Human tissue studies

Chronic exposures chronic exposure symptoms are similar to acute exposures with pulmonary lung function decrements depending on concentrations and duration of exposure. Asthma, allergies, other respiratory disorders have been observed. Breathing disorders, tumorgenic, direct and indirect genetic damage have been found in animal and/or human tissue studies. 

Kathren RL. 1987. Implications of human tissue studies. Govt Rep Announce Ind, Issue II. NTIS/DE87002063. 

Kathren RL. 1988. Implications of human tissue studies for radiation protection. Health Phys 55 315-319. 

Tables I and II summarize available human tissue studies. It would be optimal to utilize body fluids such as blood or urine. It remains to be established if blood testing will be a reliable surrogate for target tissues and if so, if one blood component is more appropriate than another. We also will need to consider half-lives of blood cells (lymphocytes and red blood cells survive longer than granulocytes), differences in repair and ability to separate blood cells. It has been reported that the initial adduction of lymphocytes and granulocytes is similar but that adduct levels are more persistent in the latter (58). Our laboratory has used lymphocytes (31-33.451 while others have studied total white blood cells (predominantly granulocytes) (36.591.

The subcellular distribution of total CLA was compared with the distribution of monounsaturated fatty acids (MUFA) and LA. It turned out that for renal as well as for testicular tissue CLA and MUFA are similarly distributed, whereas LA shows a different distribution pattern. The most prominent CLA isomers in the human tissues studied are the c,t and t,c isomers, respectively. As c,t and t,c unsaturated fatty acids show a stereochemical structure similar to that of f-MUFA, their similar distribution pattern is easily explained. The differing subcellular distribution patterns of LA and CLA, which support the results of our TFA intervention study (Hofiriiann, K., et al., submitted for publication) and the study conducted by Petridou et al. (15), underline the different physiological properties of these two fatty acids. 

JF Brennan III, Y Wang, RR Dasari, MS Feld. Near IR Raman spectrometer system for human tissue studies. Appl Spectrosc 51 201-208, 1997. 

Brennan J, Wang Y, Dasari RR and Feld MS (1997) Near-infrared Raman spectrometer system for human tissue studies. Applied Spectroscopy 51(2) 201- 208. 

Two biotin transporters have been described a multivitamin transporter present in many tissues and a biotin transporter identified in human lymphocytes. In 1997, Prasad and coworkers discovered a Na" "-coupled, saturable, structurally specific transporter present in human placental choriocarcinoma cells that can transport pantothenic acid, lipoic acid, and biotin. This sodium-dependent multivitamin transporter has been named SMVT and is widely expressed in human tissues. Studies by Said and coworkers using RNA interference specific for SMVT provide strong evidence that biotin uptake by Caco-2 and HepG2 cells occurs via SMVT thus, intestinal absorption and hepatic uptake are likely mediated by SMVT. The biotin transporter identified in lymphocytes is also Na coupled, saturable, and structurally specific. Studies by Zempleni and coworkers provide evidence in favor of monocarboxylate transporter-1 as the lymphocyte biotin transporter. 

The identification of PCB residues in fish, wildlife, and human tissues has been reported since the 1970s (9—13,20—26). The results of these analytical studies led to the ultimate ban on further use and production of these compounds. The precise composition of PCB extracts from biota samples is highly variable and depends, in part, on the specific analyte and the commercial PCB preparations associated with a contaminated area (14). PCBs found in a composite human milk sample from Michigan (26) were highly complex, and the congener composition and their relative concentrations did not resemble any of the commercial PCB preparations. This fact raises obvious problems with regard to the ha2ard assessment of PCB mixtures (27). 

The quantification of kinins in human tissues or body fluids has been limited due to the inherent difficulties in accurately measuring the concentration of ephemeral peptides. Today HPLC-based and RIA/capture-ELA measurements are established to determine kinins in human plasma, liquor or mine. Serine protease inhibitors need to be added to prevent rapid degradation of the kinins in vitro during sample preparation. Kinins and their degradation products have been studied in various biological milieus such as plasma/ serum, urine, joint fluids, kidney, lung and skeletal muscle [2]. Under normal conditions, the concentration of kinins in these compartments is extremely low for... 

Positron emission tomography (PET) makes use of a short-lived positron emitter such as fluorine-18 to image human tissue with a degree of detail not possible with x-rays. It has been used extensively to study brain function (see illustration) and in medical diagnosis. For example, when the hormone estrogen is labelled with fluorine-18 and injected into a cancer patient, the fluorine-bearing compound is preferentially absorbed by the tumor. The positrons given off by the fluorine atoms are quickly annihilated when they meet... 

We proposed to study diet and health by combining bone chemistry and histomorphometry. Diet would be determined by analysis of stable isotopes of carbon and nitrogen in bone protein and some preserved hair. In addition, trace elements would be quantitatively analyzed in preserved bone mineral. Abonyi (1993) participated in the study by reconstructing the diet from historical sources and analyzing various foods. Having analyzed human tissues for stable isotopes and trace elements, and foods for the same variables, we hoped to learn more about 19th century diet in southern Ontario, and at the same time, learn more about paleodiet reconstruction. 

Several studies of tissue distribution in humans after inhalation exposure to trichloroethylene report levels in the blood (Astrand and Ovrum 1976 Monster et al. 1976 Muller et al. 1974). Once in the bloodstream, trichloroethylene may be transported rapidly to various tissues where it will likely be metabolized. Trichloroethylene was detected in the blood of babies at birth after the mothers had received trichloroethylene anesthesia (Laham 1970), and detectable levels (concentrations not reported) have been found in the breast milk of mothers living in urban areas (Pellizzari et al. 1982). Post-mortem analyses of human tissue from persons with unspecified exposure revealed detectable levels of trichloroethylene (<1-32 pg/kg wet tissue) in most organs (McConnell et al. 1975). The relative proportions varied among individuals, but the major sites of distribution appeared to be body fat and the liver. 

The absorption and transport processes of many of the phytochemicals present in food are complex and not fully understood, and prediction of their bioavailability is problematic. This is particularly true of the lipid-soluble phytochemicals. In this chapter the measurement of carotenoid bioavailability will be discussed. The carotenoids serve as an excellent example of where too little understanding of food structure, the complexity of their behaviour in foods and human tissues, and the nature and cause of widely different individual response to similar intakes, can lead to misinterpretation of study results and confusion in our understanding of the relevance of these (and other) compounds to human health. 

Measurement of exposure can be made by determining levels of toxic chemicals in human serum or tissue if the chemicals of concern persist in tissue or if the exposure is recent. For most situations, neither of these conditions is met. As a result, most assessments of exposure depend primarily on chemical measurements in environmental media coupled with semi-quantitative assessments of environmental pathways. However, when measurements in human tissue are possible, valuable exposure information can be obtained, subject to the same limitations cited above for environmental measurement methodology. Interpretation of tissue concentration data is dependent on knowledge of the absorption, excretion, metabolism, and tissue specificity characteristics for the chemical under study. The toxic hazard posed by a particular chemical will depend critically upon the concentration achieved at particular target organ sites. This, in turn, depends upon rates of absorption, transport, and metabolic alteration. Metabolic alterations can involve either partial inactivation of toxic material or conversion to chemicals with increased or differing toxic properties. 

Middleton J, Americh L, Gayon R, et al. A comparative study of endothelial cell markers expressed in chronically inflamed human tissues MECA-79, Duffy antigen receptor for chemokines, von Willebrand factor, CD31, CD34, CD 105 and CD146. J Pathol 2005 206(3) 260-268. 

The use of vesicle cell membranes, isolated cells, and cell monolayers and intestinal tissue studies has provided valuable correlations with in situ and in vivo drug absorption in animals as well as correlations with drug absorption in clinical studies. Most prominent among the literature sources establishing correlations between in vitro tissue and cellular systems with drug absorption in humans are the work of Dowty and Dietsch [73], Lennernas et al. [74], and Stewart et al. [75],... 

Moreover, experimental reference maps of human tissues were studied p7 and Mr coordinates of identified spots were retrieved from the SWISS-2D-PAGE database, the values <3X = 0.009 pH and av = 0.0002 log Mr were assumed for spot dimension since they represent the standard case for experimental 2D-PAGE maps—normal sample loading of a tissue homogenate (ca. 1 mg total protein) and standard gel sizes (18 x 20 cm, IEF x SDS-PAGE). 

Investigations of regional differences in permeability and metabolism have been carried out using a variety of animal models [22, 29, 75, 102, 109, 112, 137]. Animal tissues (mainly from rats) are widely used in the Ussing chamber to investigate intestinal transport of drugs, and regional aspects [29, 75, 138], whereas few studies have been conducted with human tissues due to their limited availability. 

DNA array-CGFI data were provided by Sandy DeVries at Dr. Fredric Waldman s Lab at UCSF. RNA extraction experiments were technically performed by Cheng Liu and Kelly Smith. Both studies were supported by NUT grant 1 R33 CA103455. Use of human tissues has been exempted under 45 CFR 46.101 (b) and was approved by the Institutional Review Board (IRB 009071) at USC. 

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