Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice.

beta amyloid protein (Abeta) is a 40-43 amino acid peptide derived from amyloid precursor protein (APP). Abeta has been implicated as a cause of Alzheimer's disease (AD). Mice with spontaneous or transgenic overexpression of APP show the histologic hallmarks of AD and have impairments in learning and memory.

Testosterone replacement and the physiologic aspects of aging in men.

Clinical and epidemiologic studies, along with basic scientific research, have shown a trend toward androgen deficiency in aging males. The focus of the clinical investigations described here is to determine whether testosterone deficiency is a physiologic cause of the aging process and whether testosterone replacement might prevent or ameliorate a decline in quality of life associated with age-related decline in physical and psychological functioning.

Identification of age-dependent changes in expression of senescence-accelerated mouse (SAMP8) hippocampal proteins by expression array analysis.

Aging is associated with extensive cognitive impairments, although the biochemical and physiological basis of these deficits are unknown. As the hippocampus plays a vital role in cognitive functions, we have selected this tissue to analyze changes in gene expression at two different ages. Array technology is utilized to explore how gene expression in hippocampus is affected by accelerated cognitive impairment in Senescence-Accelerated Mouse (SAM P8) strain.

Risk factors for morbidity and mortality after colectomy for colon cancer.

Purpose: Comorbid conditions affect the risk of adverse outcomes after surgery, but the magnitude of risk has not previously been quantified using multivariate statistical methods and prospectively collected data. Identifying factors that predict results of surgical procedures would be valuable in assessing the quality of surgical care. This study was performed to define risk factors that predict adverse events after colectomy for cancer in Department of Veterans Affairs Medical Centers.

History of the National Kidney Foundation.

Stimulated by a mother's desire to find a cure for her child's disease, the National Kidney Foundation has grown from a small local group of interested lay persons and medical professionals Into a major national organization with affiliates around the country and national and International programming in renal research funding, patient and family services, public and professional education, and public policy advocacy.

Effect of age on calcium-dependent proteins in hippocampus of senescence-accelerated mice.

The senescence-accelerated P8 mouse (SAMP8) is a well-characterized model for the age-related decline in acquisition and retention. Calcium-dependent protein kinase C (PKC) and calcium-calmodulin-dependent protein kinase (CAM K) have been implicated in these processes in the hippocampus. Therefore, the expression of hippocampal PKC and CAM K was determined in SAMP8 mice aged 4, 8, and 12 months.

The endocrinology of aging.

Physiologic systems have substantial reserves in younger individuals. The process of aging and intercurrent pathologic processes gradually eliminate these reserves. Changes in endocrine systems, including menopause in women, androgen deficiency in men, loss of skeletal mass, decrease in growth hormone serum concentrations, and increased incidence of type 2 diabetes are all more common or certain in older individuals.

Reported and measured physical functioning in older inner-city diabetic African Americans.

Background: The impact of diabetes on disability and physical functioning in older African Americans and potential causes of the excessive disability associated with diabetes in other studies have been inadequately investigated.

Methods: A population-based survey was performed comparing 116 self-reported diabetic inner-city African Americans aged 70 years and older to 522 nondiabetic persons from the same population. A subsample (n = 168) received a physical examination focused on body habitus, upper and lower body strength, balance, and timed physical performance tasks.

Rapid assay for nitric oxide synthase using thin-layer chromatography.

A simple, sensitive, and rapid method to determine the nitric oxide synthase (NOS) activity in crude cell extracts has been developed. The method takes advantage of differential migration of arginine and citrulline on silica gel thin-layer chromatography (TLC) with the specified buffer system. We have shown that products obtained by treating [14C]arginine with crude mouse hippocampal homogenate can be separated by methanol precipitation followed by TLC.

The effects of season and alcohol intake on mineral metabolism in men.

We have examined the relationship between self-reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months.

Capacity of a low calcium diet to induce the renal vitamin D 1a-hydroxylase is decreased in adult rats.

Young animals adapt to a low calcium diet by increasing renal production of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active metabolite of vitamin D. However, the capacity of adult animals to adapt is markedly diminished. With the recent cloning of the cytochrome P450 component (CYP1a) of the renal 1-hydroxylase enzyme complex, it is now possible to determine directly the effect of dietary calcium and maturation on the expression of renal 1-hydroxylase.

The effect of aging on bone mineral metabolism and bone mass in Native American women.

Objective: To examine the effect of age on mineral metabolism and bone mineral density (BMD) of the hip and spine in Native American women.

Design: A cross-sectional study.

Setting: The Sac and Fox Nation in rural Oklahoma

Measurements: Serum measurements were made of 25 hydroxyvitamin D (25OHD), osteocalcin, and immunoreactive parathyroid hormone.

Effect of recent alcohol intake on parathyroid hormone and mineral metabolism in men.

The mechanisms by which alcohol intake, particularly moderate alcohol intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject.

Induction of the vitamin D 24-hydroxylase (CYP24) by 1,25-dihydroxyvitamin D3 is regulated by parathyroid hormone in UMR106 osteoblastic cells.

The expression of the vitamin D 24-hydroxylase is highly regulated in target tissues for 1,25-dihydroxyvitamin D3 (1,25(OH)2D), where it may modulate the action of 1,25(OH)2D. In UMR106 osteoblastic cells, 1,25(OH)2D and PTH synergistically induce 24-hydroxylase expression. The purpose of these studies was to characterize the interaction between 1,25(OH)2D and PTH with regard to the messenger RNA (mRNA) levels of the cytochrome P450 component of the 24-hydroxylase (CYP24).

Outcome after proctectomy for rectal cancer in Department of Veterans Affairs Hospitals: a report from the National Surgical Quality Improvement Program.

Objective: To define risk factors that predict adverse outcomes after proctectomy for cancer in Department of Veterans Affairs Medical Centers.

Summary Background Data: Accurate presurgical assessment of the risk of perioperative complications and death is important in planning surgical therapy.

Methods: The National VA Surgical Quality Improvement Program contains prospectively collected and extensively validated data on >287,000 patients.

Learning and memory in the SAMP8 mouse.

The SAMP8 (P8) mouse strain develops deficits in learning and memory relatively early in its lifespan. This review provides an overview of the age-related changes that occur in P8 mice. Behavioral studies with P8 mice show impaired acquisition and retention as early as 4 months of age.

Humoral and cellular immune responses following vaccination with purified recombinant hemagglutinin from influenza A (H3N2) virus.

Adults were immunized with either baculovirus-expressed, purified recombinant hemagglutinin (rHA) from influenza A/Beijing/32/92 (H3N2) virus or saline placebo and evaluated for humoral and in vitro cellular immune responses. Compared with responses in placebo recipients, vaccinees had greater postvaccination H3(Beijing/32) HA (H3)-specific lymphoproliferation and interleukin (IL)-2, IL-10, and interferon-gamma (IFN-gamma) production. Mean increases in the production of IL-10 (> or = 20-fold) and IL-2 (10-fold) were relatively greater than that of IFN-gamma (4-fold) or IL-4 (no change).

Evidence for acute renal cortical vasoconstriction after uninephrectomy.

The rate of progression of chronic renal failure (CRF) is similar for many diseases, suggesting a common, perhaps intrinsic, renal signal for its progression. The remnant nephron hypothesis of Bricker suggests that CRF may be the result of persistent compensatory renal growth (CRG). Normally, CRG after unilateral nephrectomy (uniNx) ceases within 1 week.

Inhibition of feeding by a nitric oxide synthase inhibitor: effects of aging.

Nitric oxide has been demonstrated to play a role in the modulation of food intake. With advancing age, there is a physiological decrease in food intake. The effect of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on food intake in C57BL/6Nnia mice aged 3, 12 and 24 months was studied.

Nitric oxide synthase levels in obese Zucker rats.

Nitric oxide has been demonstrated to play a role in the modulation of food intake. The Zucker fatty rat is an autosomal recessive genetic model of obesity. We measured nitric oxide synthase (NOS) in the hypothalamus and fundus of the stomach in Zucker (fa/fa) rats and their lean littermate controls (fa/?).

Reactogenicity and immunogenicity of a protein-conjugated pneumococcal oligosaccharide vaccine in older adults.

Healthy adults > or = 50 years old were immunized with either pentavalent Corynebacterium diphtheriae C7 (beta197) cross-reactive material (CRM197) protein-conjugated pneumococcal vaccine (CV) containing 10 microgram each of capsular oligosaccharides from serotypes 6B, 14, 18C, 19F, and 23F or with licensed (23-valent, 25 microgram/serotype) pneumococcal polysaccharide vaccine (PV). Adverse reactions, predominantly local in nature, occurred in 20 of 23 CV recipients versus 13 of 23 PV recipients (P<.05).

Induction of mucosal antibodies by live attenuated and inactivated influenza virus vaccines in the chronically ill elderly.

Induction of local antibody responses to influenza A virus hemagglutinin by coadministration of two vaccines was investigated. Fifty elderly nursing home residents received inactivated trivalent influenza virus vaccine intramuscularly and simultaneously were randomized to receive either bivalent live attenuated influenza A virus vaccine or saline placebo intranasally in a blinded fashion. More significant increases in anti-H1 and -H3 IgA antibodies were detectable in nasal wash specimens of subjects who received live attenuated virus vaccine than in those who received intranasal placebo.

Cytotoxic T lymphocyte responses to a liposome-adjuvanted influenza A virus vaccine in the elderly.

This randomized double-blind study evaluated cytotoxic T lymphocyte (CTL) responses of elderly volunteers after parenteral immunization with either liposome-adjuvanted (n = 23) or control subvirion (n = 26) vaccine containing detergent-split influenza A/Taiwan/1/86 (H1N1) virus. Peripheral blood mononuclear cells obtained 0, 2, and 12 weeks after vaccination were stimulated in vitro with influenza A (H1N1) virus-infected autologous cells and then assayed for influenza virus-specific cytotoxicity using autologous virus-infected target cells. CTL responses to vaccination exhibited influenza A virus heterosubtypic cross-reactivity and were mediated primarily by CD8+ effector cells.