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Biomedical subjects

J Russell

Publications and source records attributed to J Russell.

At least 163 records · Page 9Linked to original sources

Bicycle helmet use among American children, 1994.

OBJECTIVE: To estimate ownership and use of bicycle helmets among children in the US in 1994. METHODS: As part of a 1994 national telephone survey of 5,238 randomly dialed households, adult respondents reported data on bicycle helmet ownership and helmet use among 1,645 child bicyclists. Data were weighted to provide national estimates. RESULTS: It is estimated that 72.7% of children 5-14 year olds ride bicycles, that is, 27.7 million child bicyclists. Of the bicyclists, 50.2% have a helmet and 25.0% reportedly always wore their helmet when cycling. Reported helmet ownership and use increased with income and educational level and decreased with age. Among regions of the US, those with the highest proportion of states with helmet use laws in 1994 also had the highest proportion of helmet use among children. Among child bicyclists who had been seen by a health care provider in the preceding 12 months, 43.9% of those counseled to wear a bicycle helmet were reported to comply compared with 19.1% of those seen by a provider but not so counseled (p < 0.001). CONCLUSIONS: To meet the year 2000 objective of 50% of bicyclists wearing helmets, use among American children will have to double. Concerted and increased efforts to promote the wearing of bicycle helmets are necessary.

Adolescent↗

Stereotactic dose computation and plan optimization using the convolution theorem. I. Dose computation.

With Leksell Gamma Knife stereotactic radiosurgery, the dose distribution delivered by a specific helmet can be assumed to remain as a fixed-dose distribution when the shot is moved to different locations within the predefined dose calculation matrix. The convolution theorem may be implemented to take advantage of this fact for fast dose computation and plan construction. Using this technique, the shot spatial arrangement is formulated as a convolution kernel, which is theoretically a three-dimensional multi-delta function. The dose distribution is computed by the convolution of this single-shot dose distribution with the shot convolution kernel. To determine the shot arrangement, an ideal dose distribution is generated based upon the target structure. Deconvolution is then applied to find the convolution kernel which best fits the proposed ideal dose distribution. The primary task of this presentation is to focus on and describe in detail the dose computation using the convolution theorem.

Algorithms↗

Determination of residues in chromogranin A-(16-40) required for inhibition of parathyroid hormone secretion.

Chromogranin A (CGA), which is cosecreted from the parathyroid gland with PTH in response to low extracellular calcium, can be processed to amino-terminal peptides that, in turn, inhibit PTH secretion. The synthetic peptide KCIVEVISDTLSKPSPMPVSKECFE [CGA-(16-40)] is active in inhibiting secretion from freshly isolated or cultured bovine parathyroid cells. Peptide analogs in which alanine is substituted for classes of residues between the two cysteines have been synthesized and tested for biological activity. Substitution of the lysine, serine, or threonine residues by alanines does not greatly diminish biological activity. However, when the prolines are replaced by alanines or when glutamic acid and aspartic acid are replaced by alanines, the peptides do not effectively inhibit PTH secretion. Tests of synthetic peptides in which the individual glutamate or aspartate residues have been replaced showed that glutamate 37, followed by aspartate 24, are more critical for biological activity. Further experiments have shown that residues 11-15 in the natural CGA sequence do not enhance the biological activity of CGA-(16-40), whereas adding residues 6-10 restores full biological activity compared to that of CGA-(1-40). Circular dichroism experiments with CGA-(16-40) and the alanine substitution analogs show significant differences only for the peptide in which the three prolines are replaced. The inactive peptide with two glutamic acids and one aspartic acid replaced by alanine residues has the same circular dichroism spectrum as some of the peptides that are fully active. The N-terminal CGA sequences may tolerate many changes without alteration of biological activity. However, there are specific amino acid residues that are required for biological function.

Amino Acid Sequence↗

Characterization of a response element in the 5'-flanking region of the avian (chicken) PTH gene that mediates negative regulation of gene transcription by 1,25-dihydroxyvitamin D3 and binds the vitamin D3 receptor.

Analysis of the 5'-flanking region of the avian (chicken) PTH (cPTH) gene has revealed a DNA segment between -74 and -60 that is analogous to the consensus sequence for the vitamin D3 response element (VDRE). The DNA segment consists of two imperfect direct repeats, GGGTCA and GGGTGT, which are separated by a 3-bp spacer. The functionality of the putative VDRE was verified by transfection studies in opossum kidney cells using plasmid constructs that contained various regions of the cPTH gene 5'-flanking sequence and promoter fused to the gene for chloramphenicol acetyl transferase (CAT). Likewise, negative regulation of gene transcription by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was detected when the cPTH VDRE was inserted immediately upstream from truncated forms of the cPTH or the SV40 early promoter. Using gel mobility shift assays, the cPTH VDRE was compared with the human osteocalcin (hOC) VDRE, which activates gene transcription in the presence of 1,25-(OH)2D3. With a partially purified nuclear extract from dog intestine, the two VDREs produced gel shift patterns that were remarkably similar, with the exception that the binding affinity for the hOC sequence was notably greater. Both VDREs produced two major bound complexes (B1 and B2), which could be completely abolished by the addition of an excess of unlabeled hOC VDRE or a monoclonal antibody specific for the VDR protein. Furthermore, similar protein:DNA complexes were observed when either the cPTH or hOC VDRE were incubated with a mixture of purified preparations of recombinant VDR and retinoid X receptor alpha proteins. Ethylation interference analysis showed that the base contacts made by complexes B1 and B2 with the cPTH VDRE were essentially the same and were restricted primarily to the two half-site sequences.

Animals↗

A radioresistant variant derived from a human neuroblastoma cell line is less prone to radiation-induced apoptosis.

By subjecting radiosensitive human neuroblastoma IMR 32 cells to a regime of fractionated X-irradiation, a radioresistant variant, XRIMR 32, was obtained. Radiation resistance of XRIMR 32 cells was demonstrated by clonogenic and spheroid regrowth delay assays. The XRIMR 32 cultures were phenotypically unstable, with the resistant phenotype being lost after 3 passages in the absence of radiation-selective pressure, but a monoclonal cell line (clone F) was established that maintained its resistance over 35 passages without irradiation. Flow cytometry showed that exponentially growing IMR 32, XRIMR 32, and clone F cells all had very similar cell cycle distributions. Studies of initial DNA damage and repair, using the technique of neutral filter elution, revealed no differences between these lines. Chromosomal damage, as measured by micronucleus frequency following irradiation, was also seen to be very similar. However, studies of apoptosis following irradiation showed significantly higher levels of apoptosis in IMR 32 cells, compared to the resistant lines. This was true at all time points studied between 6 and 42 h after irradiation. p53 status was examined in the IMR 32 and clone F cells. No mutations were detected in exons 5-8 of the cDNA. Both lines showed increased p53 expression after irradiation. These data are consistent with the evolution of cellular resistance as a possible mechanism for the evolution of cellular radioresistance during protracted radiation regimes. However, the molecular mechanism responsible for the increased radioresistance remains to be discovered.

Apoptosis↗

Unusual case of Smith-Lemli-Opitz syndrome "type II".

We describe a fetus with abnormalities suggestive, but not typical, of severe Smith-Lemli-Opitz syndrome (SLO). Biochemical studies demonstrated that there was a defect of cholesterol biosynthesis similar to that recently discovered in children with SLO. The findings in this fetus extend even further the wide spectrum of abnormalities of the SLO phenotype, and emphasize that a genetic pathological examination and biochemical studies should always be undertaken on atypical cases, especially fetuses.

Abnormalities, Multiple↗

Implications of increased lung thallium uptake during exercise single photon emission computed tomography imaging.

Increased lung thallium uptake during exercise is an important marker of patients who are at high risk and have CAD; however, most previous studies were done with planar imaging, and therefore it is unclear whether this conclusion is also true with SPECT imaging. This study examined the lung thallium uptake during exercise SPECT imaging in 1031 patients who also underwent coronary angiography. The lung thallium uptake was increased in 309 patients (group 1) and normal in 722 patients (group 2). Compared with patients in group 2, those in group 1 had more ST segment depression (44% vs 28%, p = 0.01), previous Q-wave myocardial infarction (28% vs 17%, p = 0.0001), larger perfusion defects (24% +/- 11% vs 10% +/- 11%, p = 0.0001), and multivessel CAD by angiography (75% vs 47%, p = 0.0001). Multivariate discriminant analysis identified left ventricular dilation, reversible defects, the size of perfusion abnormality, and the extent of CAD as independent predictors of increased lung thallium uptake. Increased lung thallium uptake was more common in men than women regardless of the extent of CAD: 26% versus 11% in patients with one-vessel, 38% versus 18% in patients with two-vessel, and 51% versus 31% in patients with three-vessel disease (p < 0.001 each). Thus increased lung thallium uptake by SPECT identifies patients with more severe anatomic and functional evidence of CAD. The sex-related difference suggests the need for a sex-specific normal file for quantitative analysis.

Aged↗

Enhanced tumour uptake and in vitro radiotoxicity of no-carrier-added [131I]meta-iodobenzylguanidine: implications for the targeted radiotherapy of neuroblastoma.

In vitro and in vivo neuroblastoma models were used to determine whether improvements in tumour targeting in vivo and therapeutic efficacy in vitro could result from the use of no-carrier-added (n.c.a.) [131I]MIBG. Results were compared with use of the conventional therapy MIBG preparation (ex. [131I]MIBG) of lower specific activity which is produced by iodide exchange reaction. The efficacy of n.c.a. [131I]MIBG was compared with that of [131I]MIBG over a range of specific activities by the assessment of neuroblastoma spheroid growth delay. Whereas n.c.a. [131I]MIBG at a radioactivity concentration of 2 MBq/ml prevented the regrowth of 84% of spheroids, toxicity was significantly reduced by the addition of non-radiolabelled MIBG to the incubation medium. The time-dependent biodistribution of n.c.a. [131I]MIBG in nude mice bearing human neuroblastoma xenografts was compared with that of the conventional therapy radiopharmaceutical. The n.c.a. agent gave improved tumour uptake but also significantly greater accumulation in normal tissues known to accumulate MIBG such as heart, adrenal and skin. However, uptake and retention in the blood was unaltered. For all tissues examined, the 3-day calculations were undertaken to predict organ to tumour dose ratios which would result in human neuroblastoma patients with each of the [131I]MIBG preparations. These results suggest that significant therapeutic gain may be achieved by the use of n.c.a. [131I]MIBG as a treatment agent in neuroblastoma. neuroblastoma.

3-Iodobenzylguanidine↗

Septic patients in multiple organ failure can oxidize infused glucose, but non-oxidative disposal (storage) is impaired.

1. Patients suffering trauma and sepsis are insulin resistant, but no studies have specifically been made of patients suffering multiple organ failure. 2. We have studied exogenous glucose utilization in multiple organ failure using a combination of the hyperglycaemic glucose clamp and indirect calorimetry to quantify glucose utilization in multiple organ failure, partitioning it into oxidative and nonoxidative disposal (storage). 3. Fourteen septic patients with multiple organ failure were studied. APACHE II (Acute Physiological and Chronic Health Evaluation Mark II) scores on the day of the study ranged from 11 to 31 (median 16). Twenty percent D-glucose was infused and blood glucose was clamped at 12 mmol/l for 3 h. The results were compared with those obtained on seven healthy control subjects. 4. Glucose utilization and energy expenditure were similar in the two groups for the first 90 min of the clamp, after which glucose utilization and energy expenditure increased steadily in the control subjects but did not change in the patients. Respiratory exchange ratio rose in both groups; considered over the whole of the clamp period, respiratory exchange ratio was slightly lower in the patients than in the control subjects (P < 0.05) but not at any specific time point. Glucose oxidation rose in both groups but non-oxidative glucose disposal (storage) rose only in the control subjects. Glucose oxidation was slightly lower in the patients (P < 0.05) but not at any specific time point and there was no difference between the groups in the amount by which glucose oxidation increased. Non-oxidative disposal in the patients fell significantly (P < 0.01) over the course of the clamp and was significantly lower than in the control subjects (P < 0.01). 5. Growth hormone increased in response to glucose infusion in the patients but not in the control subjects. 6. Like patients suffering uncomplicated sepsis or trauma, patients with multiple organ failure are also insulin resistant. The defect appears to lie in an impairment of the ability to store glucose rather than oxidize it, and this may be due in part to the increase in growth hormone in patients with multiple organ failure.

Adolescent↗

Bilateral renal oncocytoma: case report and implications in renal tumour management.

Renal oncocytomas are uncommon benign tumours that have recently been recognized as a unique pathological entity. These lesions may attain considerable size; however, most present as an asymptomatic incidental finding. Although usually solitary, these tumours are occasionally multicentric or bilateral at presentation. Retrospective studies suggest that oncocytoma may account for up to 5% of tumours previously classified as well-differentiated renal cell carcinoma. At present, conservative management is hampered by difficulty in establishing a confident pre-operative or intra-operative diagnosis. A case of bilateral asymptomatic renal oncocytoma is presented, and the implications of this lesion for the management of renal tumours is discussed.

Adenoma, Oxyphilic↗

cis-Acting components of human papillomavirus (HPV) DNA replication: linker substitution analysis of the HPV type 11 origin.

Papillomavirus DNA replication requires the viral trans-acting factors E1 and E2 in addition to the host cell's general replication machinery. The origins of DNA replication in bovine and human papillomavirus genomes have been localized to a specific part of the upstream regulatory region (URR) which includes recognition sites for E1 and E2 proteins. To fine map cis-acting elements influencing human papillomavirus type 11 (HPV-11) DNA replication and to determine the relative contributions of such sites, we engineered consecutive linker substitution mutations across a region of 158 bp in the HPV-11 origin and tested mutant origins for replication function in a cell-based transient replication assay. Our results both confirm and extend the findings of others. E2 binding sites are the major cis components of HPV-11 DNA replication, and there is evidence for synergy between these sites. Differential capacity of the three E2 binding sites within the origin to affect replication may be attributed, at least in part, to context. At least one E2 binding site is essential for replication. The imperfect AT-rich palindrome of the E1 helicase binding site is not essential since replication occurs even in the absence of this sequence. However, replication is enhanced by the presence of the palindromic sequence in the HPV-11 origin. Sequence components adjacent to the E1 and E2 binding sites, comprising AT-rich and purine-rich elements and the consensus TATA box sequence, probably contribute to the overall efficiency of replication, though they are nonessential. None of the other cis elements of the HPV-11 origin region analyzed seems to influence replication significantly in the system described. The HPV-11 origin of DNA replication therefore differs from those of the other papovaviruses, simian virus 40 and polyomavirus, inasmuch as an intact helicase binding site and adjacent AT-rich components, while influential, are not absolutely essential.

Animals↗

Vasopressin and cAMP stimulate electrogenic chloride secretion in an IMCD cell line.

Previously, we demonstrated that the mIMCD-K2 cell line, derived from the inner medullary collecting duct (IMCD) of a transgenic mouse, secretes Cl- by an electrogenic mechanism [N. L. Kizer, B. Lewis, and B. A. Stanton, Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995]. The objective of the present study was to characterize the cellular mechanisms of electrogenic Cl- secretion (IscCl) and to determine whether arginine vasopressin (AVP) and adenosine 3',5'-cyclic monophosphate (cAMP) stimulate IscCl. To this end, we measured IscCl across monolayers of mIMCD-K2 cells mounted in Ussing-type chambers. AVP increased IscCl with a Michaelis constant (Km) of 2.1 +/- 0.7 x 10(-12) M. 1-Desamino-8-D-AVP, a specific V2 receptor agonist, increased IscCl from 3.3 +/- 0.4 to 17.4 +/- 1.3 microA/cm2, 8-(4-Chlorophenylthio)-cAMP, a cell-permanent analogue of cAMP, a second messenger of AVP, increased IscCl from 1.4 +/- 0.3 to 15.2 +/- 1.2 microA/cm2. Furosemide and bumetanide, inhibitors of Na(+)-2Cl(-)-K+ cotransport, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of Cl-/HCO3- exchange, reduced IscCl when added to the basolateral solution. Our data suggest that AVP, via V2 receptors, and the second messenger cAMP stimulate IscCl and that Cl- secretion by mIMCD-K2 cells involves uptake of Cl- across the basolateral membrane by Na(+)-2Cl(-)-K+ cotransport and Cl-/HCO3- exchange and diffusion out of the cells across the apical membrane by cystic fibrosis transmembrane conductance regulator Cl- channels.

Absorption↗

Lead toxicity and public health policy.

Senior UK scientists have recently acknowledged that lead exerts neurotoxic effects at blood lead levels even as low as 10 micrograms/dL. The implications of these findings for public policy are outlined, especially in relation to contamination of drinking water, soil and household dust. Estimates of the proportion of 6 year old children with elevated blood lead levels for several locations are also provided.

Adult↗

The power of special friends: addressing the risk of child abuse through mentoring.

Since 1989 two Saint Paul, Minnesota agencies have carried on a collaborative effort called the Befriender Volunteer Project. This project is designed to address the risk factors associated with child abuse which are often inherent in families headed by an adolescent. Between November of 1993 and October of 1994 a self-study of this project was conducted. An important objective of this study was to determine how the positive elements of a successful relationship affected the risk factors in these young families. Consistent with what we know about the effects of successful helping relationships, most significant improvements in young mothers were found in the areas of hopefulness, self-esteem, and parenting skills. Of significant note was the observation of the various ways the Befriender/young mother relationship enhanced the young mothers' potential for breaking the generational cycle of risk for child abuse and neglect.

Adolescent↗

No-carrier-added iodine-131-MIBG: evaluation of a therapeutic preparation.

UNLABELLED: Iodine-131-metaiodobenzylguanidine ([131I]MIBG) is a radiopharmaceutical for imaging as well as targeted radiotherapy of neuroblastoma. It is predicted that the use of no-carrier-added [131I]MIBG, rather than the conventional low specific activity preparation, will result in an enhanced therapeutic ratio because of different transport processes in neuroblastoma compared with most normal tissues. METHODS: The main aims of the study were: (1) to determine whether [131I]MIBG of substantially greater specific activity is transported into tumor cells by the same process as the existing compound; (2) to evaluate the effect of nonradiolabeled MIBG on the cytotoxicity of no-carrier-added [131I]MIBG; and (3) to compare the biodistribution of both preparations of the radiochemical in neuroblastoma xenografts. RESULTS: Active uptake of no-carrier-added [131I]MIBG was temperature-, sodium- and oxygen-dependent; ouabain- and desmethylimipramine-inhibitable; and could be blocked competitively by monoamine inhibitors of the noradrenaline transport mechanism. The rank order of specific uptake capacity in a panel of neuroblastoma cell lines was the same for both low and high specific activity drug. Neuroblastoma spheroid regrowth was 85% inhibited by no-carrier-added [131I]MIBG at 2 MBq.ml-1. Inhibitory potency was reduced in a dose-dependent manner by nonradiolabeled MIBG. The accumulation of no-carrier-added [131I]MIBG was significantly greater in tumor, adrenal, heart and skin of tumor-bearing mice than that of the conventional therapy preparation of [131I]MIBG. CONCLUSION: These data indicate that there may be clinical advantages in the use of no-carrier-added [131I]MIBG rather than conventional [131I]MIBG.

3-Iodobenzylguanidine↗