Location of the platelet binding site in zymogen coagulation factor IX.

The assembly of the tenase complex on the surface of the platelet is an essential step in maintaining normal hemostasis as evidenced by the serious hemorrhagic diathesis associated with either factor IX (FIX) or factor VIII deficiencies. Understanding the regions and or residues of FIX crucial for proper binding to platelets has important clinical implications. The ability of FIX to bind activated platelets in the presence of 4 mmol/l CaCl2 was examined using electrophoretic light-scattering experiments.

Incidence of physician-diagnosed primary Sjögren syndrome in residents of Olmsted County, Minnesota.

Objectives: To estimate the incidence of physician-diagnosed primary Sjögren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients.

Patients And Methods: We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded.

Renal replacement therapy and orthotopic liver transplantation: the role of continuous veno-venous hemodialysis.

Background: The need for renal replacement therapy (RRT) either before or after orthotopic liver transplant (OLTX) has been reported to be a poor prognostic indicator for survival. Use of continuous veno-venous hemodialysis (CVVHD) for RRT has been reported in three series of OLTX patients with high 90-day mortality rates of 57-60%. We have examined our patient population to determine the effect of necessity and type of RRT on patient survival after OLTX.

Long-term fracture risk among infertile women: a population-based cohort study.

Nulliparity has been linked to bone loss and fractures, but the contribution of infertility is unclear. The purpose of this study was to assess the long-term risk of fractures among infertile women. In a population-based retrospective cohort study, all 658 Olmsted County, Minnesota, women with infertility (failure to conceive after 1 year despite intercourse without contraception) first diagnosed at Mayo Clinic in 1935-1964 were followed for fractures.

Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year population-based study.

Background: The incidence rates of venous stasis syndrome and venous ulcer are uncertain, and trends in incidence are unknown.

Methods: We performed a retrospective review of the complete (inpatient and outpatient) medical records of a community population (Olmsted County, Minnesota) to estimate the incidence of venous stasis syndrome and venous ulcer during the 25-year period, 1966 to 1990, and to describe trends in incidence.

Results: A total of 1131 patients received a first lifetime diagnosis of venous stasis syndrome.

Brn-3a activates the expression of Bcl-x(L) and promotes neuronal survival in vivo as well as in vitro.

The determination of cell fate plays a critical role during the later stages of embryogenesis and the early postnatal period-a time during which approximately half of neurons born during neurogenesis undergo programmed cell death. It has previously been reported that the type IV POU domain transcription factor Brn-3a plays a role in the maturation and survival of sensory neuronal populations. Indeed we have shown that the long form of Brn-3a is capable of activating expression of the antiapoptotic Bcl-2 gene and enhancing neuronal survival in cultures of sensory neurons.

Sex is all in the brain: report of a Novartis Foundation Symposium on the Neuronal and Cognitive Effects of Oestrogens, London, UK, 7-9 September 1999.

Suspicions of the impact of oestrogen beyond its traditional role in sex maturation were confirmed with the discovery of oestrogen receptors in a great variety of tissues other than just in sex organs. Recently, research findings have indicated the central nervous system as one of the prime target organs--not only does oestrogen modulate the production and actions of serotonin, acetylcholine, dopamine and norepinephrine, but it also encourages the growth of new synapses and enhances neuronal survival. Whether the many effects of oestrogen operate through classical oestrogen receptors or alternative channels remains under intense investigation.

Celery (Apium graveolens L.) parenchyma cell walls examined by atomic force microscopy: effect of dehydration on cellulose microfibrils.

Atomic force microscopy (AFM) was used to image celery (Apium graveolens L.) parenchyma cell walls in situ. Cellulose microfibrils could clearly be distinguished in topographic images of the cell wall.

Effects of body size and skeletal site on the estimated prevalence of osteoporosis in women and men.

There is growing awareness that therapeutic decision-making may be confounded by discrepancies in the prevalence of osteoporosis by World Health Organization criteria when bone density is measured at different skeletal sites. To explore this issue, we measured bone density at a variety of skeletal sites in a population-based sample of 348 men (age 22-90 years) and 351 women (age 21-93 years). Men had greater areal bone mineral density (BMD, g/cm2) than women at almost every subregion on total body, anteroposterior (AP) and lateral lumbar spine, proximal femur and forearm scans by dual-energy X-ray absorptiometry.

Relative influence of physical activity, muscle mass and strength on bone density.

In a population-based sample of 348 men (age 22-90 years) and 351 women (age 21-93 years), we evaluated the relationship of bone density assessed at a variety of skeletal sites by dual-energy X-ray absorptiometry (DXA) with various muscle mass estimates obtained also from the DXA scan and with physical activity by interview and strength assessed both subjectively and objectively. All these parameters declined with age as judged from these cross-sectional data. All estimates of total skeletal muscle mass were strongly correlated with bone density at different skeletal sites.

Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a population-based, case-control study.

Objective: We sought to determine risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum.

Study Design: We performed a population-based case-control study. All Olmsted County, Minnesota, residents with a first lifetime deep vein thrombosis or pulmonary embolism during pregnancy or post partum from 1966 to 1990 were identified (N = 90).

Secular trends in the epidemiology and outcome of Barrett's oesophagus in Olmsted County, Minnesota.

Background: The incidence of oesophageal adenocarcinoma has increased greatly. Barrett's oesophagus is a known risk factor.

Aims: To identify changes in the incidence, prevalence, and outcome of Barrett's oesophagus in a defined population.

The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study.

Objectives: To estimate the incidence and determine predictors of venous stasis syndrome and venous ulcers after deep venous thrombosis and pulmonary embolism.

Patients And Methods: This population-based retrospective cohort study reviewed medical records of 1527 patients with incident deep venous thrombosis or pulmonary embolism between 1966 and 1990. We recorded baseline characteristics, event type (deep venous thrombosis with or without pulmonary embolism or pulmonary embolism alone), leg side and site of deep venous thrombosis (proximal with or without distal deep venous thrombosis vs distal deep venous thrombosis alone), and venous stasis syndrome and venous ulcer.

Epidemiology and natural history of primary biliary cirrhosis in a US community.

Background & Aims: The epidemiology of primary biliary cirrhosis (PBC) has not been studied systematically in the United States. We report the incidence and prevalence of this condition in the general population. We also examined the validity of the Mayo natural history model for PBC among these unselected patients from the community.

Retinoic-acid-resistant neuroblastoma cell lines show altered MYC regulation and high sensitivity to fenretinide.

Background: High-dose, pulse-13-cis-retinoic acid (13-cis-RA) given after intensive cytotoxic therapy improves event-free survival for high-risk neuroblastoma (NB), but more than 50% of patients have tumor recurrence.

Procedure: We conducted multistep selection for resistance to all-trans-retinoic acid (ATRA) in NB cell lines with (SMS-KCNR and LA-N-5) or without (SMS-LHN) MYCN genomic amplification.

Results: After 12 exposures to 10 microM ATRA, the two MYCN-amplified cell lines (KCNR 12X RR and LA-N-5 12X RR) showed partial resistance to the cytostatic/differentiation effects of ATRA; complete resistance was seen in LHN 12X RR.

Synergistic cytotoxicity in solid tumor cell lines between N-(4-hydroxyphenyl)retinamide and modulators of ceramide metabolism.

Background: We previously reported that N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) treatment caused large increases of ceramide levels in neuroblastoma cell lines and induced cell death by a combination of apoptosis and necrosis through p53 (also known as TP53)-independent and caspase-independent pathways. Our goal was to determine if several molecules that inhibit enzymes involved in ceramide metabolism-L-threo-dihydrosphingosine (safingol), d, l-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP), and tamoxifen-enhanced 4-HPR-mediated cytotoxicity and/or affected ceramide levels.

Methods: Cellular lipids were quantified by radiolabeling and thin-layer chromatography.

Fracture risk among patients with Paget's disease: a population-based cohort study.

Localized disruption of bone architecture leads to an increased risk of pathological fractures in patients with Paget's disease, but the impact of the disease on overall fracture risk is unknown. We addressed this issue among 236 Olmsted County, Minnesota residents (107 women and 129 men) first diagnosed with Paget's disease from 1950 through 1994. These subjects (mean +/- SD age at diagnosis, 69.

Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women.

Whether the higher serum leptin levels in women are due to gender differences in fat mass or to other factors such as sex steroids remains unclear. In addition to sex steroids, serum insulin levels also appear to be related to leptin levels, although whether this effect is independent of the effects of body composition is unclear. The purpose of this study was to identify the major determinants of circulating serum leptin levels.

Cross-sectional versus longitudinal evaluation of bone loss in men and women.

We evaluated age- and sex-specific differences in bone density at a variety of skeletal sites in a population-based sample of 348 men (age 22-90 years) and 351 women (age 21-93 years) by dual-energy X-ray absorptiometry. Several patterns of age-related bone loss were observed, but adjustments for height (or, where possible, calculation of bone mineral apparent density) dampened the apparent rate of bone loss from most skeletal sites as judged from cross-sectional measurements at baseline. Cross-sectional data also overestimated the rate of bone loss observed longitudinally over 4 years at many sites, particularly the hip and spine; conversely, in some forearm regions, cross-sectional rates of loss underestimated the bone loss seen prospectively.

Fractures following thyroidectomy in women: a population-based cohort study.

Hip fracture risk has been associated with hyperthyroidism and thyroidectomy in men and with hyperthyroidism in women, but the influence of thyroidectomy on fracture risk in women has not been adequately addressed. The 630 Rochester, MN women who underwent thyroidectomy in 1950-1974 were followed subsequently for 12,804 person-years (retrospective cohort study) during which 601 fractures were observed. Relative to incidence rates in the community, there was no increase in overall fracture risk (standardized incidence ratio [SIR] 0.