Temporal sequence of mammary intraductal proliferations, ductal carcinomas in situ and adenocarcinomas induced by 1-methyl-1- nitrosourea in rats

An experimental model for mammary carcinogenesis has been described in which intraductal proliferations, ductal carcinomas in situ and adenocarcinomas can be readily detected and the frequency of their occurrence quantified. The objective of the experiment reported in this study was to determine the latency period between carcinogen administration and the occurrence of each of these types of lesion. A total of 150 female Sprague-Dawley rats were injected i.p. with 50 mg 1- methyl-1-nitrosourea (MNU)/kg body wt at 21 days of age. Groups of 30 rats each were killed at 7, 14, 21, 28 and 35 days post-carcinogen. Mammary intraductal proliferations were the first detected lesions and were observed in 20% of the animals at 14 days following carcinogen administration. At 21 days post-carcinogen ductal carcinomas in situ and adenocarcinomas were observed. The number of each type of lesion increased with time post-carcinogen, but the temporal pattern of occurrence was different among lesion types. The pattern of lesion occurrence was consistent with intraductal proliferations being a precursor lesion for ductal carcinomas in situ and adenocarcinomas. Furthermore, the data imply that ductal carcinomas in situ represent one pathway of morphological progression by which intraductal proliferations evolve into invasive carcinomas, but that this lesion type, as currently defined histologically, may not be an obligatory intermediate in morphologic progression. These findings are consistent with emerging evidence of multiple but distinct pathogenetic pathways leading to mammary carcinomas that display different morphological patterns and biological activities.      

Wilms' tumor and gonadal dysgenesis in a child with the 2q37.1 deletion syndrome

Here we report Wilms' tumor, gonadal dysgenesis and a bifid uterus in an 18-month-old female with a terminal deletion of the long arm of chromosome 2 [46, XX, del(2)(q37.1)]. Since Wilms' tumor has been previously reported in the 2q37 deletion syndrome, the present observation raises the question of whether a tumor susceptibility gene maps to chromosome 2q37 and suggests giving consideration to the possible occurrence of Wilms' tumor in the course of disease.     

Stromal growth factor production in irradiated lectin exposed long-term murine bone marrow cultures

Hematopoietic regulatory factors produced by adherent (stromal) cells in long-term murine bone marrow cultures have been investigated. Using an in situ double layer agar overlay system, we demonstrated that exposure of the stromal cells to 1,100-rad irradiation increased their activities in stimulating colony formation of FDC-P1, an interleukin 3 (IL 3)-responsive cell line. The colony-stimulating activities (CSAs) of the irradiated stroma also stimulated normal marrow cells to form granulocyte-macrophage, megakaryocyte, and mixed lineage colonies. Addition of the lectin pokeweed mitogen to the irradiated stroma increased the level of CSAs. The FDC-P1 CSA of the irradiated stroma was inhibited by antibodies directed against murine granulocyte- macrophage colony stimulating factor (GM-CSF) but not by those against murine IL 3. Stromal-derived CSA for marrow cells was also partially blocked by anti-GM-CSF antibodies, probably reflecting the presence of other CSAs such as CSF-1. This latter growth factor has been found to be present in conditioned media from Dexter stroma, but levels are not increased after irradiation or lectin exposure. Partially purified GM- CSF, like IL 3, stimulated FDC-P1 proliferation and granulocyte, macrophage, and megakaryocyte colony formation. These results indicate that the major terminal differentiating hormone elicited by irradiation or lectin exposure of murine marrow stromal cells is GM-CSF. This growth factor, along with CSF-1, can account for the differentiated progeny produced in this system: macrophages, granulocytes, and megakaryocytes.     

Purified interleukin-3 and erythropoietin support the terminal differentiation of hemopoietic progenitors in serum-free culture

We studied the effect of purified interleukin-3 (IL-3) and erythropoietin on colony formation by hemopoietic progenitors in serum- free cultures of spleen cells from 5-fluorouracil (5-FU)-treated mice. In the presence of IL-3 alone, most of the multilineage (three or more lineages) colonies did not contain erythroid cells. However, in the presence of IL-3 and erythropoietin, most of the multilineage colonies contained various numbers of erythroid cells. Replating experiments suggest that IL-3 maintains the growth of the progenitor cells, which could differentiate into erythroid cells. Erythropoietin facilitated the terminal differentiation and amplification of erythroid cells, although it did not sustain the growth of multipotential stem cells. Single-cell transfer experiments demonstrate that IL-3 supported the late stages of differentiation of neutrophils, macrophages, eosinophils, and megakaryocytes in the absence of lineage-specific factors. Therefore, IL-3 supports the differentiation of multilineage hemopoietic progenitors, and the terminal differentiation of most hemopoietic lineages, with the exception of the erythroid lineage.     

Cloning of the Arabidopsis RTM1 gene, which controls restriction of long-distance movement of tobacco etch virus

The locus RTM1 is necessary for restriction of long-distance movement of tobacco etch virus in Arabidopsis thaliana without causing a hypersensitive response or inducing systemic acquired resistance. The RTM1 gene was isolated by map-based cloning. The deduced gene product is similar to the alpha-chain of the Artocarpus integrifolia lectin, jacalin, and to several proteins that contain multiple repeats of a jacalin-like sequence. These proteins comprise a family with members containing modular organizations of one or more jacalin repeat units and are implicated in defense against viruses, fungi, and insects.     

Tinidazole in treatment of amoebic liver abscess in children

Tinidazole as a single drug therapy given in a single dose daily for 5 or 3 days was put to rigorous test in malnourished children. Of 25 children with amoebic liver abscess, 23 were cured. The 2 remaining cases required surgical drainage followed by other amoebicides, one subsequently dying from complicating bronchopneumonia.     

Molecular internalization of a region of myelin basic protein

The conformation of myelin encephalitogenic or basic protein (BP) was investigated with a double-antibody radioimmunoassay by studying the reaction of BP or its fragments with antibodies produced in two rabbits against peptide 43-88 linked to rabbit serum albumin. Both antisera reacted well with peptide 43-88 but showed little or no reaction with BP. Absorption of these antisera with a BP-immunoadsorbent did not remove the antibody activity against peptide 43-88. Within the region of peptide 43- 88 it was shown that peptides 68-88 and 79-88 gave an equivalent or better reaction than peptide 43-88, whereas peptides 43-67 and 64-73 had very little reactivity. In the BP fragments containing region 43-88, peptide 1-88 showed the best reactivity, peptide 20-166 showed minimal reactivity, while peptide 1-115 showed none. These data document the internal position of at least a portion of peptide 43-88 and all of residues 79-88 in the BP molecule. The much greater reactivity of peptide 1-88 as compared to peptide 1-115 suggests that the region or a portion of the region of BP containing residues 89- 115 participates in the conformational alignment of BP restricting access to peptide 79-88. After absorption with BP, neither of the antisera prepared to peptide 43-88 reacted with PNS myelin in fixed tissue sections but continued to react with CNS myelin in similarly treated sections. The present findings demonstrate the need to consider the role of shielded antigenic determinants in the investigation of antigens or of immune responses.     

Diminished frequency of interleukin-10-secreting, T-cell receptor peptide-reactive T cells in multiple sclerosis patients might allow expansion of activated memory T cells bearing the cognate BV gene

T cells responsive to T-cell receptor (TCR) determinants may regulate pathogenic Th1 responses in patients with multiple sclerosis (MS) through interleukin (IL)-10-dependent bystander suppression. In this study, innate IL-10- and interferon (IFN)-gamma-secreting T cells responsive to TCR peptides were quantified in peripheral blood mononuclear cells of MS patients and healthy controls (HC) using the ELISPOT assay. Most HC had vigorous IL-10 but low IFN-gamma frequencies to BV5S2 and BV6S1 peptides. In contrast, MS patients had significantly lower IL-10 frequency responses to the TCR peptides but normal responses to concanavalin A. Patients undergoing TCR-peptide vaccination had moderate responses that fluctuated in concert with vaccination. In an MS patient and HC, expression of BV6S1 by activated memory T cells was inversely associated with the presence of IL-10-secreting BV6S1-reactive T cells. These results suggest that MS patients have diminished frequencies of innate TCR-reactive T cells that may allow oligoclonal expansion of activated autoreactive Th1 effector cells expressing cognate V genes.     

Vaginal ultrasound as an adjunct to cervical digital examination in women at risk of early delivery

AIM: To study the utility of transvaginal ultrasound (TVU) in women at high risk of preterm delivery. METHODS: Women who were scheduled for frequent digital examinations of the cervix from 16 to 26 weeks of gestation had TVU determinations of cervical length before their clinical examinations. Clinicians were blinded to the TVU results. Therefore, clinical decision-making was independent of the unreported TVU data. The plan was to relate the ultrasound characterization of the cervix to the study's primary endpoint, the need for hospitalization prior to 26 weeks of gestation for: preterm premature rupture of membranes, preterm labor, cerclage placement, or delivery. RESULTS: Seventeen subjects completed the study. All 3 who met the primary endpoint had ultrasound cervical lengths <20 mm on earlier prenatal visits, when digital examinations of the cervix did not detect problems. A 4th woman had ultrasound lengths <20 mm (she delivered at 27(6)/(7) weeks). CONCLUSION: TVU determination of cervical length provides an earlier warning of cervical shortening than does digital examination.