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Biomedical subjects

S Hultgren

Publications and source records attributed to S Hultgren.

10 recordsLinked to original sources

Symposium report on urothelial dysfunction: pathophysiology and novel therapies.

PURPOSE: The basic premise of this symposium (Workshop 7) at the 2004 International Continence Society meeting in Paris was to elucidate different mechanisms of urothelial cell pathology, explore their impact on bladder function and discuss novel therapeutic interventions. RESULTS: The topics included 1) urothelial structure and function, 2) the role of adenosine triphosphate in urothelial signaling and cystitis, 3) lamina propria myofibroblasts and purinergic receptors, 4) antiproliferative factor involvement in interstitial cystitis, 5) the urothelium as a reservoir for bacterial infections, 6) radiation cystitis, nitric oxide and gene therapy, and 7) intravesical treatments. DISCUSSION: It was agreed that the urothelium can no longer be regarded merely as a passive barrier separating urine from the underlying tissues. The epithelial cells of the urothelium form part of an integrated network that also includes afferent and possibly efferent nerves, and suburothelial myofibroblasts. It has a central role in several functions, including bladder wall sensation, local blood flow modulation, pathogen removal and active barrier provision. These functions are achieved through several autocrine and paracrine pathways that involve transmitter release from the urothelium and its ability to integrate incoming signals through its battery of membrane receptors. Several pathological processes were discussed using this knowledge, including the role of small glycoproteins released during interstitial cystitis, the molecular basis of radiation induced urothelial damage, the origin of recurrent urinary tract infections and the mode of action of potential intravesical treatments for overactive bladder. CONCLUSIONS: Overall it was concluded that the urothelium has a key role in regulating lower urinary tract physiology and pathology.

Animals↗

Sleep disturbances in outpatients with ankylosing spondylitisa questionnaire study with gender implications.

OBJECTIVE: To study the sleep pattern in ankylosing spondylitis, and to investigate gender differences in sleep, pain, and fatigue. METHODS: Forty-three male and 27 female patients with ankylosing spondylitis completed a sleep questionnaire and the results were compared with earlier findings in 3,558 persons randomly selected from the general population. RESULTS: Too little sleep was reported by 80.8% of the female and 50.0% of the male patients, compared to 28.8% and 21.8% respectively in the reference group (p<0.0001). The main reason was pain in the pre-sleep and sleep-periods (p<0.0001). Daytime fatigue was a major problem (p<0.0001). Higher correlation was found between pain and daytime fatigue than between sleep disturbance and daytime fatigue. CONCLUSION: Sleep disturbance is a significant problem in ankylosing spondylitis. The disturbance is closely related to pain at bedtime and during the night. Gender differences exist in the subjective sleep disturbance, fatigue, and pain.

Adult↗

Systemic immunization with conserved pilus-associated adhesins protects against mucosal infections.

Colonization and infection of the bladder mucosa by Escherichia coli, the major uropathogenic organism, is dependent on the expression of pilus organelles. Type 1 pili are expressed by the majority of E. coli strains derived from patients with cystitis and pyelonephritis. FimH is the adhesin protein located at the distal tip of the heteropolymeric type-1 pilus which mediates binding to bladder cells through mannose receptors. We have shown that humoral antibody raised against two forms of purified FimH adhesin inhibited 94% (49/52) of E. coli UTI clinical isolates from binding to bladder tissue in vitro. Animals immunized with FimH-containing vaccines by a systemic route reduced colonization of the bladder mucosa in vivo in a murine cystitis model by > 99%. IgG antibody to FimH was detected in urinary samples obtained from immunized, protected mice. Passive systemic administration of immune sera from FimH-inoculated mice to naive animals also resulted in reduced colonization of bladder mucosa by uropathogenic E. coli. These studies demonstrate that systemic immunization with an anti-bacterial vaccine targeting a highly conserved adhesin on uropathogenic E. coli can induce IgG-mediated protection at a mucosal surface and may be a means of preventing recurrent and acute infections of the urogenital tract mucosa.

Adhesins, Bacterial↗

Impaired contrast sensitivity in adolescents and young type 1 (insulin-dependent) diabetic patients with microalbuminuria.

We compared neurosensorial visual function by psychophysical tests (macular recovery time and contrast sensitivity) in two well matched groups of young Type 1 (insulin-dependent) diabetic patients with micro- and normoalbuminuria, respectively. The patients had normal visual acuity (> or = 1.0) and either no retinopathy or non-proliferative retinopathy. Thirty patients with microalbuminuria (albumin excretion > or = 15 micrograms/min in a least two out of three timed overnight urine samples) were matched (age, diabetes duration, mean one-year HbA1c, gender) with normoalbuminuric (n = 27) patients. Retinopathy (50 degree colour fundus photography) was assessed by counting microaneurysms and hemorrhages as 'red spots'. Contrast sensitivity was examined for the spatial frequencies of 1.5, 3, 6, 12 and 18 cycles per degree (cpd). Macular recovery time (nyctometry) refers to the time-related (2 min) ability of the retina to regain visual acuity following exposure to bright light (photostress). Contrast sensitivity score was reduced in patients with microalbuminuria compared to those without; 18 cpd (mean and 95% confidence intervals): [4.2 (3.8-4.7) vs 5.0 (4.6-5.4), p = 0.03]. Macular recovery performance was not significantly reduced: [21.0 arbitrary units (17.5-24.6) vs 26.0 (22.6-30.7), p = 0.12]. We conclude that impaired contrast sensitivity independent of background retinopathy is shown in a group of young Type 1 (insulin-dependent) diabetic patients with low-grade microalbuminuria compared to a group of patients with normoalbuminuria.

Adolescent↗

Initiation of assembly and association of the structural elements of a bacterial pilus depend on two specialized tip proteins.

Uropathogenic Escherichia coli produce heteropolymeric surface fibers called P pili, which present an adhesin at their tip that specifically recognizes globoside receptors on the host uroepithelium. The initial attachment step is thought to be essential for pathogenesis. P pili are composite fibers consisting of a thin tip fibrillum joined end to end to a rigid helical rod. Here we show that the ordered assembly of these structures requires the activity of two proteins that are minor components of the tip fibrillum, PapF and PapK. PapF is required for the correct presentation of the adhesin at the distal end of the tip fibrillum. PapK regulates the length of the tip fibrillum and joins it to the pilus rod. We propose that these subunits function as adaptors, by providing complementary surfaces to different substructures of the pilus and promoting their proper associations. In addition, the conversion of chaperone-subunit complexes into pili depends on PapF and PapK since a papF- papK- double mutation abolishes piliation. We suggest that in addition to the adaptor functions of PapF and PapK, they are also required to initiate the formation of tip fibrillae and pilus rods.

Adhesins, Escherichia coli↗

Psychophysical visual function, retinopathy, and glycemic control in insulin-dependent diabetics with normal visual acuity.

We studied relations between psychophysical visual function and grade of retinopathy, glycemic control and clinical background data in 51 insulin-dependent diabetic patients, aged 17-47 years. Three separate qualities of visual function were examined, macular recovery time (nyctometry; 2 min adaptation), contrast sensitivity (Vistech 6000 chart; between 1.5 and 18 cycles per degree (cpd)) and colour vision (Fletcher DS8; protan/deutan and tritan). Only contrast sensitivity of 6 cpd was associated with the grade of retinopathy; reduced function was found in patients with retinopathy compared to those without. No correlations between macular recovery, contrast sensitivity and colour vision were found. None of the visual functions was significantly related to glycemic control, age, duration of diabetes, blood pressure, intraocular pressure, or urinary albumin excretion. Our data suggests that the neurosensory function of contrast sensitivity correlates more sensitively to the grade of diabetic retinopathy than macular recovery and colour vision. Cross-sectional assessments of different psychophysical visual functions seem to be of restricted clinical value as indicators of preceding glycemic control in diabetic patients with no or mild nonproliferative retinopathy.

Adolescent↗

Improved transmission electron microscopy technique for the study of cytologic material.

A modification of the technique of Coleman et al for the preparation of single cells in cytologic specimens for electron microscopy (EM) is described. By employing materials in the initial cytologic processing that are useful for EM, such as a paraformaldehyde-glutaraldehyde fixative, lactated Ringer's solution as a rinsing medium, glycerol as a mounting medium and cacodylate buffer for removal of coverslips, the use of alcohol fixatives and standard mounting media could be avoided. This preserved the cytoplasmic detail, which is usually degenerated in cells removed from cytologic specimens and processed for EM.

Biopsy, Needle↗

Mending broken slides.

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Histological Techniques↗