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Biomedical subjects

J Griffith

Publications and source records attributed to J Griffith.

At least 19 recordsLinked to original sources
PubMed1998

Significance of cytomegalovirus for long-term survival after orthotopic liver transplantation: a prospective derivation and validation cohort analysis.

BACKGROUND: Cytomegalovirus (CMV) infection and disease has been found to be associated with decreased graft and patient survival among heart transplant recipients. We sought to explore the effect of CMV infection and disease on long-term survival in orthotopic liver transplant (OLT) recipients using a derivation and validation cohort. METHODS: For derivation-validation modeling, we used data collected from two prospectively followed cohorts as the basis for multivariate analyses: 167 OLT recipients from the Boston Center for Liver Transplantation (the derivation set; median follow-up: 5.5 years, mortality: 40%) and an independent cohort of 294 OLT recipients from the Mayo Clinic (the validation set; median follow-up: 4.8 years, mortality: 27%). RESULTS: Underlying liver disease other than primary biliary cirrhosis or sclerosing cholangitis, number of units of red blood cells administered during transplantation, and donor CMV seropositivity were the pre- and intratransplant variables independently associated (P<0.01) with decreased long-term survival in the derivation cohort. For variables collected up to 1 year after transplantation, the need for retransplan. tation, CMV pneumonia, invasive fungal disease, and underlying liver disease other than primary biliary cirrhosis or sclerosing cholangitis were independently associated (P<0.01) with decreased long-term survival in the derivation cohort. The magnitude of the relationship of each pre-, intra-, and posttransplant factor with survival, as measured by the relative risk, did not significantly differ between the derivation and validation cohorts. The derivation model, incorporating pre-, intra-, and posttransplant factors, had receiver operating characteristic areas of 73% and 74% for 5-year mortality in the derivation and validation cohorts, respectively. CONCLUSIONS: Data from a derivation and an independent validation cohort demonstrate that CMV factors (reflected by either donor CMV seropositivity at transplantation, CMV pneumonia, or CMV disease within the first posttransplant year) are independently associated with decreased long-term survival in OLT recipients.

Adolescent↗
PubMed1998

Chemically induced mutations in mitochondrial DNA of human cells: mutational spectrum of N-methyl-N'-nitro-N-nitrosoguanidine.

We have observed a reproducible mitochondrial mutational spectrum in the MT1 human lymphoblastoid line treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The MNNG spectrum was distinct from the spontaneous mutational spectrum. However, our ability to observe MNNG-induced mitochondrial mutations above the high level of accumulated spontaneous mutations was dependent on the MT1 phenotype. MT1 cells are markedly resistant to the cytotoxicity but not the mutagenicity of MNNG, presumably as a result of inactivation of both copies of the hMSH6 (GTBP) mismatch repair gene. Thus, we were able to use conditions of treatment that yielded induced mitochondrial mutant fractions beyond the practical limits for human cell experiments in mismatch-proficient human cell lines. In contradistinction, when MT1 cells were treated repeatedly with maximum tolerated concentrations of (+/-) anti-benzo(a)pyrene diol-epoxide, no induced mitochondrial mutations above the spontaneous background were observed. A single dose of 4 microM MNNG (survival, 0.85) induced a mutant fraction of 8 x 10(-3) in the nuclear hypoxanthine-guanine phosphoribosyltrans. ferase gene, and a clear and reproducible pattern of seven MNNG-induced hotspot mutations was observed within the mitochondrial DNA target sequence studied (mitochondrial bp 10,030-10,130). All of the MNNG-induced hotspot mutations were G:C to A:T transitions present at frequencies between 6 x 10(-5) and 30 x 10(-5). Additional experiments supported the conclusion that MNNG-induced hotspot mutations observed were generated in living cells as a result of MNNG treatment and not from mismatch intermediates or DNA adducts converted into mutations during the PCR process.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

TRF1 promotes parallel pairing of telomeric tracts in vitro.

Human telomeres consist of long arrays of TTAGGG repeats bound to the telomere-specific proteins, TRF1 and TRF2. Here we describe the structure of in vitro complexes formed between telomeric DNA and TRF1 as deduced by electron microscopy. Visualization of TRF1 bound to DNA containing six or 12 tandem TTAGGG repeats revealed a population of DNAs containing a spherical protein complex localized just to the repeats. Mass analysis of the protein complexes suggested binding of TRF1 dimers and tetramers to the TTAGGG repeats. The DNA was not significantly compacted or extended by protein binding. TRF1 formed filamentous structures on longer telomeric repeat arrays (>/=27 repeats) consistent with the presence of an array of bound TRF1 dimers. Unexpectedly, there was a strong propensity for two telomeric tracts to form paired synapses over the TRF1 covered segment. Up to 30% of the TRF1-bound DNAs could be found in a paired configuration with a strong bias for a parallel as contrasted to an antiparallel arrangement. TRF1-induced pairing was confirmed using a ligation assay which detected the formation of DNA multimers dependent on the presence of TRF1 and a 27mer repeat array in the DNA. These findings suggests that this protein may have an architectural role at telomeres. We discuss the possibility that TRF1-dependent changes in the conformation of telomeres are involved in the regulation of telomere length.

DNA↗
PubMed1998

Relative body weight and self-esteem among African Americans in four nationally representative samples.

OBJECTIVE: Obesity is an increasingly common health problem among African Americans, especially women, in the United States. However, limited data are available on the psychological correlates of obesity in this population. This study examined the association between self-esteem and relative body weight (RBW) in four large nationally representative samples of African American individuals. RESEARCH METHODS AND PROCEDURES: Data from The Adolescent Health Care Evaluation Study, The National Longitudinal Survey of Youth, The High School and Beyond, and The National Survey of Black Americans were analyzed. Within each database, regression analyses tested the association between RBW and self-esteem while adjusting for age and sex. RESULTS: In three of the four databases, there was no significant association between RBW and self-esteem. In the only database detecting a statistically significant effect, the magnitude of the effect was small. The combined effects of RBW and its interaction with age and sex accounted for <2% of the variance in self-esteem across databases. DISCUSSION: Results suggest that elevated RBW is not associated with a poorer general self-concept, on average, among African American individuals.

Adolescent↗
PubMed1998

The health consequences of vertebral deformity in elderly Chinese men and women.

The following health consequences of vertebral deformity in Hong Kong elderly Chinese men and women were studied: the prevalence of back pain, disability due to back pain, and low morale. Lateral X-ray films were taken of the thoracic and lumbar spine of 796 community-dwelling Chinese subjects (396 men, 400 women) (aged 70-79). Subjects with one or more definitely deformed vertebra (reduction in vertebral height 3 SD or more below the mean) were classified as definite cases, those with one or more mildly deformed vertebra (reduction in vertebral height 2-2.99 SD below the mean) as mild cases, and the rest as controls. The prevalence and consequences of back pain were measured by a standardized questionnaire, and morale was measured by the Geriatric Morale Score. The relative risk (RR) and 95% confidence interval (CI) of having back pain and being depressed were calculated by logistic regression. Classifications included 16% of men and 30% of women as definite cases, 37% of men and 35% of women as mild cases, and 47% of men and 35% of women as controls. The relative risk (RR) of back pain was 2.3 (95% CI 1.4-3.9) (P < 0.05) in women with definite deformity and 1.5 (95% CI 0.9-2.5) (P > 0.05) in women with mild deformity, as compared with controls. Sixty-four percent of all men had back pain. This prevalence was much higher than figures obtained in a previous survey on low back pain. The prevalence of back pain did not differ by deformity status, but more men with vertebral deformity were on analgesic. There was no significant association between disability due to back pain and vertebral deformity in women. The RR for having a low morale score (of 5 and below) was 2.3 (95% CI 1.3-4.1) (P < 0. 05) in women with mild deformity; men with vertebral deformity did not have a low morale. It was concluded that vertebral deformity was associated with significant back pain and psychological morbidity in elderly Chinese women. Although men with vertebral deformity did not report more back pain, more were on analgesics than controls.

Aged↗
PubMed1998

Total or subtotal gastrectomy for gastric carcinoma? A study of quality of life.

The aim of this study was to compare quality of life after total gastrectomy (TG) with that after subtotal gastrectomy (STG) for gastric carcinoma. The value of the routine use of TG de principe in the treatment of gastric carcinoma, wherever the tumor may be sited in the stomach, remains controversial. The advocates of TG contend that when it can be performed safely, with relatively low operative mortality and morbidity, it yields better long-term survival than STG. Most surgeons, however, believe that the routine use of TG increases both operative mortality and morbidity and the risk of nutritional deficiency in the long term, without improving survival. TG may also be associated with poorer outcome in terms of quality of life (QOL), but the evidence for this is tenuous. Forty-seven consecutive patients who had undergone potentially curative (R0) gastric resection for carcinoma were studied: 26 had undergone TG and 21 STG. A radical D2 lymph node dissection had been performed in each, and all patients were free from recurrence at the time of the study. QOL was measured before operation and 1, 3, 6, and 12 months after operation by means of five questionnaires to measure functional outcome: the Rotterdam symptom checklist (RSCL), the Troidl index, the hospital anxiety and depression (HAD) scale, activities of daily living score, and Visick grades. Before operation there was no significant difference in QOL between the two groups of patients. At 1 year after operation, however, patients who had undergone STG had a significantly better QOL than patients who had undergone TG: Their median RSCL score was lower (10 versus 19 respectively, p < 0.05), and their Troidl index was higher (11 versus 9 respectively, p < 0.05). The QOL of patients who underwent STG was also significantly better after operation than it had been before operation, whereas the QOL of the TG group was not significantly better after operation than before operation. The QOL of patients was found to be significantly better after STG than after TG for gastric carcinoma. Because operative mortality is greater and long-term survival is no better after TG than after STG, the latter is recommended as the treatment of choice for tumors of the distal stomach.

Activities of Daily Living↗
PubMed1998

Predictive model of weapon carrying among urban high school students: results and validation.

OBJECTIVES: The purpose of this study was to identify the behavioral, psychosocial, and demographic predictors of self-reported weapon carrying among secondary school students who attend urban public schools. METHODS: Self-reported weapon carrying was measured in a schoolwide anonymous health survey conducted in two demographically comparable high schools in 1992, in Boston, Massachusetts. Indicators of self-perception, depression, stressful life events, and adolescent risk behaviors of substance use and sexual behavior, along with self-reported weapon carrying, were measured. The students in both schools were racially heterogeneous, with the majority of about 80% from black or Hispanic backgrounds. A predictive model was developed using a forward stepwise logistic regression model in one inner-city high school, and tested in a second high school. RESULTS: Self-reported lifetime weapon carrying was 32% overall. The major predictors of weapon carrying among urban secondary school students are a combination of demographic, psychosocial, behavioral, and school-related factors. This analysis indicates consistency in eight markers predictive of weapon carrying: lower age, male gender, regular marijuana use, sexual experience, having witnessed a crime, having skipped school, suicidal ideation, and having hit or "beat up" someone. Race parental education, and family composition were not significant predictors. Significant predictors of weapon carrying were marijuana use and sexual experience, each of which was consistently high in both schools. CONCLUSIONS: The model-building and validation presented in this study provide empirical evidence for three important conclusions. First, weapon carrying is associated with multiple and interrelated factors which include demographic, psychosocial, behavioral, and school-related characteristics of high school-age adolescents. Second, students with more risk factors are more likely to carry a weapon, suggesting that the variables are independent markers. Third, this study identified marijuana use and being sexually experienced as both highly predictive of weapon carrying. Implications of this study for prevention point to the need for comprehensive multidisciplinary services in high school that include mental health counseling as well as health education efforts aimed at behavior change.

Adolescent↗
PubMed1998

Late incidence of cancer after metronidazole use: a matched metronidazole user/nonuser study.

In vitro mutagenic activity and carcinogenic potential of metronidazole in certain animals raised concerns about its possible carcinogenicity in humans. We studied the late incidence of cancer after metronidazole use among persons enrolled in the Group Health Cooperative of Puget Sound, Seattle, a health maintenance organization. Randomly selected nonusers were matched on a one-to-one basis for age, gender, and year of enrollment to persons who used metronidazole on an outpatient basis during the period January 1975 to December 1983; 5,222 metronidazole user/nonuser pairs, for whom the median follow-up was 12.6 years, were analyzed. Forty-nine percent, 39.2%, 9.8%, and 2% of users had 1, 2-4, 5-9, and > or = 10 prescriptions or refills of metronidazole filled, respectively. The late (after the first 7 years of follow-up) incidence of cancer was nearly identical among users and nonusers (652 and 662 per 100,000 person-years, respectively; relative risk, 0.98; 95% confidence interval, 0.80-1.20). Age-gender stratified analysis did not reveal any association between metronidazole use and cancer. These data support no association between short-term exposure to metronidazole and cancer in humans. Although the results are reassuring, they may not extend to subjects who have used metronidazole for prolonged periods; further epidemiological studies should focus on these individuals.

Adolescent↗
PubMed1998

Reduction in vancomycin-resistant Enterococcus and Clostridium difficile infections following change to tympanic thermometers.

OBJECTIVE: To contain a nosocomial outbreak of vancomycin-resistant Enterococcus (VRE). DESIGN: Intervention study, with comparison of incidence rates before and after intervention to assess whether changes in incidence followed the intervention and were greater than expected based on trends observed before the intervention. SETTING: A 343-bed acute-care hospital serving a predominantly elderly population referred from nursing homes, as well as patients admitted from the community. METHODS: Interventions strategies were tested on three high-risk nursing stations. These included enhanced environmental sanitation; intensive staff retraining in Universal Precautions, body substance isolation, and proper use of gloves; and the use of tympanic thermometers to avoid possible rectal or oral VRE transmission during temperature taking. RESULTS: Nosocomial VRE infections were reduced by 48% 9 months after switching to tympanic thermometers; incidence of Clostridium difficile infections also was reduced. As a result, tympanic thermometers were introduced facilitywide; additional observation for 20 months showed a risk reduction of 60% for VRE and 40% for C difficile. CONCLUSION: Cross-transmission of VRE and C difficile during temperature taking may result in bowel colonization, placing the patient at increased risk for infection. This risk may be reduced by the use of tympanic thermometers.

Anti-Bacterial Agents↗
PubMed1998

Schizophrenia, sensory gating, and nicotinic receptors.

A series of human and animal investigations has suggested that altered expression and function of the alpha7-nicotinic cholinergic receptor may be responsible for the auditory sensory gating deficit characterized in schizophrenia patients and their relatives as diminished suppression of an auditory-evoked response (P50) to repeated stimuli. This finding, in conjunction with evidence for familial transmission of this sensory gating deficit, suggests a pathogenic role of the gene for the alpha7-nicotinic receptor in schizophrenia. This article considers the possible effects of this dysfunction in a broader context. Not only is this dysfunction consistent with difficulties in sensory gating, but it might also predispose patients to problems with learning efficiency and accuracy. Such learning problems could underlie schizophrenia patients' delusional thinking, hallucinations, and social dysfunction. In addition, heavy smoking in many schizophrenia patients is consistent with the high concentration of nicotine necessary to activate the receptor and with the receptor's extremely rapid desensitization. Finally, the receptor's possible role in cell growth and differentiation should be considered in connection with developmental deficits and other cellular abnormalities in schizophrenia.

Animals↗
PubMed1998

Dual phase spiral CT in the detection of small insulinomas of the pancreas.

Dual phase contrast enhanced spiral computed tomography (DPSCT) has the potential to improve detection of small insulin secreting islet cell tumours of the pancreas. Seven patients with biochemically proven insulinoma, who had previously undergone a range of negative radiological procedures, were referred for DPSCT. Images of the pancreas were obtained using 3 mm collimation in the arterial and arteriovenous perfusion phase following the rapid injection of contrast medium. Six tumours were localized in seven patients. The six insulinomas identified on DPSCT ranged in size from 6 mm to 18 mm and were located in the uncinate process (2), head (1), neck (2) and body (1). All six tumours were detected in the arterial phase and four in the arteriovenous phase. The four insulinomas detected on both perfusion phases were more conspicuous in the arterial phase in three patients and more conspicuous in the arteriovenous phase in one patient. In conclusion, high resolution arterial phase acquisition of the pancreas is very valuable in the detection of small insulinomas.

Adult↗
PubMed1997

In vitro reconstruction of the Aspergillus (= Emericella) nidulans genome.

A physical map of the 31-megabase Aspergillus nidulans genome is reported, in which 94% of 5,134 cosmids are assigned to 49 contiguous segments. The physical map is the result of a two-way ordering process, in which clones and probes were ordered simultaneously on a binary DNA/DNA hybridization matrix. Compression by elimination of redundant clones resulted in a minimal map, which is a chromosome walk. Repetitive DNA is nonrandomly dispersed in the A. nidulans genome, reminiscent of heterochromatic banding patterns of higher eukaryotes. We hypothesize gene clusters may arise by horizontal transfer and spread by transposition to explain the nonrandom pattern of repeats along chromosomes.

Aspergillus nidulans↗
PubMed1997

Human p53 binds Holliday junctions strongly and facilitates their cleavage.

Holliday junctions in DNA are generated as a product of homologous recombination events. To test the hypothesis that human p53 may bind to Holliday junctions, synthetic junctions with four approximately 75-base pair (Hol75) or approximately 565-base pair (Hol565) arms were generated. As seen by electron microscopy, under conditions in which 50-61% of the Hol565 DNAs were bound by p53, 80-96% of the p53 was located specifically at the junction with, in the latter case, only 4% of the p53 visualized at the DNA ends or along the arms. Given the large number of potential binding sites, this represents very high specificity for the junctions. Gel retardation assays using the Hol75 DNA confirm these observations, and indicate that the tight junction complexes have a half-life of greater than 4 h. The binding of p53 to three-way junctions is severalfold less than to four-way junctions. Addition of p53 greatly increases the rate of resolution of the Hol75 DNA by T4 endonuclease VII and T7 endonuclease I, two enzymes known to cleave such junctions. This latter finding further confirms the interaction of p53 with Holliday junctions and suggests that p53 binding facilitates their resolution in vivo.

Binding Sites↗
PubMed1997

Effect of cytomegalovirus infection status on first-year mortality rates among orthotopic liver transplant recipients. The Boston Center for Liver Transplantation CMVIG Study Group.

BACKGROUND: To reduce the mortality rate associated with liver transplantation, it is important to identify the risk factors for increased mortality among liver transplant recipients. It has been suggested that cytomegalovirus (CMV) infection is one such risk factor, but no studies have examined mortality rates associated with the CMV serologic status of the donor and recipient by using multivariate techniques. OBJECTIVE: To study the effect of CMV on 1-year mortality rates in orthotopic liver transplant recipients. DESIGN: Intention-to-treat analysis of a cohort. PATIENTS: 146 liver transplant recipients who were enrolled in a multicenter, randomized, placebo-controlled intervention trial. SETTING: Four university-affiliated transplantation centers. RESULTS: 1-year mortality rates for the four strata of donor and recipient CMV serologic status before transplantation were as follows: seronegative donor and recipient, 11%; seronegative donor and seropositive recipient, 22%; seropositive donor and recipient, 30%; and seropositive donor and seronegative recipient, 44% (P = 0.0091). Multivariate analysis using a time-dependent Cox proportional hazards model showed that retransplantation (relative risk, 4.6 [95% CI, 1.9 to 10.7]; P < 0.001); total number of units of blood products administered during transplantation (relative risk, 1.006 per unit [CI, 1.003 to 1.010]; P < 0.001); and presence of CMV disease (relative risk, 3.9 [CI, 1.8 to 8.5]; P < 0.001), invasive fungal disease (relative risk, 3.3 [CI, 1.5 to 7.1]; P = 0.0020), and bacteremia (relative risk, 2.5 [CI, 1.2 to 5.2]; P = 0.0136) were independently associated with higher mortality rates. If post-transplantation variables that were highly correlated with donor and recipient CMV serologic status were restricted from the model, donor and recipient CMV serologic status was the only pretransplantation variable independently associated with higher mortality rates (P = 0.002). CONCLUSION: Donor and recipient CMV serologic status is a significant pretransplantation determinant for death in liver transplant recipients.

Adult↗
PubMed1997

Saccharomyces cerevisiae MSH2, a mispaired base recognition protein, also recognizes Holliday junctions in DNA.

Genetic and biochemical studies have suggested that mismatch repair proteins interact with recombination intermediates to prevent recombination, or to limit the extent of formation of heteroduplex DNA during recombination between divergent DNA sequences. To test the idea that mismatch repair proteins regulate recombination by interacting with recombination intermediates, we investigated whether the Saccharomyces cerevisiae MutS homolog MSH2 could interact with Holliday junctions. Both filter-binding and electron-microscopic analysis showed that MSH2 bound to duplex DNA molecules containing Holliday junctions with a higher affinity than to control duplex DNA, single-stranded DNA or a control duplex DNA containing a mispaired base. The MSH2-Holliday junction complexes were also more stable than MSH2-duplex DNA complexes. This observation suggests that MSH2 protein could directly coordinate the interaction between mismatch repair and genetic recombination observed in genetic studies.

Base Composition↗