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Biomedical subjects

B Morris

Publications and source records attributed to B Morris.

At least 19 recordsLinked to original sources
PubMed1992

Regulation of the activities of African cassava mosaic virus promoters by the AC1, AC2, and AC3 gene products.

DNA fragments comprising each of the promoter regions from the geminivirus African cassava mosaic virus (ACMV) were cloned into the pUC18-based vector, pG1, producing transcriptional fusions with the beta-glucuronidase gene (GUS) and nopaline synthase terminator sequence. The relative activity of each promoter construct was analyzed by a GUS expression assay of extracts from Nicotiana clevelandii protoplasts coelectroporated with the GUS reporter constructs and constructs in which individual ACMV open reading frames (ORFs) were placed under control of a cauliflower mosaic virus 35 S promoter. Results suggest repression of the AC1 gene by its gene product, which is required for ACMV DNA synthesis. The promoter activity observed for the single promoter for the DNA A genes encoding functions of spread and the regulation of replication (AC2 and AC3 ORFs) was unaffected by coelectroporation with any of the ACMV ORF constructs. Promoters for the AV1 (coat protein) gene and the two DNA B genes (BV1 and BC1) were activated by electroporation of the AC2 ORF construct. To a lesser extent promoters for the AV1 and BV1 genes were activated with the AC3 ORF construct. The same pattern of promoter repression and activation was observed when transgenic N. benthamiana plants expressing the GUS reporter constructions were inoculated with ACMV DNA A.

DNA-Directed DNA Polymerase↗
PubMed1992

Cryptococcal peritonitis in a CAPD patient.

A 50-year-old diabetic woman with end-stage renal disease, who had been on continuous ambulatory peritoneal dialysis for 8 months, developed peritonitis caused by Cryptococcus neoformans var. neoformans. The patient was completely asymptomatic and infection was confirmed by detection of budding yeast cells in Gram-stained smears of turbid peritoneal fluid. The infection was cleared after intravenous fluconazole with delayed removal of the catheter. Fluconazole may be a suitable alternative drug in treating cryptococcal peritonitis.

Cryptococcosis↗
PubMed1992

Patterns of electrical activity and neural responses in canine proximal duodenum.

The patterns of electrical activity and neural inputs to the proximal duodenum between the pyloric sphincter and the sphincter of Oddi were studied in muscles of the dog. Smooth muscle cells in the most proximal region were electrically quiescent, but slow waves were recorded in all regions distal to the first few millimeters. Electrical activity was recorded from circular muscle cells near the myenteric and submucosal surfaces of the circular layer, and slow wave activity was similar in both regions. The nature of neural inputs was also characterized. With electrical field stimulation, responses in cells near the submucosal surface were predominantly excitatory junction potentials (EJPs); near the myenteric border responses were either inhibitory junction potentials (IJPs) or biphasic responses (i.e., small EJPs followed by IJPs). EJPs were blocked by atropine. IJPs were nonadrenergic and noncholinergic (NANC), and several experiments suggested that nitric oxide (NO), or a NO-releasing compound, serves as the inhibitory neurotransmitter in this region. Exogenous NO caused hyperpolarization of membrane potential. IJPs and the hyperpolarization response to NO were sensitive to apamin. These data describe the myogenic mechanisms and neurogenic apparatus that appear to regulate motility in the most proximal region of the duodenum.

Animals↗
PubMed1991

Therapeutic ratings and end-of-phase II conferences: initiatives to accelerate the availability of important new drugs.

To facilitate the availability of important new therapeutic agents, the Food and Drug Administration (FDA) in the mid-1970s began assigning therapeutic ratings to investigational new drugs and holding end-of-phase II conferences with drug sponsors. To determine whether these initiatives are associated with faster approvals, we examined new drug application (NDA) review times of new chemical entities (NCEs) approved during the 12-year period 1978 through 1989. Mean NDA review time for 1A drugs (22.5 months) was 22% shorter than that for 1B drugs (28.7 months), which in turn was 25% shorter than that for 1C drugs (38.4 months). For drugs approved during the recent 4-year period 1986 through 1989, however, the gap between 1A and 1C review times has narrowed considerably from 19 to 9 months. When drugs were grouped by FDA reviewing division, 1A drugs had the shortest mean review time in each division except the Cardio-Renal Division; in that division, 1B drugs had the shortest mean review time. Mean NDA review time for drugs that had end-of-phase II conferences (28.6 months) was 15% shorter than that for drugs without such conferences (33.7 months). These results suggest that NCEs that receive 1A or 1B ratings and are the subject of end-of-phase II conferences benefit by having shorter review times.

Drug Evaluation↗
PubMed1991

Analysis of the potential promoter sequences of African cassava mosaic virus by transient expression of the beta-glucuronidase gene.

DNA fragments from promoter regions of the geminivirus, African cassava mosaic virus, were cloned into pG1, a vector based on pUC18, producing transcriptional fusions with the beta-glucuronidase (GUS) gene and nopaline synthase termination sequence. The activity of each promoter construct was assessed by analysing the transient expression of GUS in Nicotiana clevelandii protoplasts. The results demonstrated that constructs containing the common region of DNA A showed much stronger promoter activity in the complementary sense than in the viral sense. These results were supported by the analysis of promoter activity in transgenic N. benthamiana plants. In comparison, in protoplasts a region upstream of the AC2 open reading frame was shown to have moderate promoter activity. Unlike DNA A, the complementary sense DNA B promoter constructs had weak activity; the viral sense DNA B promoter constructs appeared to be regulated by host factors. The implications of these results for the regulation of early and late genes are discussed.

Base Sequence↗
PubMed1991

Mutagenesis of the AC3 open reading frame of African cassava mosaic virus DNA A reduces DNA B replication and ameliorates disease symptoms.

Small insertions were made independently at each of four unique restriction sites on African cassava mosaic virus (ACMV) DNA A to disrupt the three overlapping complementary-sense open reading frames (ORFs) herein designated AC1, AC2 and AC3. The DNA A mutants were assayed for their infectivity by agroinoculation of monomeric constructs to Nicotiana benthamiana plants containing chromosomal insertions of ACMV DNA B. Disruption of the AC3 ORF alone resulted in a delay and amelioration of disease symptoms which correlated with reduced replication of DNA B. Normal replication of DNA A still carrying the AC3 ORF mutation was found in extracts from these plants. No ACMV DNA or symptoms were observed in corresponding inoculations with either the simultaneous disruption of the overlapping AC2 and AC3 ORFs or disruption of the AC1 ORF. Complementation by the inoculation of different mutant pairs produced a delay in disease symptoms followed by repair of mutated sites. A DNA A construct with the virus-sense AV1 (coat protein) ORF deleted was infectious producing typical ACMV disease symptoms. A similar construct with a larger deletion encompassing the complementary-sense AC3 ORF produced symptomless infections. The DNA recovered from plants revealed DNA A of normal size where the position of the deleted ORF was replaced with cloning vector DNA. Significantly reduced DNA B replication was observed for the AC3 deletion construct.

Blotting, Southern↗
PubMed1990

Differential peripheral expansion and in vivo antigen reactivity of alpha/beta and gamma/delta T cells emigrating from the early fetal lamb thymus.

The concentrations of different lymphocyte subsets in the blood of lambs which had been thymectomized (Tx) in utero between days 67-75 of fetal gestation were measured at birth and at various intervals during the first year of life. Compared to thymus-intact (Ti) controls, Tx lambs were severely depleted of both alpha/beta and gamma/delta T cells at birth (less than 10% of control levels). The majority of the residual alpha/beta T cells present in Tx lambs at birth were CD4+CD8-. As the Tx lambs aged, the concentration of alpha/beta T cells in blood increased steadily to reach levels around 50% of control values. In contrast, the circulating gamma/delta T cells did not expand in Tx animals and remained barely detectable throughout the observation period, although these cells accounted for 30%-60% of the T cells in the blood of Ti lambs. The expansion of alpha/beta but not gamma/delta T cells was also reflected in changes in the cellular composition of solid lymphoid organs in Tx lambs. B cell numbers were similar in both groups at birth but Tx lambs were persistently B lymphopenic from 3 weeks of age onwards. The alpha/beta T cells that had expanded in Tx lambs responded to stimulation with bacterial antigens in a way that was qualitatively similar to the response in Ti lambs. By contrast, the few gamma/delta T cells in Tx lambs responded abnormally. Our results show that although sheep alpha/beta and gamma/delta T cells are equally thymus dependent during ontogeny, the early fetal thymic emigrants which establish the two T cell lineages in the periphery have strikingly different antigen reactivities and capacities for self-renewal and expansion.

Aging↗
PubMed1990

Factors regulating the activity of striatal neurons: new perspectives from in situ hybridization histochemistry.

1. The basal ganglia contain a variety of putative peptide neurotransmitters. In situ hybridization allows changes in the levels of the mRNAs encoding these neuropeptides to be assessed at the cellular level of resolution. 2. Alterations in the activity of pathways within the basal ganglia of the rat produce distinct effects on the different neuropeptide mRNAs. 3. The evidence, where available, suggests that mRNA levels provide an index of peptide turnover. 4. This approach has consequently revealed much new information on the regulation of neuronal activity in the basal ganglia.

Animals↗
PubMed1990

Prediction of possibly preventable death: a case-control study of postneonatal mortality in southern New Zealand.

The postneonatal mortality rate in three southern regions of New Zealand was 8.1 per 1000 live births for 1979-1984. The possibly preventable postneonatal mortality rate was 7.1 per 1000 live births and data on 377 possibly preventable deaths and 936 randomly selected controls were used to develop a two-stage risk-scoring system. Logistic regression analysis was undertaken separately on two sub-samples of the total sample. The data were used to evaluate three other previously published scoring systems. The four variables used in our birth score (mother's age, parity, marital status, and birth weight) have all appeared in other scoring systems, and this score could identify a group of infants in southern New Zealand with an estimated 1.7% mortality rate in the first year of life. It is suggested that currently the only valid use of risk-scoring in this region is for the definition of a high-risk population for the purpose of evaluating potential intervention strategies.

Case-Control Studies↗
PubMed1989

FDA advisory committees and the new drug approval process.

To determine the impact of FDA advisory committee review on the approval time of new drug applications (NDAs) approved during the five-year period 1983 through 1987, we compared NDA phase lengths of reviewed new chemical entities (NCEs) with those that were not reviewed and examined the elapsed time from final committee recommendation for approval to NDA approval. Of the 95 drugs approved during the study period that met the Center for the Study of Drug Development's definition of an NCE, 40 (42%) were submitted for review--mean NDA phase length was 36.9 months versus 32.4 months for unreviewed drugs. Reviewed drugs in the neuropharmacologic division had a longer NDA phase, while those in the metabolic/endocrine and oncology/radiopharmaceutical divisions had shorter NDA phases, than unreviewed drugs in those divisions. For NCEs grouped by therapeutic rating, reviewed drugs in each category had longer NDA phases than unreviewed drugs; the difference was largest for 1-B rated drugs. The elapsed time from committee recommendation for approval to NDA approval as a percent of the total NDA phase was greatest for drugs submitted by the metabolic/endocrine division (83.0% of NDA phase) and for drugs rated 1-A (63.2%). Results indicate that advisory committee review is associated with a small overall delay in NDA approval when compared with the regulatory fate of drugs not submitted for review.

Drugs, Investigational↗
PubMed1989

Postneonatal mortality in south New Zealand: necropsy data review.

Three southern New Zealand health districts had a postneonatal mortality rate of 8.1 per 1000 livebirths and a postneonatal sudden infant death syndrome (SIDS) mortality rate of 6.3 per 1000 livebirths for the period 1979-1984. This is one of the highest reported rates of SIDS. The 429 postneonatal deaths occurring during the period were assigned to one of four groups: unpreventable (n = 52), possibly preventable non-SIDS (n = 45), SIDS with minor abnormalities at necropsy or premorbid symptoms (n = 167), and SIDS with no abnormalities at necropsy or documented premorbid symptoms (n = 165). These groups were related to obstetric and perinatal data. For those infants classified as SIDS, the winter peak of deaths was particularly marked if death occurred after 3 months of age. These older SIDS deaths had more minor abnormalities at necropsy, a longer interval between time last seen or heard alive and found dead and more thymic petechiae.

Cause of Death↗