Biomedical subjects

Eiichi Sakai

Publications and source records attributed to Eiichi Sakai.

5 recordsLinked to original sources

PubMed2005

Rapid plasticity of binocular connections in developing monkey visual cortex (V1).

The basic sets of cortical connections are present at birth in the primate visual system. The maintenance and refinement of these innate connections are highly dependent on normal visual experience, and prolonged exposure to binocularly uncorrelated signals early in life severely disrupts the normal development of binocular functions. However, very little is known about how rapidly these changes in the functional organization of primate visual cortex emerge or what are the sequence and the nature of the abnormal neural events that occur immediately after experiencing binocular decorrelation. In this study, we investigated how brief periods of ocular misalignment (strabismus) at the height of the critical period alter the cortical circuits that support binocular vision. After only 3 days of optically imposed strabismus, there was a striking increase in the prevalence of V1 neurons that exhibited binocular suppression, i.e., binocular responses were weaker than monocular responses. However, the sensitivity of these neurons to interocular spatial phase disparity was not significantly altered. These contrasting results suggest that the first significant change in V1 caused by early binocular decorrelation is binocular suppression, and that this suppression originates at a site(s) beyond where binocular signals are initially combined.

Animals↗

PubMed2005

Comparison between in situ hybridization and real-time PCR technique as a means of detecting the integrated form of human papillomavirus 16 in cervical neoplasia.

Integration of the human papillomavirus (HPV) genome is thought to be one of the causes of cancer progression. However, there is controversy concerning the physical status of HPV 16 in premalignant cervical lesions, and there have been no reports on the concordance between detection of the integrated form of HPV16 by real-time PCR and by in situ hybridization. We investigated specimens of cervical intraepithelial neoplasia (CIN) and invasive carcinomas for the physical status of HPV 16 by real-time PCR and in situ hybridization. The presence of the integrated form was detected by both real-time PCR and in situ hybridization in zero of four cases of CIN1, three of six cases of CIN2, nine of 27 cases of CIN3, and two of six cases of invasive carcinomas. Integrated HPV 16 was present in some premalignant lesions but was not always present in carcinomas. The concordance rate between the two methods for the detection of the presence of the integrated form was 37 of 43 (86%) cases. Real-time PCR and in situ hybridization were found to be complementary and convenient techniques for determining the physical status of the HPV genome. We conclude that a combination of both methods is a more reliable means of assessing the physical status of the HPV genome in cervical neoplasia.

Carcinoma↗

PubMed2005

Directional bias of neurons in V1 and V2 of strabismic monkeys: temporal-to-nasal asymmetry?

PURPOSE: Strabismus that develops shortly after birth is known to cause temporal-to-nasal eye movement asymmetries under monocular viewing. The neural mechanisms underlying this deficit are not well understood. In the current study, the hypothesis that this eye movement anomaly reflects a similar asymmetry in the directional response properties of neurons in the early stages of cortical processing was examined. METHODS: Strabismus was simulated with optical methods in infant monkeys between 4 and 14 weeks of age. When the monkeys were mature, microelectrode recording experiments were conducted in the primary visual cortex (V1) and visual area 2 (V2). After the spatial frequency of sine wave-grating stimuli for each neuron was optimized, each neuron's responsiveness to 24 directions of stimulus movement was measured. The preferred direction and the strength of directional bias were determined by a vector summation method: RESULTS: There was not an overabundance of neurons in V1 or V2 of strabismic monkeys preferring the temporal-to-nasal direction of stimulus movement. However, the average directional bias was significantly reduced in these strabismic monkeys. Interocular suppression was highly prevalent, and this suppression was stronger and more common in neurons dominated by the ipsilateral eye. CONCLUSIONS: The results suggest that the eye movement asymmetries in strabismic subjects do not result from similar asymmetries in the directional properties of V1 or V2 neurons, but rather reflect impoverished cortical signals to the brain stem nuclei that control eye movements.

Animals↗

PubMed2003

Dihydropyrimidine dehydrogenase in normal and malignant endometrium: relationship with cell proliferation and thymidine phosphorylase.

Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine salvage enzyme responsible for degradation of thymine, which is produced from thymidine by thymidine phosphorylase (TP). Our purpose was to determine the relationship between DPD, cell proliferation and TP expression in human endometrium. We examined DPD gene expression using reverse transcription-polymerase chain reaction, DPD protein levels using enzyme-linked immunosorbent assay, and DPD protein localization using immunohistochemistry in 58 normal endometria and 28 endometrial cancers. DPD gene expression was then related to the proliferating cell nuclear antigen index and to TP gene expression. DPD gene expression, which was correlated with DPD protein level, was relatively stable throughout various menstrual phases but was significantly elevated in postmenopausal status. It was significantly lower in endometrial cancer than in normal endometrium. Localization analysis revealed that DPD protein was located primarily in epithelial cells, but was also present in stromal cells. DPD gene expression correlated inversely with the PCNA index. TP gene expression pattern contrasted with that of DPD in postmenopausal and malignant endometrium. A high ratio of TP to DPD gene expression was significantly more frequent in endometrial cancer than in normal endometrium in any menstrual phase. DPD may act cooperatively with TP to affect cell function by maintaining the pyrimidine nucleotide pool balance in normal and malignant endometrium.

Cell Division↗

PubMed2002

Thymidine kinase in epithelial ovarian cancer: relationship with the other pyrimidine pathway enzymes.

TK is a pyrimidine metabolic pathway enzyme involved in salvage DNA synthesis. What roles TK may play in epithelial ovarian cancer and the relationships between TK and the other pyrimidine pathway enzymes remain unclear. We examined TK1 gene expression by RT-PCR and related it to gene expression of TS, TP and DPD in 69 samples from epithelial ovarian cancer, 8 low-malignant-potential tumors, 16 benign ovarian tumors and 34 normal ovaries. Additionally, cytosolic and serum TK activities were determined by radioenzymatic assay. TK1 gene expression, the ratio of TK1 to TS gene expression, that of TK1 to TP and that of TK1 to DPD were significantly higher in epithelial ovarian cancer than in normal ovaries. In epithelial ovarian cancer, TK1 gene expression correlated with cytosolic and serum TK activities, TS and TP gene expression and the ratio of TP to DPD gene expression. Patients with high-TK1 gene expression had a significantly poorer survival than those with low TK1 gene expression. Combined analysis demonstrated that the relative risk of cancer death for tumors with high TK1, high TS and high TP gene expression was greater than that for tumors with high TK1 gene expression alone. TK1 gene expression together with TS, TP and DPD gene expression may play important roles in influencing the malignant behavior of epithelial ovarian cancer. Combination therapy including TK inhibitor is a possible therapeutic intervention in patients with epithelial ovarian cancer.

Aged↗