1. Ten rat tissues and organs have been assayed for beta-galactosidase with phenyl beta-d-galactoside, p-nitrophenyl beta-d-galactoside, p-aminophenyl beta-d-galactoside and 4-methylumbelliferyl beta-d-galactoside as substrates. 2. The relative activities of these tissues are independent of the mode of assay, and maximum rates of hydrolysis are not greatly affected by the nature of the substrate. 3. Inhibition studies suggest the liver enzyme has no associated beta-glucosidase activity. 4. There is no cellular localization of preferential activity towards any of the four substrates in liver, kidney or spleen. 5. Evidence suggesting the non-destructive penetration of liver lysosomal membranes by p-nitrophenyl beta-d-galactoside is presented. 6. Liver lysosomal beta-galactosidase exists in multiple forms that can be separated on DEAE-cellulose, and the enzyme components that are bound to the membrane appear to be similar to those of the lysosome sap. 7. The chromatographic pattern of enzyme excreted in the urine is compared with those from the kidney, intestine, spleen and liver.

Journal Article↗

PubMed1965

Use of medical services and facilities by welfare-supported children.

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Adolescent↗

PubMed1949

Studies in detoxication. 25. The characterization of phenylglucuronide, and its rate of hydrolysis compared with that of phenylsulphuric acid.

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Journal Article↗

PubMedDate not supplied

Involvement of prostaglandins from rheumatoid synovium in inhibition of articular cartilage metabolism.

Short term incubations of articular cartilage in media from cultures of rheumatoid synovial tissue result in marked inhibition of 3H-glycine and Na235SO4 incorporation into trichloroacetic acid (TCA) insoluble macromolecules by the cartilage segments with little effect on degradation of prelabeled cartilage matrix. This inhibition is time dependent and not observed in cartilage segments incubated in media derived from rheumatoid synovia cultured in the presence of indomethacin (a specific inhibitor of prostaglandin synthesis). In addition, no indomethacin-sensitive cartilage inhibitory activity was detectable in media from cultures of normal synovia. The ether solubility of the majority of the inhibitory activity and the indomethacin sensitivity suggest that the inhibitor(s) are prostaglandins.

Animals↗

PubMedDate not supplied

Lipoprotein(a) and accelerated coronary artery disease in cardiac transplant recipients.

High concentrations of serum lipoprotein(a) (Lp(a)) are associated with an increased risk of atherosclerotic vascular disease in the nontransplanted population. However, its relation with accelerated coronary artery disease (CAD) in cardiac transplant recipients has not been reported. We measured serum Lp(a) in 130 cardiac transplant recipients undergoing routine follow-up, which included annual coronary angiography. The median Lp(a) concentration in 33 patients with CAD was 71 mg/dl, which was significantly higher than the corresponding value of 22 mg/dL in the 97 patients without CAD (p = 0.0006). Multivariant analysis showed the serum Lp(a) value to be a higher significant risk factor for CAD irrespective of the other factors included in the regression analysis. Thus a high concentration of serum Lp(a) is an important, independent risk factor for the development of accelerated CAD in transplant recipients.

Coronary Artery Disease↗

PubMedDate not supplied

Growth hormone response to desmethylimipramine in depressed and suicidal adolescents.

Desipramine 75 mg i.m. was given in the morning to 20 adolescents with major depressive disorder and 23 normal controls. Depressed adolescents secreted significantly less growth hormone (GH) over the next 2 h than did normal adolescents, although a substantial proportion of the differences were accounted for by the depressed adolescents who had a specific suicidal plan or attempt during the episode. Severity of depression or the presence of other depressive symptoms did not predict GH secretion within the depressed group. Age, sex and maturational factors in the control of GH are discussed. It is concluded that these differences in GH secretion probably reflect differences in CNS beta-adrenergic and/or serotonergic function. Suicidality and depression may have different psychobiological correlates in adolescents.

Adolescent↗

PubMedDate not supplied

Accuracy of microcentrifuged hematocrits in the emergency department.

This study tests whether hematocrits (Hcts) can be accurately measured in an emergency department by microcentrifuge technique. Prior to obtaining the results of a laboratory Hct (LAB Hct), microcentrifuged Hcts (MC Hcts) were determined on 204 emergency department patients. The average difference for LAB Hct--MC Hct was -0.539 +/- 1.64 (SD). The 95% confidence interval was (-0.76, -0.31) for the difference scores and (1.49, 1.81) for the SD. The two techniques had excellent correlation (r = 0.96). Plotting the MC Hct against the LAB Hct produced a line of best fit that essentially passed through the origin (Y intercept = 0.31) and had a slope of 1.006 (both t's < 1). When only the Hct is desired, MC Hcts can be performed in place of LAB Hcts without compromising accuracy.

Adolescent↗

PubMedDate not supplied

Development of a robust, versatile, and scalable inoculum train for the production of a DNA vaccine.

For many microbial fermentation processes, the inoculum train can have a substantial impact on process performance in terms of productivity, profitability, and process control. In general, it is understood that a well-characterized and flexible inoculum train is essential for future scale-up and implementation of the process in a pilot plant or manufacturing setting. A fermentation process utilizing E. coli DH5 for the production of plasmid DNA carrying the HIV gag gene for use as a vaccine is currently under development in our laboratory. As part of the development effort, we evaluated inoculum train schemes that incorporate one, two, or three stages. In addition, we investigated the effect of inoculum viable-cell concentrations, either thawed or actively growing, over a wide range (from 2.5 x 10(4) to 1.0 x 10(8) viable cells/mL or approximately 0.001% to 4% of final working volume). The various inoculum trains were evaluated in terms of final plasmid yield, process time, reproducibility, robustness, and feasibility at large scale. The results of these studies show that final plasmid yield remained in the desired range, despite the number of stages or inoculation viable-cell concentrations comprising the inoculum train. On the basis of these observations and because it established a large database, the first part of these investigations supports an exceptional flexibility in the design of scalable inoculum trains for this DNA vaccine process. This work also highlighted that a slightly higher level of process reproducibility, as measured by the time for the culture to reach mid-exponential growth, was observed when using actively growing versus frozen cells. It also demonstrated the existence of a viable-cell concentration threshold for the one-stage process, since we observed that inoculation of the production stage with very low amounts of viable cells from a frozen source could lead to increased process sensitivity to external factors such as variation in the quality of the raw materials used in the medium formulation. However, our analysis indicates that, despite this slight disadvantage, a one-stage inoculum train was a viable option in many situations, especially if the inoculation viable-cell concentration was kept above 4.8 x 10(6) viable cells/mL. Because it leads to a reduction in process steps and eliminates some capital investments (i.e., inoculum fermenter), when feasible a one-stage process configuration will positively impact process economics.

Bioreactors↗

PubMedDate not supplied

Development of a highly productive and scalable plasmid DNA production platform.

With the applications of DNA vaccines extending from infectious diseases to cancer, achieving the most efficient, reproducible, robust, scalable, and economical production of clinical grade plasmid DNA is paramount to the medical and commercial success of this novel vaccination paradigm. A first generation production process based on the cultivation of Escherichia coli in a chemically defined medium, employing a fed-batch strategy, delivered reasonable volumetric productivities (500-750 mg/L) and proved to perform very well across a wide range of E. coli constructs upon scale-up at industrial scale. However, the presence of monosodium glutamate (MSG) in the formulation of the cultivation and feed solution was found to be a potential cause of process variability. The development of a second generation process, based on a defined cultivation medium and feed solution excluding MSG, was undertaken. Optimization studies, employing a plasmid coding for the HIV gag protein, resulted in cultivation conditions that supported volumetric plasmid titers in excess of 1.2 g/L, while achieving specific yields ranging from 25 to 32 microg plasmid DNA/mg of dry cell weight. When used for the production of clinical supplies, this novel process demonstrated applicability to two other constructs upon scale-up in 2,000-L bioreactors. This second generation process proved to be scalable, robust, and highly productive.

Bioreactors↗

PubMedDate not supplied

Biological variations associated with change in lifestyle among the pastoral and nomadic tribes of East Africa.

The values of a number of anthropometric, cardiovascular and biochemical variables have been compared between tribal and non-tribal Samburu. Significant differences between the two groups were found for ponderal index, supra-iliac and mid-calf skinfold thicknesses, pulse rate and both systolic and diastolic blood pressures. Similar analyses were performed on samples from tribal and non-tribal Maasai; here significant differences were found for ponderal index, height, biceps skinfold thickness, pulse rate and systolic blood pressure. No significant differences were found in serum cholesterol or serum triglyceride for either the Samburu or the Maasai. Greater variability of the skinfold measurements was found in the non-tribal Samburu than in the tribal group; this effect was less marked in the Maasai. A principal component analysis and three discriminant function analyses were performed on the Samburu data. These analyses showed that the most marked difference between the tribal and non-tribal groups was in their blood pressure levels, the non-tribal sample having significantly higher mean values than the tribal members. Possible causes for the observed differences between tribal and non-tribal groups are discussed, and the findings are contrasted with those of an earlier study, in which significant differences in cholesterol but not in blood pressure were found between samples of rural and urban Maasai. This leads to the tentative hypothesis that blood pressure is affected immediately by the change in environment, whereas the effect on cholesterol levels is a longer-term one.

Adult↗

PubMedDate not supplied

Political, administrative, and economic resources for the control of poliomyelitis.

Control of any major childhood disease in developing countries is dependent on the ability of health services to reach the susceptible population and to administer appropriate therapy or preventive action. Both of these needs are addressed by the development of primary health-care services. The vaccine-preventable diseases, including poliomyelitis, are likely to be controlled only through programs that are executed through the primary health-care system. The implications of the technical aspect of poliomyelitis control on economic resources are secondary to the administrative capability of the programs to manage these technical facilities effectively. The first prerequisite of any health program is the political will on the part of the decision makers to carry it through effectively. This will be reflected in the strength of the administrative structures and the economic resources made available. At present poliomyelitis, with its clinical visibility and its appeal to humanitarian instincts, has an importance as a leader for immunization programs and thus, for primary health care.

Health Policy↗

PubMedDate not supplied

Updating the Read Codes: user-interactive maintenance of a dynamic clinical vocabulary.

The Read Codes are a hierarchically-arranged controlled clinical vocabulary introduced in the early 1980s and now consisting of three maintained versions of differing complexity. The code sets are dynamic, and are updated quarterly in response to requests from users including clinicians in both primary and secondary care, software suppliers, and advice from a network of specialist healthcare professionals. The codes' continual evolution of content, both across and within versions, highlights tensions between different users and uses of coded clinical data. Internal processes, external interactions and new structural features implemented by the NHS Centre for Coding and Classification (NHSCCC) for user interactive maintenance of the Read Codes are described, and over 2000 items of user feedback episodes received over a 15-month period are analysed.

Computer Systems↗