Biomedical subjects
B Stone
Publications and source records attributed to B Stone.
Wanted: hot industry seeks supergeeks.
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MAGE-F1, a novel ubiquitously expressed member of the MAGE superfamily.
Most known members of the MAGE superfamily are expressed in tumors, testis and fetal tissues, which has been described as a cancer/testis or "CT" expression pattern. We have identified a novel member of this superfamily, MAGE-F1, which is expressed in all adult and fetal tissues tested. In addition to normal tissues, MAGE-F1 is expressed in many tumor types including ovarian, breast, cervical, melanoma and leukemia. MAGE-F1 is encoded on chromosome 3, identifying a sixth chromosomal location for a MAGE superfamily gene. The coding region of MAGE-F1 is contained within a single exon and includes a microsatellite repeat. Sequence analysis and expression profiles define a new class of ubiquitously expressed MAGE superfamily genes that includes MAGE-F1, MAGE-D1, MAGE-D2/JCL-1 and NDN. The finding that several MAGE genes are ubiquitously expressed suggests a role for MAGE encoded proteins in normal cell physiology. Furthermore, potential cross-reactivity to these ubiquitously expressed MAGE gene products should be considered in the design of MAGE-targeted immunotherapies for cancer.
Three thenar motor branches of the median nerve.
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The effect of changes in laboratory practices on the rate of false-positive cultures for Mycobacterium tuberculosis.
CONTEXT: False-positive cultures for Mycobacterium tuberculosis have been found in nearly all DNA fingerprinting studies, but the effectiveness of interventions to reduce cross-contamination has not been evaluated. OBJECTIVE: To evaluate whether changes in laboratory policies and procedures reduced the rate of false-positive cultures. DESIGN: Retrospective study of isolates with matching DNA fingerprints. SETTING: A mycobacteriology laboratory serving an urban tuberculosis control program and public hospital system. PATIENTS: All M tuberculosis isolates processed from July 1994 to December 1999. METHODS: Isolates were fingerprinted using IS6110; pTBN12 was used to fingerprint isolates having fewer than 6 copies of IS6110. We further evaluated all patients having only one positive culture whose DNA fingerprint matched that of another isolate processed in the laboratory within 42 days. INTERVENTIONS: We changed laboratory policy to reduce the number of smear-positive specimens processed and changed laboratory procedures to minimize the risk of cross-contamination during batch processing. MAIN OUTCOME MEASURE: The rate of false-positive cultures. RESULTS: Of 13 940 specimens processed during the study period, 630 (4.5%) from 184 patients and 48 laboratory proficiency specimens grew M tuberculosis. There were no cases (0/184) of probable or definite cross-contamination, compared with the 4% rate (8/199) identified in our previous study (P =.008). We also fingerprinted a convenience sample of isolates from other laboratories in Denver; 13.6% (3/22) of these were false-positive, a rate similar to the 11.9% rate (5/42) identified for other laboratories in our previous study (P =.84). CONCLUSIONS: Laboratory cross-contamination decreased significantly after relatively simple, inexpensive changes in laboratory policies and practices. Cross-contamination continued to occur in other laboratories in Denver.
How time and circumstance changed disease management. Interview by Patrick Mullen.
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Phase variation of the gonococcal siderophore receptor FetA.
FetA, the recently characterized gonococcal ferric enterobactin receptor, exhibited extremely rapid phase variation between high- and low-expression levels. The frequency of phase variation was approximately 1.3% in both directions in gonococcal strain FA1090. FetA expression in the 'high phase' was significantly greater than the level of expression in the 'low phase'. Expression levels correlated with the number of cytosine residues in a string of cytosines located close to the transcriptional start site for fetA between the putative -10 and -35 consensus sequences. Antibody production against FetA commonly occurs in infected patients, and we therefore hypothesize that phase variation reflects a balance between the advantages of being able to use a ferric siderophore as an iron source and evasion of the host immune response.
Randomized trial of case-finding for depression in elderly primary care patients.
OBJECTIVE: To determine the effect of case-finding for depression on frequency of depression diagnoses, prescriptions for antidepressant medications, prevalence of depression, and health care utilization during 2 years of follow-up in elderly primary care patients. DESIGN: Randomized controlled trial. SETTING: Thirteen primary care medical clinics at the Kaiser Permanente Medical Center, an HMO in Oakland, Calif, were randomly assigned to intervention conditions (7 clinics) or control conditions (6 clinics). PARTICIPANTS: A total of 2,346 patients aged 65 years or older who were attending appointments at these clinics and completed the 15-item Geriatric Depression Scale (GDS). GDS scores of 6 or more were considered suggestive of depression. INTERVENTIONS: Primary care physicians in the intervention clinics were notified of their patients' GDS scores. We suggested that participants with severe depressive symptoms (GDS score >/= 11) be referred to the Psychiatry Department and participants with mild to moderate depressive symptoms (GDS score of 6 -10) be evaluated and treated by the primary care physician. Intervention group participants with GDS scores suggestive of depression were also offered a series of organized educational group sessions on coping with depression led by a psychiatric nurse. Primary care physicians in the control clinics were not notified of their patients' GDS scores or advised of the availability of the patient education program (usual care). Participants were followed for 2 years. MEASUREMENTS AND MAIN RESULTS: Physician diagnosis of depression, prescriptions for antidepressant medications, prevalence of depression as measured by the GDS at 2-year follow-up, and health care utilization were determined. A total of 331 participants (14%) had GDS scores suggestive of depression (GDS >/= 6) at baseline, including 162 in the intervention group and 169 in the control group. During the 2-year follow-up period, 56 (35%) of the intervention participants and 58 (34%) of the control participants received a physician diagnosis of depression (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.6 to 1.6; P =.96). Prescriptions for antidepressants were received by 59 (36%) of the intervention participants and 72 (43%) of the control participants (OR, 0.8; 95% CI, 0.5 to 1.2; P =.3). Two-year follow-up GDS scores were available for 206 participants (69% of survivors): at that time, 41 (42%) of the 97 intervention participants and 54 (50%) of the 109 control participants had GDS scores suggestive of depression (OR, 0.7; 95% CI, 0.4 to 1.3; P =.3). Comparing participants in the intervention and control groups, there were no significant differences in mean GDS change scores (-2.4 +/- SD 3.7 vs -2.1 SD +/- 3.6; P =.5) at the 2-year follow-up, nor were there significant differences in mean number of clinic visits (1.8 +/- SD 3.1 vs 1.6 +/- SD 2.8; P =.5) or mean number of hospitalizations (1.1 +/- SD 1.6 vs 1.0 +/- SD 1.4; P =.8) during the 2-year period. In participants with initial GDS scores > 11, there was a mean change in GDS score of -5.6 +/- SD 3.9 for intervention participants (n = 13) and -3.4 +/- SD 4.5 for control participants (n = 21). Adjusting for differences in baseline characteristics between groups did not affect results. CONCLUSIONS: We were unable to demonstrate any benefit from case-finding for depression during 2 years of follow-up in elderly primary care patients. Studies are needed to determine whether case-finding combined with more intensive patient education and follow-up will improve outcomes of primary care patients with depression.
Complex effects of melatonin: evidence for photoperiodic responses in humans?
The primary function of melatonin in mammals is to convey information about the changing length of the night in the course of the year. This information is used by photoperiodic species to ensure the correct timing of seasonally variable functions such as reproduction, coat growth, and probably the duration and organization of sleep. Melatonin appears not to be essential for circadian organization but reinforces functions associated with darkness. In diurnal humans this of course includes sleep and lowered body temperature. It may act as an adjunct to light for the maintenance of synchrony with the solar day. Exogenous melatonin can both advance and delay the timing of sleep and other circadian functions and appears to stabilize sleep to a 24 h period taken daily at an appropriate time in free running conditions. However, there is as yet little evidence that it can consistently synchronize free running strongly endogenous variables such as core temperature. Its effects on sleep in free run are complex, depend on circadian time of administration, and can in part be interpreted on a photoperiodic basis.
Non-injection substance use correlates with risky sex among men having sex with men: data from HIVNET.
Associations between substance use and sexual behavior were examined among 3220 seronegative men who have sex with men (MSM) in a HIV vaccine preparedness study. Relationships between current and past substance use and current sexual risk were evaluated using crude odds ratios and logistic regression to adjust for confounding variables. Heroin and injection drug use were uncommon (< 2%). Substances most often used were alcohol (89%), marijuana (49%), nitrite inhalants (29%), amphetamines or similarly acting stimulants (21%), cocaine 14% and hallucinogens (14%). Increased adjusted odds for unprotected sex were significantly associated with current heavy alcohol use (OR 1.66; CI 1.18, 2.33), past alcohol problems (OR 1.25; CI 1.05, 1.48), and current drug use (OR 1.26; CI 1.08, 1.48). When associations with specific drugs and nitrite inhalants were examined separately, current use of cocaine and other stimulants (OR 1.25; CI 1.01, 1.55), hallucinogens (OR 1.40; CI 1.10, 1.77), and nitrite inhalants (some (OR 1.61; CI 1.35, 1.92); heavy (OR 2.18; CI 1.48, 3.20)), were independently associated with unprotected sex. Those with past drug use or past heavy alcohol use but not currently using demonstrated no increase in sexual risk, suggesting an important role for substance-focused interventions in risk reduction efforts among MSM.
The influence of having an assigned Medicaid primary care physician on utilization of otitis media-related services.
OBJECTIVE: This study documents the influence of having an assigned Medicaid primary care physician (PCP) on the utilization of otitis media-related services. DESIGN/METHODS: This is a retrospective study using the 1991 Colorado Medicaid administrative database that followed 28 844 children <13 years who had at least 1 visit for otitis media. RESULTS: Children continuously enrolled in Medicaid throughout the entire year were >4 times (odds ratio: 4.2 and 4.89, respectively) as likely to always or sometimes have a PCP compared with children who were discontinuously enrolled. The likelihood of ever using the emergency department for an otitis media-related visit was increased by 26% and 50%, respectively, when a child sometimes or never had a PCP compared with always having a PCP. The likelihood of ever filling an antibiotic for otitis media was reduced by 23% and 34%, respectively, when a child sometimes or never had a PCP compared with always having a PCP. The likelihood of ever having otitis media-related surgery was not affected by PCP status, but young children, 13 to 18 months of age, had higher referral rates when they had an assigned PCP. CONCLUSIONS: These findings suggest that having an assigned Medicaid PCP influences the utilization patterns of some otitis media-related medical services.
Expeditious synthesis of a new hexasaccharide using transglycosylation reaction catalyzed by Bacillus (1-->3),(1-->4)-Beta-D-glucan 4-glucanohydrolase.
Enzymatic hydrolysis of barley (1-->3),(1-->4)-beta-D-glucan using a recombinant (1-->3),(1-->4)-beta-glucanase from Bacillus licheniformis gives Glc beta 4Glc beta 3Glc isolated after acetylation in 49% yield. Conventional treatment produced the corresponding beta-fluoride which was carefully de-O-acetylated. A transglycosylation reaction with this substrate, catalyzed by the title enzyme, gave Glc beta 4Glc beta 3Glc beta 4Glc beta 4Glc beta 3Glc in 20% yield.
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Closure of an asylum: the Friern study of older people.
This article reports a naturalistic study following the closure of Friern Hospital and the movement of elderly long-stay patients, who in the main suffered from severe dementia, to psychiatric nursing homes and hospital beds. It describes changes in the environments and in the patients' cognition, behaviour and use of medical services. The results suggest that psychiatric nursing homes seem able to care for the majority if patients with severe dementia. Future studies should consider whether long-stay hospital beds may, however, be necessary for those with both psychiatric and physical health needs, where increased contact with health service personnel is essential. Prospective examination of the reasons for breakdown of placements in nursing homes and the differences between those placed in various settings may help future planning of services. Relatives' opinions of the long-stay settings also require study.
Expression of the CopB outer membrane protein by Moraxella catarrhalis is regulated by iron and affects iron acquisition from transferrin and lactoferrin.
The amino acid sequence of the cell-surface-exposed, 81-kDa CopB outer membrane protein of Moraxella catarrhalis was found to be similar to those of TonB-dependent outer membrane proteins of other gram-negative bacteria. Expression of CopB was affected by the availability of iron in the growth medium, and the extent of overexpression of CopB in response to iron limitation varied widely among the M. catarrhalis strains tested. Wild-type M. catarrhalis strains were found to be able to utilize ferric citrate, transferrin, lactoferrin, and heme as sources of iron for growth in vitro. However, an isogenic copB mutant was severely impaired in its ability to utilize transferrin and lactoferrin as sole sources of iron for growth, whereas this same mutant grew similarly to the wild-type parent strain when supplied with ferric citrate as the iron source. The copB mutant was not significantly different from its wild-type parent strain in its ability to bind transferrin and lactoferrin. In addition, the wild-type parent strain and the copB mutant exhibited equivalent rates of uptake of 55Fe from ferric citrate. However, the copB mutant was markedly less able than the wild-type strain to take up 55Fe from transferrin and lactoferrin. These results indicate that lack of expression of the CopB protein exerts a direct or indirect effect on the ability of M. catarrhalis to utilize iron bound to certain carrier proteins.
Home alone: is it a risk factor for middle school youth and drug use?
This study examined the relationship between middle school/junior high student latchkey status and early experimentation and use of alcohol, tobacco, and other drugs. Students were queried about the frequency (number of times per week) and quantity (number of hours per day) of unsupervised after school days in an average week. Questions were also asked regarding their experiences with "gateway" drugs, inhalants, and steroids. Chi square analysis was used to test the strength of association. The results of this study indicated that latchkey youth (LKY) who were home alone two or more days per week were four times more likely to have gotten drunk in the past month than those youth who had parental supervision five or more times a week. Also, significant differences were observed for LKY with respect to cigarette smoking, inhalants, and marijuana use. Other findings and demographic variables were discussed as they pertain to LKY as well as suggested strategies for healthy self-care alternatives.
Factors related to early pregnancy recognition in the woman.
PURPOSE: While the precise timing of the maternal recognition of pregnancy is not known, it is known that the prevention of return to ovarian cyclicity relies on a conceptus-derived signal. METHODS: In an attempt to identify the first luteotropic signals detectable in the maternal circulation, a sensitive Leydig cell luteotropin bioassay was employed, and data were compared for nine clinically pregnant and nine nonpregnant patients in an in vitro fertilization program. Blood samples were drawn every other day for 10 days after embryo transfer (ET). RESULTS: The first detectable rise in bioactive luteotropin levels occurred between 6 and 8 days post ET. Serum E2 levels increased on the same days. Differences in luteotropin levels between pregnant and nonpregnant patients were significant between days 6 and 8 (P < 0.0001) and between days 8 and 10 (P < 0.002). CONCLUSIONS: Based on morphological studies reported by others, bioactive luteotropic signals identified in this study were detectable in the maternal circulation at about the time of trophoblast lacunae coalescing with maternal uterine blood vessels.
Menstrual cycle and social behavior in vervet monkeys.
We assessed the relationship between social behavior and the menstrual cycle in 11 adult female vervet monkeys (Cercopithecus aethiops sabaeus) living in an established, stable social group. The findings indicated that fluctuations in ovarian steroids are accompanied by behavioral changes in vervet monkeys. A significant increase in aggressive action, avoidance of social overtures, and retreats from threat occurred during the late luteal phase. However, the social environment can greatly affect behavior independent of the phase of the menstrual cycle. The 10 nondominant (or subordinate) individuals not only exhibited behavioral changes across their own menstrual cycles, but also were responsive to the dominant female's cycle. During the dominant female's late luteal phase, subordinate females significantly increased aggression and decreased social activity. Some of behavioral patterns in female vervet monkeys are therefore relatively independent of direct hormonal modulation and support the contention of the dominant female as the driving force for behavioral changes related to aggression and social interaction. The differential effect of hormones and social status and other environmental factors on behavior has not been critically evaluated in human studies of the premenstrual syndrome. The present study suggests that it is important to assess which behavioral patterns in women are hormonally mediated and which are dependent on the environment.