Bio

Academic Appointments


Professional Education


  • D.V.M., University of Tennessee, Veterinary Medicine (2004)
  • Ph.D., University of California, Davis, Ecology (1979)
  • M.A., University of California, Davis, Zoology (1975)
  • B.S., University of Hawaii, Manoa, Biology (1973)

Research & Scholarship

Current Research and Scholarly Interests


Molecular genetics of mammalian sex determination and sexual differentiation, effects of Helicobacter hepaticus, a mouse bacterial pathogen, on colon cancer models, small animal disease models.

Teaching

2013-14 Courses


Publications

Journal Articles


  • Evaluation of Zr-89-rituximab Tracer by Cerenkov Luminescence Imaging and Correlation with PET in a Humanized Transgenic Mouse Model to Image NHL MOLECULAR IMAGING AND BIOLOGY Natarajan, A., Habte, F., Liu, H., Sathirachinda, A., Hu, X., Cheng, Z., Nagamine, C. M., Gambhir, S. S. 2013; 15 (4): 468-475

    Abstract

    PURPOSE: This research aimed to study the use of Cerenkov luminescence imaging (CLI) for non-Hodgkin's lymphoma (NHL) using (89)Zr-rituximab positron emission tomography (PET) tracer with a humanized transgenic mouse model that expresses human CD20 and the correlation of CLI with PET. PROCEDURES: Zr-rituximab (2.6 MBq) was tail vein-injected into transgenic mice that express the human CD20 on their B cells (huCD20TM). One group (n?=?3) received 2 mg/kg pre-dose (blocking) of cold rituximab 2 h prior to tracer; a second group (n?=?3) had no pre-dose (non-blocking). CLI was performed using a cooled charge-coupled device optical imager. We also performed PET imaging and ex vivo studies in order to confirm the in vivo CLI results. At each time point (4, 24, 48, 72, and 96 h), two groups of mice were imaged in vivo and ex vivo with CLI and PET, and at 96 h, organs were measured by gamma counter. RESULTS: huCD20 transgenic mice injected with (89)Zr-rituximab demonstrated a high-contrast CLI image compared to mice blocked with a cold dose. At various time points of 4-96 h post-radiotracer injection, the in vivo CLI signal intensity showed specific uptake in the spleen where B cells reside and, hence, the huCD20 biomarker is present at very high levels. The time-activity curve of dose decay-corrected CLI intensity and percent injected dose per gram of tissue of PET uptake in the spleen were increased over the time period (4-96 h). At 96 h, the (89)Zr-rituximab uptake ratio (non-blocking vs blocking) counted (mean?±?standard deviation) for the spleen was 1.5?±?0.6 for CLI and 1.9?±?0.3 for PET. Furthermore, spleen uptake measurements (non-blocking and blocking of all time points) of CLI vs PET showed good correlation (R (2)?=?0.85 and slope?=?0.576), which also confirmed the corresponding correlations parameter value (R (2)?=?0.834 and slope?=?0.47) obtained for ex vivo measurements. CONCLUSIONS: CLI and PET of huCD20 transgenic mice injected with (89)Zr-rituximab demonstrated that the tracer was able to target huCD20-expressing B cells. The in vivo and ex vivo tracer uptake corresponding to the CLI radiance intensity from the spleen is in good agreement with PET. In this report, we have validated the use of CLI with PET for NHL imaging in huCD20TM.

    View details for DOI 10.1007/s11307-013-0624-0

    View details for Web of Science ID 000321972500014

    View details for PubMedID 23471750

  • Inhibition of Cellular Autophagy Deranges Dengue Virion Maturation JOURNAL OF VIROLOGY Mateo, R., Nagamine, C. M., Spagnolo, J., Mendez, E., Rahe, M., Gale, M., Yuan, J., Kirkegaard, K. 2013; 87 (3): 1312-1321

    Abstract

    Autophagy is an important component of the innate immune response, directly destroying many intracellular pathogens. However, some pathogens, including several RNA viruses, subvert the autophagy pathway, or components of the pathway, to facilitate their replication. In the present study, the effect of inhibiting autophagy on the growth of dengue virus was tested using a novel inhibitor, spautin-1 (specific and potent autophagy inhibitor 1). Inhibition of autophagy by spautin-1 generated heat-sensitive, noninfectious dengue virus particles, revealing a large effect of components of the autophagy pathway on viral maturation. A smaller effect on viral RNA accumulation was also observed. Conversely, stimulation of autophagy resulted in increased viral titers and pathogenicity in the mouse. We conclude that the presence of functional autophagy components facilitates viral RNA replication and, more importantly, is required for infectious dengue virus production. Pharmacological inhibition of host processes is an attractive antiviral strategy to avoid selection of treatment-resistant variants, and inhibitors of autophagy may prove to be valuable therapeutics against dengue virus infection and pathogenesis.

    View details for DOI 10.1128/JVI.02177-12

    View details for Web of Science ID 000313558100003

    View details for PubMedID 23175363

  • Maternal antibodies or nonproductive infections confound the need for rederivation. Journal of the American Association for Laboratory Animal Science Nagamine, C. M., Chen, L., Ho, W. Q., Felt, S. A. 2013; 52 (4): 495-498

    Abstract

    After rederivation of a mouse parvovirus (MPV)-contaminated transgenic mouse strain, serology and PCR testing of the surrogate dam showed it to be infected with mouse parvovirus strain 1 (MPV-1). The rederived pups (n = 3) also were MPVpositive, according to serology. Despite MPV seropositivity, fecal PCR tests of the pups were negative, as were serologic results from direct-contact sentinels. Only one rederived pup survived, and this male was bred successfully. None of its mates or progeny seroconverted to MPV. At 14.5 mo of age, the rederived male mouse was euthanized; tissues were collected and submitted for MPV testing; both serologic tests and PCR analysis of mesenteric lymph nodes were MPV-negative. One explanation for the rederived pups' MPV seropostivity is passive transfer of maternal antibodies or a nonproductive MPV infection. This case illustrates that although routine serological testing of surrogate mothers and pups is appropriate, any positive results should be further investigated by using transmissibility testing (fecal PCR or contact sentinels or both) prior to repeat rederivation.

    View details for PubMedID 23849450

  • Carbon Dioxide and Oxygen Levels in Disposable Individually Ventilated Cages after Removal from Mechanical Ventilation JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Nagamine, C. M., Long, C. T., McKeon, G. P., Felt, S. A. 2012; 51 (2): 155-161

    Abstract

    Disposable individually ventilated cages have lids that restrict air exchange when the cage is not mechanically ventilated. This design feature may cause intracage CO2 to increase and O2 to decrease (hypercapnic and hypoxic conditions, respectively) when the electrical supply to the ventilated rack fails, the ventilated rack malfunctions, cages are docked in the rack incorrectly, or cages are removed from the ventilated rack for extended periods of time. We investigated how quickly hypercapnic and hypoxic conditions developed within disposable individually ventilated cages after removal from mechanical ventilation and compared the data with nondisposable static cages, disposable static cages, and unventilated nondisposable individually ventilated cages. When disposable individually ventilated cages with 5 adult mice per cage were removed from mechanical ventilation, CO2 concentrations increased from less than 1% at 0 h to approximately 5% at 3 h and O2 levels dropped from more than 20% at 0 h to 11.7% at 6 h. The breathing pattern of the mice showed a prominent abdominal component (hyperventilation). Changes were similar for 4 adult mice per cage, reaching at least 5% CO2 at 4 h and 13.0% O2 at 6 h. For 3 or 2 mice per cage, values were 4.6% CO2 and 14.7% O2 and 3.04% CO2 and 17.1% O2, respectively, at 6 h. These results document that within disposable individually ventilated cages, a hypercapnic and hypoxic microenvironment develops within hours in the absence of mechanical ventilation.

    View details for Web of Science ID 000306772200003

    View details for PubMedID 22776114

  • Interleukin-16 deficiency suppresses the development of chronic rejection in murine cardiac transplantation model JOURNAL OF HEART AND LUNG TRANSPLANTATION Kimura, N., Itoh, S., Nakae, S., Axtell, R. C., Velotta, J. B., Bos, E. J., Merk, D. R., Gong, Y., Okamura, H., Nagamine, C. M., Adachi, H., Kornfeld, H., Robbins, R. C., Fischbein, M. P. 2011; 30 (12): 1409-1417

    Abstract

    IL-16 promotes the recruitment of various cells expressing CD4, a receptor for IL-16. The precise role of IL-16 in transplant rejection remains unknown; therefore, the present study investigated the contribution of IL-16 to the development of chronic rejection in heart transplants.C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into (1) IL-16-deficient (IL-16(-/-)) C57BL/6J or (b) wild type (WT) control recipients (MHC class II mismatch). Grafts were harvested at 52 days, parenchymal rejection was assessed by the ISHLT grading system, and CAV was examined morphometrically. Graft infiltrating cells were detected 10 and 52 days after transplantation. Intragraft cytokine and chemokine profiles were assessed. To confirm the role of IL-16 in CAV development, C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into C57BL/6J WT recipients treated with (1) anti-IL-16-neutralization monoclonal antibody or (b) control immunoglobulin G. Grafts were harvested at 52 days, and CAV was quantified morphometrically. Graft-infiltrating cells were examined histologically.Parenchymal rejection and CAV was significantly attenuated in donor hearts transplanted into IL-16(-/-) recipient mice compared with WT controls. Donor hearts transplanted into IL-16(-/-) recipients had a significant reduction in coronary artery luminal occlusion, intima-to-media ratio, and percentage of diseased vessels. CAV was associated with decreased donor organ inflammation, as well as donor organ cytokine (IL-1? and IL-6) and chemokine (MCP-1 and KC) protein expression. Intimal proliferation and inflammatory cell infiltration were significantly reduced in hearts transplanted into recipients treated with an IL-16-neutralization antibody.IL-16-deficiency reduced graft inflammatory cell recruitment, and allograft inflammatory cytokine and chemokine production. Therefore, IL-16 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection.

    View details for DOI 10.1016/j.healun.2011.08.017

    View details for Web of Science ID 000297385400016

    View details for PubMedID 22055099

  • Hematologic, Serologic, and Histologic Profile of Aged Siberian Hamsters (Phodopus sungorus) JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE McKeon, G. P., Nagamine, C. M., Ruby, N. F., Luong, R. H. 2011; 50 (3): 308-316

    Abstract

    Biologic samples from 18 (12 female, 6 male) Siberian hamsters (Phodopus sungorus) representing an aged colony (17 to 27 mo) were examined. Values for CBC and serum biochemical parameters were determined, and macroscopic and microscopic pathologic evaluations were performed. Blood urea nitrogen levels were significantly higher in male (54.2 ± 14 mg/dL) compared with female (35.3 ± 22 mg/dL) hamsters and correlated histologically with a higher incidence of chronic glomerulonephropathy in males (5 of 6 males; 0 of 12 females). All 18 hamsters had histologic evidence of follicular mite infestation. Half (6 of 12) of the female hamsters showed cystic rete ovarii. Other histologic findings included thymic or thyroid branchial cysts (3 of 18), focal enteritis (2 of 18), and single cases of hepatic hemangiosarcoma, renal adenoma, subcutaneous mast cell tumor, cutaneous sebaceous adenoma, cutaneous trichofolliculoma, squamous papilloma of the nonglandular stomach, epididymal cholesteatoma, pyometra, and pituitary craniopharyngeal cyst. This study is the first published report of hematologic and serum chemical values for any population of Siberian hamsters and the first published report showing a potential male predisposition for chronic progressive glomerulonephropathy and a potential female predisposition for cystic rete ovarii.

    View details for Web of Science ID 000299026400002

    View details for PubMedID 21640024

  • Helicobacter hepaticus promotes azoxymethane-initiated colon tumorigenesis in BALB/cJ-IL10-deficient mice. Int J Cancer Nagamine CM, Rogers AB, Fox JG, Schauer DB 2008; 122: 832-838
  • Proliferative pododermatitis (canker) with intralesional spirochetes in three horses. J Vet Diagn Invest Nagamine CM, Castro F, Buchanan B, Schumacher J, Craig L. 2005; 17: 269-271
  • Acute paraplegia in a young adult Long-Evans rat resulting from T-cell lymphoma. Contemp Topics Lab Anim Sci Nagamine CM, Jackson C, Beck KA, Marini RP, Fox JG, Nambiar PR 2005; 44: 53-56
  • Sex Reversal Caused by Mus musculus domesticus Y Chromosomes Linked to Variant Expression of the Testis-Determining Gene Sry Dev. Biol. Nagamine CM, Morohashi K, Carlisle C, Chang D 1999; 216: 182-194
  • Ovotestes in B6-XXSxr sex reversed mice. Dev. Biol. Nagamine CM, Capehart J., Carlisle C, Chang D 1998; 196: 24-32
  • Zfy2/1 fusion gene fails to replicate Zfy1 expression pattern in fetal gonads. Genomics Nagamine CM, Carlisle C 1997; 43: 397-398
  • Absence of correlation between Sry polymorphisms and XY sex reversal caused by M. m. domesticus Y Chromosome. Genomics Carlisle C, Winking H, Weichenhan D, Nagamine CM 1996; 33: 32-45
  • The dominant white spotting oncogene allele Kit(W-42J) exacerbates XY(DOM) sex reversal. Development Nagamine CM, Carlisle C 1996; 123: 3597-3605
  • Polymorphism of a CAG trinucleotide repeat within Sry correlates with B6.YDom sex reversal. Nature Genetics Coward P, Nagai K, Chen D, Thomas HD, Nagamine CM, Lau Y-FC 1994; 6: 245-250
  • Distribution of the molossinus allele of Sry, the testis-determining gene, in wild mice. Molecular Biology and Evolution Nagamine CM, Shiroishi T, Miyashita N, Tsuchiya K, Ikeda H, Takao N, Wu X-L, Jin M-L, Wang F-S, Kryukov AP, Akbar 1994; 11: 864-874
  • The testis-determining gene, SRY, exists in multiple copies in Old World rodents. Genetical Research Nagamine CM 1994; 64: 151-159
  • The musculus-type Y chromosome of the laboratory mouse is of Asian origin. Mammalian Genome Nagamine CM, Nishioka Y, Moriwaki K, Boursot P, Bonhomme F, Lau Y-FC 1992; 3: 84-91
  • Hst-3: an X-linked hybrid sterility gene. Genetical Research Guénet J-L, Nagamine CM, Simon-Chazottes D, Montagutelli X, Bonhomme F 1990; 56: 163-165
  • The two candidate testis-determining Y genes (Zfy-1, Zfy-2) are differentially expressed in fetal and adult mouse tissues. Genes Develop Nagamine CM, Chan K, Hake LE, Lau Y-FC 1990; 4: 63-74
  • Development and fertility of ovaries in the B6.YDom sex-reversed female mouse. Development Taketo-Hosotani T, Nishioka Y, Nagamine CM, Villalpando I, Merchant-Larios H 1989; 107: 95-105
  • Chromosome mapping and expression of a putative testis-determining gene in mouse. Science Nagamine CM, Chan K, Kozak CA, Lau Y-F 1989; 243: 80-83
  • A PCR artifact: generation of heteroduplexes. Am J Hum Genet Nagamine CM, Chan K, Lau Y-FC 1989; 45: 337-339
  • Morphological development of the gonad in tda-1 XY sex reversal. Differentiation Nagamine CM, Taketo T, Koo GC 1987; 33: 214-222
  • Linkage of the murine steroid sulfatase locus, Sts, to sex reversal, Sxr: a genetic and molecular analysis. Nucl Acid Res Nagamine CM, Michot J-L, Roberts C, Guénet J-L, Bishop CE 1987; 15: 9227-9238
  • Studies on the genetics of tda-1 XY sex reversal. Differentiation Nagamine CM, Taketo T, Koo GC 1987; 33: 223-231
  • Induction of female breeding characteristics by ovarian tissue implants in androgenic gland ablated male freshwater prawns Macrobrachium rosenbergii (de Man)(Decapoda, Palaemonidae). Int J Invert Reprod Devel Nagamine CM, Knight AW 1987; 11: 225-234
  • Masculinization of female crayfish, Procambarus clarki (Girard), by androgenic gland implantation. Int J Invert Reprod Devel Nagamine, C., Knight AW 1987; 11: 77-87
  • The use of specific DNA probes to analyze the Sxr mutation in the mouse. Development Bishop CE, Roberts C, Michot J-L, Nagamine CM, Winking H, Guénet J-L, Weith A 1987; 101 (S): 165-167
  • A radiobinding assay for H-Y antigen using monoclonal antibodies. Transplantation Nagamine C, Reidy J, Koo GC 1984; 37: 13-17
  • H-Y antigen in XO mice. Immunogenetics Koo G, Reidy J, Nagamine CM 1983; 18: 37-44
  • The development, maturation, and function of the sexually dimorphic characteristics of the Malaysian prawn, Macrobrachium rosenbergii (de Man)(Decapoda, Palaemonidae). Crustaceana Nagamine C, Knight AW 1980; 39: 141-152
  • Effects of androgenic gland ablation on the male primary and secondary sexual characteristics in the Malaysian prawn, Macrobrachium rosenbergii (de Man), with the first evidence of induced feminization in a nonhermaphroditic decapod. Gen Comp Endocrinol Nagamine C, Knight A, Maggenti A , Paxman G 1980; 41: 423-441
  • Masculinization of female Macrobrachium rosenbergii (de Man)(Decapoda, Palaemonidae) by androgenic gland implantation. Gen Comp Endocrinol Nagamine C, Knight A, Maggenti A, Paxman G 1980; 41: 442-457

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