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61.
PM Petersen NE Skakkebaek A Giwercman 《Canadian Metallurgical Quarterly》1998,106(1):24-34; discussion 34-6
This paper reviews current knowledge about the effect of testicular germ cell cancer (TGCC) on gonadal function and of cancer treatment on spermatogenesis and Leydig cell function. It is well documented that testicular cancer is associated with impaired spermatogenic function and some patients already have impairment of Leydig cell function before orchidectomy. The degree of spermatogenic dysfunction is higher than what can be explained by local tumour effect and by a general cancer effect, since patients with other malignant diseases have normal, or only slightly decreased, semen quality. Furthermore, sperm counts after orchidectomy are further reduced to less than half of the values in healthy men, even in patients cured from the cancer disease after orchidectomy alone. These observations are supported by histological investigations which have shown a high prevalence of abnormalities of spermatogenesis in the contralateral testis in patients with unilateral TGCC. The association between testicular cancer and poor gonadal function is very interesting both from a biological and from a therapeutic point of view. Firstly, the increase in incidence of testicular cancer has been suggested to be associated with a general decline in male reproductive health and it seems likely that the development of TGCC shares common aetiologic factors with development of other types of testicular dysfunction. This suggestion is supported by the observation that men with various types of gonadal dysfunction such as testicular dysgenesis, androgen insensitivity syndrome, and cryptorchidism have increased risk of testicular cancer. Secondly, the general cure rate in patients with testicular cancer exceeds 90% and the quality of life, including fertility aspects, is therefore important in the management of these patients. Spermatogenesis is already so severely impaired before treatment that fertility is lower than in healthy men. Moreover, radiotherapy and chemotherapy both induce dose-dependent impairment of spermatogenesis and recovery of spermatogenesis after treatment may be long lasting even more than five years in some patients. Sufficient androgen production is seen in the majority of the patients, but some patients suffer from testosterone deficiency. The effect of chemotherapy on Leydig cell function also seems to be dose-dependent. In conclusion there is no doubt that testicular cancer is associated with poor gonadal function even before treatment. Furthermore, the treatment of testicular cancer may have a serious impact on the gonadal function in these patients, most of whom are in the reproductive age. Moreover, the epidemiological and clinical data indicate a common aetiology between testicular germ cell cancer and other abnormalities in male reproductive health (such as infertility and cryptorchidism). These observations are in agreement with the suggestions of hormonal involvement in the aetiology of testicular cancer. Generally, men with TGCC need counselling about their reproductive function with respect to semen cryopreservation, chance of recovery of spermatogenesis, fertility, and the possible need for androgen replacement. 相似文献
62.
L Yu L Orlandi P Wang MS Orr AM Senderowicz EA Sausville R Silvestrini N Watanabe H Piwnica-Worms PM O'Connor 《Canadian Metallurgical Quarterly》1998,273(50):33455-33464
We have previously demonstrated that UCN-01, a potent protein kinase inhibitor currently in phase I clinical trials for cancer treatment, abrogates G2 arrest following DNA damage. Here we used murine FT210 cells, which contain temperature-sensitive Cdc2 mutations, to determine if UCN-01 abrogates G2 arrest through a Cdc2-dependent pathway. We report that UCN-01 cannot induce mitosis in DNA-damaged FT210 cells at the non-permissive temperature for Cdc2 function. Failure to abrogate G2 arrest was not due to UCN-01-inactivation at the elevated temperature because parental FM3A cells, which have wild-type Cdc2, were sensitive to UCN-01-induced G2 checkpoint abrogation. Having established that UCN-01 acted through Cdc2, we next assessed UCN-01's effect on the Cdc2-inhibitory kinase, Wee1Hu, and the Cdc2-activating phosphatase, Cdc25C. We found that Wee1Hu was indeed inactivated in UCN-01-treated cells, possibly just prior to Cdc2 activation and entry of DNA-damaged cells into mitosis. This inhibition appeared, however, to be a consequence of a further upstream action since in vitro studies revealed purified Wee1Hu was relatively resistant to UCN-01-inhibition. Consistent with such an upstream action, UCN-01 also promoted the hyperphosphorylation (activation) of Cdc25C in DNA-damaged cells. Our results suggest that UCN-01 abrogates G2 checkpoint function through inhibition of a kinase residing upstream of Cdc2, Wee1Hu, and Cdc25C, and that changes observed in these mitotic regulators are downstream consequences of UCN-01's actions. 相似文献
63.
Postcontrast MR angiography complements the standard spinal MR imaging study by improving detection and display of normal and abnormal intradural vessels, primarily veins. Detection of abnormal veins facilitates diagnosis of spinal vascular malformations and vascular tumors. The most useful application has been in screening for spinal dural arteriovenous fistula, in which MR angiography demonstrates the medullary vein into which the fistula drains, thus allowing noninvasive identification of the spinal level of the fistula. 相似文献
64.
EA Hassink AT Brugman-Boezeman LM Robbroeckx PN Rieu EM van Kuyk PM Wels C Festen 《Canadian Metallurgical Quarterly》1998,13(5-6):377-383
Parents play a crucial role in the life of a child suffering from an anorectal malformation (ARM), since their guidance contributes to the degree to which the child learns to cope with his or her disability. We investigated whether they experience stress in parenting such a child and also attempted to identify somatic or behavioral characteristics in the child that influence the stress of parenting. The parents of 109 children (69 males, 40 females; median age 5.9 years, range 1-18 years) with an ARM (58 low, 10 intermediate, 41 high) were studied. The Nijmegen Questionnaire on Child-rearing Situations (NQCS) was used to investigate the existing parenting situation. Behavioral characteristics of the children were studied by means of the Child Behaviour Checklist (CBCL) and the Teacher Report Form (TRF). In a semi-structured interview, we investigated how parents experienced the implications of the disability in everyday life with their child. Our study showed that as far as the perception of parenting stress is concerned, parents of children with an ARM do not differ from those with healthy primary-school children. Within the group of parents with ARM-afflicted children, the parents of older, incontinent children experienced relatively more stress, especially when the child concerned was male. With regard to the children's behavior, the parents and teachers under investigation did not report a higher than normal incidence of deviant behavior. However, when individual parents observed difficult behavior in their child, they found it harder to deal with than the incontinence for feces. Regarding the implications of the disorder for their everyday lives, parents were concerned and indicated a need for specific counselling. We conclude that having a child with a somatic affliction, in this case an ARM, does not automatically imply that the parents experience child-rearing problems. However, certain groups of parents are more at risk, i.e., parents with older, incontinent sons and parents with children exhibiting behavioral problems. In addition, our study shows that parents do have difficulties in coping with the implications of the disorder and express a need for support. We feel that patient care can be improved if aid is tailored to these specific problems. 相似文献
65.
Tumor cells that express a fusion gene comprised of Escherichia coli cytosine deaminase (CD) and herpes simplex virus type 1 thymidine kinase (TK) sequences exhibit activation of and subsequent killing by the normally innocuous prodrugs 5-fluorocytosine and ganciclovir (Rogulski et al., Hum. Gene Ther., 8: 73-85, 1997). To target localized expression of this therapeutic gene, we have constructed a recombinant adenovirus containing the CD-TK fusion gene under the control of a human inducible heat shock protein 70 promotional sequence. Strong expression of the fusion gene product was induced by heating at 41 degrees C for 1 h. Expression levels obtained were dependent on the multiplicity of infection used and the incubation time after heat shock. Heat-induced expression of the CD-TK protein significantly reduced the survival of PC-3 cells in the presence of both 5-fluorocytosine and ganciclovir. These studies represent a novel form of gene therapy for the transduction and regulation of a double suicide gene in tumor cells and may provide a unique application for hyperthermia in cancer therapy. 相似文献
66.
Cells that die by apoptosis need to be removed before lysis to preserve tissue integrity and function. Recent studies have identified components of the uptake machinery used by phagocytes, but much remains to be learnt, particularly about the recognition mechanisms and their coupling to the uptake machinery. 相似文献
67.
R Garraway WG Young T Daley D Harbrow PM Bartold 《Canadian Metallurgical Quarterly》1998,69(12):1325-1336
Early studies have demonstrated that implantation of laboratory preparations of demineralized freeze dried bone (DFDB) into the thigh muscle of mice induces ectopic osteoinduction. However, with the development of commercial preparations of DFDB for clinical use, concerns have been raised as to the osteoinductive properties of such preparations. The aim of this study was to investigate the osteoinductive potential of some commercial preparations of DFDB compared to a newly developed product which incorporates DFDB into a collagen sponge. Commercial preparations of DFDB or the DFDB/collagen sponge were inserted into the thigh muscles of 60 adult Swiss CD-1 mice. At the completion of each experimental period (7, 14, 30, 90 and 180 days), the animals were sacrificed, and the hindquarters of the mice were radiographed. The area where each graft had been placed was then excised, processed for light microscopy, and stained with hematoxylin and eosin or von Kossa's stain. Histological analysis of the DFDB/collagen sponges demonstrated significant remineralization which increased with time. Remineralization of the DFDB/collagen sponges was verified by radiographs which showed a significant increase in radiopacity over time. There was no radiographic evidence of mineralized tissue formation or remineralization in any of the commercial DFDB samples studied. At all time points studied, histological analyses failed to show evidence of bone formation for any of the preparations. The results suggest that commercially available DFDB is not osteoinductive in the murine model and question the use of such materials in clinical periodontics. The results found for the DFDB/collagen sponge indicate a different mechanism of activity from DFDB as evidenced by its rapid remineralization. The role this remineralization process has in osteoinduction is unknown and requires further study. 相似文献
68.
69.
MA Fischl DD Richman C Flexner MF Para R Haubrich A Karim P Yeramian J Holden-Wiltse PM Meehan 《Canadian Metallurgical Quarterly》1997,15(1):28-34
A significant restriction was demonstrated in the ability of herpes simplex virus type 1 virion host shutoff (vhs) mutant viruses to invade the corneal epithelium. Viral replication and invasion was confined to the areas of the cornea which were scarified prior to infection. Differences between wild-type and vhs mutant replication in corneas in vivo were 100- to 1000-fold at all timepoints postinfection. Smaller but still significant growth restrictions were observed in cultured corneal cells. This difference between in vitro and in vivo is not likely to be due to differences in cell cycle status since vhs-induced RNA degradation can occur in both cycling and noncycling cells in vitro. The vhs function is therefore important for invasion of the cornea and secondarily the nervous system and is thereby required for efficient establishment of latency. 相似文献
70.