前列腺特异抗原研究进展与挑战(摘要)

前列腺特异抗原(ＰＳＡ)发现四分之一世纪以来,已成为诊断前列腺癌最有价值的肿瘤标志物。前列腺癌在男性癌症发病中占首位。自从80年代中期第一代检测ＰＳＡ的方法问世以来,前列腺癌的发病率有了显著改变。这部分归功于ＰＳＡ检测的增加,从而使前列腺癌得到早期诊断,这有利于将癌症控制在发病早期,增加治愈的可能性。虽然ＰＳＡ是一个有效的肿瘤标志物,并具有器官特异性,但其癌症特异性不高。ＰＳＡ升高也可见于其他良性前列腺疾病,尤其当ＰＳＡ浓度在4～10μｇ/Ｌ时。这个浓度范围被称为“诊断灰色区域”。对ＰＳＡ分子结构的研究主要集中…     

Minimal forced use without constraint stimulates spontaneous use of the impaired upper extremity following motor cortex injury

The purpose of this study was to determine if recovery of neurologically impaired hand function following isolated motor cortex injury would occur without constraint of the non-impaired limb, and without daily forced use of the impaired limb. Nine monkeys (Macaca mulatta) received neurosurgical lesions of various extents to arm representations of motor cortex in the hemisphere contralateral to the preferred hand. After the lesion, no physical constraints were placed on the ipsilesional arm/hand and motor testing was carried out weekly with a maximum of 40 attempts in two fine motor tasks that required use of the contralesional hand for successful food acquisition. These motor tests were the only “forced use” of the contralesional hand. We also tested regularly for spontaneous use of the contralesional hand in a fine motor task in which either hand could be used for successful performance. This minimal intervention was sufficient to induce recovery of the contralesional hand to such a functional level that eight of the monkeys chose to use that hand on some trials when either hand could be used. Percentage use of the contralesional hand (in the task when either hand could be used) varied considerably among monkeys and was not related to lesion volume or recovery of motor skill. These data demonstrate a remarkable capacity for recovery of spontaneous use of the impaired hand following localized frontal lobe lesions. Clinically, these observations underscore the importance of therapeutic intervention to inhibit the induction of the learned nonuse phenomenon after neurological injury.     

Work Problems and Accommodations Reported by Persons Who Are Postpolio or Have a Spinal Cord Injury

A number of studies have documented early functional declines in persons with a disability. The purpose of this study was to document (1) whether employees who are aging with their disability have experienced new work problems as a consequence of functional declines and (2) whether their work problems are being accommodated adequately. Ninety-six individuals with a disability (50 who are postpolio and 46 who had a spinal cord injury) were interviewed by phone. Each had worked at least 5 years postonset and was either currently working or unemployed for less than 5 years at the time of the interview. Forty-nine of the 50 persons who are postpolio reported they had experienced functional declines in recent years, and 41 of the 50 rated the severity of their disability greater than it was when they first began working. As a result of the functional declines they had experienced, most (90.9%) of their work problems were new and would not have been significant problems for them when they first began working. The situation was very different for the group with spinal cord injuries. Only a few members of that group had experienced functional declines that were causing new problems at work. A total of 480 work problems were reported by study participants. Three out of every eight problems did not have an accommodation satisfactory to the employee. The primary reason why a satisfactory solution was not provided was that no accommodation had been identified. Employers were generally supportive of the employee's need for accommodation; they paid for 59.1% of the accommodations that had a cost and refused to provide an accommodation for only 18 of the 480 problems.     

Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy Chinese and Vietnamese children in Hong Kong

Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae was studied in 621 healthy Chinese children and 300 healthy Vietnamese children aged from 2 months to 5 years in Hong Kong. The carriage rate of H, influenzae type b in Vietnamese children was 1.3% (CI 0.04-2.63%); it was zero in Chinese. The carriage rate of non-typable H. influenzae was 5.8% (CI 1.4-7.6%) in Chinese and 65.4% (CI 58.9-69.8%) in Vietnamese. The carriage rates of S. pneumoniae were 10.8% (CI 8.3-13.2%) and 55.7% (CI 50.1-61.3%) in Chinese and Vietnamese children, respectively. Univariate and multivariate logistic regression analyses were performed to search for factors associated with differences in carriage rates of both H. influenzae and S. pneumoniae between Chinese and Vietnamese children. Although older age, smaller living area and parental smoking were associated with higher carriage rates, these could not explain the remarkably low carriage rates of both bacteria in Chinese children.     

Strangulation of the uvula by hair wrapping

A 13-month-old male presented with a hair wrapped around his uvula. The entwined hair subsequently caused autoamputation of the distal uvula. Although a non-accidental etiology has been suggested for some cases of hair strangulation of appendages, this case indicates accidental strangulation of body parts is possible.     

Application of tissue-marking ink to prostate biopsy specimens

BACKGROUND: When sextant prostate biopsy specimens are performed, noting the location from which cancer-containing cores were taken aids in treatment planning. However, many institutions include several cores in a single container, to cut costs. We have tried several methods of ink application and combining ink-labeled biopsy specimens into fewer containers with the goal of maintaining information regarding location while minimizing the expense. METHODS: Several approaches to the application of tissue-marking ink to biopsy cores, core-preparation methods, color combinations, and numbers of cores in each container were assessed. RESULTS: The ink adheres well to dry cores, but these cores often exhibit dehydration artifact. Placing the cores on a wet sponge avoids dehydration but causes ink spread. Excessive ink application occurs with eyedroppers and syringes but is avoided by touching each core with an ink-moistened cotton swab. Application of 1% acetic acid to the inked core promotes congealing of the ink onto the tissue. Yellow, orange, and red ink are more difficult to distinguish than blue, black, or green. Deciphering distinct cores when three or more cores are combined is difficult, especially if cores are fragmented. CONCLUSIONS: With our current protocol, all biopsy specimens are placed on separate moistened gauze sponges. Specimens from the right side of the prostate are marked by green ink, and those from the left side are marked by black ink with a cotton swab. After applying 1% acetic acid to each core, the left and right cores from each location are placed in a single container. This method curbs pathology expenses and maintains tumor location information.     

Intranasal or oral immunization of inbred and outbred mice with murine or human rotavirus VP6 proteins protects against viral shedding after challenge with murine rotaviruses

Intranasal (i.n.) administration of an Escherichia coli-expressed chimeric VP6 protein from the EDIM strain of murine rotavirus to adult BALB/c (H-2(d)) mice along with LT(R192G), an attenuated mutant of the mucosal adjuvant E. coli heat-labile toxin, has been found to consistently stimulate ca. 99% reductions in rotavirus shedding after subsequent EDIM challenge. This study was designed to determine the robustness of this protection, i.e. can VP6 immunization consistently protect against shedding in this model, thus, providing an indication of its potential as a vaccine. Intranasal immunization with two 8.8 microg doses of EDIM VP6 and 10 microg of LT(R192G) was found to stimulate 99% reductions in EDIM shedding in four additional strains of inbred mice belonging to three haplotypes, i.e. DBA/2 (H-2(d)), C57BL/6 (H-2(b)), 129 (H-2(b)) and C3H (H-2(k)). Protection stimulated against EDIM antigen shedding following i.n. immunization with VP6 from the human CJN strain was less (P=0.02) than induced by EDIM VP6 (86% versus 99%), but no further loss of protection was observed when the dose of CJN VP6 was reduced 100-fold. Protection against EDIM shedding was also maintained after i.n. immunization of three strains of outbred mice (CF-1, CD-1 and Swiss Webster) with either EDIM or CJN VP6, i.e. EDIM VP6 immunization reduced EDIM shedding by 99% while CJN VP6 immunization produced reductions of 86-96%. Protection stimulated by oral immunization of BALB/c mice with two 8.8 microg doses of either VP6 chimera plus LT(R192G) was not significantly different from that induced by i.n. immunization. Finally, protection found after either oral or i.n. immunization with EDIM or CJN VP6 was no different when the mice were challenged with McN, another strain of murine rotavirus. These results support further evaluation of VP6 as a vaccine.     

Parkinson's disease, CYP2D6 polymorphism, and age

OBJECTIVE: PD may be caused by genetic susceptibility to neurotoxins. CYP2D6 is a candidate gene for PD because it regulates drug and toxin metabolism, but association studies have been inconsistent. The aim of this study was to test if the CYP2D6*4 allele (poor metabolizer phenotype) is associated with earlier age at onset. METHODS: Five hundred seventy-six patients with PD and 247 subjects without PD were studied using standard diagnostic, genotyping, and statistical techniques. RESULTS: Surprisingly, mean onset age was significantly later in *4-positive patients. Frequency of *4 was significantly higher in late-onset PD than early-onset PD. When early- and late-onset PD were analyzed separately, *4 had no effect on onset age; hence, the association with delayed onset was likely an artifact of an elevated *4 frequency in late-onset PD. Contrary to a common assumption that CYP2D6 frequencies do not change with age, *4 frequency rose significantly with advancing age, both in patients with PD (from 0.16 at mean age of 56.5 years to 0.21 at mean age of 72) and subjects without PD (from 0.09 at mean age of 45.5 years to 0.21 at mean age of 72). *4 Frequencies in patients with early- and late-onset PD, although different from each other, were in agreement with similarly aged subjects without PD, suggesting the elevated *4 frequency in late-onset PD was likely an age effect, unrelated to PD. CONCLUSION: The CYP2D6*4 allele is not associated with earlier PD onset. *4 May be associated with survival. Inconsistent results from allelic association studies may have been due to an unrecognized age effect.     

Sensitivity of Escherichia coli (MutT) and human (MTH1) 8-oxo-dGTPases to in vitro inhibition by the carcinogenic metals, nickel(II), copper(II), cobalt(II) and cadmium(II)

The toxicity of Ni(II), Co(II) and Cu(II) in animals, and that of Cd(II) in cultured cells, has been associated with generation of the promutagenic lesion 8-oxo-7,8-dihydroguanine (8-oxoguanine) in DNA, among other effects. One possible source of this base may be 8-oxo-7,8- dihydro-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP), a product of oxidative damage to the nucleotide pool, from which it is incorporated into DNA. To promote such incorporation, the metals would have to inhibit specific cellular 8-oxo-dGTPases that eliminate 8-oxo-dGTP from the nucleotide pool. The present study was designed to test such inhibition in vitro on 8-oxo-dGTPases from two different species, the human MTH1 protein and Escherichia coli MutT protein. In the presence of Mg(II), the natural activator of 8-oxo-dGTPases, all four metals were found to inhibit both enzymes. For MTH1, the IC50 values (+/- SE; n = 3-4) were 17 +/- 2 microM for Cu(II), 30 +/- 8 microM for Cd(II), 376 +/- 71 microM for Co(II) and 801 +/- 97 microM for Ni(II). For MutT, they were 60 +/- 6 microM for Cd(II), 102 +/- 8 microM for Cu(II), 1461 +/- 96 microM for Ni(II) and 8788 +/- 1003 microM for Co(II). Thus, Cu(II) and Cd(II) emerged as much stronger inhibitors than Ni(II) and Co(II), and MTH1 appeared to be generally more sensitive to metal inhibition than MutT. Interestingly, in the absence of Mg(II), the activity of the enzymes could be restored by Co(II) to 73% of that with Mg(II) alone for MutT, and 34% for MTH1, the other metals being much less or non-effective. The difference in sensitivity to metal inhibition between the two enzymes may reflect the differences in the amino acid ligands, especially the cysteine ligand, outside their evolutionarily conserved Mg(II)-binding active sites, which might indicate predominantly non-competitive or uncompetitive mechanism of the inhibition. The overall results suggest that inhibition of 8-oxo- dGTPases may be involved in the mechanisms of induction of the 8- oxoguanine lesion in DNA by the metal ions studied, especially the non- redox-active Cd(II) cation.      

Cardiac rhabdomyomas and their association with tuberous sclerosis

A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas.