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Biomedical subjects

C Hussey

Publications and source records attributed to C Hussey.

13 recordsLinked to original sources

Localization of the VHR phosphatase gene and its analysis as a candidate for BRCA1.

The VH1-related human protein (VHR) gene was localized to human chromosome 17q21 in a region thought to contain the BRCA1 locus, a locus that confers susceptibility to breast and ovarian cancer. VHR encodes a phosphatase with dual specificity for tyrosine and serine residues. Thus it is a plausible candidate for a tumor suppressor gene such as BRCA1. To test this possibility, the VHR coding sequence was screened in individuals with familial breast cancer and in sporadic breast tumor and breast cancer cell lines. No mutations were detected, suggesting that the VHR gene is not BRCA1.

BRCA1 Protein↗

Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus.

A locus for familial melanoma, MLM, has been mapped within the same interval on chromosome 9p21 as the gene for a putative cell cycle regulator, p16INK4 (CDKN2) MTS1. This gene is homozygously deleted from many tumour cell lines including melanomas, suggesting that CDKN2 is a good candidate for MLM. We have analysed CDKN2 coding sequences in pedigrees segregating 9p melanoma susceptibility and 38 other melanoma-prone families. In only two families were potential predisposing mutations identified. No evidence was found for heterozygous deletions of CDKN2 in the germline of melanoma-prone individuals. The low frequency of potential predisposing mutations detected suggests that either the majority of mutations fall outside the CDKN2 coding sequence or that CDKN2 is not MLM.

Base Sequence↗

Medicare patients and alternatives to the acute care hospital.

There are many instances where hospitalized elderly patients no longer need intensive hospital care but are not ready to be discharged. One solution to this dilemma is the use of a skilled nursing facility (SNF) or some type of step-down bed, where patients can continue to receive managed care at a less intense and costly level. A major concern with using step-down beds is that while costs may be controlled, quality of care may suffer and patient outcomes may be jeopardized. From an efficiency perspective, the step-down bed can provide an excellent alternative to hospital care for the less acutely-ill patient. For alternative managed care environments to be satisfactorily received by patients and physicians, however, they must produce outcomes equal or better than those in the hospital. Some patients and diagnoses are more appropriate than others for treatment in alternative managed care environments. The judgement of appropriateness must take into account patient and physician satisfaction with the efficiency and effectiveness of the care. This paper describes how the Fallon Community Health Plan, Worcester, Mass., which regularly uses a step-down facility for patient care, assessed outcomes in terms of efficiency and effectiveness. An overview of this alternative managed care facility and its relationship to the HMO is discussed below. Several studies examining outcomes and patient and physician satisfaction are presented. Finally, the ways in which these studies represent a merger of quality assurance (QA) and utilization review (UR) methodologies are discussed.

Aged↗

Thermo-inducible gene expression in Bacillus subtilis using transcriptional regulatory elements from temperate phage phi 105.

A Bacillus subtilis/Escherichia coli shuttle plasmid vector containing a transcriptionally silent chloramphenicol acetyl transferase gene (cat-86) was constructed by ligation of pPL603 (Williams et al., 1981a) and pUC8 (Vieira and Messing, 1982) at their unique EcoRI sites. Using this "promoter probe" vector we have obtained, by direct Cm resistance selection, a collection of cloned Sau3A fragments from the temperate phage phi 105 genome exhibiting promoter activity in B. subtilis. 18 promoter plasmids were subsequently transferred to an acceptor cell containing a functional repressor gene of phage phi 105 inserted into the temperature-sensitive replicon pE194. A repressor-controlled promoter was identified on the basis of its ability to confer thermo-inducible Cm resistance. The promoter is located on a 650-bp Sau3A fragment, mapping within the 3.2-kb EcoRI-F fragment, which also contains the phi 105 repressor gene. By assaying cloned subfragments of EcoRI-F for expression of immunity against phi 105 infection, the repressor gene could be assigned to a 1.1-kb EcoRI-HindIII fragment, which partially overlaps the promoter fragment. Taken together, these results suggest that, like the cI-coded repressor in coliphage lambda, the phi 105 repressor interacts with an operator sequence mapping very close to its own gene.

Acetyltransferases↗

Antithrombin deficiency--a cause of unexplained thrombosis in vascular surgery.

Antithrombin deficiencies may be the reason for seemingly unexplained thrombosis and graft failure. We treated seven patients who developed clotting difficulties as a result of antithrombin II and/or III deficiencies. In four, arterial thrombosis occurred after arterial reconstruction--three with occluded femoral grafts and one with runoff and digital vessel thrombosis that developed during profundoplasty. Two patients has spontaneous thrombosis of the arterial system of the vessels of the lower leg, and one developed ileofemoral phlebitis. Three patients had abnormally low levels of both antithrombin II and III, whereas two had low levels of antithrombin II only and two had low levels of antithrombin III. Of the four patients in whom this disorder occurred during vascular reconstruction, three experienced graft occlusion that resulted in below-knee amputation in two. There were no common predisposing factors. Antithrombin deficiency should be suspected when there is an unusual propensity to develop thrombus, when heparin cannot prolong coagulation time, and when measurements show reduced levels of antithrombin. Fresh frozen plasma should be given initially and long-term Coumadin therapy started. Early recognition and treatment is necessary to avoid limb loss or death.

Adult↗

Arthrographic pseudoloosening of Marmor total knee in hemophilic arthropathy: report of a case.

The interpretation of loosening on the basis of contrast flow about the cement-bone interface in arthrograms of total knee arthroplasties includes special considerations. The first is that arthrography is misleading in the presence of severe cystic changes. The second is that clinical criteria should be given priority before concluding that there is loss of fixation of the prosthesis.

Adult↗

White clot syndrome. Peripheral vascular complications of heparin therapy.

Heparin sodium-induced thrombosis is insidious and difficult to diagnose. If untreated, it results in death or major amputation. We have treated seven patients with thromboses resulting from platelet aggregation induced by heparin. Four patients had acute arterial ischemia of the lower extremity, venous gangrene developed in two, and one patient had an occluded autogenous vein femoral popliteal bypass in the immediate postoperative period. The platelet count was noticeably reduced in affected patients. White platelet thrombi were noted in four patients, three of whom had acute arterial occlusion. A white thrombus was the cause of immediate failure of a femoral popliteal graft. Electron microscopic examination of these thrombi demonstrated predominantly fibrin platelet aggregates with an occasional entrapped WBC and a rare RBC. All patients receiving heparin therapy must have platelet counts performed regularly. If thrombocytopenia is detected, platelet aggregation studies are indicated. When abnormal platelet aggregation is noted, heparin therapy should be reversed with protamine sulfate and the patient treated with low-molecular-weight dextran and warfarin sodium.

Aged↗

In vitro synthesis of ribosomal RNA by Bacillus subtilis RNA polymerase.

Two kinds of hybridization competition experiments show that Bacillus subtilis RNA polymerase synthesizes ribosomal RNA (rRNA) in vitro with B. subtilis DNA as a template. First, RNA synthesized in vitro competes with the hybridization of [(32)P]rRNA synthesized in vivo to the heavy strand of B. subtilis DNA. Second, unlabeled rRNA synthesized in vivo competes with the hybridization of [(3)H]RNA synthesized in vitro to denatured DNA or heavy-strand DNA, but not to light-strand DNA. The ability of RNA polymerase holoenzyme to synthesize rRNA in vitro is not lost after extensive purification. RNA polymerase core enzyme, however, which is missing the sigma factor, synthesizes little rRNA in vitro.RNA polymerase purified from wild-type sporulating cells synthesizes little rRNA in vitro, while the in vitro synthesis of rRNA by RNA polymerase from stationary phase cells of the sporulation-defective mutant rfr 10 is apparently unimpaired.

Bacillus subtilis↗