Biomedical subjects
Publications and source records attributed to C J Harrison.
A patient with acute lymphoblastic leukemia (ALL) was found, at the time of diagnosis, to have an unusual Philadelphia chromosome (Ph1) with a satellite marker. The disease evolved into the chronic phase of chronic granulocytic leukemia (CGL), with persistance of the marker. Two months later, the patient died of ALL.
Twenty-six children, aged 2 months to 15 years, were treated with intravenous ceftriaxone sodium, 37.5 mg/kg every 12 hours, for an average of seven days. Clinical and microbiologic cures occurred in 19 of 21 patients, from whom bacterial pathogens were cultured. Ceftriaxone was not effective in treating an 18-month-old infant with periorbital cellulitis caused by relatively resistant Staphylococcus aureus. A relapse occurred in a 2-month-old infant with meningitis caused by ceftriaxone-sensitive Salmonella. Eleven patients had transient diarrhea, superficial candidiasis developed in ten patients, and one patient experienced skin flushing during administration of the antibiotic. Transient asymptomatic laboratory abnormalities were detected in 15 patients; nine patients had elevated serum concentrations of transaminases or bilirubin, 11 had thrombocytosis, three experienced eosinophilia, and one had thrombocytopenia. Transient suppression of normal flora of the intestine occurred in 21 patients. Side effects were not serious enough to warrant discontinuing ceftriaxone therapy in any patient.
Scanning electron microscopy (SEM) has been used to study the fragile X chromosome. The fragile site appears as an isochromatid gap in the majority of cases, confirming light microscope (LM) observations. SEM has allowed a more precise location of the fragile site to the Xq27 . 3 region.
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The mammary gland is a system of hollow interconnecting tubes which develops from an invasive branching cord of epithelial cells. This ultrastructural study of the developing mammary gland focuses on how the lumen forms and establishes the polarized epithelial lining of the gland. The earliest signs of lumen formation are many small cavities and crevices lined with microvilli which appear at scattered sites throughout the branching cords and neck of the gland. It is suggested that these initial small lumina form quite simply by separation of cells whose opposing faces are non-adhesive. The continuous central lumen of the gland develops by fusion and enlargement of the many small lumina. The cells adjacent to the developing lumen will form the polarized epithelial lining of the gland. Excess, more basal, epithelial cells degenerate. The lumen begins to appear when the branching pattern is almost complete. Thus, during morphogenesis, invasion by the mammary gland epithelium involves penetration of the mesenchyme by a solid cord of cells. We suggest that this cellular organization may be a fundamental characteristic of invasive epithelia and that a crucial step in the development of malignant epithelial tumours is a change in cell organization from a polarized cell sheet to a solid cord of cells which can invade.
Human metaphase chromosomes, prepared for light microscopy were examined by scanning electron microscopy. Use of an osmium impregnation technique eliminated the need for sputter-coating and allowed high-resolution visualization of uncoated specimens. Chromosomes were of three-dimensional cylindrical profile, with well-defined chromatids and centromeres. Prior to Giemsa-banding a smooth surface morphology was observed. Relaxation of chromosome integrity by Giemsa-banding pretreatment allowed resolution of several orders of chromosome structure not previously demonstrated by scanning electron microscopy. The observed organization of the chromatin fibres allowed parallels to be drawn with the radial loop model of chromosome construction as described by Marsden and Laemmli.
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The relationship between ageing and transformation has been investigated by a serial study of the changes in cell-surface morphology as normal and carcinogen-treated cells progressed in culture. A progressive increase in the density of cell surface microvilli occurred in association with the adoption of a more rounded profile and concomitant increase in the rate of cell detachment. These changes occurred earlier after carcinogen treatment, which appeared to indicate a carcinogen-induced acceleration of ageing. The alterations have also been described as characteristic of the transformed state. The observations suggest that the expression of in vitro transformation may be the result of continuous selection from a population with genetic instability and variable morphology.
Three dimensional gels of native type I collagen fibres have been used as a substratum for the growth and migration of Chinese hamster ovary cells (fibroblastoid cell line) and RPMI-3460 melanoma cells (tumorigenic cell line from Syrian hamster). Quantitative data concerning the migration of these cells from the gel surface into the 3-dimensional collagen gel matrix have been obtained. The migration of both cell types into the collagen gel matrix is not accompanied by the degradation of collagen fibres. The possible implications of these observations for tumour cell invasion in vivo are discussed.
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Recombinant herpes simplex virus type 1 (HSV-1) glycoproteins B (gB) and D (gD) were used as immunotherapeutic agents for the treatment of recurrent genital herpes in guinea pigs. Administration of a gBgD vaccine eight to 21 days after intravaginal HSV-2 inoculation significantly increased the titer of anti-HSV antibodies (P less than 0.005) while significantly reducing the frequency of subsequent herpetic recurrences (P less than 0.05). The effectiveness of gBgD immunotherapy was influenced by both the co-administration of adjuvant, the type of adjuvant, and by the timing and route of administration. These data demonstrate that recurrent HSV disease in animals with established latent infection may be favorably altered by the administration of immunogenic viral proteins.
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Isolates were obtained from 169 middle ear aspirates of 148 children with recently treated acute otitis media (RTOM) and from 123 aspirates of 84 children with previously untreated acute otitis media (UOM). In RTOM Streptococcus pneumoniae and Group A streptococcus (P less than 0.02) were recovered less frequently whereas Staphylococcus aureus (P less than 0.001) and Haemophilus influenzae (P less than 0.02) were recovered more frequently than in UOM. Patients with RTOM had more beta-lactamase-producing organisms and multiple isolates. Bilateral sterile aspirates were more common in RTOM although bilateral otitis media was more common in UOM. In RTOM most Branhamella catarrhalis isolates were co-pathogens whereas Staphylococcus epidermidis were always isolated in pure culture. Amoxicillin was the antimicrobial most frequently (83.9%) received for the recently treated episode of otitis media. In RTOM 62.4% of isolates were susceptible to previously prescribed antibiotics, suggesting that factors other than antimicrobial susceptibility are also important in the occurrence of RTOM.