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Biomedical subjects

V John

Publications and source records attributed to V John.

At least 19 recordsLinked to original sources
PubMed2003

1alpha,25-dihydroxyvitamin D(3) (calcitriol) and its analogue, 19-nor-1alpha,25(OH)(2)D(2), potentiate the effects of ionising radiation on human prostate cancer cells.

Radiotherapy with external beam radiation or brachytherapy is an established therapeutic modality for prostate cancer. Approximately 30% of patients with localised prostate cancer relapse at the irradiated site. Secondary effects of ionising radiation (IR), for example, bowel and bladder complications, are common. Thus, the search for biological response modifiers that could potentiate the therapeutic effects of radiation and limit the occurrence of serious side effects is an important task in prostate cancer therapy. 1alpha,25-Dihydroxyvitamin D(3) (calcitriol), the active metabolite of vitamin D, and its analogues are under investigation for the treatment of several malignancies including prostate cancer. Here, we report that 1alpha,25-dihydroxyvitamin D(3) and its less calcaemic analogue 19-nor-1alpha,25-(OH)(2)D(2) (Zemplar) act synergistically with IR to inhibit the growth of the human prostate cancer cells in vitro. 1alpha,25-dihydroxyvitamin D(3) potentiated IR-induced apoptosis of LNCaP cells, and nanomolar doses of 1alpha,25-dihydroxyvitamin D(3) and 19-nor-1alpha,25-(OH)(2)D(2) showed synergistic inhibition of growth of LNCaP cells at radiobiologically relevant doses of IR (1-2 Gy). At higher doses of IR, the combination of 1alpha,25-dihydroxyvitamin D(3) and IR or 19-nor-1alpha,25-(OH)(2)D(2) and IR resulted in moderate antagonism. The synergistic effect at radiobiologically relevant doses of radiation suggests that a combination of 1alpha,25-dihydroxyvitamin D(3) or 19-nor-1alpha,25-(OH)(2)D(2) with IR could permit a reduction in the dose of radiation given clinically and thus potentially reduce treatment-related morbidity.

Apoptosis↗
PubMed2002

Expression of cathepsin B, D and L protein in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common childhood autoimmune rheumatic disease and like rheumatoid arthritis (RA), it is characterized by inflammation and the progressive destruction of joints. In RA, cathepsins as proteinases play a major role in destroying synovial tissue and cartilage matrix. So far no data on cathepsin expression in pannus tissue of HA patients exist. The aim of this study was to characterize the expression levels of cathepsins B, D, H, and L in HA and to compare them with those in RA. Synovectomy tissue from 16 HA and 12 RA patients was investigated for cathepsin expression levels by Western blot analysis. Expression of cathepsins B, D and L was on comparable levels in the synovectomy tissue of HA and RA patients. The following graduation of expression was determined: cathepsin D > cathepsin L > cathepsin B. Cathepsin H was neither found to be expressed in HA nor in RA patients. The expression levels of cathepsins in pannus tissue showed no clear difference between patients with systemic JIA and patients with monoarticular JIA. In summary, the comparable expression of cathepsins B, D and L in RA and JIA synovectomy tissue suggests that they may play a similarly important role in destroying synovial tissue and cartilage matrix in the course of HA and RA.

Adolescent↗
PubMed2001

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.

Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These molecules are active in both 293 HEK cells and neuronal cultures, and exert their effect upon A beta production without affecting protein secretion, most notably in the secreted forms of the amyloid precursor protein (APP). Oral administration of one of these compounds, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, to mice transgenic for human APP(V717F) reduces brain levels of Ass in a dose-dependent manner within 3 h. These studies represent the first demonstration of a reduction of brain A beta in vivo. Development of such novel functional gamma-secretase inhibitors will enable a clinical examination of the A beta hypothesis that Ass peptide drives the neuropathology observed in Alzheimer's disease.

Administration, Oral↗
PubMed2001

A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: a pilot study.

OBJECTIVE: To study the efficacy of combination therapy with etanercept and methotrexate in patients with refractory juvenile idiopathic arthritis. METHODS: Seven children with active juvenile idiopathic arthritis refractory to at least combination therapy with methotrexate and sulfasalazine or cyclosporin A were studied. Concomitant treatment, consisting of non-steroidal drugs, corticosteroids, and methotrexate, remained unchanged. RESULTS: Six patients continued the treatment for at least 24 weeks. In the child with systemic arthritis, etanercept was stopped because of persisting spiking fever, joint pain, and rash. In the remaining children an immediate significant decrease in joint pain (p<0.05), disappearance of morning stiffness, and regression of joint swelling (p<0.05) were observed. Improvement was apparent after two injections. An immediate significant (p<0.05) decrease in erythrocyte sedimentation rate, C reactive protein, and interleukin 6 was observed. Side effects consisted of mild reactions at the injection site in two children. CONCLUSIONS: In this observational study, etanercept in combination with methotrexate was well tolerated and highly effective in treating juvenile polyarthritis but not in the patient with systemic arthritis. Combination treatment appears to be feasible in terms of toxicity and may enhance efficiency.

Adolescent↗
PubMed2001

Implant treatment planning and rehabilitation of the anterior maxilla: Part 1.

Implant-supported restorations have become very popular in the management of the partially or completely edentulous patient. Success depends on attentive treatment planning and coordinated teamwork between the surgeon and the restoring dentist. Implants placed in the anterior maxilla require special attention due to esthetic considerations. This article describes the management of a severely resorbed anterior maxilla using principles of guided bone regeneration followed by implant-supported restorations. This case illustrates some of the problems that can arise during the course of treatment.

Adult↗
PubMed2000

The p53 status in juvenile chronic arthritis and rheumatoid arthritis.

The aim of this study was to investigate the p53 status in two autoimmune diseases; juvenile chronic arthritis (JCA) and rheumatoid arthritis (RA). In a PCR-sequencing analysis of exons 4-9 of the p53 gene, no mutation was identified, except for the case of an RA synovectomy sample with two mutations of intron 7. p53 gene polymorphisms for codons 36, 47, and 213 were not detected. Codon 72 polymorphism showed an indication of an increased occurrence of the Pro/Pro allelotype in JCA. Expression of P53 protein was comparable for JCA and RA synovectomy samples. For all RA samples P53 protein was detectable, whereas one sample of a JCA patient failed to express P53 protein.

Adolescent↗
PubMed1999

Purification and cloning of amyloid precursor protein beta-secretase from human brain.

Proteolytic processing of the amyloid precursor protein (APP) generates amyloid beta (Abeta) peptide, which is thought to be causal for the pathology and subsequent cognitive decline in Alzheimer's disease. Cleavage by beta-secretase at the amino terminus of the Abeta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated carboxy-terminal fragment. Cleavage of the C-terminal fragment by gamma-secretase(s) leads to the formation of Abeta. The pathogenic mutation K670M671-->N670L671 at the beta-secretase cleavage site in APP, which was discovered in a Swedish family with familial Alzheimer's disease, leads to increased beta-secretase cleavage of the mutant substrate. Here we describe a membrane-bound enzyme activity that cleaves full-length APP at the beta-secretase cleavage site, and find it to be the predominant beta-cleavage activity in human brain. We have purified this enzyme activity to homogeneity from human brain using a new substrate analogue inhibitor of the enzyme activity, and show that the purified enzyme has all the properties predicted for beta-secretase. Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase.

Amino Acid Sequence↗
PubMed1999

Multiple transrectal ultrasound guided prostatic biopsies: morbidity and tolerance.

OBJECTIVE: Early detection of prostate cancer has become a matter of vital importance in modern societies. Ultrasound guided transrectal biopsy is the current standard urological procedure to detect prostate cancer. In this study our intention was to confirm the high tolerance and low complication rate of this procedure, facts already established in urologists' minds. MATERIAL AND METHODS: In order to evaluate the morbidity as well as the acceptance of the procedure, we investigated 120 patients who underwent ultrasound guided transrectal biopsies of the prostate, in our department from September 1995 to January 1996. All patients at each biopsy underwent 6 needle passes and took periprocedural antibiotic therapy. Alongside with recording the periprocedural side effects of this method patients answered a questionnaire in order to evaluate the pain they experienced by this procedure. RESULTS: Twenty patients were found to have prostate cancer at various stages. All patients tolerated well the whole procedure. Pain was the most common complaint among patients. Several complications were recorded; the most common of all was haematuria. Only two patients required admission to hospital because they developed fever after the procedure. CONCLUSION: Ultrasound guided transrectal biopsy of the prostate is a well-tolerated and effective method for obtaining multiple biopsy specimens from the prostate with low incidence of serious complications. Its is also accurate enough, allowing its use in everyday urology, as a diagnostic procedure.

Aged↗
PubMed1999

Child abuse and dentistry: a study of knowledge and attitudes among dentists in Victoria, Australia.

Child abuse is a disturbingly common finding in society today. In view of the high proportion of orofacial injuries seen in victims of child abuse, dentists are in a strategic position to recognize and report suspected cases. The present study of 347 dentists in Victoria, Australia, assessed the level of knowledge and attitudes among dental professionals on the important issue of child abuse. While a high level of interest was shown by the participants towards this issue, a need for further information and training in the recognition and reporting of child abuse was seen in the survey findings. While dentists at present are not legally mandated in all states of Australia to report suspected cases of child abuse, the dental profession is in a key position to play an active role in the identification and reporting of this substantial community problem.

Adolescent↗
PubMed1999

Cancer incidence in eastern Adriatic isolates, Croatia: examples from the islands of Krk, Cres, Losinj, Rab and Pag.

As an extension of previous research this study investigates the incidence of cancer in five genetic isolate island populations of the Eastern Adriatic, Croatia. Thorough anthropological research over the past three decades has established some of those populations as outstanding examples of genetic isolates. A previous study which found higher cancer incidence in 5 Eastern Adriatic islands than in a control population supported a hypothesis that among the founders of these populations there were genetic variants (especially with recessive inheritance) responsible for genetic susceptibility to certain types of cancer. This study sought to investigate cancer incidence in 5 further island populations. All cancer cases in five island populations (Krk, Cres, Losinj, Rab and Pag) over the 20-year period (1971 to 1990) was extracted from the data of the Croatian Cancer Registry. The mainland populations of Istrian and Primorsko-Goranska County, characterized by similar environmental factors but an outbred genetic structure, represented a control population. After standardization by by sex and age, cancer incidence was higher in the island populations than in the control population in both sexes. The cancer sites primarily responsible for the excess incidence were prostate, stomach and pancreatic cancer in males, and ovarian, breast, stomach, bowel, and brain cancer in females. The reasons for the increased cancer incidence are uncertain and may be due to different environmental exposure between the two populations. However, it is possible that genetic isolation and inbreeding are important factors. Further investigations of cancer in these isolate populations are warranted to explore these findings further.

Adult↗
PubMed1999

Surname as 'cancer risk' in extreme isolates: example from the island of Lastovo, Croatia.

The aim of this study was to analyze whether there are surnames which appear more frequently among the ancestors of cancer cases in a small isolate, in comparison to the ancestral surnames of the healthy controls, using the classic case-control design. The chosen setting was the island of Lastovo, Croatia, located more than 100 kilometers from the nearest coastal region. The period of study was 1970-1995, during which a total of 76 cancer cases were recorded in a population of approximately 800. The comparison of surname frequencies was performed in current and in five ancestral generations. The leading hypothesis was that, if inbreeding and common ancestry contributed to the development of the disease, then those phenomena should be reflected in increasing frequency of some surnames among ancestors, identifying the 'hidden' consanguinity, or 'following' cancer-promoting genes on the Y-chromosome. The results imply that there are surnames representing a classic "risk" for cancer, but also those "protecting" from its development, which all underscores the importance of founder effect and genetic predisposition to the disease in a small, reproductively isolated population. All of the results become more evident and increasingly significant when analyzed in more distant ancestral generations.

Case-Control Studies↗
PubMed1997

Detection of radiographic findings in lung fibrosis using storage phosphor plates.

The aim of this work was to examine the influence of the filter kernel size on the detectability of differing radiological findings in interstitial lung disease. In 97 patients with confirmed pulmonary fibrosis chest radiographs were obtained with a filmscreen system of speed class 200 and with correspondingly exposed storage phosphorous plates. The size of the filter kernel used for the image postprocessing varied between sigma 5 and sigma 70. The detectability of interstitial lung changes was evaluated independently by eight readers on the basis of a defined rating system. The results were analysed using multifactorial analysis of variance with Scheffé test at a significance level of p = 0.05. Small kernel sizes (S 5, S 10) combined with high edge enhancement were only of benefit in the imaging of septal lines, but reduced the detectability of nodular and reticular structures. Good detail detectability of both micronodules and septal lines was obtained with a medium kernel size of sigma 40. Storage phosphor radiography utilizing the appropriate choice of postprocessing parameters provides equivalent image quality for evaluating interstitial lung changes compared with a modern filmscreen technique.

Female↗
PubMed1997

[Value of lung filter, asymmetric film-screen technique and digital storage screen radiography in diagnosis of coin lesion].

AIM: To evaluate the image quality of an asymmetric film-screen combination (a-FSC), a conventional screen-film combination (FSC) at speed class 200, a lung filter, and digital luminescence radiograms in detecting pulmonary nodules. METHODS: Detail perception studies were carried out with an anthropomorphic phantom. The image systems were exposed under standardised conditions with 125 kVp. The systems' perception efficiency was evaluated on the basis of 12.240 single observations with ROC analysis. RESULTS: In the overall evaluation the a-FSC and the filter achieved equally high assessments of 0.878 +/- 0.018 and 0.860 +/- 0.21 respectively (p > 0.05). The 200 speed FSC and the storage phosphor screen radiograms did not differ significantly. In the mediastinum all the tested systems were clearly superior to the 200 speed FSC (p < 0.05). In the lung fields on the other hand the 200 speed system was given a higher assessment of 0.866 +/- 0.026. The a-FSC had slight advantages over the lung filter and the digital imagining modes (p > 0.05). CONCLUSIONS: The a-FSC and digital luminescence radiograms provide significantly more diagnostic information in the mediastinum, together with high detail detectability in the lung fields and without requiring additional dosage.

Humans↗
PubMed1996

Unsharp masking of low-dosed digital luminescence radiographs: results of a receiver operating characteristics analysis.

The extent to which the diagnostic performance of low-dosed storage phosphors can be improved by suitable image postprocessing was investigated. Storage phosphor radiographs and conventional 200- and 400-speed screen-film combinations of an anthropomorphic chest phantom with simulated nodules and linear structures were compared. The detection of test bodies was determined in a ROC analysis based on 16200 individual observations. The two analog screen-film systems did not differ significantly. As far as the storage phosphor radiographs are concerned, a higher diagnostic performance was achieved with a large filter kernel (S 40) whereas small filter kernels and edge-enhanced imaging modes reduced the detection of detail. The image quality of low-dosed storage phosphors is thus similar to high-amplification screen-film combinations if large filter kernels are used in postprocessing of the image.

Acrylic Resins↗
PubMed1996

Frequency-filtered image post-processing of digital luminescence radiographs in pulmonary nodule imaging.

AIM: The aim of the study was to optimize unsharp masking image post-processing of digital luminescence radiographs (DLR) for the representation of pulmonary nodules, and to compare DLR to screen-film radiography at two dose levels. PATIENTS AND METHODS: A total of 284 CT-validated pulmonary nodules were evaluated. One hundred and forty-nine nodules were exposed with a 200-speed screen-film combination (SFC) and 135 nodules with a 400-speed SFC, with correspondingly exposed storage phosphor images. The kernal size in digital post-processing using 'unsharp masking' was varied between S 10 (2.83 mm) and S 70 (19.80 mm). A total of 11928 individual assessments were obtained from six independent observers and evaluated in multifactorial variance analyses. RESULTS: The large filter kernels of S 40 and S 70 were on a par with the 200-speed SFC (P > 0.05). As the exposure dose was reduced, the quality of the digital image vis-à-vis the 400-speed SFC improved significantly (P < 0.05). Smaller filter kernels (S 10; S 20) producing edge-enhancement processing were significantly inferior to the analog image technique in both dose ranges (P < 0.05). CONCLUSIONS: At speed class 200, low-frequency emphasizing digital image post-processing with large filter kernels are significantly superior to high-frequency emphasizing filtrations for the recognition of pulmonary nodules. In the lower dose range DLR with large filter kernel unsharp masking processing showed significantly improved image quality compared to 400 speed SFC for the detection of pulmonary nodules.

Adolescent↗