Biomedical subjects

M Okumoto

Publications and source records attributed to M Okumoto.

At least 19 recordsLinked to original sources

PubMed1992

Genetic analysis of susceptibility to radiation-induced apoptosis of thymocytes in mice.

Genetic control of thymocyte susceptibility to radiation-induced apoptosis was investigated in BALB/cHeA, STS/A and five other strains of mice by counting pyknotic cells in a selected area of thymic cortex on histological specimens after whole-body X-irradiation. Number of dead cells increased almost linearly with doses (range 0.25-0.75 Gy) in BALB/cHeA and STS/A mice. However, dead cell counts in BALB/cHeA mice were more than twice those in STS/A mice at each dose. Of five other strains of mice, C57BL/6N and B10.BR mice exhibited a sensitive phenotype similar to BALB/cHeA mice, while C3H/HeAMsNrs and NFS/N mice showed a resistant phenotype similar to STS/A mice. A/J mice seemed to be rather resistant. A sex difference was not recognized in BALB/cHeA and STS/A mice. Resistance was dominant over susceptibility in the progenies of reciprocal crosses between the two strains, indicating an autosomal inheritance and no maternal effect. Segregation ratio of susceptible phenotype to resistant one in the backcrosses of female (BALB/cHeA x STS/A)F1 mice with male BALB/cHeA mice was not significantly different from 1:1 and all backcrosses of female (BALB/cHeA x STS/A)F1 mice with male STS/A mice exhibited a resistant phenotype. Results suggested that thymocyte susceptibility to radiation-induced apotosis is controlled by one major autosomal allele.

Animals↗

PubMed1991

Incomplete proviral genome of mouse mammary tumour virus is present on chromosome Y of NIH Swiss and some genetically related mouse strains.

An incomplete proviral genome of endogenous mammary tumour virus (MMTV) was found in DNA of several strains of mice. This MMTV-related sequence was assigned to the Y chromosome since it was clearly observed in male mice only. This MMTV provirus contained a sequence related to LTR (long terminal repeat), but not to gag-pol and env genes. NFS, NIH Swiss/S, STS/A, and DD/Tbr mice have this sequence but BALB/cHeA, SHN, SLN, C57BL/6NJcl, C3H/HeNJcl and CBA/JJcl mice are negative. In the strains containing this sequence, a DNA test for the sequence makes it possible to easily distinguish the DNAs of male or female mice.

Animals↗

PubMed1991

Strain difference in the susceptibility of thymocytes to radiation-induced apoptosis: in vitro study.

The susceptibility of thymocytes from STS/A to radiation-induced cell death was compared with that of thymocytes from BALB/cHeA. After in vitro exposure to 12 Gy X-ray, thymocytes were incubated at 37 degrees C for 8 h and then cell mortality was assessed by 0.02% erythrosin B exclusion. Cell death took place from 2 h in the incubation period, reaching a maximum at 6 h for both strains. The dose-effect on cell death at 4 h of incubation was examined after 1-24 Gy of X-irradiation. An increase in cell death was detectable even at 1 Gy in both strains. The number of dead cells in BALB/cHeA gradually increased with doses of more than 1 Gy, finally to a maximum (approximately 60%) in the dose range of 8-12 Gy, whereas the maximum cell death in STS/A was approximately 40%. The difference between the strains at maximum cell death was significant (P less than 0.005). The difference in the radiosensitivity of thymocytes between the two strains could not be attributed to a difference in the composition of their subpopulations because flow cytometric analysis based on the expression of CD4 and CD8 showed no intrinsic difference in the thymocyte subpopulations of BALB/cHeA and STS/A.

Animals↗

PubMed1991

The different activation of int genes in mammary carcinomas developed in three mouse strains harboring mouse mammary tumor viruses derived from DD/Tbr.

RNA expressions of common integration site (int) genes and several oncogenes were investigated in mammary carcinomas spontaneously developed in different three strains of mice; DD/Tbr, NIH Swiss and BALB/c which harbor DD-MMTV derived from DD/Tbr mouse. Latter two strains of mice were designated NIH/Mtv+ and BALB/Mtv+, respectively. An increased expression of int-1 (wnt-1) and int-2 genes was observed in 56% (9/16) and 50% (8/16) of mammary carcinomas of DD/Tbr mice, respectively. Either int-1 or int-2 RNAs were expressed in 81% (13/16) of the carcinomas of DD/Tbr mice. IN NIH/Mtv+ mice, activation of int-1 and int-2 was observed in 41% (7/17) and 24% (4/17) of mammary carcinomas, respectively. Either int-1 or int-2 RNAs were expressed in 47% (8/17) of the carcinomas examined in this strain. In BALB/Mtv+ mice, on the other hand, either int-1 or int-2 gene were transcribed into RNAs at low frequency (33%: 3/9). These results suggest that the frequency of activation of int genes in mammary carcinomas induced by the same DD-MMTV in three strains of mice is genetically defined characteristics of these strains, and that the involvement of int-1 and int-2 genes in virus-induced mammary carcinogenesis may be influenced by genetic properties of animals. The activation of int-1 and int-2 genes did not clearly correlate with an increase in the expression of oncogenes examined; H-ras, K-ras, N-ras, myc, raf, fgr, fms, erB, mos, and src genes.

Animals↗

PubMed1990

Genetic analysis of resistance to radiation lymphomagenesis with recombinant inbred strains of mice.

Induction of lymphomas by radiation in mice is controlled by genetic factors. We analyzed the genetic control of radiation lymphomagenesis using the CXS series of recombinant inbred strains derived from two progenitor strains: one highly susceptible to radiation induction of lymphoma [BALB/cHeA (C)] and one extremely resistant [STS/A (S)]. The best concordances between strain distribution patterns of genetic markers and resistance (or susceptibility) to radiation lymphomagenesis were observed in a region with the b and Ifa genes on chromosome 4. This indicates that one major locus controls the incidence of radiogenic lymphomas in mice. We designated this locus as the Lyr (lymphoma resistance) locus. Backcrosses of (CXS)F1 to the two progenitor strains showed an intermediate incidence of lymphomas between their parental mice and did not significantly differ from (CXS)F1 mice. This and previous observations that (CXS)F1 mice also showed an intermediate incidence, differing from both progenitor strains, indicate that more genes are involved in the resistance (or susceptibility) to lymphoma induced by irradiation.

Animals↗

PubMed1990

DNA rearrangements of the int region in spontaneous mouse mammary tumors of SHN/S and SLN/S mice.

SHN and SLN mice originating from the same Swiss albino stock are genetically very close to each other. The incidence and latent period of mammary tumor development in SHN mice were higher and shorter than those in SLN. To elucidate these differences in the behavior of mammary tumorigenesis, the frequency of insertion of mammary tumor viral genes within the int-1 and int-2 regions in spontaneous mammary tumors from their two substrains, SHN/S and SLN/S, were compared. The frequency of provirus integration into either int-1 or int-2 in DNAs from mammary tumors was 52% (11/21) in SHN/S and 45% (5/11) in SLN/S. The frequency of insertion within int-1 or int-2 could not account for the different susceptibilities of SHN/S and SLN/S.

Animals↗

PubMed1990

Lack of evidence for the involvement of type-C and type-B retroviruses in radiation leukemogenesis of NFS mice.

Southern blot analysis revealed no difference between the DNA from radiation-induced thymic lymphomas and DNA from normal NFS mice. The probes used in the Southern blot analyses used a murine leukemia virus (MuLV) env DNA probe (pXenv), which specifically hybridizes with xenotropic and recombinant viral env genes, and mouse mammary tumor virus (MMTV) DNA probes (MMTV gag-pol, MMTV env, and MMTV LTR). This suggests that radiation leukemogenesis was not associated with gross alteration of the organization of these retroviral genomes. In DNA from radiation-induced thymic lymphoma, there was no indication of gross rearrangement in the common integration site of MuLV, pim-1, or in the common integration sites of MMTV, int-1 and int-2. Dot blot analysis of RNA from radiation-induced thymic lymphomas and normal thymuses demonstrated that there was no substantial difference between them in the expression of retroviral sequences, pim-1, pvt-1, int-1, or int-2, although transcripts that could be hybridized to the retroviral sequences were slightly elevated in some radiation-induced thymic lymphomas. These results show that radiation leukemogenesis does not appear to involve the activation of endogenous type-C and type-B retroviruses.

Animals↗

PubMed1989

Effect of minimal antibiotic treatment on bacterial keratitis.

We studied the effect of minimal antibiotic therapy on pseudomonas keratitis in rabbits. Both corneas of 12 rabbits were infected with Pseudomonas aeruginosa and treated 24 and 48 h later with two drops of tobramycin or placebo. Corneal infections in antibiotic- and placebo-treated groups were comparable in appearance 24 and 48 h after inoculation. However, bacterial recovery was significantly less in eyes treated with minimal antibiotic therapy (p = 0.009). Although negative cultures were obtained from 11 of 12 antibiotic-treated eyes, bacteria could be recovered from eight of these culture negative corneas when corneas were ground and cultured. These studies suggest that minimal antibiotic therapy may impair bacterial recovery without completely eradicating live organisms.

Animals↗

PubMed1987

Use of recombinant interferon in HSV-1 recurrence in the rabbit.

The use of recombinant human interferon alpha subtype D (RIFN alpha D) was effective in reducing shedding of herpes simplex virus type-1 induced by iontophoresis of 6-hydroxydopamine and epinephrine. A post stimulation treatment schedule of RIFN alpha D, one drop four times a day was as effective as pretreatment, using the same dose regimen. The levels of interferon (IFN) present in the assay system are not sufficient to produce an antiviral effect. The levels of IFN required to suppress cell growth are substantially higher than the concentrations detected in the assay system.

Animals↗

PubMed1985

Endogenous type-C viral expression during lymphoma development in irradiated NFS mice.

The expression of the type-C retrovirus and the virus-related components in NFS mice were examined during preleukemic and leukemic phases after fractionated whole-body X irradiation. The NFS mice were highly susceptible to induction of thymoma by fractionated X irradiation. The leukemic tissues were negative for infectious type-C virus, as detected by both the XC-plaque test and mink S+ L- focus-inducing assays, but contained a substantially higher level of viral-specific RNA-dependent DNA polymerase activity and a major core protein p30 than the corresponding tissues from unirradiated age-control mice. In the preleukemic phase, the amount of p30-related antigen increased transiently in spleen. The leukemic cell lines established from radiation-induced lymphomas produced particulate entities with a buoyant density of about 1.15 g/ml. These virus-like particles lacked in vitro infectivity to mouse cells and mink lung cells and leukemogenicity in syngeneic mice. The p30-related antigens of these particles were immunologically similar to that of xenotropic virus derived from NZB mouse.

Animals↗

PubMed1979

Tretinoin and corneal epithelial wound healing.

The entire corneal epithelium of each of 16 rabbits was removed bilaterally. Tretinoin (vitamin A acid) ointment was applied topically twice daily to the eyes of one half of the experimental animals, and the ointment base alone was applied to the eyes of the other half (the controls). On days 1, 2, and 3 after the removal of the epithelium, the healing of the denuded corneas of the animals receiving tretinoin was significantly (P = .01, .01, and .05, respectively) more advanced than the healing of the corneas of the control animals.

Administration, Topical↗

PubMed1979

Combined amphotericin B and rifampin treatment of experimental Candida albicans keratitis.

In a model of experimental Candida albicans keratitis in rabbits, treatment with a combination of amphotericin B and rifampin was compared with treatment with amphotericin B alone. Both modes of therapy substantially reduced the number of organisms in the cornea below the number in untreated control corneas. In the group treated with combined therapy, there were significantly fewer organisms in the cornea after three days of therapy than in the group treated with amphotericin B alone. The results of this study indicate that the treatment of C albicans keratitis in rabbits with combined amphotericin B and rifampin is more effective than treatment with amphotericin B alone.

Amphotericin B↗

PubMed1979

Herpes simplex keratitis treatment with vitamin A.

We produced chronic experimental herpetic keratitis by dropping PH-strain herpes simplex virus on scarified rabbit corneas and then injecting the rabbits subconjunctivally with low doses of corticosteroid (namely, triamcinolone acetonide suspension). Vitamin-A-treated rabbits developed milder, more rapidly healing epithelial lesions than untreated rabbits. Whereas most of the untreated rabbits developed moderate or severe stromal disease, most of the vitamin-A-treated rabbits developed only mild stromal disease or none at all.

Animals↗

PubMed1979

Idoxuridine and bacterial corneal infection.

Corneas of 20 rabbits were treated with idoxuridine or a bland ointment before and after their inoculation with Staphylococcus aureus. The rabbit corneas treated with idoxuridine had a significantly more severe keratitis and yielded significantly greater numbers of S. aureus on culture than the rabbit corneas treated with the bland ointment.

Animals↗

PubMed1979

The microbial flora in extended-wear soft contact-lens wearers.

Of 857 cultures of material collected from the eyelids, conjunctivae, and contact lenses of 51 extended-wear soft-contact-lens wearers, 44 (5%) grew potential pathogens. The aphakic patients wearing contact lenses had fewer recoverable pathogens (24 of 295 or 8%) than a group of preoperative cataract patients (63 of 295 or 21%). On five occasions, positive cultures accompanied clinical symptoms, and on three occasions, repeated cultures grew the same potential pathogen.

Aphakia, Postcataract↗

PubMed1979

The effect of indoxole on the corneal immunologic response.

To study the effect of locally administered indoxole (with polysorbate 80) on the inflammatory and immunologic responses, we made unilateral intracorneal injections of rabbit eyes with bovine gamma globulin (BGG). The indoxole was injected subconjunctivally one day before, and 1, 2, 3, and 5 days after the BGG injection. The homolateral lymph nodes, uveal tracts, and corneas of rabbits killed on postinjection days 6 and 12 were tested for antibody-forming cells (AFC) by a modification of the Jerne plaque technique. On day 6 the indoxole-treated eyes were more inflamed and had a greater number of AFC in the tested tissues than the control eyes, but in neither of these respects was there any essential difference between the treated and control eyes on day 12. The possible mechanisms by which indoxole achieved its effect were explored.

Animals↗

PubMed1978

Treatment of herpes simplex keratitis with levamisole.

A model of chronic herpetic keratitis was developed by injecting rabbits subconjunctivally with a corticosteroid. A levamisole hydrochloride-treated group of these rabbits developed milder, more rapidly healing epithelial lesions than an untreated group. Although most of the untreated rabbits developed stromal disease, almost all of the lesions in the levamisole-treated animals were limited to the epithelium.

Animals↗

PubMed1978

The treatment of herpetic reinfection with levamisole.

The effect of levamisole on both clinical disease and virus recovery was studied in rabbits that were first infected with herpes simplex virus in one eye and then reinfected 14 days later by inoculation of the second eye. Reinfected rabbits treated with levamisole before reinfection developed significantly milder and smaller lesions than untreated controls. Virus recovery from the corneas was also less in the levamisole-treated animals than in the untreated controls.

Animals↗