Immune function did not decline with aging in apparently healthy, well-nourished women

Nutrition plays a crucial role in immune function. Most studies on age-associated changes in immunocompetence in healthy adults did not examine the nutritional status of participants extensively. Inadequate nutritional status may confound the relationship of aging and immune response. The purpose of this study was to examine age-related changes in parameters of acquired and innate immunity in healthy and generally well-nourished older (62-88 years) versus younger (20-40 years) women. Subjects were screened for participation using the health criteria of the SENIEUR protocol as well as a number of nutrition criteria related to undernutrition, and protein, iron, vitamin B12, and folate status. Young and old women did not differ in total T (CD3+), T-helper (CD4+), or T-cytotoxic (CD8+) cell number. However, older women tended to have lower T-cell proliferation response to concanavalin A (P < 0.10) and significantly reduced response to phytohemagglutinin (P < 0.05). No age-related changes were noted in natural killer cell number or cytotoxicity. Phagocytosis and subsequent oxidative burst activity also did not differ between young and old women. Most immune parameters were not compromised with aging in this cohort of apparently healthy, well-nourished women. These findings highlight the importance of simultaneous examination of health and nutritional status in studies of immune function with aging.     

The use of ratings of perceived exertion for regulating exercise levels in rowing ergometry

The purpose of this study was to examine the validity of the use of ratings of perceived exertion (RPE) to estimate and regulate exercise intensity during rowing ergometry. Nine competitive male rowers [mean age 28.6 years, (SD 6.3)] completed two rowing trials on an ergometer. The first trial (estimation) consisted of an incremental protocol designed to elicit a range of work outputs (WO) and heart rates (HR). The subjects indicated their perception of effort using a 15-point scale at each intensity level. In the second trial (production), 7–14 days later, the subjects were asked to produce exercise intensities corresponding to five levels of RPE: 15,11,17,13, and 19. Data analysis revealed high Pearson correlation coefficients between HR and RPE (r = 0.95,P < 0.01) and WO and RPE (r = 0.96,P < 0.01) during the estimation trial. In addition, significant correlations (P < 0.01) were obtained between the estimation and production trials for HR (r = 0.82) and WO (r = 0.84). Posthoc analysis of variance revealed that the observed differences in mean HR were not significant (P > 0.05) at three of the five intensity levels (RPE 15,17 and 19), but were at the two lowest RPE levels (11 and 13). Significant mean differences in WO were seen at all but RPE 17. These data support the validity of the RPE scale as a measure of physiological strain among competitive male rowers, and offer support for its use as a method of regulating the intensity of rowing ergometry, especially at higher levels.     

Multilineage potential of homozygous stem cells derived from metaphase II oocytes

Human stem cells derived from human fertilized oocytes, fetal primordial germ cells, umbilical cord blood, and adult tissues provide potential cell-based therapies for repair of degenerating or damaged tissues. However, the diversity of major histocompatibility complex (MHC) antigens in the general population and the resultant risk of immune-mediated rejection complicates the allogenic use of established stem cells. We assessed an alternative approach, employing chemical activation of nonfertilized metaphase II oocytes for producing stem cells homozygous for MHC. By using F1 hybrid mice (H-2-B/D), we established stem cell lines homozygous for H-2-B and H-2-D, respectively. The undifferentiated cells retained a normal karyotype, expressed stage-specific embryonic antigen-1 and Oct4, and were positive for alkaline phosphatase and telomerase. Teratomatous growth of these cells displayed the development of a variety of tissue types encompassing all three germ layers. In addition, these cells demonstrated the potential for in vitro differentiation into endoderm, neuronal, and hematopoietic lineages. We also evaluated this homozygous stem cell approach in human tissue. Five unfertilized blastocysts were derived from a total of 25 human oocytes, and cells from one of the five hatched blastocysts proliferated and survived beyond two passages. Our studies demonstrate a plausible "homozygous stem cell" approach for deriving pluripotent stem cells that can overcome the immune-mediated rejection response common in allotransplantation, while decreasing the ethical concerns surrounding human embryonic stem cell research.     

Interacting effects of temperature and extracellular calcium on the spontaneous release of transmitter at the frog neuromuscular junction

1. Temperature has a characteristic effect on the frequency of m.e.p.p.s at the frog neuromuscular junction; the spontaneous release of transmitter is not affected by temperature changes below 10 degrees C whereas the system is highly temperature-sensitive above 20 degrees C.2. A very similar result is obtained when the experiment is repeated in saline containing Ca(2+) buffered at 5 x 10(-7)M, suggesting that it is unlikely that the major action of temperature is to cause an increase in Ca(2+) influx.3. It is suggested that the main effect of temperature at the presynaptic terminals is a modification of [Ca(2+)](i) by an action on intracellular Ca(2+) stores.4. The interacting effects of theophylline and the divalent cation ionophore A23187 on m.e.p.p. frequency suggest that intracellular Ca(2+) stores, in addition to the mitochondria, may well be of importance in controlling [Ca(2+)](i).5. Changes in [Ca(2+)](o) produce a modification of m.e.p.p. frequency, but the details of the response are dependent on temperature. The spontaneous release of transmitter is most sensitive to an increase in [Ca(2+)](o) at 23 degrees C, whereas the greater effect is found at 13 degrees C when [Ca(2+)](o) is lowered.6. It is suggested (i) that m.e.p.p. frequency is primarily determined by [Ca(2+)](i) at the presynaptic terminals, (ii) that the presynaptic terminals are normally able to maintain [Ca(2+)](i) almost constant in spite of increases in Ca influx associated with ionophore treatment or with a rise in [Ca(2+)](o). However, if the steady-state position of [Ca(2+)](i) is previously raised by an increased efflux from intracellular stores (produced by elevated temperature or theophylline pre-treatment), increased influx causes a rise in both [Ca(2+)](i) and in m.e.p.p. frequency.     

The aniridia-Wilms tumor association: The critical role of chromosome band 11p13

The role of del (11)(p13) as a cause of aniridia, with and without Wilms tumor, is strengthened by demonstration of this chromosome aberration in 3 patients: monozygous twin girls, both of whom have aniridia and mental retardation and one of whom has a Wilms tumor; and an unrelated boy with aniridia and ambiguous genitalia. The break points defining the interstitial deletion for the twins are 11p13 and 11p15.1, while for the boy they are 11p1302 and 11p14.1. These patients and their karyotypes substantiate the critical importance of chromosome band 11p13 (or its hemizygous representation) in the development of aniridia and an associated Wilms tumor diathesis, as had been suggested previously (Riccardi VM, Sujansky E, Smith AC, Francke U, (1978): Pediatrics 61, 604-610).     

Phosphorylated KDR is expressed in the neoplastic and stromal elements of human renal tumours and shuttles from cell membrane to nucleus

Vascular endothelial growth factor (VEGF)-A is an important angiogenic factor in establishing the vasculature in renal cell carcinomas (RCCs). Since little is known about VEGF signalling in RCCs, the profile of phosphorylated KDR (pKDR) has been investigated and the intracellular location of the receptor has been examined in the present study. Using two monoclonal antibodies raised against the phosphorylated KDR epitopes (Y1059 and Y1214) known to mediate different VEGF functions, together with a commercial anti-KDR antibody and immunohistochemistry, the expression of pKDR was investigated in a series of normal (n = 25) and neoplastic kidneys (n = 54; clear cell n = 35; papillary n = 10; oncocytomas n = 8). pKDR was present in many tissue elements of both normal and neoplastic renal tissues, with strong expression in the cell membrane, cytoplasm, and nuclei of normal kidney and tumour cells, as well as endothelial cells in tumours of all histological types. Patterns and intensity were similar using both anti-pKDR antibodies. There was no significant correlation in clear cell carcinomas between pKDR expression and age (p = 0.57), tumour size (p = 0.2), gender (p = 0.59), grade (p = 0.2) or histological type (p = 0.36). To delineate further the intracellular processing that might account for the cellular distribution, confocal microscopy was also performed. Antibodies to the different phosphorylated epitopes demonstrated different intracellular staining patterns. This study shows that pKDR is present in a wide variety of renal tumours, suggesting that anti-VEGF therapy might have direct effects on tumour cells. It further suggests that cells traffic pKDR depending on the precise KDR tyrosines that are autophosphorylated in a manner that enables receptor activation to result in different functions.