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Biomedical subjects

B J Mills

Publications and source records attributed to B J Mills.

At least 37 records · Page 2Linked to original sources
PubMed1990

Bone scan: a useful test for evaluating patients with low back pain.

For many years it has been known that the sensitivity of bone scanning to the presence of destructive bony lesions favors its use in screening for bone metastases and osteomyelitis. More recently bone scanning has been routinely employed in evaluating benign skeletal pathology that may be the cause of low back pain. Bone scanning can play an important part in (1) identifying the cause of pain, (2) clarifying the significance of radiographic findings, and (3) evaluating the results of spinal surgery. This expansion of the role of nuclear medicine in diagnosing and managing low back pain is based in part upon novel diagnostic applications of 99mTc-methylene diphosphonate, a radiopharmaceutical that has been available for over 15 years. Equally important for this development, however, has been the recent availability of SPECT, a tomographic imaging technique that can be used to display the spine in a series of 6- to 8-mm thick sections. Slightly more than one-half of newly purchased gamma cameras are rotating systems suitable for bone SPECT studies. Thus, many community hospitals can now perform state-of-the-art bone scans for low back pain.

Adult↗
PubMed1990

Comparison of urinary growth hormone and IGF-I excretion in small- and appropriate-for-gestational-age infants and healthy children.

The output of urinary growth hormone (GH) and IGF-I were quantitated by RIA in 12-h urine collections obtained from infants who were preterm, small for gestational age (PT-SGA, n = 13); preterm, appropriate for gestational age (PT-AGA, n = 27); full term, small for gestational age (FT-SGA, n = 13); and full term, appropriate for gestational age (FT-AGA, n = 29); and from normal children (n = 33). The amounts of GH and IGF-I (mean +/- SEM) excreted by the PT-SGA and FT-SGA infants were not significantly lower than those excreted by the PT-AGA and FT-AGA groups, respectively [GH (micrograms/kg): PT-SGA 13.7 +/- 3.1 versus PT-AGA 14.0 +/- 2.2, FT-SGA 7.8 +/- 2.4 versus FT-AGA 6.6 +/- 1.8; IGF-I (nmol/kg): PT-SGA 0.52 +/- 0.09 versus PT-AGA 0.53 +/- 0.04, FT-SGA 0.31 +/- 0.05 versus FT-AGA 0.35 +/- 0.04]. All infant groups exhibited significantly greater outputs of urinary GH and IGF-I compared with the children (p less than 0.01). The plasma concentrations of GH in all infant groups were high, whereas the plasma IGF-I levels were low. Microalbumin and beta-2 microglobulin excretion did not correlate with urinary GH and IGF-I output. Despite the higher microalbumin output in FT babies, urinary GH and IGF-I excretion was lower in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Blood glutathione: a biochemical index of life span enhancement in the diet restricted Lobund-Wistar rat.

These experimental results demonstrate that dietary restriction in both conventional and germfree rats results in enhanced longevity compared to fullfed animals. This increase in median survival age was due to a delay of 8 months in the onset of mortality in the restricted rats. Thereafter the aging rates of the short-lived subpopulations were the same for both groups. However, the aging rate of the long-lived restricted subpopulation was greater. The blood glutathione profiles demonstrated that a GSH deficiency of aging occurred in both the restricted and the long-lived groups. These data confirmed in the rat the findings observed previously in mosquito, mouse and man and verified the generality of the GSH and longevity relationship. Of special interest is that the blood glutathione levels were consistently higher at all ages of the restricted compared to fullfed rats and decreased more slowly during senescence. These findings indicate a direct relationship between enhanced GSH status and increased longevity due to dietary restriction. Further this suggests that glutathione may be a molecular mechanism for the diet restriction and longevity phenomenon.

Aging↗
PubMed1988

Laboratory correlates of adoptive immunotherapy with recombinant interleukin-2 and lymphokine-activated killer cells in humans.

Adoptive immunotherapy with interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells (IL-2/LAK) is a technically demanding cancer therapy dependent upon large scale isolation and culture of lymphocytes. An important question is whether this technology can be accomplished routinely outside of highly specialized centers. In addition, no systematic examination of laboratory correlates of IL-2/LAK therapy in humans has been reported to date. The objectives of this report are to address two issues relevant to IL-2/LAK therapy. (a) Can IL-2/LAK therapy be accomplished outside of previously identified centers of expertise? (b) What are the relevant laboratory/clinical parameter correlations? The six institutions in the National Cancer Institute extramural trial treated 83 evaluable patients with renal cancer, malignant melanoma, or colon cancer with IL-2/LAK by a uniform protocol. Patients received 5 days of IL-2 priming, then daily leukaphereses for 5 days starting 48 h after IL-2 to harvest cells. Mononuclear cells were isolated, then cultured in roller bottles in 1-liter aliquots for 3 to 4 days at a cell density of 1.5 x 10(6) per ml with recombinant IL-2, 1500 units per ml. Cells were harvested and administered to patients with additional IL-2. Administration of IL-2 regularly induced lymphopenia and rebound lymphocytosis. Leukapheresis yields and numbers of LAK cells generated in culture and reinfused into patients correlated directly with peak lymphocyte counts achieved by IL-2 administration. Mean mononuclear cell recovery per 5 days of leukapheresis (+/- SEM) was 14.3 +/- 0.8 x 10(10). Average volume of cells cultured per patient was 95 liters (range, 41 to 235). Mean yield of cells harvested from cultures was 53%. Mean total number of LAK cells infused per patient was 7.6 +/- 0.4 x 10(10) (range, 2 to 15.2 x 10(10]. LAK activity was measured in vitro by lysis of 51Cr-labeled natural killer-resistant Daudi and fresh tumor targets. LAK effector cells regularly lysed these targets in vitro. Neither tumor reduction nor clinical toxicity correlated with dose or with cytolytic activity of LAK cells, or with other laboratory parameters including base-line lymphocyte count and IL-2-induced lymphocytosis. We conclude: (a) large quantities of LAK effector cells with tumoricidal activity can be generated routinely at different centers; (b) neither in vitro LAK activity nor numbers of LAK cells infused were predictive of clinical efficacy or toxicity. There is a need to identify other laboratory or clinical parameters more predictive of IL-2/LAK therapeutic efficacy or toxicity.

Colonic Neoplasms↗
PubMed1988

Diagnostic value of the growth hormone-releasing factor stimulation test.

Growth hormone (GH) responses to growth hormone-releasing factor (GRF) were evaluated in 55 children with growth failure. The study groups consisted of group 1, severe GH deficiency; group 2, partial GH deficiency; group 3, patients with prior cranial radiation for nonpituitary brain tumors; and group 4, children with idiopathic growth failure. Children in group 1 were unresponsive to GRF (mean GH peak +/- SEM, 1.6 +/- 0.5 ng/ml). Higher GH responses to GRF were observed in both groups 2 (17.2 +/- 4.1 ng/ml) and 3 (10.4 +/- 2.8 ng/ml). The highest GH responses to GRF were observed in group 4 (35.9 +/- 4.3 ng/ml). ANOVA revealed a significant difference between groups (F = 12.9; df = 3; p less than 0.01), and further analysis by the Scheffe and Student-Newman-Keuls tests revealed that group 4 was significantly higher than groups 1, 2, or 3 (p less than 0.05). These data suggest that GRF unresponsiveness is a reliable predictor of severe GH deficiency. In patients with partial GH deficiency or idiopathic growth failure, the GRF gives semiquantitative information about somatotrope responsivity to exogenous stimulation.

Adolescent↗
PubMed1988

Quantitation of urinary somatomedin-C and growth hormone in preterm and fullterm infants and normal children.

Urinary GH and somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) excretion were measured in 12-h urine collections obtained from 43 infants (27 stable preterm infants and 16 healthy fullterm infants) and 31 normal children, aged 3-17 yr. Urinary Sm-C/IGF-I was excreted as the free hormone, since no binding of radiolabeled Sm-C/IGF-I to any urine protein with a mol wt similar to those described for plasma Sm-C/IGF-I-binding proteins was found. The preterm infants excreted significantly more urinary GH [13.5 +/- 2.1 (+/- SE) ng/kg.12 h] than either the fullterm infants (5.3 +/- 1.6 ng/kg.12h) or the children (0.27 +/- 0.02 ng/kg.12 h; P less than 0.01). The mean urinary Sm-C/IGF-I excretion in the preterm infants (98.9 +/- 7.5 mU/kg.12 h) was comparable to that in fullterm infants (87.6 +/- 9.7 mU/kg.12 h); both groups excreted significantly more urinary Sm-C/IGF-I than children (28.4 +/- 2.1 mU/kg.12 h; P less than 0.01). The group differences were similar when the results were expressed in terms of creatinine excretion. Urinary GH excretion correlated positively with urinary Sm-C/IGF-I excretion (r = 0.68). The higher output of these peptides in rapidly growing infants and their positive correlation in urine provide additional support for the Sm hypothesis.

Adolescent↗
PubMed1987

Correction of a glutathione deficiency in the aging mosquito increases its longevity.

The decrease of tissue glutathione (GSH) concentrations in different senescent organisms gave rise to our hypothesis that a glutathione deficiency is a biochemical cause of the aging process. A rigorous test of this notion would be the correction of the deficiency and concomitant increase in life span. To this end, adult mosquitoes were fed magnesium thiazolidine-4-carboxylic acid, and their GSH levels and life spans were determined. The GSH levels increased 50-100% (P less than 0.005) regardless of the age when feeding was initiated or whether the feeding period extended over 2 days or the entire life span. Also the median life spans increased 30-38% over control values (P less than 0.005). The responses were specific for the thiazolidine carboxylate moiety, because MgCl2 had no effect. These findings confirm the GSH deficiency hypothesis and demonstrate a specific biochemical mechanism of aging that can be nutritionally modified.

Aedes↗
PubMed1986

Increased sensitivity of virus-infected cells to inhibitors of protein synthesis does not correlate with changes in plasma membrane permeability.

Semliki Forest virus-infected BHK cells or herpes simplex virus-infected Vero cells were incubated with the protein synthesis inhibitors hygromycin B and gougerotin. Infected cells take up no more [3H]hygromycin or [3H]gougerotin than do mock-infected cells, at a time p.i. at which either compound is more inhibitory to protein synthesis in infected, than in mock-infected cells. The concentrations of hygromycin and gougerotin required to inhibit protein synthesis in intact cells (irrespective of whether they are infected or not) are several orders of magnitude higher than those required in either permeabilized cells or in cell-free systems. Infected cells take up 86Rb+ at the same rate as mock-infected cells, their intracellular content of K+ is the same, and the activity of the Na+ pump is the same. It is concluded that the increased efficacy of hygromycin and gougerotin in virus-infected cells is a consequence of altered intracellular compartmentation and that increases in permeability of the plasma membrane, if any, are so small as to be undetectable by direct methods.

Animals↗
PubMed1986

Magnesium deficiency inhibits biosynthesis of blood glutathione and tumor growth in the rat.

Previously we found that blood glutathione (GSH) levels increase in response to tumor growth in the rat and that this increase is not prevented with zinc deficiency. We also found that zinc deficiency which inhibited tumor growth did not prevent this increase in blood GSH. Therefore, the objectives of this study were to determine the effects of another nutritional modification, namely magnesium deficiency, on blood GSH status and on tumor growth. Magnesium was selected because it is an obligatory cofactor in GSH synthesis and in all biosynthetic reactions involving ATP. To this end, magnesium- and zinc-deficient rats with and without tumors were compared to pair-fed control rats with and without tumors. After 32 days of depletion, the rats were killed, and blood samples were analyzed for nonprotein sulfhydryls (SH) and specifically for GSH. The key finding was that in magnesium-deficient rats with or without tumors, blood GSH levels were low and SH levels were normal indicating a decrease in GSH biosynthesis. In contrast, zinc deficiency affected SH and GSH in parallel. Thus, these two deficiencies must act by different mechanisms. The zinc data verified our earlier results obtained with a different tumor type and rat strain, for blood GSH levels increased in tumor-bearing rats fed control diets, and zinc deficiency did not prevent this increase. Depletion of magnesium or zinc was equally effective in inhibiting tumor growth. These results provide in vivo evidence of a magnesium requirement for GSH biosynthesis in rat erythrocytes. Further, the results suggest that magnesium deficiency may inhibit tumor growth by limiting GSH synthesis from SH precursors.

Animals↗
PubMed1986

Dietary nordihydroguaiaretic acid increases the life span of the mosquito.

Our previous findings indicated that a major characteristic of aging organisms is a decrease in reducing capacity. Our objectives were to correct this impairment by administration of nordihydroguaiaretic acid (NDGA), a potent reducing agent, and to determine the effect on adult longevity of the mosquito. NDGA supplements were included in the axenic larval medium or adult diet of mosquitoes of different ages. The mean adult life spans of both sexes increased 42-64% over controls (P less than 0.025), and the most effective doses were 0.001% for females and 0.005% for males. This NDGA effect was dependent on the age when feeding was initiated, since only biosynthetically active larvae and young adults were responsive. Also the effect was not due to dietary restriction. These results confirm the life span-enhancement effect of NDGA using defined conditions and establish the importance of redox status in the aging process.

Aedes↗
PubMed1986

Synergy between interleukin-2 and a second factor in the long-term growth of human T cells.

It has recently been shown that factors in addition to interleukin-2 (IL-2) are required for the proliferation or differentiation of at least some murine T-cell lines. We have previously shown that conditioned medium from human mononuclear cells stimulated with phorbol ester and staphylococcal enterotoxin A is superior to commercial sources of IL-2 for the long-term growth of human T cells. We have identified in these supernatants a non-IL-2 factor (synergistic factor, SF) which synergizes with JURKAT IL-2 in the long-term growth of human T cells. [3H]TdR incorporation by IL-2-dependent human T cells after growth in IL-2 or SF alone for 14 days was slight, but significant. By contrast, growth in a combination of SF and IL-2 for 14 days stimulated [3H]TdR incorporation 10-20-fold higher, generally equal to the high incorporation measured when cells were grown in the presence of the conditioned medium from which SF was obtained. In a standard 2-day IL-2 assay, there was no correlation between activity and long-term growth-promoting ability. These results suggest that the 14-day assay better discerns the growth-promoting activity of various factors or combinations of factors. The mechanism of this interaction between SF and IL-2 remains to be elucidated. It is clear, however, that T-cell growth factor activity, when assessed by the long-term growth of human T cells, is not due to interleukin-2 alone.

Antigens, Surface↗
PubMed1985

Cytotoxic lymphokines produced by cloned human cytotoxic T lymphocytes. I. Cytotoxins produced by antigen-specific and natural killer-like CTL are dissimilar to classical lymphotoxins.

Several cloned lines of IL 2-dependent human T cells derived from alloantigen, mitogen, or IL 2-stimulated peripheral blood lymphocytes were examined for their surface marker expression, cytolytic activity in a 51Cr-release assay, and capacity to release cytotoxic lymphokines. Thirty cell lines exhibiting either antigen-specific natural killer cell activity or lectin-dependent killer cell function, which expressed either the CD4 or CD8 surface differentiation markers, were capable of producing cytotoxin(s) in response to the lectins phytohemagglutinin and concanavalin A. Cytotoxin activity was detected on the murine L929 target cell in a 16-hr cytotoxicity assay. In contrast, several nonlytic T cell tumor lines failed to produce a soluble cytotoxin. Antibodies capable of neutralizing human alpha-lymphotoxin were completely ineffective in inhibiting the cytotoxin(s) produced by any of the cytotoxic T lymphocytes (CTL) cell lines. Comparative gel filtration and HPLC hydrophobic chromatography of alpha-lymphotoxin and CTL toxin produced by the CTL-830.B2 clone revealed significant differences in their elution profiles. The CTL-produced toxin and alpha-lymphotoxin exhibited similar kinetics of lysis of the L929 target cells, with 50% target cell lysis occurring at 10 hr. These data indicate human CTL produce a cytotoxin(s) antigenically distinct from alpha-lymphotoxin and imply that human cytolytic effector T cells are not the cellular source for the production of human alpha-lymphotoxin. The relationship of alpha-lymphotoxin and CTL toxin production was investigated in unseparated peripheral blood mononuclear cells stimulated with lectins or IL 2 for 1 and 5 days. Anti-alpha-lymphotoxin antibodies were capable of neutralizing only 30 to 50% of the cytotoxic activity in 24-hr supernatants. Cytotoxic activity in supernatants harvested after 120 hr stimulation with PHA or Con A was neutralized 70 to 100%, whereas the toxin(s) released from IL 2-stimulated lymphocytes was only neutralized 30%. These data suggest the observed heterogeneity of cytotoxic lymphokines produced by unseparated mononuclear cells depends in part on the subpopulations of effector cells responding to a given stimulus and the capacity of different subpopulations to produce distinct cytotoxins.

Cell Separation↗
PubMed1985

A 64,000 dalton matrix protein of human cytomegalovirus induces in vitro immune responses similar to those of whole viral antigen.

Human cytomegalovirus contains approximately 30 to 35 structural polypeptides. Although antibodies to several of these proteins are made during natural infection, their relationship to T cell recognition of this virus and subsequent control of infection is poorly understood. We have purified one of these proteins (HCMVgp64) that is found in abundance in infected cell lysates in order to delineate the relationship of single viral proteins to the immune response caused by the virus. HCMVgp64 induced T cell reactivity only in individuals with serologic evidence of past infection. In addition, HCMVgp64 elicited similar in vitro immune reactions as the whole virus including T cell proliferation, interleukin 2 production, and receptor expression as well as interferon production. These studies suggest that single proteins of HCMV such as HCMVgp64 are capable of inducing T cell responses and may be important in the development of immune reactivity to HCMV.

Antigens, Viral↗
PubMed1984

Production of mitogen-free immune interferon and T-cell growth factor by human peripheral blood lymphocytes induced with biotin-labeled staphylococcal enterotoxin A.

A method for the facile removal of mitogens or inducers of lymphokine production from cell culture medium of stimulated cells is described. The technique is based on the covalent attachment of biotin to mitogen or inducer and the removal of the biotinylated products from stimulated cell culture medium using immobilized avidin. Using this procedure, biotin-labeled staphylococcal enterotoxin A (SEA-B) was shown not to differ significantly from unmodified SEA in its capacity to stimulate mitogenesis and induce production of immune interferon (IFN) and T-cell growth factor (TCGF) in cultures of human mononuclear cells from peripheral blood. SEA-B was also shown not to differ from SEA in its binding to SEA antibodies. Results of mitogenicity studies and competitive radioimmune assay (RIA) measurements indicate that SEA-B is essentially completely removed from stimulated cell culture medium by absorption with avidin coupled to Sepharose 4B.

Biotin↗
PubMed1984

Acid treatment enhances IL-2 activity of conditioned medium.

Although conditioned medium (CM) from human lymphocytes or mononuclear cells is the most readily available source of interleukin-2 (IL-2) for human T cell culture, its IL-2 activity in our experience is inconsistent. It is likely that this is, at least in part, due to the presence of toxic substances in the CM. Using CM from TPA/SEA induced human mononuclear cells, we have found that acid treatment (pH 2.0, greater than 30 min) significantly improves its ability to promote T cell growth. It is postulated that the selection process which occurs in cultures of mitogen stimulated T cells may result in cells which are sensitive to mitogen-induced lymphotoxins and that these are inactivated by the acid treatment. Since acid treatment did not similarly improve the T cell growth promoting ability of PHA induced, lectin-free commercial IL-2, there must be other differences between it and our CM, which play a role in T cell growth.

Cell Survival↗
PubMed1984

The verification of a mammalian toxicant classification using a mosquito screening method.

Routine toxicity screening of substances using rodents can be time consuming and expensive. For these reasons various alternative methods have been developed, but many lack standardization and acceptance. It was hypothesized that a satisfactory classification of mammalian toxicants could be obtained using a simple mosquito (Aedes aegypti) screening method. To this end, median lethal concentration (LC50) values were determined for a wide variety of mammalian toxicants representing a range of toxicity classes. Each substance was assayed in aqueous solution by incubation for different times, up to 24 hr, using at least 30 individual larvae and six different concentrations, for valid statistical analysis. With few exceptions, the resultant toxicity classes were the same as those determined using mammalian models. This classification was validated further by the very high correlation (r = 0.97) determined between the mosquito LC50 values and the rat LD50 values. These results suggest that this mosquito method can be used to rapidly screen compounds of potential mammalian toxicity.

Aedes↗
PubMed1984

Thyroid hormone abnormalities at diagnosis of insulin-dependent diabetes mellitus in children.

Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of "euthyroid sick" or "low T3" syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values; eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.

Adolescent↗