Tomoko Nakashima

Allelic loss and reduced expression of the ING3, a candidate tumor suppressor gene at 7q31, in human head and neck cancers

Loss of heterozygosity (LOH) has been frequently detected at chromosome 7q31 region in human head and neck squamous cell carcinomas (HNSCC) and many other cancers, suggesting the existence of tumor suppressor genes (TSG). We analysed LOH at 7q31 region in 49 HNSCC by using six polymorphic microsatellite markers and found allelic deletion in 48% (22/46) of the informative cases. We detected two preferentially deleted regions, one is around D7S643 and the other around D7S486. When we redefined the map of 7q31 region according to the contiguous sequences, a recently identified gene, ING3, was found in the proximity of D7S643. ING3 protein harbors the PHD domain highly homologous among ING family proteins, in which we previously found mutations in a related gene, ING1. As only one missense mutation of the ING3 gene was found in HNSCC, we examined the expression level. Reverse-transcription-PCR analysis demonstrated decreased or no expression of ING3 mRNA in 50% of primary tumors as compared with that of matched normal samples. Especially, about 63% of tongue and larynx tumors showed the decrease and a tendency of higher mortality was observed in cases with decreased ING3 expression. All these findings suggest a possibility that the ING3 gene functions as a TSG in a subset of HNSCC.

Hypophysis surgery with or without endoscopy

OBJECTIVE Hardys operation with microscope has long been the standard method for pituitary adenoma. But a new approach via the nasal cavity using an endoscope has been adopted recently. In this study, the postoperative outcome as well as the preoperative evaluation of endoscopic hypophysectomy and non-endoscopic one were compared at our faculty. METHOD We performed the non-endoscopic transnasal hypophysectomy on 18 patients and the endoscopic transnasal hypophysectomy on thirteen patients who had a pituitary lesions from February 1996 to October 1999. As to these patients the situations from preoperation through postoperation such as chief complaints, serum hormone level, final diagnosis, tumor size, as well as operating time or blood loss during the operation were discussed precisely. Then the merits and demerits of endoscopic hypophysectomy were discussed. RESULT Five PRL-producing adenoma, three GH-producing adenoma, nine non-functioning adenoma, and two ACTH or TSH-producing adenoma were included in this discussion as endoscopic group. The age of non-endoscopic group are from 23 to 73 (49.4 in average), and they include ten males and eight females. On the other hand three PRL-producing adenoma, two GH-producing adenoma, two non-functioning adenoma, and one Rathkes cyst were included in this discussion as endoscopic group. The age of endoscopic group are from 19 to 73 (49.1 in average), and they include seven males and six females. As to non-endopscopic group the blood loss during each operation is 568 ml and operating time is 256 min in average. For endoscopic group the blood loss is 296 ml and operating time is 234 min in average. CONCLUSION By microsurgery in the pituitary operation with endoscopy, the minimal invasive surgery becomes possible by reducing blood loss and shortening operating time. During the operation cooperation between neurosurgeon and ENT surgeon is indispensable in order to perform hypophysectomy smoothly. The development of optical better aids and operation instruments for endonasal hypophysectomy is desired in the future. The navigation system was more useful than X-ray fluoroscopy to obtain the detailed information.

Role of macrophage migration inhibitory factor in paranasal sinus mucocele.

Background Little is known about the immunologic aspects and the pathogenesis of the paranasal sinus mucocele. Methods The fluids of paranasal sinus mucoceles were obtained from 12 subjects. The concentration of macrophage migration inhibitory factor (MIF), interleukin 1β, tumor necrosis factor a, and regulated on activation normal T cell expressed and secreted (RANTES) were determined by enzyme-linked immunosorbent assay, and the levels of endotoxin were detected with kinetic Turbidimetric Assay. Results MIF and endotoxin were detected in the fluid of all samples, whereas interleukin-1β and RANTES were detected in 1 and 3 subjects out of 12 samples. Tumor necrosis factor a was not detected in any of the samples. A significant positive correlation between the levels of MIF and the period with symptoms such as pain, swelling of face, and visual disturbance was observed. Conclusion These findings suggest that MIF and endotoxin may play an important role in the pathogenesis of paranasal sinus mucocele. MIF may be an important factor causing the development and exacerbation of the disease.

Hearing immaturity found by ABR and its clinical impact on otoneurological evaluation

Auditory Brainstem Response (ABR) is the most reliable and most frequently used procedure to evaluate audiological conditions in early infancy. However, several reports have demonstrated that developmental change in the central nervous system may affect the results of ABR in audiological evaluations. We examined statistically the reliability of ABR for the diagnosis of profound deafness in early childhood according to our experience over the past 12 years of follow-up in our facility. Subjects included 371 children among 1,041 children who were admitted to Kanariya-Gakuen (institute for pre-school deaf children) from April 1985 to March 1997. These children were examined with ABR to determine their hearing levels. In five cases with an abnormal hearing threshold determined by ABR and other audiological tests, repeated examinations carried out during a 5- to 6-month follow-up period revealed that they had normal hearing. Three of these children had been diagnosed previously with mental retardation and the remaining two were infants < 5 months old. The specificity and sensitivity of ABR were calculated as 97.3% and 100%, respectively. The predictive value of a positive result was 94.7%. There remains the possibility of a false negative for such cases, although the rate seems to be very low (< 0.2%).

The Alteration of Penicillin-Binding Proteins (PBPs) in Drug-resistant Streptococcus pneumoniae Isolated from Acute Otitis Media

Streptococcus pneumoniae is the micro-organism most frequently isolated from acute otitis media (AOM). Recently, drug-resistant or insensitive strains have been prevalent among pneumococcal AOM cases and were reportedly associated with persistent or recurrent otitis media. The purpose of this study was to examine the alterations of penicillin-binding proteins (PBPs) in Streptococcus pneumoniae isolated from AOM. The PBP samples from 21 clinically isolated strains were examined by 14C-penicillin binding assay and also by adding CCL and CDTR as competitors of 14C-penicillin. Reduced signals in PBP1A and PBP2X/2A were typically observed with the penicillin-resistant Streptococcus pneumoniae samples, while widely different PBP profiles were obtained in each strain of penicillin-insensitive Streptococcus pneumoniae. The competitive binding assay with penicillin-insensitive strains revealed the reduced affinity of CCL to PBPs in comparison with that of CDTR. The results of the penicillin-binding assay were consistent with the results from minimal inhibitory concentration analysis, and its potential usefulness for the prediction of drug resistance was demonstrated.