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41.
Black GF Weir RE Chaguluka SD Warndorff D Crampin AC Mwaungulu L Sichali L Floyd S Bliss L Jarman E Donovan L Andersen P Britton W Hewinson G Huygen K Paulsen J Singh M Prestidge R Fine PE Dockrell HM 《Clinical and diagnostic laboratory immunology》2003,10(4):602-611
We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-gamma) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD from Mycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens from M. tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis (MPB70), M. bovis BCG (Ag85), and M. leprae (65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovis BCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-gamma was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinant M. leprae 35-kDa and 18-kDa and purified native M. bovis BCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. The M. tuberculosis antigens ESAT-6 and MPT64 and the M. bovis antigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded to M. tuberculosis PPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure to M. tuberculosis or M. bovis is much less frequent than exposure to environmental mycobacteria such as M. avium, which have antigens homologous to the M. leprae 35-kDa and 18-kDa antigens. M. tuberculosis ESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the three M. tuberculosis antigens tested it provided the best indication of exposure to, or infection with, M. tuberculosis. 相似文献
42.
Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands 总被引:1,自引:4,他引:1
Smits LJ; Van Poppel FW; Verduin JA; Jongbloet PH; Straatman H; Zielhuis GA 《Human reproduction (Oxford, England)》1997,12(11):2572-2578
The relationship between fecundability and month of birth was investigated
in a cohort of 1526 women who married between 1802 and 1929, using only
women whose first marriage occurred before the age of 35 years. On the
basis of their time to pregnancy (TTP, calculated as time between wedding
and first birth minus gestational length), women were categorized into two
groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348)
and subfecunds (TTP >18 months, n = 118). By use of logistic regression,
cosinor functions with a period of 1 year or 6 months and variable shift
and amplitude were fitted through the monthly odds of subfecunds versus
fecunds. The best fitting curve was unimodal, with a zenith in September (P
= 0.13 for H0: no differences). Exclusion of childless women (n = 36,
minimum follow-up 5 years) from the subfecunds led to a similar curve (P
< 0.01), while childless women, as compared with fecunds, showed a birth
distribution that was best represented with a bimodal curve with zeniths in
January and July (P = 0.06). This study provides evidence for the existence
of differences in fecundability by month of birth. The cause of this
relationship is unclear, but may lie in a melatonin-dependent circannual
variability of the quality of the oocyte.
相似文献
43.
Brainstem auditory evoked potentials were bilaterally normal, and somatosensory evoked potentials were unilaterally abnormal in a patient with a large pontine infarct causing a "locked-in" syndrome. In the post mortem examination, the lesion extended unilaterally into the pontine tegmentum, partially involving the left medial lemniscus. The P14 potential was absent and the N20 potential was diminished in amplitude with right median nerve stimulation. The origin of the P14 potential has been debated in the literature. This case provides evidence for the P14 generator being located at the pontine level, in relation to a lemniscal area above the decussation of the somatosensory pathway. Evoked potentials can help to determine the tegmental extension of the pontine infarcts in the "locked-in" syndrome, especially in patients unable to cooperate with clinical examination. 相似文献
44.
A model of corrective gene transfer in X-linked ichthyosis 总被引:5,自引:0,他引:5
Freiberg RA; Choate KA; Deng H; Alperin ES; Shapiro LJ; Khavari PA 《Human molecular genetics》1997,6(6):927-933
Single gene recessive genetic skin disorders offer attractive prototypes
for the development of therapeutic cutaneous gene delivery. We have
utilized X-linked ichthyosis (XLI), characterized by loss of function of
the steroid sulfatase arylsulfatase C (STS), to develop a model of
corrective gene delivery to human skin in vivo. A new retroviral expression
vector was produced and utilized to effect STS gene transfer to primary
keratinocytes from XLI patients. Transduction was associated with
restoration of full-length STS protein expression as well as steroid
sulfatase enzymatic activity in proportion to the number of proviral
integrations in XLI cells. Transduced and uncorrected XLI keratinocytes,
along with normal controls, were then grafted onto immunodeficient mice to
regenerate full thickness human epidermis. Unmodified XLI keratinocytes
regenerated a hyperkeratotic epidermis lacking STS expression with
defective skin barrier function, effectively recapitulating the human
disease in vivo. Transduced XLI keratinocytes from the same patients,
however, regenerated epidermis histologically indistinguishable from that
formed by keratinocytes from patients with normal skin. Transduced XLI
epidermis demonstrated STS expression in vivo by immunostaining as well as
a normalization of histologic appearance at 5 weeks post-grafting. In
addition, transduced XLI epidermis demonstrated a return of barrier
function parameters to normal. These findings demonstrate corrective gene
delivery in human XLI patient skin tissue at both molecular and functional
levels and provide a model of human cutaneous gene therapy.
相似文献
45.
Doctors'' characteristics do not predict long-term glycaemic control in type 2 diabetic patients. 下载免费PDF全文
Lars J Hansen Niels de Fine Olivarius Volkert Siersma John Sahl Andersen 《The British journal of general practice》2003,53(486):47-49
Glycaemic control in type 2 diabetic patients varies widely between general practitioners (GPs). To increase our understanding of this variation, linear random effects models were used to examine the predictive value of GP characteristics on the course of annual HbA1c measurements, in 688 newly diagnosed type 2 diabetic patients between one and five years after diabetes diagnosis. We found that characteristics of centrally supported GPs, such as interest in diabetes, experience, practice type, list size, and weekly working hours, did not predict their patients' glycaemic control. 相似文献
46.
The induction of autoimmunity by viruses has been hypothesized to occur by a number of mechanisms. Coxsackievirus B4 (CB4) induces hyperglycemia in SJL mice resembling diabetes in humans. While virus is effectively cleared within 2 weeks, hyperglycemia does not appear until about 8-12 weeks postinfection at a time when replicative virus is no longer detectable. In SJL mice, reinfection with CB4 enhanced the development of hyperglycemia. As predicted, the immune system responded more rapidly to the second infection and virus was cleared more swiftly. However, while infiltrating T cells were found within the pancreas, depletion of the CD4 T cell population prior to secondary infection or use of CD8 knock-out mice had no effect on the development of virus-mediated hyperglycemia. In conclusion, enhanced hyperglycemia induced by CB4 occurs independent of the T cell response. 相似文献
47.
Cell proliferation may be evaluated by various methods, including Ki-67 immunohistochemistry and measures of telomerase activity. Both methods would theoretically show comparable increases in a given case. To evaluate the relationship between these 2 markers of proliferation in aggressive mature B-cell lymphomas, 48 cases were studied. The study group included 5 cases of mantle cell lymphoma (MCL); 6 cases of Burkitt's/Burkitt's-like lymphoma (BL); 9 cases of follicular lymphoma, grade 3 (FLC); and 28 cases of diffuse large B-cell lymphoma (DLC). Telomerase activity was measured as total product generated (TPG) units, and TPG results for the aforementioned cases were compared to the TPG results for 10 cases of reactive follicular hyperplasia. An overlap in TPG scores between reactive cases and lymphoma cases was found. Significant differences in both log TPG (P = 0.0443) and Ki-67 (P = 0.0006) were seen in the different lymphoma types. A positive correlation between Ki-67 percentage and TPG score was identified in FLC (r = 0.9281; P = 0.0003), but a poor correlation between these 2 indicators was seen in the other lymphoma types. Cluster analysis identified distinct patterns for MCL, FLC, and BL, but heterogeneous patterns for DLC. Because increases in both Ki-67 proliferation and telomerase activity are reported in normal germinal centers (GCs), these tests were also evaluated for usefulness as markers of a GC cell phenotype. Among the FLC and DLC cases, features of a GC phenotype significantly correlated with increased Ki-67 percentage (P = 0.0152), but not with increased log TPG. An elevated log TPG correlated with CD10 expression, and elevated Ki-67 percentage correlated with both CD10 and BCL-6 expression. TPG level and Ki-67 percentage did not correlate with the presence of t(14;18) or BCL-2 protein expression. Although the proliferation patterns were fairly distinctive for MCL, FLC, and BL, these studies show that markers of cell proliferation do not by themselves,identify distinct subtypes of large cell lymphomas. With the exception of FLC, the tumors exhibited poor correlation between telomerase activity and Ki-67 proliferation index. These tests did show some correlation with expression of GC cell phenotypic markers, however. 相似文献
48.
Colonic histopathology in some patients with untreated celiac sprue and refractory sprue has been said to be indistinguishable from lymphocytic colitis, but there have been no objective comparisons on which this is based. The purpose of this study was to determine the prevalence and to characterize the nature of colonic histopathology at the time of diagnosis in patients with celiac or refractory sprue. Colonoscopic biopsy specimens obtained at the time of diagnosis from 16 patients with celiac sprue, six patients with refractory sprue, nine patients with lymphocytic colitis, and five normal controls were analyzed blindly by histological and morphometric methods, quantitating the number and specific subtypes of inflammatory cells within the lamina propria and epithelium. Immunoperoxidase staining of intraepithelial lymphocytes with a monoclonal antibody to CD8 also was performed. Three of 16 patients with untreated celiac sprue (19%) were thought to have colonic histological abnormalities, which by morphometry consisted of slightly increased numbers of lymphocytes in the surface epithelium and lamina propria, many of which were CD8-positive. These abnormalities were distinguishable from lymphocytic colitis by the lack of increased overall lamina propria cellularity and surface epithelial abnormalities, and by fewer intraepithelial lymphocytes. In refractory sprue, colonic histological abnormalities were more frequent than in celiac sprue, occurring in four of six patients (67%), more pronounced, and identical to those in the lymphocytic colitis syndrome. However, colonic intraepithelial lymphocytes in lymphocytic colitis were mostly CD8-positive, whereas those in the colitis of refractory sprue rarely were. Mild colonic lymphocytosis in patients with untreated celiac sprue should be distinguished from lymphocytic colitis by the lack of surface epithelial abnormalities, the lack of increased cellularity of the lamina propria, and the lack of ongoing watery diarrhea after treatment with a gluten-free diet. In contrast, colonic histopathology in refractory sprue is indistinguishable from lymphocytic colitis, although immunohistochemical differences do exist. 相似文献
49.
A series of cards each containing a two dimensional array of identical Snellen "E's" was used to determine best eccentric visual acuity in patients with macular disease having Snellen visual acuity of 20/70 or worse. Each "full field E" card simultaneously presents the same letter to foveal and parafoveal areas. This test can therefore determine quickly if potentially useful vision is present in any area of the central visual field. In our study of 37 eyes, 70% demonstrated potential visual acuity at least two times better than visual acuity measured by conventional methods, and 20% demonstrated at least a fourfold improvement. This suggests that most patients with macular disease do not spontaneously employ their best remaining area of retina for fixation. 相似文献
50.
Gerald Batist Raymond W. Klecker Jr. Hiremagalur N. Jayaram Jean F. Jenkins John Grygiel Daniel C. Ihde Joyce L. Eddy Robert L. Fine Ian G. Kerr Jerry M. Collins 《Investigational new drugs》1985,3(4):349-355
Summary Tiazofurin (2--D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M2. Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 ± 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.Abbreviations TCAR
Tiazofurin
- HPLC
High performance liquid chromatography
- IMPD
Inosine monophosphate dehydrogenase
- WBC
white blood cell
- CPK
creatine phosphokinase
- Css
steady-state concentration 相似文献