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Biomedical subjects

R M White

Publications and source records attributed to R M White.

At least 37 records · Page 2Linked to original sources
PubMed1996

Complementary organ expression of IL-1 vs. IL-6 and CSF-1 activities in normal and LPS-injected mice.

The specific expression of pro-inflammatory cytokines may affect the functioning of organs in different ways. The results of specific cytokine bioassays used in this study show a distinct pattern of tissue expression of IL-1 IL-6 and CSF-1. Cytokine activity was assessed in conditioned media (CM) and lysates (LYS), obtained from different organs of control or lipopolysaccharides (LPS)-injected mice; LPS representing a potent inflammatory stimulus. Low constitutive levels of IL-1 could be demonstrated only in CM/LYS from organs with lymphoreticular function, such as the liver, spleen, intestine and lungs. On the other hand, IL-6 and CSF-1 were mainly detected in the CM (and not in lysates) of organs, such as the heart, kidneys, muscle and brain. LPS injection basically resulted in an accentuated form of the constitutive pattern. CSF-1 displays a similar pattern of expression to that of IL-6, best detected in CM after LPS stimulation. Thus, a mirror-image relationship emerges between the patterns of IL-1 and IL-6/CSF-1 expression in two groups of organs: those with lymphoreticular function, which manifest high IL-1 and low IL-6/CSF-1 activity, as compared to organs characterized by highly specialized and potentially vulnerable functions (such as the heart, brain, muscle and kidney), which exhibit high IL-6/CSF-1 and low IL-1 activity. Due to their defensive functions, lymphoreticular organs, which are in charge of the 'gates of entry' to the body, mount extensive IL-1-mediated inflammatory responses, even at the cost of possible tissue-damage. On the other hand, the more vulnerable internal organs mount IL-6/CSF-1-mediated responses which are milder and bear less potential for tissue damage. The distinct patterns of expression of pro-inflammatory cytokines in different organs, at steady state or under inflammatory conditions, may shed light on tissue characteristic homeostatic and defence mechanisms.

Animals↗
PubMed1996

Interleukin-6 release following scorpion sting in children.

Interleukin-6 levels were measured in the serum of ten children following severe scorpion envenomation. Measurements were taken on arrival, at the emergency room, and 12 and 24 hr after arrival. Interleukin-6 was markedly elevated in the serum of eight out of ten children on arrival. Interleukin-6 levels gradually decreased toward normal values on 12 and 24 hr measurements, but remained above control levels on all measurements. These results imply that signs and symptoms following scorpion envenomation may in part be explained by release of cytokines. Human and experimental animal studies are required in order to verify the assumption that interleukin-6 and other cytokines are involved in the pathogenesis of scorpion envenomation.

Animals↗
PubMed1996

A phase I study of methotrexate administration following 5-fluorouracil.

A priming dose of 5-fluorouracil can decrease the toxicity and retain the efficacy of high-dose methotrexate in laboratory models. This Phase I study determined the maximum tolerated dose of methotrexate that can be administered after a dose of 5-fluorouracil without leucovorin rescue. Forty-two patients received 5-fluorouracil (500 mg/m2) by bolus injection followed in 2 h by methotrexate infused over 1 h; treatment was repeated every 3 weeks. Patients received five doses of leucovorin (10 mg/m2 every 6 h); this was reduced to two doses and then to zero doses (no rescue) if less than grade 2 toxicity occurred in prior treatments. If safe, at least two patients received no leucovorin rescue with their first treatment. The dose of methotrexate was escalated in cohorts of patients, starting with a methotrexate dose of 200 mg/m2. Previously untreated patients maximally tolerated 1600 mg/m2 of methotrexate with 5-fluorouracil pretreatment. Leukopenia combined with stomatitis prevented deescalation of leucovorin doses. Fourteen percent of total courses and 15% of courses without leucovorin rescue resulted in dose limiting toxicity. MTX levels exceeded levels that require leucovorin rescue. Four of the 33 (12%) advanced head and neck cancer patients had objective responses to therapy; median survival was 10 months. Previously treated patients were less tolerant; oral and hematological toxicities were troublesome; 400 mg/m2 of methotrexate was the approximate maximum tolerated dose. Forty-seven percent of total courses and 60% of courses without leucovorin rescue resulted in dose limiting toxicity. There were no responses. Although the antineoplastic activity is poor, prior 5-fluorouracil exposure does protect tissues susceptible to methotrexate toxicity.

Adult↗
PubMed1996

Epidural hematoma of a cauda equina in a child with hemophilia A.

PURPOSE: The presenting signs, treatment, and outcome of an epidural hematoma of the cauda equina in a child with severe hemophilia are reported for the first time. PATIENTS AND METHODS: A 20-month-old boy with severe hemophilia A (factor VIII <0.01 U/ml) presented with a 12-day history of refusal to stand and constipation of 5-7 days duration. He had normal deep tendon reflexes with normal sensation and withdrawal to pinprick of his lower extremities bilaterally. He stood on his right leg, but had inversion of his left foot and refused to bear weight on his left leg. MRI revealed an epidural hematoma of the cauda equina and a distended bladder. Factor VIII replacement therapy and lumbosacral laminectomy with evacuation of the hematoma resulted in recovery of a normal gait, but bladder dysfunction persisted for 11 months. Clean intermittent catheterization (CIC) was required until bladder function returned. RESULTS: Complete neurologic recovery occurred 11 months after presentation CONCLUSION: This case demonstrates the following points: (a) an epidural hematoma of the cauda equina in a child with severe hemophilia can present with neurologic findings that are as subtle as those seen in normal children; (b) CIC can be performed safely over an extended period without factor VIII replacement; and (c) complete recovery is possible, despite prolonged bladder dysfunction and a 12-day interval between the onset of symptoms and treatment.

Cauda Equina↗
PubMed1996

A source model for efficient brachytherapy computations with Monte Carlo.

Monte Carlo techniques have the potential for producing accurate brachytherapy dose distributions in heterogeneous finite geometries. However, for routine clinical use, computational speed must be adequate. A fast, all-particle, CT-based Monte Carlo code called PEREGRINE is being developed at Lawrence Livermore National Laboratory for radiation treatment planning. As one feature, the code will produce accurate dose distributions from brachytherapy sources in heterogeneous geometries. For efficiency, brachytherapy sources in this model are treated as points or line segments. Radiation is emitted with the proper energy spectrum and (perhaps anisotropic) angular distribution. In particular, for anisotropic emission the polar angle is determined by a random-number driven empirical function constructed from a source's measured or precomputed fluence emission pattern. Source model parameters are presented for iodine and iridium sources. While designed for the PEREGRINE program, this source model can be used in any Monte Carlo code.

Biophysical Phenomena↗
PubMed1996

Differential contribution of endothelial function to vascular reactivity in conduit and resistance arteries from deoxycorticosterone-salt hypertensive rats.

The purpose of these studies was to compare changes in conduit and resistance artery function in deoxycorticosterone-salt hypertensive rats. We hypothesized that if there was a common mechanism producing changes in vascular function in hypertension, then there would be similar alterations in reactivity of conduit and resistance arteries. Helically cut strips of common carotid artery were prepared for measurement of isometric force generation, and segments of small mesenteric arteries were pressurized for video dimension analysis. Sensitivity of arteries to phenylephrine and acetylcholine was determined. Carotid arteries from deoxycorticosterone-salt hypertensive rats were more sensitive to phenylephrine than arteries from control rats, whereas mesenteric resistance arteries from hypertensive rats were less sensitive to phenylephrine. In carotid arteries, endothelial denudation or incubation with N psi-nitro-L-arginine increased phenylephrine sensitivity in control rats to the level seen in deoxycorticosterone-salt rats. These manipulations had no effect on phenylephrine sensitivity in arteries from deoxycorticosterone-salt rats. In mesenteric resistance arteries, endothelium denudation normalized the depressed phenylephrine sensitivity in arteries from hypertensive rats but had no effect on arteries from normotensive rats. This depressed phenylephrine sensitivity in deoxycorticosterone-salt mesenteric arteries was not reversed by incubation with Npsi-nitro-L-arginine. Acetylcholine-induced relaxation was depressed in carotid arteries from deoxycorticosterone-salt hypertensive rats, and Npsi-nitro-L-arginine blocked these relaxations. In contrast, acetylcholine relaxation in the mesenteric arteries from normotensive and hypertensive rats did not differ. N psi-nitro-L-arginine slightly but significantly attenuated acetylcholine dilation only in mesenteric resistance arteries from the hypertensive rats. We conclude that qualitatively different changes in vasoconstrictor sensitivity to phenylephrine occur in carotid arteries and mesenteric resistance arteries of deoxycorticosterone-salt hypertensive rats. The increased phenylephrine sensitivity in carotid arteries in this model of hypertension is due to the loss of endothelium-derived nitric oxide production. In contrast, the decreased phenylephrine sensitivity in mesenteric resistance arteries from deoxy-corticosterone-salt rats is due to a non-nitric oxide-mediated influence of the endothelium that is absent in arteries from normotensive rats.

Acetylcholine↗
PubMed1995

5-fluorouracil modulates the toxicity of high dose methotrexate.

Pretreatment with 5-fluorouracil (FU) attenuated the toxicity of high dose methotrexate (MTX) in in vitro and in vivo models. Because dose intensification of the MTX reversed the fluoropyrimidine antagonism of MTX activity in these models, administering FU before the MTX offered the potential advantage of MTX dose intensity and low toxicity without the confounding effects of leucovorin rescue. The current study was conducted to determine the maximum dose of MTX tolerated after a priming dose of FU without leucovorin rescue, and to determine the toxicities of this combination. Subjects (n = 42) received a constant dose of FU followed in 2 hours by MTX; treatment was repeated every 3 weeks. Subjects initially received five doses of leucovorin (10 mg/m2 every 6 hours); this was reduced to two doses, then to zero doses (no rescue) if less than grade 2 toxicity occurred in prior treatments. Cohorts of subjects received escalating doses of MTX in a Fibonacci fashion. At the 1250 mg/m2 dose level, almost all previously untreated subjects tolerated the elimination of leucovorin rescue, without the occurrence of severe toxicity; this was 6 to 8 times the MTX dose that generally requires leucovorin rescue to avoid severe and lethal toxicity. The 24- and 48-hour MTX levels were at a level that usually requires leucovorin rescue. Previously treated subjects were less tolerant; 400 mg/m2 of MTX was the approximate maximum tolerated dose. Prior FU exposure appeared to protect tissues normally susceptible to MTX toxicity, and allowed safe administration of high dose MTX without leucovorin rescue.

Adult↗
PubMed1994

Scientific conduct.

Explore the source record for details and available documents.

Biomedical Research↗
PubMed1994

Biases in memory for and use of inconsistent beliefs in stereotyping.

Some research has suggested that level of inconsistency of information that invalidates expectancy-based stereotypes or trait labels is one of several moderating variables that determine the memorability and use of inconsistent information (e.g. Rojahn & Pettigrew, 1992). Two experiments were designed to identify variables that moderate memory for and use of counter-stereotypic social-political beliefs that were attributed to a stereotypically identified group. In Expt 1, recall was found to be inversely related to level of inconsistency. In Expt 2, location of counter-stereotypic beliefs within a list and the order of counter-stereotypic beliefs (most-to-least vs. least-to-most inconsistent) determined the form of the relationship between recall and level of inconsistency. When counter-stereotypic beliefs were presented relatively early in a list and were ordered from least-to-most inconsistent, a positive relationship obtained; otherwise, the relationship was negative. Stereotyping was less extreme when counter-stereotypic beliefs were presented early in the least-to-most inconsistent ordering. Cognitive processes that may have produced these sets of findings were discussed.

Adolescent↗
PubMed1994

Involvement of immune responses in the eradication of IL-1 alpha gene-transduced tumour cells: mechanisms of tumour rejection and immunotherapeutical implications.

We detected a strong correlation between the constitutive expression of IL-1 alpha and reduced tumorigenicity, using fibrosarcomas which produce the cytokine spontaneously (as an aberration of the transformation process) or upon gene transfer. In fibroblasts intracellular or membrane-associated IL-1 alpha is expressed, whereas the secreted form of the cytokine (IL-1 beta) is absent. Studies on the mechanisms of tumour regression of the IL-1 alpha producing fibroblastoid cell lines indicated that IL-1 alpha potentiates the development of tumour cell-specific CTLs, which are of importance for tumour eradication. It also appears that IL-1 alpha-induced enhanced helper T-cell activity provides auxiliary signals for the growth/development of CTLs. In addition, we observed a massive lymphocytic infiltrate in IL-1 alpha producing regressing tumours which ultimately replaces the tumour's mass. Non-adaptive effector cells, activated locally by IL-1 alpha expressing fibrosarcoma cells, were also shown to contribute, to some extent, to the eradication of IL-1 alpha expressing fibrosarcomas. Local IL-1 alpha expression potentiated antigen presentation, by the malignant fibroblasts as well as by tissue-resident antigen-presenting cells, and by this anti-tumour immune responses were further potentiated. Mice, in which IL-1 alpha producing tumours regressed, developed systemic immunity and rejected a challenge with a non IL-1 producing violent tumour cell line. It appears that endogenous IL-1 alpha, being a strong inducer of cytokine production, operates a whole cytokine cascade (such as IL-6, CSFs and prostaglandins). However, studies using clonal populations have indicated that IL-1 alpha is essential for fibrosarcoma eradication, whereas the other cytokines possibly amplify and sustain its action. We assume that most naturally occurring tumours are not constitutive IL-1 alpha producers, as it would be disadvantageous for the tumour to express a cytokine which increases its immunogenicity. However, IL-1 non-producing fibrosarcomas can be induced easily to express IL-1 transiently, by treatment with cytokines/LPS, and upon the induction of the cytokine they shift from progressor to regressor tumours. We also obtained positive immunotherapeutical effects when treating mice bearing IL-1 non-producing fibrosarcomas with cells from the same line induced in vitro to express IL-1 alpha. The results may shed light on a novel parameter affecting tumour-host interactions, namely cytokine expression by the tumorous cells, and may provide the basis for new immunotherapy protocols for fibrosarcoma management.

3T3 Cells↗
PubMed1994

Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities.

PURPOSE: To investigate the evolution of deeply located high-signal-intensity abnormalities of the brain on T2-weighted MR images of patients with neurofibromatosis type 1 (NF-1). METHODS: The study consists of two patient groups: 1) retrospective evaluation of MR scans of 24 symptomatic NF-1 patients, 10 of whom were sequentially studied, and 2) prospective MR evaluations of 20 asymptomatic NF-1 subjects from 14 families; 2 of these families were sequentially studied. RESULTS: Deeply located, high-signal-intensity abnormalities on T2-weighted images were noted in 34 of 44 NF-1 subjects (77%). If NF-1 patients are grouped according to age, 28 of 30 subjects (93%) younger than 15 years had the lesions, whereas 4 of 7 subjects (57%) between 16 and 30 years, and 2 of 7 subjects (29%) older than 31 years had lesions. High-signal lesions in basal ganglia and brain stem were demonstrated in all decades with relatively high frequency. Lesions in the cerebellar white matter and dentate nuclei were mainly found in the patients younger than 10 years, and never found after the third decade. In 13 sequential studies (mean interval, 24 months), lesions appeared to increase in size in 3, remain unchanged in size in 2, and decrease in size in 7. One subject showed a mixed pattern of lesion size change. CONCLUSIONS: Deeply located high-signal-intensity lesions on T2-weighted MR images are more evident in young NF-1 patients. The underlying brain abnormality, while pathologically unproved, is probably transient.

Adolescent↗
PubMed1993

Cytokine-induced tumor immunogenicity: endogenous interleukin-1 alpha expressed by fibrosarcoma cells confers reduced tumorigenicity.

A direct correlation between the constitutive expression of IL-1 alpha and reduced tumorigenicity of fibrosarcomas was observed. This was established in fibrosarcoma cell lines which produce IL-1 alpha 'spontaneously', possibly as an aberration of oncogene-mediated transformation or upon IL-1 alpha gene transfer. In fibroblasts intracellular or membrane-associated IL-1 alpha is expressed, whereas the secreted form of the cytokine (IL-1 beta) is absent. Studies on the mechanisms of tumor regression of the IL-1 alpha-positive fibroblastoid cell lines indicated that IL-1 alpha potentiates the development of tumor cell-specific CTLs, which are of importance for tumor eradication. Thus, IL-1 alpha induces enhanced helper T cell activity which provides auxiliary signals for the growth/development of CTLs. Non-adaptive effector cells, activated locally by IL-1 alpha-expressing fibrosarcoma cells, also contribute to the eradication of IL-1 alpha-expressing fibrosarcomas. Local IL-1 alpha expression potentiated antigen presentation, by the malignant fibroblasts as well as by tissue-resident antigen-presenting cells, thus further potentiating anti-tumor immune responses. Mice, in which IL-1 alpha-producing tumors were regressed, developed an immune memory and rejected a challenge with an IL-1 non-producing violent tumor cell line. Endogenous IL-1 alpha activates a cytokine cascade (i.e., IL-6, CSF), produced by the malignant cells and possibly also by stromal cells. However, IL-1 alpha expression is essential for fibrosarcoma eradication, while other cytokines possibly amplify and sustain its action.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1993

Viscosity sensing with lamb-wave microsensor: dimethylsulfoxide solution viscosity as a function of temperature.

Recently, a new microsensor employing low-velocity ultrasonic Lamb waves was developed and demonstrated to be capable of measuring the viscosity of solutions in small volumes. The microsensor, when attached to a temperature-controlled stage, can measure viscosity as a function of temperature. In this investigation, the ultrasonic Lamb-wave oscillator is employed to experimentally measure the viscosity of dimethylsulfoxide (Me2SO) solutions as a function of temperature. The microsensor and the experimental procedure are described and results for 1M, 3M, and 5M Me2SO aqueous solutions are presented. Dimethylsulfoxide is a compound commonly employed as a cryoprotectant in cryopreservation, the low-temperature preservation of biological materials. The temperature dependence of viscosity obtained through this study can be used in determining the probability for ice nucleation in biological materials, a parameter of importance during cryopreservation.

Calibration↗
PubMed1992

Induction chemotherapy for advanced head and neck cancer: modification of response to chemotherapy by antiemetics.

Forty Stage IV head and neck cancer patients were entered on a multimodality trial of induction chemotherapy (cisplatin + infusional 5-fluorouracil), surgery, and radiation. During chemotherapy, the patients of Group A (the first 19 patients) were medicated with metoclopramide. The patients of Group B (the next 21 patients) were medicated with droperidol. The groups were comparable. The response rate (complete + partial) was 32% for Group A and 52% for Group B (p = 0.16). Primary site (p = 0.08) and surgical margin (p = 0.005) clearance of tumor were better in Group B. Nodal disease responded poorly to chemotherapy in both groups. Tumor necrosis (p = 0.006) and granulation tissue (p = 0.07) were reduced in surgical specimens after chemotherapy in Group B. The drugs were well tolerated with reversible toxicity; nausea/vomiting (p = 0.01) and weight loss (p = 0.07) after chemotherapy, were increased in Group B. The 2-year survival was 26% for Group A and 62% for Group B (p = 0.027). The median survival was 15 months for Group A and 33 months for Group B (p = 0.05). Progression-free survival improved in Group B (p greater than 0.17). These improvements in response and survival did not appear to reflect changes in surgical or radiotherapy management, but may have reflected an uninhibited effect of cisplatin in Group B. It is theorized that the metabisulfite formulated with metoclopramide altered the pharmacokinetics or pharmacodynamics of cisplatin. This resulted in the poor response to chemotherapy and poor survival in Group A. An analysis of a randomized trial comparing metoclopramide (formulated with metabisulfite) versus a control antiemetic can confirm the data presented in this pilot study. Overall, our patients survived as well as others in comparable multimodality studies in Europe and the United States.

Adult↗
PubMed1991

Attitudes toward alcoholism among psychologists and marriage, family and child counselors.

This study examines the attitudes of 589 randomly chosen licensed California psychologists and marriage, family and child counselors toward alcoholism. Their anonymous replies revealed that the two professional groups were relatively homogeneous in nature. The majority of each subscribed to the disease concept of alcoholism, recognized the importance of abstinence in problem resolution and as a treatment goal, rejected insight as a prerequisite of sobriety, believed in a positive prognosis and were extremely willing to be involved in the treatment of alcoholics. Negative attitudes toward alcoholics were expressed with respect to attribution of responsibility and a persistence of stigmatization of the alcoholic.

Adult↗
PubMed1990

Use of a surface-acoustic-wave sensor to characterize the reaction of styrene vapor with a square-planar organoplatinum complex.

A coated surface-acoustic-wave (SAW) sensor is used to probe the reaction of styrene vapor with the square-planar platinum-ethylene pi-complex, trans-PtCl2(ethylene)(pyridine). A dual-SAW delay-line oscillator configuration is employed: one oscillator is coated with a solvent-cast film of the solid platinum-ethylene complex dispersed in a poly(isobutylene) matrix, and the second oscillator is coated only with polymer. Absorbed styrene vapor displaces ethylene to form the stable styrene-substituted complex, trans-PtCl2(styrene)(pyridine), causing a decrease in the oscillator frequency from the increase of mass on the surface of the sensor. For short-term exposures, there is a linear relationship between the logarithm of the rate of frequency change and the logarithm of the styrene vapor concentration, consistent with a power-law kinetic model for the heterogeneous trapping reaction. Deviation from this relationship above 300 ppm at 25 degrees C is attributed to the onset of multilayer adsorption of styrene at the surface of the trapping reagent. The sensor response exhibits an Arrhenius temperature dependence permitting estimation of the thermal activation energy for the olefin-substitution reaction. Calculated detection limits of 3 and 0.6 ppm of styrene vapor are achieved for operation at 25 and 40 degrees C, respectively.

Chemical Phenomena↗