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Biomedical subjects

B Howard

Publications and source records attributed to B Howard.

At least 37 records · Page 2Linked to original sources

Retrovirus-mediated gene transfer of the human gamma-IFN gene: a therapy for cancer.

A retroviral vector-mediated gene transfer system was used to introduce m gamma-IFN and h gamma-IFN genes into mouse and human tumor cells, respectively. Murine tumor cell lines and primary human melanoma tumor cells were successfully transduced with gamma-IFN vector, and these transduced cells secreted measurable levels of biologically active m gamma-IFN and h gamma-IFN, respectively. Both murine and human tumor cell lines that expressed gamma-IFN exhibited increased surface expression of HLA class I antigens when tested by Western blot and FACS analysis. gamma-IFN--transduced human melanoma cells were more active in stimulating tumor-specific cytolytic activity of CTLs from melanoma patients in vitro. m gamma-IFN--transduced tumor cells were substantially less tumorigenic than the corresponding parent tumor cell lines in immune-competent mice. In addition, injection of m gamma-IFN--transduced tumor cells resulted in activation of tumor-specific CTL in vivo. We plan to use gamma-IFN--transduced autologous tumor cells to boost host immune responses as a potential therapy for human melanoma.

Animals

Effect of parathyroid hormone-related peptide supplementation of soy protein formulas in the neonatal pig model.

PTH-related peptide (PTHrP) is found in all milks, including human and pig. To define a role for PTHrP in milk, 2-day-old piglets were randomized to receive soy formula devoid of PTHrP or supplemented with 1 nM synthetic PTHrP(1-86) (n = 8 per group). The number of serum samples with detectable PTHrP by immunoassay (Incstar) and radiometric assay (Nichols) was 9 of 33 and 3 of 13 in PTHrP- and 8 of 27 and 3 of 15 in PTHrP+ formula-fed piglets and 8 of 14 and 7 of 12 in naturally suckling piglets, respectively. Serum and urine concentrations of calcium and magnesium and total and bone alkaline phosphatase were similar in both groups at 3, 6, 10, and 17 days of age. No differences were seen in bone mineral content of the tibia measured by single-photon absorptiometry (BMC 0.22 +/- 0.06 and 0.22 +/- 0.10) or dual x-ray absorption (BMC 1.43 +/- 0.36 and 1.31 +/- 0.78) either in vivo or on excised bone or by measurement of Ca, Mg, or P content or total bone ash (1.26 +/- 0.26 and 1.38 +/- 0.28 mg). Intestinal histology, serum intestinal alkaline phosphatase, and net absorption and retention of Ca, Mg, and P in balances from age 11-17 days were all similar. As in humans, however, a developmental pattern was seen for phosphorus regulation in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon

A move from hospital to community-based homes for people with learning disabilities: activities outside the home.

Eighteen people with learning disabilities who moved from hospital to community-based homes were compared with a matched group of 18 who did not. A week-long time budget diary was used to record each occasion that the person left their home, the people accompanying them on each trip, their mode of transport and their destination. The diary was completed before they left the hospital and was repeated at least 1 year later. There was a strong correlation between the number of trips made from hospital wards at baseline and the number made at follow-up in both groups. Moving from the hospital had no significant effect on the number of trips made, but it did change their nature. Movers made more trips to unsegregated facilities; they made fewer trips alone and more in groups which included both staff and residents.

Activities of Daily Living

Relative mitogenic activities of wild-type and retinoblastoma binding-defective SV40 T antigens in serum-deprived and senescent human diploid fibroblasts.

A novel gene transfer approach was used to investigate whether the retinoblastoma (Rb)-binding domain of simian virus 40 (SV40) T antigen is required for efficient T antigen-mediated stimulation of DNA synthesis is quiescent or senescent human embryo fibroblasts. In senescent cells, comparison between wild-type T antigen and a mutant defective in Rb binding (Glu-107-->Lys) revealed the latter to have approximately 15-fold lower activity. In contrast, comparison of wild-type and Rb- T antigens in serum-deprived quiescent cells revealed a much smaller (1.8-fold) difference. Surprisingly, an 18-fold differential could be induced by treating quiescent cells with the differentiating agent sodium butyrate. These results suggest that the role of Rb in control of the cell cycle is strongly dependent on the physiological state of the cell and the mechanism of growth arrest.

Antigens, Polyomavirus Transforming

Congenital pseudarthrosis.

Five cases of congenital pseudarthrosis of the clavicle were treated with open reduction and fixation with appropriate-sized contoured plates and screws. Iliac bone grafts were used to bridge the gap in four patients; local bone graft was used in the fifth patient. Consolidation was noted an average of 3 months postoperatively in all five cases. The plate and screws were removed in all patients at an average of 16 months postoperatively. Average length of follow-up for the five patients is 4 years. Roentgenograms demonstrate that the clavicle has continued to grow normally. All five patients have pain-free full range of motion and are engaged in unrestricted activities.

Bone Plates

A patient with Werner's syndrome and osteosarcoma presenting as scleroderma.

Werner's syndrome (WS) is often mistaken for scleroderma. We describe a patient with WS who presented with an enlarging, painful mass of the right knee that proved to be a juxtaarticular osteosarcoma of the distal femur. Recognition of WS and prompt investigation of any painful, enlarging masses to exclude sarcomatous degeneration will benefit these patients.

Bone Neoplasms

Evaluation of the accuracy of the home ovulation detection kit, Clearplan, at predicting ovulation.

A home ovulation testing kit, Clearplan, that detects the urinary luteinizing hormone (LH) surge was compared with basal body temperature (BBT) charts and cervical scoring as a method of ovulation prediction in 54 consecutive patients. The accuracy of all these methods was evaluated using daily serum LH measurements. Clearplan was shown to be significantly more accurate at timing ovulation than were BBT charts (P less than 0.0001) and cervical scoring (P less than 0.025). In 82%-88% of cases the kit predicted ovulation within one day and in 89%-96% of cases within two days of the serum LH surge. The kits were found to be easy to use and their potential place in clinical practice is discussed; home ovulation testing may ultimately replace serum LH assays as the method of choice in timing ovulation.

Body Temperature

Bacteria-lectin interactions in phytohemagglutinin-induced bacterial overgrowth of the small intestine.

The mechanism of phytohemagglutinin-induced bacterial overgrowth of the small bowel in the rat was studied. Interaction of the lectin with bacterial isolates selected at random from those that comprised the major population of the overgrowth was determined. In both bacterial agglutination assays and glycocalyx stabilization, no specific association between lectin and bacteria was seen. In three independent binding assays phytohemagglutinin was not found to increase bacterial adherence to washed intestinal mucosa. Phytohemagglutinin would not appear to act, therefore, as a direct ligand to mediate bacterial adherence or to modify the mucosal surface to increase bacterial adherence.

Agglutination Tests

Spontaneous osteonecrosis of the tarsal navicular in adults: imaging findings.

We encountered five otherwise healthy adults with alterations of the tarsal navicular bone compatible with spontaneous osteonecrosis. Four women had bilateral involvement and one man had unilateral involvement. The patients were 23-71 years old. The disorder was initially described by Mueller and Weiss and should not be confused with Koehler disease (osteochondrosis of the tarsal navicular in children). This group of patients was compared with five other patients (29-74 years old) with similar radiographic and clinical changes in whom an underlying disease (rheumatoid arthritis, renal failure, trauma, and lupus erythematosus) associated with osteonecrosis was known. Routine radiography in both groups defined characteristic abnormalities of the navicular bone (decreased size, a comma-shaped configuration, increased radiodensity, fragmentation, and medial or medial and dorsal osseous protrusion). MR in three patients confirmed alterations consistent with osteonecrosis. Three of the patients without underlying disease had bilateral involvement on plain films, with flat feet and hindfoot valgus deformity, leading to local pain and deformity. In a fourth patient, bilateral distribution was documented by MR as marrow alterations. Although no certain pathogenic explanation for spontaneous osteonecrosis of the tarsal navicular is known, trauma and chronic stress changes caused by physiologic pressure on the medial longitudinal arch in hindfoot valgus and increased tension forces of the plantar aponeurosis during weight-bearing (in pes planus) may be important. Discrimination of primary from secondary osteonecrosis of the tarsal navicular bone is not possible by radiologic means alone, although bilateral distribution, particularly in women, favors the diagnosis of spontaneous disease.

Adult

Septic arthritis.

Infectious arthritis is a commonly encountered clinical problem which may result from articular contamination by a wide variety of organisms. Involvement of an articulation may occur by one of four mechanisms: hematogenous spread, spread from a contiguous source of infection, direct implantation, or postoperative contamination. Distribution is typically monoarticular with a swollen, erythematous, and painful joint. The radiographic differential diagnosis includes limited rheumatoid arthritis, gout, synovial osteochondromatosis, and pigmented villonodular synovitis. In order to prevent complications, including growth disturbances, articular destruction with ankylosis, osteomyelitis, or soft tissue extension, early diagnostic arthrocentesis is important. Radiographic abnormalities, which include soft tissue swelling, joint space loss, periarticular osteopenia, and central or marginal osseous erosions, may be delayed following clinical onset of infection. Advanced imaging techniques such as scintigraphy, CT, or MRI may allow accurate diagnosis of the infectious process at an earlier stage.

Arthritis, Infectious