PubMed Health⌕ Search

Biomedical subjects

Jan M Bruder

Publications and source records attributed to Jan M Bruder.

14 recordsLinked to original sources
PubMed2006

Fabrication of polymeric replicas of cell surfaces with nanoscale resolution.

We report an approach for fabricating biomimetic surface replicas of cells with nanoscale resolution. Fixed cells serve as a template for a two-stage replica molding process. Cast from the template, the impression replica contains a reproduction of cellular topographical features indented into its surface, and cast from the impression replica, the relief replica contains a copy of these features protruding from its surface. Various polymers and cells can be utilized, and scanning electron microscopy, atomic force microscopy, and white light interferometry analyses confirm the replication of nanoscale features. These replicas are useful for investigating cellular function and for biomimetic tissue engineering.

Animals↗
PubMed2006

Effects of alendronate on bone mineral density in men with prostate cancer treated with androgen deprivation therapy.

Bone mineral density (BMD) is low in men with prostate cancer treated with androgen deprivation therapy (ADT). Intravenous bisphosphonates have been shown to prevent the bone loss, however, the effectiveness of oral bisphosphonates have not been studied in this population. In this retrospective cohort study, we examine the effect of alendronate on BMD in men with prostate cancer receiving ADT. We reviewed the charts of patients receiving ADT referred from the VA Urology Clinic for BMD measurements. Forty seven patients had follow up BMD measurements (17.6+8.3 months). Twenty-two men (47%) were also receiving alendronate 70 mg every week. There was a statistically significant difference (p<0.05) in the percent change of BMD per year at the spine (-1.29+/-0.7% vs. +1.41+/-0.7%), total hip (-0.94+/-0.6% vs. +0.97+/-0.5%), femoral neck (-2.17+/-0.7% vs. +0.32+/-0.6%) and trochanter (-2.01+/-0.7% vs. +0.79+/-0.8%) in the patients not treated compared to those treated with alendronate. In the four other measured sites at the radius (proximal, mid, ultra distal and total), there were no statistically significant differences (p>0.05). These findings confirm that bone loss occurs in men receiving ADT at all sites measured. The use of alendronate prevents bone loss at the spine and hip, but does not seem to have the same protective effect at the radius.

Absorptiometry, Photon↗
PubMed2006

Prevalence of osteopenia and osteoporosis by central and peripheral bone mineral density in men with prostate cancer during androgen-deprivation therapy.

OBJECTIVES: To determine the prevalence of osteopenia and osteoporosis by central (spine and hip) and peripheral (radius) bone mineral density (BMD) in men with prostate cancer undergoing androgen-deprivation therapy (ADT). Low BMD and fractures are prevalent in this group of men. Most published studies on ADT-related bone loss have documented the loss of BMD in the spine and hip as measured by dual x-ray absorptiometry. In one study, the loss of BMD was most pronounced at the radius. METHODS: In a chart review of patients receiving ADT, the spine and hip BMD results were recorded in 89 patients. Of these 89 patients, the BMD of the radius was also recorded in 53. RESULTS: In the 89 patients with BMD measurements of the spine and hip, 24 (26.9%) had osteoporosis of the hip or spine as defined by a T score of -2.5 or less, and 45 patients (50.6%) had osteopenia (T score -1.0 to -2.5). In the subset of 53 patients who also had the BMD of the radius measured, the results of the BMD of the radius changed the category of diagnosis in 18 patients (34%). The prevalence of osteoporosis increased from 25% to 53% when the results of the radius were included. CONCLUSIONS: Men with prostate cancer treated with ADT have a high prevalence of osteopenia and osteoporosis as determined by peripheral and central BMD measurements. The use of the peripheral BMD measurement appears to identify more patients with osteoporosis and suggests its use in the evaluation of osteoporosis in men receiving ADT.

Aged↗
PubMed2006

Upregulation of TGF-beta1 expression may be necessary but is not sufficient for excessive scarring.

Transforming growth factor beta 1 (TGF-beta1) upregulation has been implicated in hypertrophic scars and keloids, but it is unclear if it is the cause or an effect of excessive scar formation. In this study, we overexpressed TGF-beta1 in fibroblasts and characterized its role. Normal human dermal fibroblasts were genetically modified to overexpress TGF-beta1 as the wild-type latent molecule or as a mutant constitutively active molecule. TGF-beta1 secretion was measured, as were the effects of TGF-beta1 upregulation on cell proliferation, expression of smooth muscle cell alpha actin (SMC alpha-actin) and ability to contract collagen lattices. Fibroblasts were implanted intradermally into athymic mice and tissue formation was analyzed over time by histology and immunostaining. Gene-modified fibroblasts secreted approximately 20 times the TGF-beta1 released by control cells, but only cells expressing mutant TGF-beta1 secreted it in the active form. Fibroblasts expressing the active TGF-beta1 gene had increased levels of SMC alpha-actin and enhanced ability to contract a collagen lattice. After intradermal injection into athymic mice, only fibroblasts expressing active TGF-beta1 formed "keloid-like" nodules containing collagen, which persisted longer than implants of the other cell types. We conclude that upregulation of TGF-beta1 by fibroblasts may be necessary, but is not sufficient for excessive scarring. Needed are other signals to activate TGF-beta1 and prolong cell persistence.

Actins↗
PubMed2005

Neurite bridging across micropatterned grooves.

After injury, regenerating axons must navigate complex, three-dimensional (3D) microenvironments. Topographic guidance of neurite outgrowth has been demonstrated in vitro with culture substrates that contain micropatterned features on the nanometer-micron scale. In this study we report the ability of microfabricated biomaterials to support neurite extension across micropatterned grooves with feature sizes on the order of tens of microns, sizes relevant to the design of biomaterials and tissue engineering scaffolds. Neonatal rat dorsal root ganglion (DRG) neurons were cultured on grooved substrates of poly(dimethyl siloxane) coated with poly-L-lysine and laminin. Here we describe an unusual capability of a subpopulation of DRG neurons to extend neurites that spanned across the grooves, with no underlying solid support. Multiple parameters influenced the formation of bridging neurites, with the highest numbers of bridges observed under the following experimental conditions: cell density of 125,000 cells per sample, groove depth of 50 microm, groove width of 30 microm, and plateau width of 200 microm. Bridges were formed as neurites extended from a neuron in a groove, contacted adjacent plateaus, pulled the neuron up to become suspended over the groove, and the soma translocated to the plateau. These studies are of interest to understanding cytoskeletal dynamics and designing biomaterials for 3D axon guidance.

Animals↗
PubMed2004

Oral administration of biochemically active microcapsules to treat uremia: new insights into an old approach.

This paper begins with an extensive review of previous research on the degradation of non-protein nitrogen compounds for improved therapy of renal failure. During the 1970s, Malchesky established that naturally occurring strains of microorganisms were highly effective for the in vitro degradation of urea and other compounds found in urine, and that these bacteria could be conditioned with selected media to enhance growth and degradation efficiency. A few years later, Setala introduced the concept of oral delivery of lyophilized bacteria, harvested from soil, to uremic patients, for degradation of non-protein nitrogen compounds. In the 1990s, Chang proposed delivery of encapsulated genetically modified bacteria for removal of uremic waste products in vitro and in vivo. Recently, our group has pursued the idea of orally delivering formulated combinations of enzymes or modified bacteria. A new study is also described, which characterizes the capacity of a single alginate microcapsule containing a mixture of genetically modified cells and enzyme to degrade urea, uric acid and creatinine. The combination capsules were found to be effective in vitro and in vivo in a rodent model of chemically-induced renal failure. Reduction of urea concentration in vivo required co-administration of a cation exchange resin to adsorb ammonia. Increased investigative effort is warranted for these approaches which offer significant potential as an adjunct to conventional forms of dialysis.

Administration, Oral↗
PubMed2002

Is thyroid frozen section too much for too little?

BACKGROUND: The role of frozen section (FS) in thyroid disease is controversial. The goal of this study was to identify a cohort of patients who may or may not benefit from FS. METHODS: Two hundred thirty-one patients who underwent thyroidectomy were evaluated in regard to fine-needle aspiration (FNA), FS, and the extent of surgery. RESULTS: In all, 155 patients underwent FNA, 140 patients underwent FS, and 103 patients had both. A final diagnosis of malignancy was obtained in 47 of 231 patients. FNA had a sensitivity of 50% and a specificity of 99%, and FS had a sensitivity of 50% and a specificity of 100% for diagnosing malignancy. Accounting for the clinical findings and FNA results, FS results altered the extent of thyroidectomy in 1 of 103 patients. CONCLUSIONS: The increased costs for the operative time and the pathologists needed to obtain routine FS are not supported with any substantial benefit in patient outcome.

Adolescent↗
PubMed2002

Bone loss following hypogonadism in men with prostate cancer treated with GnRH analogs.

It is known that bone mineral density (BMD) is low in men who are hypogonadal. However, the rate and sites of bone loss following testosterone deficiency are not known. The resulting hypogonadism after GnRH analog therapy for the treatment of prostate cancer allows us to examine bone loss and bone resorption immediately after testosterone withdrawal. Therefore, we examined the effects of GnRH analog treatment on bone loss and bone resorption in men with prostate cancer. BMD and serum and urine concentrations of markers of bone turnover were determined in men with prostate cancer and in age-matched controls. Measurements were taken before GnRH therapy and 6 and 12 months after instituting therapy. After 12 months of GnRH therapy, the BMD of the total hip and ultra distal radius decreased significantly (P < 0.001) in men with prostate cancer compared with the controls. The mean bone loss was 3.3% and 5.3%, respectively. The observed reduction in BMD in the spine (2.8%) and the femoral neck (2.3%) did not reach statistical significance. No significant bone loss was observed in the control subjects. The concentration of the urine marker of bone resorption, N-telopeptide, was significantly increased from baseline and from controls at both 6 and 12 months in patients treated with GnRH analog therapy compared with control subjects (P < 0.05). The concentration of a serum marker of bone formation, bone-specific alkaline phosphatase, was not significantly different from baseline or from controls at 6 and 12 months. Thus, the decreased total hip and ultra distal radius BMD and increased urinary N-telopeptide concentration after testosterone withdrawal demonstrate an increase in trabecular bone loss and enhanced bone resorption. These findings demonstrate a significant loss of bone in men with prostate cancer after receiving GnRH therapy and suggest that the total hip and radius are the preferred sites for monitoring bone loss in older men. In addition, markers of bone resorption may be helpful.

Absorptiometry, Photon↗
PubMed2002

Sequence analysis of measles virus nucleocapsid transcripts in patients with Paget's disease.

It has been debated for almost 30 years whether Paget's disease of bone results from paramyxoviral infection of osteoclasts (OCs). Paramyxoviral-like nuclear inclusions are found in OCs from patients with Paget's disease, and measles virus (MV) or canine distemper virus (CDV) messenger RNA (mRNA) transcripts have been detected by in situ hybridization in bone cells from pagetic lesions. Furthermore, immunocytochemical studies have shown the presence of several paramyxoviral species in OCs from patients with Paget's disease. However, others have been unable to detect paramyxoviral transcripts in bone samples from patients with Paget's disease or marrow cultures from involved sites of patients with Paget's disease. Furthermore, no one has been able to isolate an infectious virus from pagetic bone samples or marrow cells from patients with Paget's disease, and a full-length viral gene has not been sequenced from pagetic samples. In this study, we have obtained the full-length sequence for the MV nucleocapsid (MVNP) gene in bone marrow from an involved site from a patient with Paget's disease and more than 700 base pairs (bps) of MVNP sequence in 3 other patients with Paget's disease. These sequences were undetectable in four normal marrow samples studied simultaneously. The sequences from the patients contained multiple mutations that differed from the Edmonston strain MVNP gene. These findings are consistent with the presence of a chronic MV infection in affected sites from these patients with Paget's disease.

Aged↗
PubMedDate not supplied

In vivo and in vitro degradation of urea and uric acid by encapsulated genetically modified microorganisms.

This study was undertaken to characterize the capacity of a combination of genetically modified bacteria to lower elevated levels of urea and uric acid and thus to serve as a potential adjunct to maintenance dialysis in patients with chronic renal failure. Two strains of genetically modified bacteria expressing enzymes, urease to degrade urea and uricase to degrade uric acid, were identified, combined, and dispersed in 600-microm alginate microcapsules suitable for oral administration. In 24 h in vitro experiments, 5 mL of these capsules completely cleared 95% of the urea and >99% of the uric acid from 100 mL of a challenge solution formulated to the concentration of these solutes in a presenting hemodialysis patient. The process of urea degradation was found to be intracellular and each bacterial strain was specific for its substrate. Solute degradation in vivo was evaluated with a chemically induced model of acute renal failure, using Sprague-Dawley rats. Orally administered capsules were found to remain in the gastrointestinal tract for at least 6 h. The severity of azotemia and hyperuricaemia after chemical induction of acute renal failure was reduced by 64 and 31%, respectively, on administration of the capsules. Reduction of urea concentration (but not uric acid concentration) in vivo required coadministration of an ion-exchange resin to adsorb ammonia. Oral delivery of a combination of genetically modified microorganisms should be further explored in chronic renal failure models as a useful adjunct to dialysis or to immunosorption for the treatment of uremia.

Acute Kidney Injury↗
PubMedDate not supplied

Degradation of low molecular weight uremic solutes by oral delivery of encapsulated enzymes.

An alginate microcapsule was developed that contains three enzymes (urease, uricase, and creatininase) capable of effectively degrading urea, uric acid, and creatinine, which are elevated to pathologic levels in patients with kidney failure. The capsules were evaluated in vitro and in vivo in a rodent model and evidenced considerable potential as a possible adjunctive therapy in the treatment of ESRD. In vitro, 5 mL of the capsules incorporating a quantity of enzymes in the mg range effectively degraded all the uric acid, 97% of the urea, and 70% of the creatinine within 24 hours in a 100 mL test solution simulating the concentration of these solutes in uremic plasma. Enzyme degradation of urea followed Michaelis-Menten kinetics, and the Lineweaver-Burk plots for both encapsulated enzymes and unencapsulated control animals were superimposable, indicating that mass transfer through the capsules was not rate limiting in the degradation process. A chemically induced acute renal failure model in the rat was used to evaluate the ability of encapsulated enzymes, along with an oral sorbent (ion exchange resin), to degrade uremic toxins in vivo. Encapsulated enzyme therapy decreased the severity of azotemia by as much as 70%. Preliminary scale up calculations indicated that oral delivery to humans would involve a practical and manageable quantity of enzymes. This is the first study using a combination of enzymes in a single delivery vehicle to degrade multiple uremic toxins.

Acute Kidney Injury↗
PubMedDate not supplied

Urinary calcium excretion in primary hyperparathyroidism: relationship to 25-hydroxyvitamin d status.

OBJECTIVE: To determine the prevalence of vitamin D deficiency in patients with primary hyperparathyroidism (PHPT) and evaluate the relationship between urinary calcium excretion and serum 25-hydroxyvitamin D (25-OH-D) levels in patients with PHPT. METHODS: We present a case report and a review of the medical records of patients with PHPT. Of 75 patients with PHPT substantiated by hypercalcemia and increased levels of intact parathyroid hormone (iPTH), 35 were identified with laboratory evaluation of vitamin D levels and 24-hour urinary calcium excretion. These study subjects were stratified as 25-OH-D deficient, insufficient, or replete (on the basis of serum values of <15, 15 to 25, or >25 ng/mL, respectively). Total 24-hour urinary calcium excretion and the fractional excretion of calcium (FECa) were analyzed as a function of 25-OH-D status. RESULTS: Of the 35 study subjects, 14 (40%) and 13 (37%) had 25-OH-D deficiency or insufficiency, respectively. Those patients with a 25-OH-D level <15 ng/mL had higher serum iPTH concentrations as well as lower urinary calcium excretion and FECa. No significant correlations were found, however, between 25-OH-D status and iPTH concentrations (r = -0.21; P = 0.23), total 24-hour urinary calcium excretion (r = 0.07; P = 0.7), or FECa (r = 0.04; P = 0.8). CONCLUSION: Vitamin D deficiency (25-OH-D levels <15 ng/mL) was common in our population of patients with PHPT. Urinary calcium excretion was not significantly altered by 25-OH-D deficiency in patients with newly recognized PHPT. Measurements of total urinary calcium excretion and FECa can be reliably used to rule out familial benign hypocalciuric hypercalcemia in the initial evaluation of PHPT, regardless of 25-OH-D status. Determining 25-OH-D concentrations best assesses the vitamin D status.

Adult↗