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H Law

Publications and source records attributed to H Law.

34 records · Page 2Linked to original sources
PubMed1996

Binding of O-alkyl derivatives of serotonin at human 5-HT1D beta receptors.

In humans, 5-HT1D serotonin receptors represent terminal autoreceptors, and there is some evidence that 5-HT1D ligands may be useful in the treatment of migraine. The most widely used 5-HT1D agonist is sumatriptan; however, this agent reportedly displays little selectivity for 5-HT1D versus 5-HT1A receptors. To identify novel serotonergic agents with enhanced 5-HT1D versus 5-HT1A selectivity, we attempted to take advantage of possible differences in the regions of bulk tolerance associated with the 5-position of the 5-HT binding sites for these two populations of receptors. Examination of a series of 5-(alkyloxy)tryptamine derivatives demonstrated that compounds with unbranched alkyl groups of up to eight carbon atoms bind with high affinity at human 5-HT1D beta receptors (Ki < 5 nM) but demonstrate less than 50-fold selectivity relative to 5-HT1A receptors. Alkyl groups longer than eight carbon atoms impart reduced affinity for 5-HT1A receptors whereas groups longer than nine carbon atoms lead to compounds with reduced affinity at 5-HT1D beta receptors. 5-(Nonyloxy)tryptamine (10) represents a compound with optimal 5-HT1D beta affinity (Ki = 1 nM) and selectivity (> 300-fold). Branching of the alkyl chain, to 5-[(7,7-dimethylheptyl)oxy]tryptamine (15), results in an agent with somewhat lower affinity (5-HT1D beta Ki = 2.3 nM) but with greater (i.e, 400-fold) 5-HT1D versus 5-HT1A selectivity. Replacement of the oxygen atom of 10 with a methylene group (i.e., 20), replacement of the O-proximate methylene with a carbonyl group (i.e., ester 26), or cyclization of the aminoethyl moiety to a carbazole (e.g., 34, 36) or beta-carboline (i.e., 37), result in reduced affinity and/or selectivity. None of the compounds examined displayed significant selectivity for 5-HT1D beta versus 5-HT1D alpha sites; nevertheless, compounds 10 (recently shown to have as a 5-HT1D agonist) and 15 represent the most 5-HT1D versus 5-HT1A selective agents reported to date.

Animals↗
PubMed1996

Items for assessing posthypnotic recognition amnesia with the HGSHS:A and the SHSS:C.

A procedure for assessing posthypnotic recognition amnesia is described. A set of items for the Harvard Group Scale of Hypnotic Susceptibility, Form A and for the Stanford Hypnotic Susceptibility Scale, Form C were developed and analyzed for reliability and their ability to discriminate individuals who demonstrate posthypnotic amnesia. Recognition amnesia could be assessed as reliably as recall amnesia, and posthypnotic recognition amnesia identified a select subgroup of high hypnotizable individuals who had higher scores on the screening scales. These items may prove useful for assessing posthypnotic recognition amnesia in conjunction with widely used scales of hypnotic susceptibility.

Adult↗
PubMed1994

Influence of amine substituents on 5-HT2A versus 5-HT2C binding of phenylalkyl- and indolylalkylamines.

The effect of 15 different amine substituents on 5-HT2A and 5-HT2C serotonin receptor binding was investigated for two series of compounds (i.e., phenylalkylamine and indolylalkylamine derivatives). In general, amine substitution decreases receptor affinity; however, N-(4-bromobenzyl) substitution results in compounds that bind at 5-HT2A receptors with high affinity (Ki < 1 nM) and with > 100-fold selectivity. Although parallel structural modification in the two series result in parallel shifts in 5-HT2C binding, these same modifications alter 5-HT2A binding in a less consistent manner.

Binding Sites↗
PubMed1991

Are the hepatic arteries "end arteries"?

Twenty-five autopsy livers were studied for intrahepatic arterial anastomoses. Under fluoroscopy, barium suspension at various concentrations, with or without latex, was injected into the hepatic artery. One-centimeter axial or coronal liver sections were radiographed with high-resolution mammographic technique. All films were reviewed. Seven interconnecting arterial pathways were demonstrated: subcapsular and peripheral arcades, proximal and intermediate connecting vessels, periportal arterial rete and ring, a fine parenchymal network, and connections with the gallbladder arterial system. In the six cases where a branch artery was occluded, arterial filling of the entire liver was demonstrated. The authors conclude that these interconnecting networks could account for the infrequency of hepatic infarcts, are the anatomic basis for the intrahepatic spread of malignant lesions, the "duplication" and "triplication" patterns on arteriography, and may account for the outer streaks of the arteriographic "thread and streak" sign in portal vein invaded by hepatocellular carcinoma.

Angiography↗
PubMed1990

Neutralization receptor-based immunoassay for detection of neutralizing antibodies to Escherichia coli verocytotoxin 1.

The NeutRELISA, a modification of the receptor enzyme-linked immunosorbent assay developed for the detection of verocytotoxin 1 (VT1) which permits the rapid detection of neutralizing antibodies (NAb) against this toxin, has been performed. A standard concentration of VT1 was preincubated with VT-immune or nonimmune rabbit serum. The serum-toxin mixtures were then added to microtiter plates coated with deacylated globotriosyl ceramide (lyso-Gb3). The reduction of VT1 binding to lyso-Gb3 in the immune serum-toxin mixtures compared with the VT1-Gb3 binding in the nonimmune serum-toxin mixtures was detected by using mouse monoclonal antibody to VT1. After standardization of the NeutRELISA with rabbit sera, 57 human control serum samples were tested to establish a cutoff value below which NeutRELISA results would be considered positive. Thirty-three single serum samples known to demonstrate NAb to VT1 by biological assay reproducibly demonstrated VT1 NAb when tested by the NeutRELISA. There was a close correlation between the biological VT1 neutralization assay and the NeutRELISA. This assay offers a practical, rapid, and reliable approach for the detection of NAb to VT1 and other verocytotoxins.

Antibodies, Bacterial↗
PubMed1989

Gastric glycerolipid as a receptor for Campylobacter pylori.

A species was detected in the lipid extract of human red blood cells and human and pig stomach tissue which was specifically recognised by isolates of Campylobacter pylori. The levels of this lipid were higher in human stomach antrum than in fundus and in adult compared with infant tissue samples. Chemical treatment of the purified substance suggests that it is a novel glycerolipid.

Animals↗
PubMed1989

Globotetraosylceramide is recognized by the pig edema disease toxin.

The pig edema disease toxin has been shown by a tlc glycolipid binding assay to bind specifically to globotetraosylceramide (Gb4, GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4GlcCer.). Binding was reduced for globotriosylceramide (Gb3, Gal alpha 1-4Gal beta 1-4GlcCer) and more markedly for the Forssman antigen (GalNAc alpha 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4GlcCer). Paragloboside, blood group A glycolipids, glycolipids terminating in Gal NAc beta 1-4Gal-, and glycolipids in which globoside was present as an internal sequence did not bind the toxin. Isogloboside (GalNAc beta 1-3Gal alpha 1-3Gal beta 1-4GlcCer) was efficiently recognized. This toxin is genetically related to the verotoxin (or Shiga-like) family of toxins for which Gb3 has been shown to be the receptor. The difference in susceptibility of cell lines to the cytotoxicity of the pig edema disease toxin and the Shiga and Shiga-like toxins is consistent with the difference in receptor glycolipid binding.

Animals↗
PubMed1988

Sulfogalactolipid binding protein SLIP 1: a conserved function for a conserved protein.

We have studied the species and tissue expression of the 68kD sulfogalactolipid binding protein SLIP 1, originally detected in the male germ cells of the rat (Lingwood: Can. J. Biochem. Cell Biol., 63:1077-1085, 1985). Our results show that SLIP 1 has been highly conserved during evolution and is found in the testes of all vertebrates tested. In studies in the rat, we have found that SLIP 1 is, however, tissue restricted, being found only in the brain (also a major site of sulfogalactolipid biosynthesis) in addition to the testis. SLIP 1 was also detected in mammalian oocytes. The SLIP 1 species detected in brain and oocytes retain the sulfogalactolipid-binding characteristics of rat testicular SLIP 1, indicating that, in addition to immunological features, the glycolipid-binding function of SLIP 1 is conserved in these tissues.

Animals↗
PubMed1987

Glycolipid binding of purified and recombinant Escherichia coli produced verotoxin in vitro.

Escherichia coli verotoxin (also known as Shiga-like toxin) has been implicated in the aetiology of the hemolytic uremic syndrome and hemorrhagic colitis. The glycolipid binding specificity of verotoxin purified from E. coli H30 and verotoxin cloned from bacteriophage H19B has been examined. Verotoxin from both sources binds specifically to globotriosyl ceramide containing the carbohydrate sequence galactose alpha 1-4galactose beta 1-4glucose-ceramide. Removal of the terminal galactose or substitution with N-acetylgalactosamine in beta 1-3 linkage deletes toxin binding activity. A ceramide trihexoside species, consistent with a globotriosyl ceramide structure was shown to be the major verotoxin-binding glycolipid of cultured vero cells which are routinely used to measure the cytotoxicity of toxin samples.

Bacterial Toxins↗
PubMed1985

Use of fluorescent standards in protein transfer and immunoblotting. Accurate estimation of the molecular weight of immunoreactive species.

Fluorescent protein molecular weight markers have been used to standardize the electrotransfer and subsequent immunostaining of proteins separated by sodium dodecyl sulfate-polyacrylamide electrophoresis. The method permits accurate estimation of the molecular weight of immunoreactive species despite shrinkage or swelling which may occur during transfer or staining.

Collodion↗
PubMed1982

Criteria which may influence selection of dental students.

Academic qualifications are used as either the principal or the only criteria for selection of dental students. The view is often put forward that selection procedures should also identify and take into account those non-academic attributes which are considered to be predictive of the qualities which characterize a successful dentist. The aim of this study was to identify those qualities as assessed by students, dentists and patients and to consider their implications in relation to the selection procedures in Queensland. No major factors were found which could be used to improve the existing selection procedures.

Australia↗
PubMed1982

A stable propidium iodide staining procedure for flow cytometry.

A propidium iodide (PI) staining procedure is described in which 50 micrograms/ml PI in 10(-2) M Tris, pH 7.0, with 5 mM MgCl2 is used to stain murine erythroleukemia cells (MELC) grown in suspension culture as well as single cell suspensions derived from rat kidney adenocarcinoma and human prostatic carcinoma. Specificity of staining of nuclear DNA is achieved by enzymatic removal of RNA using RNAse in the staining solution. Virtually identical histograms, with the same G1 peak height and closely similar coefficients of variation (CVs), are obtained using a wide range of RNAse concentrations on replicate samples of MELC if the incubation times are sufficiently prolonged when employing the lower enzyme concentrations. For 1 mg/ml RNAse on logarithmically growing MELC, 30 min incubation at 37 degrees C is needed to obtain a maximum G1 peak height and optimal CV and there is no significant change in the histogram if the incubation is prolonged to 4 hr. For every 4-fold decrease in RNAse concentration, the incubation time at 37 degrees C must be doubled to obtain the same maximal G1 peak height and optimal CV. Unfixed cell preparations, whether derived from suspension or monolayer cultures or from solid tumors, are stable for 2 or more weeks if stored at 4 degrees C between flow cytometric analyses and histograms are usually only minimally altered if the stained cell samples are stored for 1-2 months at 4 degrees C. Sample decay is associated with bacterial contamination. If sterile preparative techniques are used initially, subsequent contamination of the stained preparations may be minimized by adding sodium azide to the stained samples at 0.1% without influencing fluorescence intensity. Glycerine may be added to 10% and the samples slowly frozen for storage without altering DNA histogram shapes. The simplicity of sample preparation and the stability of the resulting stained cell samples makes this procedure suitable for repetitive comparative sampling of tissue and cell populations over prolonged time spans.

Animals↗
PubMedDate not supplied

Risk of germ cell malignancy in children with XY intersex versus isolated cryptorchidism by immunohistochemistry.

The risk of subsequent development of testicular germ cell neoplasia is related to presence of underlying developmental defects such as cryptorchidism, in which the risk is around 0.5%, and XY intersex with abdominal testes, in which the risk may be as high as 20-25%. We examined the hypothesis that the increased risk of germ cell malignancy in intersex testes with Y chromosome was a direct consequence of an abnormal increase in number of PLAP/CD117+ immature germ cells into postnatal life. Archival cases of uncomplicated cryptorchidism (CO) and XY intersex (INT) were identified and anonymized, and a subgroup of aged-matched cases had sections immunostained with placental alkaline phosphatase (PLAP) and CD117. From a total of 89 intersex and 105 cryptorchid cases identified, a power calculation to detect a 20% difference in expression between groups (alpha = 0.05, power = 80%) determined that 18 intersex and 36 cryptorchid cases were required. Thus, 58 cases were examined, median age 3 (range birth-11) years, including 39 CO and 19 INT. The prevalence of any PLAP+ germ cells was 2/39 (5.1%) versus 3/19 (15.7%), respectively. (Z = 1.4, p = 0.17). In contrast, 94% of cases showed presence of any CD117+ germ cells, but the frequency of CD117+ cells was not significantly different between groups (t = 0.56, p = 0.58). CD117 and PLAP identify different populations of germ cells in pediatric testes. The extent of increased risk of malignancy in XY INT is not simply related to increased numbers of immature PLAP+/CD117+ germ cells present; additional factors play a pathogenic role.

Adolescent↗
PubMedDate not supplied

Histopathological features of testicular regression syndrome: relation to patient age and implications for management.

Testicular regression syndrome (TRS) represents a congenital condition in which no normal testicular tissue can be identified following exploration for a clinically impalpable testis. A spectrum of pathological findings may be present but there is little literature systematically examining these features. We searched a pediatric histopathology database to identify cases of TRS, and the histopathological findings were reviewed and pooled with those of all previously published smaller series. A total of 117 cases were identified during the period (1989-2004), median age 2 (range birth-12) years. In 52 (44%) a nodule was identified macroscopically, median maximum diameter 0.5 (range 0.1-2.0) cm. Microscopic hemosiderin-laden macrophages were present in 85 (73%), dystrophic calcification in 52 (44%), residual testicular tubules in 12 (10%), vas deferens in 71 (61%), and epididymal tissue in 39 (33%). The prevalence of hemosiderin laden macrophages and dystrophic calcification were significantly greater in cases < or =3 years (84% versus 64% and 55% versus 32%, respectively). But there was no significant difference in the frequency of other findings between the younger and older age groups; in particular, the presence of residual testicular tubules was similar (7% versus 13%, respectively). Furthermore, there was no significant correlation between identification of a macroscopically distinct nodule and presence of residual tubular structures, tubules being identified in 6 of the 65 cases in which no clearly identifiable nodule was seen macroscopically. The presence of hemosiderin-laden macrophages and foci of dystrophic calcification showed a positive association. TRS is associated with specific histopathological features, the findings being consistent with changes secondary to intrauterine testicular torsion. Residual testicular tubules are found in 10% of cases regardless of the presence or absence of a macroscopically identifiable nodule.

Age Factors↗