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This study addresses the relationship between subjective evaluation of memory and objective cognitive dysfunction in old-old age. In a sample of 164 participants (mean age 91.9, range 87–106) drawn from a nationwide Israeli survey, 42% evaluated their memory positively and 30% negatively. Participants were no more concerned about being forgetful than younger adults. Subjective memory and concern about forgetfulness were not significantly correlated with cognitive dysfunction. Sociodemographic, physical, and well-being characteristics explained three times more variance of cognitive dysfunction than of subjective memory. The study suggests that subjective memory among old-old people who can undergo a survey interview may not reflect actual cognitive dysfunction. Apparently, the role of subjective evaluation resides in other areas of adaptation to very old age.

In order to test the hypothesis that retirement would be particularly stressful for this highly motivated cohort, forty retired members of Israeli kibbutzim (22 men, 18 women) were interviewed in an open—ended fashion, concerning their early history, their decision to join the kibbutz, their working life, and their post-retirement adaptation. Little evidence of significant psychopathology was found, and those instances were for the most part traceable to traumatic rearing in the family of orientation, rather than to current, post-retirement losses and insults. These findings are discussed in terms of the Habitat-Niche model developed by Gutmann.

The purpose of this study was to examine the factors that make for 'successful aging'. In particular, we examined the relationship between the degree of religious or traditional observance on overall life satisfaction, health, function, and activity of an elderly population. The subjects chosen were aged from 68 to 75 and were divided into two groups: 37 percent were traditionally observant ('traditional') and 67 percent religiously observant ('religious'). Overall the sociodemographic features of both groups were similar. The results of the study did show, however, that the most significant factors in influencing the subjects' life satisfaction were religiosity and functional adequacy. Our conclusions from these findings indicate that the religious observant elderly person, who is religiously active, retains a social status that earns him respect because of this activity. This status even provides him with a source of power in his social group, as a result of which he functions more effectively and is more satisfied with life.

Parathyroid hormone (PTH) is the main hormone controlling calcium concentration in the extracellular fluid (ECF) through its biological activity on bone, kidney and intestine. However, data published over the last two decades indicate that PTH may act as an immunomodulator. The purpose of the present review is to summarize the effects of PTH on various immune functions. Polymorphonuclear leukocytes of patients with chronic renal failure (CRF) and elevated blood levels of PTH showed impaired migration, reduced phagocytic and bactericidal activity, and inhibited granulocyte chemotaxis. Antibody production and T and B lymphocyte proliferation are affected by PTH, both in vivo and in vitro. Possible implications of the involvement of PTH and its fragments in CRF are discussed.

The relationship among daily cigarette consumption, washed and non-washed RBC filterability time (FT) as an indicator of erythrocyte deformability and echocardiographic left ventricular mass (LVM) were examined in 25 clinically healthy smokers and in 25 non-smoking controls matched for sex and age. FT of non-washed RBC was significantly higher in smokers than in non-smokers (25.2 +/- 3.6 vs. 16.8 +/- 2.2 min, P0.001). A highly significant linear correlation between number of cigarette consumption and FT was found. These differences were not observed when RBC were washed three times with isotonic saline. LVM was significantly greater in smokers (85.5 +/- 13.4 g/m2) than in controls (61.8 +/- 6.7 g/m2, P0.001). A linear correlation between daily cigarette consumption and LVM was observed. A positive relationship between LVM and FT of non-washed RBC was also found. These results demonstrated that LVM is significantly elevated in smokers and is linearly correlated with both cigarette consumption and RBC filtratibility. The increased deformability found in smokers may be a determinant to the cardiac hypertrophy. The association of both elevated LVM and rheological impairment may indicate unfavourable prognosis.

This current study investigated a link between stress and coping with some male infertility problems via psychoneuroimmunological theories. The study was carried out on 77 males who came to a fertility clinic for sperm diagnosis. Appraisal and coping with stress reaction to negative life events and to infertility were related to non-sperm cells within the seminal plasma. Those men who had felt strained from external events and from problems of infertility, and had used emotional escape coping strategies, were more prone to have an immunosuppressed reaction, indicated by bacteria within their plasma. Those using task focused control strategies were more prone to have an immunostimulatory reaction, indicated by white blood cells, including in some cases, sperm destroying phagocytes suggesting a possible auto-immunity reaction. When the analyses were done separately on patients with known male fertility problems in comparison with those with unexplained infertility, the two opposing psychoneuroimmun...

Background: Natural populations of most organisms, especially unicellular microorganisms, are constantly exposed to harsh environmental factors which affect their growth. UV radiation is one of the most important physical parameters which influences yeast growth in nature. Here we used 46 natural strains of Saccharomyces cerevisiae isolated from several natural populations at the ‘‘Evolution Canyon’’ microsite (Nahal Oren, Mt. Carmel, Israel). The opposing slopes of this canyon share the same geology, soil, and macroclimate, but they differ in microclimatic conditions. The interslope differences in solar radiation (200%–800% more on the ‘‘African’’ slope) caused the development of two distinct biomes. The south-facing slope is sunnier and has xeric, savannoid ‘‘African’’ environment while the north-facing slope is represented by temperate, ‘‘European’’ forested environment. Here we studied the phenotypic response of the S. cerevisiae strains to UVA and UVC radiations and to methyl methanesulfonate (MMS) in order to evaluate the interslope effect on the strains’ ability to withstand DNA-damaging agents. Methodology/Principal Findings: We exposed our strains to the different DNA-damaging agents and measured survival by counting colony forming units. The strains from the ‘‘African’’ slope were more resilient to both UVA and MMS than the strains from the ‘‘European’’ slope. In contrast, we found that there was almost no difference between strains (with similar ploidy) from the opposite slopes, in their sensitivity to UVC radiation. These results suggest that the ‘‘African’’ strains are more adapted to higher solar radiation than the ‘‘European’’ strains. We also found that the tetraploids strains were more tolerant to all DNA-damaging agents than their neighboring diploid strains, which suggest that high ploidy level might be a mechanism of adaptation to high solar radiation. Conclusions/Significance: Our results and the results of parallel studies with several other organisms, suggest that natural selection appears to select, at a microscale, for adaptive complexes that can tolerate the higher UV radiation on the ‘‘African’’ slope.

Several studies in human and experimental models indicate the existence of a partial relationship between essential hypertension (EH) and the immune system. In this study, cellular immune functions were investigated in 13 patients with untreated and uncomplicated essential hypertension (EHP) and in 10 of their offspring (EHO) and compared to 13 age- and sex-matched normotensive controls (NC) and 10 of their offspring (NCO). The total number of T cells and T cell subsets were similar in all groups examined. In the EHP, basal lymphocyte transformation without lectins was significantly lower (1,126 +/- 261 cpm of [3H]-thymidine uptake) than in the NC (3,223 +/- 736, p less than 0.01); the response to both phytohemagglutinin (PHA) and concanavalin A (ConA) revealed reduced [3H]-thymidine uptake as compared with NC (21,890 +/- 5,432 compared to 64,574 +/- 9,723 for PHA and 10,488 +/- 2,621 compared to 37,334 +/- 8,148 for ConA, respectively, p less than 0.01). However, the ability to proliferate as a response to lectins was normal. This was leading to a normal stimulation index in both groups. In the EHO, non-significant decrease in basal transformation and reduced uptake with PHA (49,537 +/- 7,478) versus NCO (69,911 +/- 7,254) and NC (64,574 +/- 9,723) were found. These findings suggest that the proliferative response of T lymphocytes is partially suppressed in EH.

Experimental dietary studies of human colorectal carcinogenesis are usually based on the AIN-76A diet, which is dissimilar to human food in source, preparation, and content. The aims of this study were to examine the feasibility of preparing and feeding rats the diet of a specific human population at risk for colorectal neoplasia and to determine whether changes in the colonic morphology and metabolic contents would differ from those resulting from a standard rat diet. The mean daily food intake composition of a previously evaluated adenoma patient case-control study was used for the "human adenoma" (HA) experimental diet. Foods were prepared as for usual human consumption and processed by dehydration to the physical characteristics of an animal diet. Sixty-four female Sprague-Dawley rats were randomized and fed ad libitum the HA or the AIN-76A diet. Every eight weeks, eight rats from each group were sacrificed, and the colons and contents were examined. Analysis of the prepared food showed no significant deleterious changes; food intake and weight gain were similar in both groups. Compared with the controls, the colonic contents of rats fed the HA diet contained significantly less calcium, concentrations of neutral sterols, total lipids, and cholic and deoxycholic acids were increased, and there were no colonic histological changes other than significant epithelial hyperproliferation. This initial study demonstrated that the HA diet can be successfully processed for feeding to experimental animals and is acceptable and adequate for growth but induces significant metabolic and hyperproliferative changes in the rat colon. This dietary model may be useful for studies of human food, narrowing the gap between animal experimentation and human nutritional research.

Uremic patients undergoing hemodialysis (HD) are known to be highly susceptible to infections. Recent data indicate that in addition to its well-known stimulating effects on red cell production, erythropoietin (EPO) may also have immunomodulating properties. The aim of this study was to examine the effect of EPO on lectin-induced T-lymphocyte transformation in uremic patients, as part of its effect on the immune response. Sixteen HD patients and 20 age- and sex-matched healthy controls were compared before and after 6 and 20 weeks of EPO treatment. T lymphocytes were analyzed for their mitogenic activity following treatment with phytohemagglutinin (PHA), concanavalin A (CON A) and anti-CD3 by measuring 3H-thymidine incorporation. HD patients showed reduced mitogenic responses to all mitogens tested, compared to healthy controls. During the 6 weeks of EPO administration, a significant increase in T-lymphocyte activity could be demonstrated following exposure to all three mitogens (PHA, from 32 +/- 2 to 45 +/- 8; CON A, from 11 +/- 3 to 25 +/- 9; anti-CD3, from 11 +/- 3 to 22 +/- 5, means +/- SD). This increase was augmented after 5 months of EPO treatment. We conclude therefore that EPO improves in vitro T-cell mitogenic proliferation, even after short periods of treatment.

In the present study, activity of polymorphonuclear leukocyte (PMNL) intracellular antioxidant enzymes, i.e. catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX), was assessed in CRF patients on hemodialysis (HD), or continuous ambulatory peritoneal dialysis (CAPD) and in healthy controls. The activity of SOD and GPX was reduced in HD and in CAPD (SOD: by 34.2 and 42%, respectively, and GPX 66 vs. 42%, respectively, taking the activity in normal controls as 100%). Catalase activity, on the other hand, was significantly augmented (298 and 175%, respectively) as compared to the healthy controls. This impairment in antioxidant enzymes activity, involved in the respiratory burst and phagocytosis, may contribute to the understanding of the reduced bactericidal ability of PMNL activity found in these patients.

We studied the increasing expression of the p53 tumor suppressor gene in Sprague-Dawley rats, chemically induced to develop colon cancer. p53 expression was evaluated histochemically at various stages of tumor progression (during a period of 40 weeks) that can be followed by colonic hyperproliferation labeled by 3H-thymidine incorporation. We found that high level nuclear expression of p53 protein correlates with progression of malignancy in carcinogen-induced animals, whereas cytoplasmic staining is related to the onset and early development of malignancy.

The aim of the present study was to examine the effect of exposing animals to 100% oxygen instead of room air on renal function and endogenous antioxidant enzymes of the postischemic reperfused rat kidney. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) were determined in the homogenate of the left kidney after 45 min of ischemia, caused by clamping the left renal artery, 10 and 90 min after reperfusion while the animals breathed room air or 100% O2. The right kidney served as a control. The possible influence of trapped blood in the clamped kidney was also investigated by the use of a correction factor based on the Hb concentration in the homogenate. The results indicate that such correction is necessary as the blood adds significant antioxidant activity. The activities of all 3 enzymes after 45 min of ischemia decreased significantly in the left (ischemic) compared to the right (control) kidney, to 64% of the control levels for catalase, 58% for SOD and 49% for GPX. After 10 min of reflow, a further decrease in the activities of catalase (to 49%) and of GPX (to 29%) was found. SOD activity, however, increased to 64%. After 90 min of reperfusion, restoration toward normal levels was noticed (SOD activity increased to 70%, catalase to 76% and GPX to 58%). Breathing 100% O2 resulted in a significant decrease in all enzyme activities (to 38.6% for catalase, 45% for SOD and to 27.4% for GPX). This inactivation can be explained by increased reactive oxygen species (ROS) activity during hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

T cell function tests were performed in 6 patients with uncomplicated essential hypertension (EH) before and after treatment with captopril, an angiotensin-converting enzyme inhibitor. Total T and T cell subsets were within normal range and were not affected by the drug. The response of PBL to lectin stimulation was significantly impaired. While the stimulation index (SI) was almost normal when washed PBL were used (32.2 +/- 6.90 with PHA and 20.17 +/- 4.1 with Con A) or after their incubation with serum taken from normal subjects (40.42 +/- 10.9 and 15.53 +/- 3.4, respectively), autologous serum significantly reduced the SI (15.04 +/- 5.9 with PHA, p less than 0.05 and 6.68 +/- 1.45 with Con A, p less than 0.005). While captopril seemed to suppress the SI of washed PBL after 1 week of treatment, it enhanced the SI from 32.21 +/- 6.91 to 55.32 +/- 10.76 for PHA and from 20.17 +/- 4.13 to 30.63 +/- 5.41 for Con A (p less than 0.001). This effect was more obvious when the stimulations were performed with normal serum (from 40.42 +/- 10.9 to 96.47 +/- 17.51 for PTH and from 15.53 +/- 3.43 to 40.02 +/- 8.0 for Con A, (p less than 0.001). These results confirm previous reports indicating that the cellular immune response is impaired in EH. It seems that an inhibitory factor found in the serum of these patients is responsible for this impairment. Our findings may suggest that this factor may be angiotensin II.

Polar organic compounds, such as dimethylsulfoxide and butyric acid, are known to induce differentiation in Friend erythroleukemia cells as well as in other cell types. It has been found that many of the compounds that induce cellular differentiation, inhibit 3H-thymidine incorporation and induce cell damage when incubated with leukemic cells from patients with acute or chronic myelogenous or acute lymphocytic leukemia. These effects are time and dose dependent. Among the compounds tested, butyrate was the most potent. Parenteral administration of butyrate (500 mg/kg/day) for ten days to a child with acute myelogenous leukemia in relapse, and resistant to conventional therapy, resulted in elimination of myeloblasts from the peripheral blood, an increase in mature myeloid cells and a reduction in 3H-thymidine uptake by the patient's peripheral blood cells. Bone marrow myeloblasts were reduced from 70-80% to 20% following the course of intravenous butyrate. No impairment of liver or renal function and no coagulation abnormalities were observed during butyrate treatment. Organic agents that induce cell differentiation may provide additional reagents for the clinical management of selected cases of leukemia.

Prostaglandin E1 and the beta-adrenergic hormone l-isoproterenol stimulated cyclic AMP formation in both nucleated and enucleated myeloid leukemic cells that could be induced to differentiate normally to mature cells by the macrophage- and granulocyte-inducing protein MGI (MGI+D+ cells). Enucleated as well as nucleated MGI+D+ cells also desensitized to these hormones, indicating that this desensitization is an extranuclear process. Nucleated or enucleated mutant myeloid leukemic cells that are not induced to differentiate (MGI-D- cells) were not desensitized to these hormones. The antitubulin alkaloids colchicine and vinblastine, but not the antimicrofilament compound cytochalasin B, increased the maximal hormone-induced formation of cyclic AMP in nucleated MGI+D+ cells but not in the MGI-D- cells. These alkaloids also inhibited the development of desensitization to l-isoproterenol and prostaglandin E1 in enucleated MGI+D+ cells. The results indicate that in MGI+D+ cells the cytoskeletal system puts constraints on the cells' ability to respond to these hormones and that these constraints are absent in the mutant MGI-D- cells. Because MGI+D+ but not MGI-D- cells can be induced to differentiate by the macrophage- and granulocyte-inducing protein, cytoskeletal constraints, which are also found in normal myeloid cells, may be necessary for cell competence to differentiate. The results support the suggestion that membrane cytoskeletal constraints generate may control the normal response and desensitization to membrane-mediated cell inducers.

The notion that parathyroid hormone (PTH) can serve as an immunomodulator was examined. T cell function tests were performed in 3 patients with primary hyperparathyroidism before and 1 month after parathyroidectomy (PTX). Three normal volunteers, age and sex matched, were used as controls. One patient with lipoma of the neck was also examined before and after surgical removal of the lesion. In the primary hyperparathyroidism patients the total T cells were lower, the suppressors were higher and the helper to suppressor ratio was significantly lower than in control subjects. The lectin-stimulated lymphocyte transformation was significantly inhibited. All these abnormalities were restored to normal after PTX. Depressed lymphocyte activity was found also in the patient with lipoma. However, no change occurred after surgery. These results support the assumption that excess blood levels of PTH may have an immunosuppressive effect.

One hundred seventeen patients visiting the colposcopic clinic were tested for the occurence of Chlamydia trachomatis infection. Twenty-one had cervical intraepithelial neoplasia (CIN) at stages I–III. The tests were performed simultaneously by direct enzymatic immunoassay (ELISA) and immunoglobulins A and G. A prevalence of 24% was found in patients who came for random examination, 38% in CIN patients, and 48% in previously cured patients. Of the 7 ELISA-positive CIN patients, 5 were IgA positive and 4 were IgG positive. Of 23 ELISA-positive random examination patients, 17 were IgA positive and 14 were IgG positive. We recommend performing Chlamydia enzyme immunoassay together with IgA and IgG tests.

Regulation of interleukin-2 and interferon-γ gene expression in renal failure. Regulated expression of interleukin-2 (IL-2) and interferon-γ (IFN-γ) genes, induced in cultured peripheral blood mononuclear cells from patients with end-stage renal disease on hemodialysis (HD; N = 13) or peritoneal dialysis (PD; N = 13), was compared to that of 32 normal donors. Culture conditions were chosen that measure the transient, phytohemagglutinin-induced expression of IL-2 and IFN-γ messenger RNA (mRNA), as well the intactness of post-transcriptional and suppressor T cell-dependent mechanisms that control this expression. The latter was achieved by analyzing the superinduction of IL-2 and IFN-γ mRNA occurring upon culture with cycloheximide or after low-dose γ-irradiation, respectively. HD subjects showed a complete loss of inducibility of the IL-2 gene, concomitant with decreased inducibility of IFN-γ mRNA. In PD subjects, by contrast, expression of IL-2 mRNA was as vigorous as in normal donors, while IFN-γ mRNA was even more strongly inducible. This difference in gene inducibility is caused by a lack of T cell function in HD subjects. The defect in IL-2 gene expression in HD subjects, occurring most likely at transcription, may underly their impaired immune function.

Uremia is associated with impairment of various cell-mediated immunity functions. The effect of parathyroid hormone (PTH) - known to be elevated in uremia - on several T cell functions has been studied. Normal peripheral blood lymphocytes incubated with increasing amounts of human PTH (HPTH) or bovine PTH (BPTH) showed a considerable decrease (up to 40%) in lectin-induced lymphocytes transformation, significant decrease in helpers to suppressors ratio, and marked inhibition of E rosette formation and T11-positive cells. PTH alone showed no cytotoxic effect on lymphocytes when incubated with or without mitogens. Glucagon, in concentrations up to 10-fold those found on uremia, had no effect on T cell function. Thus the effect of PTH was specific to the hormone action. The direct effect of PTH on normal T lymphocytes and some of their immunological responses is not clear. However, the results of this study support the hypothesis that excess blood levels of PTH may play a role in the pathogenesis of the impairment of the immune response in uremia.

A specific macrophage migration inhibition assay, using patient lymphocytes incubated with a human colonic cancer extract, was studied in 92 patients with proven colorectal cancer and in 134 other individuals (20 normal controls, 80 patients with various nonmalignant gastrointestinal diseases, and 34 patients with extracolonic malignancies). A positive response was obtained in 78 of 92 colorectal cancer patients, but in none of the 20 normal controls. A positive response occurred in four of 34 patients with extracolonic malignancies and in approximately half of patients with colonic adenomas and in one third of patients with ulcerative colitis. The significance of positive results in these patients (with diseases considered premalignant) is unclear, and is being studied further. In patients with previous resection of colorectal cancers, positive responses were frequent during the first year following resection, and rare thereafter. The results suggest that this method may be useful as a clinical marker for colorectal cancer, and warrants further technical refinement and study of specific patient populations.

1. 1. The Cape elephant shrew Elephantulus edwardi maintained a stable body temperature (37.6°C) over a wide range of ambient temperatures. 2. 2. Normal eutherian mechanisms of temperature regulation were employed in the maintenance of homeothermy. 3. 3. Water turnover rate and metabolic rate were lower than predicted for a similar-sized eutherian. 4. 4. Maximal urine concentration was fairly high (3118 ± 267 mOsm/kg) with urine osmolality largely dependent on the urea concentration. 5. 5. Relative medullary thickness of the kidney (6.61 ± 0.84) indicated a higher maximum urine concentration than found in the laboratory and reflected an arid habitat. 6. 6. E. edwardi can be classed among the “advanced” homeotherms in view of the physiological adaptations employed for survival.

Expression of lineage-associated surface antigens, was studied in 7 patients with acute undifferentiated leukemia (AUL), 3 patients with acute myeloid leukemia (AML), 4 patients with acute lymphoid leukemia (ALL) and bone marrow from 2 healthy donors, before and after exposure to the differentiating agent 12- O -tetradecanoylphorbol-13-acetate (TPA). The surface antigens were identified by monoclonal antibodies (My4, My8, My9, MO1, B 1 , CALLA, T 11 ) and formation of EA and EAC rosettes. Adherence to plastic was also assessed. Cells from the AML patients responded to TPA with an increase in myeloid antigen positive cells and other markers of differentiation. Four of the AUL patients showed, also, a large increase in the fraction of cells expressing one or more myeloid markers, in correlation with formation of EAC rosettes. In contrast, the percentage of cells expressing myeloid antigens, did not increase in the 4 ALL patients, or in the normal donors. These findings confirm the heterogeneity of undifferentiated leukemias, and suggest the hypothesis that some AUL's can be induced to express markers of early myeloid cells.

A case of an elderly man who developed severe hyponatremia and bone marrow granulomatosis while taking methyldopa is described. The hyponatremia was found to be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Bone marrow biopsy revealed granulomas. A MEDLINE search of the English literature was done, yielding only one previous report of methyldopa-induced bone marrow granulomatosis and no previous reports of methyldopa-induced SIADH.