MECHANISM OF TAXOL-INDUCED APOPTOSIS IN HUMAN BREAST CANCER CELLS

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Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression

The SENCAR stock of mice has proved to be a useful model in dissecting out the multistage nature as well as the critical mechanisms involved in skin tumorigenesis. This outbred stock was selectively bred to be susceptible to initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). In order to obtain mice more suitable for genetic analyses of tumor susceptibility and tissue transplantation studies, several inbred lines of mice were derived from the SENCAR stock. One of these lines, the SSIN mice, has a higher susceptibility to tumor promotion compared to the SENCAR stock but is very resistant to tumor progression. On the other hand, the SENCAR B/Pt mice, derived also from the outbred stock, not only have a tumor promotion susceptibility almost identical to the SSIN mice, but they also have a high susceptibility to tumor progression. In order to understand the nature of the phenotypic differences between these two inbred lines we have characterized them using several parameters and markers that are associated with the progression of papillomas to squamous cell carcinoma (SCC). In this sense we analysed the tumor multiplicity and SCC incidence, and the expression of markers of progression and cell cycle related proteins in papillomas derived from both strains. Our results showed that while both strains have a similar papilloma multiplicity and incidence the SENCAR B/Pt mice have 67% incidence of SCC, compared to 0% in the SSIN. SENCAR B/Pt papillomas at 30 weeks of promotion have a higher and aberrant expression of K13, and loss of connexin 26. TGF-beta1 was found to be over-expressed in the suprabasal and superficial cells in the SENCAR B/Pt papillomas, while it was only expressed in the superficial cell layer in those derived from SSIN. The SENCAR B/Pt papillomas also showed an enlarged proliferative compartment with overexpression of cyclin D1 and PCNA as seen by immunohistochemistry and Western blot.      

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c, during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GHdeficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 ± 2.0 to 10.1 ± 1.7cm/y; p < 0:001)and with the firstyear of observation in Group2( p < 0:001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 ± 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.     

Neonatal nosocomial respiratory infection with coronavirus: a prospective study in a neonatal intensive care unit

The aim of this prospective study was to evaluate the incidence of viral respiratory infection in hospitalized premature newborn infants and to assess the role of coronaviruses. All hospitalized premature infants with a gestational age less than or equal to 32 weeks were included. Tracheal or nasopharyngal specimens were studied by immunofluorescence for coronaviruses, respiratory syncytial virus, adenoviruses, influenza and parainfluenza viruses. Forty premature infants were included; 13 samples were positive in 10 newborns (coronaviruses n = 10; influenza 1 n = 2; adenovirus n = 1). None was positive at admission. All premature infants infected with coronaviruses had symptoms of bradycardia, apnea, hypoxemia, fever or abdominal distension. Chest X-ray revealed diffuse infiltrates in two cases. However, no significant difference was observed between infected and non-infected premature infants for gestational age, birth weight, duration of ventilation, age at discharge, incidence of apnea or bradycardia. Nosocomial respiratory tract infection with coronaviruses appears to be frequent. The clinical consequences should be evaluated in a larger population.     

Simple device for air reduction of intussusception

A new device has been developed for pneumatic reduction of childhood intussusception. The device consists of a reusable, hand-held pressure gauge and insulfflator connected to a disposable enema tip and tubing system. The assembled device permits one-handed operation which maximizes operator control of the air reduction procedure. The system has been used to evaluate 50 cases of suspected intussusception. Reduction was successful in 19 of 22 confirmed intussusceptions. This device provides a practical, simple and safe method for diagnosis and treatment of intussusception.Presented at the 32nd Annual Meeting of The Society for Pediatric Radiology, San Antonio, TX, April 5–9, 1989.     

The regulation of immunoglobulin synthesis after HLA-identical bone marrow transplantation: VI. Differential rates of maturation of distinct functional groups within lymphoid subpopulations in patients after human marrow grafting

This investigation uses different polyclonal activators of in vitro immunoglobulin production to elicit immunoregulatory profiles of B cells, T cells, T4 cells, and T8 cells from 25 recipients (13 with and 12 without chronic graft-v-host disease [GVHD] ) after HLA-identical marrow transplantation for aplastic anemia or hematologic malignancy. Pokeweed mitogen, Epstein-Barr virus, herpes simplex type 1 virus, and tetanus toxoid were used to induce immunoglobulin production as measured by a plaque assay. Multiple defects in the various lymphoid subsets were found in both groups of patients. There was defective b cell function, lack of T cell or T4 cell subset helper activity, and increased T cell, T4 cell, or T8 cell suppressor activity after stimulation with the various activators. Inconsistent B, T, T4, and T8 cell functions in the marrow graft recipients provide evidence for (a) different functional groups of cells within each subset responsive to different polyclonal activators; (b) a spectrum of immune capabilities within each phenotype lineage; (c) different patterns of immune reconstitution for each lymphocyte subset after marrow grafting; and (d) chronic GVHD altering recovery of in vitro functional responses to the different polyclonal activators.     

Twin and singleton growth patterns compared using US

Sonography has been used widely in the evaluation of singleton fetal growth. Twin gestations, however, have received less careful attention. In a statistical study of 103 twin pregnancies, the growth patterns of twin biparietal diameter (BPD), fetal femur length (FFL), and abdominal circumference (AC) were compared with those of singletons. The results of the study revealed a decrease in twin BPD growth after 31 to 32 weeks of gestation relative to singletons. Twin AC growth rate decreases after 32-33 weeks of gestation relative to singletons, but the twin FFL growth pattern does not deviate from that of singletons throughout gestation. Because of the significant difference in growth patterns of BPD and AC between twins and singletons in our population, new growth charts for twin BPD and AC are proposed.