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21.
Fjellstedt E Harnevik L Jeppsson JO Tiselius HG Söderkvist P Denneberg T 《Urological research》2003,31(6):417-425
Advances in molecular genetics have brought a deeper understanding of cystinuria. This autosomal recessive disease, which is caused by a defective tubular reabsorption of cystine and the three dibasic amino acids arginine, lysine and ornithine, results in a lifelong risk of renal stone formation because of the low solubility of cystine in urine. Mutations detected within the two genes known to be associated with cystinuria, SLC3A1 (related to type I) and SLC7A9 (related to non-type I), cannot, however, in all cases explain the disease. Inasmuch as a high urinary concentration of cystine is the basis of stone formation in these patients, our aim was to measure urinary total cystine, arginine, lysine and ornithine, in patients currently lacking a full genetic explanation for their disease. Thirty-three patients with cystinuria who were on long-term treatment with tiopronin or D-penicillamine were divided into two groups. Group 1 comprised eight patients who carried mutation in one of the SLC3A1 alleles and two patients who completely lacked mutations both in the SLC3A1 and the SLC7A9 genes, that is genetic findings discordant with the increased urinary excretion of cystine and the dibasic amino acids in these patients. Group 2 comprised 23 patients homozygous for mutations within SLC3A1, that is genetic findings in accordance with the excretion pattern of classic type I cystinuria. When the two groups were compared, Group 1 had a significantly higher total urinary excretion of cystine (p<0.01) as well as of arginine, lysine and ornithine (p<0.05) than Group 2. Also, when the two patients without mutations were excluded from the calculations, there still was a significant difference in the urinary excretion of total cystine (p<0.05). This suggests that the two patients without any detected mutations in the two known cystine transport genes also contributed to the difference. These unexpected findings indicate that an additional gene or genes participate in the urinary cystine reabsorption in the cystinuric patients who currently are without a full genetic explanation for their disease. 相似文献
22.
Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia 下载免费PDF全文
Shakkottai VG Chou CH Oddo S Sailer CA Knaus HG Gutman GA Barish ME LaFerla FM Chandy KG 《The Journal of clinical investigation》2004,113(4):582-590
Cerebellar ataxia, a devastating neurological disease, may be initiated by hyperexcitability of deep cerebellar nuclei (DCN) secondary to loss of inhibitory input from Purkinje neurons that frequently degenerate in this disease. This mechanism predicts that intrinsic DCN hyperexcitability would cause ataxia in the absence of upstream Purkinje degeneration. We report the generation of a transgenic (Tg) model that supports this mechanism of disease initiation. Small-conductance calcium-activated potassium (SK) channels, regulators of firing frequency, were silenced in the CNS of Tg mice with the dominant-inhibitory construct SK3-1B-GFP. Transgene expression was restricted to the DCN within the cerebellum and was detectable beginning on postnatal day 10, concomitant with the onset of cerebellar ataxia. Neurodegeneration was not evident up to the sixth month of age. Recordings from Tg DCN neurons revealed loss of the apamin-sensitive after-hyperpolarization current (IAHP) and increased spontaneous firing through SK channel suppression, indicative of DCN hyperexcitability. Spike duration and other electrogenic conductance were unaffected. Thus, a purely electrical alteration is sufficient to cause cerebellar ataxia, and SK openers such as the neuroprotective agent riluzole may reduce neuronal hyperexcitability and have therapeutic value. This dominant-inhibitory strategy may help define the in vivo role of SK channels in other neuronal pathways. 相似文献
23.
OBJECTIVES:To derive hardness factors for crystal phases of urinary tract stones and describe the hardness pattern in a stone population. MATERIAL AND METHODS: In a retrospective study, recordings from patients treated with extracorporeal shock-wave lithotripsy (ESWL) (stone surface area < or = 100 mm2) were used to derive hardness factors. The number of re-treatments, the number of shock waves and the energy index (the voltage in kilovolts multiplied by the number of shock waves) required for a satisfactory stone disintegration were assumed to reflect the hardness. The stone composition in 2100 patients provided the basis for an average hardness pattern. A hardness index was calculated from the fraction of each crystal phase and its hardness factor. RESULTS: The hardness factors were as follows: calcium oxalate monohydrate, 1.3; calcium oxalate dehydrate, 1.0; hydroxyapatite, 1.1; brushite, 2.2; uric acid/urate, 1.0; cystine, 2.4; carbonate apatite, 1.3; magnesium ammonium phosphate, 1.0; and mixed infection stones, 1.0. The hardness index for 114 stones (surface area 100-200 mm2) corresponded reasonably well to the ESWL treatment efforts. Calcium oxalate monohydrate, calcium oxalate dihydrate and hydroxyapatite were the most frequently encountered crystal phases in all 2100 stones. Only 21% of the stones were composed of only one crystal phase. There were two, three and more than three crystal phases in 26%, 38% and 15% of the stones, respectively. The hardness index calculated for 2100 stones ranged between 0.70 and 2.33, with a mean (SD) of 1.18 (0.15). CONCLUSIONS: The hardness factors and hardness index derived in this study might be useful for describing the stone situation in individual patients and groups of patients and for comparison of various treatment strategies. 相似文献
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26.
Thomas Kuhnt Nicole Jirsak Arndt Christian Müller Tanja Pelz Christian Gernhardt Hans-Günter Schaller Martin Janich Reinhard Gerlach Jürgen Dunst 《Strahlentherapie und Onkologie》2005,9(9):520-528
Hintergrund und Ziel:
Die Strahlentherapie bei Kopf-Hals-Tumoren führt in aller Regel zu einer Schädigung der Speicheldrüsen und somit auch zu einer dauerhaften Mundtrockenheit. Ziel dieser Untersuchung war es, eine moderne dreidimensionale Konformationsbestrahlungstechnik („three-dimensional conformal radiotherapy“ [3D-CRT]) für Kopf-Hals-Tumoren zu etablieren, um im Vergleich zur konventionellen Bestrahlungstechnik (K-RT) mit Photonen und Elektronen Xerostomien zu vermeiden. 相似文献27.
Hans-G. Klingemann 《Leukemia & lymphoma》1992,8(6):421-429
Relapse after marrow transplantation occurs despite total body irradiation and high doses of chemotherapy used to prepare the recipient. Recurrence rate is particularly high after autologous transplantation. In order to eliminate minimal residual disease persistent after marrow grafting, immunotherapy is currently being explored as a treatment modality that is non-cross-reactive with radiation and chemotherapy. This review describes first clinical results on the use of interferons and interleukin-2 in marrow transplant recipients as well as attempts to induce graft-versus-leukemia effects. 相似文献
28.
Philipp Alexander Bergmann Thomas Lange Frank Siemers Hans-Günther Machens J?rn Andreas Lohmeyer Thomas Namdar Peter Leonhard Stollwerck Stefan Zimmermann Peter Mail?nder 《European journal of plastic surgery》2012,35(1):19-24
Silicone implants have been used for breast augmentation for more than 45 years. Complications, in particular capsular contracture,
occur with an incidence of <10% and up to 60%. We investigated the influence of the surface of breast implants on the formation
of capsular contracture by comparing silicone with titanium-coated silicone. Seventeen smooth saline-filled silicone (group
A) and 14 saline-filled titanium-coated silicone (group B) implants were implanted in female Wistar rats. After 12 and 36 weeks,
the implants and capsules were extracted; histological and immunohistochemical staining was performed. The evaluation of the
capsules was performed by two examiners in a double-blinded manner. Histologically, no significant difference in total capsule
thickness was found. There was a significant difference in synovial-like metaplasia layer (SLM) thickness between groups A
and B (p = 0.041). Regarding implantation time (12 vs. 36 weeks), a significant difference was found in SLM thickness (p = 0.021). Immunohistochemical staining indicated a significantly lower infiltration with inflammatory cells in group B. A
significant correlation (p = 0.019) between a thick SLM layer and inflammatory cell infiltration was detected. Titanium-coated silicone implants reduce
SLM thickness and capsular inflammatory cell infiltration. These findings postulate that titanium-coated silicone implants
might point out a new chance in the prevention of capsular contracture. 相似文献
29.
This study aimed at formulating simplified estimates of ion-activity products of calcium oxalate (AP(CaOx)) and calcium phosphate (AP(CaP)) in mouse urineto find the most important determinants in order to limit the analytical work-up. Literature data on mouse urine composition was used to determine the relative effect of each urine variable on the two ion-activity products. AP(CaOx) and AP(CaP) were calculated by iterative approximation with the EQUIL2 computerized program. The most important determinants for AP(CaOx) were calcium, oxalate and citrate and for AP(CaP) calcium, phosphate, citrate, magnesium and pH. Urine concentrations of the variables were used. A simplified estimate of AP(CaOx) (AP(CaOx)-index(MOUSE)) that numerically approximately corresponded to 10(8) × AP(CaOx) was given the following expression:[Formula: see text]For a series of urine samples with various composition the coefficient of correlation between AP(CaOx)-index(MOUSE) and 10(8) × AP(CaOx) was 0.99 (p = 0.00000). A similar estimate of AP(CaP) (AP(CaP)-index(MOUSE)) was formulated so that it approximately would correspond numerically to 10(14) × AP(CaP) taking the following form:[Formula: see text]For a series of variations in urine composition the coefficient of correlation was 0.95 (p = 0.00000). The two approximate estimates shown in this article are simplified expressions of AP(CaOx) and AP(CaP). The intention of these theoretical calculations was not to get methods for accurate information on the saturation levels in urine, but to have mathematical tools useful for rough conclusions on the outcome of different experimental situations in mice. It needs to be emphasized that the accuracy will be negatively influenced if urine variables not included in the formulas differ very much from basic concentrations. 相似文献
30.