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Biomedical subjects

J Champion

Publications and source records attributed to J Champion.

35 records · Page 2Linked to original sources

Retinal effects of the frequency-doubled (532 nm) YAG laser: histopathological comparison with argon laser.

Retinal lesions produced in Dutch Cross rabbits with a frequency-doubled (532 nm) YAG laser in single pulse mode (30-100 microJ) and in train of uniform pulses (2.6 and 7.5 mJ) underwent histopathological examination by light and electron microscopy. The results were compared to argon laser lesions (11 and 15 mJ) in the same animals. Low-energy single-pulse YAG lesions produced separation of the neural retina from the retinal pigmented epithelium (RPE), while higher energies caused severe disruption of retinal structures with moderate damage to the RPE. A striking and consistent finding of all the single-pulse lesions was the presence of red blood cells between the RPE and neural layers. The findings appear to support a process of mechanical disruption. In contrast, the lesions produced by a uniform train of pulses showed well-defined damage to RPE and photoreceptors with no red blood cells between these two layers, no choroidal damage, and relatively little disruption of the inner retina. The typical argon lesion evidenced cellular damage from the RPE through all retinal layers. Leukocytes in the choroid contained "holes" or vacuoles not seen in YAG lesions. Both the uniformly pulsed YAG laser burst and argon laser produced effects consistent with a thermal process. Some differences between argon and YAG burst were observed. The results suggest that there may be a clinical potential for the 532-nm burst YAG in treating retinopathies.

Animals↗

Effective cisplatin (DDP) based chemotherapy in the treatment of hepatoblastoma.

Nine of 11 patients with hepatoblastoma treated with cisplatin (DDP) based chemotherapy had a complete (CR) or partial (PR) remission. Five of these patients had measurable pulmonary disease and four achieved a CR of pulmonary lesions. The average interval of disease control following DDP was three times that of Adriamycin (ADR). DDP is an effective agent in the treatment of hepatoblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Relapsed Wilms' tumor. Factors affecting survival and cure.

To identify factors contributing to extended survival among patients with relapsed Wilms' tumor, we assessed 10 clinical and biologic variables thought to have predictive value. With a median follow-up of 6 years, 32 (20%) of 156 patients who achieved complete remission have relapsed. Twenty-four have died with recurrent tumor, and eight are surviving for 2 to 12 years from diagnosis. Only time to relapse, or length of initial complete remission, had a significant influence on survival. Of 11 patients with complete remissions lasting longer than 12 months, six have died--compared with seven of 10 having remissions of 6 to 12 months and 11 of 11 with shorter remissions (p = 0.014). Surgery alone was the curative therapy in three of the eight surviving patients. Until more effective chemotherapy regimens are developed, an aggressive surgical approach may be indicated in selected patients with relapsed Wilms' tumor.

Child, Preschool↗

The value of computerized tomography as a routine follow-up procedure for patients with Wilms' tumor.

We performed routine computerized tomography (CT) of the chest and abdomen on patients treated for Wilms' tumor and reviewed the records of all patients who relapsed (10 patients) and 43 additional patients followed for at least 1 year. Routine chest radiographs and abdominal ultrasounds were compared with 210 CT examinations (107 chest and 103 abdomen). CT examinations were obtained at 6 months for stage I (13 patients) and at 3, 8, and 15 months for stages II, III, and IV (40 patients). Of the 10 patients who relapsed, only 2 were documented by CT scan in the absence of clinical symptomatology and presence of normal radiographs and ultrasound. Eight relapses were diagnosed by physical examination, chest radiograph, or ultrasound and confirmed by CT scan. Questionably abnormal CT scans were obtained in 7 patients, only 1 of whom eventually relapsed. Since only 2 of 210 routine CT examinations were the the only indicator of relapse, we conclude that the routine use of CT for follow-up in Wilms' tumor is not warranted.

Evaluation Studies as Topic↗

Regulation by estrogen receptor of vitellogenin gene transcription in Xenopus hepatocyte cultures.

We have used primary cell cultures of hepatocytes from male or female Xenopus laevis to study the mechanisms by which estrogen induces vitellogenin gene transcription and how primary exposure to estrogen renders cells more responsive to secondary stimulation. We have characterized the estrogen receptor in hormonally naïve cells and in hepatocytes treated with estrogen under a variety of conditions. Under all conditions the receptor has a Kd congruent to 4 X 10(-10) M. Hormonally naïve male cells contain 300 binding sites whereas female cells or male cells previously exposed to estradiol exhibit 6-7-fold higher levels. In parallel cultures, the absolute rate of vitellogenin gene transcription was determined by hybridization of newly synthesized RNA pulse-labelled with [3H]uridine to cloned Xenopus vitellogenin cDNA. Naïve male cells on primary stimulation with estradiol synthesized vitellogenin mRNA at an average rate of approximately 150 moles/cell/h compared to 1200 moles/cell/h for cells previously exposed to estrogen, thus bearing a close correlation with receptor number. Furthermore, we show that the kinetics of the induced up-regulation of receptor exactly parallel those of the increase in the rate of vitellogenin gene transcription upon secondary hormonal stimulation following various periods of primary exposure to estrogen. Addition of cycloheximide to cell cultures during primary estrogen treatment abolishes both receptor up-regulation and increased rate of vitellogenin gene transcription on secondary stimulation. In addition, primary treatment with the antiestrogen tamoxifen prevents both receptor up-regulation and an enhanced rate of transcription or accumulation of vitellogenin mRNA on secondary hormonal exposure. These results demonstrate that estrogen treatment of male Xenopus hepatocytes results in the rapid up-regulation of its own receptor to female levels via new receptor synthesis, and that receptor number is rate-limiting in vitellogenin gene transcription.

Animals↗

Signal sequences, secondary modification and the turnover of miscompartmentalized secretory proteins in Xenopus oocytes.

The cytoplasm of the Xenopus oocyte can be altered by the microinjection of proteins and the regulatory responses to such perturbations can then be studied. We have investigated proteolytic systems within the oocyte which may be involved in the maintenance of the integrity of the different subcellular compartments. Thus primary translation products, made in the wheat germ system under the direction of frog liver, chicken oviduct, rat liver rapidly sedimenting endoplasmic reticulum, rat seminal vesicle, guinea pig mammary gland or honey been venom gland RNA, were injected into oocytes. Their stability in the frog cell cytosol was in general low compared to that of their processed counterparts. The latter were usually obtained by collecting the heterologous proteins exported by RNA-injected oocytes. Electrophoretic analysis of oocytes injected with particular primary and processed polypeptides permitted measurement of the stabilities of proteins differing only by the presence or absence of a detachable signal sequence, or by the presence of a specific secondary modification. The effect of the latter on protein stability appears slight. However, the presence of a detachable signal sequence destabilizes those miscompartmentalized secretory proteins which are otherwise stable. Indeed all other results are consistent with this concept for they show that primary translation products are in general much less and are never more stable than their processed counterparts. Thus we provide evidence that errors of compartmentation can be corrected in living cells and that this process is often facilitated by the properties conferred on a protein by a detachable signal sequence.

Animals↗

Intrarenal angiotensin I conversion at normal and reduced renal blood flow in the dog.

Intrarenal conversion of angiotensin I (ANG I) to angiotensin II (ANG II) under conditions of normal and reduced renal blood flow (RBF) elicited by constriction of the renal artery was examined in pentobarbital-anesthetized dogs. In eight animals, tracer doses of 125I-ANG I (5-12 pmol) were injected into the renal artery and 125I-ANG I, 125I-ANG II, and 125I-labeled metabolites were measured in renal venous effluent by high-voltage paper electrophoresis. The mean conversion of ANG I to ANG II during a single passage through the kidney was 21.8 +/- 2.1% at control RBF. When RBF was decreased by 25 and 53%, percent ANG I conversion was not altered significantly. In six dogs percent conversion of 125I-[Sar1, Ile5]ANG I, an ANG I analogue refractory to hydrolysis by aminopeptidases, was 18.1 +/- 1.7% at control RBF and did not change significantly when the RBF was reduced by 55%. Although there were severalfold increases in renal renin secretion rate and net ANG I generation rate during reduced RBF, net renal ANG II formation rate did not change significantly. These data indicate that there is substantial conversion of ANG I in a single passage through the dog kidney and that intrarenal ANG I conversion is independent of RBF even under conditions in which renin secretion rate and ANG I generation rate are increased severalfold.

Angiotensin I↗

Antibody responses to Epstein-Barr virus-specific DNase in relation to the prognosis of juvenile patients with nasopharyngeal carcinoma.

We have examined serial sera from 17 juvenile patients with nasopharyngeal carcinoma (NPC) for their capacity to neutralize the activity of Epstein-Barr virus (EBV)-specific DNase. The results revealed that NPC patients who became long-term survivors (LTS) without evidence of the disease either never possessed significant levels of antibodies to the enzyme or showed a gradual decline in the number of EBV DNase units neutralized from an elevated level at diagnosis to an insignificant figure several years later. All the 10 LTS neutralized less than 4, and some neutralized less than 2 units of the enzyme 3 or more years after the initial diagnosis. In contrast, serial sera from juvenile patients who died of NPC neutralized over 10 and as many as 25 units of EBV DNase either persistently until death occurred or with transient declines during unmaintained remissions. Rises and declines in the neutralizing activity were, with few exceptions, accompanied by corresponding changes in the titers of IgA and IgG antibodies to EB viral capsid antigen and to the diffuse component of the early antigens. Although the number of juvenile NPC cases available for study was small, the observations suggest that the EBV DNase neutralization test may serve to provide information on the prognosis of the patients.

Adolescent↗

Nasopharyngeal carcinoma in American Children: Epstein-Barr virus-specific antibody titers and prognosis.

Seven American juvenile patients with undifferentiated or nonkeratinizing nasopharyngeal carcinoma (NPC) were examined serially for Epstein-Barr virus (EBV)-specific antibody spectra and titers in sera. At diagnosis, all showed antibody patterns characteristic of NPC: i.e., high titers of IgG antibodies to viral capsid antigen (VCA) and to the diffuse (D) component of the early antigen complex. Six patients had IgA antibodies to VCA, and four to the D component. In the patients who responded to therapy with complete and maintained remissions, the IgG antibodies to D and the IgA antibodies to VCA and D decreased to undetectable levels within 12 to 30 months. By contrast, of the four patients who responded only transiently to therapy, three showed substantial increases and one continuously high titers of IgG anti-D and IgA anti-VCA. The increases in antibody titers preceded clinical recognition of recurrent tumors by 1 to 6 months. Three of these patients have died and the fourth is alive with disease. These data indicate that American juvenile NPC does not differ from the adult disease observed anywhere in the World. They reaffirm the potential usefulness of EBV-specific serology in the diagnosis and prognosis of NPC and the monitoring of patients following therapy.

Adolescent↗

The sequestration, processing and retention of honey-bee promelittin made in amphibian oocytes.

Messenger RNAs from one kind of secretory cell can be introduced into the cytoplasm of another: the heterologous proteins formed by the recipient cell are usually processed and topologically segregated in the manner characteristic of the donor cell. Xenopus oocytes injected with honey-bee venom gland RNA provide some support for this generalization, but also reveal important exceptions to it. Thus, the frog cell makes a small polypeptide whose partial sequence matches perfectly that of insect promelittin, except that the product formed in oocytes ends at the C terminus with a glycine as opposed to a glutamine amide residue. N-terminal heterogeneity is seen in protoxin made in oocytes and venom gland cells, and species shorter by two residues are seen in both tissues. We suggest that the oocyte contains a dipeptidylpeptidase. Promelittin made in oocytes is barely detectable in the cytosol but is found associated with a vesicle fraction which also contains some newly synthesized endogenous oocyte proteins. The association with vesicles is long-lasting; thus promelittin is retained slightly more efficiently than sequestered oocyte proteins, and an incubation period of about two weeks is required to reduce by half the amount of these endogenous vesicle proteins. Thus neither promelittin nor any products derived from it are secreted rapidly. Gel analysis fails to reveal promelittin in the medium surrounding the oocyte, although traces can be detected by assaying for a characteristic heptapeptide. Such small amounts could result from slow secretion or leakage. Melittin could not be detected by gel analysis or peptide assay. The retention of the honey-bee protein within the frog cell is discussed in terms of the specificity of the processing systems and secretory pathways of venom gland cells and oocytes. We suggest that whilst some export mechanisms function efficiently in a wide variety of cells, others do not, and may even be restricted to specific cell types.

Amino Acid Sequence↗

The Xenopus oocyte as a surrogate secretory system. The specificity of protein export.

Combining messenger RNA from one kind of secretory cell with the cytoplasm of another such cell can reveal the nature and specificity of protein export mechanisms. We show that messenger RNAs from secretory cells of chickens, rats, mice, frogs, guinea-pigs, locusts and barley plants, when injected into Xenopus oocytes, direct the synthesis and export of proteins. Chicken ovalbumin, Xenopus albumin, mouse thyroid-stimulating hormone, locust vitellin and guinea-pig milk proteins were identified using specific antibodies, whilst chicken lysozyme and ovomucoid, rat albumin, Xenopus vitellogenin and rat seminal vesicle basic proteins were identified provisionally from their molecular weights. Certain endogenous proteins are sequestered and secreted although most oocyte proteins are not exported. Similarly the major polyoma viral protein and the simian virus 40 and polyoma tumour antigens are retained within the oocyte. Radioactive proteins exported by oocytes programmed with chicken oviduct or Xenopus liver RNA are not re-exported in detectable amounts when injected into fresh oocytes, nor is there secretion of chicken oviduct or guinea-pig mammary gland primary translation products prepared using wheat germ extracts. Thus the export of secretory proteins from oocytes cannot be explained by leakage and may require a cotranslational event. The secretory system of the oocyte is neither cell-type nor species-specific yet is highly selective. We suggest that the oocyte can be used as a general surrogate system for the study of gene expression, from transcription through translation to the final subcellular or extracellular destination of the processed protein.

Animals↗

Attitudes of the dental team to the provision of care for people with learning disabilities.

The aim of this study was to report on the evaluation of an attitude scale for General Dental Practitioners (GDPs) and Dental Auxiliaries/Professionals Complementary to Dentistry (PCDs), to determine the reliability of the scale with these two groups and to note any inter-group differences. Seventy-four GDPs and 89 PCDs completed the self-administered questionnaires. The main outcome measures were reliability statistics, attitude scores, and factor analysis statistics. Reliability was satisfactory for both groups. PCDs scored consistently higher than GDPs on this attitude scale. Six factors were found to underlie the responses of GDPs, accounting for 62% of the variance. Seven factors were found to underlie the responses of PCDs, accounting for 65% of the variance. PCDs expressed more positive views about provision of care for patients with learning disabilities than did GDPs. Factor analysis revealed that GDPs were concerned about effectiveness of treatment and the stress related with treating patients with disabilities. PCDs appeared to be more concerned with the human rights of people with learning disabilities and how they fit into society.

Adolescent↗