Bronchus associated lymphoid tissue (BALT) in human lung: its distribution in smokers and non-smokers.

BACKGROUND--Bronchus associated lymphoid tissue (BALT) is a normal component of the lung's immune system in many animals and may be analogous to gut associated lymphoid tissue (GALT). This study aimed at assessing the nature and extent of BALT in human lung and determining whether its expression is induced within the human airway in response to smoking. METHODS--Paraffin embedded, formalin fixed full thickness bronchial wall sections were examined from 31 whole lung specimens derived from both smokers and non-smokers. Samples were taken from throughout the bronchial tree to include main stem bronchi, lobar bronchi and segmental bronchi, as well as first to third generation carinae. Standard 4 microns step sections were stained by haematoxylin and eosin and immunocytochemical methods to show foci of BALT. RESULTS--Examination of 256 airway sites detected 46 foci of BALT. These differed from those described in other mammals in being distributed throughout the bronchial tree, in being found in relation to bronchial glandular epithelium as well as luminal bronchial epithelium, and in lacking any accompanying M cells. Analysis by smoking status showed that the expression of BALT was significantly more common in smokers than non-smokers (82% (14/17) v 14% (2/14) respectively). CONCLUSIONS--The findings support the view that BALT in humans is an integral feature in a comparatively small proportion of lungs from non-smokers while being significantly more prominent in lungs from smokers. The tissue shows several important differences from that described in other mammals.     

Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation

The stromal stem cell fraction of many tissues and organs has demonstrated to exhibit stem cell properties such as the capability of self-renewal and multipotency, allowing for multilineage differentiation. In this study, we characterize a population of stromal stem cells derived from menstrual blood (MenSCs). We demonstrate that MenSCs are easily expandable to clinical relevance and express multipotent markers such as Oct-4, SSEA-4, and c-kit at the molecular and cellular level. Moreover, we demonstrate the multipotency of MenSCs by directionally differentiating MenSCs into chondrogenic, adipogenic, osteogenic, neurogenic, and cardiogenic cell lineages. These studies demonstrate the plasticity of MenSCs for potential research in regenerative medicine.     

Mesenchymal stem cell tissue engineering: techniques for isolation, expansion and application

Mesenchymal stem cells (MSCs) are undifferentiated multipotent cells which reside in various human tissues and have the potential to differentiate into osteoblasts, chondrocytes, adipocytes, fibroblasts and other tissues of mesenchymal origin. In the human body they could be regarded as readily available reservoirs of reparative cells capable to mobilize, proliferate and differentiate to the appropriate cell type in response to certain signals. These properties have triggered a variety of MSC-based therapies for pathologies including nonunions, osteogenesis imperfecta, cartilage damage and myocardial infarction. The outcome of these approaches is influenced by the methodologies and materials used during the cycle from the isolation of MSCs to their re-implantation. This review article focuses on the pathways that are followed from the isolation of MSCs, expansion and implantation.     

Endoscopic tissue characterization by frequency-domain fluorescence lifetime imaging (FD-FLIM)

Tissue characterization by endoscopic fluorescence imaging of endogenous or exogenous fluorochromes is a promising method for early cancer detection. However, the steady-state fluorescence contrast between healthy tissue and lesions such as early-stage carcinomas is generally poor. The authors propose to improve this contrast by using the additional information contained in the fluorescence lifetime (FLT). The FLT of several fluorochromes is sensitive to their physico-chemical environment. The FLT can be measured by frequency-domain methods. The excitation light from a continuous wave (CW) laser is modulated in amplitude at radio-frequencies by an electro-optic modulator, and delivered to the tissue via an optical fibre. The endoscopie site is imaged by an endoscope on to an optical device. The gain of the fluorescence image detector is also modulated at the same frequency for homodyning. The tissue fluorescence image is recorded at several phases between the excitation and the detection modulations during an acquisition cycle. With these images, an image processor calculates the apparent FLT for each pixel and constructs a lifetime image of the endoscopie site. This process is performed at quasi-video frequencies. The influence of various physical parameters (modulation frequency, number of images by cycle, shot noise, tissue optical properties etc.) has been investigated by analytical analysis, simulation methods and experimentation. Preliminary results obtained on human tissues are also presented to illustrate the potentiality of the method.     

Familial amyloid polyneuropathy type I (Portuguese): distribution and characterization of renal amyloid deposits

Renal amyloidosis has been considered rare and late in the evolution of the transthyretin (TTR) familial amyloid polyneuropathy (FAP) of the Portuguese type (type I). Renal biopsy has been performed systematically in 14 patients with FAP type I before liver transplantation. In all patients, TTR Met30 mutation was shown. Seven had proteinuria or abnormal microalbuminuria, whereas seven others had no urinary abnormalities. All had renal amyloid deposition predominantly in the medulla. Glomerular and vascular involvement was more prominent in patients with urinary abnormalities. Patients with the most extensive renal lesions represented a subgroup with a low score of polyneuropathy disability, a high prevalence of nephropathy in the proband generation, or a late onset for relatives with nephropathy. Immunohistochemistry studies showed that the amyloid substance corresponded to transthyretin. We have shown that renal TTR-derived amyloid deposition is common in patients with FAP type I, even in the absence of urinary abnormalities. The clinical presentation of nephropathy is not a late occurrence in the disease.     

Collagen types. Molecular structure and tissue distribution.

The collagens are products of a superfamily of closely related genes. Currently, there are 13 described collagens encompassing at least 25 separate genes. The collagen molecules can be categorized into four classes. Class I consists of molecules that form the banded collagen fibers that are readily seen by routine electron microscopy. The banded fibers are heterogenous with respect to collagen type, containing at least two and often three collagen types in each fibril. This multiplicity is believed to effect the rate of fibril growth and the final fibril diameter. Class II contains collagens that adhere to the surface of the banded fibrils. The function of these molecules is not yet known. The third Class consists of molecules that form independent fiber systems. These include the basement membrane, beaded filaments, anchoring fibrils, and the network surrounding hypertrophic chondrocytes. The last class contains several collagens with unknown fiber forms, and whose functions are unclear. Tissues contain multiple fiber forms and therefore many individual collagen types. Bone is no different, and there are presently four known collagens in the bone cortex. This article summarizes knowledge of the structures and functions of the collagen superfamily.     

Renal osteodystrophy (I)

Renal bone disease represents one of the major complications of end-stage renal disease, accounting for the numerous and various changes at bone level, determined by abnormal calcium and phosphorus homeostasis and by changes in calcitriol and PTH synthesis. PTH represents as well a major uraemic toxin, exerting profound systemic effects, particularly at the cardiovascular level. PTH synthesis is mainly controlled by changes in calcium-phosphorus balance and calcitriol production by the kidneys. Several others factors are important in the development of secondary hyperparathyroidism: acidosis, autonomisation of PTH secretion and peripheral (target-organ) resistance to PTH actions. Although bone biopsy represents the definitive diagnostic test to differentiate between osteitis fibrosa, low-turnover bone disease and bone involvement unrelated to disturbed calcium metabolism (i.e. beta 2-microglobulin-related amyloidosis), plasma intact PTH generally exhibits a reasonably good relation with bone histology parameters. Moreover serum bone-specific alkaline phosphatase isoenzyme, serum pyridinoline and the novel serum markers for bone turnover are highly specific and correlate with bone histomorphometry parameters, so that, preventive and therapeutic strategies should be re-evaluated based solely on biochemical parameters.     

Renal osteodystrophy(II)

Renal bone disease represents one of the major complications of end-stage renal disease, accounting for the numerous and various changes at bone level, determined by abnormal calcium and phosphorus homeostasis and by changes in calcitriol and PTH synthesis. PTH represents as well a major uraemic toxin, exerting profound systemic effects, particularly at the cardiovascular level. PTH synthesis is mainly controlled by changes in calcium-phosphorus balance and calcitriol production by the kidneys. Several others factors are important in the development of secondary hyperparathyroidism: acidosis, autonomisation of PTH secretion and peripheral (target-organ) resistance to PTH actions. Although bone biopsy represents the definitive diagnostic test to differentiate between osteitis fibrosa, low-turnover bone disease and bone involvement unrelated to disturbed calcium metabolism (i.e. beta 2-microglobulin-related amyloidosis), plasma intact PTH generally exhibits a reasonably good relation with bone histology parameters. Moreover serum bone-specific alkaline phosphatase isoenzyme, serum pyridinoline and the novel serum markers for bone turnover are highly specific and correlate with bone histomorphometry parameters, so that, preventive and therapeutic strategies should be re-evaluated based solely on biochemical parameters.     

Human adipose‐derived stem cells: isolation,characterization and applications in surgery

The ideal stem cell for use in functional tissue engineering needs to be abundantly available, harvested with minimal morbidity, differentiated reliably down various pathways and able to be transplanted safely and efficaciously. Adult human adipose tissue contains a population of mesenchymal stem cells, termed ‘adipose‐derived stem cells’ (ASC), which seem to fulfil most, if not all, of these criteria. ASC can be harvested readily, safely, and in relative abundance by modern liposuction techniques. They are capable of differentiating into other mesenchymal tissue types, including adipocytes, chondrocytes, myocytes and osteoblasts. They also show angiogenic properties, with recent evidence of a potential role in healing radiotherapy‐damaged tissue, possibly due to their secretion of vascular endothelial growth factor. Similarly, they may have a role in healing chronic wounds, and as such are being investigated in phase 1 trials for their ability to aid healing of recurrent Crohn’s fistulae. Subsequently they have a wide range of potential clinical uses in all fields of surgery. This article reviews the current and potential clinical applications of ASC in relation to surgery, as well as methods for their isolation, differentiation and molecular characterization.     

Renal calculi: pathogenesis, diagnosis, and medical therapy.

Selective medical therapy of nephrolithiasis is highly effective in preventing new stone formation. A remission rate of greater than 80% and an overall reduction in individual stone formation rate of greater than 90% can be obtained in patients with nephrolithiasis. In patients with mild to moderate severity of stone disease, virtually total control of stone disease can be achieved with a remission rate of greater than 95%. The need for stone removal may be dramatically reduced by an effective prophylactic program (Fig 6). Selective pharmacological therapy of nephrolithiasis also encompasses the advantages of overcoming nonrenal complications as well as averting certain side effects that may be caused by nonselective medical therapy. Despite these advantages, it is clear that selective medical therapy cannot provide total control of stone disease. A satisfactory response requires continued, dedicated compliance by patients to the recommended program and a commitment by the physician to provide long-term follow-up and care.     

Hypertension, microalbuminuria and renal dysfunction: the Renal Dysfunction in Hypertension (REDHY) study

AIMS: We assessed the prevalence of kidney dysfunction evaluated by different methods to estimate glomerular filtration rate (GFR) in a wide group of nondiabetic hypertensive patients, without cardiovascular (CV) complications and without known renal disease, participating in the Renal Dysfunction in Hypertension (REDHY) study. METHODS: A total of 1,856 hypertensive individuals (mean age 47 +/- 14 years; men 53%), free from diabetes mellitus and CV complications, and consecutively attending our outpatient hypertension center, were enrolled. Patients with a body mass index >35 (calculated as kg/m(2)) were excluded. The GFR was estimated by the creatinine clearance rate (CrCl), the simplified Modification of Diet in Renal Disease Study prediction equation (MDRD), the Cockcroft-Gault formula (CG) and the Mayo Clinic quadratic equation (Mayo). A 24-hour urine sample was collected to evaluate CrCl and albumin excretion rate (AER). Albuminuria was defined as an AER greater than 20 microg/min. RESULTS: The prevalence of albuminuria was 23.4% (22.7% microalbuminuria and 0.7% macroalbuminuria). Mild renal dysfunction (defined as 24-hour AER >20 microg/min in presence of eGFR > or =60 ml/min per 1.73 m(2)) was found in a proportion of patients ranging from 20.3% using CrCl, to 18.4% using the MDRD equation. The prevalence of overt renal insufficiency (estimated GFR <60 ml/min per 1.73 m(2)) was higher when CrCl (10.8%) or the MDRD equation (10%) was used to estimate the GFR, instead of the CG (7.4%) or Mayo equation (5.4%) (p<0.0001). CONCLUSIONS: Mild renal dysfunction and overt renal insufficiency are highly prevalent among subjects with nonmalignant arterial hypertension without CV complications. However, the prevalence of moderate-to-severe renal function impairment is strongly influenced by the method used to estimate the GFR.