Biomedical subjects

L Kenner

Publications and source records attributed to L Kenner.

22 records · Page 2Linked to original sources

PubMed1994

Prognostic importance of human papilloma virus typing in squamous cell papilloma of the bronchus: comparison of in situ hybridization and the polymerase chain reaction.

Thirty-one solitary bronchial squamous cell papillomas (SCPs) with variable degrees of dysplasia, one combined with larynx papilloma and small cell carcinoma in the contralateral lung, and 12 papillomas combined with invasive squamous cell carcinomas (SCCs) were investigated for the presence of human papilloma virus (HPV) DNA by in situ hybridization (ISH) and the polymerase chain reaction (PCR). Benign SCPs showed an association with HPV type 11 and rarely with type 6, whereas type 16 or 18, sometimes in combination with type 31/33/35, was found in SCPs associated with SCCs. In one patient HPV type 18- and 31/33/35-positive benign SCP preceded the recurrence of HPV 18-positive SCP (this time combined with carcinoma) by 2 years. Patients with SCP exhibiting HPV 16 or 18 positivity are at high risk for the development of SCC. Virus typing seems to be a better prognostic indicator than grading of dysplasia or age relationship. Virus typing by the PCR is more sensitive compared with ISH, but positive cells cannot be determined; ISH is less sensitive than the PCR but permits a definite designation of the cell types that have integrated HPV sequences into their DNA. Our data suggest that HPV typing should be performed in every bronchial SCP.

Adult↗

PubMed1993

Tumor induction by ras and myc oncogenes in fetal and neonatal brain: modulating effects of developmental stage and retroviral dose.

Introduction into fetal rat brain cells of a replication-defective retroviral vector harboring v-Ha-ras and v-gag-myc rapidly causes the induction of highly malignant undifferentiated neuroectodermal tumors following transplantation into the brains of syngeneic hosts [Wiestler, et al. (1992) Cancer Res. 52: 3760-3767]. In the present study, we have investigated the modulating effect of the developmental stage of neural target cells and of the dose of the retroviral vector used in the grafting experiments. Exposure of fetal cells from embryonic day (E)12 or E14 produced a 100% incidence of malignant neuroectodermal tumors which led to the death of recipient animals after a median latency period of 32 days. A 100-fold reduction of the virus dose from 2.062 x 10(6) to 2.062 x 10(4) focus-forming units/ml resulted in a lower tumor incidence of 25%. Of six neural grafts exposed to v-Ha-ras and v-myc at E16, only one showed evidence of tumorigenesis (low-grade astrocytoma and hemangioma). All other transplants were morphologically normal for observation periods of 26 weeks, indicating a marked loss of transforming activity of ras and myc in more advanced stages of brain development. In retrovirus-exposed donor cells which caused the development of neural tumors in recipient rats, malignant transformation was also evident during culture in vitro, usually after 9-12 days. Oncogene complementation was also studied in the newborn rat brain. After microinjection of the retroviral vector into the brain at postnatal day (P)0, P1 and P3, 5 out of 20 animals (25%) developed a total of seven brain tumors. Histopathologically, three of these neoplasms were malignant neuroectodermal tumors which, in contrast to those induced in fetal brain transplants showed evidence of focal glial and/or neuronal differentiation. In addition, we observed one oligodendroglioma, two hemangiomas and a malignant hemangioendothelioma. These data indicate that neural precursor cells and endothelia of the rat brain represent the major target cells for the complementary action of ras and myc and that the use of target cells from later developmental stages (E16 and postnatal) leads to the induction of both primitive and more differentiated neoplasms.

Animals↗

PubMed1993

Increased susceptibility for CsA-induced hepatotoxicity in kidney graft recipients with chronic viral hepatitis C.

CsA-induced hepatotoxicity is a rare disorder in renal transplant recipients when low doses are administered and whole blood trough levels of CsA are regularly monitored. However, there is controversy about the clinical value of measuring CsA-metabolites, whose contribution to immunosuppression and toxicity is not fully understood. To assess the relation between low-dose CsA therapy and hepatotoxicity, we studied 128 renal transplant recipients attending our nephrology clinic. Eight of these patients had markedly elevated liver function tests. Three patients while receiving very low doses of oral CsA (< 3.8 mg/kg of body weight) presented marked derangements of CsA metabolism with abnormally increased CsA-metabolite levels. Parent drug levels were in the normal range. All 3 patients had chronic infection with hepatitis C virus and revealed histomorphologic evidence of hepatotoxicity. Hepatic dysfunction normalized when CsA was withdrawn or reduced by 50%. It is likely that hepatitis C virus infection interferes with CsA metabolism and/or biliary CsA-excretion and thus is responsible for CsA and/or metabolite-induced hepatotoxicity despite very low doses of CsA.

Chemical and Drug Induced Liver Injury↗

PubMed1984

Ethnic and sex differences in response to clinical and induced pain in chronic spinal pain patients.

There is widely held clinical opinion and some tentative research justification for stereotypic or ethnic and sex differences in response to pain. To more adequately test this notion, 60 chronic spinal pain patients (black, Mexican American, and Caucasian, with ten men and ten women per group), all having persistent spinal pain for over 1 year, were studied. They were administered the ischemic pain test, a numerical estimate of spinal pain, and two independent raters scaled the amount of pain emphasis, based upon the patient's physical condition and pain behaviors. Results showed ethnic differences on the ischemic test (a psychophysiologic scaling technique used to approximate clinical pain and pain tolerance) with Mexican Americans describing the highest levels. Women of all ethnic groups tended to be judged as emphasizing their pain more than men, based upon judgment of their pain behaviors, and upon their own numerical estimates of pain. They also indicated that they more nearly approached their pain tolerance. It was concluded that while ethnic and sex differences were found, stereotypic responses were not uniform, and tended to be related to the manner in which that pain was assessed. These results are discussed in light of cultural differences.

Adult↗