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41.
V Pucholt J S Fitzsimmons K Gelsthorpe M A Reynolds R D Milner 《Journal of medical genetics》1980,17(6):447-452
HLA typing of 33 families with one or more children suffering from congenital adrenal hyperplasia confirmed that the gene for 21-hydroxylase deficiency is closely associated with the HLA region. Analysis of two families in which recombination of chromosome 6 had occurred indicated that the gene locus is between the A and D loci of the HLA region. The rare allele Bw47 was observed in 18 parents and was always associated with the carrier state for 21-hydroxylase deficiency. 相似文献
42.
43.
A. Bartoli Brenda A. Cross A. Guz S. K. Jain M. I. M. Noble Diana W. Trenchard 《The Journal of physiology》1974,240(1):91-109
1. The inhalation of CO(2) produces a tachypnoea only in the presence of intact vagus nerves; the present study was designed to examine the mechanism of this phenomenon in the dog.2. Closed-chest cardiopulmonary bypass was established in dogs weighing 16-24 kg, anaesthetized with chloralose. When the ;bypass' was established pulmonary blood flow ceased, P(A, CO2) was reduced and the respiratory rate slowed. 3-10% CO(2) in O(2) could then be inhaled without change in the level of P(a, CO2) set at the oxygenator.3. The addition of CO(2) in these concentrations to the inspired oxygen resulted in an increase in respiratory frequency, maximal at the first breath and sustained for the 1 min period of exposure. The increase in respiratory frequency was due to a shortening of expiratory duration. Inspiratory duration did not change. The response was absent after vagotomy.4. Inert gases in O(2), given as a control, had no effect on breathing.5. The effect of raising P(a, CO2) (by increasing the concentration of CO(2) in the gas equilibrating the blood in the oxygenator), was primarily to increase tidal volume.6. The ventilatory effect of inspiring CO(2)/O(2) mixtures was shown to be additive to the effect of raising P(a, CO2).7. These experiments show that an afferent vagal reflex originating from the lungs causes tachypnoea, when a dog, on ;bypass', inhales low concentrations of CO(2) in O(2). 相似文献
44.
45.
Pachytene quadrivalents are described in a male heterozygous for a balanced reciprocal translocation between the long arms of chromosomes 10 and 11. The break points of the translocation occur at 10q23 and 11q24. The main chromomere patterns of the bivalents correspond to the main G bands in mitosis and are sufficiently pronounced to allow the identification of bivalents 10 and 11 in normal spermatocytes. 相似文献
46.
Recurrent Bacteremia Caused by a “Flexispira”-Like Organism in a Patient with X-Linked (Bruton’s) Agammaglobulinemia 下载免费PDF全文
Susan Weir Brenda Cuccherini Anne M. Whitney Marsha L. Ray John P. MacGregor Arnold Steigerwalt Maryam I. Daneshvar Robbin Weyant Betty Wray John Steele Warren Strober Vee J. Gill 《Journal of clinical microbiology》1999,37(8):2439-2445
Helicobacter spp., except for Helicobacter cinaedi, have only rarely been reported in cases of septicemia. A patient with X-linked (Bruton's) agammaglobulinemia was found to have persistent sepsis with a Helicobacter-like organism despite multiple courses of antibiotics. His periods of sepsis were associated with leg swelling thought to be consistent with cellulitis. The organism was fastidious and required a microaerophilic environment containing H(2) for growth. Optimal growth was observed at 35 to 37 degrees C on sheep blood, CDC anaerobe, and Bordet-Gengou agars. Serial subcultures every 4 to 5 days were required to maintain viability. The organism was strongly urease positive and showed highest relatedness to Helicobacter-like organisms with the vernacular name "Flexispira rappini" by 16S rRNA gene sequence analysis. Genomic DNA hybridization studies, however, found 24 to 37% relatedness to "F. rappini" and even less to other Helicobacter spp. Although the organism phenotypically resembles "Flexispira" and Helicobacter, it is thought to represent a new taxon. The patient's infection was eventually cleared with a prolonged (5-month) course of intravenous imipenem and gentamicin. 相似文献
47.
The kidney plays a major role in maintaining and controlling systemic acid–base homeostasis by reabsorbing bicarbonate and secreting protons and acid-equivalents, respectively. During postnatal kidney development and adaptation to changing diets, plasma bicarbonate levels are increasing, the capacity for urinary acidification maturates, and the final morphology and distribution of intercalated cells is achieved. In adult kidney, at least two types of intercalated cells (IC) are found along the collecting duct characterised either by the expression of AE1 (type A IC) or pendrin (non-type A IC) where non-type A IC are found only in the convoluted distal tubule, connecting tubule and cortical collecting duct. Here we investigated in mouse kidney the relative mRNA abundance, protein expression levels and distribution of several proteins involved in renal acid–base transport, namely, the Na+/HCO3
– cotransporter NBC1 (SLC4A4), the Na+/H+-exchanger NHE3 (SLC9A3), two subunits of the vacuolar H+-ATPase [ATP6V0A4 (a4), ATP6V1B1 (B1)], the Cl–/HCO3
– exchangers AE1 (SLC4A1) and pendrin (SLC26A4). Relative mRNA abundance of all transport proteins was lowest at day 3 after birth and increased thereafter in parallel with protein levels. The numbers of type A and non-type A IC in the cortical collecting duct (CCD) increased from day 3 to days 18 and 24, whereas the number of IC in the CCD with apical staining for the vacuolar H+-ATPase subunits a4 and B1 decreased from day 3 to days 18 and 24, respectively. In addition, cells with characteristics of non-type A IC (pendrin expression, basolateral expression of vacuolar H+-ATPase subunits) were found in the inner and outer medulla 3 days after birth but were absent from the medulla of 24-day-old mice. Taken together, these results demonstrate massive changes in mRNA and protein expression levels of several acid–base transporters during postnatal kidney maturation and also show changes in intercalated cell phenotype in the medulla during these processes. 相似文献
48.
M. A. Goodale N. P. Foreman A. D. Milner 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1978,31(3):445-457
Summary Rats with either bilateral ablations of superior colliculus, bilateral ablations of visual cortex, or sham operations were trained to run across a large arena towards a small illuminated target which varied in location from trial to trial. An impairment in this visually-guided running was apparent in the cortical group, but not in the collicular group. When, in a second experiment, the spatial relationships within the apparatus were changed by extending the entry-tunnel some distance into the arena, the running of the cortical group became even more impaired, while the collicular animals continued to run towards the targets under efficient visual control. In a third experiment, the effect of introducing a novel flashing light in various locations around the perimeter of the arena was investigated. It was found that unlike the other two groups, the collicular animals showed no orienting reflex to the novel stimulus when it was presented outside a broad central area of the visual field.The authors acknowledge the financial support of the Science Research Council (grant no B/RG/61112) 相似文献
49.
Bradley Q. Fox Peninah F. Benjamin Ammara Aqeel Emily Fitts Spencer Flynn Brian Levine Elizaveta Maslak Rebecca L. Milner Benjamin Ose Michael Poeschla Meghna Ray Maeve Serino Sahaj S. Shah Kelly L. Close 《Clinical Diabetes》2021,39(2):160
To the best of our knowledge, there are no published data on the historical and recent use of CGM in clinical trials of pharmacological agents used in the treatment of diabetes. We analyzed 2,032 clinical trials of 40 antihyperglycemic therapies currently on the market with a study start date between 1 January 2000 and 31 December 2019. According to ClinicalTrials.gov, 119 (5.9%) of these trials used CGM. CGM usage in clinical trials has increased over time, rising from <5% before 2005 to 12.5% in 2019. However, it is still low given its inclusion in the American Diabetes Association’s latest guidelines and known limitations of A1C for assessing ongoing diabetes care.The availability of reliable continuous glucose monitoring (CGM) systems has proven to be a major innovation in diabetes management and research. Most current CGM systems are approved for 7- to 14-day use and use a wire-tipped glucose oxidase sensor inserted in subcutaneous tissue to monitor glucose concentrations in interstitial fluid. One implanted CGM system is approved for longer-term use (90–180 days); it operates with fluorescence-based technology. CGM sensors record a glucose data point every 1–15 minutes (depending on the system), collecting far more granular data and information on glycemic patterns than self-monitoring of blood glucose (SMBG) alone. Real-time CGM or intermittently scanned CGM systems send data continuously or intermittently to dedicated receivers or smartphones, whereas professional CGM systems provide retrospective data, either blinded or unblinded, for analysis and can be used to identify patterns of hypo- and hyperglycemia. Professional CGM can be helpful to evaluate patients when other CGM systems are not available to the patient or the patient prefers a blinded analysis or a shorter experience with unblinded data.In the 20 years since CGM systems first became available to people with diabetes, technological improvements, particularly pertaining to accuracy and form factor, have made CGM increasingly viable for both patient use and clinical investigation (1,2). Average sensor MARD (mean absolute relative difference; a summary accuracy statistic) has decreased from >20 to <10% (3–10), including two systems that do not require fingerstick calibrations and three that are approved to be used for insulin dosing (11). Concurrently, size, weight, and cost of CGM systems have all decreased, while user-friendliness and convenience have increased (12).To encourage use of CGM-derived data, researchers and clinicians have worked to develop a standard set of glycemic metrics beyond A1C. In 2017, two international groups of leading diabetes clinical and research organizations published consensus definitions for key metrics, including clinically relevant glycemic cut points for hypoglycemia (<70 and <54 mg/dL), hyperglycemia (>180 and >250 mg/dL), and time in range (TIR; 70–180 mg/dL) (13,14).CGM-derived metrics provide far greater precision and granularity than is possible with SMBG or A1C data alone (Table 1), enabling clinicians and investigators to better represent inter- and intraday glycemic differences with metrics such as TIR, glycemic variability, and time in hypoglycemia and hyperglycemia (15). Crucially, CGM also allows for the accurate measurement and detection of nocturnal glycemia (16). The use of these metrics enables a more comprehensive understanding of glycemic management that can facilitate individualized treatment for people with diabetes or prediabetes. Although A1C is a useful estimate of mean glucose over the previous 2–3 months, especially when evaluating population health, it is important to include other glycemic outcomes in clinical trials. Furthermore, there is emerging evidence suggesting that TIR predicts the development of microvascular complications at least as well as A1C (17,18).TABLE 1Benefits of CGM Compared With A1C Alone in Assessing Glycemia
Open in a separate windowDespite recent standardization of metrics and an emerging consensus around the importance of including CGM-derived outcomes in clinical trials, to our knowledge, there has been no attempt to estimate the historical and current use of CGM in clinical trials of pharmacological agents for diabetes. We sought to analyze the use of CGM in trials of currently available pharmaceutical agents for the treatment of diabetes. 相似文献
CGM | A1C Alone |
---|---|
Facilitates real-time readings of blood glucose levels | Requires SMBG |
Provides information on glucose variability, including duration of hypo- and hyperglycemia and nocturnal glycemia | Does not provide information on acute glycemic excursions and time in biochemical hypoglycemia and hyperglycemia |
Correlates strongly with 3 months of mean glucose, TIR, and hyperglycemia metrics | Measures average glucose during the past 2–3 months |
Provides information on direction of and rate of change in glucose levels | Does not provide information on direction of or rate of change in glucose levels |
Provides TIR data (time spent between 70 and 180 mg/dL) | Does not have TIR measurement capability |
50.
Schindler I Rice NJ McIntosh RD Rossetti Y Vighetto A Milner AD 《Nature neuroscience》2004,7(7):779-784
When we reach out to pick something up, our arm is directed to the target by visuomotor networks in the cortical dorsal stream. However, our reach trajectories are influenced also by nontarget objects, which might be construed as potential obstacles. We tested two patients with bilateral dorsal-stream (parietal lesions, both of whom were impaired at pointing to visual stimuli (optic ataxia). We asked them to reach between two cylinders, which varied in location from trial to trial. We found that the patients' reaches remained invariant with changes in obstacle location. In a control task when they were asked to point midway between the two objects, however, their responses shifted in an orderly fashion. We conclude that the dorsal stream provides the visual guidance we automatically build into our movements to avoid potential obstacles, as well as that required to ensure arrival at the target. 相似文献