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991.
    
In the yeast Saccharomyces cerevisiae, mutations in vacuolar protein sorting (VPS) genes result in secretion of proteins normally localized to the vacuole. Characterization of the VPS pathway has provided considerable insight into mechanisms of protein sorting and vesicle-mediated intracellular transport. We have cloned VPS9 by complementation of the vacuolar protein sorting defect of vps9 cells, characterized its gene product, and investigated its role in vacuolar protein sorting. Cells with a vps9 disruption exhibit severe vacuolar protein sorting defects and a temperature-sensitive growth defect at 38 degrees C. Electron microscopic examination of delta vps9 cells revealed the appearance of novel reticular membrane structures as well as an accumulation of 40- to 50-nm-diameter vesicles, suggesting that Vps9p may be required for the consumption of transport vesicles containing vacuolar protein precursors. A temperature-conditional allele of vps9 was constructed and used to investigate the function of Vps9p. Immediately upon shifting of temperature-conditional vps9 cells to the nonpermissive temperature, newly synthesized carboxypeptidase Y was secreted, indicating that Vps9p function is directly required in the VPS pathway. Antibodies raised against Vps9p immunoprecipitate a rare 52-kDa protein that fractionates with cytosolic proteins following cell lysis and centrifugation. Analysis of the VPS9 DNA sequence predicts that Vps9p is related to human proteins that bind Ras and negatively regulate Ras-mediated signaling. We term the related regions of Vps9p and these Ras-binding proteins a GTPase binding homology domain and suggest that it defines a family of proteins that bind monomeric GTPases. Vps9p may bind and serve as an effector of a rab GTPase, like Vps2lp, required for vacuolar protein sorting.  相似文献   
992.
    
The synthesis, antibacterial activities, murine pharmacokinetic and infection model data for a range of aryl and heteroaryl ketone derivatives of monic acid (2a) are reported. The best results were found for the 3-furyl and 2-methoxy thiazol-5-yl analogues.  相似文献   
993.
    
OBJECTIVE: To evaluate the impact of laparoscopy on the management of children with a unilateral impalpable testis. PATIENTS AND METHODS: The study population consisted of 27 children who underwent a primary inguinal exploration for a unilateral impalpable testis. RESULTS: Twelve of 27 (44%) children had inguinal or 'peeping' testes and 10 of 27 (37%) had blind-ending vasa and vessels in the inguinal canal; four of these 10 had atrophic tubular tissue in the excised remant. Four of 27 (15%) had blind-ending vasa and vessels proximal to the internal ring. Only one child had a testis proximal to the internal ring. Only the four children (15%) with blind-ending vasa and vessels proximal to the internal ring would have benefited from a laparoscopy by avoiding an inguinal exploration. CONCLUSIONS: Because of the time, expense and limited usefulness of laparoscopy in altering the management of children with a unilateral unpalpable testis, we reserve laparoscopy for cases where inguinal exploration has failed.  相似文献   
994.
    
Rett syndrome and Angelman syndrome are neurodevelopmental disorders characterized by severe intellectual disability, microcephaly, speech disturbance, movement disorders with gait and/or truncal ataxia, and occasionally a similar facial appearance. Both conditions can be difficult to diagnose in girls early in their clinical course and can be difficult to distinguish from each other. Genomic imprinting is a known association in Angelman syndrome and previously has been suggested in Rett syndrome. Our aim was to evaluate the methylation status in a cohort of classical patients with Rett syndrome, using a methylation system for chromosome 15q11-13. Methylation analysis of chromosome 15 has not been previously reported in Rett syndrome. Furthermore, we document the clinical features of 31 girls with classical Rett syndrome and confirm the phenotypic similarities between Rett syndrome and Angelman syndrome. The methylation studies in these girls with Rett syndrome were normal. This excludes an imprinting error of the Angelman syndrome critical region on chromosome 15 (15q11-13) as an association with Rett syndrome, and indicates that methylation studies may be useful in distinguishing Rett syndrome from Angelman syndrome in young patients with an overlapping clinical phenotype. A normal methylation pattern, however, does not exclude the diagnosis of Angelman syndrome and clear distinction between the two syndromes will evolve over time.  相似文献   
995.
    
Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant skin diseases characterized by blistering, due to mechanical stress-induced degeneration of basal epidermal cells. It is now well-established that the three major subtypes of EBS are genetic disorders of the basal epidermal keratins, keratin 5 (K5) and keratin 14 (K14). Here we show that a rare subtype, referred to as EBS with mottled pigmentation (MP), is also a disorder of these keratins. Affected members of two seemingly unrelated families with EBS-MP had a C to T point mutation in the second base position of codon 24 of one of two K5 alleles, leading to a Pro: Leu mutation. This mutation was not present in unaffected members nor in 100 alleles from normal individuals. Linkage analyses mapped the defect to this type II keratin gene (peak logarithm of odds score at phi = 0 of 3.9), which is located on chromosome 12q11-q13. This provides strong evidence that this mutation is responsible for the EBS-MP phenotype. Only conserved between K5 and K6, and not among any of the other type II keratins, Pro-24 is in the nonhelical head domain of K5, and only mildly perturbs the length of 10-nm keratin filaments assembled in vitro. However, this part of the K5 head domain is likely to protrude on the filament surface, perhaps leading to additional aberrations in intermediate filament architecture and/or in melanosome distribution that are seen ultrastructurally in patients with the mutation.  相似文献   
996.
    
During a 24-month period 446 children with diarrhea and 16 controls had examination of their stools for leukocytes and for occult blood. Fecal leukocytes were found in 36, 16 and 18% of children with Salmonella-Shigella-Campylobacter, rotavirus or enterotoxigenic Escherichia coli, or cryptosporidial diarrhea, respectively. Similarly 43, 39 and 38% of these groups, respectively, as well as 13% of controls had occult blood. Notably 70% of 10 Shigella cases had fecal leukocytes. In 166 children with mixed pathogens leukocytes were seen in 27 and 8% of children with Salmonella-Shigella-Campylobacter or noninvasive pathogen, respectively. Likewise 44 and 18% of these groups had occult blood. Agreement between both tests being positive was poor, the highest result being 50% for Shigella. Dysentery combined with both tests positive was associated with 15 (88%) cases of invasive agents present in stool cultures, and combination of dysentery with fecal leukocytes was associated with 21 (72%) cases of invasive agents recovered. The results of these tests should be interpreted in the context of the clinical situation. A combined clinical-epidemiologic and screening tests-based approach to infectious diarrhea of childhood is suggested.  相似文献   
997.
Atomic force microscopy (AFM) and photon correlation spectroscopy (PCS) were used for monitoring of the procedure for cytochrome CYP11A1 monomerization in solution without phospholipids. It was shown that the incubation of 100 μM CYP11A1 with 12% Emulgen 913 in 50 mM KP, pH 7.4, for 10 min at T = 22°C leads to dissociation of hemoprotein aggregates to monomers with the monomerization degree of (82 ± 4)%. Following the monomerization procedure, CYP11A1 remained functionally active. AFM was employed to detect and visualize the isolated proteins as well as complexes formed between the components of the cytochrome CYP11A1-dependent steroid hydroxylase system. Both Ad and AdR were present in solution as monomers. The typical heights of the monomeric AdR, Ad and CYP11A1 images were measured by AFM and were found to correspond to the sizes 1.6 ± 0.2 nm, 1.0 ± 0.2 nm and 1.8 ± 0.2 nm, respectively. The binary Ad/AdR and AdR/CYP11A1mon complexes with the heights 2.2 ± 0.2 nm and 2.8 ± 0.2 nm, respectively, were registered by use of AFM. The Ad/CYP11A1mon complex formation reaction was kinetically characterized based on optical biosensor data. In addition, the ternary AdR/Ad/CYP11A1 complexes with a typical height of 4 ± 1 nm were AFM registered.  相似文献   
998.
Human well-being depends on the entrainment of endogenous circadian rhythms of biological functions and the sleep-wake rhythm. Although the incidence of otherwise healthy subjects with chronically altered sleep-wake rhythms is rather low, the investigation of these patients provides new sights into circadian entrainment mechanisms. We therefore examined the circadian rhythm of circulating melatonin and the sleep-wake rhythm in five patients with chronic sleep-wake rhythm disorders and ten age-matched healthy controls. All patients showed altered circadian melatonin rhythm parameters in relation to their sleep-wake cycle compared to age-matched controls. These alterations were random, i.e., independent of the type, the duration, and the age of onset of the disorder. The melatonin onset to sleep onset interval varied between the patients and the melatonin acrophase to sleep offset interval was prolonged in four patients. These findings indicate individual phase relations between the circadian melatonin rhythm and the sleep-wake cycle in patients with chronic sleep-wake rhythm disorders. Since the prolonged melatonin acrophase to sleep offset interval was the most consistent finding independent of aetiological origins, this abnormality may be one possible maintaining factor in chronic sleep-wake rhythm disorders due to reduced phase-resetting properties of the circadian pacemaker. Furthermore, rather low circadian melatonin amplitudes and a subsensitivity to daylight may maintain the disorder in at least some patients.  相似文献   
999.
Tissue gain and efficiency and carcass characteristics of seventy-eight Angus steers were compared on three feed intake regimens and serially slaughtered at 6 months to 6 years. The regimens were: (A) continuous ad ad libitum feeding, (B) restricted to gain about 0.45 kg daily and (C) restricted as in B until 6 months before slaughter then fed ad libitum. Steers, regardless of feeding regimen, made their greatest gains up to 12 months of age and became less efficient after that time. Steers fed ad libitum had the highest percentage of fat but the lowest percentage of lean and bone when compared with steers fed for restricted gain. Carcasses of the steers fed ad libitum contained more lean and fat at each slaughter age. Average daily gain, feed efficiency and percentage of lean and bone decreased with age; and feed intake, slaughter grade, dressing percent, taste panel desirability and percent of fat tended to increase with age. All steers reached their maximum growth in height at withers, depth of chest and length of body at about 3 years. Steers that were restricted up to 6 months before slaughter showed compensatory growth during their ad libitum feeding period and during the first 12 months of the study; protein and fat were produced most efficiently by this growth. It would appear that it is possible to modify fat deposition by changing feed intake level.  相似文献   
1000.
Ureterovaginal fistula is an uncommon complication of pelvic operations, seen most often after Wertheim's hysterectomy. We report 12 cases of ureterovaginal fistulas seen during a 20-year period, all of which followed operations for benign gynecologic conditions. Most patients had no urinary symptoms until the sudden onset of incontinence 1 to 4 weeks postoperatively. Diagnosis was established readily by a combination of excretory urography, cystography, cystoscopy, retrograde pyeloureterography and dye studies. In our series only 1 patient was treated by primary nephrectomy, while 11 underwent ureteroneocystostomy: 2 with a Boari flap and 9 by a direct method. Reconstruction failed in 2 patients, 1 of whom required a secondary nephrectomy.  相似文献   
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