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Biomedical subjects

J R Smith

Publications and source records attributed to J R Smith.

At least 325 records · Page 18Linked to original sources

Optional exon in the 5'-untranslated region of 3-hydroxy-3-methylglutaryl coenzyme A synthase gene: conserved sequence and splicing pattern in humans and hamsters.

3-Hydroxy-3-methylglutaryl coenzyme A synthase (hydroxymethylglutaryl-CoA synthase, EC 4.1.3.5) is a negatively regulated enzyme in the synthetic pathway for cholesterol, isopentenyl tRNA, and other isoprenoids. The 5'-untranslated region of the mRNA for Chinese hamster hydroxymethylglutaryl-CoA synthase contains an optional exon of 59 nucleotides located 10 nucleotides upstream of the translation start site. About 50% of the mRNAs contain this exon, and the other 50% lack it owing to differential intron splicing. We show that the two transcripts are found in similar ratios in multiple tissues of the Syrian hamster, including the brain. The relative amounts of the two transcripts in brain and liver are constant from day 0 to day 75 of life. A similar alternative splicing pattern for hydroxymethylglutaryl-CoA synthase was observed in three human tissues: cultured fibroblasts, fetal adrenal gland, and fetal liver. A cDNA for human synthase had 90% homology to the hamster sequence in the region corresponding to the optional exon. This sequence contains a 20 out of 26 nucleotide match with the sequence immediately upstream of the initiator AUG codon in the mRNA for hamster hydroxymethylglutaryl-CoA reductase, the enzyme that follows the synthase in the isoprenoid biosynthetic pathway. These findings raise the possibility that the optional exon plays an important, conserved functional role in humans and hamsters.

Aging↗

Serum immunoglobulins and lymphocyte subsets in chronic lymphocytic leukemia.

The concentrations of serum immunoglobulins were correlated to the stage of disease and the proportions of peripheral blood lymphocyte subsets in 25 untreated patients with B-cell chronic lymphocytic leukemia (CLL). Diminished levels of at least one serum immunoglobulin were present in 77% of all patients with CLL and 73% of patients with Stage 0 disease. The mean concentration of IgG, IgM, and IgA decreased with advancing stage of CLL. The percentages of total T, T-helper (TH), and T-suppressor (TS) cells in the peripheral blood were less in patients with CLL than in healthy persons, but the absolute concentrations of total T, TH, and TS cells were greater in patients with CLL than controls (P less than 0.02). The absolute number of B-cells (P less than 0.01) and null cells (P less than 0.001) was also increased in patients with CLL, particularly those patients in advanced stages of CLL. These findings suggest that the hypogammaglobulinemia associated with CLL first occurs during the earliest stage of disease and may be related to the alterations in the proportion of peripheral blood lymphocytes.

Adult↗

Functional simian virus 40 T antigen is expressed in hybrid cells having finite proliferative potential.

Simian virus 40-transformed human cells fused with other independently derived simian virus 40-transformed cells and tumor-derived cells containing activated H-ras and N-ras oncogenes yielded hybrids capable of indefinite division. Fusions with various other immortal cells yielded hybrids that had limited division potential. T antigen expressed in limited-division hybrids was functional for the induction of cellular DNA synthesis.

Antigens, Polyomavirus Transforming↗

Analysis of a four-year experience with depth electrodes and a two-year experience with subdural electrodes in the evaluation of ablative seizure surgery candidates.

Chronically implanted depth and subdural electrodes have both been shown to be satisfactory means of localizing epileptogenic foci. Utilizing bilateral mesial temporal depth electrodes, we have localized mesial temporal foci in a large percentage of patients. Depth electrode investigation of a more limited number of patients with suspected extramesial temporal foci has not been as reliable in giving localizing information. We have more recently used subdural electrodes to investigate this latter category of patients, and preliminary findings suggest that this technique may be of localizing value in several subcategories.

Electrodes, Implanted↗

Bone marrow transplantation in canine mucopolysaccharidosis I. Effects within the central nervous system.

Five dogs with mucopolysaccharidosis I, a model of human Hurler/Scheie syndrome, were transplanted with marrow from phenotypically normal littermates at 5 mo of age. At 3 and 9 mo posttransplantation, biopsies of cerebral cortex, liver, and cerebrospinal fluid were obtained. The alpha-L-iduronidase levels in these tissues were 0.8-7.4, 26-45, and 6.3-14.9% of the paired donor tissues, respectively. Although iduronidase was present in relatively low levels in the recipients' brains and cerebrospinal fluid at both biopsy times, reduction in brain glycosaminoglycan (GAG) was comparable to that observed in liver. Ultrastructural studies of cells within the transplanted dogs' brains showed less lysosomal distension and storage product than in affected, nontransplanted, littermate controls. The most marked clearing of stored GAG was in cells surrounding blood vessels, but decreased lysosomal storage in neurons and glial cells was also observed. Urinary GAG excretion also decreased to near normal levels by 5 mo posttransplantation.

Animals↗

Limbic evoked potentials predict site of epileptic focus.

Limbic evoked potentials (LEPs) were recorded from intracerebral electrodes in the hippocampi of seven preoperative epilepsy surgery patients. LEPs were evaluated using amplitude, form, and asymmetry by raters blinded as to the side of electrographically proven seizure onset. Raters correctly predicted the side of focus in all four patients with proven unilateral temporal lobe seizure onset. Further, LEP amplitudes in two patients with bilateral independent temporal lobe seizure onset were markedly diminished compared with one patient with a nontemporal lobe seizure onset. LEP recordings may assist in determination of the site of epileptogenic pathology.

Epilepsies, Partial↗

Maternal plasma bicycling PGE2 levels following vaginal administration of prostaglandin E2 pessaries in full term pregnancies.

Plasma levels of bicyclic PGE2 (PGE2M) were measured after administration of a 5mg, PGE2 slow release hydrogel pessary and a 3mg vaginal tablet (Upjohn). Twenty-four women of low parity with favourable induction features were randomised to receive either the hydrogel pessary or the vaginal tablet. A single pessary was administered and amniotomy was performed after 4 hours. Augmentation with oxytocin was carried out after amniotomy if required. Both groups showed a rise in plasma PGE2 levels in keeping with the release profiles of the pessaries. Wide interindividual differences in absorption were found.

Administration, Intravaginal↗

Existence of high abundance antiproliferative mRNA's in senescent human diploid fibroblasts.

Polyadenylated RNA isolated from senescent human diploid fibroblasts (HDF) inhibited DNA synthesis in proliferation-competent cells after microinjection, whereas polyadenylated RNA from young HDF had no inhibitory effect. Polyadenylated RNA from young cells made quiescent by removal of serum growth factors had a slight inhibitory effect on DNA synthesis. The abundance level of inhibitor messenger RNA (mRNA) from senescent cells was estimated at 0.8 and that of quiescent cells at 0.005 percent. These results demonstrate the existence of one or more antiproliferative mRNA's in nonproliferating normal human cells; these RNA's code for factors that either work antagonistically to initiators of DNA synthesis or regulate the expression of the initiators in some way. The abundance level of the inhibitory mRNA in senescent cells indicates the feasibility of developing a complementary DNA probe that will be useful in studying cell cycle control mechanisms.

Cell Division↗

Observations on the use of an inactivated canine parvovirus vaccine.

Data are presented on studies of field and experimental use of a formalin-inactivated canine parvovirus vaccine. There was an absolute correlation between a single successful vaccination and subsequent protection against clinical disease. Unsuccessful vaccinations were consistently associated with the presence of maternal antibody at the time of vaccination. The vaccine induced an antibody response within two days and anamnestic responses within 24 hours. It is suggested that a single successful vaccination probably protects against clinical parvovirus disease for life.

Animals↗

Progressive non-infectious anterior vertebral fusion.

Four cases of progressive non-infectious anterior vertebral fusion are described. Three cases remain relatively asymptomatic, but one has developed spinal cord compression secondary to an acute angled kyphosis. The clinical, radiological, and pathological features are reviewed and some comparisons with the spinal changes in thalidomide embryopathy are made.

Adolescent↗

A method for reducing the noise generated in digitizing or analog recording of EEG data.

Magnetic recording and/or analog-to-digital conversion add noise to the data. This paper describes a method for reducing the noise added to EEG data by recording and digitizing. A linear filter is described which pre-emphasizes the EEG before recording or digitizing; a second filter then recovers the original signal after playback. The technique can result in a factor of 10 (20 dB) improvement of the signal-to-noise ratio of high frequency EEG components.

Analog-Digital Conversion↗

The use of a multidisciplinary committee to manage the risk of suicide in a VA domiciliary.

The White City Domiciliary in Virginia created a multidisciplinary committee to provide immediate assessment and management of patients with suicidal and violent behavior. The study concludes that the committee effectively participated in crisis evaluation and intervention and has been accepted as a valuable quality assurance clinical and management tool.

Crisis Intervention↗