bluuebunny/crossref_metadata_2025 huggingface dataset:
BASAL CELL CARCINOMA IN THE HEAD AND NECK
Authors: AFZELIUS LARS‐ERIK , EHNHAGE ANITA , NORDGREN HANS
Published: August 2010

A scoring system for judging the aggressiveness of basal cell carcinomas of the head and neck is devised, based upon 258 tumours from 123 patients. This system is discussed, and we suggest using the depth of growth, the degree of palisading and the narrow epithelial strand formation (narrow strands) as a scoring basis. It is shown that tumours located on the ear are more aggressive than tumours in other places. Tumours on the nose often recur, even though their histological picture is not that aggressive. This phenomenon is also discussed. For proper scoring, an excisional biopsy should be performed unless the tumour is very small. Recurrent tumours and tumours treated with X‐ray also have a higher score.
ACTION ON VARIOUS EXPERIMENTAL TUMOUR‐HOST SYSTEMS OF METHOXY‐SUBSTITUTED GLYCEROL ETHERS INCORPORATED INTO THE FEED
Authors: BOERYD BERNT , HALLGREN BO
Published: August 2010

The effect on the growth and spread of tumours by methoxy‐substituted glycerol ethers incorporated into the feed has been tested on a broad spectrum of tumour‐host systems. Inhibitory effects on tumour growth were noted mainly by 1‐0‐(2‐methoxy‐hexadecyl) glycerol and on Melanoma B16, Lewis Lung Tumour, MCA‐sarcoma MCG101 and the lymphomas LAA and P1534. Spontaneous metastasis formation from Melanoma B16 and two MCA‐sarcomas was inhibited.
CONGOPHILIC SUBSTANCE WITH GREEN DICHROISM IN HIP JOINTS IN AUTOPSY MATERIAL
Authors: LADEFOGED CHRISTIAN , CHRISTENSEN HANS EWALD
Published: August 2010

Cartilage and fibrous capsular tissue from the hip joints of 30 unselected autopsies have been examined for the presence of congophilic substance with green dichroism (CS‐GD). Ninety‐three per cent of the cases had CS‐GD in the joint cartilage and 43 per cent contained amyloid deposits in the capsule. The relation of these substances to age and the relation of CS‐GD to the upper and lower parts of the femoral head cartilage have been studied, as well as the inter‐relationship between the presence of CS‐GD in the cartilage and amyloid deposits in the capsule within each joint.
DIAGNOSTIC VALUE OF MODIFIED FINE‐NEEDLE ASPIRATION BIOPSY OF THE KIDNEY IN GLOMERULAR DISEASES
Authors: HELIN HEIKKI
Published: August 2010

43 renal fine‐needles aspirates, obtained with a modified sampling technique were subjected to ultrastructural examination with the aim of assessing the diagnostic value of this method in various glomerular diseases. Findings in the aspiration specimens, consisting of solitary glomeruli, were regarded as diagnostic in 35% of the cases. When considered together with clinical data, the fine‐needle aspiration biopsies were suggestive of diagnosis or provided valuable information in a further 49% of the cases. Due to the small outer diameter of the fine‐needle, 0.7 mm, complications following this kind of biopsy are practically negligible. Thus, it offers a safe alternative to the conventional renal biopsy methods utilizing large‐bored cutting needles in cases where biopsies with these methods are contraindicated.
XANTHOGRANULOMATOUS PYELONEPHRITIS
Authors: MØLLER JENS CHR. , KRISTENSEN INGRID B.
Published: August 2010

Nineteen cases of xanthogranulomatous pyelonephritis (XP) were studied. There was a close relation to pyonephrosis, and urinary tract obstruction was present in all cases but one which represented the tumorous variety of XP. The degree of xanthogranulomatous involvement was correlated to the severity of the acute inflammatory affection as evidenced by the clinical findings and the urographical excretory function. The topography of the xanthogranulomas was related to the level of urinary tract obstruction in accordance with the pattern of reaction common to obstructive pyelonephritis. Haemorrhage and considerable fibrous thickening and stenosis of arteries surrounding the xanthogranulomatous foci were conspicious features. Based upon a morphological staging it was shown that the structural changes (towards fibrosis) were parallelled by a series of cellular events indicating removal of intracellular lipids in xanthoma cells by transformation to lipofuscin and transport in PAS‐positive interstitial macrophages. This was comparable to the findings in experimental XP suggesting a similar and simple way of pathogenesis. It is concluded that XP — with the possible exception of the tumorous variety — can be ascribed to local resorption phenomena caused by concurrent factors usually involved in pyelonephritis, urinary tract obstruction being the essential precondition, focal haemorrhage and ischaemia contributary elements.
DISTRIBUTION OF ATHEROSCLEROSIS IN HUMAN DESCENDING THORACIC AORTA
Authors: SVENDSEN EINAR , EIDE TOR J.
Published: August 2010

A morphometric study of 49 randomly selected human aortas is reported with regard to the distribution of atherosclerotic lesions in the descending thoracic aorta (DTA). The intercostal artery area (ICA‐area) revealed a higher degree of atherosclerosis compared with the remaining part of the DTA. The difference was more striking at overall lower grades of atherosclerosis of the DTA. The ventral aspect of the DTA in the proximal and caudal thirds showed a higher degree of atherosclerosis compared with the middle third. The atherosclerotic indices of the proximal and distal areas correlated significantly with increasing heart weights but not for the middle third. The explanation of this is, presumably, irregular flow conditions. For the distal part a possible effect of continuous pounding of an enlarged heart upon the ventral aspect of the descending thoracic aorta is discussed.
EFFECT OF ESTRADIOL AND PROGESTERONE ON THE ADENYLATE CYCLASE ACTIVITY IN GRAFTS OF 3‐METHYLCHOLANTHRENE INDUCED CARCINOMAS IN THE MOUSE UTERINE CERVIX
Authors: KVINNSLAND STENER , LØNNING PER EYSTEIN , FORSBERG JOHN‐GUNNAR
Published: August 2010

Grafts from a methylcholanthrene induced mouse uterine cervical carcinoma (NMRI mice) were grown in neonatal female mouse hosts. The hosts were treated for 12 days with estradiol and progesterone alone or in combination. Controls were injected with the solvent (olive oil) only. Pieces from every graft were used for histological study, for study of the proliferation rate and for study of the adenylate cyclase activity in homogenate. All the grafts were well differentiated squamous carcinomas and the histological picture was the same irrespective of hormonal treatment. The proliferation rate was the same in control grafts as in those from hosts treated with hormones. Grafts from progesterone and progesterone/estradiol injected hosts had significantly higher levels of adenylate cyclase activity compared with grafts from control hosts. Estradiol alone resulted in a trend towards increased activity but the difference to controls was not statistically significant.
MICROFILAMENTS IN CELLS ASSOCIATED WITH INDUCED HETEROTOPIC BONE FORMATION IN GUINEA PIGS
Authors: NILSEN RUNE
Published: August 2010

Sera from patients with active chronic hepatitis were used to demonstrate actin microfilaments in cells of a bone‐induced model. Demineralized and freeze‐dried allogenic dentine was implanted in the abdominal muscles of Guinea pigs. After 21 and 28 days the tissue was excised and showed: a) resorption areas of the dentine contained dentinoclasts and macrophages. b) osteoid and bone and c) areas of fibroblastic proliferation. Osteoblasts and young osteocytes showed the strongest fluorescent staining. Electron microscopy of these cells demonstrated abundant 5–7 nm microfilaments interpreted as actin in the outer parts and cell projections, in which some microtubules also were observed. Fewer microfilaments were present in mature osteocytes although the cell projections in mineralized bone also showed microfilaments. Microfilaments were also found in some dentinoclasts where the actin was located in projections from the ruffled border protruding into the dentine. The localization in the ruffled border corresponded to the distribution of the fluorescent staining of actin. The high amount of actin in osteoblasts and osteocytes may be correlated to the synthesis and transport of the new matrix components. The microfilaments in the clear sealing zone of dentinoclasts were considered to have a function in the sealing of the ruffled border.
PULMONARY BLASTOMA
Authors: JACOBSEN MARIANNE , FRANCIS DORTHE
Published: August 2010

Eleven cases of pulmonary blastoma are presented, the largest series reported from one department to date. The frequency of pulmonary blastoma was found to be 0.5 per cent of all primary lung cancers. The variegated histologic appearance of the tumour and the diverging metastatic pattern are described in detail. In light of the complex histological picture and the biological behaviour a suggestion of the histogenesis of pulmonary blastoma is attempted.
CORONARY ATHEROSCLEROSIS IN MIDDLE‐AGED AND ELDERLY FINNISH MEN. PATHOLOGICAL STUDY OF CORONARY ARTERIES IN VIOLENT AND SUDDEN CORONARY DEATHS
Authors: RISSANEN VILJO
Published: August 2010

The occurrence of coronary atherosclerosis was studied in 271 Finnish men aged 40 years or more, of whom 143 had met a violent death and 128 had died suddenly of coronary heart disease (CHD). A coronary stenosis was found in half of the men who had met a violent death and were over 50 years old. The occurrence of the stenosis was closely related to the extent of the raised atherosclerotic lesions (RI.) and to the degree of the plaque calcification. In 60% of the sudden deaths (SD) the extent of RL did not differ from that in violent deaths. The stenosis patterns in these SD were similar to those in living CHD patients. The remaining SD had an extreme stage of coronary artery involvement, i.e. extensive plaques with severe obstructive changes. The men in this study series of violent deaths born in various parts of the country did not differ with regard to the extent of RL. Within the upper half of the RL area range, men born in the east were consistently shown to have a stenosis, while the occurrence in men from the western counties was more random. Severe stages of coronary artery involvement tended to be more frequent in SD patients born in the east than in those born in the west. It was concluded that there are probably two background factors concerning the difference in CHD mortality between men in western and eastern Finland: 1) the tendency to form a stenosis by the advancement of RL extent is stronger, and 2) the progressive development of coronary artery disease in CHD patients is more frequent in the east than the west.
HEART PATHOLOGY IN RATS FED PARTIALLY HYDROGENATED FISH OIL, RAPESEED OIL OR PEANUT OIL FOR 30 WEEKS.
Authors: SVAAR H. , LANGMARK F. T.
Published: August 2010

132 maleSprague‐Dawleyrats were given diets for 30 weeks including rapeseed oil with 41.4% erucic acid, partially hydrogenated fish oil with 15.1% docosenoic acids, or peanut oil with no docosenoic acids. Four diets were isocaloric and contained respectively 21% rapeseed oil (8.7% w/w erucic acid). 10.5% rapeseed oil and 10.5% peanut oil (4.4%. w/w erucic acid). 21% partially hydrogenated fish oil (3.2% w/w docosenoic acids) and 21% peanut oil. The fifth diet contained 4.3% peanut oil. The relative heart weights increased in rats fed rapeseed oil and partially hydrogenated fish oil, and abnormally enlarged hearts were found in 32% of the rats fed 21% rapeseed oil and in 5% of those fed 10.5%, rapeseed oil. Heart lesions consisting of focal or confluent destruction of muscle cells were seen in all groups. The incidence was 96% and the average severity grade 2.5 when 21% rapeseed oil was given, and 61% and 1.3 respectively when 10.5% rapeseed oil was given Minor heart lesions were found in 14% of the rats fed 21% partially hydrogenated fish oil, in 39% of those fed 21% peanut oil and in 12% when 4.3% peanut oil was given. It is concluded that partially hydrogenated fish oil is markedly less cardiopathogenic than high erucic rapeseed oil. The heart lesions that were found do not differ in incidence, severity or morphology from those found when peanut oil was given. or from those reported when other control fats and oils are given to rats for prolonged feeding periods.
SOMATOPETAL TRANSPORT OF HORSERADISH PEROXIDASE FOLLOWING INCORPORATION INTO AXONAL SPROUTS AND AXONS IN NEUROMAS AFTER NERVE TRANSECTION
Authors: OLSSON TOMAS
Published: August 2010

Horseradish peroxidase (HRP) applied to the proximal stump of the facial nerve of the mouse 5 h after section diffused into the endoneurium and was incorporated by endocytosis into axons densely packed with organelles. By 24 h to 16 days after the section, uptake of the tracer into profiles of outgrowing axonal sprouts rich in vesicles and vacuoles was registered. Subsequently HRP accumulated in corresponding perikarya. Tracer transport from neuromas was demonstrated 32 and 64 days after section. In this way influences from outgrowing nerve sprouts and axons in neuromas may reach nerve cell bodies.
INTESTINAL METAPLASIA WITH COLONIC‐TYPE SULPHOMUCINS IN THE GASTRIC MUCOSA; ITS ASSOCIATION WITH GASTRIC CARCINOMA
Authors: SIPPONEN P. , SEPPÄLÄ K. , VARIS K. , HJELT L. , IHAMÄKI T. , KEKKI M. , SIURALA M.
Published: August 2010

The occurrence of intestinal metaplasia with colonic‐type sulphomucins: (abbreviated: s‐IM or s‐positive IM) in the gastric mucosa was studied in 125 patients with gastric carcinoma (GCA), 62 patients with pernicious anemia (PA), 301 and 183 first‐degree relatives of GCA and PA patients, 406 outpatients and in 358 controls matched from a large population sample. The sulphomucins (s‐mucins) were demonstrated histochemically in endoscopic biopsy specimens by using high iron diamine and Alcian blue (pH 1) methods. The prevalence of s‐IM, especially the strongly s‐positive IM, was significantly higher in GCA patients than in other series or controls of the same age group. Further, s‐IM was significantly more common in PA patients and its prevalence higher in GCA relatives and outpatients than in other series or controls. The occurrence of s‐IM was also age‐dependent and dependent on the extent of IM. It was suggested that the occurrence of s‐IM can be used as a sign of lesions that are more closely associated with GCA than IM is in general.
AUTOLOGOUS IMMUNE COMPLEX NEPHRITIS AND DOCA‐NaCl LOAD: A NEW MODEL OF HYPERTENSION
Authors: TIKKANEN ILKKA , FYHRQUIST FREJ , MIETTINEN AARO , TÖRNROTH TOM
Published: August 2010

In order to explore immunological features of hypertension, we studied autologous immune complex nephritis (Heymann nephritis) combined with DOCA‐NaCl treatment. This combination resulted in hypertension and increased heart weight whereas DOCA‐NaCl treatment alone induced only a slight elevation of blood pressure and a moderate increase in heart weight. Nephritic rats without DOCA‐NaCl load remained normotensive, their heart weights being comparable to those of controls. This new model of hypertension was neither characterized by azotemia nor by reduced renal excretory capacity. Hypertension was not renin‐angiotensin‐dependent. DOCA‐NaCl treatment accelerated the development of proteinuria. In the hypertensive rats, systolic blood pressure correlated to daily urinary protein excretion. Renal histopathology revealed changes resembling those of malignant nephrosclerosis. Immunohistology and electron microscopy showed a typical membranous glomerulonephritis in all immunized animals. It was concluded that immune complex disease of the Heymann nephritis type may interfere with normal hemodynamic adaptation to hypervolemic sodium load, resulting in hypertension.
SURFACE CHANGES IN THE ARTICULAR CARTILAGE OF RABBIT KNEE DURING IMMOBILIZATION. A SCANNING ELECTRON MICROSCOPIC STUDY OF EXPERIMENTAL OSTEOARTHRITIS
Authors: CANDOLIN T. , VIDEMAN T.
Published: August 2010

Osteoarthritis was produced by the immobilization of rabbit knees in extension for 1–8 weeks (with a subsequent mobilization period of 0 or 8 weeks). The development of articular surface changes in the tibia, the femur and the patella was examined with scanning electron microscopy (SEM). During the development of osteoarthritis the normal undulations and fine regular fibre network disappeared, the number of fibres and the variation in the thickness of the fibre bundles increased, and scaly irregularities appeared. Some degenerative changes in the contralateral, non‐immobilized hind limb also appeared. The normal features of the articular surface of the patella differed from that of the tibial and femoral condyles. The changes seen with SEM correlated well with histological and biochemical results of earlier studies, but, at 1 week of immobilization, the SEM changes were more readily apparent than the histological changes. The SEM method seems to be useful for the study of articular surfaces;
STAINING OF RAT THYROID PARAFOLLICULAR (C‐) CELLS WITH THE SEVIER‐MUNGER SILVER TECHNIQUE
Authors: Wilander Erik , Juntti‐Berggren Lisa , Lundqvist Monalill , Grimelius Lars
Published: August 2010

The argyrophil silver stain of Grimelius and of Sevier‐Munger was studied in rat thyroid parafollicular (C‐) cells after formalin and Bouin fixation. The strongest and most easily reproducible staining reaction was obtained in tissues fixed with Bouin's fluid and stained by the Sevier‐Munger technique. The identity of the argyrophil cells as the calcitonin‐containing C‐cells was established by re‐staining the same sections with calcitonin antibodies according to the method of Sternberger.
THE ANTRAL GASTRIN‐PRODUCING CELLS IN DUODENAL ULCER PATIENTS
Authors: NIELSEN H. OVERGAARD , JENSEN K. BIRGER , CHRISTIANSEN L. A.
Published: August 2010

A density study of the antral gastrin‐producing cells has been performed, before and after eight weeks of treatment with a histamine H2‐receptor antagonist (cimetidine 1 g per day), in a series of 38 patients suffering from chronic duodenal ulcer. The treatment produced a significant increase in numerical density and a decrease in mean cell volume. The volume density of the cells was unchanged, suggesting that the elevated serum‐gastrin during treatment may be the result of gastrin‐cell hyperplasia, without change in the total gastrin‐cell volume. The authors suggest that G‐cell hyperplasia demonstrated during cimetidine treatment may be a factor of importance with regard to the rapid recurrence of many ulcers after discontinuation of the treatment.
TALC DUST PNEUMOCONIOSIS
Authors: BERNER A. , GYLSETH B. , LEVY F.
Published: August 2010

Various types of mineral dust can induce interstitial pulmonary fibrosis, but there is no definite correlation between lung X‐ray findings, tissue lesions and the type of dust. In this paper, we report on the post mortem verification of talcosis by lung tissue analysis, using light microscopy, scanning electron microscopy, energy dispersive x‐ray microanalysis and x‐ray diffractometry.
TUMOR CLASSIFICATION BY ELECTRON MICROSCOPY OF FINE NEEDLE ASPIRATION BIOPSY MATERIAL
Authors: COLLINS V. P. , IVARSSON BIRGITTA
Published: August 2010

The application of fine needle aspiration biopsy cytology to tumor diagnosis and classification is gaining increased acceptance. The classification of some poorly differentiated tumors may prove particularly difficult for the cytologist as well as for the pathologist. In such cases electron microscopic examination of fine needle aspiration biopsy material can be of great assistance. A simple, yet dependable, technique is described for the study of such material. The method has been shown to be of decisive importance in the classification of 80% of a selected series of cases submitted to ultrastructural analysis. Using this method, a preoperative diagnosis can be obtained in otherwise equivocal cases.
LYSOZYME IN NEOPLASTIC PANETH CELLS OF A JEJUNAL ADENOCARCINOMA
Authors: REITAMO S. , REITAMO J. J. , KONTTINEN Y. T. , COLLAN Y. , SIPPONEN P.
Published: August 2010

This is the first reported case in which neoplastic cells not of granulocytic or monocytic origin have been shown to contain lysozyme. A highly differentiated metastasizing adenocarcinoma of the jejunum is presented. Areas of the tumour contained cells resembling Paneth cells, that is, they contained cytoplasmic granules which 1) stained red with Masson's trichrome and 2) were shown to contain lysozyme by an immunoperoxidase technique. No argentaffin cells could be identified within the tumour. Staining of mucosubstance revealed large intestine‐type sulfated glycoproteins in the tumour tissue. The presence of lysozyme‐containing neoplastic Paneth cells suggests that the tumour: 1) originated from the mucosal crypts, and 2) had a high degree of cellular differentiation.
CARDIOVASCULAR LESIONS IN SPRAGUE‐DAWLEY RATS INDUCED BY LONG‐TERM TREATMENT WITH CAFFEINE
Authors: JOHANSSON SONNY
Published: August 2010

Male Sprague‐Dawley rats were treated with phenacetin, phenazone or caffeine in the diet or with combinations of these chemicals for up to 117 weeks. Twenty of twenty‐eight rats receiving caffeine only developed moderate to severe myocardial fibrosis compared with five control rats, in spite of the fact that the control rats had a sixteen weeks longer average life‐span. Four caffeine‐treated rats had histologic evidence of acute myocardial infarction which was not found in any of the other rats. Forty percent of the rats treated with caffeine only or with caffeine and phenacetin in combination were found to have periarteritis nodosa‐like lesions in the mesenteric vessels. Seventy‐nine percent of the rats treated with caffeine only and 52 percent of those treated with caffeine and phenacetin died from cardiovascular disease, compared with 17 percent among the control rats. Thus, long‐term administration of caffeine to Sprague‐Dawley rats is associated with markedly reduced life‐span due to cardiovascular disease.
INTERACTION OF FELINE SARCOMA VIRUS (FeSV) AND MYCOPLASMA
Authors: LARSSON ERIK , WESTERMARK BENGT , PONTÉN JAN
Published: August 2010

A factor present in the supernatant of an established human glioma cell line U‐251 MG strongly suppresses feline sarcoma virus (FeSV) focus forming activity on feline embryo fibroblasts. The factor was identified as mycoplasma arginini. The enriched mycoplasma fraction had no cytpathogenic effect on the glioma cells or on the embryonic feline indicator cells. An antiserum prepared against this strain of mycoplasma abolished the inhibition. The exact mechanism is not known but arginine depletion in the medium seems to be an important factor.
TUMOUR INDUCTION IN SYRIAN HAMSTERS FED A COMBINATION OF AMINOPYRINE AND NITRIT
Authors: BERGMAN F. , WAHLIN T.
Published: August 2010

Hamsters fed a aminopyrine/sodium nitrit mixture in drinking water showed a high incidence of intrahepatic bile duct tumours. Chenodeoxycholic acid was not found to have any promoting effect on the liver carcinogenicity induced by this combination of aminopyrine and sodium nitrit in hamsters.
CARCINOMA OF THE PARATHYROID GLAND
Authors: HOLCK SUSANNE , PEDERSEN NIELS TINGGAARD
Published: August 2010

The morphological features of a functional parathyroid carcinoma in a 34‐year‐old female are presented. The case was unique in the high frequency of mitotic figures permitting a tentative diagnosis of malignancy already on frozen sections. The parathyroid nature of the lesion was established ultrastructurally by demonstration of secretory granules, glycogen particles and lipid material within the cytoplasm. Also noteworthy was the presence of annulate lamellae, denoting rapidly growing tissue. Few examples of this lesion are at hand, and ultrastructural studies which provide valuable information regarding the site of origin, have previously been recorded in only 6 publications.
THE EFFECT OF INCREASED CARDIAC PRESSURE LOAD AND VOLUME LOAD ON THE SIZE OF MYOCARDIAL INFARCTION FOLLOWING CORONARY ARTERY OCCLUSION
Authors: TORNLING G. , CARLSSON S. , UNGE G. , LJUNGQVIST A.
Published: August 2010

The size of the myocardial infarction following standardized coronary artery occlusion was studied in rats with myocardial hypertrophy due to increased pressure load (aortic stenosis) and increased volume load (swimming exercise). The infarction was significantly smaller in the latter than in the former group. In normal control rats the infarction was larger than in the swimming‐exercised rats and smaller than in the rats with aortic stenosis, but these differences were not statistically significant. The observations support the idea that the myocardial capillary neoformation previously shown to be induced by physical exercise may limit the infarction following coronary artery occlusion, whereas the absence of such a capillary reaction in pressure‐induced cardiac hypertrophy renders the myocarcium more vulnerable to damage by a coronary occlusion. The size and distribution of the infarction was highly variable, as was the configuration of the infarction in the individual heart. For an accurate determination of the size of the infarction, serial sectioning of the whole heart is necessary, with a distance between the sections examined not exceeding 0.5 mm.
THYROID GLAND MORPHOLOGY AFTER LITHIUM TREATMENT
Authors: Fauerholdt Lis , Vendsborg Per
Published: August 2010

The morphological changes in the thyroid gland following lithium treatment lasting from a few months to 15 years are described, based on 5 cases. A pronounced pleomorphism of the epithelial cells was found.
FLOW CYTOMETRIC DNA ANALYSIS OF ANAL CANAL EPITHELIUM AND ANO‐RECTAL TUMOURS
Authors: FENGER C. , BICHEL P.
Published: August 2010

Flow cytometric DNA analysis was performed on mucosal biopsies from the various epithelial types normally present in the anal canal, i.e. colo‐rectal epithelium, ATZ‐epithelium and squamous epithelium as well as from rectal and anal adenocarcinomas and squamous carcinomas of the anal canal. Normal colo‐rectal mucosa show homogeneous cell populations with diploid DNA values, while adenocarcinomas contain diploid as well as aneuploid cell populations, regardless of location in the rectum or in the anal canal. The ATZ‐epithelium shows a dominating normoploid population with a small »hyperdiploid« peak. Polyploid nuclei were not found. The findings indicate that the ATZ‐epithelium is related to metaplastic epithelium rather than to urothelium. The variants of squamous carcinoma in this study were rather poorly differentiated, but the FCM‐analysis showed a near diploid population with a high proliferative activity. The number of cases, however, is too small to be conclusive.
TUMOURS IN ICELAND
Authors: THORHALLSSON PALL , TULINIUS HRAFN
Published: August 2010

Malignant tumours of the kidney occurring in Iceland during the years 1955 ‐ 1974 were studied pathologically and typed histologically according to a classification proposed, but not yet published, by the World Health Organisation. Histological material was available from 89.2% and 84.0% of registered male and female patients respectively. Among males, renal cell carcinomas constituted 91.8%, transitional pelvic carcinomas 5.5% and nephroblastomas 2.7% of classified tumours. The corresponding figures for females were renal cell carcinomas 96.7%, transitional pelvic carcinomas 0.8%, and nephroblastomas 2.5%. The most frequent cell type of renal cell carcinoma group in both sexes was the combination of clear and granular cells, and the most frequent architecture was the combination of solid and tubular patterns. Renal cell carcinomas composed of pure granular cells were found in 22% of males and in 14% of females, and granular cells in combinations with all other cell types were also more common in males. In Iceland renal cell carcinoma is the fifth commonest malignant tumour in males and the tenth in females. The excess of granular cell tumours among males corresponds roughly to, and may account for, the sex difference in the frequency of renal cell carcinomas.
PROTECTING OUR CHILDREN FROM SEX OFFENDERS: HAVE WE GONE TOO FAR?
Authors: Costigliacci Steven J.
Published: August 2010

On July 27, 2006, U.S. President George W. Bush signed into law the Adam Walsh Child Protection and Safety Act. This federal statute was created to serve as a tougher, more modern improvement of its predecessor in the ongoing effort to protect children from dangerous sexual predators. However, the Act did not amend the controversial federal mandate that all 50 states include the crimes of kidnapping and false imprisonment against a minor, committed by a nonparent, and without any sexual motivation or misconduct, as a crime requiring a wrongdoer to register as a sex offender. This Note demonstrates how the kidnapping and false imprisonment requirements of the Adam Walsh Act have led to a misuse of state sex offender registries to the detriment of the children they claim to protect. The solution that this Note proposes will provide each individual state with the freedom to decide how, if at all, these contentious offenses will fit into its sex offender registry, taking into consideration the state's unique statutory language, available child protective resources, and constitutional limitations. As a result, petty criminals who do not pose any real or specific threat to children will no longer be grouped with the most dangerous and violent sexual predators, child protective funds will be better utilized, and the public's attention will be refocused on the real threats to children, thereby satisfying the spirit and purpose of the Adam Walsh Act.
Review article: the current pharmacological therapies for hepatic encephalopathy
Authors: BASS N. M.
Published: August 2010

Effective treatment options for hepatic encephalopathy are limited. Based on the principle that intestinal‐derived ammonia contributes to the pathogenesis of hepatic encephalopathy, current therapeutic approaches are directed at reducing bacterial production of ammonia and enhancing its elimination.

Non‐absorbable disaccharides are first‐line therapy for hepatic encephalopathy, but published clinical studies evaluating their safety and efficacy are limited. Alternative therapies such as benzodiazepine receptor antagonists, branched‐chain amino acids, and l‐ornithine‐l‐aspartate also have limited clinical data supporting their use.

Studies of antibiotics indicate that they are effective in the treatment of hepatic encephalopathy, but adverse effects and concerns about long‐term safety have limited the widespread use of most.

Rifaximin is a minimally absorbed antibiotic that concentrates in the gastrointestinal tract and is excreted mostly unchanged in faeces. It has been studied extensively in the treatment of hepatic encephalopathy and appears to confer therapeutic benefits greater than those of placebo and non‐absorbable disaccharides and at least comparable with those of systemic antibiotics. Rifaximin was also well tolerated in patients with hepatic encephalopathy and is not associated with clinical drug interactions or clinically relevant bacterial antibiotic resistance.

In conclusion, non‐absorbed antibiotics such as rifaximin offer a favourable benefit–risk ratio in the treatment of hepatic encephalopathy and may help to improve patient outcomes.
Premarital Cohabitation and the Timing of First Marriage*
Authors: Wu Zheng
Published: August 2010

L'engouement soudain et récent à l'égard de l'union libre avant le mariage au Canada et dans les pays occidentaux industrialisés est un phénomène sans précédent. Cet article étudie le rôle de l'union de fait en tant qu'élément déterminant de la transition vers un premier mariage. Les données historiques de l'Enquête sociale générale de 1990 ont révélé que l'union de fait retarde le moment du premier mariage d'environ 26% chez les femmes et de 19% chez les hommes. Cette caractéristique reste importante et signifiante après correction du facteur de sélectivité relative à l'union de fait. L'analyse prouve également qu'il existe un phénomène d'autosélection en faveur de l'union de fait. Il semble que l'expérience de l'union libre en tant que telle influe sur les attitudes des individus à l'égard du mariage et diminue leur propension à se marier.

The recent surge in premarital cohabitation in Canada and other Western industrial countries is unprecedented. This paper examines the role of cohabitational experiences as a determinant of the transition to first marriage. Using union history data from the 1990 General Social Survey, I find that cohabitational experiences delay the timing of first marriage by about 26% for women and 19% for men. This effect remains substantial and significant after I correct for the selectivity of cohabitation. The analysis also reveals evidence of selection into cohabitation. It appears that the experience of cohabiting itself affects the attitudes of individuals toward marriage and decreases their propensity to marry.
Kinase as Scaffold
Authors: Ray L. Bryan
Published: August 2010

A lipid kinase coordinates cell migration by binding to a small GTPase.
Muscle Building with Myc-Nick
Authors: Gough Nancy R.
Published: August 2010

A cleaved form of Myc acts in the cytoplasm to regulate microtubule dynamics and contributes to muscle cell differentiation.
Prevalence and Dissemination of
oqxAB
in
Escherichia coli
Isolates from Animals, Farmworkers, and the Environment
Authors: Zhao Jingjing , Chen Zhangliu , Chen Sheng , Deng Yuting , Liu Yahong , Tian Wei , Huang Xianhui , Wu Congming , Sun Yongxu , Sun Yan , Zeng Zhenling , Liu Jian-Hua
Published: August 2010

OqxAB has recently been identified as one of the mechanisms of plasmid-mediated quinolone resistance (PMQR). Compared to what is observed for other PMQR determinants, there is a paucity of data with regard to the prevalence and epidemiology of OqxAB and its contribution to resistance to different antimicrobials. In this study, the prevalence and dissemination of
oqxAB
and other PMQR genes in
Escherichia coli
isolates from animals, farmworkers, and the environment in 2002 in China were investigated. Of the 172
E. coli
isolates, 39.0% carried
oqxA
, while only 4.1%, 2.9%, and 0.6% carried
qnr
(1
qnrB6
isolate, 5
qnrS1
isolates, and 1
qnrD
isolate),
qepA
, and
aac(6′)-Ib-
cr
, respectively. Among the 33 isolates from farmworkers, 10 (30.3%) were positive for
oqxA
.
oqxAB
was associated with IS
26
and was carried on the 43- to 115-kb IncF transferable plasmid. Transconjugants carrying
oqxAB
showed 4- to 16-fold increases in the MICs of quinolones, 16- to 64-fold increases in the MICs of quinoxalines, 8- to 32-fold increases in the MICs of chloramphenicol and trimethoprim-sulfamethoxazole, and 4- to 8-fold increases in the MICs of florfenicol compared to the levels for the recipient. The pulsed-field gel electrophoresis (PFGE) analysis showed that the high levels of prevalence and dissemination of
oqxA
B
in
E. coli
in animal farms were primarily due to the transmission of plasmids carrying
oqxAB
, although clonal transmission between human and swine
E. coli
isolates was observed. It is concluded that
oqxAB
was widespread in animal farms in China, which may be due to the overuse of quinoxalines in animals. This study warrants the prudent use of quinoxalines in food animals.
High-Resolution Crystal Structure of the Subclass B3 Metallo-β-Lactamase BJP-1: Rational Basis for Substrate Specificity and Interaction with Sulfonamides
Authors: Docquier Jean-Denis , Benvenuti Manuela , Calderone Vito , Stoczko Magdalena , Menciassi Nicola , Rossolini Gian Maria , Mangani Stefano
Published: August 2010

Metallo-β-lactamases (MBLs) are important enzymatic factors in resistance to β-lactam antibiotics that show important structural and functional heterogeneity. BJP-1 is a subclass B3 MBL determinant produced by
Bradyrhizobium japonicum
that exhibits interesting properties. BJP-1, like CAU-1 of
Caulobacter vibrioides
, overall poorly recognizes β-lactam substrates and shows an unusual substrate profile compared to other MBLs. In order to understand the structural basis of these properties, the crystal structure of BJP-1 was obtained at 1.4-Å resolution. This revealed significant differences in the conformation and locations of the active-site loops, determining a rather narrow active site and the presence of a unique N-terminal helix bearing Phe-31, whose side chain binds in the active site and represents an obstacle for β-lactam substrate binding. In order to probe the potential of sulfonamides (known to inhibit various zinc-dependent enzymes) to bind in the active sites of MBLs, the structure of BJP-1 in complex with 4-nitrobenzenesulfonamide was also obtained (at 1.33-Å resolution), thereby revealing the mode of interaction of these molecules in MBLs. Interestingly, sulfonamide binding resulted in the displacement of the side chain of Phe-31 from its hydrophobic binding pocket, where the benzene ring of the molecule is now found. These data further highlight the structural diversity shown by MBLs but also provide interesting insights in the structure-function relationships of these enzymes. More importantly, we provided the first structural observation of MBL interaction with sulfonamides, which might represent an interesting scaffold for the design of MBL inhibitors.
Discovery and Analysis of 4
H
-Pyridopyrimidines, a Class of Selective Bacterial Protein Synthesis Inhibitors
Authors: Ribble Wendy , Hill Walter E. , Ochsner Urs A. , Jarvis Thale C. , Guiles Joseph W. , Janjic Nebojsa , Bullard James M.
Published: August 2010

Bacterial protein synthesis is the target for numerous natural and synthetic antibacterial agents. We have developed a poly(U) mRNA-directed aminoacylation/translation protein synthesis system composed of phenyl-tRNA synthetases, ribosomes, and ribosomal factors from
Escherichia coli
. This system, utilizing purified components, has been used for high-throughput screening of a small-molecule chemical library. We have identified a series of compounds that inhibit protein synthesis with 50% inhibitory concentrations (IC
50
s) ranging from 3 to 14 μM. This series of compounds all contained the same central scaffold composed of tetrahydropyrido[4,3-
d
]pyrimidin-4-ol (e.g., 4
H
-pyridopyrimidine). All analogs contained an
ortho
pyridine ring attached to the central scaffold in the 2 position and either a five- or a six-member ring tethered to the 6-methylene nitrogen atom of the central scaffold. These compounds inhibited the growth of
E. coli
,
Staphylococcus aureus
,
Streptococcus pneumoniae
,
Haemophilus influenzae
, and
Moraxella catarrhalis
, with MICs ranging from 0.25 to 32 μg/ml. Macromolecular synthesis (MMS) assays with
E. coli
and
S. aureus
confirmed that antibacterial activity resulted from specific inhibition of protein synthesis. Assays were developed for the steps performed by each component of the system in order to ascertain the target of the compounds, and the ribosome was found to be the site of inhibition.
The Development of Ciprofloxacin Resistance in
Pseudomonas aeruginosa
Involves Multiple Response Stages and Multiple Proteins
Authors: Su Hsun-Cheng , Ramkissoon Kevin , Doolittle Janet , Clark Martha , Khatun Jainab , Secrest Ashley , Wolfgang Matthew C. , Giddings Morgan C.
Published: August 2010

Microbes have developed resistance to nearly every antibiotic, yet the steps leading to drug resistance remain unclear. Here we report a multistage process by which
Pseudomonas aeruginosa
acquires drug resistance following exposure to ciprofloxacin at levels ranging from 0.5× to 8× the initial MIC. In stage I, susceptible cells are killed
en masse
by the exposure. In stage II, a small, slow to nongrowing population survives antibiotic exposure that does not exhibit significantly increased resistance according to the MIC measure. In stage III, exhibited at 0.5× to 4× the MIC, a growing population emerges to reconstitute the population, and these cells display heritable increases in drug resistance of up to 50 times the original level. We studied the stage III cells by proteomic methods to uncover differences in the regulatory pathways that are involved in this phenotype, revealing upregulation of phosphorylation on two proteins, succinate-semialdehyde dehydrogenase (SSADH) and methylmalonate-semialdehyde dehydrogenase (MMSADH), and also revealing upregulation of a highly conserved protein of unknown function. Transposon disruption in the encoding genes for each of these targets substantially dampened the ability of cells to develop the stage III phenotype. Considering these results in combination with computational models of resistance and genomic sequencing results, we postulate that stage III heritable resistance develops from a combination of both genomic mutations and modulation of one or more preexisting cellular pathways.
Comparative Biochemical and Computational Study of the Role of Naturally Occurring Mutations at Ambler Positions 104 and 170 in GES β-Lactamases
Authors: Kotsakis Stathis D. , Miriagou Vivi , Tzelepi Eva , Tzouvelekis Leonidas S.
Published: August 2010

In GES-type β-lactamases, positions 104 and 170 are occupied by Glu or Lys and by Gly, Asn, or Ser, respectively. Previous studies have indicated an important role of these amino acids in the interaction with β-lactams, although their precise role, especially that of residue 104, remains uncertain. In this study, we constructed GES-1 (Glu104, Gly170), GES-2 (Glu104, Asn170), GES-5 (Glu104, Ser170), GES-6 (Lys104, Ser170), GES-7 (Lys104, Gly170), and GES-13 (Lys104, Asn170) by site-specific mutagenesis and compared their hydrolytic properties. Isogenic comparisons of β-lactam resistance levels conferred by these GES variants were also performed. Data indicated the following patterns: (i) Lys104-containing enzymes exhibited enhanced hydrolysis of oxyimino-cephalosporins and reduced efficiency against imipenem in relation to enzymes possessing Glu104, (ii) Asn170-containing enzymes showed reduced hydrolysis rates of penicillins and older cephalosporins, (iii) Ser170 enabled GES to hydrolyze cefoxitin efficiently, and (iv) Asn170 and Ser170 increased the carbapenemase character of GES enzymes but reduced their activity against ceftazidime. Molecular dynamic simulations of GES apoenzyme models, as well as construction of GES structures complexed with cefoxitin and an achiral ceftazidime-like boronic acid, provided insights into the catalytic behavior of the studied mutants. There were indications that an increased stability of the hydrogen bonding network of Glu166-Lys73-Ser70 and an altered positioning of Trp105 correlated with the substrate spectra, especially with acylation of GES by imipenem. Furthermore, likely effects of Ser170 on GES interactions with cefoxitin and of Lys104 on interactions with oxyimino-cephalosporins were revealed. Overall, the data unveiled the importance of residues 104 and 170 in the function of GES enzymes.
Toll-Like Receptor 2 Deficiency Results in Impaired Antibody Responses and Septic Shock during
Borrelia hermsii
Infection
Authors: Dickinson Gregory S. , Piccone Heather , Sun Guizhi , Lien Egil , Gatto Louis , Alugupalli Kishore R.
Published: August 2010

Overwhelming bacteremia is a leading cause of death. To understand the mechanisms involved in protective antibody and pathological inflammatory responses during bacteremia, we have been studying the murine model of
Borrelia hermsii
infection. Toll-like receptor (TLR) signaling plays an important role in generating the rapid anti-
B. hermsii
antibody responses required for the resolution of bacteremia. Using NF-κB reporter assays, we found that
B. hermsii
activates TLR2 and TLR9. However, TLR2
−/−
TLR9
−/−
mice exhibited an impairment in anti-
B. hermsii
antibody responses similar to that of TLR2
−/−
mice. Moreover, the impairment in the antibody responses of TLR2
−/−
mice or TLR2
−/−
TLR9
−/−
mice coincides with an order-of-magnitude-higher bacteremia, and death results from septic shock, as evidenced by a dysregulated systemic cytokine response and characteristic organ pathology. Since TLR2 appears to be the major extracellular sensor stimulated by
B. hermsii
, we hypothesized that during elevated bacteremia the activation of intracellular sensors of bacteria triggers dysregulated inflammation in TLR2
−/−
mice. Indeed, blocking the internalization of
B. hermsii
prevented the induction of inflammatory cytokine responses in TLR2-deficient cells. Furthermore, we found that
B. hermsii
activates the cytoplasmic sensor nucleotide-binding oligomerization domain 2 (NOD2). Macrophages deficient in both TLR2 and NOD2 have impaired cytokine responses to
B. hermsii
compared to cells lacking TLR2 alone, and
B. hermsii
-infected TLR2
−/−
NOD2
−/−
mice exhibited improved survival compared to TLR2
−/−
mice. These data demonstrate that TLR2 is critical for protective immunity and suggest that, during heightened bacteremia, recognition of bacterial components by intracellular sensors can lead to pathological inflammatory responses.
Arachidonic Acid Metabolism Regulates
Escherichia coli
Penetration of the Blood-Brain Barrier
Authors: Zhu Longkun , Maruvada Ravi , Sapirstein Adam , Malik Kafait U. , Peters-Golden Marc , Kim Kwang Sik
Published: August 2010

Escherichia coli
K1 meningitis occurs following penetration of the blood-brain barrier, but the underlying mechanisms involved in
E. coli
penetration of the blood-brain barrier remain incompletely understood. We have previously shown that host cytosolic phospholipase A
2
α (cPLA
2
α) contributes to
E. coli
invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier, but the underlying mechanisms remain unclear. cPLA
2
α selectively liberates arachidonic acid from membrane phospholipids. Here, we provide the first direct evidence that host 5-lipoxygenase and lipoxygenase products of arachidonic acid, cysteinyl leukotrienes (LTs), contribute to
E. coli
K1 invasion of HBMEC and penetration into the brain, and their contributions involve protein kinase C alpha (PKCα). These findings demonstrate that arachidonic acid metabolism regulates
E. coli
penetration of the blood-brain barrier, and studies are needed to further elucidate the mechanisms involved with metabolic products of arachidonic acid for their contribution to
E. coli
invasion of the blood-brain barrier.
Specific and Nonspecific B-Cell Function in the Small Intestines of Patients with Whipple's Disease
Authors: Geelhaar Anika , Moos Verena , Schinnerling Katina , Allers Kristina , Loddenkemper Christoph , Fenollar Florence , LaScola Bernard , Raoult Didier , Schneider Thomas
Published: August 2010

Whipple's disease is a chronic multisystemic infection caused byTropheryma whippleithat is characterized by arthritis, weight loss, and diarrhea. The immunological defects in the duodenal mucosa, the site of major replication of the agent underlying the pathogenesis of Whipple's disease, are poorly understood. Mucosal immunoglobulins are essential for the defense against intestinal pathogens; therefore, we analyzed the B-cell response in duodenal specimens and sera of Whipple's disease patients. Whereas systemic immunoglobulin production was affected only marginally, duodenal biopsy specimens of Whipple's disease patients contained reduced numbers of immunoglobulin-positive plasma cells and secreted less immunoglobulin compared to healthy controls but showed a weak secretory IgA response towardT. whipplei.ThisT. whipplei-specific intestinal immune response was not observed in controls. Thus, we were able to demonstrate that general mucosal immunoglobulin production in Whipple's disease patients is impaired. However, this deficiency does not completely abolishT. whipplei-specific secretory IgA production that nonetheless does not protect from chronic infection.