Exo-rhodopsin: a novel rhodopsin expressed in the zebrafish pineal gland

The zebrafish, a useful animal model for genetic studies, has a photosensitive pineal gland, which has an endogenous circadian pacemaker entrained to environmental light-dark cycles [G.M. Cahill, Brain Res. 708 (1996) 177-181]. Although pinopsin has been found in the pineal glands of birds and reptiles, the molecular identity responsible for fish pineal photosensitivity remains unclear. This study reports identification of a novel opsin gene expressed in the zebrafish pineal gland. The deduced amino acid sequence is similar to, but not identical (74% identity) with that of canonical rhodopsin in the zebrafish retina. This novel rhodopsin is expressed in the majority of pineal cells but not in retinal cells, and hence named exo-rhodopsin after extra-ocular rhodopsin. This study first shows that two different rhodopsin genes are expressed in an individual animal each within a unique location. A phylogenetic analysis indicated that the exo-rhodopsin gene was produced by a duplication of the rhodopsin gene at an early stage in the ray-finned fish lineage. As expected, the exo-rhodopsin gene was found in the medakafish and European eel genomes, suggesting strongly that exo-rhodopsin is a pineal opsin common to teleosts. Identification of exo-rhodopsin in the zebrafish provides an opportunity for studying the role of pineal photoreceptive molecules by using genetic approaches.     

Total Esophagectomy versus Proximal Esophagectomy for Esophageal Cancer at the Cervicothoracic Junction

To investigate the adequate extent of esophagectomy and lymphadenectomy for an esophageal cancer localized at the cervicothoracic junction, the mortality and morbidity rates, survival rates, and patterns of recurrence were retrospectively analyzed in two groups—14 patients who underwent total esophagectomy with or without laryngectomy and 15 patients who underwent proximal esophagectomy with or without laryngectomy—at Kurume University Hospital from 1981 to 1996. Proximal esophagectomy with or without laryngectomy resulted in a lower hospital mortality rate and better overall survival for patients who underwent curative esophagectomy compared with total esophagectomy with or without laryngectomy. Multivariate analysis indicated that the extent of esophagectomy (total esophagectomy versus proximal esophagectomy) was not a prognostic factor. The incidence of recurrence was not different between the two groups. Lymph node metastasis or recurrence from such esophageal cancers was localized to the neck and upper mediastinum. For an esophageal cancer localized at the cervicothoracic junction, therefore, proximal esophagectomy with or without laryngectomy and with cervical and upper mediastinal lymphadenectomy could be better indicated for preselected patients.     

Effect of the consumption of ethanol on the microcirculation of the human optic nerve head in the acute phase

PURPOSE: The effect of the consumption of ethanol on the circulation of the optic nerve head (ONH) in the human eye in the acute phase and its mechanism were studied. METHODS: Eleven volunteers drank a bottle of beer (633 ml) with or without ethanol (29.5 g). Normalized blur (NB), a quantitative index of blood flow velocity, was measured in the temporal site of the ONH. NB, blood pressure (BP) and pulse rate (PR) were measured before, immediately after, and every 15 minutes for 90 minutes after consumption. Intraocular pressure (IOP) and plasma ethanol concentration were measured before, and 30 and 90 minutes after consumption. Genotyping of the aldehyde dehydrogenase (ALDH) 2 gene was also performed. RESULTS: NB in the ONH increased significantly from 15 to 45 minutes after consumption of ethanol and the maximum increase was 14% at 15 minutes. IOP was lowered at 90 minutes after consumption, but it was not significant. Mean BP was lowered significantly after 60 minutes. PR and ocular perfusion pressure did not change. A significant correlation was found between plasma ethanol concentration at 30 minutes and maximum NB. NB in the ALDH 2-deficient group was significantly larger from 15 to 45 minutes after consumption than in the proficient group. CONCLUSION: It appeared that the consumption of ethanol can increase the blood flow in the human ONH in the acute phase through decreased resistance in blood vessels induced by acetaldehyde, a metabolite of ethanol.     

Inhibition of cell growth in culture by quinones

Quinones were studied for their growth inhibitory effect on cultured malignant cells. HCT-15 cells derived from human colon carcinoma were used for these experiments. Quinones used were arbutin in the benzoquinone group, juglone and lawsone in the naphthaquinone group, alizarin, emodin, 1,8-dihydroxyanthraquinone, and anthraquinone in the anthraquinone group, and xanthone. Cultured cells were incubated with various concentrations of the quinones for four days in a 5% CO2 incubator, after which cell numbers were counted and significance of differences was analyzed by Student's t test. Anthraquinones and naphthaquinones used in these experiments were more effective than the monocyclic quinone. The 50% suppression dose was less than 12.5 micrograms/ml for them. The number of OH groups seemed to play an important role in the degree of the cell growth inhibition: anthraquinones with 2 or 3 OH groups were more effective than those with no OH group like, 9,10-dioxoanthracene and xanthone. In fact, anthraquinones with no OH group and xanthone were not significantly effective. Flow cytometric histograms revealed a specific pattern; that is, lawsone and juglone in the naphthaquinone group and alizarin and 1,8-dihydroxy-anthraquinone in the anthraquinone group blocked mainly the S phase, and emodin in the anthraquinone group blocked the G1 to S phase of the cell cycle.     

Purification and characterization of an anti-inflammatory factor (AIF) from bovine serum.

An anti-inflammatory factor (AIF) was highly purified from normal bovine serum. The purified AIF was a polysaccharide which was formed from a low molecular substance Pro-AIF by macromolecularization. AIF showed potent inhibitory activities against carrageenin induced edema in rats and PMN-leucocyte chemotaxis. It showed no inhibition in cutaneous reaction with serotonin, bradykinin or a mediator releaser compound 48/80. No inhibition was also observed in thermally induced pain, reversed passive Arthus reaction and adjuvant polyarthritis in rats. With these results, the role of AIF in inflammation was discussed.     

Oral challenge with cow's milk in patients with IgA nephropathy--estimation of serum antibodies to cow's milk protein]

The author investigated the serum levels of antibodies against casein, beta-lactoglobulin and lactalbumin before and after challenging with cow's milk in 35 patients with IgA nephropathy, 18 with primary glomerulonephritis except for IgA nephropathy (GN control) and 11 healthy volunteers (H control). Blood samples were obtained at fasting, and at 30, 60, 120 and 180 min after oral challenging with 400 ml of cow's milk. IgA and IgG anti-cow's milk proteins antibodies were analyzed by ELISA. The same challenge was tested after administration of the antiallergic agent, sodium cromoglycate (SCG), in 11 patients with IgA nephropathy and 4 H controls. Serum levels of IgA anti-casein, -beta-lactoglobulin and lactalbumin antibodies in patients with IgA nephropathy were significantly higher than in control groups before challenging. However, those of IgG antibodies were not. The percent change of antibody titer after challenging with cow's milk did not elevate in any group, except for the level of IgA anti-beta-lactoglobulin antibody at 60 min in IgA nephropathy. Cases in which challenging produced marked elevation above the M + 2SD of the levels found in H control were expressed as "positive". The number of "positive" cases was 16 (45.7%) with IgA nephropathy, but none with GN control. There was no significant correlations between "positive" and "negative" cases with IgA nephropathy in clinical manifestations. In 3 out of 4 "positive" patients with IgA nephropathy, the levels of IgA antibody were suppressed after administration of SCG. It is concluded that the serum levels of IgA antibodies against cow's milk proteins are significantly elevated in IgA nephropathy, and are inhibited in elevation after oral challenge with cow's milk by administration of an antiallergic agent in some patients with IgA nephropathy.     

Carcinoma of the cervix: Value of dynamic magnetic resonance imaging in assessing early stromal invasion

Background The purpose of this study was to assess the accuracy of contrast-enhanced magnetic resonance imaging (dynamic MR imaging) in the evaluation of preinvasive and early invasive cancer of the cervix. Methods Twenty-nine women with untreated squamous cell carcinoma of the cervix with either no stromal invasion or early stromal invasion underwent pretreatment MR imaging and dynamic MR imaging within 4 weeks of surgical evaluation. The images were evaluated for tumor detection and compared with results of histologic examination of the surgical specimens. Results The lesions in 17 cases with histologically proven stromal invasion of 4 mm or greater were detected with dynamic MR imaging, whereas lesions in only 8 of these cases were detected with T2 imaging. In 9 cases with stromal invasion between 4.0 mm and 5.0 mm, lesions were represented as early phase focal enhancement on dynamic MR images, but not detected on T2-weighted images. In the 12 cases with less than 4 mm stromal invasion, no lesions were visualized on either T2-weighted images or dynamic MR images, except in 1 case of glandular involvement without stromal invasion that appeared as enhancement on early-phase dynamic MR imaging. Conclusion Dynamic MR imaging detected more lesions of early stromal invasion in pretreatment imaging for cervical cancer than nonenhanced MR imaging.     

Association of Loss of Heterozygosity at the p53 Locus with Chemoresistance in Osteosarcomas

Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite insensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 ( p 53) and 13q14 ( Rb ) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p 53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p 53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss ( P <0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p 53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas.