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Biomedical subjects

D M Houston

Publications and source records attributed to D M Houston.

30 records · Page 2Linked to original sources
PubMed1990

A morphometric study of the canine colon: comparison of control dogs and cases of colonic disease.

The microstructure of the canine colon was described morphometrically. The artifacts induced by administration of enemas and biopsy technique were studied by comparing biopsy specimens to tissues obtained at necropsy from 15 normal dogs. Biopsies from control dogs and clinical cases of colonic disease were then evaluated quantitatively, and histological abnormalities which might clarify mechanisms underlying large bowel dysfunction in the dog were sought. In control dogs, gland length and diameter, epithelial, goblet cell and mucosal mast cell numbers, and intraepithelial lymphocyte and mitotic indices were remarkably uniform throughout the colon. Minor variations were found in the proximal and distal regions of the colon. An apparent shortening of glands, and a reduction in mucous goblets and intraepithelial lymphocytes in biopsies were attributed to suboptimal orientation and irritation caused by enemas. The only significant difference from controls identified by morphometric analysis of biopsies from clinical cases was fewer epithelial cells lining longitudinal sections of glands. It was concluded that failure to identify morphometric variations in the colonic mucosa of clinical cases might reflect either a biased, homogeneously mild clinical syndrome in this group, or the possibility that in many of the clinical cases, a functional rather than physical abnormality was involved. The proprial inflammatory cell population was not examined quantitatively; further investigation of this component is merited.

Animals↗
PubMed1989

Design, synthesis, antineoplastic activity, and chemical properties of bis(carbamate) derivatives of 4,5-bis(hydroxymethyl)imidazole.

A series of bis(carbamate) derivatives of 1,2-substituted 4,5-bis(hydroxymethyl)imidazoles were prepared and evaluated against murine P388 lymphocytic leukemia. Electron-withdrawing substituents at either N-1 or C-2 gave rise to inactive compounds. However, electron-donating substituents gave active compounds and the 2-(methylthio)-1-methyl derivative 2i (carmethizole), as the bis(N-methylcarbamate), was found to be very active. The derivative 2i, referred to by the name carmethizole, was also shown to be active against the MX-1 mammary xenograft, the human amelanotic melanoma cell line (LOX) xenograft, the M5076 sarcoma, and L1210 lymphocytic leukemia. The solution stability, water solubility, pKa, and log P of carmethizole are also reported.

Animals↗
PubMed1989

The relationship between cognitive failure and self-focused attention.

The Cognitive Failures Questionnaire and the Self-Consciousness Scale were administered to a sample of undergraduate students. The Private Self-Consciousness and Social Anxiety subscales were significantly correlated with CFQ, suggesting that dispositional self-focused attention may be one underlying cause of cognitive failure. Similarities in the relation between CFQ, SCS and task performance are discussed.

Achievement↗
PubMed1987

Ivermectin toxicosis in a dog.

Ivermectin, a broad-spectrum antiparasitic agent, was believed responsible for signs of CNS dysfunction in a dog. Within 2 hours of oral administration of ivermectin, the dog had hind limb ataxia. Neurologic signs progressed rapidly until the dog was in a semicomatose state at admission 20 hours later. The dog improved gradually under supportive care. The ivermectin had been given for suspected endoparasitism. Clinical signs were similar to those reported in dogs with clinical and experimental exposure to ivermectin.

Animals↗
PubMed1985

Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 8. Molecular dissections of carbocyclic 3-deazaadenosine as inhibitors of S-adenosylhomocysteine hydrolase.

A series of 9-(hydroxyalkyl)-3-deazaadenines, which are analogues of the carbocyclic derivative of 3-deazaadenosine (3-deaza-C-Ado), were synthesized. The analogues were tested as inhibitors of bovine liver S-adenosyl-L-homocysteine (AdoHcy) hydrolase (EC 3.3.1.1) and as inhibitors of vaccinia virus (WR) replication in clone 929 mouse L cells and the results were compared to those observed for the parent compound, 3-deaza-C-Ado. 4-Amino-1-(2,3-dihydroxy-1-propyl)imidazo[4,5-c]pyridine (14), the analogue which included the 1'-, 2'-, and 3'-carbons of 3-deaza-C-Ado, was the most active inhibitor toward purified AdoHcy hydrolase. The inhibitory effect of 14 (Ki = 768 nM) on AdoHcy hydrolase was significantly less than that observed for 3-deaza-C-Ado (Ki = 4 nM). Analogue 14 also exhibited inhibitory activity against vaccinia virus replication, but the activity was less than that observed with 3-deaza-C-Ado. 4-Amino-1-(4-hydroxy-1-butyl)imidazo[4,5-c]pyridine (15) showed little or no inhibitory activity toward AdoHcy hydrolase, but it did exhibit antiviral effects comparable to 14. These results suggest that 3-deaza-C-Ado and analogue 14 may be producing their antiviral effects by altering a critical viral methylation (e.g., methylation of the 5'-cap of viral mRNA), whereas analogue 15 may be acting through an alternative mechanism.

Adenosylhomocysteinase↗
PubMed1985

Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 9. 2',3'-Dialdehyde derivatives of carbocyclic purine nucleosides as inhibitors of S-adenosylhomocysteine hydrolase.

A series of purine (e.g., adenine, N6-methyladenine, 8-azaadenine, 3-deazaadenine) carbocyclic nucleosides, nucleoside 2',3'-dialdehydes, and nucleoside 2',3'-diols were synthesized as potential inhibitors of bovine liver S-adenosyl-L-homocysteine (AdoHcy) hydrolase (EC 3.3.1.1) and as potential inhibitors of vaccinia virus replication. The 2',3'-dialdehydes were prepared by periodate oxidation of the corresponding carbocyclic nucleosides. Reduction of the intermediate dialdehydes with sodium borohydride afforded the corresponding 2',3'-diols. Of the nucleosides tested, the most potent inhibitors of AdoHcy hydrolase were the adenine analogue (Ki = 110 +/- 38 nM) and the 3-deazaadenine analogue (Ki = 4 +/- 0.9 nM), which were reversible, competitive inhibitors. In contrast, the 2',3'-dialdehydes produced irreversible inhibition of AdoHcy hydrolase, resulting in incorporation of two to four molecules of the dialdehyde per molecule (tetramer) of the enzyme. On the basis of an Ackermann-Potter analysis, the following "apparent" Ki values were determined for the 2',3'-dialdehydes: adenine analogue, 61 nM; 8-azaadenine analogue, 57.5 nM; and 3-deazaadenine analogue, 32 nM. The nucleoside 2',3'-diols were substantially less effective as inhibitors of AdoHcy hydrolase, requiring millimolar concentrations to achieve significant inhibition. When tested for their ability to inhibit vaccinia virus replication, several carbocyclic nucleosides (e.g., adenine and 3-deazaadenine analogues) and several nucleoside 2',3'-dialdehydes (e.g., adenine, N6-methyladenine, 8-azaadenine, and 3-deazaadenine analogues) exhibited good antiviral effects. A good correlation existed between a compound's inhibitory effects on AdoHcy hydrolase and its antiviral effects, suggesting that the inhibition of viral replication is caused by inhibition of a critical methylation reaction, e.g., methylation of the 5'-cap of viral mRNA.

Adenosylhomocysteinase↗
PubMed1985

Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 10. Base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine.

A series of base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine, a carbocyclic nucleoside, were synthesized and evaluated as inhibitors of S-adenosyl-L-methionine-dependent methyltransferases, including catechol O-methyltransferase, phenylethanolamine N-methyltransferase, and histamine N-methyltransferase. The base-modified analogues (8-azaadenine, 3-deazaadenine, and N6-methyladenine) were prepared by reaction of the corresponding carbocyclic 5'-chloro-5'-deoxynucleosides with the anion of homocysteine generated in situ either from L-homocystine or S-benzyl-L-homocysteine in Na/liquid NH3 or with DL-homocysteine thiolactone in alkaline solution. S-Aristeromycinyl-D-homocysteine was prepared with use of D-homocystine in the Na/liquid NH3 reaction. The sulfoxide and sulfone analogues were prepared by oxidation of S-aristeromycinyl-L-homocysteine. The various base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine were inactive as inhibitors of catechol O-methyltransferase. In contrast, the 3-deaza analogue was a good inhibitor (Ki = 20.5 +/- 1 microM) of phenylethanolamine N-methyltransferase whereas S-aristeromycinyl-D-homocysteine was an excellent inhibitor (Ki = 10.4 +/- 2.4 microM) of histamine N-methyltransferase. On the basis of these results, it would appear that the structural requirements for the binding S-aristeromycinyl-L-homocysteine are similar to those for binding S-adenosyl-L-homocysteine. Therefore, these carbocyclic analogues have the potential of being better inhibitors in vivo, because they should be more stable to metabolism than the ribosyl analogues.

Animals↗
PubMedDate not supplied

The beginnings of word segmentation in english-learning infants.

A series of 15 experiments was conducted to explore English-learning infants' capacities to segment bisyllabic words from fluent speech. The studies in Part I focused on 7.5 month olds' abilities to segment words with strong/weak stress patterns from fluent speech. The infants demonstrated an ability to detect strong/weak target words in sentential contexts. Moreover, the findings indicated that the infants were responding to the whole words and not to just their strong syllables. In Part II, a parallel series of studies was conducted examining 7.5 month olds' abilities to segment words with weak/strong stress patterns. In contrast with the results for strong/weak words, 7.5 month olds appeared to missegment weak/strong words. They demonstrated a tendency to treat strong syllables as markers of word onsets. In addition, when weak/strong words co-occurred with a particular following weak syllable (e.g., "guitar is"), 7.5 month olds appeared to misperceive these as strong/weak words (e.g., "taris"). The studies in Part III examined the abilities of 10.5 month olds to segment weak/strong words from fluent speech. These older infants were able to segment weak/strong words correctly from the various contexts in which they appeared. Overall, the findings suggest that English learners may rely heavily on stress cues when they begin to segment words from fluent speech. However, within a few months time, infants learn to integrate multiple sources of information about the likely boundaries of words in fluent speech.

Child Language↗
PubMedDate not supplied

A comparison of indirect blood pressure monitoring techniques in the anesthetized cat.

OBJECTIVE: To determine the accuracy of three indirect blood pressure monitoring techniques (oscillometric technique [OS], Doppler [DOP], and optical plethysmography [OP] [blood pressure determined with a pulse oximeter waveform]) when compared with direct arterial pressure measurement in cats. STUDY DESIGN: Prospective study. ANIMAL POPULATION: Eight healthy (five female, three male), domestic short-hair cats weighing 3.5 +/- 0.8 kg METHODS: Cats were anesthetized with isoflurane. The inspired concentration of isoflurane was adjusted to produce mild hypotension (80 to 100 mm Hg direct systolic), moderate hypotension (60 to 80 mm Hg direct systolic), and severe hypotension (< 60 mm Hg direct systolic). Indirect pressure measurements were obtained from the thoracic limb and compared with concurrent direct measurement using regression analysis and a modification of Bland and Altman's technique. RESULTS: All three techniques underestimated systolic pressure. OS produced the best prediction of systolic pressure with a bias +/- precision of -15.9 +/- 8.1 mm Hg. DOP and OP were relatively inaccurate with a bias +/- precision of -25 +/- 7.4 mm Hg and -25 +/- 7.5 mm Hg. All three techniques correlated well with direct pressure with r values of 0.81, 0.88, and 0.88 for OS, DOP, and OP. DOP and OP provided an accurate prediction of direct mean arterial pressure with a bias +/- precision of -0.8 +/- 6 mm Hg and 0.6 +/- 5.5 mm Hg. Correlation was good between DOP and mean arterial pressure with r = 0.89. Correlation was also good between OP and mean arterial pressure with r = 0.90. CONCLUSIONS: OS provided the most accurate prediction of direct systolic pressure. DOP and OP provided a good prediction of mean arterial pressure in the cat. CLINICAL RELEVANCE: All three of these techniques are useful for detecting trends. Direct monitoring of blood pressure should be considered if accurate blood pressure measurement is required.

Analysis of Variance↗
PubMedDate not supplied

Idiopathic, asymptomatic thrombocytopenia in Cavalier King Charles spaniels: 11 cases (1983-1993).

The medical records of 11 Cavalier King Charles spaniels with idiopathic, asymptomatic thrombocytopenia and large-to-giant platelets were identified from a 10-year retrospective search using the Veterinary Medical Data Base at Purdue University. Eight of the dogs had been treated with various immunosuppressive drugs. Six of the treated dogs remained thrombocytopenic, one was not reevaluated, and one developed a normal platelet count. The underlying etiology of idiopathic, asymptomatic thrombocytopenia in Cavalier King Charles spaniels has not been identified, but this condition could represent a congenital macrothrombocytopenic disorder.

Animals↗