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Biomedical subjects

H E Wilson

Publications and source records attributed to H E Wilson.

At least 19 recordsLinked to original sources
PubMed2002

When typical is atypical: mycobacterial infection mimicking cutaneous vasculitis.

Patients with systemic lupus erythematosus (SLE) who present with skin disease pose the clinician with diagnostic challenges. The skin disease can reflect an increase in systemic disease activity suggested by other features of active lupus and, as such, usually responds well to more aggressive immunosuppressive therapy. Other possibilities of skin disease include drug eruptions, skin disease unrelated to SLE and, more rarely, opportunistic skin infection. In patients who show a poor response to more aggressive immunosuppressive therapy, consideration must be given to the possibility of opportunistic infection. A high index of suspicion will allow prompt treatment. We describe two patients with SLE who developed cutaneous atypical mycobacterial infection during immunosuppressive therapy. The diagnosis of cutaneous vasculitis was considered in both cases, but subsequent skin biopsy revealed the correct diagnosis. This report illustrates the importance of skin biopsy in patients with suspected cutaneous lupus who are not responding to immunosuppressive therapy.

Adult↗
PubMed2001

Monoclonal antibodies to the carboxy-terminal Ea sequence of pro-insulin-like growth factor-IA (proIGF-IA) recognize proIGF-IA secreted by IM9 B-lymphocytes.

Insulin-like growth factor-I (IGF-I) circulates in human serum as a 7 kDa peptide but analysis of IGF-I cDNAs predicts two pro-hormone precursors (proIGF-IA and proIGF-IB) with distinct C-terminal E domains. The function of these precursors, and the E peptides generated on cleavage to mature IGF-I, is unknown, largely because of a lack of tools for distinguishing precursors from constituent peptides. We used a synthetic Ea peptide to develop monoclonal antibodies (MAbs) which can recognize the carboxy-terminal sequence of proIGF-IA. These were characterized using proIGF-IA generated by transfected HEK293 cells. The anti-proIGF-IA MAbs immunoprecipitated two peptides (19--21 and 14 kDa) which were also recognized by MAbs to mature IGF-I. The proIGF-IA MAbs could also detect peptides of 9 and 4 kDa predicted to be Ea peptides. Treatment with N -glycosidase proved the 19--21 kDa and 9 kDa bands to be glycosylated proIGF-IA and Ea peptide respectively. Using these antibodies, we have identified proIGF-IA secreted from the IM9 B-lymphocyte cell line. This work paves the way for studies on proIGF-IA and Ea peptide regulation and function.

Antibodies, Monoclonal↗
PubMed1996

Structural variation of the pseudoautosomal region between and within inbred mouse strains.

The pseudoautosomal region (PAR) is a segment of shared homology between the sex chromosomes. Here we report additional probes for this region of the mouse genome. Genetic and fluorescence in situ hybridization analyses indicate that one probe, PAR-4, hybridizes to the pseudoautosomal telomere and a minor locus at the telomere of chromosome 9 and that a PCR assay based on the PAR-4 sequence amplifies only the pseudoautosomal locus (DXYHgu1). The region detected by PAR-4 is structurally unstable; it shows polymorphism both between mouse strains and between animals of the same inbred strain, which implies an unusually high mutation rate. Variation occurs in the region adjacent to a (TTAGGG)n array. Two pseudoautosomal probes can also hybridize to the distal telomeres of chromosomes 9 and 13, and all three telomeres contain DXYMov15. The similarity between these telomeres may reflect ancestral telomere-telomere exchange.

Animals↗
PubMed1995

YAC cloning Mus musculus telomeric DNA: physical, genetic, in situ and STS markers for the distal telomere of chromosome 10.

Three Mus musculus DBA/2 YAC libraries were constructed using a half-YAC telomere cloning vector. This functional complementation approach yields libraries which include terminal restriction fragments of the mouse genome. Screening all three libraries led to the isolation of 32 independent clones which carry linear YACs containing the mouse terminal repeat sequence, (TTAGGG)n. These YACs provide a resource to isolate regions of the mouse genome close to chromosome termini and excluded from existing conventional YAC libraries. To demonstrate their utility, a hybridization probe was isolated from Mtel-1, the first (TTAGGG)n-containing YAC isolated. This probe detects a approximately 70 kb Kpnl fragment in the mouse genome which is sensitive to pretreatment with BAL31 exonuclease. A PCR-based genetic marker generated from the sequence of this probe maps 4.4 cM from the most distal anchor locus on chromosome 10 in the EUCIB interspecific backcross. STS primers for this locus, D10Hgu1, were used to isolate YAC 110F4 from a commercially available mouse YAC library. Fluorescence in situ hybridization demonstrates that YAC 110F4 hybridizes to the distal telomere of chromosome 10. Clones in this collection of telomere YACs therefore partially overlap clones in conventional YAC libraries, and thus the previously unavailable terminal regions of the mouse genome can now be linked with the developing mouse STS YAC contig. Genetic markers such as D10Hgu1 allow the ends of the mouse genetic map to be defined, thus closing the map.

Animals↗
PubMed1995

CENP-B binds a novel centromeric sequence in the Asian mouse Mus caroli.

Minor satellite DNA, found at Mus musculus centromeres, is not present in the genome of the Asian mouse Mus caroli. This repetitive sequence family is speculated to have a role in centromere function by providing an array of binding sites for the centromere-associated protein CENP-B. The apparent absence of CENP-B binding sites in the M. caroli genome poses a major challenge to this hypothesis. Here we describe two abundant satellite DNA sequences present at M. caroli centromeres. These satellites are organized as tandem repeat arrays, over 1 Mb in size, of either 60- or 79-bp monomers. All autosomes carry both satellites and small amounts of a sequence related to the M. musculus major satellite. The Y chromosome contains small amounts of both major satellite and the 60-bp satellite, whereas the X chromosome carries only major satellite sequences. M. caroli chromosomes segregate in M. caroli x M. musculus interspecific hybrid cell lines, indicating that the two sets of chromosomes can interact with the same mitotic spindle. Using a polyclonal CENP-B antiserum, we demonstrate that M. caroli centromeres can bind murine CENP-B in such an interspecific cell line, despite the absence of canonical 17-bp CENP-B binding sites in the M. caroli genome. Sequence analysis of the 79-bp M. caroli satellite reveals a 17-bp motif that contains all nine bases previously shown to be necessary for in vitro binding of CENP-B. This M. caroli motif binds CENP-B from HeLa cell nuclear extract in vitro, as indicated by gel mobility shift analysis. We therefore suggest that this motif also causes CENP-B to associate with M. caroli centromeres in vivo. Despite the sequence differences, M. caroli presents a third, novel mammalian centromeric sequence producing an array of binding sites for CENP-B.

Animals↗
PubMed1994

Mouse centromere mapping using oligonucleotide probes that detect variants of the minor satellite.

Cytologically, the centromere is found at the very end of most Mus musculus chromosomes, co-localizing with an array of minor satellite sequences. It is separated from the euchromatin of the long arm by a large domain of heterochromatin, composed in part of arrays of major satellite sequences. We used oligonucleotide probes that specifically detect regions of sequence variation found in certain cloned minor satellite sequences. They detect a limited subset of the minor satellite arrays in the mouse genome, based on both pulsed-field gel electrophoresis and in situ hybridization data, and provide direct molecular genetic markers for individual centromeres in some inbred mouse strains. Array size polymorphisms detected by these probes map to positions consistent with the centromeres of chromosomes 1 and 14 in the BXD recombinant inbred (RI) strains. The genetic distances between these minor satellite arrays and loci on the long arms of chromosomes 1 and 14 are consistent with repression of meiotic recombination in the heterochromatic domains separating them. The existence of chromosome-specific minor satellite sequences implies that the rate of sequence exchange between non-homologous chromosomes relative to the rate between homologous chromosomes is much lower than has previously been postulated. We suggest that the high degree of sequence homogeneity of mouse satellite sequences may instead reflect recent common ancestry.

Animals↗
PubMed1988

Outcome of prophylactic and therapeutic cranial irradiation in disseminated small cell lung carcinoma: a Southwest Oncology Group Study.

The issue whether cranial radiotherapy (RT) should be used prophylactically (PCI) or therapeutically (TCI) in small cell lung carcinoma (SCLC) is considered controversial by some oncologists. Trying to clarify this issue we have performed a retrospective analysis of a Southwest Oncology Group (SWOG) protocol for disseminated SCLC. Three Hundred and seventy-seven cases had no evidence of metastases to the brain (MB). One hundred and forty four of those had PCI. Seventy one cases were diagnosed of MB, and 64 received TCI. We confirmed previous reports showing a low percentage of brain relapse with PCI (around 5%), with minimal immediate morbidity. We also confirmed a high percentage of objective response (90%) with TCI, (although we had no response information in 40% of them) with long duration of response of 33 weeks. Brain relapse after TCI was only 18%. Only long-term survivors had brain relapse as survival of relapsing patients was longer than those without brain relapse (45 weeks versus 33 weeks, p = 0.06). However, 20 (31%) of the 65 with initial MB died within 6 weeks of registration, some without completing RT to brain. In the majority, cause of death was considered related directly to brain damage, or indirectly as sepsis developed in patients whose poor performance status was considered to be caused by their brain symptoms. When comparing patients with and without MB, the former had (a) worse survival (24 versus 32 weeks, p = 0.02) and (b) higher proportion of patients with poor initial performance status (50% versus 34%, p = 0.04). Although the possibility of long-term morbidity with PCI is deterring some oncologists from recommending it, our data show that MB creates a real chance for immediate morbidity and this should not be ignored. The pros and cons of both approaches and some new recommendations for PCI are discussed.

Brain↗
PubMed1986

Effect of age on therapeutic outcome in advanced diffuse histiocytic lymphoma: the Southwest Oncology Group experience.

To study the influence of chronologic age on treatment outcome in patients with advanced, diffuse large-cell (histiocytic) lymphoma (DHL), we reviewed the results of two recent Southwest Oncology Group (SWOG) clinical trials. From 1974 to 1982, members entered 307 eligible patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without bleomycin, and CHOP with or without immunotherapy using BCG, levamisole, or both. Complete response (CR) rates declined progressively with advancing age: 65% in those under 40, 60% in the 40 to 54 age group, 55% in the 55 to 64 age group, and 37% in those 65 and older (P = .001). Likewise, survival decreased significantly in older patients: medians were 101 +, 52, 34, and 16 months, respectively (P less than .001). Treatment guidelines included an initial dose reduction of 50% for patients aged 65 or older and for younger patients with bone marrow compromise. Despite protocol specifications, 23 of 81 patients aged 65 or older received initial full-dose therapy. When these patients were compared with younger patients on whom full-dose chemotherapy was started, survival curves, but not CR rates, were still significantly different. There were no significant differences in duration of CR or frequency of treatment complications. These data suggest that older age is associated with a worse prognosis in advanced DHL. Moreover, the initial dose reduction for patients aged 65 or older may have contributed to their inferior outcomes.

Adult↗
PubMed1986

Eosinophilic alveolitis in acute respiratory failure. A clinical marker for a non-infectious etiology.

Two patients with acute respiratory failure requiring mechanical ventilation were found to have eosinophilic alveolitis on bronchoalveolar lavage and lung biopsy studies. Neither patient had evidence of lung infection or parasitic disease and both rapidly improved following treatment with corticosteroids. Lung eosinophilia in this setting is unusual, since the stress reaction that accompanies severe illness usually causes a rapid drop in circulating eosinophil levels. Eosinophilic alveolitis in such patients may be a useful clinical marker for non-infectious acute lung injury that is responsive to corticosteroid therapy.

Acute Disease↗
PubMed1985

Institutional performance in application of the FAB classification of acute leukemia. The Southwest Oncology Group experience.

Institutional performance in application of the French-American-British (FAB) classification of acute leukemia in The Southwest Oncology Group is presented, demonstrating a disparity between institutional and expert performance. A significant improvement is shown with an educational effort coupled with experience in use of the classification, and the importance of cytochemistry in the use of the classification is illustrated. A simplification of the classification, merging M1, M2, and M4 as M7, is proposed. This simplification improves institutional performance in use of the classification, while preserving distinctions that appear clinically important.

Acute Disease↗
PubMed1985

Reproducibility of the French-American-British classification of acute leukemia: the Southwest Oncology Group Experience.

After initial French-American-British (FAB) diagnosis by a multiinstitutional Southwest Oncology Group panel, slides of acute leukemia cases were recirculated to panel members for second review. The reproducibility of the FAB classification is analyzed. The classification is reproducible in the 70% range in panel reviewer hands and allows remarkable reproducibility in the morphologic and cytochemical distinction of acute lymphoid leukemia (ALL) from acute myeloid leukemia (AML). The limitations of a morphologic and cytochemical classification of acute leukemia are discussed. A simplification of the FAB system, merging M1, M2, and M4 as M7, is proposed; this simplification improves the system's reproducibility.

Acute Disease↗
PubMed1985

Low-dose deoxycoformycin in lymphoid malignancy.

Deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase (ADA), was explored for its antineoplastic potential in 28 patients with advanced lymphoid malignancy. Both normal and malignant B lymphocytes have low levels of ADA activity, and low doses of dCF profoundly inhibit this enzyme in the peripheral blood of patients with chronic lymphocytic leukemia (CLL). The low doses of dCF administered in this trial (4 mg/m2) were not associated with prohibitive toxicity. Five of 28 patients had an objective response. Four additional patients had clinical improvement. No significant difference in the pretreatment ADA activity existed between responding patients and treatment failures. The demonstration of responses to dCF following failure on standard alkylating agents suggests that dCF may not be cross-resistant with current agents used to treat CLL. Additional studies should be pursued using low-dose dCF in patients with advanced malignancy.

Adenosine Deaminase Inhibitors↗
PubMed1983

Preoperative reductive chemotherapy for locally advanced carcinoma of the oral cavity, oropharynx, and hypopharynx.

Recent reports have documented that five year survivals have not really improved as a result of combined therapy programs utilizing surgery and radiation therapy. The pattern of treatment failure seems to have changed in that such combined programs offer improved local and regional control but only to have patients develop distant metastases. The need for some form of systemic treatment was obvious. In 1977, a pilot study was initiated at the Ohio State University to evaluate a particular four drug combination and its effectiveness against squamous cell carcinoma of the head and neck. The initial results revealed an acceptable risk-benefit ratio to evaluate this regimen in a group of patients who had previously received no treatment. This report details the final results of the pilot study designed to evaluate response rates in previously untreated locally advanced squamous cell carcinoma of the oral cavity, oropharynx, and hypopharynx. During the 15 month duration of this study there were 58 patients who were evaluable. The overall response to a combination of cis-platinum, vincrinstine, methotrexate, and bleomycin was 66%. All toxicities occurred in less than 10% of the patients except for nausea and vomiting, which occurred to a mild to moderate degree in three quarters of the patient population. There was no increase in surgical or radiotherapeutic complications as a result of utilizing initial chemotherapy. This four-drug combination is now being evaluated to test its impact on survival as a Southwest Oncology Group study.

Antineoplastic Agents↗
PubMed1983

Comparison of chemotherapy alone versus chemotherapy and radiation therapy of extensive small cell carcinoma of the lung.

In a randomized study 145 patients with extensive small cell carcinoma of the lung were treated with chemotherapy alone (Cytoxan, CCNU, methotrexate) or with the same drug regimen and with radiation therapy to the brain, chest, and abdomen. One hundred eighteen of these patients were evaluable. Those patients receiving radiation had a better response rate (55% vs 31%, P = .016) but significantly greater toxicity. There was no significant difference in rates of complete response (7% vs 8%) or in survival (median 18.4 vs 15.3 weeks) between the two groups overall. The median survival of those patients with a partial response to therapy was 18 weeks; for those achieving a complete response it was 46 weeks. However, a clear difference in survival comparing responders with non-responders was evident only for patients who were assigned to chemotherapy alone. Partial regressions have little, if any, correlation with improvement in survival. Therapy in this disease must be oriented toward inducing complete response.

Aged↗
PubMed1983

Adriamycin versus adriamycin plus cis-diamminedichloroplatinum (DDP) in advanced transitional cell bladder carcinoma. A Southwest Oncology Group study.

Patients with advanced transitional cell bladder carcinoma were randomized to receive either adriamycin alone, or adriamycin plus DDP. Overall response (CR + PR) was 8/41 (19%) for adriamycin alone versus 16/37 (43%) for the combination (p = 0.02). Median response duration was 14 weeks for adriamycin versus 25 weeks for the combination (p = 0.17). Median survival was 28 weeks on adriamycin versus 31 weeks on the combination (p = 0.82). Median survival of responders was 43 weeks, and for patients with stable disease it was 29 weeks. This was significantly better than for those with increasing disease at 15 weeks (p = 0.02). Increased frequency of leukopenia and gastrointestinal toxicity were seen with the combination. Cardiotoxicity and nephrotoxicity were not prohibitive.

Carcinoma, Transitional Cell↗