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Biomedical subjects

S M Ford

Publications and source records attributed to S M Ford.

35 records · Page 2Linked to original sources

Localization and imaging with radioiodine-labeled monoclonal antibodies in a xenogeneic tumor model for human B-cell lymphoma.

Two MoAbs directed towards human B-cell malignancies have been studied in a preclinical animal model to evaluate their potential for in vivo imaging and therapy of B-cell lymphomas. Anti-B1 reacts with virtually all immunoglobulin-bearing malignancies and non-T acute lymphoblastic leukemia. Anti-J5 reacts with the common acute lymphoblastic leukemia antigen found on non-T acute lymphoblastic leukemia and follicular lymphomas. Anti-T1 which recognizes the CD5 antigen on most T-cell leukemias and lymphomas was used as a control antibody. These monoclonal antibodies were radiolabeled with 125I or 131I by the ICl method. Namalwa (B-cell) and MOLT-4 (T-cell) tumors were grown s.c. in irradiated nude mice. The highest tissue concentration of 125I-labeled anti-J5 in Namalwa-bearing mice was in blood and tumor. The tumor/blood ratio ranged from 0.7-1.2, with the highest ratio 4 days after injection. Pharmacokinetic analysis indicated that the t1/2 beta of anti-J5 from blood and other tissues ranged from 40-50 h, while the t1/2 beta for tumor averaged 65 h. The area under the curve of tumor was 2- to 5-fold higher than the area under the curve of liver, kidney, skin, and muscle. The peak tissue levels of 125I-labeled anti-B1 in Namalwa-bearing mice were again in blood and tumor and 6 days following injection more than 5-fold greater activity was found in tumor compared to normal tissues other than blood. The tumor/blood ratio was 1.2 and 0.7 at 4 and 6 days after injection. 125I-labeled anti-B1 showed minimal uptake in antigen-negative MOLT-4 tumors and 125I-labeled anti-T1 showed little uptake in Namalwa tumors. Scintigraphic images were obtained following the injection of 131I-labeled anti-J5 and anti-B1 in nude mice bearing Namalwa tumors. These results indicate that radiolabeled anti-J5 and anti-B1 show promise as diagnostic and possibly therapeutic agents for human B-cell lymphoma, although there may be a limitation to clinical utility due to cross-reactivity with some normal cells.

Animals↗

Role of desacetylation in the detoxification of cephalothin in renal cells in culture.

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.

Acetylation↗

Comment on the evolution of claw-like nails in callitrichids (marmosets/tamarins).

A recently proposed scenario for the evolution of a unified complex of exudativory, vertical clinging, and claw-like nails in callitrichids is examined. Consideration of behaviors and morphologies exhibited by Callimico goeldii leads to a decoupling of this "complex," with the early occurrence of claws and vertical clinging in the callitrichid lineage and only later, in some descendents, the development of exudativory and possible related behaviors.

Animals↗

Subfossil platyrrhine tibia (primates: Callitrichidae) from Hispaniola: a possible further example of island gigantism.

A distal right tibia described by G.S. Miller in 1929 (Smithsonian Misc. Coll. 82[5]:1-16) on the island of Hispaniola is shown to be that of a heretofore unknown extinct platyrrhine and is informally referred to as Ceboid M. Its affinities appear to be with the dwarfed callitrichids, especially Saguinus. It is suggested that Ceboid M represents yet another case of gigantism in the Antilles, in response to a lack of both competitors and predators. A reconsideration of the affinities of Xenothrix mcgregori from Jamaica is suggested.

Animals↗

Iris atrophy in sickle cell disease.

Iris atrophy, of unknown origin and believed to be secondary to the vaso-occlusive process of sickle cell disease, has been observed in 25 eyes of 22 patients (two SS disease, 20 SC disease). The crude prevalence was highest in males with SC disease, in whom 14.7% of patients were affected. Iris atrophy was closely associated with proliferative sickle retinopathy in the same eye. Analysis of haematological indices failed to reveal any significant differences between patients with and without iris atrophy. The characteristics and distribution of iris atrophy are described as well as the histopathology in one 68-year-old male patient with SS disease.

Adolescent↗

Transient vasopressin-resistant diabetes insipidus of pregnancy.

A case of transient vasopressin-resistant diabetes insipidus is reported, which developed during the seventh month of pregnancy and remitted postpartum. The patient was resistant to large doses of deamino-D-arginine vasopressin as well as to aqueous pitressin. She was treated with hydrochlorothiazide. Evidence that prostaglandins may play a role in this syndrome is discussed.

Adult↗

Transient vasopressin-resistant diabetes insipidus of pregnancy.

A case of transient vasopressin-resistant diabetes insipidus is reported which developed during the seventh gestational month. Polyuria reached 4-6 L daily and urine osmolality remained dilute despite 21 hours of water deprivation followed by 5 U intramuscularly of aqueous pitressin, as well as four days of treatment with intranasal DDAVP (0.1-0.5 mL every 12 hours). Urinary excretion of prostaglandin E2, 1384 ng/24 hours, was fourfold that in nongravid subjects and a plasma arginine vasopressin level of 12 pg/mL was recorded. Indomethacin had no effect on urine osmolality but decreased urine volume markedly. Hydrochlorothiazide, also, decreased urine volumes, and this drug was used to manage the patient until delivery. The syndrome remitted in the puerperium, the patient concentrating her urine to 938 mOsm/kg when tested several months postpartum.

Adult↗

Macular vasculature, visual acuity, and irreversibly sickled cells in homozygous sickle cell disease.

Observations of visual acuity and the conjunctival, macular, and perimacular vascularity have been assessed in patients with homozygous sickle cell (SS) disease. There were 17 matched pairs, each consisting of one patient with a high count (greater than or equal to 15%) and one with a low count (less than or equal to 5%) of irreversibly sickled cells (ISCs). The macular vascular bed was assessed by measurements of the foveal avascular zone (FAZ), perimacular avascular zones, and counts of perimacular vascular abnormalities (perimacular counts). Small foveal avascular zones and high perimacular counts were commoner in younger than older patients and there was a significant inverse correlation between size of the FAZ and the perimacular count. These observations were compatible with the hypothesis that perimacular vessel anomalies represent the early vaso-occlusive phase which progresses to ischaemia and the formation and enlargement of avascular areas. Visual acuity was assessed by Snellen's test type and by measuring contrast sensitivity. There was no obvious relationship between acuity measured by the 2 methods and no relationship between acuity and observations of macular vascularity. High ISC counts were significantly related to abnormalities of the conjunctival vasculature, but no relationship was noted with abnormalities of the macular vasculature or with visual acuity.

Adult↗

Choroidal neovascularisation induced by photocoagulation in sickle cell disease.

Choroidal neovascularisation occurred in 35 out of 57 (61%) patients during a trial of xenon are photocoagulation in proliferative sickle retinopathy. Nineteen patients manifested abnormal vessel systems in the plane of the retina which tended to be benign, not enlarging, and without complications (choroidoretinal neovascularisation). In 16 patients the abnormal vessel systems grew into the vitreous, tended to increase in size, and to be associated with vitreous haemorrhage and retinal traction (choroidovitreal neovascularisation). Both forms of neovascularisation were significantly more common at younger ages. Treatment was generally unsatisfactory, frequently resulting in further enlargement of the lesions. Although the natural history of choroidal neovascularisation and its ultimate effect on visual function remains to be recorded, these lesions constitute a common and potentially serious complication of xenon are photocoagulation in proliferative sickle retinopathy as currently performed.

Adolescent↗