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Biomedical subjects

J Stock

Publications and source records attributed to J Stock.

At least 19 recordsLinked to original sources

Early carotid atherosclerosis in overweight non-diabetic individuals is associated with subclinical chronic inflammation independent of underlying insulin resistance.

Overweight in children and young adults is an increasing problem in Western industrialized countries with potential impact on cardiovascular morbidity. Whether early arterial wall thickening in these subjects mainly results from the often associated insulin resistance syndrome or from increased subclinical chronic inflammation probably triggered by adipose tissue is still under discussion. We therefore determined insulin sensitivity index (ISI) by performing an euglycaemic hyperinsulinaemic glucose clamp (insulin infusion rate 1 mU/kg/min) and high-sensitivity C-reactive protein (hsCRP) levels in relation to the intima-media thickness (IMT) at the common carotid artery (high resolution ultrasound; 13 MHz) in 81 young (age 33 +/- 1 years), moderately overweight subjects. To reduce the number of confounding variables, subjects with disturbances in glucose metabolism (75 g oral glucose tolerance test) and hypertension were excluded. As expected, higher BMI was positively correlated with increased IMT (r = 0.358; p = 0.001). After multiple regression analysis, hsCRP levels independently correlated to IMT (r = 0.251; p = 0.03), even after adjusting for age, sex, BMI, ISI, LDL cholesterol and smoking as cofactors. However, taking all above listed factors into account, glucose-clamp assessed insulin sensitivity was not correlated with IMT. Thus, overweight might trigger inflammatory mechanisms leading to vascular wall hypertrophy independent of the insulin resistance syndrome already early in life.

Adult↗

[Indicators of incipient atherosclerosis: demonstration of endothelial dysfunction with high-resolution ultrasound].

Endothelial function is thought to play a central role in the process of atherosclerosis, and in the pathogenesis of arterial hypertension and chronic heart failure. In the last decade a non-invasive ultrasound technique has been developed to measure endothelium-dependent vasodilation of the brachial artery which allows quantification of endothelial function. This method is based upon results in basic research, which show increased endothelial NO-production following the impact of shear forces on the endothelial surface. The resulting vasodilation can be quantified with high resolution ultrasound (7-13 MHz). The advantage of this technique is its non-invasive nature, which allows a risk-free use even in young individuals. Repeated measurements to control the success of medical intervention are also not problematic. Despite the possibility of widespread use because of its deceptively simple protocol, there are numerous factors affecting flow-mediated vascular reactivity. Details of the methods applied, variations in examination procedure, image acquisition, subjects preparation, equipment, training requirements and data interpretation are reviewed in this paper. Clinical studies of cardiovascular disease, risk factor profiles and the prognostic impact of measuring flow-mediated vasodilation are also discussed.

Arteriosclerosis↗

CD95/CD95 ligand-independent potentiation of treosulfan cytotoxicity by BSO in malignant glioma cells in vitro and in vivo.

The glutathione synthase inhibitor, buthionine sulfoximine (BSO), specifically enhances the cytotoxic effects of treosulfan in human glioma cells. BSO depletes glutathione and greatly enhances treosulfan cytotoxicity in all the 12 human malignant glioma cell lines examined. None of these cell lines showed enhanced susceptibility to CD95L- or tumor necrosis factor (TNF)-alpha-induced apoptosis when glutathione is depleted. The combination of serial systemic BSO applications (300 mg/kg) and a single systemic dose of treosulfan (2.5 g/kg) reduced the growth of intracranially growing rat C6 gliomas in vivo by 73% whereas treosulfan alone reduced tumor growth by 16% and BSO alone had no effect. BSO lowered glutathione levels to 25-30% in peripheral blood mononuclear cells (PBMC) and to 50% in the glioma tissue. The glutathione levels in the non-tumor-bearing contralateral hemisphere were unaffected by systemic BSO treatment. The main side effects of treosulfan, gastrointestinal and bone marrow toxicity, were not significantly enhanced by BSO.

Animals↗

Linking structural variability in long bone diaphyses to habitual behaviors: foragers from the southern African Later Stone Age and the Andaman Islands.

The cross-sectional distribution of cortical bone in long bone diaphyses is highly responsive to mechanical loading during life, yet the relationship between systemic and localized influences on skeletal structure remains unclear. This study investigates postcranial robustness throughout the body among adults from two groups of foragers with different patterns and modes of mobility, to determine whether there is evidence for upper vs. lower body localization of skeletal robustness. The samples used for this comparison are from the southern African Later Stone Age (LSA; n = 65, male = 33, female = 28) dating from ca. 10,000 to 2,000 B.P., and 19th century indigenous Andaman Islanders (AI; n = 36, male = 17, female = 16). The LSA were highly mobile foragers who did not exploit offshore marine resources. In contrast, the AI had tightly constrained terrestrial, but significant marine, mobility. Geometric properties of cortical bone distribution in the diaphyses of the clavicle, humerus, femur, tibia, and first metatarsal are compared between the samples, providing a representation of skeletal robustness throughout the body. Multivariate ANOVA shows the AI to have significantly stronger clavicles and humeri, while the LSA femora, tibiae, and first metatarsals are stronger than those of the AI. These patterns, in which upper and lower limbs show biomechanical properties that are consistent with habitual behaviors, suggest localized osteogenic response. Although postcranial robustness appears to be correlated with overall limb function, the results suggest that more proximal elements within the limb may be more responsive to mechanical loading.

Adult↗

Signal transduction: response regulators on and off.

High resolution structures of the active phosphorylated forms of two-component response regulators have recently been reported. The results provide a basis for understanding how metabolic energy is coupled to signal transduction in cellular regulatory networks.

Adenosine Triphosphatases↗

Signal transduction: hair brains in bacterial chemotaxis.

The conserved cytoplasmic domains of bacterial chemotaxis receptors are a fibrous arrangement of alpha-helical coiled coils that look a lot like hair. Such bundles of alpha-helical filaments mediate sensory-motor responses in all prokaryotic cells. How do they work? Very nearly perfectly is probably as good an answer as any.

Bacterial Physiological Phenomena↗

The ultrasonic description of postpubertal testicles in men who have undergone prepubertal orchiopexy for cryptorchidism.

PURPOSE: We provide a sonographic description of postpubertal testicles in patients who have undergone prepubertal orchiopexy with placement of a suture through the tunica albuginea. MATERIALS AND METHODS: Testicular ultrasound was performed in men who had undergone prepubertal testicular fixation for cryptorchidism using a suture passed through the tunica albuginea. Comparison was made to the sonographic appearance of cryptorchid testicles not secured with a fixating suture through the tunica albuginea. The operative report for each patient was reviewed with specific attention to use and type of suture material, and age at orchiopexy. RESULTS: Ultrasonography was performed on 22 men in whom a tunica albuginea fixating suture was placed during orchiopexy for cryptorchidism. Average patient age at orchiopexy was 5.6 years and median time from orchiopexy to this examination was 14.8 years. Right cryptorchidism existed in 64% of the men. No significant difference was noted in size between the 2 testicles in any patient. Ultrasonography did not identify any parenchymal abnormalities. A tunica albuginea calcification with posterior shadowing on the side of fixation was noted in 32% of patients, of whom 3 had calcified areas evident on physical examination. An area of subtunical hypoechogenicity was noted in 14% of patients. All tunical abnormalities were associated with the use of chromic suture. The remaining 12 patients (54%) had normal sonographic and physical examinations. The control group comprised 6 men who underwent orchiopexy without a fixating suture through the tunica albuginea. These men were examined identically and no sonographic abnormalities were noted in the tunica albuginea or testicular parenchyma. At a median of 16 months no patient had been diagnosed with testicular cancer or had a change in testicular self-examination. CONCLUSIONS: Tunica albuginea calcifications and hypoechogenic cysts are common ultrasonic findings in men who have undergone orchiopexy using a suture passed through the tunica albuginea. Parenchymal lesions should not be considered secondary to this procedure and must be treated as de novo abnormalities. These changes seem to be induced by the use of a fixating suture through the tunica albuginea.

Adolescent↗

Signal transduction: Gyrating protein kinases.

Recently determined structures have linked histidine kinases with class II topoisomerases, the DNA repair enzyme MutL and the molecular chaperone Hsp90. This surprising finding may foreshadow a shift in our understanding of energy coupling mechanisms in signal transduction networks.

Adenosine Triphosphatases↗

Müllerian duct remnants: surgical management and fertility issues.

PURPOSE: We reviewed our experience with mullerian duct remnants, also known as prostatic utricular and mullerian duct cysts, to advance further the understanding of the surgical management of these challenging congenital anomalies. The indications, merits and disadvantages of each surgical approach are presented, and the effects of mullerian duct remnants and their treatment on future fertility are discussed. MATERIALS AND METHODS: We reviewed the records of 26 patients 1 month to 19 years old with mullerian duct remnants who were seen between January 1984 and October 1998. Clinical presentation included perineoscrotal hypospadias in 10 cases, urinary retention and/or difficult voiding in 7, urinary tract infection in 6, acute scrotum in 2, and recurrent hemospermia and dysuria in 1. RESULTS: Of the 26 patients 13 required surgical intervention for various symptoms and to correct large diverticula. The surgical approach was transvesical transtrigonal in 8 cases, extravesical in 2, perineal in 2 and posterior sagittal in 1. Transurethral fulguration was performed in 2 cases. The initial surgical approach was successful in 11 of the 13 patients. One patient required conversion to a transvesical transtrigonal approach due to inadequate exposure during attempted perineal excision. Two cases treated with transurethral fulguration failed to resolve completely, and in 1 excision was required using the transvesical transtrigonal technique. A total of 13 patients were treated nonoperatively, including 10 in whom the condition was discovered incidentally during screening for perineoscrotal hypospadias. In 5 of the 10 patients urinary tract infection subsequently developed and they were maintained on long-term chemoprophylaxis. CONCLUSIONS: By tailoring the surgical approach to the type of mullerian duct remnant and the relevant anatomical relationships a high degree of success may be achieved with minimal morbidity.

Adolescent↗

Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice.

Cathepsins have been implicated in the degradation of proteins destined for the MHC class II processing pathway and in the proteolytic removal of invariant chain (Ii), a critical regulator of MHC class II function. Mice lacking the lysosomal cysteine proteinase cathepsin S (catS) demonstrated a profound inhibition of Ii degradation in professional APC in vivo. A marked variation in the generation of MHC class II-bound Ii fragments and presentation of exogenous proteins was observed between B cells, dendritic cells, and macrophages lacking catS. CatS-deficient mice showed diminished susceptibility to collagen-induced arthritis, suggesting a potential therapeutic target for regulation of immune responsiveness.

Animals↗

A receptor scaffold mediates stimulus-response coupling in bacterial chemotaxis.

The mechanism of stimulus-response coupling in bacterial chemotaxis has emerged as a paradigm for understanding general features of intracellular signal transduction both in bacterial and eukaryotic cells. Until recently it was thought that the mechanism involved reversible stochastic interactions between dimeric receptors freely diffusing in the cytoplasmic membrane and several soluble signal transduction proteins within the cytoplasm. Recent results have shown that this view is an oversimplification. The receptors and most of the signal transduction proteins are organized together in a higher ordered structure at one pole of the bacterial cell. The scaffolding network within this structure appears to be composed of C-terminal alpha-helical extensions of the membrane chemoreceptor proteins held together in a lattice by tandem SH3-like domains. Results suggest that stimuli are detected through the perturbations they induce in scaffolding architecture.

Bacterial Outer Membrane Proteins↗

Bacterial chemotaxis: the five sensors of a bacterium.

The components of the Escherichia coli chemosensory system have been identified and their activities characterized, but how sensory information is processed to give an integrated response remains an open question.

Bacterial Proteins↗

Synchrony in telomere length of the human fetus.

Telomere length, measured by terminal restriction fragments, was examined in tissues from human fetuses of gestational ages estimated as 15-19 weeks. The length of telomeres was similar in most fetal tissues. However, there were significant variations in telomere length among fetuses, with no apparent relationship between gestational age and telomere length. We conclude that synchrony in telomere length exists among tissues of the human fetus. This synchrony is apparently lost during extrauterine life.

Body Weights and Measures↗

Photoactivation turns green fluorescent protein red.

In the few years since its gene was first cloned, the Aequorea victoria green fluorescent protein (GFP) has become a powerful tool in cell biology, functioning as a marker for gene expression, protein localization and protein dynamics in living cells. GFP variants with improved fluorescence intensity and altered spectral characteristics have been identified, but additional GFP variants are still desirable for multiple labeling experiments, protein interaction studies and improved visibility in some organisms. In particular, long-wavelength (red) fluorescence has remained elusive. Here we describe a red-emitting, green-absorbing fluorescent state of GFP that is generated by photoactivation with blue light. GFP can be switched to its red-emitting state easily with a laser or fluorescence microscope lamp under conditions of low oxygen concentration. This previously unnoticed ability enables regional, non-invasive marking of proteins in vivo. In particular, we report here the use of GFP photoactivation to make the first direct measurements of protein diffusion in the cytoplasm of living bacteria.

Escherichia coli↗

Mood swing.

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Health Care Reform↗