The natural history of homocystinuria due to cystathionine beta-synthase deficiency

An international questionnaire survey has been conducted to define better the natural history of homocystinuria due to cystathionine beta-synthase deficiency and permit evaluation of treatment. Data were compiled for 629 patients. Among patients not discovered by newborn screening, B6-responsive individuals on the average have significantly better mental capabilities (mean IQ, 79) than do B6-nonresponsive individuals (mean IQ, 57). Time-to-event curves are presented for the other major clinical abnormalities produced by this disease. Each occurred at significantly lower rates in untreated B6-responsive than in untreated B6-nonresponsive patients, as shown by the following examples: (1) dislocation of optic lenses (at age 10, chances of dislocation: 55% and 82%, respectively); (2) initial clinically detected thromboembolic events (at age 15, chances of having had such an event: 12% and 27%, respectively); (3) radiologic detection of spinal osteoporosis (at age 15, chances of such osteoporosis having been detected: 36% and 64%, respectively); and (4) mortality (at age 30, chances of not surviving: 4% and 23%, respectively). Methionine restriction initiated neonatally prevented mental retardation, retarded the rate of lens dislocation, and may have reduced the incidence of seizures. Pyridoxine treatment of late-detected B6-responsive patients retarded the rate of occurrence of initial thromboembolic events. Following 586 surgical procedures, 25 postoperative thromboembolic complications occurred, six of which were fatal. Reproductive histories were reported predominantly for B6-responsive patients. Living offspring of either men or women patients had few abnormalities. The evidence is inconclusive whether untreated maternal cystathionine beta-synthase deficiency leads to excessive fetal loss. Only 13% of patients detected in screening programs of newborns and classified as to B6-responsiveness were B6-responsive, compared to 47% among late-detected patients. Current screening programs that identify neonatal hypermethioninemia may be preferentially failing to detect B6-responsive patients.     

Factors influencing respiration data in freshwater sediment

Sediment respiration (oxygen consumption and CO₂ evolution) was measured in freshwater sediment samples using both flask- and core-microcosms, and the estimates were compared. Oxygen consumption data were also compared in flask-microcosms constructed with sediment samples of different masses, sediment: water ratios, and storage times. Furthermore, sediment respiration was examined under different incubation conditions of temperature and agitation. O₂ consumption was markedly higher in flask-microcosms than in sediment core-microcosms, when compared on a per g dry weight basis. However, when the results were expressed as O₂ consumed per unit surface area, the values were more similar. CO₂ evolution was less dependent on surface area as evidenced by similar CO₂ values per g sediment in both microcosms. In addition, the effect of sediment mass on O₂ consumption and CO₂ evolution was examined. Both O₂ consumption and CO₂ evolution (expressed as µmole g^–1 dry weight sediment) decreased significantly with increasing sediment mass between 3 and 12 g dry weight. Maximum O₂ consumption per unit headspace was measured when a wet sediment mass between 10.0 and 20.0 g was used in the flask-microcosms. It was also shown that the sediment: water ratio, agitation, incubation temperature, and previous storage time of sediment all affected the respiration estimates. Initial O₂ consumption and CO₂ evolution in flasks were significantly higher in flasks with a decreased sediment: water ratio (1:1 versus 1:2), increased flask agitation, and increased incubation temperature (15 °C versus 5 °C). Also, respiration decreased significantly over the first 100 days of storage at 4 °C.     

Initiation of chromosome replication after induction of DnaA protein synthesis in a dnaA(null) rhn mutant of Escherichia coli

The kinetics of initiation of chromosome replication after induction of DnaA protein synthesis was studied in a dnaA(null) rnh mutant of Escherichia coli. DnaA protein synthesis was induced to different extents using the wild-type dnaA gene controlled by a lac promoter. Initiation of chromosome replication from oriC, measured as an increase in origin to terminus ratio, took place at different times after addition of an inducer dependent on the DnaA protein synthesis rate. The first initiations always occurred when DnaA protein had accumulated approximately to the average wild-type concentration (24 ng of DnaA protein per ml cells at OD₄₅₀= 1.0) At a low DnaA protein accumulation rate one synchronous round of replication was obtained after 30min of induction. The initiation kinetics obtained when DnaA protein accumulated rapidly was complicated and indicated that other factors might also be involved.     

Abnormal synthesis of dolichol-linked oligosaccharides in carbohydrate-deficient glycoprotein syndrome

Carbohydrate-deficient glycoprotein syndrome (CDGS) is a raremetabolic disorder presenting in infancy with severe neurologicinvolvement and variable multisystemic abnormalities. Diagnosisrelies upon the detection of abnormal serum glycoprotein isoformson isoelectric focusing (IEF) gels. Carbohydrate structuralanalyses were performed on the N-linked oligosaccharides ofserum     

Stand and neighbourhood parameters as determinants of plant species richness in a managed forest

Abstract. Patterns of species richness in a managed forest were related to ecological factors at two spatial scales. Local variables within a plot (5 m × 5 m) included 13 soil classes and nine stand classes. Neighbourhood variables were defined within a 25 m radius from the focal plot and were measured using a Neighbourhood Diversity Index (NDI - total diversity of different stand classes) and nine Neighbourhood Scores (NS - relative dominance of a given stand class). 224 species were registered in the survey of which 138 were true forest species. Local parameters (stand and soil class) were weak predictors of total and forest species richness. High total and forest species richness were significantly related to high values of NDI (i.e. heterogeneous neighbourhoods). Regression trees showed that total species richness was best predicted by the amount of roadside habitat in the neighbourhood and NDI. Forest species richness was positively related to NDI and negatively related to the amount of coniferous stands in the neighbourhood.     

The initiation mess?

This review concerns the mechanisms which control initiation of chromosome replication in enterobacteria with respect to cell growth. Initiation control is commonly separated into positive and negative regulatory mechanisms. Four main points are advanced concerning these different aspects of initiation control. (i) The average concentration of the initiator protein DnaA is proportional to the origin concentration, i.e. the origin per cell mass ratio and, thus, inversely proportional to the very often used term of the 'initiation mass'. (ii) The time of initiation of chromosome replication in the cell cycle is set by DnaA protein accumulating to a threshold level, which in concert with a number of other factors allows for a co-operative formation of the initiation complex. (iii) The time of initiation is not determined by the interaction with these other factors or by the transient interaction between newly replicated origins ( oriC  ) and the cell surface. (iv) The aberrant initiation phenotype observed in various mutants, including dnaA (ts) mutants, might be due to a defective pre-initiation DnaA– oriC interaction or it might be due to a defect in the protection of newly initiated origins from reinitiation. Many of these points are discussed and evaluated in view of recent developments concerning the regulation of chromosome replication in Escherichia coli     

Frequency- and voltage-dependent effects of disopyramide in canine Purkinje fibers

The voltage- and frequency-dependent blocking actions of disopyramide were assessed in canine Purkinje fibers within the framework of concentrations, membrane potentials, and heart rates which have relevance to the therapeutic actions of this drug. Vmax was used to assess the magnitude of sodium channel block. Disopyramide produced a concentration- and rate-dependent increase in the magnitude and kinetics of Vmax depression. Effects on activation time (used as an estimate of drug effect on conduction) were exactly analogous to effects on Vmax. A concentration-dependent increase in tonic block was also observed. Despite significant increases in tonic block at more depolarized potentials, rate-dependent block increased only marginally with membrane potential over the range of potentials in which propagated action potentials occur. Increases in extracellular potassium concentration accentuated drug effect on Vmax but attenuated drug effect on action potential duration. Recovery from rate-dependent block followed two exponential processes with time constants of 689 +/- 535 ms and 15.7 +/- 2.7 s. The latter component represents dissociation of drug from its binding site and the former probably represents recovery from slow inactivation. A concentration-dependent increase in the amplitude of the first component suggested that disopyramide may promote slow inactivation. There was less than 5% recovery from block during intervals equivalent to clinical diastole. Thus, depression of beats of all degrees of prematurity was similar to that of basic drive beats. Prolongation of action potential duration by therapeutic concentrations of drug following a long quiescent interval was minimal. However, profound lengthening of action potential duration occurred following washout of drug effect at a time when Vmax depression had reverted to normal, suggesting that binding of disopyramide to potassium channels may not be readily reversed. Variable effects on action potential duration may thus be attributed to a block of the window current flowing during the action potential being partially or over balanced by block of potassium channels. Purkinje fiber refractoriness was prolonged in a frequency-dependent manner. Disopyramide did not significantly alter the effective refractory period of basic beats but did increase the effective refractory period of sequential tightly coupled extra stimuli. The results can account for the antiarrhythmic actions of disopyramide during a rapid tachycardia and prevention of its initiation by programmed electrical stimulation.     

Surgical treatment of thyrotoxicosis.

A retrospective study of thyrotoxic patients treated by subtotal thyroidectomy between 2 and 21 years ago in the north-east of Scotland showed that 20% of the patients could not be identified or traced at the time of the survey. The thyroid status of 40% of patients followed up was abnormal.It is now accepted that radioiodine treatment of thyrotoxicosis is followed by a significant incidence of late onset hypothyroidism, and life-long follow-up is regarded as obligatory. The findings in this study indicate that similar methods of aftercare are required for surgically treated patients and for all patients receiving thyroxine-replacement therapy.