Biomedical subjects
Publications and source records attributed to R M Bernstein.
A 48-yr-old female on immunosuppressive therapy for fibrosing alveolitis and polymyositis developed a septic arthritis of the left middle finger proximal interphalangeal joint, tenosynovitis of the left palm and osteomyelitis of the right hindfoot due to infection with Mycobacterium marinum. Such widespread and severe bone and joint involvement has not been described previously with this organism.
BACKGROUND: Follicular transplantation is a method of hair restoration surgery that uses hair in its naturally occurring groups, called follicular units. Using the follicular unit exclusively in the transplant, the surgeon can create hair patterns that closely mimic nature. OBJECTIVE: To focus on various aesthetic aspects of the follicular transplantation procedure including hair distribution, hairline design, and crown restoration. Racial variations that affect the transplant will also be examined. METHODS: Follicular transplantation is performed according to techniques detailed in a previous publication (Bernstein et al. Int J Aesthet Rest Surg 1995; 3: 119-32). RESULTS: Excellent cosmetic results can be achieved when aesthetic decisions are made that allow the surgeon to recreate hair patterns already provided by nature. A case study will be presented. CONCLUSIONS: The small size of follicular implants enables the surgeon great versatility in their placement. Follicular transplantation will ensure a natural looking transplant if used with good aesthetic judgment and careful planning.
We have measured the urinary excretion of total protein, albumin and retinol binding protein (RBP) in random urine specimens obtained from 40 female patients with systemic lupus erythematosus (SLE). Thirty-three of these patients had no clinical evidence of any renal impairment (non-renal SLE); seven had overt renal disease (renal SLE). RBP:creatinine ratios were significantly higher in non-renal SLE patients compared with female controls (P = 0.002). There was no significant difference between urine total protein concentrations, albumin:creatinine or total protein:creatinine ratios in non-renal SLE patients when compared with controls, despite approximately 20% of these patients having elevated excretion of total protein or albumin. All seven renal SLE patients had elevated albumin:creatinine ratios but only four of them had an increased RBP:creatinine ratio. Of 29 non-renal SLE patients who had urinary total protein concentrations below 0.2 g/L, (i.e. approximating to a negative protein dipstick), 14 had increases in either albumin or RBP:creatinine ratios. Only two patients had increases in both. In the absence of clinical evidence of renal disease, increases in urinary albumin or RBP excretion could indicate subclinical nephropathy and measurements may have a role in the early diagnosis and subsequent monitoring of renal disease in SLE.
BACKGROUND: Follicular transplantation is a method of hair restoration surgery that uses hair in its naturally occurring groups called follicular units. By using the follicular unit exclusively in the transplant, the surgeon can move extensive quantities of implants in a single session to complete the hair restoration in as few sessions as possible. OBJECTIVE: To briefly review the salient features of follicular transplantation, to discuss how the patient should be evaluated for the follicular transplant procedure, and to provide guidelines for the planning of the first and subsequent transplant sessions. This paper will examine: 1) ways to anticipate future hair loss, 2) how to assess donor reserves, 3) what can be accomplished in a single transplant session, 4) how to plan for subsequent sessions, and 5) how to manage the patient with diffuse androgenetic alopecia. METHODS: Follicular transplantation is performed according to techniques detailed in a previous publication (Bernstein et al. Int J Aesthet Rest Surg 1995;3:119-32). RESULTS: Excellent cosmetic results can be achieved when there is meticulous attention to transplanting intact follicular units, when the extent of balding is accurately assessed, and when the finite nature of the donor supply is respected. CONCLUSIONS: Because of their small "physiologic" size, follicular implants enable the surgeon to transplant large numbers in a single session. Follicular transplantation will greatly increase the benefits of the hair restoration procedure when the patient is thoroughly evaluated and when the procedure is undertaken after careful short- and long-term planning.
The rearrangement of antibody and T-cell receptor gene segments is indispensable to the vertebrate immune response. All extant jawed vertebrates can rearrange these gene segments. This ability is conferred by the recombination activating genes I and II (RAG I and RAG II). To elucidate their origin and function, the cDNA encoding RAG I from a member of the most ancient class of extant gnathostomes, the Carcharhine sharks, was characterized. Homology domains identified within shark RAG I prompted sequence comparison analyses that suggested similarity of the RAG I and II genes, respectively, to the integrase family genes and integration host factor genes of the bacterial site-specific recombination system. Thus, the apparent explosive evolution (or "big bang") of the ancestral immune system may have been initiated by a transfer of microbial site-specific recombinases.
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Abstract Interferon gamma (IFNgamma) is an important cytokine with immunomodulatory properties that include activation of immune cells and induction of class I and class II major histocompatibility complex antigens. In this study a retroviral vector was used to introduce the IFNgamma gene into EMT6 tumor cells to assess the effect of IFNgamma gene expression on tumor immunogenicity. Transfectants were selected in G418-containing tissue-culture medium and were determined to express the inserted IFNgamma gene by reverse transcriptase/polymerase chain reaction. Flow-cytometric analysis revealed that parental unmodified EMT6 cells constitutively expressed only class I MHC and were poorly responsive to exogenous IFNgamma stimulation, whereas class II MHC was induced in IFNgamma-transfected cells. The induction of class II MHC in IFNgamma-transfected cells correlated with the expression of a mouse class II transactivator gene that was dormant in unmodified or mock-transfected cells. In addition, IFNgamma-gene-transfected tumor cells were found to secrete up to 17 ng IFN (equivalent to 75 units/10(6) cells) by enzyme-linked immunosorbent assay (ELISA). Whereas parental EMT6 cells grew unchecked, the growth of genetically modified tumor cells was significantly inhibited in immunocompetent mice. Rechallenge of animals that rejected an IFNgamma-transfected EMT6 clone (EMT6-B17) with parental EMT6 cells resulted in tumor rejection, suggesting that IFNgamma-transfected EMT6 cells were able to induce long-term immunity. Mixing experiments using gene-transfected and unmodified tumor cells demonstrated that 10% of IFNgamma-transfected cells in the population was sufficient to protect mice against subsequent challenge with tumorigenic EMT6 cells. These studies demonstrate that the immunogenicity of tumor cells that are poorly responsive to exogenous IFNgamma can be enhanced by inserting and expressing the IFNgamma transgene. These findings also suggest a role for class II MHC in reducing tumorigenicity of the EMT6 tumor and inducing long-term tumor immunity.
We determined the sequence of 18 DNA clones encoding VH regions of sandbar shark and bull shark. All of these sequences exhibit key structural coding features characteristic of known VH genes of higher vertebrates. These VH sequences disclosed considerable diversity, and can be divided into six families according to the criterion of 80% DNA sequence identity. The overlapping of some VH gene clones to two or more families is a particular feature found in carcharhine sharks, which suggests that VH diversification is a continuing process. The basic sequence patterns of heavy-chain V regions found in all representative gnathanstomes and in VH of the shark heavy immunoglobulin IgW provides evidence for selection of canonical residues in all VH structures. Elasmobranch VH sequences can be divided into two classes or clans, one comprising the 'classical' VH set and the other comprising VHS related to those of IgW (V omega). Phylogenetic analyses place the VH cluster as the root of all the classic VHS and indicates that the V omega set is most probably that of the primordial heavy chain.
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With the development of recombinant DNA technology, it has become feasible to clone, construct, and express fully human immunoglobulin molecules. Here we report a novel methodology to make human antitumor single-chain Fv (scFv) antibodies from tumor-infiltrating B lymphocytes. We isolated and expanded tumor-infiltrating B lymphocytes from melanomas in the presence of Epstein-Barr virus. The transformed B cells secreting tumor-specific antibodies were identified and cloned by limiting dilution. From one B cell clone with specific melanoma reactivity, we captured the immunoglobulin variable region genes VH and Vk by PCR, sequenced the genes, and linked them together by PCR assembly with the use of a (Gly4Ser)3 linker. The scFv gene was then cloned into the pET21d vector and expressed. The obtained scFv protein with a M(r), of 29,000 was purified and biotinylated for further characterization. The scFv demonstrated specific tumor reactivity to 21 of 24 different melanoma cell lines and not to 14 nonmelanoma tumor cell lines, such as breast, ovarian, and colon cancer cells lines; normal human melanocytes as well as normal human leukocytes. These results were obtained in (a) a tumor cell ELISA, (b) fixed cell immunofluorescence, and (c) live cell flow cytometry. The immunoprecipitation results indicated that a protein antigen of M(r) 45,000 was recognized by the scFv. Since we reported previously that about 70% of human tumors of different histological types contain tumor-infiltrating B lymphocytes producing specific antitumor antibodies, this approach offers a rapid, effective method by combining in vitro B-cell expansion and PCR gene cloning to elucidate the repertoire of the human antitumor immune response and to make human monoclonal antitumor antibody molecules.
Recently it has been observed that administration of intravenous immunoglobulin (IVIG) can have profound effects on a wide variety of diseases related to the dysregulation of the immune system. The mechanisms which explain these activities are poorly understood. Human IVIG and various Cohn plasma fractions contain autoantibodies directed against T cell receptors (Tcr). Previous studies have shown that IVIG contains autoantibodies against T cell receptor peptides. In order to further our understanding of autoantibody specificities, a single chain Tcr (scTcr) was constructed by recombinant DNA techniques from the variable alpha and variable beta chains of the Jurkat cell line. Anti-Tcr autoantibodies were isolated from IVIG and Cohn fractions I + III using a scTcr affinity column. This scTcr affinity purified material reacted with the surfaces of T cells at 10 micrograms/ml whereas non-purified IVIG did not. Sera from patients with rheumatoid arthritis (RA) as well as serum from patients with systemic lupus erythematosus (SLE) reacted with the scTcr at levels above that of normals.
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Spontaneous rupture of the tibialis anterior tendon is an uncommon occurrence that most often affects men in their fifth to seventh decades. These ruptures occur through abnormal tendons, but may cause little disability. Early repair does seem to improve the likelihood of a good result, however. The following is a case report, and the English literature is reviewed.
A cDNA fragment corresponding to a highly evolutionarily conserved region of the major anion transport protein band 3 was cloned from lamprey mRNA using PCR homology probing. This is the first report providing evidence for a band-3 like transporter in the lowest vertebrates, the agnathostomes. Semi-quantitative PCR showed expression similar to that of higher vertebrates. Lamprey serum contains antibody-like molecules that bind to synthetic peptides of band 3 comprising senescent cell antigen, an aging antigen that terminates the life of cells. The high degree of homology found in nucleic acid and derived proteins sequence and the reaction of "antibodies" in lamprey serum with senescent cell antigen peptides of band 3 suggests that lamprey band 3 plays a role comparable to that in higher vertebrates.
This randomized, controlled trial tests the efficacy of a computerized prompting system for test ordering. The system, makes use of the sensitivity, specificity, positive and negative predictive values of tests. It was tested using clinical vignettes in an academic family medicine center with first and second year residents. We found that there was a 38% decrease in the numbers of tests ordered (p < .01) and a 12% decrease in the costs of tests ordered by using the prompting system. We suggest that when used at the point of the patient encounter, this system has the potential for promoting more appropriate test ordering and for saving considerable health care dollars.
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Caffey's disease is a cortical hyperostosis, which presents during infancy. Etiology remains unclear. Familial occurrence has been documented in the literature. Reported here is infantile cortical hyperostosis that occurred in a father and his two daughters. The familial occurrence would suggest a genetic basis for Caffey's disease; however, it remains consistent with infection by an agent with a long latency period as has been strongly suggested in Paget's disease.