Biomedical subjects

J S Morris

Publications and source records attributed to J S Morris.

At least 19 recordsLinked to original sources

PubMed1995

Plasma levels of the antioxidant selenium and risk of myocardial infarction among U.S. physicians.

The well-known antioxidant properties of selenium have been linked to a lower incidence of cardiovascular disease in humans, but the findings remain controversial. To explore whether the plasma selenium level predicts risk of myocardial infarction (MI), we analyzed prospectively collected plasma samples in a nested case-control study among participants in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene. Blood specimens were collected between August 1982 and December 1984 and stored at -80 degrees C. All infarcts were documented by medical records. This study is based on 251 subjects who had infarctions and an equal number of healthy controls, matched by age, smoking status, and time from randomization. The mean +/- SD levels of plasma selenium were 114.4 +/- 15.1 ng/g in the cases with MI, and 113.2 +/- 15.7 ng/g in controls (paired t = 0.94, p = 0.35). Conditional logistic regression analysis by quintile of plasma selenium levels showed no suggestion of any protective effect of selenium; subjects in the highest quintile had a relative risk of 1.27 (95% confidence interval 0.71 to 2.29) when compared with the bottom quintile, and 1.53 (95% confidence interval 0.61 to 3.84) after adjustment for other cardiovascular risk factors. These data provide no evidence for an association between increased plasma selenium and reduced risk of MI at the current levels of selenium intake within the U.S.

Adult↗

PubMed1995

Prospective study of toenail selenium levels and cancer among women.

BACKGROUND: Inverse associations between selenium status and cancer risk have been observed in animal studies, ecologic studies, and some case-control and prospective studies. Whereas results of some prospective studies have suggested an overall inverse relationship between selenium levels and cancer, other prospective studies have failed to confirm this finding. Prospective data on women are particularly limited because fewer women than men have been studied prospectively. PURPOSE: The aim of this study was to prospectively examine the relationship between selenium levels in toenails (previously shown to reflect selenium intake) and incidence of cancer among women. METHODS: The Nurses' Health Study cohort began in 1976 with 121,700 female nurses aged 30-55 years living in 11 U.S. states. In 1982, we requested toenail clippings from the members of the cohort, and 62,641 participants with no history of cancer returned these clippings. During 41 months of follow-up, 503 cases of cancer other than breast cancer (results previously reported) or nonmelanoma skin cancer were analyzed. For each case patient, a control subject was chosen from women who remained free of diagnosed cancer, matched by age and by date of nail return. RESULTS: No inverse association was observed between selenium levels in toenails and cancer risk. The age- and smoking-adjusted relative risk (RR), comparing the highest with the lowest quintile of toenail selenium level, was 1.44 (95% confidence interval [CI] = 0.97-2.13), and the trend across quintiles was marginally significant (two-sided P = .06). Comparing the highest with the lowest decile, the RR (age- and smoking-adjusted) was 1.77 (95% CI = 1.04-3.02). When these data were combined with the data from 434 breast cancer case patients and their matched control subjects identified in parallel from this same cohort, the RR comparing the highest with the lowest quintile was 1.24 (95% CI = 0.93-1.65). Toenail selenium level was not inversely associated with cancer at any major site, including uterine cancer, colorectal cancer, melanoma, ovarian cancer, or lung cancer (after adjusting for smoking); in fact, nonsignificant positive associations were observed at several sites. CONCLUSIONS: Toenail selenium levels were not inversely associated with cancer risk in this study. IMPLICATIONS: These data, in conjunction with previous findings of no association between toenail selenium status and breast cancer risk, strongly suggest that higher selenium intake within the range consumed by most U.S. women (as reflected by toenail selenium levels) is not protective against overall cancer incidence in women.

Adult↗

PubMed1995

Serum antibodies from malaria-exposed people recognize conserved epitopes formed by the two epidermal growth factor motifs of MSP1(19), the carboxy-terminal fragment of the major merozoite surface protein of Plasmodium falciparum.

The major merozoite surface protein of Plasmodium falciparum (PfMSP1) is a candidate antigen for a malaria vaccine. A 19-kDa C-terminal processing product of PfMSP1 (PfMSP1(19)) is composed of two domains sharing a cysteine-rich motif with epidermal growth factor (EGF) and is the target of monoclonal antibodies which block erythrocyte invasion in vitro. We have evaluated human antibody responses to PfMSP1(19) by using recombinant proteins representing the EGF motifs encoded by the two main alleles of the MSP1 gene. We find that both EGF motifs are antigenic but that only 10 to 20% of malaria-exposed individuals have serum antibodies that recognized either of the motifs. When both EGF motifs were expressed together as a single protein, they were recognized by more than 40% of sera from malaria-exposed individuals. Major epitopes recognized by human antibodies are dependent upon the correct tertiary structure of the protein and are cross-reactive between the different allelic sequences of PfMSP1(19). This suggests that antibodies induced by vaccination with one or the other allelic forms of the protein could recognize all strains of P. falciparum. Immunoglobulin G (IgG) subclass-specific enzyme immunoassays indicate that PfMSP1(19) antibodies are predominantly of the IgG1 subclass.

Adolescent↗

PubMed1995

Transcription-independent turnover of I kappa B alpha during monocyte adherence: implications for a translational component regulating I kappa B alpha/MAD-3 mRNA levels.

We identified I kappa B alpha/MAD-3 as an immediate-early gene in human monocytes that is expressed in response to a variety of signals, including adhesion, lipopolysaccharide, and phorbol myristate acetate. Within 5 min of monocyte adhesion, the level of the I kappa B alpha protein is markedly diminished but is rapidly replaced in a cycloheximide-sensitive manner within 20 min. Accompanying the rapid turnover of the I kappa B alpha protein is simultaneous translocation of NF-kappa B-related transcription factors to nuclei of adhered monocytes. The demonstration that NF-kappa B can regulate I kappa B alpha/MAD-3 gene transcription in other cell types suggested that the rapid increase in steady-state I kappa B alpha/MAD-3 mRNA levels we observed within 30 min of monocyte adherence would result from NF-kappa B-dependent transcriptional stimulation of the I kappa B alpha/MAD-3 gene. Nuclear run-on analyses indicated that, instead, while several immediate-early cytokine genes, such as the interleukin 1 beta (IL-1 beta) gene, were transcriptionally activated during monocyte adhesion, the rate of I kappa B alpha/MAD-3 gene transcription remained constant. The adherence-dependent increase in I kappa B alpha/MAD-3 mRNA levels was also not a consequence of mRNA stabilization events. Interestingly, while increases in both IL-1 beta and I kappa B alpha/MAD-3 mRNA levels were detected in nuclei of adherent monocytes, cytoplasmic levels of IL-1 beta mRNA increased during adherence whereas those of I kappa B alpha/MAD-3 mRNA did not. Taken together, our data suggest that two interactive mechanisms regulate monocytic I kappa B alpha/MAD-3 mRNA levels. We propose that adherent monocytes regulate nuclear processing (or decay) of I kappa B alpha/MAD-3 mRNA, thereby increasing mRNA levels without stimulating I kappa B alpha/MAD-3 gene transcription. Moreover, since inhibition of protein synthesis leads to accumulation of I kappa B alpha/MAD-3 mRNA without stimulating I kappa B alpha/MAD-3 gene transcription, we suggest that low cytoplasmic levels of I kappa B alpha/MAD-3 mRNA are maintained by a translation-dependent degradation mechanism.

Antibodies, Monoclonal↗

PubMed1994

Transdermal nicotine for active ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis. METHODS: We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12). CONCLUSIONS: The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.

Administration, Cutaneous↗

PubMed1994

Human monoclonal antibody developed against ovarian cancer cell surface antigen.

BACKGROUND: Murine monoclonal antibodies (MoAb) potentially can be used in the radioimmunodetection and radioimmunotherapy of cancer. However, the administration of these radiopharmaceuticals to humans often leads to induction of human anti-murine antibodies (HAMA). HAMA has many disadvantages, which could decrease efficacy of the murine MoAb. The purpose of this work was to produce human monoclonal antibody against a human ovarian cancer cell surface antigen (OCCSA), which was not present in normal ovarian cells. This 200-kilodalton OCCSA also was used in the present study for characterizing the human monoclonal antibody. METHODS: Human monoclonal antibodies were produced in vitro by fusion of mutant myeloma cells, selected from GM1500, with human lymphoid cells immunized in vitro with purified OCCSA: The human monoclonal antibody was characterized using the following techniques: sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), native-PAGE, Western blotting followed by protein-A gold staining, immunodiffusion assays, and fluorescent antibody assays. RESULTS: Human monoclonal antibody, TC5 (immunoglobulin G1), was produced and purified. It was found to be specific for ovarian cancer, while also reacting with an early stage breast cancer. TC5 did not react with any normal (i.e., nonneoplastic) cells of the ovary, uterus, cervix, endocervix, or fallopian tube, nor did it react with normal lung, heart, pancreas, liver, or breast tissue. CONCLUSION: Human-human hybridomas produced human monoclonal antibody against OCCSA: The human monoclonal antibody, TC5, was specific for ovarian and breast cancer. TC5 did not react with any normal tissue tested. Future work will focus on the in vivo characterization of the human monoclonal antibody, after labeling with radionuclides.

Antibodies, Monoclonal↗

PubMed1994

Production of no-carrier-added 64Cu from zinc metal irradiated under boron shielding.

BACKGROUND: Positron emission tomography offers advantages for radioimmunodiagnosis of cancer but requires radionuclides of appropriate half-life that have high specific activity and high radio-purity. This work was designed to develop a viable method to produce and purify 64Cu, which has high specific activity, for positron emission tomography. METHODS: 64Cu was produced at the University of Missouri Research Reactor by the nuclear reaction, 64Zn(n,p)64Cu. Highly pure zinc metal (99.9999%) was irradiated in a specially designed boron nitrite lined container, which minimized thermal neutron reactions during irradiation. A new two-step procedure was developed to chemically separate the no-carrier-added 64Cu from the zinc metal target. RESULTS: 64Cu recovery for 24 runs averaged 0.393 (+/- 0.007) mCi per milligram of zinc irradiated. The boron-lined irradiation container reduced unwanted zinc radionuclides 14.3-fold. Zinc radionuclides and non-radioactive zinc were separated successfully from the 64Cu. The new separation technique was fast (2 hours total time) and highly efficient for removing the zinc. The zinc separation factor for this technique averaged 8.5 x 10(-8), indicating less than 0.0000085% of the zinc remained after separation. Thus far, the highest 64Cu specific activity at end of irradiation was 683 Ci/mg Cu, with an average of 512 Ci/mg Cu for the last six analyzed runs. CONCLUSION: The boron-lined irradiation container has sufficient capacity for 75-fold larger-sized zinc targets (up to 45 g). The new separation technique was excellent for separating 64Cu, which appears to be a radionuclide with great potential for positron emission tomography.

Boron↗

PubMed1994

Detection of ovarian cancer by 198Au-labeled human monoclonal antibody.

BACKGROUND: There is no reliable method for the early diagnosis of ovarian cancer. Radiolabeled monoclonal antibodies have potential to assist in early diagnosis, but they are limited by problems that include antibody specificity, stability, and immunoreactivity, as well as patient reactions to the antibodies used. METHODS: Methods were developed to 198Au-label a human monoclonal antibody (TC5 antibody), developed against an ovarian cancer cell surface antigen. Antigen binding sites on the TC5 antibody were protected with sepharose 4B affinity chromatography before 198Au-labeling. The 198Au-labeled TC5 antibody was evaluated with biopsy specimens in a blind study. The immunoreactivity of radiolabeled TC5 antibody also was evaluated in slot-blot experiments with extracts of the biopsy specimens. RESULTS: The 198Au-labeled TC5 antibody had high binding reaction to all biopsy specimens (six of six) pathologically diagnosed as ovarian cancer (serous and endometrioid adenocarcinoma). The radiolabeled TC5 antibody did not bind to any normal (non-neoplastic) specimens (zero in ten), with one exception. One "normal" ovary specimen had high binding of radiolabeled TC5 antibody, and metastatic ovarian cancer was diagnosed 4 months later. The TC5 antibody labeled with 198Au, without protecting antigen-binding sites, did not bind to any biopsy specimens. CONCLUSIONS: The affinity-labeling method was necessary to protect antigen-binding sites and preserve the immunoreactivity of the TC5 antibody. The 198Au-labeling method may be an ideal technique to evaluate monoclonal antibodies in vitro. The TC5 antibody had high sensitivity and specificity for detecting ovarian cancer.

Antibodies, Monoclonal↗

PubMed1994

Haematological risk factors for pregnancy outcome in Jamaican women with homozygous sickle cell disease.

OBJECTIVE: To examine the association between fetal outcome and the steady state haematology of mothers with homozygous sickle cell disease. DESIGN: A retrospective observational study. The data were taken from dockets kept at the Sickle Cell Clinic and verified by interview with 45% of the patients. SETTING: The Sickle Cell Clinic at the University Hospital of the West Indies or two peripheral clinics operated by the staff of the MRC Laboratories. SUBJECTS: All women aged 14 years or older with homozygous sickle cell disease who had experienced at least one pregnancy in the period 1977 to 1986. MAIN OUTCOME MEASURES: Three fetal outcomes including miscarriages, perinatal deaths, and birthweight. RESULTS: There were 270 singleton pregnancies in 175 women with an overall fetal wastage of 32.2%. There was a significant increased risk of perinatal death with low maternal fetal haemoglobin level, but there were no haematological associations with miscarriages or birthweight. CONCLUSIONS: These data suggest that maternal steady-state haematology has little influence on fetal outcome, with the exception that mothers with high HbF levels are less prone to perinatal deaths. Further study is required to investigate acute haematological changes associated with pregnancy.

Abortion, Spontaneous↗

PubMed1994

Ulcerative colitis in a husband and wife.

The case histories of a husband and wife who developed ulcerative colitis after 28 years of marriage are described. It is hoped this report will stimulate the systematic study of inflammatory bowel disease occurring in both partners of a marriage and clarify the comparative importance of constitutional and environmental factors in its pathogenesis.

Colitis, Ulcerative↗

PubMed1993

Use of tamoxifen in the control of canine mammary neoplasia.

Ninety-three bitches which had undergone mammary tumour surgery were entered into a clinical trial to examine the effects of ovariohysterectomy (spaying) at the time of mammary surgery and the use of the drug tamoxifen in preventing the recurrence of the tumour and/or the development of new mammary tumours. Twenty-three of the bitches which had been spayed were allocated tamoxifen but only 18 of them complied with the treatment and in nine of these the treatment was stopped owing to side effects (mostly oestrogenic). Too few animals were studied to draw conclusions about the possible preventative effects of tamoxifen on mammary neoplasia, but the high percentage of bitches affected by oestrogen-like side effects may reduce the compliance of owners and prevent tamoxifen being widely used in dogs.

Animals↗

PubMed1993

Serum micronutrients and the subsequent risk of oral and pharyngeal cancer.

To investigate the relationship between serum micronutrients and the subsequent risk of oral and pharyngeal cancer, a nested case-control study was conducted within a cohort of 25,802 adults in Washington County, MD, whose blood samples were collected in 1974 and stored at -70 degrees C for subsequent assays. The serum levels of nutrients in 28 individuals who developed oral and pharyngeal cancer during 1975 to 1990 were compared with levels in 112 matched controls. Serum levels of all individual carotenoids, particularly beta-carotene, were lower among subjects who developed oral and pharyngeal cancer. The risks of this malignancy decreased substantially with increasing serum level of each individual carotenoid. Persons in the highest tertile of total carotenoids had about one-third the cancer risk as those in the lowest tertile. High serum levels of alpha-tocopherol also were related to a low oral cancer risk in later years, but the risks were elevated significantly with increasing serum levels of gamma-tocopherol and selenium. The findings from this study are consistent with many previous epidemiological investigations of dietary factors for oral and pharyngeal cancer and provide further evidence for the potential role of carotenoids and alpha-tocopherol in the chemoprevention of these malignancies.

Carotenoids↗

PubMed1993

A comparison of the bioeffects of four different modes of stone therapy on renal function and morphology.

A variety of therapeutic options exists for removal of symptomatic renal calculi, including extracorporeal shock wave lithotripsy, percutaneous nephrostolithotomy and open pyelolithotomy or nephrolithotomy. Although lithotripsy offers the advantage of reduced patient morbidity, the relative alterations in renal function and morphology for each of the respective treatment modalities have not been completely assessed. We evaluated 17 pigs (40 to 50 lb.) for evidence of histologic and functional renal changes after a pyelotomy (N = 3) or nephrotomy (N = 4), piezoelectric lithotripsy (N = 5), or placement of a percutaneous nephrostomy tube with balloon dilation (N = 5). Pathologic evaluation one month after treatment revealed no renal scarring in the animals that underwent a pyelotomy and minimal parenchymal fibrosis in the nephrotomy and lithotripsy groups (0.014 +/- 0.001% and 0.015 +/- 0.002%, respectively). In contrast, the percutaneous nephrostomy group demonstrated 1.53 +/- 0.4% of the treated kidney to be involved by scarring (p < 0.001). Despite the statistically significant increase in renal scarring after percutaneous nephrostomy, neither creatinine and PAH clearances nor renal plasma flows changed significantly among the four treatment groups. Moreover, no change in renal function after treatment was observed when compared with baseline evaluations. All four therapeutic options for renal stone removal appear to result in small amounts of renal parenchymal damage but are not associated with significant alterations in renal function.

Animals↗

PubMed1993

Major renal lacerations with a devitalized fragment following blunt abdominal trauma: a comparison between nonoperative (expectant) versus surgical management.

Of 43 patients who sustained blunt trauma resulting in a major renal laceration with a devitalized fragment 27 had coexisting intraperitoneal and renal injuries for which emergency celiotomy and repair of the nonurological trauma were done. Management of the renal injuries consisted of simultaneous renal exploration with 23% urological morbidity in 13 cases or expectant management with 85% urological morbidity in 14 cases. In this latter patient population infected urinomas and perinephric abscesses seeded from coexisting enteric or pancreatic injuries were the most common complication (57%). The remaining 16 of the 43 patients sustained renal lacerations without associated intraperitoneal injuries and all were managed expectantly with 38% urological morbidity. These findings suggest that renal exploration and surgical repair significantly improve the prognosis only in patients with simultaneous intraperitoneal and renal injuries (p < 0.01).

Abdominal Injuries↗

PubMed1993

Laser photocoagulation for proliferative retinopathy in sickle haemoglobin C disease.

The effect of sectoral, scatter laser photocoagulation on proliferative sickle retinopathy (PSR) was investigated by reviewing fluorescein angiograms of 88 sickle cell-haemoglobin C patients enrolled in a controlled, randomised trial. Follow-up was for a median period of 2.9 years. Complete infarction of all PSR in an eye occurred in 7 of 74 treated eyes and 2 of 60 control eyes. Treatment resulted in significantly greater regression (decrease in number or size of PSR lesions) in eyes of patients aged < 25 years at enrollment but not in eyes of patients > or = 25 years at enrollment. Infarction of individual PSR lesions was significantly more common in treated eyes. Treated PSR was significantly more likely to infarct if small (< 15 degrees circumferential involvement) and if flat rather than elevated. New PSR was significantly less likely to develop in treated eyes.

Adult↗

PubMed1993

A 1-y trial of the effect of high-selenium bread on selenium concentrations in blood and toenails.

The concentration of selenium in toenail clippings and blood reflects dietary intake better than does intake calculated from dietary data because of the highly variable selenium concentration in different samples of the same food. However, the time course of selenium intake in relation to subsequent concentrations in toenail clippings is unclear. Therefore, 12 males were fed high-dose (4.91 mumol Se/d), medium-dose (2.61 mumol Se/d), or control (0.41 mumol Se/d) whole-wheat-bread for 1 y and the concentration of selenium was measured in toenail clippings collected every 12 wk for 2 y. Toenail selenium concentration was unaffected by dietary intake in the previous 3 mo and appeared to provide a time-integrated measure of intake over a period of 26-52 wk. Use of selenium concentration in toenail clippings may be an alternative to blood when a measure of long-term average intake is desired. The absence of a short-term effect of diet on toenail selenium concentration also makes this a useful marker of intake in retrospective studies.

Adult↗

PubMed1992

Maternal zinc and fetal neural tube defects.

Among the factors implicated in the heterogeneous etiology of neural tube defects (NTDs) is the trace element zinc (Zn). In a case-control study, we collected midtrimester maternal toenail samples for multiple trace element analyses, including Zn, which were assayed by neutron activation analysis. We studied 17 women with NTD offspring and 1,787 controls. The crude OR for NTD comparing Zn values greater than normal range to normal Zn values was 3.2 (95% CI 1.1,9.7). These results were not materially affected when adjustment was made for folic acid supplementation. An overall increased risk for NTD associated with increasing toenail Zn was also evident. A matched subset of 17 cases and 73 controls yielded a crude OR of 3.1 (95% CI 0.9,10.3) when cases with elevated Zn (greater than or equal to 120 ppm) were compared to those with normal Zn. Matched analyses controlling for folic acid supplements, family history of NTD, assay batch, age of mother and year of delivery yielded an OR of 5.0 (95% CI 1.1,21.6). This study reveals an association between increased toenail Zn in the second trimester of pregnancy and the risk of having a child with an NTD. Whether Zn sequestration has resulted in relative Zn deficiency at the site of neural tube closure remains uncertain.

Case-Control Studies↗

PubMed1992

Conjugative plasmids in Bordetella avium.

Three of five antibiotic-resistant plasmids isolated from virulent strains of Bordetella avium were found to be conjugative. A physical and genetic map of one of these plasmids, the 51.5-kb plasmid p4093, revealed that the area of p4093 responsible for streptomycin and tetracycline resistance was located in a region consisting of a cluster of restriction enzyme recognition sites, whereas the remainder of p4093 contained relatively few restriction sites. Additionally, the genes involved in the conjugative ability of p4093 were clustered in at least two widely separated regions of the plasmid.

Bordetella↗