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Biomedical subjects

J G Jones

Publications and source records attributed to J G Jones.

At least 37 records · Page 2Linked to original sources

An integrated (2)H and (13)C NMR study of gluconeogenesis and TCA cycle flux in humans.

Hepatic glucose synthesis from glycogen, glycerol, and the tricarboxylic acid (TCA) cycle was measured in five overnight-fasted subjects by (1)H, (2)H, and (13)C NMR analysis of blood glucose, urinary acetaminophen glucuronide, and urinary phenylacetylglutamine after administration of [1,6-(13)C(2)]glucose, (2)H(2)O, and [U-(13)C(3)]propionate. This combination of tracers allows three separate elements of hepatic glucose production (GP) to be probed simultaneously in a single study: 1) endogenous GP, 2) the contribution of glycogen, phosphoenolpyruvate (PEP), and glycerol to GP, and 3) flux through PEP carboxykinase, pyruvate recycling, and the TCA cycle. Isotope-dilution measurements of [1,6-(13)C(2)] glucose by (1)H and (13)C NMR indicated that GP in 16-h-fasted humans was 10.7 +/- 0.9 micromol.kg(-1).min(-1). (2)H NMR spectra of monoacetone glucose (derived from plasma glucose) provided the relative (2)H enrichment at glucose H-2, H-5, and H-6S, which, in turn, reflects the contribution of glycogen, PEP, and glycerol to total GP (5.5 +/- 0.7, 4.8 +/- 1.0, and 0.4 +/- 0.3 micromol.kg(-1).min(-1), respectively). Interestingly, (13)C NMR isotopomer analysis of phenylacetylglutamine and acetaminophen glucuronide reported different values for PEP carboxykinase flux (68.8 +/- 9.8 vs. 37.5 +/- 7.9 micromol.kg(-1).min(-1)), PEP recycling flux (59.1 +/- 9.8 vs. 27.8 +/- 6.8 micromol.kg(-1).min(-1)), and TCA cycle flux (10.9 +/- 1.4 vs. 5.4 +/- 1.4 micromol.kg(-1).min(-1)). These differences may reflect zonation of propionate metabolism in the liver.

Acetaminophen↗

CT appearance of some colonic villous tumors.

OBJECTIVE: A review was made of the CT studies and pathology reports of four patients with surgically resected colonic villous adenomatous tumors, two of whom had focal carcinomatous invasion. CONCLUSION: Two patients had villous tumors with IV contrast-enhancing convolutional gyral patterns. The other two patients had tumor masses that showed oral contrast medium collecting in surface interstices, analogous to findings with barium enemas. One of the latter also had an unusual cluster of mesenteric vessels adjacent to the lesion.

Adenoma, Villous↗

A critical step in metastasis: in vivo analysis of intravasation at the primary tumor.

Detailed evaluation of all steps in tumor cell metastasis is critical for evaluating the cell mechanisms controlling metastasis. Using green fluorescent protein transfectants of metastatic (MTLn3) and nonmetastatic (MTC) cell lines derived from the rat mammary adenocarcinoma 13762 NF, we have measured tumor cell density in the blood, individual tumor cells in the lungs, and lung metastases. Correlation of blood burden with lung metastases indicates that entry into the circulation is a critical step for metastasis. To examine cell behavior during intravasation, we have used green fluorescent protein technology to view these cells in time lapse images within a single optical section using a confocal microscope. In vivo imaging of the primary tumors of MTLn3 and MTC cells indicates that both metastatic and nonmetastatic cells are motile and show protrusive activity. However, metastatic cells show greater orientation toward blood vessels and larger numbers of host cells within the primary tumor, whereas nonmetastatic cells fragment when interacting with vessels. These results demonstrate that a major difference in intravasation between metastatic and nonmetastatic cells is detected in the primary tumor and illustrate the value of a direct visualization of cell properties in vivo for dissection of the metastatic process.

Adenocarcinoma↗

Quantitation of gluconeogenesis by (2)H nuclear magnetic resonance analysis of plasma glucose following ingestion of (2)H(2)O.

We present a simple (2)H NMR assay of the fractional contribution of gluconeogenesis to hepatic glucose output following ingestion of (2)H(2)O. The assay is based on the measurement of relative deuterium enrichment in hydrogens 2 and 3 of plasma glucose. Plasma glucose was enzymatically converted to gluconate, which displays fully resolved deuterium 2 and 3 resonances in its (2)H NMR spectrum at 14.1 T. The signal intensity of deuterium 3 relative to deuterium 2 in the gluconate derivative as quantitated by (2)H NMR was shown to provide a precise and accurate measurement of glucose enrichment in hydrogen 3 relative to hydrogen 2. This measurement was used to estimate the fractional contribution of gluconeogenesis to hepatic glucose output for two groups of rats; one group was fasted for 7 h and the other was fasted for 29 h. Rats were administered (2)H(2)O to enrich total body water to 5% over the last 4-5 h of each fasting period. For the 7-h fasted group, the hydrogen 3/hydrogen 2 enrichment ratio of plasma glucose was 0.32 +/- 0.09 (n = 7). This indicates that gluconeogenesis contributed 32 +/- 9% of total hepatic glucose output with glycogenolysis contributing the remainder. For the 29-h fasted group, the hydrogen 3/hydrogen 2 enrichment ratio of plasma glucose was 0.81 +/- 0.10 (n = 6), indicating that gluconeogenesis supplied the bulk of hepatic glucose output (81 +/- 10%).

Administration, Oral↗

Effect of a screening-based prevention policy on prevalence of early-onset group B streptococcal sepsis.

OBJECTIVE: To assess the effectiveness and feasibility of implementing the Centers for Disease Control and Prevention (CDC) screening-based guidelines for preventing early-onset group B streptococcal sepsis. METHODS: We compared prevalence of early-onset group B streptococcal sepsis after institution of the CDC screening-based protocol (October 1, 1995 through August 31, 1999) with that of historical controls (January 1, 1992 through June 30, 1995). We reviewed medical records for a cohort of deliveries of at least 23 weeks' gestation (January 1, 1996 through December 31, 1996) for group B streptococcal colonization status, risk factors, and intrapartum antibiotic prophylaxis. RESULTS: The prevalence of early-onset group B streptococcal sepsis was 1.16 per 1000 (36 of 31, 133) live births before and 0.14 per 1000 (four of 28,733) live births after institution of the CDC protocol (P <.001). Maternal colonization was known for 95.3% of the 7168 women who delivered (January 1, 1996 through December 31, 1996) at or after 37 weeks' gestation. Of 2174 women who qualified for intrapartum antibiotic prophylaxis, 1871 (86.1%) received it before delivery. There was 93. 8% compliance with intrapartum antibiotic prophylaxis for women who delivered vaginally and 53.2% compliance for women who delivered by cesarean. CONCLUSION: Institution of the CDC screening-based protocol was accomplished at a specialty women's hospital, staffed by full-time faculty and community physicians, with 93.8% compliance for vaginal deliveries, and was associated with an 88% reduction in early-onset group B streptococcal sepsis.

Adolescent↗

Discriminating between the effect of shunt and reduced VA/Q on arterial oxygen saturation is particularly useful in clinical practice.

There is an extensive literature on methods for discriminating between an increased shunt and a reduced ratio of ventilation to perfusion. In this review we prefer the terms "VA/Q" and "reduced or low VA/Q" rather than "V/Q inequality" to refer to the effects on arterial oxygenation of reducing V/Q below 0.8 to about 0.1. Almost without exception the conventional methods for measuring shunt and reduced VA/Q are invasive as well as technically complex. For most clinicians who are dealing with a hypoxemic patient the relevance of these entities is not so obvious as to justify the time and difficulty in either understanding or measuring them. However this review shows that, while an increased shunt and a decreased VA/Q both reduce arterial oxygen saturation (SaO2) at a particular inspired oxygen concentration (PIO2), the effect of shunt and reduced VA/Q have important clinical differences on the relationship between PIO2 and SaO2. The review also outlines a simple non-invasive method for measuring shunt and reduced VA/Q which illustrates the value of discriminating between them in clinical practice.

Diagnosis, Differential↗

Anaesthesia and saccadic eye movements.

During the last 10 years, there has been a vast increase in day-case surgery under general anaesthesia, but this has not been accompanied by research into the residual cognitive and motor effects during recovery from anaesthesia. Part of the explanation for this phenomenon is the lack of a suitable biophysical monitor of anaesthetic sedation. This review discusses one of the most commonly used of these biophysical monitors - namely saccadic eye movements. In particular, the efficacy of peak saccadic velocity as a monitor of sedation will be evaluated. In addition, the physiology and pharmacology of saccadic eye movements will be discussed within the context of developing other parameters of saccadic eye movements as novel biophysical monitors of anaesthetic sedation.

Anesthesia Recovery Period↗

Measurement of blood volume in surgical and intensive care practice.

Clinical studies to assess the benefits of blood transfusion or haemodilution in critical illness should take account of measured CBV before, during and after intervention. As mentioned above, surrogate measures of CBV are inadequate and studies based on these must be considered incomplete, because they cannot distinguish between effects of changes in haemoglobin concentration and changes in blood volume. The choice of a suitable technique for measuring CBV depends on the facilities available locally. In general, methods based on labelled red cells are more reliable but are technically demanding and time consuming. Those based on albumin are likely to yield false high values and this is particularly true in all patients with impaired capillary integrity. The most promising plasma marker is hydroxyethyl starch which may be particularly useful when the polysaccharide is labelled with a fluorescent dye. Attaching fluorescein to hydroxyethyl starch is not difficult and, should demand be sufficient, it may well become available from manufacturers who are already capable of providing other fluorescent polysaccharides. The clinical benefits of such a development would include more rational schedules of i.v. fluid and blood transfusion management in surgical and intensive care patients.

Blood Volume↗

Use of combined microautoradiography and fluorescence in situ hybridization to determine carbon metabolism in mixed natural communities of uncultured bacteria from the genus Achromatium.

Combined microautoradiography and fluorescence in situ hybridization (FISH) was used to investigate carbon metabolism in uncultured bacteria from the genus Achromatium. All of the Achromatium species identified in a freshwater sediment from Rydal Water, Cumbria, United Kingdom, which were distinguishable only by FISH, assimilated both [(14)C]bicarbonate and [(14)C]acetate. This extends previous findings that Achromatium spp. present at another location could only utilize organic carbon sources. Achromatium spp., therefore, probably exhibit a range of physiologies, i.e., facultative chemolithoautotrophy, mixotrophy, and chemoorganoheterotrophy, similar to other large sulfur bacteria (e.g., Beggiatoa spp.).

Acetates↗

Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen.

Glycogen-targeting subunits of protein phosphatase-1, such as protein targeting to glycogen (PTG), direct the phosphatase to the glycogen particle, where it stimulates glycogenesis. We have investigated the metabolic impact of overexpressing PTG in liver of normal rats. After administration of PTG cDNA in a recombinant adenovirus, animals were fasted or allowed to continue feeding for 24 hours. Liver glycogen was nearly completely depleted in fasted control animals, whereas glycogen levels in fasted or fed PTG-overexpressing animals were 70% higher than in fed controls. Nevertheless, transgenic animals regulated plasma glucose, triglycerides, FFAs, ketones, and insulin normally in the fasted and fed states. Fasted PTG-overexpressing animals receiving an oral bolus of [U-(13)C]glucose exhibited a large increase in hepatic glycogen content and a 70% increase in incorporation of [(13)C]glucose into glycogen. However, incorporation of labeled glucose accounted for only a small portion of the glycogen synthesized in PTG-overexpressing animals, consistent with our earlier finding that PTG promotes glycogen synthesis from gluconeogenic precursors. We conclude that hepatic PTG overexpression activates both direct and indirect pathways of glycogen synthesis. Because of its ability to enhance glucose storage without affecting other metabolic indicators, the glycogen-targeting subunit may prove valuable in controlling blood glucose levels in diabetes.

Adenoviridae↗

Malignant Brenner tumor mimicking a primary squamous cell carcinoma of the cervix.

An 86-year-old female presented with a necrotic cervical mass that was biopsy-proven squamous cell carcinoma. She had an elevated CA-125 and a pelvic mass. At surgery, this mass was found to be of adnexal origin and contiguous with the cervix. Histology showed a malignant Brenner tumor with abundant squamous differentiation eroding the cervix and simulating a primary cervical malignancy. We describe this case and review the literature on metastatic tumors to the cervix.

Aged↗

Effects of low-dose isoflurane on saccadic eye movement generation.

The effects of 0.15% quasi-steady-state end-tidal isoflurane on two saccadic eye-movement tests were examined in five volunteers using a newly devised computer-based recording system. The tests were saccadic latency and a countermanding task, the latter being an indicator of the highest levels of conscious performance. A moving light-emitting diode target was displayed on a screen and in the saccadic-latency task the latency of eye movement to the target was measured. In all five subjects the latency increased with anaesthetic by an amount which varied from 8 to 45 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In the countermanding task, the subject had to voluntarily inhibit movement to the target. Again anaesthetic increased the latency of response, which varied from 6 to 33 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In these studies it appeared that two tasks, one a simple latency test and the other, the countermanding task, requiring higher cortical processing were equally impaired at subanaesthetic concentrations of isoflurane.

Anesthetics, Inhalation↗

Examination of a rheological profile for blood using micropore filters.

Various techniques have been used to assess the flow properties of blood and blood cells in a range of clinical situations. Filtration through microfilters offers a single technique for measuring the flow properties of all cellular components of blood in one experiment but depends on an assumed ability to recognize cells that make up <10% of leucocytes. The remaining leucocytes, labelled fast leucocytes, were previously presumed to be lymphocytes and granulocytes. This study confirmed the identities of these fast leucocytes as those of lymphocytes and granulocytes in undiluted blood. The transit time for lymphocytes (1.2 s) and granulocytes (1.6 s) is close to that recorded for fast leucocytes (1.7 s). The resistance of each type of blood cell to flow through 5 microm filters was defined in this study as the product of the concentration of that cell in blood and its transit time through a pore in the filter. The total resistance to flow of healthy blood through the filter is 4.46 x 10(7) s/ml and is attributed to plasma (2.7%), red cells (25.9%), fast leucocytes (25.3%) and slow leucocytes (46.1%). In a cohort of 21 men with peripheral arterial disease the total resistance was increased to 7.82 x 10(7) s/ml and attributed to plasma (1.5%), red cells (14.5%), fast leucocytes (21.0%) and slow leucocytes (63.00%). This analysis therefore provides a single test for assessing the flow properties of all the cellular components of blood and plasma.

Blood Viscosity↗

"Crack" cocaine-induced syndrome mimicking sarcoidosis.

A 39-year-old man with a history of frequent "crack" cocaine use of several years' duration presented with progressive dyspnea. Evaluation revealed bilateral interstitial pulmonary infiltrates and hilar adenopathy, diffuse pulmonary uptake of gallium, and markedly elevated serum angiotensin-converting enzyme activity. Open lung biopsy revealed interstitial and perivascular collections of histiocytes containing refractile, polarizable material, presumably inhaled along with the cocaine. Paratracheal lymph nodes were enlarged, reactive, and contained similar polarizable material. The well-formed, non-necrotizing granulomata characteristic of sarcoidosis were not present in either tissue specimen. To our knowledge, the association of chronic crack cocaine inhalation with this constellation of clinical findings, typically seen in sarcoidosis, has not previously been described.

Adult↗