Biomedical subjects
Publications and source records attributed to A C Robinson.
We report two cases of cervical mycobacterium avium-intracellulare lymphadenitis in siblings which developed within one month of each other. There was no underlying immunodeficiency but the children lived in close proximity to a pigeon loft.
Two alleles of ftsA, a gene that encodes an essential cell division protein in Escherichia coli, have-been mapped at the nucleotide level. The mutations are located inside domains that are conserved in an ATP-binding protein family. The ftsA2 mutation lies in the adenine-binding domain, and the ftsA3 in the ribose-binding domain. The defect in ampicillin binding to PBP3 described for allele ftsA3 is allele-specific. This supports the hypothesis of the existence of different domains in FtsA having different functions.
Squamous carcinomas of the oro-pharynx are associated with a high incidence of distant metastases at post-mortem. A case of a massive distant metastasis from a squamous cell carcinoma of the tonsil is presented. This occurred despite excellent local control. The pathology and the possible management implications are discussed.
The murine immune response to baculovirus-produced human immunodeficiency virus type-1 (HIV-1)p24 was examined after injection by three different routes: subcutaneously (s.c.), intraperitoneally (i.p.) and intravenously (i.v.). Both antigen-specific T-cell proliferation and serum antibody were induced by i.p. injection. In contrast, s.c. and i.v. injection of antigen resulted in specific antibody generation alone. Lympho-proliferative responses seen after i.p. injection were confined to splenocytes, and were greater after a low dose of antigen than after a high dose. p24-specific proliferation was not detected in lymph node cells. CD4:CD8 ratios were normal in lymph nodes and spleen at all times, irrespective of the dose or route of administration. p24-specific serum IgG antibodies were detected in all animals after the second injection of antigen. After s.c. and i.v. administration of high doses of antigen, the median antibody titres continued to rise after a third injection, but plateaued in animals injected by the i.p. route. In contrast, low doses of antigen given i.p. increased the median titre during and after the course of four injections. A low antigen dose given s.c. resulted in a plateau of median titre between the third and fourth injections. In i.v.-injected animals the median titre decreased between the third and fourth injections. IgG1 p24-specific antibodies were detected in all immunized mice, whereas IgM antibodies were detectable only following i.p. injection of antigen.
Eight cases of attico-antral cholesteatoma were studied by transmission electron microscopy concentrating on the mechanisms involved in intercellular adhesion. Desmosomes were found in large numbers throughout the epidermis and were arranged in various orientations around the keratinocytes. Those desmosomes found in the stratum corneum were significantly less dense than those in deeper layers and were associated with a large number of intercellular spaces, which would reduce the cohesive strength of this layer. The tortuous basement membrane features numerous hemidesmosomes along its length. The findings of this study were compared with previous ultrastructural observations made on the pars flaccida and pars tensa of the tympanic membrane and external canal skin. This revealed that the morphological characteristics of cholesteatoma resemble pars flaccida and external canal skin rather than pars tensa. The implications of these findings are discussed.
Percutaneous nephrostomies (PCN) were performed in 25 patients with uterine cervical malignancy between November 1982 and December 1987 at the Christie Hospital and Holt Radium Institute. Group 1 consisted of eight patients with untreated disease; group 2 consisted of eight cases with recurrent tumour; and group 3 consisted of nine patients with obstructive uropathy related to previous treatment. Six patients in group 1 subsequently received radical radiotherapy, and two of them were alive and disease free (33%) ten months later. Further active treatment was only possible in two of the patients with recurrence and overall median survival was only 51 days. All patients in group 3 had normalization of their renal function post-nephrostomy and prior to definitive management of the obstruction. We conclude that the technique should be considered in patients who had no previous treatment and in patients with treatment-related complications. Its value in recurrent disease is limited.
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A case of oncocytoma of the larynx is presented. These lesions are rarely found in the larynx, and have been more commonly described in the salivary and thyroid glands. The histopathological diagnosis is often difficult and the light microscopy can be unreliable for oncocytic lesions. For a more accurate definition of these tumours, the use of histochemical stains together with electron microscopy are advocated. With adequate surgery, the prognosis is excellent, and tumours are unlikely to recur. This paper discusses the management of a patient with a benign oncocytoma of the true vocal cord, and presents a review of the world literature.
Four cases of otitis externa secondary to radiotherapy are described. This fairly common complication of irradiation to the head and neck, may impede a satisfactory completion of the therapy. Water precautions and regular otoscopic examination of the ears should be encouraged as prevention or early recognition of the condition is essential for the well being of the patient. The treatment of established otitis externa consists of frequent aural toilet and the application of weak antiseptic solutions. However, complete resolution will not occur until the cutaneous reaction has fully settled.
Strains of Azotobacter vinelandii which contain defined deletions within the nifD and nifK genes which encode, respectively, the alpha and beta subunits of the MoFe protein of nitrogenase were analyzed. When synthesized without its partner, the beta subunit accumulated as a soluble beta 4 tetramer. In contrast, when the alpha subunit was present without its partner, it accumulated primarily as an insoluble aggregate. The solubility of this protein was increased by the presence of a form of the beta subunit which contained a large internal deletion, such that the alpha subunit could participate in the assembly of small amounts of an alpha 2 beta 2 holoprotein. When synthesized alone, the beta subunit was remarkably stable, even when the protein contained a large internal deletion. The alpha subunit, however, was much more rapidly degraded than the beta subunit, both when it was synthesized alone in its native background and when it was synthesized with its beta subunit partner in a foreign background. Antibodies raised against purified alpha 2 beta 2 MoFe protein recognized epitopes only on the nondenatured beta subunit and not on the nondenatured alpha subunit. Our findings that all epitopes for the alpha2beta2 tetramer appeared to be on the beta subunit, that the beta subunit assembled into beta4 tetramers, and that the alpha subunit alone was very insoluble, combined with the previous finding that the Fe protein binds to the beta subunit (A. H. Willing, M. M. Georgiadis, D. C. Rees, and J. B. Howard, J. Biol. Chem. 264:8499-8503, 1989) all suggest that the beta subunit has a more surface location than the alpha subunit in the alpha2beta2 tetramer.
In the majority of individuals, impaction of cerumen in the external auditory canal does not occur, and it is only a fraction of the population who regularly need to consult their physician for aural toilet. In this study we looked at the clinical features associated with recurrent cerumen impaction in 20 individuals. This was complemented by an examination of the cerumen plugs taken from their ears and hydrated to analyze the morphology of the keratin sheets, which had been observed in a previous study to constitute over one-half of the volume of impacted cerumen. In a further eight patients with cerumen, impaction plugs of cerumen were removed and subjected to histological examination. We observed that excessively long sheets of undivided keratin could be isolated from the hydrated cerumen plugs and that these sheets of keratin morphologically resembled the superficial layers of the stratum corneum of normal human deep external auditory canal skin. Based on these observations, we propose that cerumen impaction is the result of a failure in the normal keratinocyte separation which occurs in the superficial external auditory canal.
Nitrogenase is composed of two component proteins, the iron protein (Fe protein) and the molybdenum-iron protein (MoFe protein). The Fe protein is a Mr 60,000 dimer of identical subunits with one bridging [4Fe-4S] center. It serves as a one-electron donor to the MoFe protein in a reaction that is coupled to MgATP hydrolysis. The MoFe protein is an alpha 2 beta 2 tetramer of Mr 220,000 which contains four [4Fe-4S] clusters and two iron-molybdenum cofactor (FeMo cofactor) centers. The exact structure of FeMo cofactor is not known, but it is believed to form the active site of the enzyme. Using specifically constructed deletion mutants of Azotobacter vinelandii, we have previously shown that the Fe protein, but not the MoFe protein, is required for FeMo cofactor biosynthesis (Robinson, A. C., Dean, D. R., and Burgess, B. K. (1987) J. Biol. Chem. 262, 14327-14332). During the partial purification of a FeMo cofactor-deficient form of the MoFe protein from one of these mutants (DJ54, delta nifH), we have discovered that, in addition to biosynthesis, the Fe protein-MgATP complex is involved in FeMo cofactor insertion into the MoFe protein. This insertion process is also sensitive to a number of other parameters (e.g. salt, pH, temperature, protein concentration). Based on our experimental data, we present a model for how this insertion reaction might take place, in which the Fe protein-MgATP complex binds the FeMo cofactor-deficient form of the MoFe protein and stabilizes a specific conformation of the MoFe protein that has the FeMo cofactor binding site exposed and available for coordination by preformed FeMo cofactor.
We report a patient with mycosis fungoides of 20 years standing who developed mixed cellularity Hodgkin's disease. Full investigation, including biopsy, is essential when recurrent mycosis fungoides is suspected to outrule a second lymphoma as the results may affect management. Case History A Caucasian male presented aged 41 years with an eczematous rash affecting his trunk and upper and lower limbs. There was no lymphadenopathy/organomegaly or mucosal disease. Biopsy showed mucosis fungoides. This was controlled over the next two decades with simple emulsifying creams and topical corticosteroids, the disease remaining confined to the skin. Nineteen years after the diagnosis of mucosis fungoides, he developed an isolated left groin node, biopsy of which showed mixed cellularity Hodgkin's disease. Staging investigations were undertaken and the patient was found to have stage 1A disease (Ann Arbor). He was treated with combination chemotherapy (Nitrogen Mustard, Vincristine, Procarbazine and Prednisolone) and has had no recurrence of his Hodgkin's lymphoma, follow-up being seven years. His mycosis fungoides skin lesions improved temporarily with the cytotoxic therapy, but have subsequently progressed to the tumorous stage. Only temporary improvements in these lesions have resulted from total skin electron therapy, local electron irradiation and P.U.V.A.
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Suppression of salivary flow is of value in the management of salivary fistulae and sialectasia. It may also be beneficial in mentally defective patients and those with neurological palsies lacking control of their salivation. Nine patients were treated by irradiation to the parotid gland to control salivary flow; eight had complete resolution of symptoms and one had partial relief. Irradiation was effective as primary treatment and after failed surgery and/or drug treatment. Low doses were effective and there were no significant acute or long-term side effects. Its use avoids long-term medication and their potential side effects and may reduce the need for surgery.
The middle ear cavity is exposed and vulnerable to waterborne infection in patients with grommets, perforated tympanic membranes and after radical mastoidectomy. Patients suffering from chronic otitis externa and those receiving radiotherapy to the head and neck also have an increased susceptibility to such infections. Many advocate the use of waterproof ear protectors in such patients when swimming. The choice of a suitable ear protector is complicated as many are now available commercially. This study was therefore designed to evaluate the degree of protection afforded by seven different ear protectors in a group of six swimmers. A very sensitive, original method of water detection was devised incorporating a pH indicator strip. The results showed conclusively that cotton wool coated in paraffin jelly BPC was the most effective method of ear protection and was found to be comfortable and easy to use. Other methods, including custom-made silicone rubber plugs, were not adequate in sealing the external auditory canal and are considerably more expensive.
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Eighteen patients with perennial rhinitis were evaluated in this double-blind cross-over trial comparing beclomethasone dipropionate (BDP) aqueous nasal spray with terfenadine tablets. Both treatments were effective in reducing symptom scores but BDP was significantly better than terfenadine in relieving running nose and sneezing (P less than 0.05). BDP also had a greater effect on reducing nasal inflammation than terfenadine. Although the clinicians and patients assessed both therapies to be equi-effective, significantly more patients preferred the BDP treatment (P less than 0.003). Overall, BDP therapy proved more beneficial than terfenadine therapy in this small group of perennial rhinitis sufferers.