Expression of insulin-like growth factor 1 receptor in primary breast cancer: immunohistochemical analysis

Insulin-like growth factor-1 receptor (IGF-1R) has been implicated in regulation in tumor growth. The results of previous studies performed by radioimmunoassay are conflicting, and the prognostic significance of IGF-1R expression in primary breast cancer is still controversial. IGF-1R expression was evaluated in formalin-fixed, paraffin-embedded tissue of 210 primary breast cancer patients by using anti-IGF-1R antibody. The clinicopathologic variables and 5-year disease-free survival were studied, and their correlations between IGF-1R expressions were investigated. IGF-1R overexpression was observed in 43.8% of tumors. IGF-1R overexpression had no correlation with prognosis or with other clinicopathologic parameters, such as age, tumor size, nodal status, histologic grade, hormone receptor status, and human epidermal growth factor 2 status. Though its prognostic value in breast cancer is limited, immunohistochemical evaluation of IGF-1R by using this monoclonal antibody may be useful in translational research using archived material.     

Coincident stimulation of convergent cortical inputs enhances immediate early gene induction in the striatum

The effect of coincident stimulation of convergent corticostriatal inputs was analyzed by the induction of immediate early genes in striatal neurons. Cortical motor areas were stimulated through implanted electrodes in awake, behaving rats, and the induction of the mRNAs encoding the immediate early genes (IEGs) c-fos and arc was analyzed in the striatum with in situ hybridization histochemistry. In the first experiment, unilateral stimulation of the medial agranular cortex, orofacial region of the lateral agranular cortex or the forelimb region of the lateral agranular cortex resulted in IEG induction in the striatum, which was restricted to the topographically related area receiving input from the stimulated cortical area. In a second experiment, stimulation parameters were altered, including frequency, number of pulses/train, and number of trains/s. These parameters did not have a significant effect on IEG induction. Notably, in some cases, in which there was IEG induction not only in the stimulated cortical region, but also in the homologous area in the contralateral hemisphere, very robust IEG induction was observed in the striatum. In a third experiment, the orofacial regions of the lateral agranular cortex of both hemispheres were stimulated coincidently. All of these animals showed robust striatal IEG induction. This IEG induction was attenuated by pretreatment with an NMDA antagonist MK-801. In a fourth experiment, we tested whether the coincidence of bilateral cortical stimulation contributed to the efficacy of striatal IEG induction. Either alternating stimulation or coincident stimulation of non-homologous cortical regions produced significantly lower striatal IEG induction than obtained with coincident stimulation of homologous cortical areas. Enhanced striatal IEG induction occurred in indirect striatal neurons, labeled with enkephalin, but was also present in a large number of enkephalin-negative neurons, most of which are likely direct pathway neurons. These results suggest that regional and temporal convergence of cortical inputs enhances striatal IEG induction.     

Interruption of the lordosis reflex of female rats by ventral midbrain stimulation.

The lordosis reflex, dorsiflexion of the vertebral column, is an estrogen-dependent, essential element of female sexual behavior in rodents. Unilateral electrical stimulation of the midbrain ventral tegmental area through a chronically implanted electrode in freely moving, estrogen-primed ovariectomized female rats caused a rapid and strong suppression of the lordosis reflex in response to either male mounts or manual cutaneous stimuli. The interruption occurred in a graded manner to increased stimulus intensity, with a threshold at 30 microA. The optimal frequency was at 75-125 Hz. After the termination of electrical stimulation, lordosis performance returned promptly to the pre-stimulation level. No aversive response accompanied the blockade of lordosis. Electrical stimulation specifically blocked lordosis, without disrupting the proceptive components of female sexual behavior. In 10 animals tested, concomitant injection of dopamine receptor blocker pimozide tended to offset the effects of electrical stimulation in 2 cases. Interruption of the lordosis reflex might be mediated by projections from the ventral tegmental area, which activate a descending pathway inhibitory to the lordosis reflex arc at or below the lower brain stem.     

Identification of ligand recognition sites in heat-stable enterotoxin receptor, membrane-associated guanylyl cyclase C by site-directed mutational analysis.

Guanylyl cyclase C (STaR), a receptor protein for heat-stable enterotoxin (STa) elaborated by Escherichia coli, is associated with and spans the plasma membrane of mammalian intestinal cells. The extracellular domain functions in the binding of STa and the association of each domain to an oligomeric form. Two amino acid residues, Arg-136 and Asp-347, were identified as the residues binding to STa in the extracellular domain of pig STaR by site-directed mutagenesis and analysis of expression on 293T cells. Replacement of these residues by other amino acid residues resulted in the loss of binding of pig STaR to STa, and as a result, STa-induced guanylyl cyclase activity was eliminated. Furthermore, mutation in a region (from Asp-347 to Val-401) which is close to the transmembrane domain caused a significant reduction in both STa-binding activity and guanylyl cyclase catalytic activity. These results suggest that the region adjacent to the transmembrane domain plays an important role in facilitating a favorable conformation of STaR for STa binding.     

Cold-adaptation of human rotavirus

A human rotavirus strain was cold-adapted for possible future use as a live vaccine. The original strain was isolated in 1980 in primary cynomolgus monkey kidney cells and has a serotype I and subgroup II antigenicity. The virus was serially passaged in African green monkey kidney cells; it was cultivated at 37 degrees C at the first stage of passages, and the cultivation temperature was then shifted down stepwise by 3 degrees C per each 10 passages. Finally the virus was passaged 10 times at 25 degrees C (total passage number of 55). The virus formed small-size plaques with irregular shaped borders at 31 degrees C. Growth at 25 degrees C of the cold-adapted virus was higher than that of the original virus. There was no difference between the migration patterns of 11 dsRNA segments in polyacrylamide gel electrophoresis of the original and the cold-adapted viruses.     

Adjuvant Activity of 6-Amino-6-Deoxy-Muramyldipeptides and Their Acylamino Derivatives on the Induction of Delayed Hypersensitivity to Azobenzenearsonate-N-Acetyl-l-Tyrosine in Guinea Pigs

The 6-amino-6-deoxy-N-acetylmuramyldipeptides and their 6-acylamino derivatives were shown to be active as adjuvants on the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-l-tyrosine in guinea pigs. However, 6-acylamino-6-deoxy-N-(acyl)muramyldipeptides were inactive as adjuvants.     

Angiomyomatous hamartoma and associated stromal lesions in the right inguinal lymph node: a case report

Angiomyomatous hamartoma is a rare disease with a predisposition for the inguinal lymph nodes. A 51-year-old male patient visited a local hospital because of a right inguinal mass, measuring 3 x 4 cm in size, which was resected. The resected specimen showed irregularly distributed thick-walled vessels in the hilum, extending into the medulla and focally into the cortex of the node, eventually becoming more dispersed and associated with smooth muscle cells splaying into sclerotic stroma. These findings are compatible with an angiomyomatous hamartoma. Another tumor-like mass appeared shortly after the resection at the same location, but was not an angiomyomatous hamartoma, rather it was composed of edematous stromal tissue with proliferating smooth muscle cells. The stromal component included thick-walled blood vessels and lymphatics. Although it could not be determined whether these associated changes in the surrounding stroma are a cause or an effect of angiomyomatous hamartoma, they indicate the clinical difficulty in determining an appropriate area of resection and may provide clues to the pathogenesis of angiomyomatous hamartoma.     

Transplantation of labeled fetal spinal cord fragments into juvenile myelin-deficient rat spinal cord

Minced and triturated fragments from the spinal cord of normal rat fetuses (15-18 days gestation) labeled with the fluorescent dye fast blue (FB) were successfully transplanted into juvenile myelin-deficient rat spinal cord under direct observation. Clusters of myelinated fibers were found subsequently in the recipient spinal cord, and, by fluorescence microscopy, clusters of FB-labeled cells were found at corresponding sites. The results indicate that the surgical approach used is suitable for transplantation of tissue fragments into a defined region of juvenile rat spinal cord, that FB can be used to locate the transplanted cells subsequently, and that FB does not interfere with maturation of the donor glia or with myelin formation.