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Biomedical subjects

M La Regina

Publications and source records attributed to M La Regina.

8 recordsLinked to original sources
PubMed1995

Age-related decrease of plasma testosterone in SAMP8 mice: replacement improves age-related impairment of learning and memory.

Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4-month-old P8 mice did not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels.

Aging↗
PubMed1994

Immunotherapy with keyhole limpet hemocyanin: efficacy and safety in the MB-49 intravesical murine bladder tumor model.

The antitumor activity and potential toxicity of a clinical-grade keyhole limpet hemocyanin preparation (KLH-Immune Activator; KLH-IA) were determined in the MB-49 intravesical murine bladder tumor model. Mice were immunized subcutaneously with KLH-IA two weeks prior to intravesical implantation of MB-49 tumor cells. Treatment consisted of intravesical KLH-IA (10 or 100 micrograms.) 1, 4, 7, 14 and 21 days after implantation. Control animals either were not immunized prior to tumor implantation and KLH-IA treatment, or were immunized with KLH-IA and treated with the vehicle. By 4 weeks after implantation tumor outgrowth in the treated groups was significantly decreased (p < 0.01, Fisher's Exact) relative to the control groups. Prior subcutaneous immunization was required to elicit antitumor activity of KLH-IA; thus, the mechanism of action is immune-mediated and not due to spurious interference with tumor implantation by intravesical instillations. Animals treated with a dissociated form of KLH exhibited decreased tumor outgrowth approaching, but not attaining, significance (p < 0.09, Fisher's Exact). A separate toxicity study in which KLH-IA was given subcutaneously (4 mg./kg.), intraperitoneally (40 mg./kg.), or intravesically (40 mg./kg.) disclosed no significant gross or histopathologic abnormalities except for mild-to-moderate papillary hyperplasia in all catheterized animals. These results establish the efficacy and safety of KLH-IA in mice and suggest that clinical trials for intravesical treatment of superficial bladder cancer may be warranted.

Adjuvants, Immunologic↗
PubMed1993

A region in the C-terminus of adenovirus 2/5 E1a protein is required for association with a cellular phosphoprotein and important for the negative modulation of T24-ras mediated transformation, tumorigenesis and metastasis.

We have examined a series of small deletion mutants within exon 2 of the adenovirus 2/5 E1A oncogene product, the 243R protein, for immortalization, ras cooperative transformation, tumorigenesis and metastasis. Compared with wild-type 243R, various deletion mutants located between residues 193 and 243 cooperated more efficiently with ras to induce large transformed foci of less adherent cells that were tumorigenic and metastatic. However, the greatest enhancement of transformation (comparable to that obtained with a deletion of the C-terminal 67 amino acids) was observed with a mutant carrying a deletion of residues 225-238. This mutant was also more defective in immortalization. These results suggest that this 14 amino acid region may contain a function that is important for immortalization and negative modulation of tumorigenesis and metastasis. To identify cellular proteins that may associate with the exon 2-coded region of E1A (C-terminal half) and modulate its transformation potential, we constructed a chimeric gene coding for the C-terminal 68 amino acids of E1a fused to bacterial glutathione-S-transferase (GST). This fusion protein was used to purify cellular proteins that bind to the C-terminal region of E1a. A 48 kDa cellular protein doublet (designated CtBP) was found to bind specifically to the GST-E1a C-terminal fusion protein as well as to bacterially expressed full-length E1a (243R) protein. It also co-immunoprecipitated specifically with E1a. Analysis of a panel of GST-E1a C-terminal mutant proteins indicates that residues 225-238 are required for the association of E1a and CtBP, suggesting a correlation between the association of CtBP and the immortalization and transformation modulating activities of exon 2. CtBP is a phosphoprotein and the level of phosphorylation of CtBP appears to be regulated during the cell cycle, suggesting that it may play an important role during cellular proliferation.

Adenovirus E1A Proteins↗
PubMed1992

Transmission of sialodacryoadenitis virus (SDAV) from infected rats to rats and mice through handling, close contact, and soiled bedding.

Thirty mice and six rats were exposed through handling, soiled bedding, or close contact to rats previously inoculated with sialodacryoadenitis virus (SDAV). All exposed rats developed coronaviral antibody without clinical signs or lesions of SDAV infection. Exposed mice had no lesions or clinical signs of coronavirus infection. Mice exposed by handling or by soiled bedding did not develop coronavirus antibody. Two of 10 mice exposed to SDAV-inoculated rats by close contact were coronavirus seropositive when tested 3 weeks postexposure. SDAV-inoculated rats and mice developed coronavirus lesions and antibody. These results suggest that rat-to-rat transmission of SDAV is likely via fomites or handling; however, rat-to-mouse transmission is unlikely when animals are housed and husbanded using modern techniques. Results also suggest that coronavirus antibody in mice is due to exposure to mouse coronavirus and not to rat coronaviruses.

Animal Husbandry↗
PubMed1989

Enhanced ras oncogene mediated cell transformation and tumorigenesis by adenovirus 2 mutants lacking the C-terminal region of E1a protein.

Mutants of adenovirus 2 E1a defective in coding for the C-terminal 61 or 67 amino acids of a 243 amino acid (243R) protein are defective in immortalization of primary baby rat kidney (BRK) cells. However, they cooperate with T24 ras in oncogenic transformation more efficiently than wt. BRK cells transformed by the E1a C-terminal mutants and T24 ras induce rapidly growing tumors in syngeneic rats and athymic mice whereas cells transformed by the wt 243R and ras oncogene are not tumorigenic in syngeneic rats and can only induce slowly growing tumors in athymic mice. Cells transformed by the E1a mutants and ras oncogene also induce rapid metastatic tumors whereas cells transformed by the wt 243R and T24 ras can not do so. The increased tumorigenic ability exhibited by the 243R mutants does not appear to be due to differential levels of expression of p21 ras. Our results suggest that the C-terminal region of the 243R protein may have a novel function in suppression of cell transformation, tumorigenesis and tumor progression.

Adenoviridae↗
PubMed1986

Francisella tularensis infection in captive, wild caught prairie dogs.

An adult, wild caught prairie dog was found dehydrated and ataxic, with severe diarrhea. Gross necropsy lesions consisted of scattered pinpoint white foci throughout the liver and spleen. A massive, purulent bronchopneumonia was found also. Direct fluorescent antibody tests and culture of spleen and liver samples confirmed a diagnosis of tularemia.

Animals↗
PubMed1980

Effects of antibiotic treatment on the occurrance of experimentally induced proliferative ileitis of hamsters.

The effects of three antibiotics on hamsters inoculated with a ground suspension of proliferative ilea were evaluated. All antibiotics were administered in the drinking water. Tetracycline hydrochloride (400 mg/liter drinking water) was most effective in reducing the number of hamsters which developed proliferative ileitis. Dimetridazole (500 mg/liter drinking water) was less effective than tetracycline. Neomycin (125 mg/liter drinking water or 10 mg/hamster) had no effect when compared to untreated inoculated control hamsters.

Animals↗