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Biomedical subjects

J Newman

Publications and source records attributed to J Newman.

At least 19 recordsLinked to original sources

Crystallization and preliminary X-ray analysis of three serotypes of foot-and-mouth disease virus.

Foot-and-mouth disease viruses from serotypes O, A and C have been crystallized. The particular strains studied include O1K, A10(61), A22 Iraq 24/64, A24 Cruzeiro and C-S8c1. In addition, crystals have been grown of G67, a monoclonal antibody neutralization escape mutant derived from O1K, and of virus R100, recovered after the establishment of a persistent infection in baby hamster kidney cells with C-S8c1. Empty particles, capsids which lack the RNA genome, have also been crystallized for subtypes A22 Iraq 24/64 and A10(61). In almost all cases, crystals suitable for high resolution structure determination were obtained from (NH4)2SO4 or mixtures of polyethylene glycol and NH4Cl.

Aphthovirus

The ultrastructure of oesophageal carcinomas: multidirectional differentiation. A transmission electron microscopic study of 43 cases.

Forty-three oesophageal carcinomas, comprising 15 squamous cell carcinomas, 22 adenocarcinomas, 5 small cell carcinomas, and 1 adenosquamous carcinoma, were examined by transmission electron microscopy. The ultrastructural features of each tumour type are detailed. Multi-directional differentiation (heterogeneity) was observed in 11 cases: 5 squamous cell carcinomas with focal glandular features; 4 adenocarcinomas with focal squamous features; and 2 small cell carcinomas, one with glandular and the other with squamous features. Abnormal distributions of desmosomes in squamous cell carcinomas and of polarity of tumour cells in adenocarcinomas are described.

Adenocarcinoma

Production and functional characterization of a recombinant fragment of von Willebrand factor (vWF): an antagonist to platelet receptor GP Ib.

We expressed a recombinant peptide fragment (Ser445-Val733) of human von Willebrand factor (vWF), containing the binding domain for the platelet receptor of GP Ib, in E. coli. This 33 kD peptide blocks binding of the intact vWF molecule to GP Ib in the presence of modulators. Thus, it offers potential as an antithrombotic agent. High level expression was achieved in a plasmid construct driven by the bacteriophage T7 promoter. The peptide was solubilized from inclusion bodies in strong chaotrope, then reduced and alkylated. Following purification, formulation at pH 3.5, and lyophilization, the reconstituted experimental product (RG 12986) exists as an equilibrium of monomer and dimer species. When formulated above pH 5.0, soluble aggregates are formed; these solutions have less bioactivity than RG 12986. Interestingly, the non-aggregated state of RG 12986 remains conserved following dilution and incubation with platelet-poor plasma. The overall purification/low pH formulation strategies may be applicable to other E. coli recombinant proteins having a tendency to aggregate following removal of chaotrope near physiologic pH when in a concentrated format.

Cloning, Molecular

Effects of chemotherapy on ultrastructure of oesophageal adenocarcinoma.

AIMS: To compare and contrast the ultrastructural appearance of resected oesophageal adenocarcinomas treated with preoperative chemotherapy with that of non-treated resected controls; and to determine the usefulness of this method in the assessment of the effectiveness of the chemotherapeutic regimen. METHODS: Ten resected oesophageal adenocarcinomas treated with preoperative chemotherapy--mitomycin-C, ifosfamide, and cisplatin (MIC)--were examined by transmission electron microscopy and their appearance compared with that of 13 concurrent untreated resected oesophageal adenocarcinomas. RESULTS: The treated adenocarcinomas showed cytotoxic damage although complete tumour eradication was not achieved. In all 10 treated cases a variable proportion of the neoplastic cells showed unusual degenerative and necrotic changes not seen in untreated cases. In the most affected carcinomas the stroma contained increased numbers of inflammatory cells. CONCLUSIONS: This ultrastructural method is useful for the assessment of the in vivo effect of MIC.

Adenocarcinoma

Structural and compositional changes associated with chlorine inactivation of polioviruses.

Chlorine inactivation of polioviruses resulted in the loss of viral ribonucleic acid, converting the viruses from 156S particles to 80S particles. However, it was found that virus inactivation occurred before the ribonucleic acid was released from the virions. Extraction of ribonucleic acid from partially inactivated virus suspensions indicated that chlorine inactivation was due to degradation of the ribonucleic acid before release and that ribonucleic acid loss was a secondary event. The empty 80S capsids had the same isoelectric point and ability to attach to host cells as infective virions. Thus, no major capsid conformational changes occurred during chlorine inactivation.

Capsid

Hormone replacement therapy in the menopause: a suitable animal model.

Female CBA mice, aged 11 months, were treated cyclically with oral ethynyl oestradiol or oestrone sulphate for 3 months. The ovaries of all animals appeared to be atrophied. Target tissues throughout the genital tract showed a response to both oestrogens. Electron microscopy of both the endometrium and the urothelium demonstrated morphological changes characteristic of increased cellular metabolic activity in the treated mice. Endometrial hyperplasia developed in both treatment groups but more pronounced epithelial changes occurred with oestrone sulphate. This hyperplasia was accompanied by a doubling in the number of uterine cytoplasmic oestrogen receptors. A 50% fall in serum levels of luteinizing hormone in the treated mice revealed that the hypothalamic-pituitary system was still intact. Both oestrogens improved skeletal balance by changes in cortical-endosteal bone remodelling. The results suggest that the CBA strain of mouse is a suitable model for the study of the human climacteric and its response to hormone replacement therapy.

Animals

Circulating thrombin time anticoagulant in a procainamide-induced syndrome.

Circulating anticoagulants are unusual in drug-induced syndromes. We evaluated the prolonged thrombin time of plasma from a patient with a procainamide-induced syndrome. This defect was shown to be due to a circulating anticoagulant that was not of fibrin or fibrinogen origin and that prolonged thrombin and reptilase clotting times of plasma. Subclinical doses of heparin sodium induced hemorrhagic manifestations in this patient. Following cessation of heparin therapy, the circulating anticoagulant persisted but the bleeding tendency abated. All clinical and laboratory manifestations of this syndrome abated gradually following cessation of procainamide therapy.

Aged

Injury to the brachial plexus as a result of diagnostic arteriography.

Six cases of brachial plexus injury within the brachial sheath are reported following axillary-brachial arteriography. Direct compression resulted from leakage of arterial blood into the space formed by the fascial sheath. In one, hemorrhage occurred several days after arteriotomy. Early decompression and arteriorrhaphy resulted in restoration of normal function. Permanent nerve damage resulted when surgical decompression was delayed.

Aged

Treatment of hepatic metastases with a combination of hepatic artery infusion chemotherapy and external radiotherapy.

Systemic chemotherapy has given good results when compared with that of patients who received no chemotherapy. When resection was performed, the results are slightly better. The group of patients who underwent combined therapy, using infusion chemotherapy, radiation and systemic chemotherapy, had the best results. It appears that infusion chemotherapy and radiotherapy can improve the palliation available for patients with metastases in the liver from carcinoma of the colon and rectum and warrants further investigation.

Adult

Giving and getting surgery in Utah: an urban-rural comparison.

Using the Blue Cross/Blue Shield and Medicare records for 1 year in Utah, we examined the pattern of surgical performance for 15 selected procedures. Only 60% of those identifying themselves as general surgeons had their specialty boards. General practitioners performed 24% of the procedures. Urban general practitioners performed proportionately more surgery than did their rural counterparts. There was no clear pattern of difference in fees or length of stay by specialty or board certification status. For most procedures studied, at least a third of the rural patients had their operations in urban hospitals. In only 3% of the cases did an urban physician operate in a rural hospital. The pattern of surgery for rural and urban residents was strikingly similar.

Certification