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Biomedical subjects

M B Jacobs

Publications and source records attributed to M B Jacobs.

At least 19 recordsLinked to original sources

Antibody response to IR6, a conserved immunodominant region of the VlsE lipoprotein, wanes rapidly after antibiotic treatment of Borrelia burgdorferi infection in experimental animals and in humans.

Invariable region (IR)(6), an immunodominant conserved region of VlsE, the antigenic variation protein of Borrelia burgdorferi, is currently used for the serologic diagnosis of Lyme disease in humans and canines. A longitudinal assessment of anti-IR(6) antibody levels in B. burgdorferi-infected rhesus monkeys revealed that this level diminished sharply after antibiotic treatment (within 25 weeks). In contrast, antibody levels to P39 and to whole-cell antigen extracts of B. burgdorferi either remained unchanged or diminished less. A longitudinal analysis in dogs yielded similar results. In humans, the anti-IR(6) antibody titer diminished by a factor of > or =4 in successfully treated patients and by a factor of <4 in treatment-resistant patients. This result suggests that the quantification of anti-IR(6) antibody titer as a function of time should be investigated further as a test to assess response to Lyme disease therapy or to determine whether a B. burgdorferi infection has been eliminated.

Adult↗

Analysis of Borrelia burgdorferi vlsE gene expression and recombination in the tick vector.

Expression and recombination of the antigenic variation vlsE gene of the Lyme disease spirochete Borrelia burgdorferi were analyzed in the tick vector. To assess vlsE expression, Ixodes scapularis nymphs infected with the B. burgdorferi strain B31 were fed on mice for 48 or 96 h or to repletion and then crushed and acetone fixed either immediately thereafter (ticks collected at the two earlier time points) or 4 days after repletion. Unfed nymphs also were examined. At all of the time points investigated, spirochetes were able to bind a rabbit antibody raised against the conserved invariable region 6 of VlsE, as assessed by indirect immunofluorescence, but not preimmune serum from the same rabbit. This same antibody also bound to B31 spirochetes cultivated in vitro. Intensity of fluorescence appeared highest in cultured spirochetes, followed by spirochetes present in unfed ticks. Only a dim fluorescent signal was observed on spirochetes at the 48 and 96 h time points and at day 4 postrepletion. Expression of vlsE in vitro was affected by a rise in pH from 7.0 to 8.0 at 34 degrees C. Hence, vlsE expression appears to be sensitive to environmental cues of the type found in the B. burgdorferi natural history. To assess vlsE recombination, nymphs were capillary fed the B. burgdorferi B31 clonal isolate 5A3. Ticks thus infected were either left to rest for 4 weeks (Group I) or fed to repletion on a mouse (Group II). The contents of each tick from both groups were cultured and 10 B. burgdorferi clones from the spirochetal isolate of each tick were obtained. The vlsE cassettes from several of these clones were amplified by PCR and sequenced. Regardless of whether the isolate was derived from Group I or Group II ticks, no changes were observed in the vlsE sequence. In contrast, vlsE cassettes amplified from B. burgdorferi clones derived from a mouse that was infected with B31-5A3 capillary-fed nymphs showed considerable recombination. It follows that vlsE recombination does not occur in the tick vector.

Animals↗

C-terminal invariable domain of VlsE may not serve as target for protective immune response against Borrelia burgdorferi.

VlsE, the variable surface antigen of the Lyme disease spirochete, Borrelia burgdorferi, contains two invariable domains, at the amino and carboxyl termini, respectively, which collectively account for approximately one-half of the entire molecule's length and remain unchanged during antigenic variation. It is not known if these two invariable domains are exposed at the surface of either the antigen or the spirochete. If they are exposed at the spirochete's surface, they may elicit a protective immune response against B. burgdorferi and serve as vaccine candidates. In this study, a 51-mer synthetic peptide that reproduced the entire sequence of the C-terminal invariable domain of VlsE was conjugated to the carrier keyhole limpet hemocyanin and used to immunize mice. Generated mouse antibody was able to immunoprecipitate native VlsE extracted from cultured B. burgdorferi B31 spirochetes, indicating that the C-terminal invariable domain was exposed at the antigen's surface. However, this domain was inaccessible to antibody binding at the surface of cultured intact spirochetes, as demonstrated by both an immunofluorescence experiment and an in vitro killing assay. Mouse antibody to the C-terminal invariable domain was not able to confer protection against B. burgdorferi infection, indicating that this domain was unlikely exposed at the spirochete's surface in vivo. We concluded that the C-terminal invariable domain was exposed at the antigen's surface but not at the surface of either cultured or in vivo spirochetes and thus cannot elicit protection against B. burgdorferi infection.

Amino Acid Sequence↗

Integration of women's health into an internal medicine core curriculum for medical students.

The authors describe their year-long collaboration to analyze and integrate the elements of women's health into their medical school's core curriculum in internal medicine for the third-year clerkship. Such a process was necessary because the current curriculum was inadequate in its treatment of women's health (e.g., little or no coverage of issues pertaining to women in teaching about certain disorders; lack of female subjects in many research studies; study designs' using standards derived from manifestations of diseases in men; the cross-discipline aspects of women's health). The authors illustrate the new curriculum by discussing the revised module in pulmonary medicine; they detail the steps they took to uncover problems and omissions in the existing curriculum and in the literature on the topic, and how they remedied these. (For example, in a case involving a man with pulmonary embolus, one of the new questions for students is "What questions would you ask if this patient were a woman?") They comment on the challenges they faced in revising the curriculum, including lack of protected time, lack of sufficient data about women's health, inherent sex and gender bias in the literature and educational materials, need to make students aware of the importance of sex and gender considerations in patient care, and the ingrained bias of faculty, including the authors. Their process can be adapted and used to integrate curricula in other emerging interdisciplinary fields, such as cross-cultural medicine and gay and lesbian health. The authors conclude that collaboration between students and faculty, as illustrated in their own efforts, is one way to ensure that future practitioners are optimally trained to treat patients in the ever-changing field of medicine.

Attitude of Health Personnel↗

Weaving women's health across clinical clerkships.

Clerkship directors have an opportunity to develop consensus on learning objectives for women's health issues and to develop curricula that cross disciplinary boundaries. A collaborative interdisciplinary approach assures proper sequencing of knowledge and skill acquisition, conserves educational resources, and reflects the values of connectedness and patient-centeredness that are central to women's health. The informal networks and the institutional structures that bring clerkship directors together for discussion of a variety of educational issues promote such collaboration. The authors describe three approaches to designing and implementing women's health curricula and discuss how each might be applied to the topic of domestic violence: adding free-standing courses to existing curricula, often as electives; delegating pieces of the women's health curriculum to existing courses; and creating new interdisciplinary curricula that then are integrated into the general curriculum. Each has advantages and disadvantages. Ideally, models for curriculum design will reflect the collaborative patient-centered models upon which the field of women's health is based. Such models enhance program effectiveness by taking advantage of discipline-based expertise while allowing for the sharing of both educational responsibilities and educational resources.

Clinical Clerkship↗

Orbital tuberculoma masquerading as an orbital malignancy.

BACKGROUND: Orbital tuberculosis is exceedingly rare in areas where tuberculosis is non-endemic. A case of childhood orbital tuberculosis is reported, which the authors believe to be the first reported case of orbital tuberculosis in the Australasian region. METHODS/RESULTS: The patient a 6-year-old boy presented with proptosis and was initially mistaken to have an orbital malignancy. Treatment with antituberculous drugs resulted in resolution of the condition. CONCLUSION: This case served as a timely reminder of the need to keep awareness of the extrapulmonary manifestations of tuberculosis alive even in developed countries. A high index of suspicion for this eminently treatable disease in the appropriate clinical situation is particularly important when migrant communities from high-prevalence areas are involved.

Antitubercular Agents↗

Quartz crystal microbalance detection of Vibrio cholerae O139 serotype.

A piezoelectric (PZ) quartz crystal microbalance (QCM) biosensor for the rapid detection of Vibrio cholerae serotype O139 has been developed. The antibody to this serotype was immobilized on the gold transducer surface of a 10 MHz AT cut PZ crystal. Solutions containing known antigen concentrations were then incubated for 1 h on the antibody-bound transducer. The biosensor was able to detect 10(5) cells per ml of O139 versus a background of O1 (Ogawa) serotype.

Antigen-Antibody Reactions↗

Enhancing the training of internal medicine residents at Stanford by establishing a model group practice and raising its clinical educators' status.

The education of residents is shifting to the ambulatory care setting. In addition, there is a growing trend toward managed care and increasing competition for patients to be served by "real-world" practices. The authors describe the formation and operation of a program that was established in 1981 at the Stanford University School of Medicine to respond to these changes: the Stanford Medical Group (SMG), a model group practice in internal medicine that operates within the academic medical center. Because raising the status of the clinician-educator faculty was a critical issue for the SMG, the authors also describe the Medical Center Professoriate, a separate faculty track created in 1989 to recognize and reward Stanford's clinician-educators. The authors conclude that the SMG has succeeded in its training and patient care goals and has weathered the great changes in the health care environment that have taken place since 1981. They also report that the separate faculty track is serving its purpose well. They hope that educators and program directors at other academic medical centers may find the descriptions of the SMG and the professoriate useful in solving similar problems.

California↗

Gynecomastia. A bothersome but readily treatable problem.

Although breast enlargement in boys and men can cause both psychological and physical distress, the disorder is rarely serious and is readily treatable. Several factors can lead to the estrogenic excess that causes growth of breast tissue. Dr Jacobs describes a patient with gynecomastia related to cirrhosis of the liver who responded promptly to a brief course of tamoxifen citrate therapy.

Adult↗