood patch was performed at 48 h, and this initially relieved the headache. After discharge from hospital, and 14 days after the dural puncture, the headache recurred, together with expressive dysphasia, poor co-ordination and sensory loss in the right arm. A magnetic resonance imaging scan demonstrated a left sided subdural haematoma, which was drained successfully with complete recovery.

Adult↗
PubMed2001

Abnormal corticospinal function but normal axonal guidance in human L1CAM mutations.

L1 cell adhesion molecule (L1CAM) gene mutations are associated with X-linked 'recessive' neurological syndromes characterized by spasticity of the legs. L1CAM knock-out mice show hypoplasia of the corticospinal tract and failure of corticospinal axonal decussation and projection beyond the cervical spinal cord. The aim of this study was to determine if similar neuropathology underlies the spastic diplegia of males hemizygous for L1CAM mutations. Studies were performed on eight carrier females and 10 hemizygous males. Transcranial magnetic stimulation excited the corticospinal tract and responses were recorded in biceps brachii and quadriceps femoris. In contralateral biceps and quadriceps the responses had high thresholds and delayed onset compared with normal subjects. Ipsilateral responses in biceps were smaller, with higher thresholds and delayed onsets relative to contralateral responses. Subthreshold corticospinal conditioning of the stretch reflex of biceps and quadriceps was abnormal in both hemizygous males and carrier females suggesting there may also be a reduced projection to inhibitory interneurones. Histological examination of post-mortem material from a 2-week-old male with an L1CAM mutation revealed normal corticospinal decussation and axonal projections to lumbar spinal segments. These data support a role for L1CAM in corticospinal tract development in hemizygous males and 'carrier' females, but do not support a critical role for L1CAM in corticospinal axonal guidance.

Adolescent↗
PubMed2001

The crossing of the spinothalamic tract.

The question whether the spinothalamic and spinoreticular fibres cross the cord transversely or diagonally was investigated in cases of anterolateral cordotomy and in a case of thrombosis of the anterior spinal artery. The pattern of sensory loss following transection of the anterolateral quadrant of the cord consists of a narrow area of decreased nociception and thermanalgesia at the level of the incision; it extends for 1-2 segments cranial and cordal to the incision. This area is immediately cranial to the area of total loss of these modalities. This pattern of sensory loss is explained as follows. The cordotomy incision transects two groups of fibres: those that are already within the anterior and anterolateral funiculi and those that are crossing the cord. The area of total thermanaesthesia and analgesia is due to transection of fibres that are already within this region. The area of partial sensory loss is due to transection of the fibres that are crossing the cord at that level. Owing to the craniocaudal extent of the branches of the dorsal roots, there is an overlap of their collaterals that results in every spinothalamic neurone receiving an input from several dorsal roots. The narrow cordotomy incision thus divides the few fibres crossing at that level, causing diminished noxious and thermal sensibility over a few segments above and below the incision. These facts can be accounted for only on the assumption that these spinothalamic fibres are crossing the cord transversely. This evidence of transverse crossing was found in the cervical, thoracic and lumbar segments. There were three of 63 cordotomies for which this explanation of the partial sensory loss could not be maintained. Although no explanation has been suggested, this is unlikely to be due to the fibres crossing the cord diagonally.

Afferent Pathways↗
PubMed2001

Lashing out.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed2001

Malakoplakia involving the abdominal wall, urinary bladder, vagina, and vulva: case report and discussion of malakoplakia-associated bacteria.

A 29-year-old woman presented with a 3-month history of multiple purulent discharging nodules involving her lower abdomen, vulva, and left thigh. Physical examination also disclosed vaginal nodules and a left pelvic mass. Cystoscopy revealed multiple mucosal nodules and a perforation of the left vesical wall that appeared to communicate with the pelvic mass. Biopsies of the vesical and vulvar nodules revealed malakoplakia. Surgery and antibiotic therapy resulted in regression of all the lesions.

Abdominal Muscles↗
PubMed2001

The effect of isolated soy protein on plasma biomarkers in elderly men with elevated serum prostate specific antigen.

PURPOSE: We performed a randomized double-blind crossover pilot study in elderly men with elevated prostate specific antigen (PSA) on the effects of the daily consumption of 2 soy beverages, each containing 20 gm. of isolated soy protein, on the isoflavone concentration in blood and urine, and on the 3 serum biomarkers cholesterol, PSA and the soluble p105 component of the p185erbB-2 proto-oncogene. MATERIALS AND METHODS: A total of 34 men supplemented their diet by consuming 1 of 2 soy protein beverages assigned randomly twice daily for a 6-week period. In a second 6-week period they consumed the other soy protein beverage. The beverage ISP+ provided 42 mg. of genistein and 27 mg. of daidzein daily, whereas the other beverage, ISP-, provided only 2.1 and 1.3 mg. of these isoflavones daily, respectively. Blood and 24-hour urine samples were obtained before the study, at 2-week intervals during the study and 2 weeks after study completion. RESULTS: ISP+ and to a lesser extent ISP- substantially increased the serum concentration and urinary output of the isoflavones and their metabolites. Serum cholesterol was significantly decreased by ISP+ irrespective of the order in which the 2 soy beverages were administered and in apparent correlation with the total isoflavone concentration. There was no significant effect of the soy beverages on serum PSA and p105erbB-2 values. CONCLUSIONS: This study reveals that short-term exposure of elderly men with elevated serum PSA values to soy protein containing isoflavones decreases serum cholesterol but not the serum biomarkers PSA and p105erbB-2.

Aged↗
PubMed2001

Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day.

BACKGROUND: Medical therapy for genital warts remains suboptimal. The topical interferon and cytokine inducer, imiquimod, has been proved effective for the treatment of external genital and perianal warts, but there is a substantial difference in the response rates between men and women. When 5% imiquimod cream is applied three times a week up to 16 weeks, approximately two thirds of women treated with imiquimod achieve complete clearance of genital warts, whereas only about one third of men clear completely. GOAL: This study was undertaken to determine whether more frequent application of topical imiquimod cream would improve the rate of genital wart clearance in men. STUDY DESIGN: A randomized treatment trial involving adult men with biopsy-proven genital warts was conducted at nine centers in the United States and Canada using four different application frequencies. RESULTS: Complete clearance rates during the 16-week treatment period were as follows for the different imiquimod treatment frequencies: three times a week (35 %), once daily (28 %), twice daily (24%), and three times a day (27%)(P = 0.88). The four treatment groups all showed comparable reductions in the total lesion area, with a median of more than a 90% reduction in the lesion area by the end of treatment. There was a significant increase in the incidence and severity of local skin reactions including erythema, vesicle formation, ulceration, and excoriation as the dosing frequency increased from three times a week to three times a day. CONCLUSIONS: In this study, the optimal dosage regimen was the approved three times a week regimen. More frequent application (up to three times a day) did not improve clearance and was associated with an increase in local adverse events.

Adult↗
PubMed2001

Improving general practitioners' assessment and management of suicide risk.

Standards for assessing and managing suicide risk were developed and incorporated into a guidance manual for general practitioners. The effects of the manual on opinions and practice were evaluated using a quasi-experimental controlled before/after design, comparing participating general practitioners with others who did not use the manual. Thirty four general practitioners participated over a six-month period. The intervention group showed changes in perceptions, with increased satisfaction with their own methods and in their recognition and assessment of suicide risk. Their practice changed, with increased recording of relevant factors in notes. The comparison group did not change in these ways. It is concluded that general practitioners' practice and opinions in assessing and managing suicide risk were significantly improved using a minimal intervention. Given the importance of the topic and the small size of this study, further research is needed, examining changes in professional practice, knowledge and attitudes.

Affective Symptoms↗
PubMed2001

The effects of restricted energy and fluid intake on simulated amateur boxing performance.

This study examined the effects of serial reductions in energy and fluid intake on two simulated boxing performances separated by 2 days recovery. Eight amateur boxers (age: 23.6 +/- 3.2 years; height 175 +/- 5 cm; body mass [BM] 73.3 +/- 8.3 kg [Mean +/- SD]) performed two simulated boxing bouts (BB) under normal (N-trial) and restricted (R-trial) diets in a counterbalanced design over 5 days. The trials were separated by a 9-day period of normal dietary behavior (X-trial). BM was recorded on days 1, 3, and 5 of each trial. Simulated bouts of three, 3-min rounds with 1-min recovery were completed on days 3 (BB1) and 5 (BB2) of each 5-day trial. Punching force (N) was recorded from 8 sets of 7 punches by a purpose-built boxing ergometer. Heart rate (fC) was monitored continuously (PE3000 Polar Sports Tester, Kempele, Finland), and blood lactate (BLa) and glucose (BG) were determined 4-min post-performance (2300 StaPlus, YSI, Ohio). Energy and fluid intakes were significantly lower in the R-trial (p < .05). Body mass was maintained during the N-trial but fell 3% (p < .05) during the R-trial. There were no significant differences in end-of-bout fC or post-bout BG, but BLa was higher in the N- than the R-trial (p < .05). R-trial punching forces were 3.2% and 4.6% lower, respectively, compared to the corresponding N-trial bouts, but the differences did not reach statistical significance. These results suggest that energy and fluid restrictions in weight-governed sports do not always lead to a significant decrease in performance, but because of the small sample size and big variations in individual performances, these findings should be interpreted with care.

Adult↗
PubMed2001

Identification and characterization of a chitinase antigen from Pseudomonas aeruginosa strain 385.

A chitinase antigen has been identified in Pseudomonas aeruginosa strain 385 using sera from animals immunized with a whole-cell vaccine. The majority of the activity was shown to be in the cytoplasm, with some activity in the membrane fraction. The chitinase was not secreted into the culture medium. Purification of the enzyme was achieved by exploiting its binding to crab shell chitin. The purified enzyme had a molecular mass of 58 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a pI of 5.2. NH2-terminal amino acid sequencing revealed two sequences of M(I/L)RID and (Q/M/V)AREDAAAAM that gave an exact match to sequences in a translated putative open reading frame from the P. aeruginosa genome. The chitinase was active against chitin azure, ethylene glycol chitin, and colloidal chitin. It did not display any lysozyme activity. Using synthetic 4-methylumbelliferyl chitin substrates, it was shown to be an endochitinase. The Km and kcat for 4-nitrophenyl-beta-D-N,N'-diacetylchitobiose were 4.28 mM and 1.7 s(-1) respectively, and for 4-nitrophenyl-beta-D-N,N',N"-triacetylchitotriose, they were 0.48 mM and 0.16 s(-1) respectively. The pH optimum was determined to be pH 6.75, and 90% activity was maintained over the pH range 6.5 to 7.1. The enzyme was stable over the pH range 5 to 10 for 3 h and to temperatures up to 50 degrees C for 30 min. The chitinase bound strongly to chitin, chitin azure, colloidal chitin, lichenan, and cellulose but poorly to chitosan, xylan, and heparin. It is suggested that the chitinase functions primarily as a chitobiosidase, removing chitobiose from the nonreducing ends of chitin and chitin oligosaccharides.

Antibodies, Bacterial↗
PubMed2001

Tissue-specific transgenic knockdown of Fos-related antigen 2 (Fra-2) expression mediated by dominant negative Fra-2.

Fos-related antigen 2 (Fra-2) is a member of the Fos family of immediate-early genes, most of which are rapidly induced by second messengers. All members of this family act by binding to AP-1 sites as heterodimeric complexes with other proteins. However, each appears to have a distinct role. The role and biology of Fra-2 are less well understood than those of its relatives c-Fos, Fra-1, and FosB; moreover, Fra-2 target genes remain largely unknown, as does the basis of its selective effects on transcriptional activity. To pursue these issues, we created a transgenic rat line (NATDNF2) in which a dominant negative fra-2 (DNF2) gene is strongly expressed in the pineal gland; tissue selectivity was achieved by putting the DNF2 gene under the control of the rat arylalkylamine N-acetyltransferase (AANAT) regulatory region, which targets gene expression to a very restricted set of tissues (pineal gland >> retina). Expression of AANAT is normally turned on after the onset of darkness in the rat; as a result, pineal DNF2 expression occurs only at night. This was associated with marked suppression of the nocturnal increase in fra-2 mRNA and protein levels, indicating that DNF2 expression inhibits downstream effects of Fra-2, including the maintenance of high levels of fra-2 gene expression. Analysis of 1,190 genes in the NATDNF2 pineal gland, including the AANAT gene, identified two whose expression is strongly linked to fra-2 expression: the genes encoding type II iodothyronine deiodinase and nectadrin (CD24).

3T3 Cells↗
PubMed2001

Manubriosternal joint dislocation in contact sport.

A 17 year old man developed chest pain and shortness of breath immediately after a scrummage while playing rugby football. A lateral chest radiograph showed a dislocated manubriosternal joint, with no associated injuries. This has not been previously reported in a sporting setting. This injury should be considered in flexion-compression injury of the thorax.

Adolescent↗
PubMed2001

Molecular genetic delineation of 2q37.3 deletion in autism and osteodystrophy: report of a case and of new markers for deletion screening by PCR.

We recently studied a patient who meets criteria for autistic disorder and has a 2q37 deletion. Molecular cytogenetic studies were carried out using DNA isolated from 22 different 2q37 mapped BACs to more precisely define the extent of the chromosome deletion. We also analyzed 2q37 mapped polymorphic markers. In addition DNA sequences of BACs in the deletion region were scanned to identify microsatellite repeats. We describe four new polymorphic microsatellite repeat markers in the 2q37.3 region. These markers enabled us to determine the parental origin of the deletion in our patient. DNA from 8-13 unrelated individuals was used to determine heterozygosity estimates for these markers. We review four genes deleted in our patient - genes whose known functions and sites of expression in the brain and/or bone make them candidates for involvement in autism and/or the osteodystrophy observed in patients with 2q37.3 deletions.

Adolescent↗
PubMed2001

Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB.

Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-kappaB in vitro, we observed a long-lasting sustained activation of NF-kappaB in the absence of decreased IkappaBalpha in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-kappaBp65. A comparable increase in NF-kappaBp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-beta peptide (Abeta) to the transmembrane receptor for AGE (RAGE) results in protein synthesis-dependent sustained activation of NF-kappaB both in vitro and in vivo. Infusion of AGE-albumin into mice bearing a beta-globin reporter transgene under control of NF-kappaB also resulted in prolonged expression of the reporter transgene. In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-kappaB (p50/p65) from the cytoplasm into the nucleus for >1 week. Sustained NF-kappaB activation by ligands of RAGE was mediated by initial degradation of IkappaB proteins followed by new synthesis of NF-kappaBp65 mRNA and protein in the presence of newly synthesized IkappaBalpha and IkappaBbeta. These data demonstrate that ligands of RAGE can induce sustained activation of NF-kappaB as a result of increased levels of de novo synthesized NF-kappaBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF-kappaB activation observed in hyperglycemia and possibly other chronic diseases.

Adult↗