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Biomedical subjects

B Gibson

Publications and source records attributed to B Gibson.

At least 73 records · Page 4Linked to original sources

Type VII collagen antibody LH 7.2 identifies basement membrane characteristics of thin malignant melanomas.

A monoclonal antibody (LH 7.2) to the carboxy terminal of type VII collagen has been used in an indirect immunoperoxidase method on frozen sections of biopsies of benign compound and intradermal cellular naevi, dysplastic naevi, and malignant melanomas, to label the epidermal basement membrane. Benign intradermal naevi had an intact membrane with the dermal naevus cell component lying beneath it. Compound naevi showed proliferating junctional nests of naevus cells pushing through the membrane towards the dermis beneath. In contrast, dysplastic naevi and melanomas showed a progressive displacement of the membrane downwards. Thin lesions were confined above the membrane. With increasing tumour thickness, discontinuities in the membrane were seen and foci of invasive growth through the line of the membrane were identified. These studies suggest that the good prognosis of thin melanomas is associated with confinement of the tumour within an expanded epidermis above the basement membrane.

Antibodies, Monoclonal↗

A comparison of antibodies to type VII and type IV collagen laminin and amnion as epidermal basement membrane markers.

We have compared four monoclonal antibodies which label basement membrane components using an indirect immunoperoxidase method in frozen sections of skin biopsies. The antibodies LH 7.2 and GB3 showed expression limited to epidermal and adnexal basement membrane. Antibodies to laminin and type IV collagen also decorated dermal blood vessels and stromal components. The antibodies LH 7.2 and GB3 are more suitable for labelling epidermal basement membrane in the study of cutaneous lesions.

Antibodies, Monoclonal↗

Neonatal haemostasis.

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Blood Platelet Disorders↗

Autologous bone marrow transplantation with monoclonal antibody purged marrow for high risk acute lymphoblastic leukemia.

Fifty-four patients with acute lymphoblastic leukemia (ALL: 1 relapse, 21 high risk first complete remission (CR 1), 29 second CR (CR 2), and 3 third CR (CR 3) were treated by autologous bone marrow transplantation at three centers. Before storage, the marrows were purged ex vivo with appropriate MAbs RFAL3 (CD10), SB4 (CD19), and RFT2 (CD7), with rabbit serum as the source of complement. All patients received total body irradiation either 750 cGy (middose 15 cGy/min) as a single fraction or 6 x 200 cGy over 3 days (midline dose 16 cGy/min) with lung shielding from 1,100 cGy. The patients who received 750 cGy also received cyclophosphamide or the same drug combined with ara-C or prednisone, teniposide, vincristine, ara-C, and dauno-rubicin. Patients receiving 200 cGy x 6 also received either cyclophosphamide, melphalan, or ara-C and cyclophosphamide. Three patients died of post transplantation complications (interstitial pneumonia, hepatitis B liver necrosis, or encephalitis). This gives a procedure related mortality of 5%. Nonfatal complications were 10 cases of septicemia, 4 interstitial pneumonia, 2 interstitial nephritis, 1 veno-occlusive disease (VOD), and 1 case of hemolytic uremic syndrome. The patient autografted in relapse died of relapse within 2 months. In CR 1 6 or 21 patients have had a relapse, and the actuarial leukemia free survival from CR is 65% (median follow-up 16 months). In CR 2-3 18 of 32 patients have relapsed, and the actuarial leukemia free survival is 31% (median follow-up 18.5 months) from CR. Twelve patients have achieved an inversion, (i.e., present CR longer than previous CR), with a further seven with the potential to achieve inversion. We conclude that ABMT in high risk ALL has a low procedure related mortality (5%), and there are few other complications. The in vitro purging with MAbs had no adverse effect on bone marrow reconstitution, but this study was not designed to demonstrate its antileukemic efficacy. The actuarial leukemia free survival time in the present study for patients with high risk CR 1 and the inversions in CF 2-3 are promising and indicate a potential beneficial effect of ABMT.

Antibodies, Monoclonal↗

Prevention of graft-versus-host disease by ex vivo T cell depletion: reduction in graft failure with augmented total body irradiation.

Graft-versus-host disease prevention was attempted in 35 consecutive patients with hematological malignancy who received bone marrow from an HLA match sibling donor who was depleted of T cells ex vivo. Five of the first 8 patients who received cyclophosphamide 60 mg/kg on 2 consecutive days followed by fractionated total body irradiation (TBI) (6 x 2 Gy) had graft failure. The subsequent 27 patients had received an extra fraction of TBI (7 x 2 Gy), and only one failed to have stable engraftment. There were no differences in nucleated cell dose, granulocyte-macrophage colony-forming units, or T cell numbers given to the two groups. Neutrophil but not platelet regeneration of those patients who successfully grafted was slower than in a group of historical controls receiving unmanipulated marrow. Significant graft-versus-host disease was prevented with no increase in relapse rate. We suggest that engraftment can be reliably achieved by augmenting the TBI conditioning in recipients of T cell-depleted matched allogeneic bone marrow.

Adolescent↗

The immunochemistry of neisserial LOS.

The outer membrane glycolipids of Neisseria lack long polysaccharides and are properly termed lipooligosaccharides (LOS). A Neisseria strain makes from two to six LOS of Mr 3150-7100. Different species commonly make LOS of identical Mr and epitope content. Oligosaccharide (OS) differences account for physical heterogeneity. OS consist of a conserved triantenary basal oligosaccharide, two linear segments of (n) hexose residues that determine OS mass, and terminal sequences similar to those of glycosphyngolipids. Epitope expression is linked to physical heterogeneity and conditioned by the molecular environment of the outer membrane. Serotype epitopes are expressed on Mr-restricted LOS. LOS regulate complement activation onto the bacterial surface and, hence, immune lysis.

Antigens, Bacterial↗

Scottish validation study of Cancer Registration data childhood leukaemia 1968-1981. Bone marrow review--II.

Following a review of central leukaemia registration data for Scottish children 1968-1981 a retrospective assessment of leukaemia type was made by inspection of bone marrow slides. Only 57% of slides were still available and in 72% of these the review panel confirmed the initial diagnosis of leukaemia and its type. In eight cases the panel disagreed with the diagnosis or the type of leukaemia designated. Central slide review at diagnosis in childhood leukaemia is essential if subsequent epidemiological studies are to be meaningful.

Adolescent↗

Late effects of total body irradiation.

Late effects of chemo-radiotherapy conditioning before bone marrow transplantation (BMT) are being increasingly recognised in long-term survivors, particularly children. They can be divided into two categories: those affecting hormonal status and those affecting specific organ function. All women treated develop ovarian failure with low levels of beta-oestradiol and raised values of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In males, raised FSH and LH values are found with normal testosterone levels but most patients have azoospermia. In children, puberty is usually but not invariably delayed by treatment but can be induced by appropriate hormone replacement. Compensated hypothyroidism was found in 6/30 children. Growth hormone secretion may be impaired especially if previous cranial irradiation has been given. In children, a reduction in sitting height has been observed. Cataract has occurred in 20% of children between 3 and 6 years after treatment. Two second tumours have been observed. No other major organ toxicities have been encountered.

Adult↗

Effect of spinal irradiation on growth.

Standing height, sitting height, and leg length were measured in 79 patients (aged 16-30 years), who had been given craniospinal irradiation (n = 37) or cranial irradiation (n = 42) in childhood for a brain tumour and had completed their growth. Their measurements were compared with established standards for sitting height and leg length in British children (aged 16-18 years). To examine the effects of spinal irradiation on spinal growth independent of growth hormone deficiency we analysed the leg length (LL) minus sitting height (SH) standard deviation score (SDS) and used the cranial group as controls. There was an overall significant difference between the median craniospinal LL-SH SDS (1.98) and the median cranial LL-SH SDS (0.545). Within the craniospinal group there was a significant correlation with age at treatment, but there was no such correlation for the cranial group. After splitting age at treatment into three groups (0 less than 5, 5 less than 10, and 10-15 years) there was a significant difference between the LL-SH SDS of the craniospinal and cranial groups for each of the age ranges. In conclusion, spinal irradiation has a profound effect on spinal growth and the younger the child is when given irradiation the greater the subsequent skeletal disproportion. Our most conservative figures indicate that the eventual loss in height is 9 cm when irradiation is given at 1 year, 7 cm when given at 5 years, and 5.5 cm when given at 10 years.

Adolescent↗

Airway obstruction in LeFort fractures.

Airway obstruction associated with fractures of the midfacial skeleton can be life-threatening if not recognized promptly and treated appropriately. One hundred seventeen patients with LeFort fractures were treated between 1978 and 1984. Of the 117 patients, 21 had a LeFort I fracture, 46 had a LeFort II fracture, 14 had a LeFort III fracture, and 36 had various combinations of the three types of LeFort fractures. Thirty-one patients (26.5%) presented with airway obstruction, decreased respiration, or both, requiring either tracheotomy or endotracheal intubation. Of the 31 patients undergoing emergent tracheotomy or endotracheal intubation, 26 (83.9%) had loss of consciousness relating to their injuries. Thirty-nine (33.3%) additional patients had an elective tracheotomy either at the time of surgical repair of their fractures or for prolonged endotracheal intubation. Age and sex of the patients played no role in the incidence of airway complications in patients with LeFort fractures. Patients with LeFort III fractures and those with associated injuries such as mandible fracture, laryngeal and pharyngeal injury, and chest or closed head injury are at greater risk for requiring emergent control of the airway.

Adolescent↗

A prospective study of the histological changes in the skin in patients receiving bone marrow transplants.

Fourteen patients who received a bone marrow transplant (BMT) as treatment for leukaemia were included in a prospective study of the histological changes in the skin. The aim of this study was to improve the early diagnosis of graft-versus-host disease (GVHD). It was found that the clinically 'normal' pre-transplant skin was in some cases histologically abnormal on H & E examination in patients who were on regular maintenance cytotoxic chemotherapy. These changes were similar to some of the features of GVHD. Immunocytochemistry, although not specific, was found to be helpful in the diagnosis of some cases of GVHD. Suggestive features included a reduction in the numbers of Langerhans cells, an increase in the number of suppressor (OKT8+) cells in the dermal infiltrate and the presence of Ia positivity of the keratinocytes in the epidermis.

Adult↗