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Biomedical subjects

Y Collan

Publications and source records attributed to Y Collan.

At least 73 records · Page 4Linked to original sources

Transmural differences in ischaemic heart disease: a quantitative histologic study.

To evaluate the possible transmural differences in the structure of left ventricular myocardium in patients with ischaemic heart disease, 45 human hearts were examined with morphometric methods. There were 10 control hearts, 10 hearts with coronary atherosclerosis but without myocardial infarction, 11 hearts with acute subendocardial infarction and 14 hearts with acute transmural infarction. The following histoquantitative parameters were separately estimated for both subendocardium and subepicardium in each heart: the volume fraction of diffuse connective tissue, the mean fiber diameter and the numerical density of arterioles. Diffuse myocardial fibrosis was more severe in subendocardium in all groups, the highest values were found in hearts with acute subendocardial infarction. In all groups the numerical density of arterioles was higher in subendocardium. The numerical density of arterioles was increased in respect to the controls in both subendocardium and subepicardium in hearts with coronary atherosclerosis without evidence of myocardial infarction and in hearts with acute subendocardial infarction. The possible pathophysiological implications for ischaemic heart disease are discussed on the basis of these results. The results suggest different pathophysiological mechanisms in subendocardial and transmural myocardial infarction. They also suggest that transmural differences should be considered when the findings of endomyocardial biopsies are evaluated.

Adult

Comparative liver toxicity of various erythromycin derivatives in animals.

The hepatotoxicity of a new erythromycin derivative, erythromycin acistrate (EA, 2'-acetyl erythromycin stearate), was compared with that of erythromycin stearate (ES), erythromycin estolate (EE) and erythromycin-11,12 cyclic carbonate (EC) in 4-5-day, 28-day and 6-month oral toxicity studies in rats and dogs. In the 4-day rat study, EC caused fatty metamorphosis in the liver. ES caused similar, but milder changes at a dose nearly five times higher. The 5-day dog study revealed markedly increased serum alanine aminotransferase (S-ALAT), serum aspartate aminotransferase (S-ASAT), serum alkaline phosphatase (S-APHOS) and serum gamma-glutamyl transpeptidase (S-gamma-GT) values in the EC- and EE-groups, and slightly elevated S-ALAT values also in the EA- and ES-groups. Microscopy revealed cholangitis, pericholangitis and phlebitis in the portal areas in the EC-group at all doses. Epithelial hyperplasia was observed also in the bile ducts. EE caused similar but milder changes. The changes in the EA-group were small, but mildly atypical bile duct epithelium was seen in female dogs receiving 2 x 200 mg/kg of EA. The ES-group was practically without changes and very much like the EA-group. Thus the dog proved to be a more sensitive model for assessing the hepatotoxicity of erythromycin derivatives. In the 28-day studies, only EA and ES were investigated. In the rat study, slightly elevated serum enzyme levels within the normal range were measured in the high-dose regimens of both drugs. In the dog study, 300 mg/kg of EA caused slightly elevated S-ALAT in males, but the values returned to normal after a 2-week off-dose period. Only EA was studied in the 6-month study. In male rats, 400 mg/kg of EA caused slightly elevated enzyme levels and neutral fat droplets in centrilobular hepatocytes. In male dogs given 150 mg/kg of EA, S-ALAT, S-APHOS, and S-gamma-GT values were elevated after four weeks of treatment but returned to normal thereafter. No severe changes were seen in the liver histopathology. In conclusion, EC and EE were clearly hepatotoxic in dogs, and EC also in rats. EA, and to a somewhat lesser extent ES, showed signs of mild hepatotoxicity only at high doses. This evidently reversible effect was considered a common characteristic of erythromycins.

Animals

Oral cancer in children under 15 years of age. A clinicopathological and virological study.

11 malignant tumours of the oral region in children under 15 years of age were diagnosed in Finland during the 20-year period from 1961 to 1980; the age adjusted annual incidence rate being 0.31 per 1,000,000 children. 5 cases were intraoral cancer and 5 cases malignant tumours of the major salivary glands. The formalin-fixed tumours were studied using the in situ DNA hybridization technique for Adenovirus, group II, Epstein-Barr and human papillomavirus, type 16. For the first time, evidence was provided for the presence of Epstein-Barr virus in a malignant salivary gland tumour, implicating a possible etiological role for this virus in salivary gland neoplasms.

Adolescent

Reproducibility of mitotic counts and identification of mitotic figures in malignant glial tumors.

Quantitative pathology is a rapidly growing field of pathology. This field is developing methods allowing greater objectivity and better reproducibility in diagnostic decisions. The introduction of quantitative pathology as a teaching subject in medical education will help this field to become more widely and more correctly applied. Courses on quantitative pathology are organized yearly by the Department of Pathology at the University of Ancona. The 1986 course emphasized training of students in understanding basic problems such as variation caused by tissue processing, instrumentation, data handling and interpretation, and variation between observers. In this paper we describe experiments performed during the course on identification and quantitation of mitoses in malignant glial tumors. The participants, i.e. students of the postgraduate Pathology School, could identify mitoses with a 'substantial' reproducibility. However, when the observers were allowed freely to choose the fields to count, the reproducibility was 'slight'. The study suggests that sampling rules should be applied which secure reproducible application of morphometric method also on condition of free selection of fields. Because the application of such rules needs expertise in histopathology, it seems that morphometric method can best be applied by histopathologists themselves.

Glioma

Cancer-associated antigen CA 15-3 in the diagnostics of breast tumours.

The serum concentration of the new marker CA 15-3 was determined by a kit method, which is based on the use of two different monoclonal antibodies 115D8 and DF3, in a coated tube immunoradiometric technique. The mean CA 15-3 values in breast cancer patients (n = 40) were significantly higher than in patients with benign breast disease (n = 52, p less than 0.001) and in control subjects (n = 32, p less than 0.001). When we used the cut-off level 35 kU/l for CA 15-3, 0/32 of control subjects, 1/52 (2%) of patients with benign breast disease, 8/40 (20%) of all breast cancer patients, 6/19 (32%) of breast cancer patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were above this level. Among the same patients the CEA serum test was positive at a cut-off level of 5 micrograms/l in 7/40 (18%) cancer cases, and in 6/19 (32%) of cancer patients with nodal involvement. When we used the cut-off level 35 kU/l for CA 15-3 and 5 micrograms/l for CEA 1/52 (2%) of patients with benign breast disease, 10/40 (25%) of all breast cancer patients, 7/19 (37%) patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were positive in one or both of the tests. The serum CA 15-3 and CEA values were higher in patients with tumour size above 2 cm in diameter than in patients with smaller tumours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Intravascular bronchioloalveolar tumor.

A 17-year-old girl was operated for a solitary well-circumscribed pulmonary parenchymal tumor and reoperated ten times for multiple recurrent similar pulmonary tumors during 24 years. Histologic examination revealed the so-called intravascular bronchioloalveolar tumor (IVBAT) in all instances. The patient died from pneumonia superimposed on decreased respiratory function 24 years after the onset of disease. This is the longest survival so far reported in IVBAT. The treatment was surgical in all phases of the disease, and the patient did not receive radiotherapy or cytostatic drug therapy. Mediastinal and pleural tumor nodules were removed 17 years from the first pulmonary operation, and 24 years after the first operation a fibrous tumor was removed from the retroperitoneal space. Immunohistologically, the tumor cells were positive for vimentin-type of intermediate filaments, in line with their mesenchymal nature. Endothelial markers, Factor VIII-related antigen and Ulex europaeus I lectin binding, were not found in convincingly neoplastic cells, and Schwann cell, epithelial cell, muscle cell, and histiocytic markers were absent. Thus, IVBAT appears to be a low-grade malignant mesenchymal neoplasm, composed of poorly differentiated mesenchymal cells, whose exact nature remains undefined with the currently used cell-type markers.

Adolescent

Squamous cell carcinoma of the tongue in children.

Only 14 case reports of squamous cell carcinoma of the tongue in children under 15 years of age had been published until 1980. One was reported in Finland as a second tumor in a patient with retinoblastoma. According to the Finnish Cancer Registry, which covers the whole population, three cases of squamous cell carcinoma of the tongue in children under 15 years of age have been diagnosed in Finland during the 20 years from 1961 to 1980; the age-adjusted annual incidence rate being 0.13 per 1,000,000 children per year. According to the available material, the prognosis of squamous cell carcinoma of the tongue in children is poor. The treatment has followed the guidelines for adults.

Adolescent

Sampling in diagnostic morphometry: the influence of variation sources.

The variation sources relevant to a diagnostic morphometric study were analysed. The influence of each source was estimated in two experiments, performed in systems applying computer assisted interactive morphometry. In the first experiment one observer measured the areas of a large number of nuclei in a section from a grade II transitional cell carcinoma of the bladder. In the second experiment two groups of researchers, from Ancona and Kuopio, measured one field from five different samples of transitional cell tumours (including the case of grade II carcinoma). It turned out that pure interobserver variation was responsible for about a half of the total variation present in the diagnostic system. When the variation characteristics of the diagnostic system had been determined, the number of nuclei that had to be measured to reach a defined level of accuracy could be estimated. Such an estimate was also dependent on the predefined expectancy probability of reaching a correct estimate. The study showed that group morphometry (statistical, investigative morphometry) and diagnostic morphometry must be understood as two different approaches in histopathology. By applying group morphometry, good research results can be gathered with cruder measurements than in diagnostic morphometry. Because investigations in group morphometry are more standardized than in diagnostic morphometry, a larger number of structures has to be measured in diagnostic histopathology for the same level of accuracy.

Analysis of Variance

Effect of testosterone and anabolic steroids on the size of sebaceous glands in power athletes.

The effect of testosterone and anabolic steroids on the size of sebaceous glands was studied by means of interactive morphometry in skin biopsies of power athletes. The subjects used self-administered high doses of testosterone and anabolic steroids during a 4-week strength training period. After 4 weeks' use of hormones, the area of sectioned sebaceous glands enlarged significantly by a factor of 89.2% (p less than 0.005). The number of cells in the so-called differentiating cell pool (DCP) and in the undifferentiated cell pool (UCP) also increased significantly (p less than 0.025, p less than 0.05, respectively). The size of the area occupied by UCP cells increased significantly (p less than 0.05). The study suggests that high doses of testosterone and anabolic steroids lead to an enlargement of sebaceous glands in male power athletes.

Adult

Human papillomavirus DNA in squamous cell carcinomas of the larynx demonstrated by in situ DNA hybridization.

A series of 116 consecutive laryngeal squamous cell carcinomas were analyzed using an in situ DNA hybridization technique with 35S-labelled human papillomavirus (HPV) DNA probes to demonstrate the DNA of HPV types 6, 11, 16 and 30, in routinely processed, paraffin-embedded biopsies. The lesions were also assessed on light microscopy for HPV-suggestive morphological features, and by indirect immunoperoxidase (IP-PAP) technique to demonstrate the expression of HPV structural proteins (viral antigens). A total of 15/116 (12.9%) of the tumors were shown to contain the DNA of at least one HPV type. HPV 11 was the most frequent DNA type, found in 9/116 (7.8%) of the lesions, followed by HPV 16 (5.2%), and HPV 6 (4.3%). Noteworthy is the failure to disclose the recently described HPV type 30 DNA (suggested to be specific for laryngeal carcinomas) in any of the 116 carcinomas studied. Double infections (more than one HPV type) were disclosed in 5 (33.3% of the HPV DNA-positive) carcinomas: HPV 6 and 11, 1 case; HPV 6 and 16, 2 cases, and HPV 11 and 16, 2 cases. Light microscopic morphology was HPV-suggestive in 6 (40%) of the 15 HPV DNA-positive lesions, but HPV antigen expression could be demonstrated in one of these tumors only (6.7%). The present findings provide support to the concept on HPV as an etiological agent in laryngeal squamous cell carcinoma, most probably acting synergistically with chemical carcinogens. In addition to the 'high risk' HPV 16, a risk to develop a laryngeal malignancy may be associated with the 'low risk' types HPV 6 and 11 as well, previously demonstrated in benign laryngeal papillomas only.

Biopsy

Artifacts in ultrastructure of respiratory cilia caused by various fixation procedures and different types of handling.

The ciliary ultrastructure with different fixatives and buffer combinations and artifacts caused by handling the specimens was studied in samples from respiratory mucosa. After different standard fixatives the ciliary ultrastructure did not vary much. Glutaraldehyde in cacodylate gave the best result; the contrast was good and the cell membrane did not show undulation and so many blebs as with other fixatives. With old 4% formaldehyde + 1% glutaraldehyde inphosphate the cytoplasm was darker and the contrast was not as good as with a fresh fixative. Mechanical damage caused rupture of the cell membrane and sometimes changes in axonemal architecture. These findings are similar to those often seen in human samples. The axonemal architecture was always intact if the cell membrane was intact.

Animals

Application of morphometry in tumor pathology.

The application of morphometry in tumor pathology is discussed, e.g., its use in studying the biology of tumors, in creating tumor classification(s), in creating methods for the identification of a tumor in the diagnostic context, and in characterizing diagnostic histopathology in absolute terms. In traditional subjective diagnostic histopathology, reproducibility can be defined satisfactorily, but the definition of accuracy is ambiguous; in morphometric histopathology, a satisfactory definition is found for both concepts but it may be difficult to separate them in practice. Morphometric histopathology can study parameters measured from sections or parameters derived from the primary measurements through calculations. In the histopathology of tumors, the following parameters have turned out to be specially valuable: densitometric measurements of nuclei, nuclear area, perimeter and form factors, nucleolar parameters, the number of mitotic cells per area, the cellularity, the volume fraction of the epithelium, and parameters associated with the fraction of tumor tissue in the sample. The standard deviation or other moments of the distribution of these measurements can be more relevant than the mean values of the results. This indicates that more attention should be given to sampling rules, which are important in defining the efficiency of the methods. For rational application of morphometric methods, it is very important to make a distinction between group morphometry and diagnostic morphometry. The latter engenders numerous sources of variation (variation in section thickness, variation in tissue processing, variation in the techniques of measurement, interobserver variation, interlaboratory variation, variation due to subjective interpretation, etc.), which are usually better controlled in group morphometry. The influence on morphometric parameters of variation in section thickness and tissue shrinkage during processing are discussed.

Animals

Toxicity of richterite in hemolysis test and macrophage cultures.

Richterite is a fibrous mineral associated with apatite deposits in eastern Finland. Fibre size features suggest potential toxicity but no data is available of fibrogenic effects on human lungs. The toxicity of richterite in a hemolysis test and in lung macrophage cultures was studied. In the hemolysis test richterite-rich samples showed the same degree of hemolysis as titanium dioxide whereas anthophyllite, crocidolite, chrysotile, wollastonite and quartz samples had distinctly higher degree of hemolysis. In the macrophage toxicity assay the percentage of dead cells was counted, and LDH, ASAT and acid phosphatase were determined from the culture medium. In this assay richterite showed lower toxicity than anthophyllite, crocidolite, chrysotile or quartz but gave higher values than titanium dioxide. Wollastonite showed similar level of toxicity. Differences were statistically highly significant. The results suggest that richterite (with wollastonite) belongs to a group of fibrous minerals which have distinctly smaller biological effect than traditional asbestos minerals.

Animals

Mushroom poisoning due to Cortinarius speciosissimus: electron microscope study in rats.

The effects of a poisonous mushroom, Cortinarius speciosissimus, on rat kidney were studied by transmission electron microscopy. Suspension of dried mushroom (500 mg/kg body weight) was administered as a single dose directly into the esophagus. The kidneys were fixed by perfusion, and both cortex and medulla were sampled. C. speciosissimus toxin acted primarily on the epithelial cells of the proximal tubules. No changes were seen in the glomeruli. First ultrastructural changes were observed at 2 days in the renal cortex. The most prominent damage occurred at 5 days, when most of the proximal tubular cells appeared necrotic. Dark bodies (diameter 0.15-0.5 micron) spaced by 25-45 nm were frequently found in the damaged tubular cell nuclei. Regeneration of the tubular cells was seen at 10 days. After 2 months, increased amount of collagen fibres were seen between tubules. The nuclear changes in the damaged tubular cells and the slowly manifesting toxicity suggest that C. speciosissimus toxin acts on nuclei or nucleoli and/or metabolic pathways associated with them.

Animals

Ethylenethiourea and nabam induced alterations of function and morphology of thyroid gland in rats.

Male Wistar rats were given 0-200 mg/l of nabam and 0-300 mg/l of ethylenethiourea (ETU) in drinking water ad libitum for 28 d to study their effect on thyroid gland function and morphology. Blood samples for RIA hormone assays (T3, T4, TSH) were taken and thyroids of each rat were dissected out for routine light and electron microscopic analysis after sacrifice performed under CO2 anesthesia. Nabam (8.4-30.5 mg/kg bw/d) inhibited dose-dependently T4-secretion and increased T3-secretion, but had no effect on basal TSH-secretion. ETU (10.6-23.4 mg/kg bw/d) inhibited dose-dependently T4- and T3-secretion. ETU also increased basal TSH-secretion tenfold, obviously due to the lack of negative feedback by T4 and T3. Light microscopic analysis revealed neither nabam nor ETU induced morphological alterations in thyroids. Both but especially ETU induced, ultrastructural changes, namely increased number of myelin bodies, dilatation of the rough endoplasmic reticulum, and increased vacuolization in the epithelial cells of thyroid follicles. The functional alterations are obviously connected with, and preceed slight ultrastructural degenerative changes in thyroid follicle epithelial cells even at low doses of nabam, and ETU, after a short-term oral administration.

Animals

Histopathological and morphometrical analysis applied to skin changes in NMRI mice induced by dithranol (anthranil) and its acyl analogs.

Histology and morphometric changes in skin lesions of NMRI mice caused by dithranol and its acyl analogs, with and without pretreatment with dimethylbenzanthracene (DMBA) are described. The course of neoplastic progression seems to have three distinct phases (normal skin, hyperplasia, papilloma), each characterized by typical architectural and cellular changes. The parameters reflecting the nuclear size increased in the above order and the differences between the groups were highly significant. Nuclear shape changes did not take place, as shown by the almost constant form factor. The study demonstrates the value of the morphometric methodology in characterizing quantitative nuclear changes in mouse skin models.

9,10-Dimethyl-1,2-benzanthracene