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71.
G A McClellan H C Nipper M J Horn W D Burris K Hodges S Monaco R S Cox 《American journal of clinical pathology》1991,95(5):743-748
Labor use ratings assigned to instruments by the Workload Recording Method (WRM) do not change with batch size or walk-away time use. The authors evaluated the effect of both on the labor use of the analyzers Paramax B6100 (Baxter Paramax, Irvine, CA) and Ektachem 700 (Eastman Kodak, Rochester, NY) by timing all worked and walk-away intervals on both instruments. Extrapolation of the data to a workload of slightly more than 1.1 million tests showed that reapportionment of tests to various batch sizes caused Paramax-Ektachem labor cost differences to fluctuate between $37,254 and $34,995. When the minimum usable walk-away interval length was varied from 1 to 20 minutes, Ektachem savings over Paramax increased from $8,700 to $61,400. The WRM predicted a constant $29,050 labor cost advantage for Ektachem over Paramax. If other instruments show similar labor use characteristics with respect to batch size and walk-away utility, laboratory managers who do not consider these factors may fail to select the most cost-effective instruments for their laboratories. 相似文献
72.
Mutations in the TSC2 gene: analysis of the complete coding sequence using the protein truncation test (PTT) 总被引:4,自引:0,他引:4
Mutations in the TSC2 gene on chromosome 16p13.3 are responsible for
approximately 50% of familial tuberous sclerosis (TSC). The gene has 41
small exons spanning 45 kb of genomic DNA and encoding a 5.5 kb mRNA. Large
germline deletions of TSC2 occur in <5% of cases, and a number of small
intragenic mutations have been described. We analysed mRNA from 18
unrelated cases of TSC for TSC2 mutations using the protein truncation test
(PTT). Three cases were predicted to be TSC2 mutations on the basis of
linkage analysis or because a hamartoma from the patient showed loss of
heterozygosity for 16p13.3 markers. Three overlapping PCR products,
covering the complete coding sequence of mRNA, were generated from
lymphoblastoid cell lines, translated into 35S-methionine labelled protein,
and analysed by SDS-PAGE. PCR products showing PTT shifts were directly
sequenced, and mutations confirmed by restriction enzyme digestion where
possible. Six PTT shifts were identified. Five of these were caused by
mutations predicted to produce a truncated protein: (i) a sporadic case
showed a 32 bp deletion in exon 11, and a mutant mRNA without exon 11 was
produced; the normal exon 10 was also spliced out; (ii) a sporadic case had
a 1 bp deletion in exon 12 (1634delT); (iii) a TSC2-linked mother and
daughter pair had a G-->T transversion in exon 23 (G2715T) introducing a
cryptic splice site causing a 29 bp truncation of mRNA from exon 23; (iv) a
sporadic case showed a 2 bp deletion in exon 36; (v) a sporadic case showed
a 1 bp insertion disrupting the donor splice site of exon 37 (5007+2insA),
resulting in the use of an upstream exonic cryptic splice site to cause a
29 bp truncation of mRNA from exon 37. In one case, the PTT shift was
explained by in-frame splicing out of exon 10, in the presence of a normal
exon 10 genomic sequence. Alternative splicing of exon 10 of the TSC2 gene
may be a normal variant. Three 3rd base substitution polymorphisms were
also detected during direct sequencing of PCR products. Confirmed mutations
were identified in 28% of the families studied and on the assumption that
half of the sporadic cases should have TSC2 mutations, a crude estimate of
the detection rate would be 60%. This compares favourably with other
screening methods used for TSC2, notably SSCP, and since PTT involves much
less work it may be the method of choice.
相似文献
73.
Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair 总被引:7,自引:3,他引:7
The association between MSHR coding region variation and hair colour in
humans has been examined by genotyping 25 red haired and 62 non-red
Caucasians, all of whom were 12 years of age and members of a twin pair
study. Twelve amino acid substitutions were seen at 11 different sites,
nine of these being newly described MSHR variants. The previously reported
Val92Met allele shows no association with hair colour, but the three
alleles Arg151Cys, Arg160Trp and Asp294His were associated with red hair
and one Val60Leu variant was most frequent in fair/blonde and light brown
hair colours. Variant MSHR genotypes are associated with lighter skin types
and red hair (P < 0.001). However, comparison of the MSHR genotypes in
dizygotic twin pairs discordant for red hair colour indicates that the MSHR
gene cannot be solely responsible for the red hair phenotype, since five of
13 pairs tested had both haplotypes identical by state (with three of the
five having both identical by descent). Rather, it is likely that
additional modifier genes exist, making variance in the MSHR gene necessary
but not always sufficient, for red hair production.
相似文献
74.
Mahadevaiah SK; Odorisio T; Elliott DJ; Rattigan A; Szot M; Laval SH; Washburn LL; McCarrey JR; Cattanach BM; Lovell-Badge R; Burgoyne PS 《Human molecular genetics》1998,7(4):715-727
An RNA-binding motif (RBM) gene family has been identified on the human Y
chromosome that maps to the same deletion interval as the 'azoospermia
factor' (AZF). We have identified the homologous gene family (Rbm) on the
mouse Y with a view to investigating the proposal that this gene family
plays a role in spermatogenesis. At least 25 and probably >50 copies of
Rbm are present on the mouse Y chromosome short arm located between Sry and
the centromere. As in the human, a role in spermatogenesis is indicated by
a germ cell-specific pattern of expression in the testis, but there are
distinct differences in the pattern of expression between the two species.
Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are
female due to a position effect resulting in non-expression of Sry ;
sex-reversing such mice with an Sry transgene produces males with a high
incidence of abnormal sperm, making this the third deletion interval on the
mouse Y that affects some aspect of spermatogenesis. Most of the copies of
Rbm map to this deletion interval, and the Yd1males have markedly reduced
Rbm expression, suggesting that RBM deficiency may be responsible for, or
contribute to, the abnormal sperm development. In man, deletion of the
functional copies of RBM is associated with meiotic arrest rather than
sperm anomalies; however, the different effects of deletion are consistent
with the differences in expression between the two species.
相似文献
75.
Vaughan JR; Farrer MJ; Wszolek ZK; Gasser T; Durr A; Agid Y; Bonifati V; DeMichele G; Volpe G; Lincoln S; Breteler M; Meco G; Brice A; Marsden CD; Hardy J; Wood NW 《Human molecular genetics》1998,7(4):751-753
A mutation in exon 4 of the human alpha-synuclein gene was reported
recently in four families with autosomal dominant Parkinson's disease (PD).
In order to examine whether mutations in this exon or elsewhere in the gene
are common in familial PD, all seven exons of the alpha- synuclein gene
were amplified by PCR from index cases of 30 European and American
Caucasian kindreds affected with autosomal dominant PD. Each product was
sequenced directly and examined for mutations in the open reading frame. No
mutations were found in any of the samples examined. We conclude that the
A53T change described in the alpha- synuclein gene is a rare cause of PD or
may even be a rare variant. Mutations in the regulatory or intronic regions
of the gene were not excluded by this study.
相似文献
76.
V Savin L Karniski F Cuppage G Hodges A Chonko 《Laboratory investigation; a journal of technical methods and pathology》1985,52(1):93-102
Alterations in both glomerular filtration rate and tubular transport occur in clinical gentamicin nephrotoxicity. We have studied the function of isolated tubules and glomeruli from rabbits treated with gentamicin. Gentamicin was administered subcutaneously to sexually immature (1400 to 1800 gm) or sexually mature (3800 to 4600 gm) New Zealand White rabbits in a dose of 15 mg/kg twice a day. Immature rabbits were treated for 28 to 31 days and developed only minimal renal insufficiency. About one-half of the mature rabbits developed azotemia. The mature rabbits that did not become azotemic were sacrificed after 28 to 30 days, and those that became azotemic were killed when their serum creatinine reached 2.5 mg/dl or higher (10 to 24 days). Animals were anesthetized and kidneys were removed for histologic examination and isolation of tubules and glomeruli. The ratio of p-aminohippuric acid (PAH) concentration in isolated tubule cells to that in medium after incubation in 3H-PAH (1 microM) at 37 degrees C for 30 minutes (T/M PAH) was used as an indicator of transport capacity of tubules. T/M PAH ratios averaged 196 +/- 18 and 111 +/- 21 for control immature and mature rabbits, respectively, and 135 +/- 22, 80 +/- 16, and 9 +/- 2 for gentamicin-treated immature and mature nonazotemic and mature azotemic rabbits, respectively. Glomeruli were isolated and filtration induced in vitro by a transcapillary oncotic gradient. Ultrafiltration coefficient, Kf, of glomeruli of immature and mature control rabbits averaged 3.78 +/- 0.29 and 5.84 +/- 0.51 nl/minute X mm Hg. Kf from gentamicin-treated immature rabbits averaged 2.82 +/- 0.20 and from mature azotemic rabbits 3.14 +/- 0.44 nl/minute X mm Hg. Kf of both mature and immature rabbits were decreased compared with controls (p less than 0.01). When all animals were considered, relative glomerular filtration rate, estimated from 1/serum creatinine, was positively correlated with the T/M PAH and Kf. When only experimental animals were studied, 1/serum creatinine and T/M PAH were also correlated. Decreased glomerular filtration rate and dysfunction of proximal tubules were also correlated with abnormal tubule histology. We suggest that injury to glomeruli and tubules may represent independent manifestations of gentamicin toxicity. Dysfunction may be present even when there are only mild histologic changes and glomerular filtration rate is near normal. Kf does not appear to limit glomerular filtration rate after treatment with gentamicin; rather, some direct or indirect effect of tubular injury may determine the decrement in glomerular filtration rate. 相似文献
77.
Grimstone SK Hodges PW 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2003,151(2):218-224
This study evaluated the degree to which the disturbance to posture from respiration is compensated for in healthy normals
and whether this is different in people with recurrent low back pain (LBP), and to compare the changes when respiratory demand
is increased. Angular displacement of the lumbar spine and hips, and motion of the centre of pressure (COP), were recorded
with high resolution and respiratory phase was recorded from ribcage motion. With subjects standing in a relaxed posture,
recordings were made during quiet breathing, while breathing with increased dead-space to induce hypercapnoea, and while subjects
voluntarily increased their respiration to match ribcage expansion that was induced in the hypercapnoea condition. The relationship
between respiration and the movement parameters was measured from the coherence between breathing and COP and angular motion
at the frequency of respiration, and from averages triggered from the respiratory data. Small angular changes in the lumbopelvic
and hip angles were evident at the frequency of respiration in both groups. However, in quiet standing, the LBP subjects had
a greater displacement of their COP that was associated with respiration than the control subjects. The LBP group had a trend
for less hip motion. There were no changes in the movement parameters when respiratory demand increased involuntarily via
hypercapnoea, but when respiration increased voluntarily, the amplitude of motion and the displacement of the COP increased
in both groups. The present data suggest that the postural compensation to respiration counteracts at least part of the disturbance
to posture caused by respiration and that this compensation may be less effective in people with LBP. 相似文献
78.
Gompels MM Hodges E Lock RJ Angus B White H Larkin A Chapel HM Spickett GP Misbah SA Smith JL;Associated Study Group 《Clinical and experimental immunology》2003,134(2):314-320
We have undertaken a retrospective study of antibody deficient patients, with and without lymphoma, and assessed the ability of specific polymerase chain reaction (PCR) primers to determine if the detection of clonal lymphocyte populations correlates with clinical and immunohistochemical diagnosis of lymphoma. We identified 158 cases with antibody deficiency presenting during the past 20 years. Paraffin-embedded biopsy specimens or slides were available for analysis in a cohort of 34 patients. Of these patients, 29 had common variable immunodeficiency, one X-linked agammaglobulinaemia, one X-linked immunoglobulin deficiency of uncertain cause and three isolated IgG subclass deficiency. We have confirmed that lymphoma in antibody deficiency is predominantly B cell in origin. Clonal lymphocyte populations were demonstrated in biopsies irrespective of histology (16/19 with lymphoma and 11/15 without). Isolated evidence of clonality in biopsy material is therefore an insufficient diagnostic criterion to determine malignancy. Furthermore, our data suggest that clonal expansions are rarely the result of Epstein-Barr virus-driven disease. 相似文献
79.
A male infant is described in whom congenital anomalies were recognized prenatally by ultrasound examination. The infant was delivered following spontaneous labor and died approximately 15 min after birth. An autopsy revealed major anomalies in the central nervous system (holoprosencephaly with premaxillary agenesis), the gastrointestinal system (esophageal atresia) and the heart (tetralogy of Fallot). Chromosomal studies revealed recombinant chromosome 5 [46,XY, rec(5), dup q, inv(5)(p15q32)], resulting in partial trisomy 5q and partial monosomy 5p. Cytogenetic investigation of the family revealed a pericentric inversion of chromosome 5 in the father and paternal grandmother, 46,XY (and XX, respectively,) inv(5)(p15q32). The congenital anomalies in this infant are more extensive and severe than previously reported in cases of recombination aneusomy involving chromosome 5. 相似文献
80.
Bakakos P Smith JL Warner JO Vance G Moss CT Hodges E Lanham S Howell WM 《The Journal of allergy and clinical immunology》2001,107(6):1089-1094
BACKGROUND: Peanut is one of the most common foods causing allergic reactions and is the most common cause of fatal and near-fatal food-related anaphylaxis. Little is known of the immunologic mechanisms that underlie peanut allergy. OBJECTIVES: In this study we examined clonality of the T-cell response (TCR) to peanut in MHC class II identical, peanut allergy-discordant sibling pairs. METHODS: Four sibling pairs were investigated. The TCR repertoire was analyzed before and after in vitro stimulation of PBMCs with crude peanut or PHA, as control for general/nonspecific reactivity. Eighteen TCR-Vbeta families were examined by flow cytometry. Where significant differences in incidence of particular TCR-Vbeta families were observed, PCR familyspecific cDNA amplification and gene scanning were performed. RESULTS: After stimulation with peanut, no selective expansion of any TCR-Vbeta subpopulation was observed with flow cytometry, in either the peanut-allergic or nonallergic siblings, with the exception of 1 peanut-allergic subject who demonstrated a significant increase of TCR-Vbeta11(+) cells (0.3%-5.9% of the total CD3(+) cells). However, gene scanning revealed predominant single-size PCR products for TCRBV11 in all peanut-allergic subjects after peanut stimulation. TCRBV11 polyclo-nality was observed in allergic and nonallergic subjects before peanut stimulation and in nonallergic subjects after peanut stimulation. In comparison, all subjects, before and after stimulation with peanut, showed polyclonality for TCRBV2. CONCLUSIONS: Our results argue for clonal or oligoclonal TCRs to crude peanut and indicate that changes in the TCRBV11 subpopulation are restricted to peanut-allergic subjects after stimulation with crude peanut allergen. 相似文献