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Biomedical subjects

D A Bell

Publications and source records attributed to D A Bell.

At least 181 records · Page 10Linked to original sources

The antiphospholipid syndrome: prevalence among patients with stroke and transient ischemic attacks.

PURPOSE: The prevalence of the antiphospholipid syndrome was determined prospectively in patients presenting with stroke and transient ischemic attacks. An attempt was made to define a subset of stroke patients at risk for this syndrome on the basis of their clinical features. PATIENTS AND METHODS: Fifty-one consecutive patients with stroke and transient ischemic attacks were assessed. Tests used for the laboratory diagnosis of the antiphospholipid syndrome included four phospholipid-dependent coagulation tests for detection of the lupus anticoagulant, and two enzyme-linked immunosorbent assays for antibodies to phospholipid. RESULTS: Three of 51 patients (6%, 95% confidence intervals 0% to 12.0%) had a lupus anticoagulant and the clinical features of the antiphospholipid syndrome. Seven patients had clinical features suggestive of the syndrome but negative laboratory tests. Those patients who were clinically unlikely to have this syndrome also had negative laboratory tests. CONCLUSION: In a series of 51 unselected patients presenting with stroke and transient ischemic attacks, three had the antiphospholipid syndrome. The clinical features of this syndrome are helpful in identifying this group of patients. The role of the lupus anticoagulant in the pathogenesis of stroke remains to be defined.

Adolescent↗

Ovarian serous borderline tumors with stromal microinvasion: a report of 21 cases.

The clinicopathologic features of 21 cases of otherwise typical serous borderline tumors that contained small foci of stromal invasion were reviewed. The mean age of the patients was 43 years and six of them were pregnant at the time of diagnosis. Nineteen tumors were stage I, one was stage III (para-aortic lymph node involvement) and one was stage IV (parenchymal liver metastasis). The tumor invaded the stroma predominantly as individual cells or nests or clusters of cells with abundant eosinophilic cytoplasm (17 cases), as small confluent nests with a cribriform pattern (two cases) and as rounded aggregates of papillae (two cases). Seven women were treated with bilateral salpingo-oophorectomy and hysterectomy; 13 had less than bilateral oophorectomy. Of the 17 patients for whom followup data were available, 16 were without evidence of disease 1 to 11 (mean, 5.2) years postoperatively, and one patient had a serous borderline tumor with microinvasion in a conserved contralateral ovary 2.8 years postoperatively, but was well 6 months after a partial oophorectomy. These data suggest that serous borderline tumors with microinvasion have a prognosis similar to that of the usual serous borderline tumor, and that conservation of the contralateral ovary and uterus may be acceptable therapy in young women who wish to preserve their fertility.

Adolescent↗

Evaluation of the mutagenicity of combustion particles from several common biomass fuels in the Ames/Salmonella microsome test.

We have evaluated the mutagenicity of dichloromethane extracts of combustion particles from several biomass fuels that are commonly used in developing countries in Salmonella strains TA98 +/- S9 and TA100 +/- S9. Combustion-particle extracts from dried cow dung and crop residue exhibited mutagenic potencies similar to wood-smoke extracts (0.0-1.0 rev./microgram extract). However, extracts from coconut-shell-smoke particles showed relatively potent direct-acting mutagenicity (1.6 rev./micrograms, TA98-S9). Results from testing this sample in nitroreductase- and acetylase- deficient strains TA98NR and TA98 (1,8-DNP-6) revealed no contribution from nitroarenes.

Air Pollution↗

Comparative study of idiotypes on monoclonal antibodies derived from patients with lupus and leprosy and from normal individuals.

A collaborative study was performed to compare the expression of a series of idiotypes defined on human anti-DNA and other autoantibodies. Three panels of human monoclonal antibodies were tested: eight derived from patients with systemic lupus erythematosus (SLE); 13 from an individual with lepromatous leprosy; and 38 from normal subjects. The following rabbit anti-idiotype sera were used: one (RId16/6) raised against the lupus-derived monoclonal anti-DNA antibody 16/6, four (RId8E7, RId4G7, RId4D5 and RIdTH9) against leprosy-derived monoclonal antibodies of various specificities, and one (anti-4.6.3) against a normal-derived anti-DNA monoclonal (KIM 4.6). In addition, two other anti-idiotypes were used--one a murine monoclonal (3I), the other a rabbit polyclonal (RIdD)--which had been raised against polyclonal anti-DNA antibodies from lupus serum. Further experiments were performed with immunoabsorbed fractions of RId8E7. Direct-binding and competition assays were used. All of the anti-idiotypes produced different patterns of positivity among the three panels of human monoclonal antibodies, with the exception of RId8E7 and RId4G7, which showed considerable concordance. There was a tendency towards anti-idiotypes being disease- or group-specific: thus anti-4.6.3 failed to bind to any of the lupus or leprosy-derived monoclonals, while RId16/6 and RId8E7 bound most strongly to the lupus- and leprosy-derived antibodies respectively. KIM 4.6 itself was bound only weakly by RId16/6, while 16/6 was not recognized by anti-4.6.3; 16/6 was, however, bound by 3I, while KIM 4.6 was not. 3I bound to several other monoclonals but RIdD, which has been shown to be specific for the anti-DNA fraction of lupus serum, did not bind to any of them. These results indicate that the majority of these anti-idiotype preparations recognize largely separate sets of determinants. The monoclonal antibodies which bind to DNA may be only partly representative of anti-DNA antibodies in the serum of lupus patients.

Antibodies, Anti-Idiotypic↗

Serous borderline tumors of the peritoneum.

The clinicopathological features of 25 cases of peritoneal serous neoplasms histologically identical to noninvasive implants of ovarian serous borderline tumors but with minimal or no ovarian surface involvement were reviewed. The patients ranged in age from 19 to 53 (mean, 31) years; 18 of them were under 35 years of age. Infertility and abdominal pain were the most common presenting complaints. An extraovarian mass was present in two patients; adhesions or granularity of peritoneal surfaces were described in 23 of them. In 21 cases only the pelvic peritoneum was involved; the upper abdominal peritoneum was involved additionally in four cases. Most of the women were treated by hysterectomy, bilateral salpingo-oophorectomy, and omentectomy; six of them received chemotherapy postoperatively and two received both chemotherapy and radiation therapy. Nine women had a more limited operation to preserve their fertility. The 25 patients were followed for 4 to 13.9 (mean, 8) years. There was no clinical evidence of recurrence in 21 women. Borderline tumor recurred in two patients, who remained well for 1.7 and 2 years after excision of the recurrent tumor. Invasive low-grade serous carcinoma of the peritoneum developed in one woman who was living with extensive intra-abdominal tumor at the last follow-up examination. One woman died of disseminated SBT, which was diagnosed cytologically but not confirmed by biopsy.

Adult↗

Serous psammocarcinoma of the ovary and peritoneum.

We report 11 cases of serous psammocarcinoma, a rare variant of serous carcinoma characterized by massive psammoma body formation and low-grade cytological features. The patients ranged in age from 36 to 76 (mean of 57) years. The tumors were stage three in every case (three stage IIIA, seven stage IIIB, and one stage IIIC). Eight of the patients had ovarian psammocarcinomas with ovarian tumors measuring 5-22 (mean of 11) cm in diameter; the other three patients had primary peritoneal psammocarcinomas. The surfaces of the ovarian tumors were smooth and intact in seven of eight ovarian psammocarcinomas. Cysts were present in six of eight ovarian tumors, and the solid portions were typically gritty or granular. Necrosis was not seen. Microscopically there was destructive invasion of ovarian stroma or vascular invasion in the ovarian tumors; the extraovarian tumor implants were invasive of intraperitoneal viscera in five cases. The epithelium was arranged in small nests with no areas of solid epithelial proliferation, and at least 75% of the epithelial nests were associated with psammoma body formation. No more than moderate nuclear atypicality was identified in any case. No mitotic figures were found in 10 of the tumors, with a single mitotic figure identified in the other tumor. Follow-up data for more than 1 year was available for six patients, with two patients lost to follow-up and three patients followed without evidence of recurrence for less than 1 year. One patient died of tumor 6 1/2 years after presentation, and five patients were alive without evidence of recurrent tumor 3-10 (mean of 8.3) years after presentation. Although based on a small number of cases, these data suggest that the clinical behavior of psammocarcinoma more closely resembles that of borderline serous tumors than of serous carcinomas of the usual type, following a protracted course and being associated with a relatively favorable prognosis.

Adenocarcinoma, Papillary↗

Pre- and postoperative imaging of vascularized fibular grafts.

Free vascularized fibular grafting, in which the peroneal artery is harvested with the fibula, is a popular procedure for filling osseous defects and for treatment of femoral head avascular necrosis. Preoperative vascular imaging is required in all patients to detect the origin of the peroneal artery, to measure the length available for the vascular pedicle, and to evaluate for the normal continuation of the three major vessels of the lower leg. Magnetic resonance imaging of the lower leg with use of gradient-recalled acquisition in a steady, state was performed in 35 patients to evaluate vascular anatomy. Surgical correlation was available in 91% of cases, and in these 100% accuracy was demonstrated. Postoperative radiographs showed that grafts placed for osseous defects in the upper extremity were incorporated and hypertrophied extremely quickly, while those placed in the major weight-bearing bones of the lower extremity were much more prone to complications including delayed union, fracture, and infection. Vascularized grafts placed in the femoral head and neck for avascular necrosis incorporate only in the cephalic portion and should be watched carefully for signs of early and progressive femoral head collapse.

Adolescent↗

Immunogenic DNA-related factors. Nucleosomes spontaneously released from normal murine lymphoid cells stimulate proliferation and immunoglobulin synthesis of normal mouse lymphocytes.

The cell-free supernatants of normal spleen and thymus lymphocytes in short-term culture release low molecular weight (LMW) DNA protein molecules that have an immunoproliferative effect (polyclonal B cell activation) in vitro. We have determined that the protein-LMW DNA complexes responsible for these effects are nucleosomal constituents of chromatin, since the mitogenically active fractions of these cell-free supernatants contain the constituents of core histones (H3, H2A, H2B, H4) together with LMW DNA (140-180 bp), and since the immunoproliferative effects of these cell-free supernatants could be mimicked by various other nucleoprotein preparations (including calf thymus and chicken erythrocyte nucleosomes). The spontaneous cellular release of cleaved chromatin constituents in vitro can be attributed to a form of programmed cell death termed apoptosis, since the cultured spleen cells exhibited (a) morphologic evidence consistent with this process by electron microscopy, and (b) evidence of intracellular cleavage of chromatin which, like apoptosis, could be blocked with ZnSO4. This resulted in inhibition of the extracellular release of nucleosomal constituents as well as the immunoproliferative effects of the cell-free supernatants. The immunoproliferative effect of nucleosomes released from cells during apoptosis could be responsible for previously observed spontaneous in vitro anti-DNA and anti-histone antibody responses of murine spleen cells, and in vivo in normal lymphoid tissues, resulting in renewed cellular proliferation after cell death. In pathological states, this could result in abnormal polyclonal B cell proliferation and autoantibody formation.

Animals↗

Magnetic resonance imaging of vascular anatomy before vascularized fibular grafting.

Magnetic resonance images of the leg were made preoperatively to show the vascular anatomy in twenty-nine patients (thirty-five legs) who were between the ages of fourteen and forty-one years and in whom we planned to use the fibula as a vascular graft. The fibula was harvested as a graft in thirty-two legs, and this allowed us to compare the images with the anatomical findings at operation. In these thirty-two legs, the branching pattern, the measured distance to the bifurcation of the peroneal artery, and all vascular anomalies in the area were accurately detected. No graft was taken from the other three legs. We recommend that imaging of the vascular anatomy of the leg be done before using the fibula as a vascular graft in order to detect the precise point of origin of the peroneal artery from the posterior tibial artery, to estimate the length of the vascular pedicle, and to evaluate the role of the three major vessels in supplying blood to the leg. All these aims can be accomplished with the aid of angiography, but we have found that gradient-recalled acquisition in the steady state (GRASS) magnetic-resonance imaging is more cost-effective and is associated with less morbidity. It is not adequate for older patients who have arterial stenosis or atherosclerosis or for patients who have some other underlying vascular disease. Metallic hardware may cause artefacts that obscure the vascular anatomy.

Adolescent↗

Analysis of variable region genes encoding a human anti-DNA antibody of normal origin. Implications for the molecular basis of human autoimmune responses.

In order to investigate the genetic basis for natural anti-DNA immune responses, we isolated and sequenced the variable gene elements (VH and VL) encoding an anti-DNA antibody expressed by a human hybridoma of normal origin (Kim4.6) and compared these sequences with those reported for four other human anti-DNA antibodies. The Kim4.6 antibody leader and VH segments were identical in nucleotide sequence with the VH1.9III germ-line VH3 gene, and the Kim4.6VL segment showed 98% nucleotide sequence identity with a V lambda I subgroup gene expressed in a Burkitt's lymphoma. Comparative analysis of Kim4.6 and other human hybridoma anti-DNA antibodies indicated that anti-DNA immune responses are diverse in terms of VH and VL gene utilization but may exhibit a bias toward rearrangement of VH genes that are over-represented in the fetal pre-B cell repertoire. Moreover, Kim4.6 and three of four other sequenced human anti-DNA antibodies appear to use a germ-line diversity gene, DXP'1, which may represent a counterpart of the DFL16.1 segment utilized in murine responses to the hapten nitrophenyl. Taken together, our findings indicate that anti-DNA immune responses can be encoded by nonmutated VH genes and that the elements and molecular mechanisms which engender this response are essentially the same among natural and lupus-associated anti-DNA antibodies. Our data also suggest that natural autoimmune responses originate early in B cell ontogeny as is consistent with the hypothesis that autoreactivity plays a major role in shaping the normal immune repertoire.

Amino Acid Sequence↗

Galactose consumption and metabolism in relation to the risk of ovarian cancer.

In a case-control study, consumption of dairy foods by 235 white women with epithelial ovarian cancer and by 239 control women, and activity of red blood cell galactose-1-phosphate uridyl transferase (transferase) in a subset of 145 cases and 127 controls were determined. Yogurt was consumed at least monthly by 49% of cases and 36% of controls. The mean transferase activity of cases was significantly lower than that of controls. When a ratio of lactose consumption to transferase (L/T) was calculated, cases had a mean L/T of 1.17 compared with 0.98 for controls; there was a highly significant trend for increasing ovarian cancer risk with increasing L/T ratio. Lactose consumption may be a dietary risk factor and transferase a genetic risk factor for ovarian cancer.

Adult↗

The prevalence of primary Sjögren's syndrome in a multiple sclerosis population.

A central nervous system illness closely resembling multiple sclerosis has been described in patients with primary Sjögren's syndrome. From these reports, the estimated prevalence of this syndrome could be similar to that of multiple sclerosis in a high-frequency area. We evaluated 192 consecutive patients in our multiple sclerosis clinic to determine if such cases had gone unrecognized. We did not find any patients with clinical or serological evidence of primary Sjögren's syndrome. We conclude that it is rare for neurological manifestations of Sjögren's syndrome to mimic multiple sclerosis in our population.

Adult↗

Role of skin lesions in the Salem witchcraft trials.

In the late 17th century, several hundred people were tried for the crime of practicing witchcraft in Salem Village, Massachusetts. Twenty-four people died before the Superior Court of Judicature dismissed the remaining cases and Governor Phips pardoned and granted amnesty to all of the accused and convicted. The evidence used to convict a person of being a witch included spectral evidence confessions, and apparent proof of that person's alleged supernatural abilities. Also used as evidence were skin lesions characteristic of what were termed "devil's marks" or "witch's marks." It was believed that the devil would confirm his pact with a witch by giving her or him a mark of identification. Devil's marks included a variety of skin lesions described as flat or raised, red, blue, or brown lesions, sometimes with unusual outlines. Witch's marks were most probably supernumerary nipples. It was believed that familiars (agents of the devil, usually in animal form) would receive sustenance by being suckled. In the Salem witchcraft trials, a variety of skin lesions were used as confirmatory evidence that the accused person had made a pact with the devil, but there is no indication in the trial transcripts that anyone was convicted based on this evidence alone.

Dermatology↗

Primary mucinous carcinoid tumor of the ovary. A case report.

A case of primary ovarian mucinous carcinoid tumor in a 36-year-old woman is described. The tumor was present in the wall of a mature teratoma and microscopically showed tubules and glands containing goblet cells interspersed among columnar to cuboidal cells with uniform round nuclei and granular cytoplasm. The cytoplasm of the tumor cells contained argyrophil granules on Grimelius stains. Immunohistochemical stains utilizing antibodies against carcinoembryonic antigen, chromogranin, and pancreatic polypeptide were positive. Although primary mucinous carcinoid tumors are generally believed to exhibit more aggressive behavior than other categories of carcinoid tumors, the patient was treated conservatively with a right salpingo-oophorectomy and remains well 3 years later, suggesting that unilateral salpingo-oophorectomy and careful follow-up are adequate therapy in a young woman when the tumor is confined to the ovary.

Adenocarcinoma, Mucinous↗

Expression in systemic lupus erythematosus of an idiotype common to DNA-binding and nonbinding monoclonal antibodies produced by normal human lymphoid cells.

Rabbit antiserum raised against a normal-derived monoclonal anti-DNA antibody KIM 4.6.3 (IgM lambda) was used for idiotype analyses. This anti-serum (anti-4.6.3 ID) was rendered specific for KIM 4.6.3 idiotype (4.6.3 ID) by absorption with normal human IgM and IgG. The specificity of anti-4.6.3 was shown by its ability to bind to KIM 4.6.3 antibody but not to normal human IgM and IgG, by inhibition of anti-4.6.3 ID reactivity with KIM 4.6.3 antibody by the homologous monoclonal antibody and by the ability of anti-4.6.3 ID to inhibit the binding of single stranded DNA with KIM 4.6.3 antibody. The 4.6.3 ID was found to be commonly expressed since it was detected among 33% (10/30) DNA and 32% (23/72) non-DNA-reactive monoclonal antibodies that were obtained from five different unrelated normal individuals. The binding to ssDNA of the majority of idiotype positive anti-DNA antibodies however was not blocked by anti-4.6.3 ID suggesting that among these other monoclonal antibodies its expression is outside of the antigen binding site. The 4.6.3 ID, which was present among some normal-derived monoclonal IgM molecules was also found at a high frequency (90%) in the sera of patients with systemic lupus erythematosus (SLE) but only at a low frequency (24%) and concentration in normal sera. The level of 4.6.3 ID in SLE did not correlate with serum IgM and IgG nor with anti-DNA antibody concentrations. Idiotypic relatedness between SLE serum antibodies and monoclonal anti-DNA antibodies of normals implies the existence of a cross-reactive idiotype family and implies that a conserved common gene or closely related genes exist in the germ line encoding these 4.6.3 ID positive antibodies some of which are not exclusively associated with nucleic acid reactivity. The expression of these germ line genes in vivo thus distinguishes SLE from normals.

Antibodies, Monoclonal↗

Peritoneal implants of ovarian serous borderline tumors. Histologic features and prognosis.

The clinicopathologic features of 56 cases of ovarian serous borderline tumors (SBT) associated with peritoneal implants were reviewed. Data from 368 person-years of follow-up (median follow-up, 6.0 years) were analyzed to investigate the possibility that the histologic features of implants of this type of tumor may correlate with the prognosis. Eighty-five percent of the 56 patients were clinically free of tumor at the time of death or at last contact. Thirteen percent of the patients died of tumor, and one patient (2%) was alive with widespread progressive tumor. The product-limit estimate of the probability of death from tumor (+/- standard error) was 4% (+/- 3%) at 5 years and 23% (+/- 9%) at 10 years. The following three histologic features of the implants correlated with an adverse prognosis: (1) invasion (P = 0.0004), (2) severe cytologic atypia in both invasive and noninvasive implants (P = 0.0008) and in noninvasive implants alone (P = 0.02), and (3) the presence of mitotic activity in both types of implants (P = 0.02) and in noninvasive implants alone (P = 0.02). The only other feature that correlated with the prognosis was the presence of residual tumor postoperatively as assessed by the surgeon (P = 0.01). The product-limit estimate of death of tumor in patients with at least one of these four adverse prognostic factors was 56% (+/- 20%) at 10 years. Whether or not the patients received radiation therapy, chemotherapy, or both had no statistically significant effect on the outcome. These data and the results of a stratified analysis suggest that patients may benefit from additional therapy if adverse prognostic factors are present, especially invasiveness or severe cytologic atypia. It is unlikely that additional therapy is necessary in patients without adverse prognostic features, because no deaths occurred in this group.

Adult↗