Ocular surface changes after excimer laser phototherapeutic keratectomy

PURPOSE: To study the ocular surface disorder in patients with Avellino, granular, and lattice dystrophy, band keratopathy, and corneal leukoma before and after excimer laser phototherapeutic keratectomy. DESIGN: A prospective case-controlled study. PARTICIPANTS: A total of 45 eyes of 33 patients with superficial corneal opacities seen at Kobe Kaisei Hospital, Department of Ophthalmology, and 40 eyes of 20 normal control subjects were studied. INTERVENTION: The subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, tear film break up time (BUT), Schirmer test, tear film lipid layer interferometry, and conjunctival impression cytology. MAIN OUTCOME MEASURES: The patients and the control subjects were compared for prephototherapeutic keratectomy (PTK) tear function parameters, tear film lipid layer interferometry grade, goblet cell density, and conjunctival squamous metaplasia grade. Alterations of these parameters within 3 months after PTK were also looked for. RESULTS: The average pre-PTK corneal sensitivity and tear film break up time were lower in patients compared with control subjects before PTK. Tear film lipid layer interferometry grade and conjunctival squamous metaplasia grades were higher in the patients than the controls before PTK. All these parameters improved gradually and significantly after PTK. Goblet cell density was significantly lower in the patients compared with controls before PTK. Schirmer test results and goblet cell density did not show any significant alterations after PTK. CONCLUSIONS: Concurrent improvements in corneal sensitivity, tear film break up time, lipid layer interference grades, and conjunctival squamous metaplasia grades all point to the favorable effects of PTK on the ocular surface by improving the stability of the tear film and ocular surface health through attainment of a regular corneal surface and probably inducing qualitatively/quantitatively better mucin production by a healthier epithelium after PTK.     

Graded contusion model of the mouse spinal cord using a pneumatic impact device

OBJECTIVE: This study examined the effects of varying magnitudes of controlled spinal cord impact to the mouse spinal cord on neurological and histopathological variables to obtain a mouse model of spinal cord injury (SCI). METHODS: A laminectomy of the T10 vertebra was performed on anesthetized C57BL/6 mice. A pneumatic pressure-driven impact was performed on the spinal cord through the dura mater. Experimental groups were subdivided according to the energy of impact (0.25-mm-deep deformations): Group 1 (n = 5), impact velocity at 1 m/s; Group 2 (n = 5), impact velocity at 2 m/s; and Group 3 (n = 5), impact velocity at 3 m/s. Functional deficits over time were evaluated up to 28 days after SCI by testing hindlimb reflex and coordinated motor function. The extent of the lesions was analyzed histopathologically and quantified by a morphometric measurement. RESULTS: Mice of all groups exhibited profound functional deficits immediately after injury and subsequent gradual symptomatic recovery. The degrees of recovery were precisely correlated with the magnitudes of impact. The extent of resultant cord lesions was highly reproducible among animals, with little variance: means +/- standard deviation, 0.86 +/- 0.06/100 mm3 in Group 1; 2.4 +/- 0.28/100 mm3 in Group 2; and 11.0 +/- 1.0/100 mm3 in Group 3. CONCLUSION: Our results indicate that this model provides constant functional and histopathological lesions according to impact energy. This new mouse model of SCI opens a new avenue for studies investigating roles and/or effects of specific genes in the recovery process of SCI.     

Cleavage and polyadenylation specificity factor (CPSF)-derived peptides can induce HLA-A2-restricted and tumor-specific CTLs in the majority of gastrointestinal cancer patients

To identify CTL-directed antigens in gastrointestinal cancer, we have investigated antigens recognized by the HLA-A2-restricted CTL line established from T cells infiltrating into colon cancer and report herein cleavage and polyadenylation specificity factor (CPSF) as a potent antigen holding peptides capable of inducing CTLs. Five peptides at amino acid positions 250-258, 392-400, 534-542, 1296-1304 and 1359-1368 of CPSF, which were recognized by the CTL line, were found to have the ability to induce HLA-A2-restricted and tumor-specific CTLs in peripheral blood mononuclear cells of the majority (69%, 11/16) of gastrointestinal cancer patients with different HLA-A2 subtypes. Thus, these peptides might be appropriate molecules for use in the peptide-based specific immunotherapy of HLA-A2(+) patients with gastrointestinal cancers.     

Carney complex: report of a Japanese case associated with cutaneous superficial angiomyxomas,labial lentigines,and a pituitary adenoma

We report the case of a 12-year-old female patient who manifested multiple cutaneous angiomyxomas and labial pigmented lesions. Although the familial history was not confirmed in the present case, autosomal dominant inheritance has been reported to be involved in the pathogenesis of this condition. In addition to the cutaneous complications, magnetic resonance (MR) images revealed the presence of a pituitary adenoma, which provoked an elevation of serum growth hormone (GH) level. On the other hand, no significant symptoms such as cardiac myxoma, myxoid fibroadenoma of the breast, or adrenocortical complaints suggesting Cushing syndrome, were detected. In the Japanese literature, only a few cases of this disorder have been described in the form of brief reports. There have been only a few similar cases described in the dermatological field, except for one report diagnosed as Carney complex in 1990. Therefore, the present case seems to be the first Japanese case of typical Carney complex manifesting major clinical complications, including angiomyxomas, lentigines, and a pituitary adenoma, which induced endocrine overactivity.     

Estrogen blocks 3-nitropropionic acid-induced Ca2+i increase and cell damage in cultured rat cerebral endothelial cells

Systemic administration of 3-nitropropionic acid (3-NPA, a mycotoxin) induces brain damage accompanied by disturbance in the blood-brain barrier (BBB). Since the endothelial cells are important components of the BBB and the first target of a systemic intoxication, in the present study, the effect of 3-NPA on primary cultured rat brain endothelial cells (rBECs) was examined by studying intracellular Ca(2+) ([Ca(2+)](i)) response using imaging techniques with fura-2. rBECs were prepared using a method of Kis et al. [Eur. J. Pharmacol. 368 (1999) 35-42] and Szabo et al. [Neurobiology 5 (1997) 1-16]. Almost all cells were immunoreactive to antibody against the factor VIII-related antigen (von-Willebrand factor). They showed a typical dose-dependent increase of [Ca(2+)](i) in response to ATP or bradykinin. Low concentrations of 3-NPA (1.7 mM, 3.4 mM) caused no changes, and a medium concentration (6.8 mM) increased the [Ca(2+)](i) gradually and progressively, and the increase was reversed incompletely back to the resting level after washing. A high concentration (13.6 mM) increased the [Ca(2+)](i) irreversibly. These elevations of [Ca(2+)](i) were absent in a Ca(2+)-free medium. In endothelial cells treated with 17beta-estradiol (above 10(-5) M) or with a selective estrogen receptor modulator, tamoxifen (5 x 10(-7) M), no elevation of [Ca(2+)](i) was observed with 3-NPA treatment. The response to ATP was impaired after application of 3-NPA, but it was preserved by cotreatment with 17beta-estradiol or tamoxifen. An estrogen receptor antagonist ICI 182,780 inhibited these effects by 17beta-estradiol or tamoxifen. Lysosomal neutral red uptake and TUNEL experiments revealed the necrotic but not apoptotic cell death at least in this acute stage. Data indicate that a medium to high concentration of 3-NPA induces damage on rBECs as revealed by an accumulation of [Ca(2+)](i), but the damage was protected by cotreatment with 17beta-estradiol or tamoxifen, suggesting that estrogen may be protective for the brain vascular damage via estrogen receptor.     

High-tension electrical injury to the heart as assessed by radionuclide imaging

To evaluate cardiac complications associated with electrical injury, 7 patients with high-tension electrical injury (6,600 V alternating current) underwent 201Tl and 123I-metaiodobenzylguanidine (MIBG) imaging in addition to conventional electrocardiographic and echocardiographic assessments. Electrocardiography showed transient atrial fibrillation, second degree atrioventricular block, ST-segment depression, and sinus bradycardia in each patient. Echocardiography showed mild hypokinesis of the anterior wall in only 2 patients, but 201Tl and 123I-MIBG myocardial scintigraphy showed an abnormal scan image in 6/7 and 5/6 patients, respectively. Decreased radionuclide accumulation was seen primarily in areas extending from the anterior wall to the septum. Decreased radionuclide accumulation was smaller in extent and milder in degree in 123I. MIBG than in 201Tl imaging. These results suggest that even in patients without definite evidence of severe cardiac complications in conventional examinations, radionuclide imaging detects significant damage due to high-tension electrical injury, in which sympathetic nerve dysfunction might be milder than myocardial cell damage.     

The prognostic significance of RCAS1 expression in squamous cell carcinoma of the oesophagus.

Overexpression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) protects cancer cells from immune attack and might be related to poor prognosis in several cancers. We investigated the immunoreactivity of RCAS1 and its correlation with clinicopathological features in 95 patients who underwent surgical resection for oesophageal squamous cell carcinoma. Thirty-two of the 95 (33.7%) cases were strongly positive for RCAS1. RCAS1 showed significant correlations with age and stage grouping. Expression of RCAS1 was associated with shorter postoperative survival. Multivariate analysis indicated that RCAS1 positivity was an independent negative prognostic factor. Our study establishes RCAS1 as a novel prognostic marker for surgically resected oesophageal squamous cell carcinoma.     

Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents.

This study reports that a selective COX-2 inhibitor JTE-522inhibits both in vitro and in vivo growth of human lung cancer cells as a single agent. Furthermore, the adjunct use of JTE-522 is shown to significantly enhance treatment efficacy of conventional anticancer drugs not only in vitro but also in vivo without causing any noticeable side effects. Indeed, IC(50)s of various anticancer agents in vitro were reduced by up to 70%, whereas the combination therapy of JTE-522 with docetaxel and vinorelbine inhibited tumor growth in vivo by 65 and 55%, respectively. Taken together, these findings suggest that the use of a selective COX-2 inhibitor in the treatment of lung cancer may be promising, especially because of its enhancement of the treatment efficacy of conventional anticancer agents without compromising quality of life.