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Biomedical subjects

R Tompkins

Publications and source records attributed to R Tompkins.

At least 19 recordsLinked to original sources
PubMed1991

Bile duct carcinoma in the elderly. A rationale for surgical management.

Recent studies have advocated the nonoperative treatment of elderly patients with bile duct cancer using biliary endoprostheses. In addition to a 30-day mortality rate of 9%, disadvantages with this approach include lack of a definitive diagnosis and the inability to assess resectability. For comparison, we reviewed 42 consecutive cases of bile duct cancer managed surgically at UCLA (from 1954 to 1988) among patients age 70 years or older. Histologic confirmation of bile duct cancer was obtained for 40 surgical patients (95%) in the series. The 30-day mortality rate was 10%. There was a trend to more aggressive surgical management during the study, with a concomitant doubling in survival rates (from 21% among patients treated between 1954 and 1978 to 53% among patients treated between 1979 and 1988 at 1 year after surgery.) We conclude that elderly patients should not be denied surgical evaluation of malignant neoplasms of the bile duct simply on the basis of age.

Adenocarcinoma↗
PubMed1991

Diffuse bile duct tumors: guidelines for management.

The majority of patients with bile duct cancer have small focal adenocarcinomas localized to the upper, middle, or lower third of the bile duct. In contrast, a small subgroup of patients have been identified with bile duct tumors that are diffuse, involving multiple segments of the extrahepatic biliary tract. Among 186 patients with documented bile duct cancer treated at the UCLA Medical Center between 1954 and 1988, 13 patients (7%) had diffuse lesions. Patients with diffuse tumors had markedly poorer survival rates than did those with focal lesions. As diffuse tumors are not amenable to resection, surgical management consists primarily of establishing suitable biliary drainage. All patients with bile duct cancer should undergo careful intraoperative evaluation to exclude a diffuse lesion before tumor resection.

Adult↗
PubMed1987

Effect of tetraploidy on dendritic branching in neurons and glial cells of the frog, Xenopus laevis.

Morphological aspects of four different groups of Golgi impregnated brain cells from a tetraploid strain of Xenopus laevis frogs were compared to analogous cells in comparably sized diploid frogs. The cells examined included neurons from the telencephalon, caudal hypothalamus, and optic tectum, and radial glial cells from the optic tectum. The brains of tetraploid frogs appeared grossly normal and were the same size and contained similar cell types as diploid brains. As observed in previous studies on polyploid amphibia, somal diameters increased significantly in tetraploid cells for each of the four groups of cells examined. Also, the total length of the dendritic arbors in tetraploid brain cells increased significantly by factors ranging from 1.4 to 2.4 times the total length of the analogous processes in diploid cells. Tetraploid neurons in the telencephalon and hypothalamus increased their arbor lengths predominantly by increasing the number of dendritic branches, while maintaining the average distance between branch points in the dendritic segments. In contrast, the tetraploid large pear-shaped neurons in the optic tectum had significantly longer terminal dendritic segments than the analogous diploid neurons, although these tetraploid neurons maintained their average number of dendritic segments per cell. Tetraploid tectal radial glial cells appeared to increase both their number of branches and the lengths of their terminal segments. Thus, the mode by which tetraploid brain cells achieved longer dendritic arbors varied from cell type to cell type. These results suggest a hypothetical basis for possible effects of genomic size on vertebrate brain structure and evolution at the cellular level.

Animals↗
PubMed1987

Unresponsive, a behavioral mutant in Xenopus laevis: electrophysiological studies of the neuromuscular system.

Normal Xenopus laevis embryos begin movements at 1 day after fertilization. Embryos homozygous for the unresponsive mutation fail to move until 4 days after fertilization (just prior to feeding), after which they recover slowly. Electrophysiological studies were undertaken to determine the focus of this mutation. Formamide treatment of normal embryos was used to produce a phenocopy of the unresponsive condition, permitting direct comparisons between mutant and normal embryos. Intracellular recordings from muscle cells were obtained in formamide-treated and untreated preparations with both normal and unresponsive animals. Local electrical stimulation evoked either isolated endplate potentials and action potentials or after-discharges of these events in all preparations. A decrease in illumination also caused a burst of endplate potentials and action potentials. Therefore, the electrophysiology of the neuromuscular junction in unresponsive appears qualitatively normal; the effect of the mutation on the motor system is probably distal to the neuromuscular junction, either at or subsequent to excitation-contraction coupling.

Animals↗
PubMed1987

Role of natural killer cells in resistance to Cryptococcus neoformans infections in mice.

Previous studies have suggested a possible role for natural killer (NK) cells in resistance to some fungal infections, including Cryptococcus neoformans infections. The role of NK cells in early clearance of C neoformans from tissues and in long-term survival was studied in mice following intravenous inoculations of the organism. Mice treated with anti-asialo GM1 antiserum to temporarily reduce NK activity demonstrated an increase in colony-forming units (CFU) of C neoformans in the lung 24 hours after an intravenous inoculation of the organism. CFU in liver, spleen, kidney, and brain were not different in anti-asialo GM1 antiserum-treated versus control mice. An NK-specific reagent, anti-NK 1.1 monoclonal antibody, was used to deplete mice of NK cells in vivo for at least 14 days without affecting other natural defenses. The number of C neoformans retained in the lungs 24 hours after inoculation of the organism was significantly greater in NK cell-depleted mice than in controls, although CFU in other organs were unaffected. Following the intravenous inoculation of C neoformans, the survival of anti-NK 1.1-treated mice was not different from control mice. The effect of NK cell activity on resistance to C neoformans was also determined after an intratracheal inoculation of the organism. Mice pretreated with anti-NK 1.1 demonstrated no increases in CFU in the lungs, spleen, or brain as compared with controls. These data indicate that NK cells can play a role in vivo in early resistance against C neoformans if the organism is delivered via the intravenous route. However, NK cells do not play a role in either determining survival after an intravenous inoculation nor in resistance during an infection acquired via the respiratory tract.

Animals↗
PubMed1985

Developmental mutants isolated from wild-caught Xenopus laevis by gynogenesis and inbreeding.

Xenopus laevis obtained from indigenous African populations are a rich source of mutants affecting development. Gynogenesis and inbreeding were used to isolate mutants affecting development from wild-caught Xenopus laevis females. Fourteen mutants were recovered from eight females tested. One mutant was recovered from each of two females. This load of 1.875 developmental mutants per female is similar to that found in the axolotl (Ambystoma mexicanum), a urodele amphibian, and is only slightly less than the load of mutants with major developmental effects found in Drosophila and man. These results suggest that the anuran amphibian Xenopus laevis, an ancestrally tetraploid species, has undergone extensive diploidization of developmentally important loci and that gynogenesis and inbreeding of wild-caught animals can provide adequate mutants at diploid loci for developmental genetic studies.

Animals↗
PubMed1985

Regulation in the neural plate of Xenopus laevis demonstrated by genetic markers.

To follow the subsequent history of grafted tissue in experiments designed to study regulation and commitment in the amphibian neural plate, previous workers have relied on graft scars, vital dyes applied externally to cells, or xenoplastic grafts. Each of these methods has been criticized on the grounds that they do not indicate unambiguously the origins of individual cells within the operated host. To overcome these difficulties, homoplastic, genetically marked embryonic grafts were taken from the prospective spinal neuroectoderm of triploid and tetraploid Xenopus laevis frogs and transplanted to presumptive eye and prosencephalic regions of the neural plate of diploid X. laevis embryos. Orthotopic presumptive eye grafts also were done. Marked cells were scored in section either by nucleolar number or computerized nuclear size analysis. Of 28 heterotopically grafted embryos that survived to stage 41, when the retina has differentiated, prospective spinal cord neuroectoderm in eight animals gave rise to cell types unique to the eye. The remaining 20 survivors appeared to be mosaic. These results substantiate claims of regulation in the neural plate and extend these observations to the level of individual cell types, a level of resolution not previously obtained in other studies.

Animals↗
PubMed1984

Two healing patterns correlate with different adult neural connectivity patterns in regenerating embryonic Xenopus retina.

Nasal and temporal one-third-sized eye fragments, formed by ablation at stage 32-33 of Xenopus laevis embryos, heal and, in about 50% of the cases, survive to make eyes in the postmetamorphic animal which have mappable visuotectal projections. The majority of nasal one-third eyes have duplicate projections whereas the majority of temporal one-third eyes have unduplicated projections. Most nasal one-third eye fragments and a minority of temporal eye fragments heal by the extrusion of cells from the center of the cut edge into the region of the ablation, forming a tongue of cells between the distal cut edges. This healing pattern is correlated with duplicated visuotectal projections. Most temporal one-third fragments and a minority of nasal one-third fragments heal by rounding up; that is, the distal cut edges collapse to meet in the region of the ablation. This healing pattern is correlated with the formation of unduplicated visuotectal projections. During tongue formation, neurons and undifferentiated cells are transferred from the original fragment into the tongue in a disorderly array, but quickly re-form normal retinal order. We propose that the tongue cells retain their original determination to connect to the same tectal positions as the fragment from which they originated, despite their new positions, and that this mosaicism, coupled with cell movement into the tongue, established duplicate visuotectal projections.

Animals↗
PubMed1983

A clinical trial of fibroblast transplantation for the treatment of mucopolysaccharidoses.

This paper reports the clinical and biochemical results in six patients with Hurler disease (Mucopolysaccharidosis IH; McKusick 25280), two patients with Hunter disease (Mucopolysaccharidosis II; McKusick 25285) and one patient with Sanfilippo B disease (Mucopolysaccharidosis IIIB; McKusick 25292) who were treated by fibroblast transplantation. Except for one patient who died for a coincidental reason, the patients have been studied for between 2.5 and 4.5 years. The clinical course of the disease was not materially altered. There was no evidence that the patients had developed immune responses against the transplanted fibroblasts. Transplantation did not produce measurable levels of either alpha-L-iduronidase (EC 3.2.1.76) in the leukocytes from patients with Hurler disease or of N-acetyl-alpha-D-glucosaminidase (EC 3.2.1.50) in the plasma of the patients with Sanfilippo B disease. Under the conditions used for the assay, leukocytes from the patients with Hunter disease had detectable levels of residual alpha-L-idurono-2-sulphate sulphatase activity which were increased after the transplants, although these changes were of inconstant size and their time course was not consistently related to the transplantations. Cytogenetic studies in cases where the donor was of the opposite sex detected only cells of the recipient's sex among the fibroblasts grown from biopsies of the transplantation sites. The technique used would have detected a donor to recipient cell ratio of 1:100. We found no consistent long-term trends in the excretion patterns of glycosaminoglycans and oligosaccharides from either a quantitative or qualitative point of view which could be specifically related to the transplantation. The combined administration of immunosuppressive doses of prednisolone and azathioprine was associated with an increased excretion of the lower molecular weight glycosaminoglycans. We conclude that fibroblast transplantation is not therapeutically useful in the diseases studied.

Acetylglucosaminidase↗
PubMed1983

Allograft rejection in Xenopus laevis following larval thymectomy.

Xenopus laevis thymectomized at stages 41 through 49 accept first set allografts, while animals thymectomized at stage 51 or older reject allografts in times similar to intact animals. However, thymectomy at progressively earlier stages results in a greater proportion of animals unable to reject second set grafts. In some animals, the allograft response remains deficient even after multiple challenges. The results indicate that alloreactive cells are thymus dependent, and suggest that the thymus processes precursor thymocytes starting upon its formation at around stage 41. The processed cells, competent to respond to alloantigens, are released to the periphery almost immediately. While an increasing pool of processed T cells accumulates during stages 41-49, the persistent defective allograft response displayed by animals thymectomized during these stages suggests that early thymectomy may leave a population of alloreactive cells qualitatively defective in some subpopulation necessary for normal allograft responses, or that any residual cells processed prior to thymectomy are capable of only limited clonal expansion.

Animals↗
PubMed1983

Tolerance maintenance depends on persistence of the tolerizing antigen: evidence from transplantation studies on Xenopus laevis.

In order to assess the role of antigen persistence in the tolerant state, tolerance was induced in Xenopus laevis by the embryonic transplantation of whole eyes or tail tissue. Both types of transplants were seen to heal in and persist, with no signs of immunological incompatibility. At metamorphosis, tail resorption occurred and grafted tail tissue was lost. Eye transplants were maintained through metamorphosis in most eye grafted animals. Eye graft recipients which had maintained the transplant were observed to accept challenge skin allografts from donors of the same genotype as the eye donor in all but one case, while recipients which had lost the eye transplant at metamorphosis or had the eye transplant experimentally removed sometimes did not accept the challenge skin graft. Animals tail grafted as embryos did not accept post metamorphic skin grafts from donors of the same genotype as the tail tissue donor, but rejection was not accelerated. It is proposed that tolerance induction is dependent on the presence of appropriately presented antigen at a time when precursor thymocyte cells are migrating to the thymus, prior to their processing into alloreactive cells, and that tolerance maintenance is dependent upon the persistence of the tolerizing antigen.

Age Factors↗
PubMed1982

Electroconvulsive therapy and memory dysfunction: is there evidence for prolonged defects?

The authors reviewed 39 papers which concern the long-term effects of electroconvulsive therapy (ECT) on human memory. Although the authors caution that methodological considerations preclude a decisive assessment, the majority of the studies suggest that ECT does not normally produce prolonged memory defects. Some recent studies do document subtle but persistent defects several months after ECT, especially in personal autobiographical material. These defects appear to be more annoying than seriously incapacitating. Variables considered important in an ideal design of studies on ECT and memory are discussed.

Amnesia↗
PubMed1979

Clarification of studies on the origin of thymic lymphocytes.

The thesis that lymphocytes originate in situ by the direct transformation of epithelial cells within the thymic primordium in anurous frogs is untenable. On the contrary, in both the leopard frog and the African clawed toad, the lymphocytes that first appear in the embryonic thymus are derived from extrathymic lymphopoietic cells that invaded the developing organ. The exact source of origin of the invading lymphopoietic cells remains problematic.

Animals↗
PubMed1977

Neuroanatomy of Spastic, a behavior mutant of the mexican axoloti: Purkinje cell distribution in the adult cerebellum.

The spastic mutant, found in the Mexican axolotl, shows swimming coordination and equilibrium deficiencies. Histological analyses of wild-type and spastic mutant cerebella previously characterized in physiological studies revealed changes in Purkinje cell location in the mutant auricle or vestibulo-cerebellum. Purkinje cells are "translocated" ventrally correlated with a similar translocation of vestibular single units described previuosly (Ide, '77). Where wild-type Purkinje cells are distributed from the surface to a depth of 250 micrometers, mutant Purkinje cells are "crowded" between 250 and 350 micrometers. Although mutant granule cells are present, boundaries between granule cell and Purkinje cell zones are less precise in mutants. Cerebellar nucleus cells are translocated medially, failing to organize into the discrete cell group appearing in wild-type. Cerebellar white matter tracts and fibers show changes, both in orientation with respect to the underlying tegmentum, and in fascicular organization. Obvious changes in the gross anatomy of the cerebellum are confirmed in reconstructions which define cell and fiber translocation. Thus, the spastic gene is compatible with differentiation of all cerebellar elements, but appears to alter interactions between cells, or between cells and the external milieu. Although all cell types are present in the mutant cerebellum, they fail to attain their proper positions along all three body axes.

Ambystoma↗