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Biomedical subjects

J C Morgan

Publications and source records attributed to J C Morgan.

13 recordsLinked to original sources

Wild-type and mutant forms of v-src differentially alter neuronal migration and differentiation in vivo.

The effects of three different forms of v-src on brain cell development were determined in vivo. Recombinant retroviral vectors encoding the marker lacZ (control) and either wild-type v-src or SH2 or SH3 domain-deleted forms of v-src (deltaSH2 or deltaSH3, respectively) were used to infect neuronal progenitor cells in the embryonic chicken midbrain (optic tectum; OT). Embryos were injected in the OT with retroviral concentrates on embryonic day (E) 3 and sacrificed at E6, E9, and later in development. Patterns of cell proliferation, migration, and differentiation of lacZ-marked clonal cell progeny were then analyzed. Relative to lacZ-only controls, cell clone size at E6 was significantly increased for v-src-, unchanged for deltaSH2-, and smaller for deltaSH3-injected embryos. At E9, deltaSH2 cell clones were significantly larger than controls, suggesting increased survival from normal programmed cell death. Radial neuronal migration was impaired for v-src and deltaSH3 clones, whereas tangential neuronal migration was enhanced along fiber tracts in v-src and deltaSH2 clones. Moreover, radial glial cell development and differentiation was hindered in v-src and deltaSH3 clones. These experiments demonstrate that ectopic v-src signaling alters proliferation, migration, survival, and differentiation of developing brain cells and suggest that src signaling pathways are involved in these developmental processes. Furthermore, certain effects of v-src on brain cells require specific src homology domains.

Animals↗

Two mutations in the locus control region hypersensitivity site-2 (5' HS-2) of haplotype 19 beta s chromosomes alter binding of trans-acting factors.

There are five major haplotypes associated with sickle cell anemia (SS). Individuals homozygous for haplotypes 3 (Senegal) and 31 (Saudi Arabian) have high fetal hemoglobin (HbF) levels (15 to 30% of total hemoglobin) whereas individuals homozygous for haplotypes 17 (Cameroon), 19 (Benin), and 20 (Bantu) have low HbF levels (1 to 10%). We previously identified several point mutations in the LCR 5'HS-2 that were specific for haplotype 19 beta s chromosomes (compared to the GenBank HUMHBB reference sequence, T-->G at position 8580, A-->G at position 8598, and A-->T at position 9114). We postulated that one or more of these mutations may alter the binding of specific trans-acting factors and ultimately affect the expression of HbF in these sickle cell patients. We performed gel mobility shift assays using 32P-end-labeled double-stranded 19mers corresponding to each of the LCR 5'HS-2 normal (GenBank) and mutant sequences. Nuclear extracts prepared from HeLa and HEL cells were used in our experiments and neither the normal nor mutant sequence at position 8580 bound trans-acting factors in either nuclear extract. The 8598 mutant increased binding of Sp1; using purified protein and both nuclear extracts. HEL extracts were used to quantify the increase in Sp1 binding to the 8598 mutation and we found an increase in binding of 66 and 47%, respectively, in two shifted bands. The 9114 mutation sharply decreased binding of an unknown trans-acting factor by 74%. This factor was present in both HeLa and HEL nuclear extracts.

Base Sequence↗

Students who work.

A study of 1,800 Kentucky high school students revealed that working students demonstrate a remarkable diversity of work experience and uses of earnings while not differing markedly from nonworking students in school experience. The data, both quantitative and qualitative, suggest that conventional wisdom is not sufficient to capture fully the current realities of students who work; however, unresolved theoretical issues remain.

Achievement↗

Renal allograft rejection. Functional impairment of kidney epithelial cell monolayers mediated by lymphokine-activated killer cells and by antibody.

A continuous line of human kidney epithelial cells was cultured to confluency on porous membranes, and the formation of intercellular tight junctions was monitored by measuring increases in the trans-monolayer electrical resistance. Typical monolayers developed functioning tight junctions within 4 days of culture and showed an increase in resistance of 1840 +/- 440 ohms (mean +/- SD; n = 5) at this time. Conventional 51Cr release assays showed that suspended kidney cells were lysed by specific antibody and complement but were relatively resistant to lysis mediated by lymphokine-activated killer cells. However, when antibody and complement or LAK cells were added to functioning kidney cell monolayers the electrical resistance of the monolayers was rapidly reduced in both cases. In the absence of trans-monolayer resistance the ion gradients essential for renal tubular function will not be supported. These results indicate that the ability of a cytotoxic effector cell to liberate 51Cr from suspended kidney cells may not be a sensitive assay for the ability of these effector cells to impair the function of structured kidney cell monolayers. It is possible that significant kidney dysfunction may occur during renal allograft rejection by failure of trans-epithelium resistance in the absence of widespread epithelial cell lysis.

Animals↗

Physiologic assessment of surgical diagnosis-related groups.

Although (diagnostic related groups) DRGs were originally devised as a research instrument for the evaluation of medical resource allocation, no studies have been reported that compare the actual physiologic status of patients with DRG classification. At the Westchester Medical Center, a University tertiary referral center, 100 consecutive high-risk elective surgical patients entered a preoperative intensive care unit for a prospective analysis of physiologic assessment, resource utilization, DRG classification, and outcome. Swan-Ganz catheters inserted 1 or 2 days before surgery were used to compute physiologic profiles and stage according to previously published criteria. Risk was determined by age, associated conditions, and magnitude of the proposed operation. There were no patients in stage 1; 55% in stage 2; 41% in stage 3; and 4% in stage 4, which accounted for three of the four total deaths. The 41% of patients over age 70 all had DRG comorbidity factors, but none died. All in stages 3 and 4 had comorbidity factors, as did 87% in stage 2. In 53% of the patients, the physiologic profile provided data necessary for preoperative "fine tuning"; in 37%, for volume expansion; in 23%, for inotropic therapy; and in 17%, for pulmonary therapy. Reoperation was required in 17% and contributed to the long average length of stay (LOS) of 24.5 days. In spite of case severity and comorbidity factors, LOS in the postoperative ICU was only 3 days. There were no significant differences in patients with cancer DRGs. Significant differences between stages 2 and 3 were found for pulmonary wedge pressure, right ventricular stroke work, pulmonary vascular resistance, and pulmonary shunt fraction. The 4% who died all had advanced liver disease. Although the DRG system as set up by the Health Care Financing Administration (HCFA) correctly predicts that age and comorbidity factors lead to increased utilization of resources, the extent to which they underestimate the increased needs of these patients will lead to financial disaster. Compensation for comorbidity factors and advanced age are not cumulative, but patients over 70 had an average of 2.5 comorbidity factors and required an average 26.5 days hospitalization. DRGs allowed only 15% extra reimbursement for these complex cases. High-risk, referred surgical patients are much sicker than they appear to the DRG system, and in all 100 cases compensation was grossly inadequate.

Age Factors↗

Air gun injuries of the abdomen in children.

From July 18, 1978 to Sept 15, 1982, four boys were treated for air gun injuries of the abdomen at the North Carolina Baptist Hospital, Winston-Salem. Three patients had wounds of one or more of the hollow viscera, and one patient had an injury only of the liver. There was no morbidity or mortality following repair. Some present-day air (pneumatic) weapons have muzzle velocities that equal or exceed those of common civilian handguns, and they are frequently used by unsupervised children. These weapons are not restricted and regulated as are other firearms, and are believed to be incapable of serious injury other than to the eye. These cases and others in the literature dispute that belief.

Abdominal Injuries↗

Bacterial and fungal oxidation of dibenzofuran.

Cunninghamella elegans and a mutant strain (B8/36) of Beijerinckia both oxidized dibenzofuran to 2,3-dihydroxy-2,3-dihydrodibenzofuran. The bacterial metabolite was extremely unstable and, in the presence of acid, was rapidly converted into a mixture of 2- and 3-hydroxydibenzofuran. In contrast, the 2,3-dihydroxy-2,3-dihydrodibenzofuran formed by C. elegans was stable and only yielded 2- and 3-hydroxydibenzofuran when heated under acidic conditions. The results suggest that Beijerinckia B8/36 and C. elegans form the respective cis- and trans-isomers of 2,3-dihydroxy-2,3-dihydrodibenzofuran. C. elegans also oxidized dibenzofuran to 2- and 3-hydroxydibenzofuran under conditions that would not lead to the dehydration of the trans-dihydrodiol. These observations implicate the initial formation of dibenzofuran- 2,3-epoxide in the fungal oxidation of dibenzofuran. Beijerinckia B8/36 also produced a second unstable dihydrodiol that was tentatively identified as cis-1,2-dihydroxy-1,2-dihydrodibenzofuran. This compound gave 2-hydroxydibenzofuran as the major dehydration product and the cis relative stereochemistry was suggested by the isolation and characterization of an isopropylidine derivative. A preparation of cis-naphthalene dihydrodiol dehydrogenase and cell extracts of the parent strain of Beijerinckia oxidized both bacterial dihydrodiols to catechols. Cell extracts prepared from C. elegans catalysed an analogous oxidation of trans-2,3-dihydroxy-2,3-dihydrodibenzofuran to 2,3-dihydroxydibenzofuran. The latter product was also isolated and identified from culture filtrates. The results suggest that bacteria and fungi utilize different mechanisms to initiate the oxidation of dibenzofuran.

Bacteria↗

The subacute phase of alcoholism.

Aggressive intervention in the medical and psychosocial problems of the subacute phase of alcoholism allows the physician to assume a holistic approach to the alcohol-addicted individual and provides a basis for eventual arrest of the chronic disease. A variety of metabolic abnormalities and physiologic disorders require attention. Management of psychologic problems requires the use of rational authority, early psychotherapy, judicious short-term psychopharmacology and use of available community resources.

Acute Disease↗