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Biomedical subjects

L Hough

Publications and source records attributed to L Hough.

At least 19 recordsLinked to original sources

Giant-block twist grain boundary smectic phases.

Study of a diverse set of chiral smectic materials, each of which has twist grain boundary (TGB) phases over a broad temperature range and exhibits grid patterns in the Grandjean textures of the TGB helix, shows that these features arise from a common structure: "giant" smectic blocks of planar layers of thickness l(b) > 200 nm terminated by GBs that are sharp, mediating large angular jumps in layer orientation between blocks (60 degrees < Delta < 90 degrees ), and lubricating the thermal contraction of the smectic layers within the blocks. This phenomenology is well described by basic theoretical models applicable in the limit that the ratio of molecular tilt penetration length-to-layer coherence length is large, and featuring GBs in which smectic ordering is weak, approaching thin, melted (nematic-like) walls. In this limit the energy cost of change of the block size is small, leading to a wide variation of block dimension, depending on preparation conditions. The models also account for the temperature dependence of the TGB helix pitch.

Journal Article↗

Dynamics of histamine H(3) receptor antagonists on brain histamine metabolism: do all histamine H(3) receptor antagonists act at a single site?

Thioperamide, the prototypical histamine H(3) receptor antagonist, acts at the brain histamine H(3) autoreceptor to promote the release and metabolism of neuronal histamine, resulting in higher brain levels of the metabolite tele-methylhistamine. However, unlike thioperamide, several new histamine H(3) receptor antagonists enter the central nervous system (CNS), block brain histamine H(3) receptors and increase histamine release without increasing brain tele-methylhistamine levels. Experiments were performed presently in an attempt to understand these results. Consistent with previous findings, thioperamide significantly increased the content and synthesis rate of tele-methylhistamine in mouse and rat brain. In contrast, the histamine H(3) receptor antagonists GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and clobenpropit did not affect tele-methylhistamine synthesis rate in mouse whole brain. The histamine H(3) receptor ligand GT-2016 (5-cyclohexyl-1-(4-imidazol-4-ylpiperidyl)pentan-1-one) had no effect on tele-methylhistamine levels in any rat brain region and decreased tele-methylhistamine synthesis rates in the mouse whole brain. To examine the possibility that these histamine H(3) receptor antagonists might prevent the methylation of newly released histamine, they were co-administered with thioperamide to determine their effects on the thioperamide-induced stimulation of tele-methylhistamine synthesis. GT-2016 significantly reduced the thioperamide-induced activation of tele-methylhistamine synthesis in mouse whole brain and in several regions of rat brain. Although further clarification is needed, these results suggest that some histamine H(3) receptor antagonists may promote the release of neuronal histamine, but also act to reduce histamine methylation in vivo by an unknown mechanism.

Analysis of Variance↗

Indications and results of combined anterior-posterior approaches for spine tumor surgery.

Spinal instrumentation currently allows gross-total resection and reconstruction in cases of malignancies at all levels of the spine. The authors analyzed the results in 110 patients who underwent surgery for primary and metastatic spinal tumors over a 5-year period (1989-1993) at a single institution. Major primary sites of tumor included breast (14 cases), chordoma (14 cases), lung (12 cases), kidney (11 cases), sarcoma (13 cases), plasmacytoma (10 cases), and others (36 cases). Prior to surgery, 55 patients (50%) had received prior treatment. Forty-eight patients (44%) were nonambulatory, and severe paraparesis was present in 20 patients. Fifty-three patients (48%) underwent combined anterior-posterior resection and instrumentation. 33 (30%) underwent anterior resection with instrumentation, 18 (16%) underwent anterior or posterior resection alone, and the remaining six patients (5%) underwent posterior resection and instrumentation. Major indications for anterior-posterior resection included three-column involvement, high-grade instability, involvement of contiguous vertebral bodies, and solitary metastases. Postoperatively, 90 patients improved neurologically. The overall median survival was 16 months, with 46% of patients surviving 2 years. Fifty-three patients (48%) suffered postoperative complications. Despite the high incidence of complications, the majority of patients reported improvement in their quality of life at follow-up review. Our findings suggest that half of all patients with spinal malignancies require combined anterior-posterior surgery for adequate tumor removal and stabilization.

Adult↗

Influence of blood group and secretor status on carbohydrate structures in human gastric mucins: implications for peptic ulcer.

1. The content and distribution of carbohydrate was examined in mucus glycopolypeptides from human antral mucosae. 2. The mean amount of carbohydrate per 1000 amino acid residues was found to be similar in glycopolypeptides with A, B or H activity. It was slightly, though significantly, less in glycopolypeptides lacking these determinants, because carbohydrate chains were of a shorter average length than in the A-, B- or H-active preparations. This difference was reflected in the sizes of oligosaccharide-alcohols released from representative glycopolypeptides with alkaline borohydride. 3. Differences between A-, B- or H-active and non-secretor glycopolypeptides in terms of the mean number of carbohydrate chains per 1000 amino acid residues were found to be small, and without significance. 4. The average number of peripheral monosaccharide units per 1000 amino acid residues was greater in A-active than in H-active, and least in non-secretor, glycopolypeptides. This order was reversed for monosaccharide units incorporated into skeletal (core plus backbone) structures. The difference in each case was statistically significant. 5. These findings suggest that the increased risk of peptic ulcer associated with blood group O and non-secretor status is unlikely to be attributable to an inherent deficiency in the protective mucus layer, linked to differences between mucins that are associated with A, B or H activity. Other hypotheses linked to infection with Helicobacter pylori are examined.

Blood Group Antigens↗

Surgical treatment of spinal cord compression from epidural metastasis.

PURPOSE: A retrospective study of the results of neoplastic cord compression was undertaken to determine the effectiveness of surgical treatment and to assess quality of life in patients undergoing extensive procedures with potential morbidity. PATIENTS AND METHODS: Over a 5-year period (1989 to 1993), a total of 110 patients underwent surgery. Fifty-five patients (50%) had undergone prior treatment, including 47 (43%) who had failed to respond to prior irradiation (RT). Before surgery, 48 patients (44%) were nonambulatory, with severe paresis being present in 20. Surgery included staged anterior-posterior resections in 53 patients (48%), anterior resections in 33 (30%), and posterior resection in six (5%), all of whom required spinal instrumentation for reconstruction; only 18 patients underwent resection without instrumentation. RESULTS: Postoperatively, 90 patients (82%) were improved, both in terms of pain relief and ambulatory status. Fifty-three patients (48%) experienced postoperative complications, related statistically to the following three factors: age over 65 years, prior treatment, and presence of paraparesis. The overall median survival duration was 16 months, with 46% alive at 2 years. Apart from primary tumor, the presence of preoperative paraparesis had the most significant impact on survival. CONCLUSION: Our data suggest that the effective surgical treatment of neoplastic compression requires anterior-posterior resection in most patients to achieve the goal of total tumor resection, with the majority requiring instrumentation. Long-term survival is feasible in a subset of patients with this aggressive surgical approach.

Adult↗

Thio and epidithio derivatives of methyl beta-lactoside.

Treatment of methyl beta-lactoside with triphenylphosphine-carbon tetrabromide in pyridine gave the 3',6'-anhydro-6-bromo-6-deoxy derivative, from which 6-thio derivatives were prepared, and methyl 3',4'-O-isopropylidene-beta-lactoside gave the 6,6'-dibromo-6,6'-dideoxy derivative. A dibromide was prepared also from methyl 4',6'-O-benzylidene-beta-lactoside by bromination with Ph3P-CBr4, acetylation, and then treatment with N-bromosuccinimide. Various 6,6'-dithio derivatives were prepared from the 6,6'-dibromide by nucleophilic substitution reactions. Reaction of the 6,6'-dibromide with thiourea led to the 6,6'-epidithio derivative and, with potassium tricarbonate, the bridged 6,6'-trithiocarbonate was formed. The 6,6'-dibromo derivative underwent selective nucleophilic substitution to give a variety of 6'-bromo-6-thio derivatives. Likewise, with azide, the 6-azide was formed first, followed by the 6,6'-diazide and the product of elimination, the 6-azido-5%-ene. Raney nickel-mediated desulphuration of the various 6,6'-dithio derivatives afforded methyl 6,6'-dideoxy-beta-lactoside and desulphuration of the 6'-bromo-6-thio derivatives could be accomplished without reductive dehalogenation to give methyl 6'-bromo-6,6'-dideoxylactoside.

Carbohydrate Sequence↗

Learning collaboration in a laboratory setting.

Collaboration is a process that contributes in many ways to improved nursing care. Before collaboration can be practiced effectively, the component skills must be learned. This paper describes a course for graduate students that was developed for this purpose. The students learn basic skills in the classroom and apply them to patients in a laboratory setting. An overview of collaboration, the collaboration course, and clinical application is presented.

Aged↗

Synthesis of 1-deoxy-6-epicastanospermine and 1-deoxy-6,8a-diepicastanospermine.

Extension of the carbon spine of 2,3;4,5-di-O-isopropylidene-beta-D-fructopyranoside by oxidation at C-1 followed by a Wittig reaction using the phosphorane Ph3P = CHCO2Et gave an oct-4-ulose derivative, which was then transformed into the key intermediate 1-azido-1,2,3-trideoxy-D-arabino-oct-4-ulose. Catalytic hydrogenolysis of this azide, followed by reductive amination between the resulting 1-amino substituent and the 4-keto-group then gave a mixture of pyrrolidines. After sulphonylation at the terminal 8-position, the pyrrolidines were then cyclised further between the nitrogen and C-8 to give 1-deoxy-6-epicastanospermine and 1-deoxy-6,8a-diepicastanospermine.

Alkaloids↗

Plasma fibronectin synthesis in normal and injured humans as determined by stable isotope incorporation.

In humans, plasma fibronectin decreases early after operative injury, burn, or trauma, followed by a rapid restoration with a secondary decline typically observed if such patients become septic. We determined the rate of plasma fibronectin and plasma fibrinogen synthesis in normal subjects and injured patients using a stable isotope incorporation technique with [15N]glycine. During a constant 14-h infusion of [15N]glycine, the enrichment of [15N]glycine in both the free plasma glycine precursor pool as well as the urinary hippurate pool was determined; the latter used as an estimate of intracellular hepatic precursor enrichment. [15N]Glycine enrichment in both plasma fibronectin and fibrinogen was also quantified. The synthesis rate (Js/V) expressed in micrograms per milliliter of plasma per hour and the fractional synthesis rate (FSR) expressed as percentage of the plasma pool produced per day were determined. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into urinary hippurate was 35.35 +/- 1.46%/d, whereas the Js/V was 4.45 +/- 0.19 micrograms/ml plasma per h. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into free plasma glycine was 14.73 +/- 0.63%/d, whereas the Js/V was 1.98 +/- 0.09 micrograms/ml plasma per h. Early (2-3 d) after burn injury, fibronectin synthesis was increased (Js/V = 5.74 +/- 0.36; P less than 0.05), whereas later after injury, fibronectin synthesis began to decline (Js/V = 3.52 +/- 0.24; P less than 0.05) based on 15N enrichment of urinary hippurate. In contrast, the Js/V and FSR of plasma fibrinogen, a well-documented acute-phase plasma protein, revealed a sustained elevation (P less than 0.05) after injury in both the trauma and burn patients. Thus, plasma fibronectin synthesis is elevated early postinjury, which may contribute to the rapid restoration of its blood level. However, once fibronectin levels have normalized, the synthesis of plasma fibronectin appears to decline.

Adult↗

The synthesis of some fluoro derivatives of sucrose.

2,3,1',3'4',6'-Hexa-O-benzylsucrose was obtained by mild acid-catalysed hydrolysis of the 4,6-O-isopropylidene derivative and then converted into its 4,6-di-O-mesyl derivative. Selective displacement of this disulphonate with fluoride anion (from tetrabutylammonium fluoride) then afforded the 6-fluoro-4-mesylate. Removal of the protecting groups yielded 6-deoxy-6-fluorosucrose, which was characterised as its crystalline hepta-acetate. A derivative of 6-deoxy-6-fluoro-galacto-sucrose was formed when the above 6-fluoro-4-mesylate was subjected to nucleophilic displacement with benzoate anion.

Chemical Phenomena↗

Transformations of cellobiose derivatives into analogues of lactose.

The preparation of benzyl beta-cellobioside 2,3,6,2',3'-pentabenzoate (2b) via a 4',6'-benzylidene acetal in 27% overall yield from cellobiose is described. This pentabenzoate has been utilised for conventional syntheses of the 6'-amino-, 4'-amino-, and 4',6'-diamino-analogues of lactose, via the 4',6'-dimesylate. In addition, reaction of the pentabenzoate 2b with sulphuryl chloride initially afforded the 6'-chloro derivative, which was then slowly transformed into a mixture of the 4',6'-dichloro-lactoside and an isomer in which the non-reducing ring of the disaccharide had been transformed into a 3',6'-dideoxy-3',6'-dichloro-gulopyranoside. The latter probably arose by neighbouring-group participation by the 3'-benzoloxy group prior to the introduction of the secondary 3'-chloro substituent. The former dichlorocompound was subsequently converted into 4',6'-dideoxy-4',6'-dichloro-lactose. It was found that the rate of nucleophilic displacement at C-4' of a cellobioside was much lower than that for the corresponding alpha-linked disaccharide, maltose. Furthermore, nucleophilic displacement at C-4' of a lactoside was accompanied by substantial elimination, to give the 4'-ene, together with some cleavage of the interglycosidic bond. tthe origins of these effects are discussed.

Cellulose↗

IgA and IgM cytoplastic inclusions in a series of cases of chronic lymphocytic leukaemia.

Seventy-two cases of typical chronic lymphocytic leukaemia were screened by electron microscopy for the presence of intracytoplasmic immunoglobulin crystals. Immunoglobulin inclusions were found in four cases. Immunofluorescent studies showed that the inclusions contained IgA in two cases and IgM in the other two patients. Lambda light chain specificity was demonstrated in all four cases. The ultrastructure of the inclusions was identical in each patient except that in one of the IgA cases the inclusions were found in the perinuclear cistern in addition to the more usual location within cisternae of rough endoplasmic reticulum. Surface immunofluorescence showed mu heavy chains in the two cases displaying IgM crystal formation, but in the two IgA patients, no alpha heavy chains were demonstrable at the cell surface. The possible significance of these findings is discussed in relation to the existing literature.

Cytoplasm↗