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Immunophenotypic and genotypic characterization of B-cell chronic lymphocytic leukemia patients from northern Italy.

BACKGROUND AND METHODS: Immunoglobulin (Ig) gene expression and rearrangements provide information about cell lineage, clonality and differentiation of neoplastic lymphoid cells. We performed flow cytometry and Southern blot analysis in 25 patients with chronic lymphocytic leukemia (CLL) from the Po River delta region (Northern Italy), in order to correlate surface immunological phenotype and heavy and light chain gene rearrangements with clinical stages. RESULTS: In these 25 CLL cases, as in the larger group of 165, k-positive (k+) patients were more frequent than lambda-positive (lambda +) ones by a ratio of 59:41, with a predominance of lambda + in stage II (46:54) and of K+ in stage IV (77:23). However, the survival behavior of lambda + and k+ patients was not statistically different. Ig gene rearrangements were found in all patients in accordance with the immunophenotype. When Ig gene analysis was performed on two different occasions in 7 of the 8 who received chemotherapy, there was an increase in the percentage of the germline band. This variation was inversely related to changes in WBC count. In the treated subject who showed a reduction of both WBC count and the germline, there was rapid disease progression and short survival. CONCLUSIONS: Analysis of Ig gene rearrangements in our CLL patients demonstrated: i) the monoclonality of neoplastic cells; ii) no correlation between rearrangements and clinical stages, and iii) that this analysis may be a useful tool in evaluating biological behavior in selected CLL cases showing a discrepancy between hematological data and clinical response to therapy.

Clone Cells↗

Construction of an allogenic chimeric mouse model for the study of the behaviors of donor stem cells in vivo.

BACKGROUND: It is essential to establish an animal model for the elucidation of the biological behaviors of stem cells in vivo. We constructed a chimeric animal model by in utero transplantation for investigation of stem cell transplantation. METHODS: This chimerism was achieved by injecting the stem cells derived from the bone marrow of green fluorescence protein (GFP)-transgenic mice into fetal mice at 13.5 days of gestation. Several methods such as polymerase chain reaction (PCR), real-time PCR, fluorescence-assisted cell sorting (FACS) and fluorescence in situ hybridization (FISH) were used for the observation of donor cells. RESULTS: Under a fluorescence microscope, we observed the GFP cells of donor-origin in a recipient. PCR, FACS analysis and FISH indicated chimerism at various intervals. Real-time PCR indicated that some donor cells existed in chimera for more than 6 months. CONCLUSIONS: Allogenic stem cells may exist in recipients for a long time and this allogenic animal model provides a useful tool for studying the behavior of hematopoietic stem cells and also offers an effective model system for the study of stem cells.

Animals↗

Taking bitewing radiographs in preschoolers using behavior management techniques.

Radiographs are essential diagnostic tools to enable dentists to make adequate decisions and treatment plans. Treatment plans for young children, however, are quite often based on no or less than ideal radiographs. Getting successful bitewing radiographs from young children demands both behavior management techniques and adequate equipment. This report reviews the literature, and presents a modified technique of taking radiographs in young children. The technique was successfully used with 156 three-to-five-year-old children from Yakima County, Washington. Behavioral management of the children employed several techniques: building rapport, tell-show-do, modeling, positive reinforcement and increasing the child's sense of control. The equipment and placement technique were designed to be as atraumatic as possible. Positive experiences in the dental office often enhance a child's future cooperation. The techniques presented are simple to learn and use in treating very young children.

Behavior Therapy↗

Cholinergic cell loss and cognitive impairments following intraventricular or intradentate injection of colchicine.

Bilateral injections of colchicine (3.5 or 7.0 micrograms/0.5 microliters/site) into either the dentate gyrus or the lateral cerebroventricles (i.c.v.) of Sprague-Dawley rats produced specific behavioral, histopathological and neurochemical alterations. Colchicine, administered via either route, produced impairments in the performance of a radial-arm maze task which did not subside during 8 weeks of testing. Intradentate colchicine decreased (1) the thickness of both blades of the dentate granule cell layer, (2) the size of the overlying molecular layer, (3) hippocampal volume, and (4) the number of cholinergic neurons in the medial septum/vertical limb of the diagonal band (MS/VLDB). I.c.v. administration of colchicine did not alter any index of hippocampal morphology but did significantly decrease the number of cholinergic neurons in the MS/VLDB. An analysis of the time course of cholinotoxicity revealed that both intradentate and i.c.v. colchicine decreased choline acetyltransferase (ChAT) activity and high affinity choline uptake (HAChU) in the hippocampus at 1 and 3, but not 9, weeks following surgery. Furthermore, i.c.v. colchicine decreased ChAT activity in the septum at both 3 and 9 weeks following surgery. Neither route of administration altered ChAT or HAChU in the frontal cortex, olfactory bulb or striatum. The decreases in presynaptic cholinergic parameters were paralleled by a reduction in acetylcholinesterase staining in the hippocampus which appeared to recover within 9 weeks. These data suggest that intradentate colchicine produces either (i) transsynaptic degeneration of cholinergic neurons due to a loss of their target sites (granule cells in the dentate gyrus), (ii) a direct cholinotoxic effect, or (iii) a combination of these mechanisms. The i.c.v. injection of colchicine appears to exert a direct toxic effect on cholinergic neurons and/or nerve terminals that results in the death of these neurons. Colchicine may be a useful tool for investigating the behavioral and neurobiological properties of the septohippocampal cholinergic pathway and its response to injury.

Animals↗

Concordance of risk factors in female spouses of male patients with coronary heart disease.

PURPOSE: Shared environment may put marital partners at increased risk for coronary heart disease (CHD). In this study, the authors examined the degree of concordance of risk factors between men with CHD (n = 177) and their spouses, and described the risk profiles of both patients and spouses. Risk factors examined were smoking, hypertension, obesity, cholesterol level, diet, and exercise. METHODS: Data were collected 2 months after the cardiac event using the Behavioral Risk Factor Surveillance System tool. Concordance between patient and spouse pairs was evaluated using Pearson correlation coefficients (r) for continuous data and phi coefficients (phi) for nominal data. RESULTS: Significant concordance was found between patient and spouse pairs for body mass index, history of smoking, current smoking status, frequency of exercise, miles per exercise session, and the amount of fat and fiber in the diet. There was no significant spousal concordance in relation to the diagnosis of hypertension, systolic and diastolic blood pressure (BP), cholesterol level, history of high cholesterol, current exercise program, duration of exercise, and amount of salt in the diet. Thus, although the physiological indicators of risk (e.g., BP) were not significantly related among marital partners, behavioral indicators of risk (e.g., smoking) were significantly related. CONCLUSIONS: The findings suggested that shared lifestyles of marital partners may result in greater risk of CHD for female partners of men with CHD. Furthermore, lifestyle interventions that specifically target the marital partners as a unit may be more efficacious than individual patient education strategies.

Adult↗

Stromelysin-3 is expressed by aggressive meningiomas.

BACKGROUND: Stromelysin-3 (ST3) that belongs to the metalloproteinase family is proposed to play a role in tumor invasion. The purpose of this work was to study the variation of ST3 expression in meningiomas. METHODS: Twenty atypical meningiomas were retrieved from the Pathology Department's files at Hopital de Bellevue, Saint-Etienne, France. They were compared with 20 benign meningiomas randomly selected from the same file. The tumors were classified using standard histologic criteria. Frozen sections of the tumors were immunostained for ST3 and MIB-1 to evaluate the proliferative activity of tumor cells. RESULTS: The study included 5 fibrous meningiomas, 10 transitional meningiomas, 20 syncitial meningiomas, 2 secretory meningiomas, 2 microcystic meningiomas, and 1 angiomatous meningioma. Stromelysin-3 was expressed within the stromal and neoplastic cells of only 1 benign meningioma and 13 atypical meningiomas. The MIB-1 proliferation index was significantly higher in the meningiomas expressing ST3 (Student t test: P < 0.001). The invasion of bone, muscle, and brain by meningiomas as well the recurrence were statistically correlated with their ST3 expression (Kruskal-Wallis nonparametric correlation test, P = 0.001 and P = 0.008, respectively). CONCLUSIONS: Stromelysin-3 might play an important role in the invasiveness of meningiomas. Therefore, considering, ST3 in association with evaluation of the MIB-1 proliferating index may be an useful tool to assess the behavior of meningiomas.

Adult↗

Neuroimmunomodulation: a brief review. Can conditioning of natural killer cell activity reverse cancer and/or aging?

Modern scientific evidence of interactions among the nervous, endocrine, and immune systems dates from the late nineteenth century, although this concept was certainly known to the ancients in Asia, Europe, Africa, and the Americans. Within the past two decades, the mechanisms of these interactions, known today as neuroimmunomodulation (NIM), have been investigated, from the subcellular to the behavioral levels, using the modern tools of receptor and membrane physiology, biochemistry, pharmacology, immunology, chronobiology, and genetics. One of the best demonstrations of neural-immune interactions was classical (Pavlovian) conditioning of immune responses, first reported by Metal'nikov et al. at the Pasteur Institute in the 1920's. Within the past 10 years, my colleagues at the University of Alabama in Birmingham and the Gerontology Research Center in Italy, and I, in experiments with mice, demonstrated (a) a 3- to 39-fold enhancement of natural killer (NK) cell activity by conditioning; (b) reversal of an otherwise fatal cancer (myelo-MOPC-104 E) by perinoculation conditioning ; and (c) that very old animals can be similarly conditioned to increase, many fold, their NK activity in the absence of an antigen. NK cells are among the body's first-line defenses against cancer and viral infections. Research on NIM and its mechanisms is growing exponentially; indeed, it may be the fastest growing field in biomedical sciences. (The International Society for NIM, founded only a few years ago, now has active members in 40 countries.) This revolution in the basic sciences will undoubtedly lead to a corresponding revolution in clinical practice and, most importantly, in the area of preventive medicine.

Aging↗

An approach to the management of the pruritus of cholestasis.

The cause of the pruritus of cholestasis is unknown. It is inferred that pruritus results from the accumulation in plasma of substances that are made in the liver and excreted in bile under physiologic conditions. The idea of neurotransmitters as important mediators in the pruritus of cholestasis has evolved over the past several years. There is evidence to suggest that endogenous opioids contribute to the pruritus of cholestasis and, for the first time, specific treatment for the pruritus has been instituted. The deficiency of studying pruritus with subjective methodology alone has been overcome with the development of objective methodology to study the behavioral manifestation of pruritus, scratching behavior. The use of this tool allows the definition of clear objective end-points, scratching activity, for inclusion in clinical trials.

Antipruritics↗

Cholesterol-phospholipid interaction in membranes. 1. Cholestane spin-label studies of phase behavior of cholesterol-phospholipid liposomes.

The effect of cholesterol concentration on the thermotropic phase behavior of aqueous phospholipid multi-bilayers was monitored by means of electron spin resonance spectroscopy (ESR) of a cholestane spin-label (CSL). The spin-label itself induces an additional transition in several different phospholipids, which is attributed to local melting around the spin probe. In contrast, cholesterol prevents its neighboring phospholipids from undergoing fluidization. Small additions of cholesterol affect the position of the probe-induced lipid mobilization curve. The phospholipid main gel-liquid-crystal transition, which is also observed as a separate change in probe mobilization, is not affected by low concentrations of cholesterol. These observations indicate the presence of two phases, a cholesterol-rich phase and a pure phospholipid phase, and indicate that CSL preferentially enters the cholesterol-rich phase. Addition of more than 20 mol % cholesterol abolishes the bulk phospholipid phase. This is evidenced by the disappearance of the gel-liquid-crystal transition as observed by ESR. However, the CSL-induced transition is present at all concentrations of cholesterol and CSL. The behavioral differences between the two sterols caution against using this probe as a direct substitute for cholesterol. However, it remains a useful tool for monitoring the phase behavior of cholesterol-phospholipid bilayer systems.

Cholestanes↗

A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects.

Controlled cortical impact (CCI), using a pneumatically driven impactor to produce traumatic brain injury, has been characterized previously in both the ferret and in the rat. In the present study, we applied this technique to establish and characterize the CCI model of brain injury in another species, the mouse, evaluating cognitive and histopathologic outcome. In anesthetized (sodium pentobarbital, 65 mg/kg) male C57BL mice, we performed sham treatment (no injury, n = 12) or CCI injury (n = 12) at a velocity of 5.7-6.2 m/sec and depth of 1 mm, using a 3-mm diameter rounded-tip impounder, positioned over the left parietotemporal cortex (parasagittal). At this level of injury, we observed highly significant deficits in memory retention of a Morris water maze task 2 days following injury (p < 0.001). Postmortem histopathologic analysis performed at 48 h following injury revealed substantial cortical tissue loss in the region of impact and selective hippocampal neuronal cell loss in the CA2, CA3, and CA3c regions, using Nissl staining. Analysis of degenerating neurons using modified Gallyas silver staining techniques demonstrated consistent ipsilateral injury of neurons in the cortex adjacent to the impact site and in the dentate gyrus of the ipsilateral hippocampus. Bilateral degeneration was observed at the gray matter-white matter interface along the corpus callosum. Glial fibrillary acidic protein (GFAP) immunohistochemistry revealed extensive reactive gliosis appearing diffusely through the bilateral cortices, hippocampi, and thalami at 48 h postinjury. Breakdown of the blood-brain barrier was demonstrated with antimouse IgG immunohistochemistry, revealing extravasation of endogenous IgG throughout the ipsilateral cortex, hippocampus, and thalamus. These results suggest that this new model of parasagittal CCI in the mouse mimics a number of well-established sequelae observed in previously characterized brain injury models using other rodent species. This mouse model may be a particularly useful experimental tool for comparing behavioral and histopathologic characteristics of traumatic brain injury in wild-type and genetically altered mice.

Animals↗

Perceptions of physical therapists toward patient education.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the perceptions of physical therapists regarding their involvement in patient education. We developed a questionnaire to assess procedures or activities taught, methods or tools used, important physical therapist behaviors, techniques used to assess the effectiveness of teaching, barriers to delivering effective education, relative value of patient care activities as compared with other activities, and factors contributing to the development of teaching skills. SUBJECTS AND METHODS: The questionnaire was sent to 300 American Physical Therapy Association members nationwide chosen by a random sample. Two hundred questionnaires, or 69% of the eligible responses were used in the data analysis. RESULTS: Most respondents indicated they teach 80% to 100% of their patients. Nearly all respondents teach range-of-motion techniques, home programs, and treatment rationale through the use of demonstration and verbal discussion. Most respondents recognize the importance of many therapist behaviors related to patient teaching and use observation and evaluation to assess the effectiveness of their teaching. Barriers to patient education most frequently cited were psychological factors of the patient. Interaction with patients was considered most important to the development of respondents' teaching skills. CONCLUSION AND DISCUSSION: Implications and suggestions for further research are discussed.

Attitude of Health Personnel↗

The religious medical model: holy medicine and the Spiritual Behavior Inventory.

This paper describes the history and basis of the Spiritual Inventory from its beginning. Initially, the Inventory took the form of a casual interview. The advantage of an interview is clinical judgment and the ability to diagnose the spirituality of the patient. Analysis of spiritual behavior is a useful clinical tool. This paper also includes a detailed explanation of the role of the rabbi-physician.

Adaptation, Psychological↗

Reframing research on sexual behavior and HIV.

This review of recent studies examines the conceptual and methodological tools that are used to understand sexual behavior and HIV. Whereas surveys have provided reliable indicators of behavior, their validity is uncertain, their correlation with biological indicators tenuous, and the explanations they offer limited. Microlevel research has called into question the rationalizing, medically informed, and risk-averse frameworks used in the public health literature on HIV and behavior, but its impact has been limited. Thus, surveys and qualitative research have proceeded along two separate tracks, and this separation has hampered our understanding of sexual behavior. A small but growing number of studies, however, provide examples of less-compartmentalized research that avoids oversimplification. They show that expanding the models that drive research in this area is possible, and that efforts to combine disciplinary perspectives result in deeper understandings of knowledge, risk perceptions, attitudes, and behavioral change.

HIV Infections↗

The elevated requirement for methionine by transformed rat liver epithelial cells in vitro.

Growth constants appear to constitute a useful tool in comparing the behavior for transformed and untransformed cells in culture. The substitution of homocysteine for methionine in culture medium caused a greater depression of growth with 3/4 of the transformed epithelial and with 10/14 other cell lines tested compared to the growth depression seen in similar untransformed lines. The greater growth depression exhibited by transformed lines on methionine-deficient, homocysteine-supplemented medium could generally be attributed to: 1. Greater growth of transformed cells in complete medium, and 2. The lower levels of methyltransferase generally found in the transformed lines. Finally methyltransferase appears to be a major determinant of growth of both normal an transformed cells growing in a methionine-deficient, homocysteine-supplemented medium.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Intersection tests for single marker QTL analysis can be more powerful than two marker QTL analysis.

BACKGROUND: It has been reported in the quantitative trait locus (QTL) literature that when testing for QTL location and effect, the statistical power supporting methodologies based on two markers and their estimated genetic map is higher than for the genetic map independent methodologies known as single marker analyses. Close examination of these reports reveals that the two marker approaches are more powerful than single marker analyses only in certain cases. Simulation studies are a commonly used tool to determine the behavior of test statistics under known conditions. We conducted a simulation study to assess the general behavior of an intersection test and a two marker test under a variety of conditions. The study was designed to reveal whether two marker tests are always more powerful than intersection tests, or whether there are cases when an intersection test may outperform the two marker approach.We present a reanalysis of a data set from a QTL study of ovariole number in Drosophila melanogaster. RESULTS: Our simulation study results show that there are situations where the single marker intersection test equals or outperforms the two marker test. The intersection test and the two marker test identify overlapping regions in the reanalysis of the Drosophila melanogaster data. The region identified is consistent with a regression based interval mapping analysis. CONCLUSION: We find that the intersection test is appropriate for analysis of QTL data. This approach has the advantage of simplicity and for certain situations supplies equivalent or more powerful results than a comparable two marker test.

Animals↗

Hemispheric asymmetries of limb-kinetic apraxia: a loss of deftness.

OBJECTIVES: Unlike patients with ideomotor apraxia who make temporal and spatial errors and patients with ideational or conceptual apraxia who make content errors, patients with limb-kinetic apraxia have loss of deftness, including fine and precise movements, independent finger movements, and difficulty coordinating simultaneous movements. This study was conducted to learn the relationship between limb-kinetic apraxia and hemisphere dysfunction by using selective hemisphere anesthesia, the Wada test. METHODS: Subjects were 90 patients undergoing Wada testing for intractable epilepsy. They were divided into typical (right-handed with left hemisphere language dominance) and atypical (nonright-handed, or without left hemisphere language dominance). Before and during Wada testing, subjects were shown line drawings of tools, four for each hand tested. After being shown each picture, subjects pantomimed the use of this tool. A behavioral neurologist and neuropsychologist scored the pantomimes for the presence of limb-kinetic errors. RESULTS: For the typical group, during left hemisphere anesthesia, the limb-kinetic errors made by the right and left hands did not differ, but during right hemisphere anesthesia the left hand made more errors than the right. Unlike the typical subjects, when the left hemisphere was anesthetized, the atypical subjects made more errors with their right hands than left. However, similar to the typical subjects with right hemisphere anesthesia, the atypical subjects made more left- than right-hand limb-kinetic errors. CONCLUSIONS: For people with typical brain organization, the left hemisphere mediates motor deftness for both hands, but the right hemisphere primarily controls deftness for the left hand. For people with atypical brain organization, each hemisphere primarily controls deftness for the contralateral hand.

Adult↗

Reaction times for hand movements made in response to visual versus vibratory cues.

Reaction times were determined for monkeys and humans who made wrist flexion and extension movements in response to vibratory and visual cues. Humans initiated movements approximately 50 msec sooner in response to vibratory as compared to visual cues. For monkeys, this difference was approximately 100 msec. Mean daily reaction times for monkeys and humans improved with practice until they reached a steady level of performance. Increased differences between vibratory and visual reaction times were weakly correlated with increased age of humans. The increase in the differences appeared to result from decreased reaction times by older subjects for vibratory-cued movements; reaction times for visually cued movements did not consistently vary across the age range of subjects tested (19-36 years). The results obtained using this novel paradigm suggest that it may be a useful tool for simultaneously testing behavioral performance or neurological function during somatosensorimotor and visuomotor tasks.

Adult↗

Use of an autobioluminescent Campylobacter jejuni to monitor cell survival as a function of temperature, pH, and sodium chloride.

The effects of storage temperature (4, 22, and 30 degrees C), pH (4.0 to 8.5), and sodium chloride concentration (0.25 to 7.5%, wt/vol) on the survival of a strain of Campylobacter jejuni ATCC 35921 with an autobioluminescent phenotype (generated from the fusion of luxCDABE genes from Xenorhabdus luminescens to the C. jejuni flaA promoter) in Mueller-Hinton broth under aerobic conditions were determined. At comparable pHs, autobioluminescent C. jejuni cells die most rapidly at 30 degrees C and most slowly at 4 degrees C. For example, at pH 5.5, a 1.2-log decrease in the cell count was observed after 4 days of storage at 4 degrees C, while 3.7- and 4.8-log reductions in cell numbers were observed after 4 days of storage at 22 and 30 degrees C, respectively. At 4 degrees C, C. jejuni was sensitive to NaCl concentrations of > or = 2.5%. However, the degree of inactivation at this storage temperature was also significantly lower than that observed at 22 degrees C, which, in turn, was substantially lower than that observed at 30 degrees C. In the presence of different NaCl concentrations at 22 and 30 degrees C, a strong correlation (r = 0.98) between plate count and bioluminescence output was obtained. However, at low pHs (4.0 and 4.5) and/or a low storage temperature (4 degrees C), bioluminescence did not correlate well with plate count. Despite these limitations, an autobioluminescent phenotype of C. jejuni proved to be a useful tool for studying the behavior of C. jejuni exposed to environmental stresses.

Campylobacter jejuni↗