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41.
In the human hypothalamus, arginine-vasopressin (AVP) is produced for a major part by the neurones of the supraoptic nucleus (SON). Since plasma AVP levels in men were reported to be higher than those of women and we did not find a sex difference in the neurone number, a higher vasopressinergic neurone activity was supposed to be present in the SON of men. Therefore we studied the size of the Golgi-apparatus (GA), which has been demonstrated previously to be a sensitive parameter for protein synthetic ability of neurones, in 15 men and 17 women ranging in age from 29 to 94 years. A polyclonal antibody against immunoaffinity purified MG-160, a sialoglycoprotein of the medial cisternae of the GA was applied on paraffin-embedded sections containing the dorsolateral SON (dl-SON) from which 90-95% of neurones are vasopressinergic. SON areas that contain oxytocin (OT) cells were excluded on the basis of adjacent sections stained with a monoclonal antibody against OT. By means of an image analysis system the size of the GA and the cellular profile area were determined in dl-SON neurones with a nucleolus. Our results showed indeed an age-dependent sex difference in the size of the GA that appeared to be twice as large in young men (< or = 50 years old) than in young women of the same age. The size of the GA increased with age in women but not in men. In addition, the mean cell profile area, another measure for neuronal activity, was significantly larger in young men than in young women and was in old women larger than in young women. In conclusion, these data show the presence of a sex-dependent age-difference in the activity of vasopressinergic neurones in dl-SON which may relate to differences in AVP and sex hormone levels and kidney AVP receptors. 相似文献
42.
Propionibacterium as a cause of postneurosurgical infection in patients with dural allografts: report of three cases 总被引:6,自引:0,他引:6
OBJECTIVE AND IMPORTANCE: Although Propionibacterium acnes is a common inhabitant of human skin, it is an uncommon pathogen in postoperative infections. We report three cases of postoperative wound infection/osteomyelitis caused by P. acnes. CLINICAL PRESENTATION: Three patients underwent craniotomy for a supratentorial meningioma and had a dural allograft at the time of closure. The patients presented several weeks after surgery with clinical evidence of a wound infection. INTERVENTION: All patients were diagnosed with P. acnes infection and treated for this pathogen with appropriate antibiotics. The bone flap was removed in two patients. After antibiotic therapy, all patients demonstrated no further evidence of infection. CONCLUSION: To our knowledge, this is the first published report of P. acnes infection in patients with a dural substitute. The source of infection cannot be confidently ascertained; however, two patients had strains of P. acnes from one brand of graft, which were indistinguishable by pulsed field gel electrophoresis typing. 相似文献
43.
Randall ME Barrett RJ Spirtos NM Chalas E Homesley HD Lentz SL Hanna M 《International journal of radiation oncology, biology, physics》1996,34(1):139-147
PURPOSE: To determine outcomes and treatment toxicities in patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAI). METHODS AND MATERIALS: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIIA (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papillary (n = 21, 50%); other (n = 21, 50%); Grade 1 (n = 1, 2%); 2 (n = 14, 33%); 3 (n = 27, 54%); residual disease after initial surgery (present: n = 23, 55%; absent: n = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients. RESULTS: Of 37 patients with known SRA status after chemotherapy, 21 (57%) were grossly positive, 4 (11%) were microscopically positive, and 12 (32%) were negative. Based on measurements recorded following initial laparotomy and surgical reassessment, progression during chemotherapy was noted in 40%, stage disease in 37%, and objective response in 23%. Toxicity during hyperfractionated WAI was limited and reversible. No patient beginning WAI failed to complete or required a significant treatment break. Following WAI, six patients underwent laparotomies for abdominal symptoms; five had recurrent disease. Five additional patients were managed conservatively for small bowel obstruction (SBO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more likely to require management for gastrointestinal morbidity (p = 0.0021). Considering all eligible patients, median disease-free and overall survivals were 18.5 and 39 months, respectively. Considering patients completing chemotherapy and WAI, median disease-free and overall survivals were 24 and 46 months, respectively. CONCLUSIONS: (a) Disease progression occurred within three cycles of cisplatin and cyclophosphamide chemotherapy in 40% of patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma. (b) Following limited chemotherapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radiation-related toxicity was observed in only three patients (8.6%) in the absence of recurrent disease. Late gastrointestinal morbidity was significantly associated with the administration of a pelvic radiotherapy (RT) boost. (d) Short duration chemotherapy followed by SRA and hyperfractionated WAI without a pelvic boost is a promising management option for patients with optimal Stage III ovarian cancer. A Phase III trial will be necessary to determine how this treatment strategy compares with chemotherapy or RT alone in this patient population. 相似文献
44.
D F Swaab 《Neurobiology of aging》1991,12(4):317-324
In organs other than the brain, cell activation seems to increase "wear and tear," e.g., by increased free-radical formation, and so to cause an increased rate of aging. However, activation of nerve cells within the physiological range seems to lead to maintenance of neurons during aging and in Alzheimer's disease, possibly by preferentially stimulating the action of protective mechanisms such as DNA repair. This "use it or lose it" principle might explain why certain neurons degenerate in aging or Alzheimer's disease while others do not, and why recovery of various neuronal systems during aging has been obtained by restoration of the missing stimulus. Consequently, neuronal activation might provide a means of prolonging its optimal function for the full length of our natural life span. 相似文献
45.
Fernando Santos James C. M. Chan James D. Hanna Kazuhiko Niimi Richard J. Krieg Jr Martha D. Wellons 《Pediatric nephrology (Berlin, Germany)》1992,6(3):262-266
To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX,n=40), GH-treated nephrectomized rats (NX+GH,n=18), sham-operated rats fed ad libitum (SHAMAL,n=27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF,n=10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean±SEM) 49±3 and 54±4 mg/dl, respectively, compared with 16±4 and 19±0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0±3.3 g) and length (3.5±0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2±4.0 g,P<-0.0001 and 4.1±0.2 cm,P<-0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2±5.0 g) and length (3.4±0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81±2 mg/dl versus 55±3 mg/dl in SHAMAL (P0.0001), was not increased in the NX+GH group, 87±3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities. 相似文献
46.
47.
Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type. 总被引:6,自引:0,他引:6
William D Foulkes Kelly Metcalfe Ping Sun Wedad M Hanna Henry T Lynch Parviz Ghadirian Nadine Tung Olufunmilayo I Olopade Barbara L Weber Jane McLennan Ivo A Olivotto Louis R Bégin Steven A Narod 《Clinical cancer research》2004,10(6):2029-2034
PURPOSE: BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied. EXPERIMENTAL DESIGN: ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America. There were 208 BRCA1 mutation carriers, 88 BRCA2 carriers, and 804 women without a known mutation. We stratified the patients by mutation status, grade, age, and histological type and calculated the percentage of ER-positive tumors within each stratum. RESULTS: BRCA1 mutation carriers were more likely to have ER-negative breast cancers than were women in other groups, after adjustment for age, grade, and histological subtype (P < 0.001). Only 3.9% of BRCA1-related breast cancers were ER-positive cancers occurring in women in their postmenopausal years. The direction and magnitude of the change in ER status with increasing age at diagnosis in BRCA1 carriers was significantly different from in BRCA2 carriers (P(intercept) = 0.0002, P(slope) = 0.04). Notably, changes in ER status with age at diagnosis for BRCA1 carriers and noncarriers were almost identical (P(slope) = 0.98). CONCLUSIONS: The strong relationship between the presence of a BRCA1 mutation and the ER-negative status of the breast cancers is neither a consequence of the young age at onset nor the high grade but is an intrinsic property of BRCA1-related cancers. The ER-negative status of these cancers may reflect the cell of origin of BRCA1-related cancers. 相似文献
48.
Wayne L. Furman John H. Rodman Margaret E. Tonda Xiaolong Luo Bettye Arnold Neyssa Marina Leslie Garrison Roberta Hanna Charles B. Pratt William H. Meyer 《Cancer chemotherapy and pharmacology》1997,41(3):229-236
A hemopoietin with the ability to accelerate both platelet and granulocyte recovery after intensive chemotherapy would have
great clinical utility. The recombinant fusion protein composed of human granulocyte-macrophage colony-stimulating factor
and interleukin-3 (PIXY321), showed some promise in early adult trials. However, studies for pediatric patients are limited,
and there are no systematic data on the pharmacokinetics of PIXY321 given over prolonged periods at current dosage levels.
Purpose: To determine the safety, clinical effects and plasma concentrations of increasing doses of PIXY321 in children treated with
myelosuppressive chemotherapy. Methods: A total of 39 children with relapsed or high-risk solid tumors were enrolled in this phase I/II study. PIXY321 was administered
once or twice daily by subcutaneous injection in total doses of 500 to 1000 μg/m2 per day for 14 days after each course of chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). Pharmacokinetic
studies were performed on day 1 of the first course in 33 patients and repeated on day 14 in 13 patients (once-daily schedule
only). Results: Although mild local skin reactions and fever were frequent, no dose-limiting toxicity was identified at the maximum dose
studied (1000 μg/m2 per day). There were no statistically significant differences in chemotherapy-induced hematologic toxicity with increasing
doses of PIXY321 or with twice-daily vs once-daily dosing. On day 1, the median PIXY321 clearance was 657 ml/min per m2 (range 77–1804 ml/min per m2) and the median half-life was 3.7 h (range 2.1–20.8 h). On day 14, clearance increased in all patients studied (median increase
63%), with a corresponding decrease in the median 12-h concentration (from 1.2 to 0.25 ng/ml). Maximum concentrations were
<1 ng/ml in 81% of patients, and only two patients had maximum plasma concentrations equivalent to those required for consistent
activity in vitro. Conclusions: The recombinant fusion protein PIXY321 proved safe in children treated with myelosuppressive ICE chemotherapy but had no
demonstrable clinical benefits. The pharmacokinetic studies suggest that the observed lack of hematologic benefit may be explained
by low plasma concentrations resulting from increased clearance with prolonged administration. Moreover, the significant increase
in PIXY321 systemic clearance in the absence of increased circulating myeloid cells suggests that the upregulation of either
extravascular compartment hematopoietic progenitor cells or nonhematopoietic cells may play an important role in controlling
circulating concentrations of this unique cytokine. These findings highlight the importance of a thorough assessment of the
systemic disposition of cytokines when determining the dose and schedule necessary to achieve clinical activity in patients.
Received: 29 January 1997 / Accepted: 9 May 1997 相似文献
49.
The extracellular signal-regulated protein kinase-1 and -2 (ERK1 and ERK2), also referred to as the p44/42 mitogen-activated protein kinase (p44/42 MAP kinase), plays an essential role in neuronal signal transduction, but its function involved in nociceptive response has not been deeply studied yet. Here we report immunohistochemical evidence that p44/42 MAPK might be critical in nociceptive response. We found that after formalin was injected into the perioral skin of the upper lip of mice, the number of activated p44/42 MAPK-like immunoreactive neurons was significantly increased in the laminae I and II of the caudal subnucleus of the trigeminal spinal nucleus (Sp5C). The positive neurons and fibers were mostly concentrated in the middle portion of Sp5C dorsoventrally, where the afferent fibers innervating the skin of the upper lip are terminated. The reactive products were localized in perikarya, dendrites, nuclei, and diffusely in the neuropil. The present result suggests that p44/42 MAPK may be important in the transmission and modulation of noxious information in Sp5C. 相似文献
50.
Fernández-Guasti A Kruijver FP Fodor M Swaab DF 《The Journal of comparative neurology》2000,425(3):422-435
The present study reports for the first time the distribution of androgen receptor immunoreactivity (AR-ir) in the human hypothalamus of ten human subjects (five men and five women) ranging in age between 20 years and 39 years using the antibody PG21. Prolonged postmortem delay (72:00 hours) or fixation time (100 days) did not influence the AR-ir. In men, intense nuclear AR-ir was found in neurons of the horizontal limb of the diagonal band of Broca, in neurons of the lateromamillary nucleus (LMN), and in the medial mamillary nucleus (MMN). An intermediate nuclear staining was found in the diagonal band of Broca, sexually dimorphic nucleus of the preoptic area, paraventricular nucleus, suprachiasmatic nucleus, ventromedial nucleus, and infundibular nucleus, whereas weaker labeling was found in the bed nucleus of the stria terminalis, medial preoptic area, dorsal and ventral zones of the periventricular nucleus, supraoptic nucleus, and nucleus basalis of Meynert. In most brain areas, women revealed less staining than men. In the LMN and the MMN, a strong sex difference was found. Cytoplasmic labeling was observed in neurons of both sexes, although women showed a higher variability in the intensity of such staining. However, no sex differences in AR-ir were observed in the bed nucleus of the stria terminalis, the nucleus basalis of Meynert, or the islands of Calleja. Species differences and similarities of the AR-ir distribution are discussed. The present results suggest the participation of androgens in the regulation of various hypothalamic processes that are sexually dimorphic. 相似文献