Biomedical subjects
W Smith
Publications and source records attributed to W Smith.
Inhibition of gastric H+, K+ adenosine triphosphatase (ATPase) by substituted naphthylalkylimidazoles.
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Development of a dual label fluorescence technique that can be utilized to elucidate the mechanism of action of monoclonal antibody-drug conjugates.
A method is described that allows the simultaneous visualization and relative assessment of both the antibody and drug components of monoclonal antibody-drug conjugates at the target cell membrane. The antibody is detected by a fluorescein-conjugated anti-mouse immunoglobulin serum while the drug is visualized by rhodamine avidin or phycoerythrin-streptavidin binding to a biotinylated anti-Vinca alkaloid monoclonal antibody. This technique was effective in demonstrating the cell surface localization of a monoclonal antibody-Vinca alkaloid conjugate to human lung adenocarcinoma cells grown in vitro and was also used to demonstrate targeting of the conjugate in vivo to the membranes of these same tumor cells grown as a nude mouse xenograft. This method was also utilized to help elucidate the mechanism of action of monoclonal antibody-drug conjugates.
Tumour therapy with Vinca alkaloids targeted by a hybrid-hybrid monoclonal antibody recognising both CEA and Vinca alkaloids.
The functional properties of a hybrid-hybrid monoclonal antibody (MAb) recognising both CEA and Vinca alkaloids have been explored in vivo in nude mice xenografted with MAWI, a human colorectal tumour. The hybrid-hybrid MAb localises specifically onto CEA-expressing tumour tissue and, furthermore, is able to target Vinca alkaloids to tumour. Under the influence of the hybrid-hybrid MAb a profound change in the bio-distribution patterns of the Vinca alkaloids is observed. Therapeutic data produced in this in vivo model indicates that treatment with Vinca alkaloids in conjunction with hybrid-hybrid MAb is significantly more effective in suppressing tumour growth of established tumour xenografts than the Vincas when given as free drug.
Use of the barium enema in the diagnosis of necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is associated with considerable morbidity and mortality in infants. The diagnosis relies heavily upon radiographic and clinical features. Failure to accurately diagnose NEC is associated with a risk of complications and death, however overdiagnosis also causes both morbidity and mortality as well as excessive medical costs. This report documents the use of barium enema to evaluate suspected clinical or radiographic NEC in 31 premature infants with ambiguous clinical and radiographic signs. The enema was normal in 26 infants and no treatment for NEC was given. Only one of these infants developed signs of NEC subsequent to the examination. Five infants had radiographic evidence of colitis including small ulcerations, spasm, intramural extravasation of barium and mucosal irregularity. Two of the five positive cases are pathologically documented. The barium enema can represent a significant improvement in the specificity of the diagnosis of NEC. Its greatest value is in the exclusion of NEC in ambiguous cases.
Eccrine and squamous differentiation in Merkel cell carcinoma. An immunohistochemical study.
Of the 42 Merkel cell carcinomas that we studied, two showed numerous tubular structures within sheets and nests of small cells. The small cells stained for both neuron-specific enolase and keratin. The keratin decorated a dot-like paranuclear structure. The ducts stained positively for carcinoembryonic antigen (CEA) and CF-1 (cystic fibrosis-1, a monoclonal antibody that only stains eccrine duct and acrosyringium). Electron microscopy performed on one case showed cytoplasmic dense-core neurosecretory granules and intercellular lumina lined by cells containing microvilli. These ultrastructural and immunohistochemical features support the concept of eccrine differentiation in these tumors. A third case contained foci of typical keratinizing squamous cell carcinoma admixed with sheets of small cells. The immunohistochemical and ultrastructural characteristics of this tumor were essentially similar to those of a conventional Merkel cell carcinoma. Our findings suggest that Merkel cell carcinomas, similar to neuroendocrine tumors from other anatomic sites arise from a primitive totipotential stem cell that has the capacity to differentiate along different cell lines.
The use of a GnRH analogue for ovulation induction for tubal gamete transfer.
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Hippel-Lindau disease: MR imaging.
Hippel-Lindau disease is an auto-somal-dominant disorder characterized by tumors arising from the central nervous system and abdominal viscera. Because of its progressive nature, frequent multisystem radiologic evaluation of affected persons and family members at risk is desirable for early detection and treatment. During a 2-year study, magnetic resonance (MR) imaging of the head, spine, and abdomen was used for screening and follow-up in 26 members of nine families with the disease. In addition to 13 previously diagnosed cases, five cases were newly diagnosed during the study. Lesions causing significant morbidity and mortality--such as cerebellar and spinal cord hemangioblastoma, renal cell carcinoma, and pheochromocytoma--were correctly depicted with MR imaging, sometimes before symptoms had developed and before the lesions could be seen with other imaging modalities. Central nervous system abnormalities were most clearly shown, but MR imaging also adequately demonstrated abdominal visceral abnormalities. It is therefore highly useful in the diagnosis and follow-up of Hippel-Lindau disease.
Oligosymptomatic hypocalcaemia in a patient with impaired parathyroid hormone activity.
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Giant cell arteritis of the tongue presenting as macroglossia.
While the tongue has been noted to be involved in giant cell arteritis, there are no recorded instances in which the disease has been confined to the tongue. We describe a patient who presented with macroglossia and was found to have a necrotizing vasculitis with giant cells on lingual biopsy. No other evidence for systemic vasculitis was detected. This is the first case report of an isolated vasculitis of the tongue.
Reduction of ectopic pregnancy by ultrasound methods.
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Reduction of ectopic pregnancy by injection under ultrasound control.
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Multiple congenital anomalies syndrome with myopathy in chromosome 16 abnormality.
An abnormality of chromosome 16 in an eight year-old male was associated with a multiple congenital anomalies syndrome characterized by myopathy, cataracts, blepharophimosis, microcephaly, failure to grow, profound mental retardation, moderate sensorineural hearing loss, grand mal seizures, bilateral inguinal hernia, and thoracolumbar kyphoscoliosis. Magnetic resonance imaging of the head demonstrated absence of the corpus callosum and extensive loss of brain parenchyma in the occipital regions. Chromosome analysis from peripheral blood of the patient showed a recombinant chromosome 16 [46, XY, rec (16), dup (p13.1----p13.3) del (q22----q24)]. The mother had a pericentric inversion of chromosome 16 [46, XX, inv(16) (p13.1;q22)]. Independent recombinant DNA studies have shown that the breakpoints of these chromosomal rearrangements flank the alpha-globin gene cluster locus.
Intracardiac tumor (rhabdomyoma) diagnosed by in utero ultrasound: a case report.
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Construction and characterisation of a hybrid-hybrid monoclonal antibody recognising both carcinoembryonic antigen (CEA) and vinca alkaloids.
Recent developments of hybridoma technology have allowed us to prepare a bispecific monoclonal antibody recognising both the tumour-associated antigen carcinoembryonic antigen (CEA) and the cytostatic vinca alkaloids. The yields of the hybrid-hybrid 28.19.8 monoclonal after affinity chromatography purification are close to 50% of the total Ig produced. The hybrid-hybrid has a molecular weight ca. 150,000 daltons. The heavy chains of the hybrid-hybrid are a gamma 1 heavy chain from the parental anti-CEA monoclonal and a gamma 2a heavy chain from the anti-vinca alkaloid donor lymphocytes.
Specific in vitro and in vivo drug localisation to tumour cells using a hybrid-hybrid monoclonal antibody recognising both carcinoembryonic antigen (CEA) and vinca alkaloids.
By using a bispecific monoclonal antibody recognising both carcinoembryonic antigen (CEA) and the cytostatic vinca alkaloid drugs we have been able to show specific tumour localisation of vinca alkaloids. In vitro studies with sections of human colorectal tumours have demonstrated that the hybrid-hybrid 28.19.8 monoclonal is able to specifically localise vindesine to cells expressing CEA. Furthermore, the hybrid-hybrid 28.19.8 localises in vivo preferentially to tumour tissues in nude mice bearing the MAWI human xenograft tumour. This tumour-bound hybrid-hybrid monoclonal antibody induces profound changes in the bio-distribution of vinca alkaloid drugs, targeting them specifically to tumour tissues.
Increased therapeutic effect of vinca alkaloids targeted to tumour by a hybrid-hybrid monoclonal antibody.
Unmodified vinblastine (VLB) targeted through one of the antigen combining sites of the hybrid-hybrid 28.19.8 monoclonal is potentially more effective in suppressing the growth of established MAWI tumour xenografts implanted on nude mice than free VLB in the absence of the targeting agent, presumably due to an increased local drug concentration. Our efficacy results in this study suggest that drug, specifically removed from the circulation by hybrid-hybrid antibody previously located to the tumour mass, can be made available in a pharmacologically active from. Histological analysis of the treated tumours revealed dramatic changes in the tumour organisation with only a few surviving tumour cells with altered morphology.