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Biomedical subjects

C Gulmann

Publications and source records attributed to C Gulmann.

13 recordsLinked to original sources

Array-based proteomics: mapping of protein circuitries for diagnostics, prognostics, and therapy guidance in cancer.

The human proteome, due to the enormity of post-translational permutations that result in large numbers of isoforms, is much more complex than the genome and alterations in cancer can occur in ways that are not predictable by translational analysis alone. Proteomic analysis therefore represents a more direct way of investigating disease at the individual patient level. Furthermore, since most novel therapeutic targets are proteins, proteomic analysis potentially has a central role in patient care. At the same time, it is becoming clear that mapping entire networks rather than individual markers may be necessary for robust diagnostics as well as tailoring of therapy. Consequently, there is a need for high-throughput multiplexed proteomic techniques, with the capability of scanning multiple cases and analysing large numbers of endpoints. New types of protein arrays combined with advanced bioinformatics are currently being used to identify molecular signatures of individual tumours based on protein pathways and signalling cascades. It is envisaged that analysing the cellular 'circuitry' of ongoing molecular networks will become a powerful clinical tool in patient management.

Biomarkers, Tumor↗

Telomerase activity in proximal and distal gastric neoplastic and preneoplastic lesions using immunohistochemical detection of hTERT.

BACKGROUND: The incidence of distal (corpus and antrum) gastric adenocarcinoma is decreasing with a simultaneous increase in incidence of proximal (cardia) adenocarcinoma. Epidemiological studies suggest that they may represent different diseases but corroborative molecular data are scarce. Intestinal metaplasia may have a lower malignant potential in the proximal stomach but regardless of the locations, its specificity as a predictor of carcinoma is low. AIMS: The aim of this study was to establish whether human telomerase reverse transcriptase expression differs at various points in proximal versus distal gastric carcinogenesis and to test the utility of human telomerase reverse transcriptase expression as a marker of cancer risk in intestinal metaplasia. MATERIAL AND METHODS: Wax-embedded tissue from proximal and distal stomach including normal mucosa (n=86), intestinal metaplasia (n=83) and carcinoma (n=101) were used and slides were immunostained for human telomerase reverse transcriptase and pRb and scored semi-quantitatively. RESULTS: The results showed that in both proximal and distal stomach, human telomerase reverse transcriptase expression rates increased from normal mucosa to cancer. High rates of human telomerase reverse transcriptase expression were seen in the proliferative zones of glands in intestinal metaplasia. In both the locations, loss of pRb expression correlated with higher human telomerase reverse transcriptase expression. CONCLUSIONS: In conclusion, telomerase activity appears to be an early event in both proximal and distal gastric carcinogenesis and human telomerase reverse transcriptase is expressed in intestinal metaplasia. Telomerase re-expression may be facilitated by pRb inactivation.

Aged↗

Miniature tissue microarrays for HercepTest standardisation and analysis.

AIMS: To assess the practicality of using a miniature tissue microarray (TMA) with several examples of each HercepTest score from 0 to 3+ as a control for routine HercepTest immunohistochemistry. METHODS: A TMA was constructed from in house cases of breast cancer where HercepTest on the whole sections showed scores 0, 1+, 2+, or 3+. The TMA, which measured 5 x 5 mm, was designed with four rows (each representing scores 0, 1+, 2+, and 3+), with five 0.6 mm cores from separate cases. In all, 20 individual cases were represented and the TMA took less than one hour to construct. Fifty sequential 4 microm sections were cut from the TMA to maximise the number of available sections. They were stored at 4 degrees C for 1-270 days and when a case needed HercepTest staining the section was added to the TMA tissue control slide. RESULTS: All slides contained tissue spots and immunohistochemical staining was consistent throughout the time period. CONCLUSIONS: The miniature TMA with examples of all HercepTest scores described here is an ideal tissue control and can be used as a visual reference for scoring a case. Slides stored at 4 degrees C could be used for up to 270 days.

Breast Neoplasms↗

Biopsy of a biopsy: validation of immunoprofiling in gastric cancer biopsy tissue microarrays.

AIMS: Tissue microarrays offer an efficient way of examining a large number of tumour cases on a single glass slide. A major concern, however, is tumour heterogeneity. Also, the use of tissue microarrays in biopsy material is unexplored. The purpose of the present study was to assess the possibility and validity of arraying three 0.6-mm cores per case in endoscopic gastric cancer biopsies for immunophenotyping. METHODS AND RESULTS: Thirty-eight cases were studied with immunohistochemical staining for p53, CD44v6 and vascular endothelial growth factor. Full tissue sections were compared with triple core-tissue microarrays. Thirty-six cases contained three cores with tumour, one case contained two cores with tumour and one case contained only a single core with viable tumour and was excluded. Three further cores had been lost from three separate cases on the sections for immunohistochemistry. kappa values for whole-sections versus tissue microarrays ranged between 0.77 and 0.94. p53 immunohistochemical staining (interpretation as + or -) yielded the best result with only 1/37 mismatches, whereas CD44v6 (graded both for intensity and extent) showed 3/37 mismatches. The small depth of tissue in cores from biopsies necessitates all cores being arrayed flush with the face of the recipient wax block for maximizing the number of sections available. Compared with the first section over 30 additional 4- micro m sections were available before the first case (with one core left) had to be excluded and 80 sections before half the tissue cores were lost. CONCLUSIONS: It is impracticable to array more than 120-150 cores per block. Tissue microarray with three cores per case is feasible and valid for studying biopsy material.

Adult↗

Cytokeratin 7/20 and mucin expression patterns in oesophageal, cardia and distal gastric adenocarcinomas.

AIMS: The current study examined cytokeratin (CK)7 and 20 as well as MUC1-6 immunoprofiles in oesophageal, gastric and gastro-oesophageal junction (GOJ) adenocarcinomas. The aim was to compare expression patterns in these locations as aids to accurate classification of these morphologically similar carcinomas which all may involve the GOJ. METHODS AND RESULTS: Tissue microarrays were constructed using tissue from 14 oesophageal, 78 gastric and 39 GOJ adenocarcinomas. Sections were immunostained with CK7, CK20, MUC1, MUC2, MUC5AC and MUC6. The results of this study showed no differences in CK7 and CK20 expression patterns in the three locations. MUC2 expression was higher proximally (43% of oesophageal, 28% of GOJ and 17% of gastric carcinomas) and MUC6 expression was higher distally (7% of oesophageal, 28% of GOJ and 15% of gastric carcinomas). MUC1 expression was associated with higher pTNM-stage. CONCLUSIONS: CK 7/20 profiles have no role in distinguishing tumours of the three locations. Mucin expression patterns differed in oesophageal and gastric adenocarcinomas, although not sufficiently to classify individual cases. GOJ adenocarcinomas showed a mucin expression pattern that was partly 'gastric', and partly 'oesophageal'. MUC1 expression was associated with a higher pTNM stage.

Adenocarcinoma↗

Chronic osteomyelitis mimicking sarcoma.

This report describes a rare case of chronic osteomyelitis in a 60 year old man mimicking a soft tissue sarcoma. Chronic osteomyelitis is an infrequent cause of a soft tissue mass and is usually diagnosed clinically by a combination of radiology and microbiology. Rarely, COM can mimic a primary bony neoplasm, but this is the first reported case where it mimicked a soft tissue sarcoma. The clinical, radiological, and histological appearances of this case will be discussed.

Chronic Disease↗

The juxtaglomerular apparatus in young type-1 diabetic patients with microalbuminuria. Effect of antihypertensive treatment.

BACKGROUND: Our goal was to investigate the effect of antihypertensive drugs on the juxtaglomerular apparatus (JGA) in young type-1 diabetic patients with microalbuminuria. METHODS: Twelve patients were allocated to treatment with either an angiotensin-converting enzyme inhibitor (group 1, six subjects) or a beta-receptor blocker (group 2, six subjects). A comparable group of nine patients without antihypertensive treatment provided reference values (group 3, nine subjects). Renal biopsies were taken at baseline and after a median of 40 months (groups 1 and 2) and 30 months (group 3). Using light microscopy with 1microm serial sections of the plastic-embedded biopsies, volumes of the JGA and glomerulus and areas of the macula densa and lumina of the afferent and efferent arterioles were obtained. RESULTS: A significant decrease of the volume of the JGA (P=0.026) and of the volume of the JGA relative to that of its corresponding glomerulus (P=0.0005) was noted in the reference group only. Negative correlations existed between the increase in the luminal area of the afferent arteriole and mean diastolic blood pressure in the study period in group 1 (P=0.024) and group 2 (P=0.032). CONCLUSIONS: Our results showed that a decrease in the size of the JGA is offset by antihypertensives. The negative correlation between the change in the luminal area of the afferent arteriole and mean diastolic blood pressure in groups 1 and 2 suggest that renal protection in antihypertensive treatment may be through a better constriction of the afferent arteriole protecting the glomerulus from systemic blood pressure.

Adolescent↗

Long-term studies of the juxtaglomerular apparatus in young microalbuminuric type 1 diabetic patients.

AIM: To determine the long-term changes of the juxtaglomerular apparatus in incipient diabetic nephropathy. METHODS: Three renal needle biopsies were performed on 15 young type I diabetic patients with microalbuminuria; at baseline and after an average of 2.4 and 8.2 years. Using light microscopy, 1 microm serial sections of the plastic-embedded biopsies were investigated and volumes of the juxtaglomerular apparatus and glomerulus and areas of the macula densa and lumina of the afferent and efferent arterioles were measured. RESULTS: From baseline to second follow-up there was a significant decrease in JGA relative to glomerular volume. There was an increase in luminal area of the efferent arteriole which was paralleled by (non-significant) changes in the afferent arteriole. CONCLUSION: Over a period of 8.2 years JGA size remained stable, but decreased relative to glomerular size. Also, an increase in luminal area was noted in efferent arterioles. This may be due to increased single nephron blood flow secondary to nephron loss.

Adolescent↗

Renal arterioles in patients with type I diabetes and microalbuminuria before and after treatment with antihypertensive drugs.

Antihypertensive drugs can slow or even reverse the progression of diabetic nephropathy at the microalbuminuric stage. This study was performed to obtain quantitative data on changes in the renal arterioles in a follow-up study. Twelve patients with type I diabetes and with microalbuminuria were allocated to treatment for 3 years with either an ACE inhibitor (group I, 6 patients) or a beta blocker (group II, 6 patients). Baseline and follow-up renal needle biopsy specimens were taken and serially sectioned at 1 microm for light microscopy, enabling identification of arterioles as afferent or efferent. Thin sections for electron microscopy were made at 50-microm intervals, and micrographs were taken of arteriolar profiles. Matrix volume fraction of the media and a calculated matrix thickness were obtained. At baseline, structural parameters were higher than normal values. At follow-up all patients were normoalbuminuric. Both groups showed only minor changes in arteriolar structures over 3 years. In the afferent arterioles in group II there was a significant increase in the matrix volume fraction of the media, and there was a tendency to an increase in matrix thickness in both groups. In the efferent arterioles there were no significant changes in parameters. There were no differences between the two groups in arteriolar structural changes from baseline to follow-up. Thus, this study shows a slight but significant matrix accumulation in the afferent arterioles during treatment with antihypertensive drugs. This may have implications for the progression to overt nephropathy, which indicates a need for more long-term studies of treatment with antihypertensive drugs in incipient nephropathy in type I diabetes.

Adolescent↗

Entrance, exit, and reentrance of one shot with a shotgun.

The case being reported is one of a homicidal shotgun fatality with an unusual wound pattern. A 34-year-old man was shot at close range with a 12-gauge shotgun armed with No. 5 birdshot ammunition. The shot entered the left axillary region, exited through the left infraclavicular region, and thereafter penetrated the left side of the neck, causing tearing of the left common carotid artery and the right internal carotid artery. The entrance wound in the axilla was larger than the other wounds, and before autopsy it was believed that the shotgun had been fired twice, causing one wound in the neck and one wound perforating the infraclavicular region and exiting through the left axillary region. Thus, this case shows that unusual wound patterns in shotgun fatalities can easily lead to incorrect assumptions with regard to number and direction of shots fired unless thorough investigation is carried out postmortem.

Adult↗

Enlargement of the juxtaglomerular apparatus in insulin-dependent diabetes mellitus patients with microalbuminuria.

Kidney biopsies from 15 insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria were investigated to obtain quantitative data on the juxtaglomerular apparatus. The IDDM patients were young and normotensive with a mean duration of microalbuminuria of 2 years. Eight healthy kidney donors served as controls. Measurements taken by light microscopy, using 1-microm serial sections of epon blocks, included volumes of the juxtaglomerular apparatus and of glomeruli, areas of the macula densa and luminal area of the juxtaglomerular (afferent and efferent) arterioles at the level of the glomerular vascular pole. The volume of the juxtaglomerular apparatus was significantly larger in the IDDM group than in controls [6.08 (2.96-18.8) 10(4) microm3 vs 3.48 (1.84-5.21) 10(4) microm3, P=0.003, median and (range)], as was the volume of the juxtaglomerular apparatus relative to glomerular volume [1.89(1.28-4.21)% vs 1.48 (1.13-1.71)%, P=0.004]. The area of the macula densa was also larger in the IDDM patients (1370 microm2 vs 937 microm2, P=0.03). Luminal areas of the afferent and efferent arterioles and the ratio between them did not differ significantly between the two groups. In conclusion, the juxtaglomerular apparatus is enlarged more than would be expected from the glomerular hypertrophy in IDDM patients with microalbuminuria.

Adolescent↗