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Biomedical subjects

R Hunter

Publications and source records attributed to R Hunter.

At least 19 recordsLinked to original sources

Signet-ring carcinoma in Crohn's disease presenting as a neck mass.

We report a case of signet cell carcinoma of the colon in a patient with Crohn's disease. Signet cell carcinoma, also termed linitis plastica, is an unusual malignancy of the colon and is rarely associated with Crohn's disease. In general, metastatic disease is evident at the time of diagnosis, and the prognosis is uniformly poor. The radiographic, endoscopic, and histological features are discussed.

Carcinoma, Signet Ring Cell

Technetium-99m labelling of bis-oxime ligands.

The synthesis and labelling of a new bis-amide-oxime ligand E,E-2,9-bis(hydroxyimino)-4,7-diaza 5,6-dioxodecane (AdO) with 99mTc has been achieved. Protein binding, partition coefficient and tissue distribution of this complex and two related bis-amine-oxime ligands is reported. The biodistribution of the complexes are disappointing with only limited brain and myocardial uptake. Structures for the complex are postulated.

Animals

An outbreak of Norwalk-like gastroenteritis associated with contaminated drinking water at a caravan park.

During the 1989 Christmas holiday period, a large outbreak of gastroenteritis occurred among persons staying at a caravan park in southern New South Wales. Review of local hospital records found that 77 per cent of patients presenting with infective diarrhoea between 29 December and 3 January had stayed at the caravan park. In a retrospective cohort study we compared rates of illness among caravan park patrons exposed to different water sources. Stools were tested for pathogens and convalescent sera for viral antibodies. Rain and reticulated river water sampled from the caravan park were tested for bacteria and viruses. Of 351 persons interviewed at the caravan park, 305 (87 per cent) reported an illness characterised by diarrhoea, vomiting and abdominal pain. Of 196 persons who used reticulated river water for drinking or ablutions, 175 (89 per cent) became ill compared with 47 of 72 persons (65 per cent) who did not use this water (relative risk 1.4, 95 per cent confidence interval 1.2 to 1.6). The outbreak was probably caused by a 27-28 nm small round structured virus found in the stool from one ill person. High levels of faecal coliforms in the reticulated river water and enterovirus in sediment samples suggest that the outbreak was caused by sewage contaminating the reticulated river water through a break in the pipe directly over the underground water tanks. To prevent such outbreaks, poor water and sewerage system layouts should be avoided and nonpotable water should be clearly labelled. Where feasible, all camping-ground water should stem from town supplies.

Abdominal Pain

Abnormalities in rCBF and computed tomography in patients with Alzheimer's disease and in controls.

The pattern of abnormal distribution of the single photon emission computed tomography (SPECT) cerebral blood flow tracer 99m-technetium-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was investigated in 14 patients with clinically diagnosed Alzheimer's disease (AD) who subsequently had post-mortem confirmation of the disease and also in 14 elderly control subjects. These abnormalities were compared with computed tomography (CT) scans to investigate the degree to which the focal SPECT deficits were due to atrophy. The results show that SPECT imaging with 99Tcm-HMPAO and CT scanning both have a higher incidence of abnormality in AD patients than in controls and that the difference between patients and controls is greater with SPECT than with CT. Frontal SPECT and CT abnormalities in moderate/severe Alzheimer's disease occur as frequently as temporal/occipital abnormalities but the latter are rare in control subjects. Around 50% of the SPECT deficits occur in CT normal brain regions, showing that atrophy is not the sole cause of SPECT deficits.

Aged

A rapid method for localized mutagenesis of yeast genes.

We have developed a simple procedure for the localized mutagenesis of yeast genes. In this technique the region of interest is first amplified under mutagenic polymerase chain reaction (PCR) conditions. Cotransformation of the PCR product with a gapped plasmid containing homology to both ends of the PCR product allows in vivo recombination to repair the gap with the mutagenized DNA. This procedure is efficient, allows targeting of specific regions for mutagenesis, and requires no subcloning steps in Escherichia coli.

DNA, Fungal

Effects of a single dose of the acetylcholinesterase inhibitor velnacrine on recognition memory and regional cerebral blood flow in Alzheimer's disease.

The effects of a single oral dose of the acetylcholinesterase inhibitor velnacrine maleate on word and object recognition memory and regional uptake of 99mTc-exametazime were examined in patients with Alzheimer's disease. Word recognition memory was marginally improved 2 h after 75 mg velnacrine. With the same dose of velnacrine a relative increase in superior frontal uptake of 99mTc-exametazime was shown with single photon emission computed tomography (SPECT). This suggests increased regional perfusion and metabolism as a consequence of cholinergic stimulation. The effect did not co-vary with the degree of memory improvement, but, instead, more cognitively impaired patients showed a greater increase in tracer uptake after velnacrine, suggesting cholinergic hypersensitivity in the brains of Alzheimer patients.

Aged

Adjuvant activity of non-ionic block copolymers. IV. Effect of molecular weight and formulation on titre and isotype of antibody.

The adjuvant activity of block copolymers varies with the lengths of the chains of polyoxypropylene (POP) and polyoxyethylene (POE). This project evaluated the adjuvant activity of new copolymers with long polyoxypropylene chains in mice immunized with TNP-hen egg albumin in 2% squalone-in-water emulsions. Two of the new copolymers, L141 and L180.5, not only stimulated higher antibody titres to TNP than older preparations, but also induced a higher percentage of the IgG2 isotypes. The smaller older copolymers, L101 and L121, induced higher absolute levels of IgG3 antibody and relative increases in IgG1. Incorporation of immunomodulators (cell wall skeletons, monophosphoryl lipid A or threonyl muramyl dipeptide) increased mean IgG titres but also increased variability of responsiveness among individuals.

Adjuvants, Immunologic

The pattern of cerebral activity underlying verbal fluency shown by split-dose single photon emission tomography (SPET or SPECT) in normal volunteers.

Uptake of 99mTc-Exametazime, a marker of relative regional cerebral blood flow has been determined with Single Photon Emission Tomography (SPET or SPECT) in 20 healthy, elderly female subjects during neuropsychological challenge. Each subject was studied under basal conditions after injection of 125 MBq 99mTc-Exametazime. Without moving the head of the subject, they were scanned again after injection of 375 MBq 99mTc-Exametazime. The second injection was made in 10 subjects during a test of verbal fluency, usually regarded as a test of the integrity of function of the left frontal cortex. In the other 10 subjects the second injection was made during simple verbalization (counting). This method of splitting the normal full dose of 99mTc-Exametazime allows a novel comparison between basal and active conditions for different brain regions. Verbal fluency was associated with reduced uptake bilaterally in the region of the basal ganglia and in left temporal (peri-sylvian) cortex when compared with calcarine cortex, an unstimulated reference sensory area. By contrast, counting produced relative activation, greatest in frontal and parietal areas. Thus, a clinically relevant neuropsychological test can be characterized metabolically by a pattern of regional brain activity, whose localization cannot readily be predicted from classical studies of brain lesions. Reduction of regional uptake may suggest an important role for deactivation or inhibition of function in human cognition. The involvement of basal ganglia and temporal areas is of particular interest in relation to the investigation of functional psychiatric illness.

Aged

Inspection time, psychometric intelligence and clinical estimates of cognitive ability in pre-senile Alzheimer's disease and Korsakoff's psychosis.

Ten pre-senile Alzheimer's patients, 11 patients with Korsakoff's psychosis and 11 age- and pre-morbid intelligence-matched controls were given a test of Inspection Time, which estimates the efficiency of visual encoding or iconic memory. Alzheimer's patients had impaired Inspection Time while the Korsakoff group performed very similarly to the controls. Inspection Time performance correlated significantly with psychometric tests of cognitive ability and with clinical tests of cognitive ability (Mini Mental State Examination and Cambridge Mental Disorders of the Elderly Examination). The early stage of information processing measured by the Inspection Time procedure appears to be damaged by the Alzheimer's disease process, and to impose a rate-limiting effect on a wide variety of mental tests.

Alcohol Amnestic Disorder

Cerebral pharmacodynamics of physostigmine in Alzheimer's disease investigated using single-photon computerised tomography.

The effects of physostigmine on patterns of rCBF in patients with pre-senile Alzheimer's disease were studied using 99mTc-labelled HMPAO SPECT. Regional CBF increased in the left cortex relative to right, with the most significant effect in left frontal and higher frontal regions. Measures of regional brain function, such as SPECT, are an important complement to psychological test batteries in understanding the effects in brain of putative antidementia drugs. SPECT brain imaging could extend our understanding of the action of psychotropic drugs in other major psychiatric illnesses.

Aged

Reduced plasma oestrogen stimulated neurophysin and delayed response to oestrogen challenge in Alzheimer's disease.

Plasma concentrations of oestrogen stimulated neurophysin (ESN) were reduced in 28 patients with Alzheimer's disease (AD) compared with 14 age-matched controls, 16 patients with other presenile dementias and 12 patients with major depressive disorder. The ESN response to oestrogen challenge was delayed in 10 AD patients compared with 7 age-matched controls. Reduced basal and oestrogen stimulated plasma ESN may be related to impaired responsiveness of the hypothalamo-neurohypophysial neurons and/or a reduction in the amount of pituitary ESN available for release. Plasma ESN measurements may be of value for excluding the diagnosis of AD in patients with dementia who present before the age of 65.

Administration, Oral

Free sphingosine formation from endogenous substrates by a liver plasma membrane system with a divalent cation dependence and a neutral pH optimum.

Long-chain (sphingoid) bases may serve as another category of "lipid second messenger" because they inhibit protein kinase C and affect multiple cellular functions. Free sphingosine has been found in rat liver (Merrill, A. H., Jr., Wang, E., Mullins, R. E., Jamison, W. C. L., Nimkar, S., and Liotta, D. C. (1988) Anal. Biochem. 171, 373-381); hence, this study determined if liver plasma membranes contain free long-chain bases and have the ability to form them from endogenous enzymes and substrates. Isolated plasma membranes contained 0.45 nmol of sphingosine/mg of protein which, based on the recovery of the membranes, was equivalent to 3.5 +/- 1.2 nmol/g of liver and at least half of the total free sphingosine in liver. When the membranes were incubated at 37 degrees C, the amount increased at an initial rate of 5-25 pmol/min/mg, resulting in a 2-3-fold increase over an hour. Sphingosine formation required divalent cations, was optimal at neutral to alkaline pH, and was temperature-dependent. Activities with these characteristics were not identified in microsomes or lysosomes (lysosomal activities with acidic pH optima were detected, however); hence, they appear to reflect a separate plasma membrane system. Sphingosine formation was stimulated by ceramides either added exogenously or formed endogenously by treating the membranes with sphingomyelinase (but not endoglycoceramidase). Sphingomyelin hydrolysis to ceramide was also observed during incubation of the plasma membranes alone. Some of the properties of this system resembled the neutral sphingomyelinase and ceramidase activities of liver. While the physiological significance of this endogenous sphingosine is not known, this system has the appropriate subcellular location to provide sphingosine as a participant in signal transduction.

Animals