Mass spectral study of derivatives of the four bilirubin-IX isomers

The beta, gamma and delta isomers of bilirubin-IX show a decreased stability as compared with the IXalpha isomer; characteristic mass spectra are obtained only for the tetrakis-(trimethylsilyl) derivatives of the IXalpha and IXgamma isomers. Hydrogenation of the vinyl substituents increases the thermal stability of the bilirubins and gives rise to a characteristic mass spectrum for the tetrakis-(trimethylsilyl) derivative of meso-bilirubin-IXdelta. The ethyl anthranilate azopigments derived from the four bilirubins yield characteristic mass spectra, except for the two unstable divinyl substituted azodipyrroles (mol. wt. 416), derived from bilirubin-IXbeta and IXdelta. The corresponding mol. wt. 420 azopigments derived from the hydrogenated bilirubins are thermally stable. Elucidation of mass spectral fragmentation pathways is facilitated by the varying positions of the substituents and by deuterium labelling, and permits the assignment of structures to the various isomeric azodipyrroles.     

Long posterior flap amputation in geriatric patients with ischaemic disease

A series of 165 primary amputations performed on 148 patients at Queen Mary's Hospital, Roehampton, from 1967 to 1975 is reported. The average age of these patients was 70 years, the oldest being 95. Those aged 70 years and over are considered in special detail. The problems of management of these elderly patients are complex, involving medical, surgical, and social problems. The object of treatment is to restore these patients to their previous way of life with the shortest possible time in hospital. Every patient is assessed with a view to arterial surgery, and amputation is avoided where possible by a lumbar sympathetic block or direct arterial surgery. When amputation cannot be avoided a below-knee level is selected if possible. A long posterior flap technique is used which forms a myoplasty of the gastrocnemius muscle; thus the ischaemic anterior tibial skin is avoided. Before the operation the patient is assessed by a specialist team and the management is discussed in detail. Every patient is kept in hospital until rehabilitation is achieved to the point of independence inside the home. Of the 90 patients in the group aged 70 years and over, 22% had above-knee amputations and 75% had below-knee amputations, with the result that 69% of the latter were discharged home walking. This result is contrasted with the smaller number who had an above-knee amputation. Below-knee amputation gives the elderly patient a better chance of walking because of the use of the patellar tendon bearing prosthesis. When followed up 36% of those patients with below-knee amputation were fully independent for periods exceeding six months. The price of a below-knee level of amputation is a longer hospital stay, but the quality of function and mobility obtained by the patient makes this worth while.     

Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure

Eleven patients with chronic renal failure and presumed secondary hyperparathyroidism developed a syndrome of medial calcinosis of the arteries and painful ischemic ulcers of the fingers, legs, or thighs, or any combination of the three. Five patients required maintenance hemodialysis; six had functioning renal homografts. Severe hyperphosphatemia had existed in each; seven showed roentgenographic evidence of subperiosteal resorption. Similarities are evident between the lesions and experimentally produced calciphylaxix. The lesions demonstrated a relentless, progressive course, with serious morbidity and mortality. Hyperplastic or adenomatours parathyroid tissue was removed from ten of 11 patients unergoing surgical procedures; healing followed in seven patients. Treatment with phosphate-binding antacids to lower serum phosphorus levels may prevent this syndrome. Total or subtotal parathyroidectomy should be considered when ischemic skin lesions appear in uremic patients or in renal transplant recipients.     

The Australian brushtail possum (Trichosurus vulpecula) gonadotrophin alpha-subunit: analysis of cDNA sequence and pattern of expression

Substantial evidence has accumulated to suggest that in the near future implementation of the veto-cell-suppressor concept in the treatment of kidney allograft recipients might lead to the establishment of life-long specific allograft tolerance in the absence of further immunosuppressive therapy. Veto suppression prevents the generation of antigen-specific T-helper and cytotoxic T lymphocytes in vitro provided that the T-lymphocyte precursors specifically recognize antigenic peptides associated with the major histocompatibility complex molecules class II and class I, respectively, expressed on the surface of the veto-active cell. Data from a large number of experimental and clinical studies strongly indicate that veto-active cells function in vivo and are capable of preventing allograft rejection. Thus, donor-cell-mediated veto activity is the most likely explanation for the well-known graft tolerizing effect of pretransplant donor blood transfusions in kidney graft recipients. A prerequisite for a veto-active environment in vivo is the establishment of lymphoid microchimerism, in which veto-active donor and recipient cells mutually downregulate potential alloaggression.     

Intracellular localisation of urea-cycle enzymes in liver (author's transl)

Enzymes of the Krebs-Henseleit urea-cycle were localized by means of differential centrifugation and fractional tissue extraction in rat liver and in human liver. Argininosuccinatlyase (ASAL) and Argininosuccinatsynthetase (ASAS) represent enzymes of the soluble cytoplasmic fraction. Ornithine-ketoacid-transaminase(OKT), carbamyl-phosphate-synthetase (CPS) and ornithine-carbamyl-transferase (OCT) are localized in the mitochondrial and nuclei fractions of the liver cell. Most of the arginase activity is bound to subcellular structures (probably to nuclei). A small portion of arginase-activity was found in the soluble cytoplasmatic fraction. The enzymes of the Krebs-Henseleit urea-cycle are equally distributed in rat liver and in human liver. Differences in the subcellular localisation of (mitochondrial) enzymes in human liver could be attributed to mitochondrial breakage during tissue preparation and do not represent in-vivo conditions.     

Limbic dysfunction in schizophrenia and mania. A study using 18F-labelled fluorodeoxyglucose and positron emission tomography

BACKGROUND: Diagnostic classes (derived from CATEGO) can be correlated with regional brain metabolism in patients with major psychiatric disorders. METHOD: Seventeen patients with schizophrenia, 15 with mania, 10 with depression and 10 healthy Volunteers were examined with positron emission tomography (PET) and 18F-labelled fluorodeoxyglucose, as a marker for glucose metabolism. The number of possible comparisons of regions of interest was reduced by principal-components analysis, and differences in factor scores were determined between diagnostic groups. RESULTS: Four independent factors, representing distributed brain systems, emerged: an anterior-posterior (1), a left-right temporal (2), a temporofrontal (3), and a mediofrontal (4) system, of which (1), (2) and (3) were abnormal in schizophrenia, (1) and (2) in mania, and (1) in depression. CONCLUSIONS: Abnormal patterns of metabolism could be detected, in decreasing order, in schizophrenia, mania and depression. Some of these abnormalities are likely to be due to medication, but others will be associated with structural or functional abnormalities of the frontolimbic system in the diagnostic groups.     

A neuronal ryanodine receptor mediates light-induced phase delays of the circadian clock

Circadian clocks are complex biochemical systems that cycle with a period of approximately 24 hours. They integrate temporal information regarding phasing of the solar cycle, and adjust their phase so as to synchronize an organism's internal state to the local environmental day and night. Nocturnal light is the dominant regulator of this entrainment. In mammals, information about nocturnal light is transmitted by glutamate released from retinal projections to the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Clock resetting requires the activation of ionotropic glutamate receptors, which mediate Ca2+ influx. The response induced by such activation depends on the clock's temporal state: during early night it delays the clock phase, whereas in late night the clock phase is advanced. To investigate this differential response, we sought signalling elements that contribute solely to phase delay. We analysed intracellular calcium-channel ryanodine receptors, which mediate coupled Ca2+ signalling. Depletion of intracellular Ca2+ stores during early night blocked the effects of glutamate. Activators of ryanodine receptors induced phase resetting only in early night; inhibitors selectively blocked delays induced by light and glutamate. These findings implicate the release of intracellular Ca2+ through ryanodine receptors in the light-induced phase delay of the circadian clock restricted to the early night.     

Service feature modeling: modeling and participatory ranking of service design alternatives

The design of software-intensive service systems involves and affects numerous stakeholders including software engineers, legal and business experts as well as a potentially large number of consumers. In consequence, the challenge arises to adequately represent the interests of these groups with respect to service design decisions. Specifically, shared service design artifacts and participatory methods for influencing their development in consensus are required, which are not yet state of the art in software service engineering. To this end, we present service feature modeling. Using a modeling notation based on feature-oriented analysis, our approach can represent and interrelate diverse service design concerns and capture their potential combinations as service design alternatives. We further present a method that allows stakeholders to rank service design alternatives based on their preferences. The ranking can support service engineers in selecting viable alternatives for implementation. To exploit this potential, we have implemented a toolkit to enable both modeling and participative ranking of service design alternatives. It has been used to apply service feature modeling in the context of public service design and evaluate the approach in this context.