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J Little

Publications and source records attributed to J Little.

At least 91 records · Page 5Linked to original sources
PubMed1993

Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

OBJECTIVE: To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas. DESIGN: Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer. SETTING: Nottingham. SUBJECTS: 147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls). MAIN OUTCOME MEASURES: Relative risk of developing colorectal adenomas according to frequency and duration of use of analgesics. RESULTS: Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0.49 (95% confidence interval 0.3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0.66 (0.4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal anti-inflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0.8)), although the numbers reporting prolonged prescribed use were small. CONCLUSIONS: These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia.

Acetaminophen↗
PubMed1993

A novel UDP-Glc-specific glucosyltransferase catalyzing the biosynthesis of 6-O-glucosides of bile acids in human liver microsomes.

Two active site-directed photoaffinity analogs, 5-[beta-32P]azido-UDP-glucuronic acid and 5-[beta-32P]azido-UDP-glucose, were used for the characterization of UDP-sugar-utilizing enzymes in human liver microsomes. Both compounds were recognized by human microsomal proteins: major photolabeled bands of 50-56 kDa were detected. Both photoincorporations were competitively decreased by increasing concentrations of either UDP-Glc or UDP-GlcUA, indicating a high affinity for both nucleotides. The patterns of photoaffinity labeling in the 50-56-kDa range by the two probes were significantly different, indicating the presence of different UDP-GlcUA- and UDP-Glc-specific enzymes of similar molecular mass. The presence of a UDP-Glc-dependent transferase was confirmed by the identification of an enzymatic activity catalyzing the formation of glucosides of the 6 alpha-hydroxylated bile acid hyodeoxycholic acid (3 alpha, 6 alpha-diOH (HDCA)) in the presence of UDP-Glc. The specific activity of 1.5-3.2 nmol/min/mg of protein was similar to that of 6 alpha-glucuronidation of HDCA. The apparent Km for UDP-Glc estimated with HDCA was 280 microM, and the formation of HDCA glucosides was strongly inhibited by UDP-GlcUA (apparent Ki = 7 microM). Evidence is presented that HDCA-specific UDP-glucuronosyltransferase (clone UGT2B4) expressed in V79 cells is not involved in glucosidation of HDCA and is not photolabeled with 5-[beta-32P]azido-UDP-Glc. Rigorous structure identification of the biosynthetic product proved that HDCA was glucosidated at the 6-position. Thus, this UDP-Glc-dependent activity catalyzing the biosynthesis of 6-O-glucosides of 6 alpha-hydroxylated bile acids represents a new pathway in the metabolism of these bile acids.

Adolescent↗
PubMed1993

Induction of differentiation in a B lymphoma X B lymphocyte hybrid line. II. Intraclonal heterogeneity in growth, secretion of IgM, and cytokine production in response to lipopolysaccharide.

Murine B lymphocyte clones have proven to be useful models to study aspects of B lymphocyte growth and development. It had been previously shown that induction of TH2.2 (B lymphoma X B lymphocyte) with LPS resulted in differentiation into IgM-secreting cells (a feature similar to other B cells lines such as BCL1), and secretion of granulocyte-macrophage-CSF. Many transformed and nontransformed lines (including TH2.2) have been shown to generate progeny heterogenous in size and secretion of product when exposed to mitogen. We extend this study to demonstrate heterogeneity in secretion of IgM, granulocyte-macrophage-CSF, IL-3, and IL-6 in LPS-induced TH2.2. Clones generated by limiting dilution were heterogenous with respect to size, type, and quantity of product secreted. Microscopic clones ranged from 10 to about 1000 cells in size and could not be grown further; the majority secreted one product (mainly IgM). These clones were very efficient secretors of IgM and probably consist mainly of terminal-secreting cells. Microscopic clones secreting cytokine were also efficient producers. Visible clones from LPS-induced cultures grew to the same size as uninduced clones and were often restricted in secretion of products. Although the majority secreted three of four products (52%), many secreted IgM only or IgM and one cytokine. Although there was a strong tendency for clones to secrete multiple products, almost every secretory phenotype could be found. Amounts of different products secreted were not correlated, suggesting an additional level of independent control of this variable. Restriction of secretion was not due to genetic variation because visible clones originally restricted in secretion almost always produced all products when expanded and retested. These findings indicate that cells of TH2.2 were heterogeneous with respect to growth and secretion in the presence of LPS and were individually programmed for differentiative responses. The programming of cells was not permanent, but subject to dynamic change.

Animals↗
PubMed1993

Colorectal adenomas and energy intake, body size and physical activity: a case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

Most case-control studies of colorectal cancer have shown a positive association with energy intake. In contrast studies which have considered physical activity have found the most active to have a lower risk of colonic cancer and obesity appears to be no more than weakly related to colorectal cancer. We therefore compared energy intake determined by a diet history interview, self-reported height and weight, together with measures of lifetime job activity levels and leisure activity in the year prior to interview in 147 cases with colorectal adenomas and two control groups (a) 153 age-sex matched FOB-negative subjects (b) 176 FOB-positive subjects in whom no adenoma or carcinoma was found. Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals () adjusted for age, sex and social class. No association with weight or body mass index was found. The only association with physical activity found with both control groups was an inverse association with running or cycling for half an hour continuously at least once a week RR 0.46 (0.2-1.3) compared with control group (a), and RR = 0.32 (0.1-0.8) compared with (b), but few subjects engaged in such activity. There was an inverse association with energy intake (trend chi 2 = 5.3, P < 0.025) in the comparison with control group (a) only, a finding which is consistent with those of two previous studies of asymptomatic adenoma.

Adenoma↗
PubMed1993

Colorectal adenomas and diet: a case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

Diets high in animal fat and protein and low in fibre and calcium are thought to be factors in the etiology of colorectal cancer. Intakes of these nutrients were determined in three groups participating in a randomised trial of faecal occult blood (FOB) screening. A diet history was obtained by interview from 147 patients with colorectal adenomas, 153 age and sex matched FOB-negative controls (a) and 176 FOB-positive controls without colorectal neoplasia (b). Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence limits (increases) adjusted for age, sex and social class. After adjustment for total energy intake, no associations were found with total, saturated or mono-unsaturated fat, or calcium intake. For total fibre intake there were non-linear relationships with both control groups with the crude RR for highest quintiles of total fibre intake compared to the lowest being 0.6, although this pattern was no longer apparent after adjustment for energy intake with group (a). In comparison with group (b) cereal fibre intake showed a more consistent inverse relationship with adenoma prevalence with the RR for ascending quintiles of intake being 1.0, 0.7 (0.3-1.6), 0.5 (0.3-1.1), 0.7 (0.4-1.4) and 0.3 (0.1-0.6) (trend chi 2 = 8.80, p = 0.003). In comparison with group (a), the adjusted RR for the highest quintile of cereal fibre intake compared with the lowest was 0.6, but no clear trend was apparent. There was an unexpected positive relationship between adenomas and polyunsaturated fat intake with the RR for having an adenoma being 1.0, 2.8 (1.3-6.1), 1.6 (0.7-3.4), 3.5 (1.6-7.5) and 2.3 (1.1-5.0) for ascending quintiles of polyunsaturated fat intakes (trend chi 2 = 4.8, P = 0.03) in comparison with group (a) only. Our data, while providing no support for the role of dietary animal fat or protein, do support the protective role of dietary cereal fibre in the etiology of colorectal adenomas.

Aged↗
PubMed1993

The Chernobyl accident, congenital anomalies and other reproductive outcomes.

Studies of the association between the Chernobyl accident in April 1986 and reproductive outcome, with particular reference to congenital anomalies, are reviewed. All of the studies so far have been based on the detection of a change in frequency over time. An increased frequency of trisomy 21 in the former West Berlin in January 1987, and increases in the frequency of neural tube defects in several small hospital-based series in Turkey, are not confirmed in larger and more representative series in Europe. No clear changes in the prevalence at birth of anomalies which might be associated with the accident are apparent in Byelorussia or the Ukraine, the republics with the highest exposure to fallout. However, these data are difficult to interpret as the methods of acquisition have not been described and they have not yet been reported in full. Thus, there is no consistent evidence of a detrimental physical effect of the Chernobyl accident on congenital anomalies. This is also the case for other measured outcomes of pregnancy. There is evidence of indirect effects--an increase in induced abortions substantial enough to show as a reduction in total births, due to anxieties created. Data are not available on the reproductive outcomes of women pregnant at the time of the accident who were evacuated from the 30 km zone of immediate contamination, of workers in the plant at the time of the accident or of decontamination workers. Moreover, no data are available from several of the other countries closest to the Chernobyl area.

Abortion, Induced↗
PubMed1993

The fine line.

Explore the source record for details and available documents.

Activities of Daily Living↗
PubMed1993

Pharmacological characterization of cloned human NK-2 (neurokinin A) receptor expressed in a baculovirus/Sf-21 insect cell system.

Using the novel ligand [4,5-3H-Leu9]neurokinin A ([4,5-3H-Leu9] NKA) in a receptor binding assay, we characterized the pharmacology of a cloned neurokinin NK-2 receptor from human lung (hNK-2R), expressed in baculovirus-infected Sf-21 insect cells. Functional hNK-2R cDNA clones were isolated from human lung using a polymerase chain reaction-based methodology. hNK-2R was cloned into pAcYM1, a vector designed to couple expression to the polyhedrin promoter, and the recombinant baculovirus was isolated and used to infect Sf-21 insect cells. hNK-2R expression levels were monitored by Northern blots and 125-I-NKA binding assays. Isolates demonstrating the highest specific binding of 125-I-NKA were grown and membrane preparations from high-speed centrifugations were prepared from both hNK-2R-expressing and wild-type virus-infected cells. [3H]NKA bound in a protein-dependent, saturable (Bmax = 820 +/- 167 fmol/mg of protein), and highly specific (88 +/- 5%) manner to hNK-2R, but not to membranes from cells infected with wild-type virus (14 +/- 8%, 7 +/- 10 fmol/mg of protein). [3H]NKA binding was rapid (k1 = 0.085 nM-1 x min-1) and reversible (t1/2 = 4-5 min). Equilibrium binding experiments demonstrated binding to a mixture of receptors in high and low affinity states (Kd1 = 2.28 +/- 0.26 nM and Kd2 = 266 +/- 91 nM). Binding to hNK-2R was greatly enhanced (400%-600%) by Ca2+ and Mg2+ (EC50 values of 30 microM and 140 microM, respectively), whereas guanosine-5'-O-(3'-thio)triphosphate and guanosine-5'-(beta, gamma-imido)diphosphate were inhibitory. Competition experiments with agonists also demonstrated binding to high and low affinity states, with the following order of potency: NKA > [Nle10]NKA(4-10) > [beta-Ala8]NKA(4-10) >> substance P; Senktide and the NK-1 antagonist CP96,345 (10 microM) did not inhibit binding. Inhibition of binding by selective NK-2 antagonists was consistent with a single affinity state and demonstrated the following order of affinity: SR48,968 >> MEN10,376 > L659,877 > R396. These data suggest that infection of Sf-21 cells with baculovirus expression vector harboring the cDNA of hNK-2R resulted in expression of high affinity, G protein-coupled hNK-2R, with pharmacological selectivity compatible with the NK-2A receptor subtype.

Animals↗
PubMed1993

Characterization of bradykinin receptors in guinea pig gall bladder.

Specific binding of [3H]bradykinin (BK) to guinea pig gall bladder (GPGB) membranes was protein dependent, rapid (Kon = 0.067 min-1) with high affinity (Kd = 0.45 +/- 0.02; n = 3), saturable (Bmax = 546 +/- 56 fmol/mg of protein) and showed no cooperativity (nH = 1.19 +/- 0.08). A BK B2 receptor type was indicated by the rank order of potency for inhibition of binding by B2 antagonists, [(D)Arg-[Hyp3,Thi5,(D)Tic7-Oic8]-bradykinin (HOE140) > (D)Arg-[Hyp3,(D)HypE(transpropyl)7-Oic8]-bradykinin (NPC17731) > (D)Arg-[Hyp3,Thi5, (D)Tic7-Tic8]-bradykinin (NPC16731) > (D)Arg-[Hyp3,(D)Phe7]-bradykinin (NPC567)] and agonists (BK = kallidin = Tyr(Me)8-BK > Tyr8-BK,> Hyp4-kallidin) as well as inactivity of the B1 agonist des(Arg9)-BK. Nonhydrolyzable GTP analogs (GTP-gamma-S and guanylyl-5'-imido-diphosphate) produced 80% inhibition of specific binding suggesting receptor coupling to guanine nucleotide-binding proteins. BK increased polyphosphoinositide hydrolysis in chopped GPGB in a concentration-dependent manner (0.01-300 microM; EC50 = 414 +/- 171 nM; n = 3-9 tissues/concentration). HOE140 and NPC16731, inhibited BK-induced polyphosphoinositide hydrolysis but only the latter appeared competitive (pKb 8.09 +/- 0.19, n = 3). U73122, an inhibitor of phospholipase C pathway, also inhibited BK-induced turnover in GPGB (IC50 = 46.9 +/- 17.3 nM). BK produced a concentration-related contraction of isolated strips of GPGB. Indomethacin significantly decreased both the potency and efficacy of BK whereas thiorphan, a neutral endopeptidase inhibitor, and/or captopril, an angiotensin-converting enzyme inhibitor, enhanced potency.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Severe burns resulting from magnetic resonance imaging with cardiopulmonary monitoring. Risks and relevant safety precautions.

Cardiopulmonary monitoring may be desirable during magnetic resonance imaging (MRI) of hemodynamically unstable patients, but must be performed with great caution. This case report describes a severe burn associated with pulse oximetry use during MRI scanning. Risk of this injury is greatest in infants and in individuals with obtundation, general anesthesia, insensate limbs or impairments of verbal communication. Several safety precautions are described. Preparation and monitoring of patients undergoing MRI scanning with cardiopulmonary monitoring should be performed only by specially trained personnel.

Burns↗
PubMed1992

Reduced risk of colorectal cancer among recent generations in New Zealand.

Male and female age standardised mortality and incidence rates of colorectal cancer have increased over the most recent 30 years in New Zealand. Among men and women aged 40 to 74, age standardised mortality and incidence rates increased 18 to 105%. However, age standardised mortality and incidence rates among younger men and women have declined from 14 to 69%. Analysis of trends in age specific mortality and incidence rates indicates that the occurrence of colorectal cancer has been declining equally for men and women in successive cohorts born about 1943 to 1953 in New Zealand. This decline in the frequency of colorectal cancer among recent generations was apparent for both the right and left sides of the colon and the rectum. Age-specific trends in coronary heart disease and breast cancer differed from those apparent for colorectal cancer, suggesting that the factors producing the reduction in colorectal cancer risk may affect these diseases among different age groups or may not be of major aetiological importance in these diseases. These trends provide empirical evidence that the occurrence of colorectal cancer can be reduced by at least 50% with a substantial component of the risk being determined before the age of 30. Further study is needed to establish whether changes in risk factors at older ages contribute to the prevention of the disease.

Adult↗
PubMed1992

Monoclonal antibodies to Gliocladium roseum, a potential biological control fungus of sap-staining fungi in wood.

Immunological probes were developed to discriminate between a potential biological control fungus and sap-staining fungi present in wood. This paper describes the production of monoclonal antibodies to isolated cell wall fragments of the biological control fungus Gliocladium roseum. Two monoclonals, designated 6A5 and 3F12, were characterized. Their specificity was assessed by ELISA, by immunogold silver staining light microscopy, by immunogold electron microscopy, and by immunoblotting. Monoclonal 6A5 specifically recognized G. roseum and closely related species and did not react with any of 21 sap-staining fungi tested. Monoclonal 3F12 recognized most of the biological control fungi tested and also showed reactivity with two of the 21 sap-staining fungi. Both monoclonals appeared to recognize carbohydrate epitopes of the cell wall in G. roseum. Although the antibodies were produced against the cell wall of fungus grown in liquid culture, they also detected specific fungi in wood and, therefore, can be used for studies of wood colonization by fungi and for investigations of the interactions between different fungi growing on wood.

Antibodies, Fungal↗
PubMed1991

Evaluation of an interleukin-1 receptor antagonist in the rat acetic acid-induced colitis model.

The anti-inflammatory activity of the IL-1 receptor antagonist, IL-1ra, was evaluated in the acetic acid (HOAc)-induced model of colitis in rats. Animals treated with 10 mg/kg IL-1ra or vehicle were evaluated for general health, acute phase response, and colonic in flammation 24 hours after the initiation of inflammation. A significant decrease in the accumulation of neutrophils in the colonic mucosa as measured by myeloperoxidase activity was seen in animals with HOAc induced colitis that were treated intraperitoneally with IL-1ra when compared to animals with colitis that had been treated with vehicle. IL-1ra also reduced colonic necrosis measured grossly, although there was no effect on the histology IL-1ra had a modest effect on the HOAc-induced acute phase response, as indicated by changes in the serum iron, albumin and transferrin, but the results were not statistically significant. The number of circulating erythrocytes and neutrophils was significantly increased in animals with HOAc-induced colitis and treated with IL-1ra, suggesting that IL-1ra under these experimental conditions inhibited the migration of neutrophils to the injured colon and also the overall intestinal necrosis in the colon as assessed by gross pathology. IL-1ra may be useful as an intestinal anti-inflammatory agent.

Acetates↗
PubMed1991

For those left behind. An educational inpatient rehabilitation program.

1. An interdisciplinary program model was developed for the treatment of mentally ill individuals remaining in long-term state mental institutions that focused on self-maintenance, social functioning, and community living skills. 2. Patients were categorized according to their levels of functioning and diagnoses, and were assigned to programs that were developed to meet the needs of a specific group of patients. 3. The goals of the program were to enhance the quality of life for the patients; promote self-direction and capacity for self-care by increasing the patient's opportunities to make life decisions; and prepare the patients to live in a less restrictive environment.

Activities of Daily Living↗