Light (L) chain dimers expressed by multiple myeloma cells and collected as Bence-Jones proteins from the urine of human subjects were tested for their ability to form deposits in fibroblast monolayer cell cultures. Bence-Jones proteins from subjects with primary amyloidosis associated with L chains were shown to form fibrillar deposits by the in vitro assay introduced in this report. Filaments interspersed with nascent collagen could be detected after only 48 h. Deposition of L chains continued over a period of 72 h culminating in the appearance of dense fibrils with widths of 80-100 A and a variety of lengths. Formation of amyloid-like fibrils was accompanied by interference with the maturation of the collagen produced by the fibroblast cells. Fibrils composed of the Mcg lambda-type L chain were deposited between collagen fibers, thus expanding them laterally and leading to their partial disintegration. Mature collagen was completely missing from fibroblast monolayers exposed to the Sea lambda chain and the Jen kappa chain. Collagen with the characteristic striped pattern matured normally in control samples, such as those not dosed with amyloid precursors or those treated with a non-amyloidogenic Bence-Jones protein (e.g., the Hud lambda chain dimer). By immunochemical techniques using fluorescein- and gold-labeled anti-L chain antibodies, amyloidogenic L chains were shown to decorate the strands of nascent collagen. This observation suggests that amyloidogenic L chains are concentrated in the extracellular matrix by monovalent antigen-antibody type reactions. The capacity of the Mcg L chain dimer to bind collagen-derived sequences was tested by soaking crystals with a collagenase substrate, PZ-Pro-Leu-Gly-Pro-D-Arg. Difference Fourier analysis at 2.7 A resolution indicated that the PZ-peptide is a site-filling ligand. It could not be removed from the active site by perfusion of the crystal with ammonium sulfate crystallizing media. Similar experiments with the collagen-derived peptide (Pro-Pro-Gly)(5) showed substantial hysteresis effects extending from one end of the Mcg dimer to the other. After the ligand was withdrawn, the active site of the Mcg dimer could no longer bind the PZ-peptide. However, if the active site was first blocked by the PZ-peptide and subsequently exposed to the (Pro-Pro-Gly)(5) peptide, the difference Fourier map was indistinguishable from that obtained with the PZ-peptide alone. We concluded that amyloidogenic L chains such as the Mcg dimer could be concentrated in the perivascular space by binding to normal tissue constituents. These components include nascent collagen, which can be deterred from maturing as a result of this binding. Participation in such pathological activity is also self-destructive to the amyloidogenic L chains, which lose their binding capabilities for collagen-derived peptides and also become susceptible to irreversible conversion to amyloid fibrils. All of these events may be prevented by prior treatment of the amyloidogenic L chains with site-filling ligands. (c) 2000 John Wiley & Sons, Ltd.

Amyloid↗

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Are rhinoplasty patients potentially mad?

Rhinoplasty patients have long been considered to be psychologically unstable and therefore a "risky" group upon which to operate. Patients who had rhinoplastic operations more than 5 years ago were contacted by post and their psychological health assessed by the use of psychometric tests. The results show no evidence to support earlier suggestions that requests for rhinoplasty may be early symptoms of severe psychiatric disease. However, several points do emerge. Male patients show more symptoms of anxiety and depression than normal, and female patients who give no history of injury preceding their operation behave in a more extrovert and sociable manner than normal. Furthermore, patients of both sexes who give no history of injury before their operation, even though pleased with the operative results, are more self-conscious of their appearance than those who were injured prior to their rhinoplasty.

Adolescent↗

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Baylisascaris procyonis larva migrans in a puppy: a case report and update for the veterinarian.

Baylisascaris larva migrans (LM) has been recognized as a cause of central nervous system (CNS) disease in puppies. A presumptive antemortem diagnosis is based on a history of raccoon exposure, clinical signs, cerebrospinal fluid eosinophilic pleocytosis, and peripheral blood eosinophilia. Early diagnosis is critical for treatment or prevention of disease in other dogs, animals, or humans exposed to the suspected contaminated area. In the present case, an antemortem diagnosis was not made, emphasizing the importance of postmortem examination in cases of CNS disease in puppies.

Animals↗

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A survey of obstetric malpractice in western frontier areas.

A mail survey of 524 physicians in the frontier areas of Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming, and the rural areas of Utah was conducted; 286 valid responses were collected (54.6%). Of the respondents, 97% had at some time practiced obstetrics, and, of those now practicing obstetrics, 39% reported they would discontinue providing obstetrical care within the next year. Of those stopping, 95% indicated that malpractice was a major factor in their decision. Of the respondents, 74% indicated that access to obstetric services would be a problem in their areas if they discontinued this type of care.

Humans↗

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Implications of pregnancy for residents and their training programs.

This study investigated the implications of pregnancy on residents and their training programs and how programs have planned for pregnancy disruptions compared to other employers. We received questionnaires from 236 male and female residents and their families who had experienced at least one pregnancy during their training. Results for female residents were compared with working spouses of male residents. Approximately half of the female residents reported that their programs had formal leave policies compared to 70% of the working spouses. The average amount of leave taken by residents was considerably less than that taken by the spouse group. For both groups, 35% of all pregnancies were unplanned; 19% of these without benefit of birth control. Approximately 30% of both groups said they should have timed their pregnancies differently. Female residents were more likely to perceive their pregnancies as a stressful time. Despite this greater stress, female residents were equally as unlikely as spouses of male residents to miss work for pregnancy-related causes. This study supports the need for better planning for pregnancy during residency training.

Adult↗

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Using microcomputers in rural preceptorships.

Current U.S. health manpower forecasts indicate an oversupply of physicians. In the Intermountain Region this oversupply is concentrated in the medical and surgical subspecialties, not in primary care specialties. Students cite fear of not knowing all that a general field requires as a reason for focusing their studies in a narrow area. Because ambulatory care experiences are not required of medical students at Utah, it is difficult to recruit students into the primary care specialties. One means of exposing students to primary care and rural medicine is through the clinical preceptorship. Beginning in 1985, with a grant from the National Library of Medicine, clinical students who elected the rural family practice preceptorship were given lap-top microcomputers to take with them to their preceptorship sites. Students were taught how to operate the computer and how to perform a MEDLINE search. Student evaluations of the experience were high and students reported feeling less concerned about the knowledge explosion and positive about improving their ability to access current medical literature. It is anticipated that by teaching students how to use this technology to provide better patient care, they will be more likely to consider primary care practices in rural areas.

Family Practice↗

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Characteristics of medical school applicants: implications for rural health care.

Physicians seem to prefer to practice in communities where there is already an adequate number of physicians, rather than in underserved rural areas. Virtually all studies examining this problem base their data on subjects who are already within or beyond the medical education process. Thus, such studies may obscure the degree to which practice site preferences are a result of the medical education selection process, or to what degree they were present in the premedical student population. Medical school applicants were surveyed about their intended practice site choices, as well as a number of characteristics thought to be correlated with intended practice sites. Eleven characteristics were found to be associated with intended practice sites. A disproportionately large number of applicants intended to practice in mid-size communities, a disproportionately low number of applicants in rural areas. There was no statistically significant difference in the acceptance rates of applicants who planned to practice in rural areas and those who did not.

Adult↗

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Personality types of family practice residents as measured by the Myers-Briggs type indicator.

This study was initiated to test the hypothesis that individuals currently choosing family practice as a career are likely to have different personality types than those who previously pursued general practice. Incoming residents to the University of Utah Family Practice Residency Program were compared to a group of private primary care physicians serving rural areas. Personality types were determined by administering the Myers-Briggs Type Indicator to both groups. Results showed that the current resident group differed significantly from the primary care physician group and that the residents' personality types were similar to personality types of faculty in other studies. This raises the concern that many family practice residents may not choose to practice in underserved areas. Further studies need to follow personality types through medical school and residency training and into practice to help determine which prospective physicians are likely to choose a primary care career and a rural practice. This information may be useful in health manpower planning and in examining admissions policies of medical schools and residencies.

Family Practice↗

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Recent discoveries regarding swine dysentery.

Explore the source record for details and available documents.

Animals↗