Human stem cell assays in immune-deficient mice

Much of our understanding of the organization of the cells that comprise the hematopoietic system and the cellular and molecular mechanisms that regulate their development is derived from mouse models. However, knowledge of the human hematopoietic system and identification of human stem cells have, until recently, been hampered by the absence of in vivo assays that measure their repopulation capacity. The development of methods to transplant normal and leukemic human hematopoietic cells into immune-deficient SCID mice provides the foundation for human stem cell assays. This review will focus on recent evidence that normal and leukemic human stem cells can be assayed in these systems.     

Phase behavior of ternary blends containing dimethylpolycarbonate,tetramethylpolycarbonate and poly[styrene‐co‐(methyl methacrylate)] copolymers (or polystyrene)

The miscibility and phase behavior of ternary blends containing dimethylpolycarbonate (DMPC), tetramethylpolycarbonate (TMPC) and poly[styrene‐co‐(methyl methacrylate)] copolymer (SMMA) have been explored. Ternary blends containing polystyrene (PS) instead of SMMA were also examined. Blends of DMPC with SMMA copolymers (or PS) did not form miscible blends regardless of methyl methacrylate (MMA) content in copolymers. However, DMPC blends with SMMA (or PS) blends become miscible by adding TMPC. The miscible region of ternary blends is compared with the previously determined miscibility region of binary blends having the same chemical components and compositions. The region where the ternary blends are miscible is much narrower than that of binary blends. Based on lattice fluid theory, the observed phase behavior of ternary blends was analyzed. Even though the term representing the Gibbs free energy change of mixing for certain ternary blends had a negative value, blends were immiscible. It was revealed that a negative value of the Gibbs free energy change of mixing was not a sufficient condition for miscible ternary blends because of the asymmetry in the binary interactions involved in ternary blends. Copyright © 2004 Society of Chemical Industry     

The binding of substrates and inhibitors to the metal center of myoinositol monophosphatase

The synthetic substrate anthraniloyl-beta-glycerol-P binds to myoinositol monophosphatase with a Kd = 5 microM at pH 7.5. The anthraniloyl chromophore, excited at 330 nm, sensitizes the long lived luminescence of bound Tb(III) at 490, 545, 585 and 620 nm. Assuming a mechanism of radiationless energy transfer, the actual distance of separation between the donor-acceptor pair was calculated to be R = 10 A. Tb(III) binds to the monophosphatase with a Kd = 2 microM, whereas Ca-(II) displaces the lanthanide at concentrations above 0.1 mM. The binding studies support the notion that Tb(III), Ca(II) and Mg(II) interact with a common binding site on the protein. Phosphate ion, a strong competitive inhibitor, perturbs the luminescence of bound Tb(III), whereas the substrate beta-glycero-P has no effect on the luminescence yield and long-lived emission of bound Tb(III). It is suggested that the phosphate group of the substrate is not in direct contact with the metal ion coordinated to several amino acid residues of the enzyme.     

Abnormal behavioral responses to fenfluramine in patients with affective and personality disorders. Correlation with increased serotonergic responsivity

Serotonergic responsivity was assessed in 20 psychiatric patients by the prolactin response to a fenfluramine challenge test. During the fenfluramine challenge 6 of 20 patients (30%) spontaneously reported psychopathologic reactions that included: increased anxiety/agitation, psychotic symptoms, illusions, mood elevation, and anergia. The time of peak behavioral symptoms (2.5 +/- 0.8 hrs) corresponded closely to the time of peak increase in prolactin levels (3.0 +/- 1.1 hr). Abnormal behavioral responders had statistically significant greater increases in prolactin 1 to 4 hr after fenfluramine when compared to normal responders. Patients who developed an abnormal psychopathologic response to fenfluramine were characterized by higher levels of anxiety and agitation at the time of admission to the hospital but otherwise were not distinguishable on the basis of severity of other psychiatric symptoms. This study suggests that increased serotonergic transmission may trigger anxiety, psychosis, and mood elevation in specific vulnerable individuals, whereas other patients with similar psychiatric illnesses are not affected.     

A case-mix classification system for medical rehabilitation

Dissatisfaction with Medicare's current system of paying for rehabilitation care has led to proposals for a rehabilitation prospective payment system, but first a classification system for rehabilitation patients must be created. Data for 36,980 patients admitted to and discharged from 125 rehabilitation facilities between January 1, 1990, and April 19, 1991, were provided by the Uniform Data System for Medical Rehabilitation. Classification rules were formed using clinical judgment and a recursive partitioning algorithm. The Functional Independence Measure version of the Function Related Groups (FIM-FRGs) uses four predictor variables: diagnosis leading to disability, admission scores for motor and cognitive functional status subscales as measured by the Functional Independence Measure, and patient age. The system contains 53 FRGs and explains 31.3% of the variance in the natural logarithm length of stay for patients in a validation sample. The FIM-FRG classification system is conceptually simple and stable when tested on a validation sample. The classification system contains a manageable number of groups, and may represent a solution to the problem of classifying medical rehabilitation patients for payment, facility planning, and research on the outcomes, quality, and cost of rehabilitation.     

Inhalation toxicity of 1,6-hexanediamine dihydrochloride in F344/N rats and B6C3F1 mice

1,6-Hexanediamine (HDA) is a high production volume chemical which is used as an intermediate in the synthesis of paints, resins, inks, and textiles and as a corrosion inhibitor in lubricants. Two- and 13-week studies of the toxicity of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice using whole-body inhalation exposure. Both species were evaluated for histopathologic and reproductive effects, and rats were examined for clinical chemistry and hematologic changes. In the 2-week inhalation studies, animals were exposed to 10-800 mg HDDC/m3, 6 hr per day. All rats, all female mice, and two of five male mice in the high-exposure group died before the end of the study. Surviving mice in this group had a dose-dependent depression in body weight gain. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in both species. Treatment-related histopathologic lesions included inflammation and necrosis of the laryngeal epithelium of both species and the tracheal epithelium of mice, as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In the 13-week inhalation studies, animals were exposed to HDDC at concentrations of 1.6-160 mg/m3 for 6 hr per day, 5 days per week. In addition to the base study groups, a supplemental group of rats at each exposure level was included to assess the effect of HDDC on reproduction. No treatment-related changes in organ weights or organ-to-body-weight ratios occurred in rats, and no treatment-related clinical signs or gross lesions were seen in either species. Chemical-related microscopic lesions were limited to the upper respiratory tract (larynx and nasal passages) in the two highest exposure groups and were similar in both species. These lesions included minimal to mild focal erosion, ulceration, inflammation, and hyperplasia of the laryngeal epithelium, in addition to degeneration of the olfactory and respiratory nasal epithelium. HDDC caused no significant changes in sperm morphology or vaginal cytology and no significant adverse effects on reproduction in rats or mice. Hematologic and clinical chemistry changes in rats were minor and sporadic and were not accompanied by related histologic findings. HDDC did not increase the frequency of micronucleated erythrocytes in mice.(ABSTRACT TRUNCATED AT 400 WORDS)     

Expression of a human homeobox-containing gene is regulated by 1,25(OH)2D3 in bone cells

The seasonal variation in the nutrient composition of Enhydra fluctuans and Marsilea quadrifolia, two edible semi-aquatic plants, was studied in order to promote their consumption as green leafy vegetables. Both plants had a high crude protein content throughout all harvesting seasons. Enhydra fluctuans had a low ash content and was a good source of beta-carotene (3.7 to 4.2 mg/100 g on a fresh weight basis). Marsilea quadrifolia exhibited wide fluctuations between seasons and was not very promising in nutrient composition when compared to other commonly used green leafy vegetables.     

Clinical applications of fundus reflection densitometry

Fundus reflection densitometry or retinal densitometry is a non-invasive technique to examine the visual photopigment kinetics in living eyes. The technique is based on the comparison of the reflected light from the fundus in a fully light adapted eye (when all visual photopigment has been bleached) with the reflected light following complete dark adaptation (when the retina contains its maximum amount of visual photopigment). The technique provides a measure of the density of visual photopigment, its time constant of regeneration, its distribution and spectral characteristics if measured at a series of wavelengths. Fundus reflection densitometry in the human eye was introduced 40 years ago. Presently, it is the only available technique from which direct and objective insight can be obtained into visual photopigment. This knowledge is particularly relevant in eyes where abnormalities of photoreceptor function are suspected. This paper summarizes the current knowledge of fundus reflection densitometry in the diseased and in the aging human retina, gathered over the last 30 years. Considerable improvements of the instrument for clinical purposes have been obtained, and are also discussed.