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Biomedical subjects

J Nicholls

Publications and source records attributed to J Nicholls.

At least 37 records · Page 2Linked to original sources
PubMed2000

The changing role of the medical illustrator.

The annual meeting of the Australian Institute of Medical and Biological Illustration in Melbourne in November 1998 included keynote addresses from Richard Morton and Robin Williams. Both speakers looked at the future of the medical illustration profession, and in particular the impact of new technology. This matter was also addressed by Joe Nicholls in a presentation given at the Institute of Medical Illustrators' Annual Symposium in Warwick, UK, in September 1998. This paper is a synthesis of the ideas presented by these three speakers and elaborates on common themes in their presentations.

Education, Medical↗
PubMed1999

The time course of histologic remission after treatment of patients with nasopharyngeal carcinoma.

BACKGROUND: The objective of this study was to define the time course of histologic remission and to evaluate the prognostic significance of delayed histologic remission of patients with nasopharyngeal carcinoma (NPC). METHODS: Between 1986-1994, 803 patients underwent serial postradiotherapy nasopharyngeal biopsies. Patients with positive histology underwent repeated biopsies every 2 weeks until the biopsies were found to be negative or, if remission did not occur by the 12th week after radiotherapy, treatment was initiated for persistent disease. Patients with positive histology found after the fifth week but who achieved spontaneous remission before the twelfth week were considered to have delayed histologic remission. Negative histology by the sixth week was considered early histologic remission. The outcome of patients with delayed histologic remission, early histologic remission, and persistent disease were compared. RESULTS: Six hundred and seventeen patients (76.8%) had negative histology within 12 weeks of the completion of radiotherapy and 55 (6.9%) had persistent disease at Week 12. In 131 patients (16.3%) spontaneous remission was observed in repeat biopsies after initial positive histology. With increasing time after radiotherapy, the incidence of positive histology decreased but more patients were found to have persistent disease. Patients with early and delayed histologic remission had 5-year NPC control rates of 82.4% and 76.8%, respectively (P = 0.35) versus a 40% NPC control rate among patients with persistent disease (P < 0.001). The 5-year survival rates were 75.3%, 79.4%, and 54.2%, respectively, for the 3 groups (P < 0.001). CONCLUSIONS: A high proportion of early positive histology remitted spontaneously. Delayed histologic remission in NPC patients is not a poor prognostic factor and additional treatment is not necessary. A confirmatory biopsy at 10 weeks is recommended before the initiation of salvage treatment.

Biopsy↗
PubMed1999

Avascular necrosis in patients treated with BEP chemotherapy for testicular tumours.

Avascular necrosis (AVN) is known to occur after combination chemotherapy for lymphomas and leukaemias that includes high dose corticosteroids, but it has been reported rarely in patients with solid tumours. We describe five recent cases in young men with testicular tumours (three of which were of good prognosis), who had been treated with chemotherapy using dexamethasone as an antiemetic. Dexamethasone is a low cost and effective antiemetic, but it may be responsible for inducing AVN in patients receiving chemotherapy for solid tumours. A prospective survey of the frequency of AVN is justified to quantify the extent of the problem.

Adult↗
PubMed1998

Epstein-Barr virus expression within keratinizing nasopharyngeal carcinoma.

Three stages of maturation can be seen in keratinizing nasopharyngeal carcinomas. These stages are similar morphologically to basal cells, intermediate and superficial squamous cells seen in normal squamous epithelium. Taking advantage of such a diverse tumour cell population, 10 keratinizing nasopharyngeal carcinoma (NPC) were examined by in situ hybridization for the presence of latent Epstein-Barr Virus (EBV) using EBV encoded RNAs (EBERs) and by immunohistology for the presence of EBV early antigen-diffuse (EA-D) and the 350/220 kd membrane glycoprotein of the EBV. The basal cell-like tumour cells are mainly infected latently with the virus; viral replication was found in isolated intermediate squamous cells, whilst superficial squamous cells are largely depleted of all the viral markers. We used a control series of nonkeratinizing nasopharyngeal carcinomas composed of undifferentiated and poorly differentiated tumour cells and EBV latency was present in these tumours. Viral replication was detected by RT-PCR, in the undifferentiated tumours but viral replication was not seen by immunohistology. The possible relationship between EBV life cycle in these tumours and tumour cell differentiation is discussed in the light of these findings.

Antibodies, Monoclonal↗
PubMed1998

Identification of cytotoxic T cell epitopes within Epstein-Barr virus (EBV) oncogene latent membrane protein 1 (LMP1): evidence for HLA A2 supertype-restricted immune recognition of EBV-infected cells by LMP1-specific cytotoxic T lymphocytes.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) and latent membrane proteins (LMP) are the only antigens consistently expressed in malignancies such as nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD). Since EBNA1 is not recognized by EBV-specific cytotoxic T lymphocytes (CTL), there is increasing interest in the identification of the potential target epitopes within LMP1. Although LMP1-specific CTL have been isolated from seropositive individuals, earlier attempts to identify the peptide epitopes recognized by these T cells have been unsuccessful. In the present report we used a novel protocol to identify CTL epitopes within LMP1 which can be recognized by both polyclonal and clonal CTL. Firstly, a computer-based program was employed to identify the potential HLA-binding peptides within LMP1. Polyclonal CD8+ CTL were then isolated from seropositive donors that recognized the peptide epitopes YLLEMLWRL and YLQQNWWTL from LMP1 in association with HLA A2. Limiting dilution analysis of the memory CTL response revealed that the LMP1-specific CTL response constitutes a minor component of the CTL response in healthy virus carriers. Interestingly, analysis of YLLEMLWRL-specific CTL revealed that these CTL were able to lyse EBV-infected B cells expressing different HLA A2 supertype alleles including A*0201, A*0202, A*0203, A*0204, A*0206, A*6802 and A*6901. These data strongly support the notion that HLA class I supertype-restricted CTL may be of significant use in the development of peptide-based immunotherapeutics against EBV-associated malignancies in different ethnic populations.

Alleles↗
PubMed1998

Perinuclear anti-neutrophil cytoplasmic antibodies in ulcerative colitis after restorative proctocolectomy do not correlate with the presence of pouchitis.

BACKGROUND: Although perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) expression is strongly associated with ulcerative colitis, its relationship with the occurrence of pouchitis after restorative proctocolectomy is uncertain. METHODS: Serum p-ANCA was assayed using both indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) in 49 patients, of whom 25 had, and 24 had not, developed pouchitis. Control sera were obtained from 15 healthy volunteers. RESULTS: By means of indirect immunofluorescence, p-ANCA was detected in 45.8% of patients without and in 48% with pouchitis (NS). Twenty-three (46.9%) of the 49 colitis patients were p-ANCA-positive, compared with none of the 15 controls (P < 0.01). By means of ELISA, p-ANCA positivity was present in 50% of patients without and in 68% with pouchitis (NS). CONCLUSION: Whereas p-ANCA was associated with ulcerative colitis as compared with normal individuals, it was not associated with pouchitis. Thus it is unlikely to be a suitable pre-operative marker to identify those patients who will develop pouchitis.

Adult↗
PubMed1998

Combined hepatocellular-cholangiocarcinoma: a clinicopathological study.

Combined hepatocellular-cholangiocarcinoma (HCC-CC) is an uncommon form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. We reviewed 21 cases of this tumour diagnosed between 1972 and 1996 (patient age range 16-79 years; mean patient age 49.7 years; 18 male and three female patients). Histologically, the majority (n = 18) of tumours were 'mixed' tumours, in which areas of hepatocellular and biliary epithelial differentiation were intimately mixed within the same tumours. Two patients had separate tumours in which discrete nodules of HCC and CC occurred in the same livers. One patient had a 'fibrolamellar' tumour that histologically simulated the fibrolamellar variant of HCC, but some of the tumour cells were mucin-producing cells. Of the 21 cases, mucin was demonstrable in 16 and, in the few mucin-negative tumours, electron microscopic studies confirmed the presence of the dual differentiation. The tumours frequently exhibited an invasive character with frequent venous permeation, direct invasion into adjacent liver parenchyma and tumour microsatellite formation, similar to that of ordinary HCC. Histological evidence of cirrhosis or chronic hepatitis was present in 77.8% of patients and 75% of patients were hepatitis B surface antigen positive. Raised serum alpha-fetoprotein (AFP) levels (above 300 ng/mL) were present in 61.5% of patients and AFP was detected immunohistochemically in 55% of tumours. The overall survival times of patients with HCC-CC were short. In conclusion, HCC-CC showed clinical and pathological features more akin to those of ordinary HCC than to CC.

Adult↗
PubMed1997

Characterization of adenosine receptors on rat ileum, ileal longitudinal muscle and muscularis mucosae.

Adenosine receptors were studied in isolated rat ileum, ileal longitudinal muscle and muscularis mucosae, using a range of agonists and an antagonist. In the rat ileal longitudinal muscle adenosine receptor agonists relaxed the tissues. N6-cyclopentyladenosine (CPA) was more potent than 5'-N-ethylcarboxamidoadenosine (NECA) or adenosine and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (1 nM) gave a 5-fold parallel shift to the right of the concentration-response curves to both CPA and NECA corresponding to an apparent pA2 value of 9.6 suggesting that the agonists relax via adenosine A1 receptors. In the intact ileum adenosine receptor agonists also relaxed the tissue but NECA and CPA were equipotent. DPCPX (3 nM) however inhibited responses to both CPA and NECA with dose-ratios of 8 and 15.6, corresponding to pA2 values of 9.3 and 9.7, respectively. DPCPX (300 nM) gave a much greater shift to the right of the concentration-response curve to NECA with a dose-ratio of 769, corresponding to an apparent pA2 of 9.4. This suggests that the agonists are acting at adenosine A1 receptors to cause relaxation of the whole tissue. Adenosine receptor agonists contracted rat ileal muscularis mucosae with a potency order indicative of an A adenosine receptor. DPCPX (3-100 nM) antagonized responses to CPA giving a linear Schild plot with a slope close to unity and a pA2 of 8.4 suggesting an action on adenosine A1 receptors.

Adenosine↗
PubMed1997

Residual mass following chemotherapy of seminoma.

BACKGROUND: The residual mass so frequently found after chemotherapy of advanced seminoma may consist entirely of benign tissue or may contain residual disease amenable to adjuvant therapy. PATIENTS AND METHODS: A detailed retrospective analysis was performed on 45 patients treated with cisplatin based chemotherapy for advanced seminoma between 1978 and 1994. RESULTS: The probability of a residual mass after chemotherapy was higher if the pre-treatment mass diameter was > 5 cm (78% versus 15%, P = 0.0009). Of 33 patients with residual masses following cisplatin chemotherapy, 4 were explored surgically showing fibrosis only, 15 were treated by adjuvant radiotherapy and 14 were managed by observation alone. Recurrence occurred in 2 of 14 patients managed by observation and in 2 of 15 managed by radiotherapy. There was no evidence that risk of recurrence was related to diameter of residual mass. CONCLUSION: Residual masses persisted following cisplatin based combination chemotherapy for seminoma in 73% of cases. In our study, recurrence was rare and there was no evidence that this was influenced by either the size of the residual mass or the use of adjuvant therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

T-cell intravascular lymphomatosis (angiotropic large cell lymphoma): association with Epstein-Barr viral infection.

AIMS: Intravascular lymphomatosis (IVL) is a very rare non-Hodgkin's lymphoma characterized by proliferation of lymphoma cells in the vascular lumina without involvement of adjacent parenchymal tissue. IVL is predominantly of B-cell lineage, but occasional cases of T lineage IVL involving almost exclusively the skin have been described. A case of IVL that occurred initially in the epididymis of a patient with an antecedent nasopharyngeal carcinoma was studied to define the clinicopathological features associated with this unique presentation. METHODS AND RESULTS: This lymphoma was studied by standard histological and immunophenotyping methods. The results showed lymphoma cells confined within the blood vessels, which expressed leucocyte common antigen, and T-cell markers CD3 and UCHL-1. The T-cell origin of the IVL prompted investigations for an association with Epstein-Barr virus infection (EBV). In-situ hybridization with digoxigenin-labelled anti-sense RNA probes to EBV encoded RNA (EBER) showed strong signals in the nuclei of virtually all of the lymphoma cells. CONCLUSIONS: EBV infection of the malignant cells was demonstrated by in-situ hybridization. This case suggests that T-cell IVL may be another EBV related human neoplasm. This observation will need to be validated by further studies.

Fatal Outcome↗
PubMed1997

Use of a newly developed technique to isolate rat pinealocytes and study the effects of adenosine agonists on melatonin production.

Recent studies have suggested a role for adenosine in the regulation of rat pineal melatonin synthesis. The data, however, are conflicting and therefore the aim of this study was to characterize adenosine receptors more fully in vitro by using a range of selective adenosine agonists and the adenosine antagonist 8-sulphophenyltheophylline (8-SPT). A simple method for the mechanical separation of rat pinealocytes was developed. Pinealocytes were briefly (15 min) incubated with drugs followed by a 4 hr drug-free incubation period after which melatonin concentrations in the incubation medium were measured by radioimmunoassay. The beta-adrenoceptor agonist isoprenaline gave a dose-related increase in melatonin production, demonstrating that this pinealocyte preparation technique is suitable to evaluate the effect of drugs on pineal melatonin synthesis. Our results show that adenosine, N6-(phenylisopropyl)adenosine (R-PIA) and 2-p-(2-carboxethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS21680) did not affect melatonin synthesis alone or in combination with isoprenaline. However 5'-N-ethylcarboxamidoadenosine (NECA) (100 microM) potentiated the stimulatory effect of isoprenaline (3 microM) on pineal melatonin production and this effect appeared to be antagonized by 8-SPT (50 microM). These results are consistent with activation by NECA of an A2b adenosine receptor.

Adenosine↗
PubMed1997

Evolutionary dynamics of genetic variation in Epstein-Barr virus isolates of diverse geographical origins: evidence for immune pressure-independent genetic drift.

The question whether immune pressure exerted by cytotoxic T lymphocytes (CTLs) can influence the long-term evolution of genetically stable viruses such as Epstein-Barr virus (EBV) has generated considerable scientific interest, primarily due to its important implications for the overall biology of the virus. While arguing for a role of CTLs in the evolution of viruses, it is important to differentiate between genetic variation in virus and immune recognition of these variant virus by CTLs. To assess the role of genetic selection in the long-term evolution of EBV, we have analyzed a large panel of type 1 EBV isolates from African, Southeast Asian, Papua-New Guinean (PNG), and Australian Caucasian individuals. Seven different regions of the EBV genome, which include nine CTL epitopes restricted through a range of HLA class I alleles, were sequenced and compared. Although numerous nucleotide changes were identified within these isolates, comparison of synonymous and nonsynonymous substitutions in the CTL epitope indicated that the genetic variation was generated mostly independently of immune selection pressure. Surprisingly, an inverse correlation between genetic variation within certain CTL epitopes and the frequency distribution of HLA alleles that present the CTL epitopes was seen, suggesting that the evolutionary pressures on the CTL epitopes of the virus may be toward their conservation rather than their inactivation. Furthermore, molecular evolutionary genetic analysis of nucleotide sequences revealed that viral isolates from PNG are evolving as a lineage distinct from isolates from African, Southeast Asian, and Australian Caucasian individuals.

Amino Acid Sequence↗