bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward a Total Synthesis of Macrocyclic Jatrophane Diterpenes – Concise Route to a Highly Functionalized Cyclopentane Key Intermediate
Authors: Mulzer Johann , Giester Gerald , Gilbert Michael 
Published: June 2005

AbstractA total synthesis of the biologically potent jatrophane diterpenes pepluanin A (1) and euphosalicin A (2) is being aimed at. En route to these targets, a concise synthesis of the nonracemic cyclopentane building block 74 was developed. Key steps were a Claisen–Eschenmoser rearrangement of the enantiomerically enriched allylic alcohol 14 to amide 34 (Scheme 7), a hydroxy‐lactonization of 40 to 43 (Scheme 9), followed by trans‐lactonization to 72, which was subjected to a Davis hydroxylation to 69 (Scheme 17). Eventually, compound 69 was converted into the enol triflate 74. This material should prove suitable for an annulation of the macrocyclic ring characteristic of the desired jatrophanes 1 and 2. Less‐successful approaches are also discussed due to their intrinsically valuable information content.
Dynamic contrast‐enhanced MRI for assessing the disease activity of multiple myeloma: A comparative study with histology and clinical markers
Authors: Nosàs‐Garcia Sílvia , Moehler Thomas , Wasser Klaus , Kiessling Fabian , Bartl Reiner , Zuna Ivan , Hillengass Jens , Goldschmidt Hartmut , Kauczor Hans‐Ulrich , Delorme Stefan 
Published: June 2005

AbstractPurposeTo examine whether parameters of dynamic, contrast‐enhanced MRI (DCE MRI) reflect the degree of infiltration and vessel density in corresponding bone marrow biopsy specimens.Materials and MethodsThe pelvis of 24 patients with multiple myeloma (MM) was examined using contrast‐enhanced DCE MRI. Biopsy was obtained from the spina iliaca posterior superior. Using a two‐compartment model (assuming one intravascular and one interstitial compartment), the parameters amplitude (A, the maximum, relative signal increase over baseline) and the exchange rate constant (kep, describing the redistribution of contrast agent from the interstitial into the intravascular compartment) in the biopsied region were calculated and compared with the histological and clinical data.ResultsDCE MRI parameters were significantly higher in lesions with marked infiltration than with mild or no infiltration (P < 0.05). The amplitude normalized to that in the iliac artery (An), but not kep, was higher in lesions with high vessel‐density at histology (P = 0.01). Higher kep levels were found in presence of increased serum immunoglobulins.ConclusionIncreased contrast uptake in the bone marrow of MM patients indicates at least moderate tumor involvement. Furthermore, the contrast enhancement correlates with vessel‐density and serum markers of disease activity. J. Magn. Reson. Imaging 2005;22:154–162. © 2005 Wiley‐Liss, Inc.
Excess plasma proteins as a cause of chronic inflammation and lymphoedema: Biochemical estimations
Authors: Gaffney R. M. , Casley‐Smith J. R. 
Published: June 2005

AbstractThe subcutaneous tissue of rats was injected with plasma, PVP or saline. Precautions were taken to avoid Immunological reactions and the release of mediators. The repeated injection of plasma proteins caused changes typical of chronic inflammation in the skin and to a much greater extent in the fascia. Coumarin significantly reduced the extent of this inflammatory reaction in the skin but not in the fascia. It increased the numbers of cells in the skin and may have stimulated them to lyse the excess protein. After 32 days, PVP injection caused some of the changes seen in chronic inflammation, but to a much lesser extent than those found with plasma. The only effect of coumarin was to reduce the water content of the skin (and hence the skin weight).It is concluded that the accumulation of excess proteins in the tissues can indeed cause chronic inflammation. In particular, chronic lymphoedema can be regarded as a form of chronic inflammation. It is also concluded that in the presence of excess protein, the benzopyrone, coumarin, is capable of stimulating cells, other than macrophages, in the skin.
Transmission electron microscopy of human oesophageal carcinomas
Authors: Robinson K. M. , Gregory M. A. 
Published: June 2005

AbstractTwelve human oesophageal carcinoma samples were examined by both light and electron microscopy in order to characterise the ultrastructural features of this neoplasm. Those samples from well differentiated tumours contained abundant tonofilaments, mainly in a paranuclear position, while cells from poorly differentiated tumours displayed few such filaments but had more prominent cytoplasmic organelles. Desmosomes were well developed in all samples, some of which displayed numerous clearly defined intracellular desmosomes not necessarily associated with cell membrane material. Myelinoid figures were abundant and the bizarre forms which were present in some samples may be related either to abnormal metabolism or to viral activity. Glycogen, lipid droplets and intermediate filaments, possibly related to basement membrane material were observed in several samples, No single feature diagnostic for carcinoma of the oesophagus emerged from this study, but several structural similarities between oesophageal and other carcinomas were noted.
The glomerular basal lamina in hereditary nephritis
Authors: Yoshikawa N. , Cameron A. H. , White R. H. R. 
Published: June 2005

AbstractCharacteristic ultrastructural alterations of the glomerular basal lamina have been reported in hereditary nephritis. The basal lamina is irregularly thickened and the lamina densa shows replication with a “basket weave” pattern, enclosing electron‐lucent lacunae which frequently contain small dense particles. However there is controversy regarding the specificity of this lesion in hereditary nephritis. To determine the specificity, 366 renal biopsies from 310 children were studied retrospectively. Twenty‐four out of 27 patients with hereditary nephritis showed the characteristic changes of the basal lamina and they were widespread in 17.Two patients with recurrent haematuria but no family history of deafness or haematuria showed similar extensive changes and are regarded as new mutant cases of hereditary nephritis.Similar changes were seen in 17 of the 281 patients with other conditions but were always localized to a few capillary loops. We conclude that a widespread “basket weave” pattern appears to be confined to hereditary nephritis and is seen in the great majority of such cases.
Furosemide induced hepatotoxicity
Authors: Walker R. M. , McElligott T. F. 
Published: June 2005

AbstractFurosemide‐induced (400mg/kg ip) hepatotoxicity progressing to centrilobular necrosis was studied by light and electron microscopy in Swiss white mice. Centrilobular glycogen depletion and cytoplasmic foaminess, usually accompanied by extensive vacuolation, were detectable by light microscopy 1 1/2 hr after furosemide. Centrilobular congestion and hydropic single cell necrosis developed after 3 hr. Electron microscopy revealed disaggregation of polyribosomes, vesiculation of endoplasmic reticulum, an endocytic origin for the vacuolation, and a definite sequence in the development of congestion. Vacuolation coincided with loss of microvilli and resulted in detachment of sinusoidal lining cells from hepatocytes. Small vacuoles apparently formed at the sinusoidal margin of hepatocytes by fusion of microvilli. Congestion and occlusion of sinusoidal lumens developed as a consequence of erythrocytes entering the enlarged Disse space, possibly through pores in the lining cells, and thence entering endocytic vacuoles. The vacuolation, loss of microvilli and terminal hydropic degeneration suggest an important role for the plasma membrane in the development of furosemide‐induced hepatotoxicity. Comparisons with known membrane toxins support this concept.
Direct evidence that inflammatory multinucleate giant cells form by fusion
Authors: Murch A. R. , Grounds Miranda D. , Marshall C. A. , Papadimitriou J. M. 
Published: June 2005

AbstractMultinucleate giant cells (MGC) are believed to be formed by fusion of macrophages. In a chimaeric mouse composed of two histoincompatible strains each homozygous for one of the two isoenzymic forms of glucose‐6‐phosphate isomerase it was found that hybrid enzyme was produced in MGC‐rich leucocytic exudates. This hybrid can only occur if nuclei of the two different strains reside within a common syncytial cytoplasm, demonstrating unequivocally that macrophage fusion occurred between cells of the two strains. Since the two strains were histoincompatible it appears that no strain specific recognition is necessary for fusion to occur.
Rat pancreas allotransplantation: A short term comparison of rejection patterns with different methods of exocrine drainage
Authors: Lindsey N. J. , Nolan M. S. , Slater D. N. , Savas C. P. , Boyle P. F. , Herold A. , Beck S. , Fox M. 
Published: June 2005

AbstractPancreas transplantation has been performed in the rat to study the effect on rejection of duct ligation, duct obliteration and duct open intraperitoneal drainage. On day six, an acceleration of graft damage was seen in the duct ligated and obliterated allografts compared to the duct open group. However, by day 11, rejection was complete in all three groups. In comparison with pancreatic isografts, the histological diagnosis of rejection can be difficult to define, particularly in the duct ligated and obliterated groups. The most useful criterion was the localisation of the cellular infiltrate to the walls of small veins and within the islets of Langerhans.
A quantitative histomorphologic analysis of lymph node granulomas in sarcoidosis in relation to radiological stage I and II
Authors: van Maarsseveen A. C. M. Th. , Veldhuizen R. W. , Stam J. , Alons C. L. , Mullink H. 
Published: June 2005

AbstractIn a detailed study of granulomas in lymph nodes of 19 patients with Sarcoidosis we assessed and correlated a number of features, with size, development and radiographic staging of the disease. Except with the epithelioid cells the number of constituent cells (lymphocytes, giant cells and polymorphs), size, confluency and degree of necrosis of the granulomas were found to be very variable within a single gland. This indicates that the granulomas are in different stages of activity at a given time. All the features studied showed little or no correlation with the radiographic staging, which suggests that the latter is not a good index of the extent of the disease.
The regression of oestradiol‐induced pituitary tumours in the rat
Authors: Treip C. S. 
Published: June 2005

AbstractWistar rats of both sexes were implanted subcutaneously with oestradiol pellets (25 mg). The pellets were removed in two groups of animals after 120 and 220 days of implantation; in other animals the pellets were left for 230 and 370 days. The animals in whom pellets were left implanted all had large pituitary tumours. The animals from whom the pellets had been removed had pituitaries larger than normal, but much smaller than those in which the implants had been left. The results suggest that oestradiol‐induced pituitary tumours are totally hormone‐dependent and are not autonomous neoplasms. Oestradiol‐induced testicular atrophy was also reversible.
The binding of peroxidase‐labelled lectins to human breast epithelium. III—altered fucose‐binding patterns of breast carcinomas and their significance
Authors: Walker Rosemary A. 
Published: June 2005

AbstractTissue sections from 80 human breast carcinomas have been examined for evidence of binding of the two fucose‐specific lectins, Lotus tetragonolobus and Ulex europeus I, with enzymes utilized as an indicator system. Both singlestaining and double‐staining methods (Lotus tetragonolobus‐peroxidase and Ulex europeus I‐alkaline phosphatase) have been employed. In contrast to normal breast in which there is consistent reactivity of all epithelium with Lotus tetragonologus a variable loss of binding has been found within carcinomas. Surprisingly, this bears no relationship to tumour differentiation; nor does it correlate with local lymph node metastasis. Ulex europeus I has a variable reactivity with carcinomas, as it does with normal breast epithelium, and this likewise has no correlation with differentiation. However, a relationship has been found between specific patterns of binding and axillary lymph node status. The value of using two lectins with the same major sugar specificity but having different binding affinitics is illustrated in this study, in which differences in behavioural characteristics have been identified between fucose‐containing glycoconjugates having minor structural variations.
Alterations in the biophysical properties of the human endothelial cell plasma membrane induced by a chemotactic tripeptide: Correlation with enhanced adherence of granulocytes
Authors: Kirkpatrick Charles J. , Melzner Ingo 
Published: June 2005

AbstractHuman umbilical vein endothelial cells in monolayer culture were used to study the effects of the chemotactic tripeptide, N‐formylmethionylleucylphenylalanine (FMLP), on structure and function of the endothelium. Endothelial cell morphology was unaffected by concentrations of 10−8−10−4 M. No effect on endothelial cell proliferative capacity, as measured by the DNA content of cultures, was seen at the FMLP concentrations studied (10−8−10−6 M). Using fluorescent molecular probes to investigate FMLP‐induced alterations in membrane structure, it was shown using the monomer–excimer method with pyrene decanoic acid that FMLP caused a marked restructuring of the plasma membrane. This took the form of a restriction of the surface available to the lipophile reporter molecules, probably caused by a molecular reorganization of the membrane protein component. Experiments with diphenylhexatriene indicated that FMLP did not make the plasma membrane of the endothelial cell more fluid. Concomitant with these changes in the physical properties of the membrane, an FMLP‐induced increase in granulocyte adherence to the endothelial cells was observed. A theoretical model is presented correlating granulocyte adherence with the lateral mobility of lipids in the endothelial cell membrane. The significance of the FMLP‐induced increase in granulocyte adherence to endothelial cells for the pathogenesis of sepsis is discussed.
Paranodal tumour in breast cancer: Extranodal extension versus vascular spread
Authors: Hartveit F. 
Published: June 2005

AbstractA detailed histological study of the axillary nodes from 98 breast carcinoma patients, in which 5 and 10 year follow‐up data was available, has been undertaken. The presence of tumour cells in efferent vessels appears to be the only factor which is a marker of poor prognosis. Contrary to previous reports the direct infiltration of tumour cells through the nodal capsule into perinodal fat and connective tissue is of no prognostic significance. Distinction between site and type of tumour growth within nodes is thus essential for prognostic evaluation.
Cell surface characterization of the human osteoclast: Phenotypic relationship to other bone marrow‐derived cell types
Authors: Horton M. A. , Rimmer E. F. , Lewis D. , Pringle J. A. S. , Fuller K. , Chambers T. J. 
Published: June 2005

AbstractAmong the differentiated progeny of stem cells transplantable by bone marrow are osteoclasts, the multinucleate cells which are the major agents of bone resorption. Although the osteoclast is well characterized from a structural and functional standpoint, its development and origin are still far from clear. We have used monoclonal antibodies to investigate the interrelationship between osteoclasts and other haemopoietic cells in man. We have analysed the distribution of 19 granulocyte–monocyte antigens in eight reactivity clusters on the non‐neoplastic osteoclasts present within nine osteoclastomas (syn. giant cell tumours of bone) and a single example of aneurysmal bone cyst. We found that osteoclasts are antigenically effete, failing to express granulocyte‐monocyte, common leucocyte or other haemopoietic determinants; the only monocyte antigens detected on osteoclasts are My‐7 and two closely related specificities, MCS.2 and DüHL60.4, which are also expressed by tissues outside the haemopoietic system. Our findings, taken together with recent transplantation studies, cast further doubt on the view that osteoclasts are specialized bone‐resorbing macrophage‐derived giant cells, and support a hypothesis that they are the end product of fusion of a hitherto unidentified circulating mononuclear cell type, the preosteoclast, which constitutes a cell lineage separate from those originating from the conventional multipotential haemopoietic stem cell, although still of bone marrow origin.
Fetal and neonatal bile acid synthesis and metabolism — Clinical implications
Authors: Balistreri W. F. 
Published: June 2005

SummaryIt has become apparent that with sophisticated technology we are now able to recognize defective bile acid metabolism in a wide variety of disease states. Recognition of specific aberrations, such as inborn errors in bile acid metabolism manifesting as neonatal cholestasis, offers new opportunities for therapeutic intervention. Future studies should determine the incidence of inborn errors in patients with enigmatic and unexplained liver diseases such as idiopathic neonatal hepatitis.
Clinical approach to inherited metabolic diseases in the neonatal period: A 20‐year survey
Authors: Saudubray J. M. , Ogier H. , Bonnefont J. P. , Munnich A. , Lombes A. , Hervé F. , Mitchel G. , Poll Thé B. , Specola N. , Parvy P. , Bardet J. , Rabier D. , Coudé M. , Charpentier C. , Frézal J. 
Published: June 2005

SummaryEvery newborn with unexplained neurological deterioration, ketosis, metabolic acidosis or hypoglycaemia should be suspected of having an inherited error of intermediary metabolism. Many of these conditions can be diagnosed clinically with the aid of simple laboratory investigations. Since a substantial number of these diseases respond well to treatment but may otherwise be fatal, and in order to assure adequate prenatal diagnosis in subsequent pregnancies, a high index of suspicion and rapid diagnosis are necessary in the face of the clinical presentations described. According to three major clinical presentations observed in 218 neonates with inborn errors of intermediary metabolism (neurological distress ‘intoxication’ type, neurological distress ‘energy deficiency’ type and hypoglycaemia with liver dysfunction) and according to the proper use of few laboratory investigations, we propose a method of diagnosis which groups these children into five categories. Initial therapy, and sophisticated investigations can be planned on the basis of this grouping.
A clinician's view of the mass screening of the newborn for inherited diseases: Current practice and future considerations
Authors: Sardharwalla I. B. , Wraith J. E. 
Published: June 2005

SummaryThe case for or against mass screening for inherited diseases is discussed. There is universal acceptance for mass screening for phenylketonuria and congenital hypothyroidism. The case for mass screening for galactosaemia and for maple syrup urine disease is not very strong; they could be considered under the heading of ‘urgent screening of the sick newborn’. It is difficult to find good arguments for mass screening for congenital adrenal hyperplasia. For screening for glucose‐6‐phosphate dehydrogenase deficiency and sickle cell disease, the established criteria for mass screening do not apply. A simple tool for early detection is now available and the population afflicted with a mutant gene which causes major health problems should receive special attention from its government. It is too early to offer any comment about cystic fibrosis screening; further developments must be awaited.
Prospects for gene therapy now and in the future
Authors: Akhurst R. J. 
Published: June 2005

SummaryAdvances in gene technology and cell biology have supplied the means to undertake human gene therapy in the near future. Techniques have been developed for the efficient introduction of gene sequences into the pluripotential stem cells of the haematopoietic system and our increased understanding of gene‐regulatory mechanisms should allow therapeutic gene expression levels to be obtained.Gene therapy should, at present, be termed gene supplementation since it will involve the addition of corrective genes to the host cell genome. It may only be used to treat recessively inherited disorders. Prospects for the future include the use of homologous recombination to correct or replace defective genes, allowing the treatment of dominantly inherited diseases.
Partial lyonisation of steroid sulphatase gene in single hair roots
Authors: Willems P. J. , de Bruijn H. W. A. , Groenhuis A. , Mooyaart B. R. , Berger R. 
Published: June 2005

AbstractSteroid sulphatase (STS) activity was measured in single hair roots from 9 patients with X‐linked ichthyosis, 7 obligate heterozygotes, 12 male controls and 12 female controls. STS activity was deficient (<0.3 pmol dehydroepian‐drosterone (DHEA) in 5 h per hair root) in the patients as compared to male controls (4.6±1.8 pmol DHEA in 5 h per hair root). All single hair roots from obligate heterozygotes showed STS activity (3.0±0.9 pmol DHEA in 5 h per hair root). Female controls had a significantly higher STS activity (6.0±1.8 pmol DHEA in 5 h per hair root) than male controls (p<0.05) and heterozygotes (p<0.001). Both the female‐male sex ratio of control STS activity (1.3) and the absence of STS‐deficient hair roots in heterozygotes confirm previous evidence for incomplete lyonisation of the X‐linked steroid sulphatase gene.
Regional distribution of the phenylalanine‐sensitive ATP‐sulphurylase in brain
Authors: Matsuo K. , Hommes F. 
Published: June 2005

AbstractThe regional distribution of the phenylalanine‐sensitive ATP‐sulphurylase in fetal calf brain coincides with demyelinated lesions observed in the central nervous systems of untreated PKU patients. This would be expected if this species of ATP‐sulphurylase played a role in the pathogenesis of brain dysfunction in the untreated or poorly controlled phenylketonuria patient.
HPRT‐Deficiency associated with normal PRPP concentration and APRT activity
Authors: Gordon R. B. , Keough D. T. , Emmerson B. T. 
Published: June 2005

AbstractDeficiencies of HPRT are usually associated with increased concentrations of PRPP and increased levels of APRT activity in erythrocytes. We report the case of a male with a partial deficiency of HPRT in whom these two parameters were normal. The clinical features of this patient were those associated with severe hyperuricaemia and gout. Studies of intact erythrocytes showed rates of incorporation of [14C]hypoxanthine and of [14C]adenine into purine nucleotides which were almost indistinguishable from normal. However, HPRT activity in erythrocyte lysates was only 9% of normal. In cell extracts of cultured lymphoblasts, the HPRT activity was 20% of control values and the APRT activity was normal. The PRPP concentration and the rate ofde novo purine synthesis in cultured lymphoblasts were both intermediate between controls and lymphoblasts from patients with the Lesch‐Nyhan syndrome.