Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas

The PTEN/MMAC1 ( PTEN ) gene was identified as a tumor suppressor gene encoding a cytoplasmic protein that controls cellular processes. To investigate the potential role and the alteration of the PTEN gene in soft tissue sarcomas (STSs), we searched for homozygous deletion and promoter hypermethylation in a series of 48 STSs that was composed of malignant fibrous histiocytoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, including 2 cases with a mutation that we previously reported; differential polymerase chain reaction and methylation-specific polymerase chain reaction, respectively, were used for the analyses. Furthermore, to determine whether PTEN gene alterations are involved in the down-regulation of PTEN expression, we examined the expression of PTEN protein in 38 cases in which paraffin-embedded tissues were available for immunohistochemical analysis. In addition to our previous results showing that 2 (4%) of 51 cases had a PTEN mutation, promoter methylation was recognized in 6 (13%) of 48 cases, and homozygous deletion was detected in 1 (2%) of 48 cases in the current study. Of 6 cases with promoter methylation of PTEN gene, 5 were malignant peripheral nerve sheath tumor. Decreased expression of PTEN protein was recognized in 11 (29%) of 38 STS cases. Of 9 cases with PTEN alterations (6 cases with promoter methylation, 2 with mutation, and 1 with homozygous deletion), 3 (33%) showed decreased expression of PTEN protein. Furthermore, decreased expression of the PTEN gene showed a statistically significant correlation with high MIB-1 labeling index in 38 STS cases examined ( P = .0441). In conclusion, promoter methylation and homozygous deletion of the PTEN gene were found to be relatively rare events in cases of STS, as is mutation of the gene. Of 9 cases with a PTEN alteration, 3 (33%) showed a decrease in PTEN expression, indicating that PTEN gene alterations seem to play a minor role in the inactivation of PTEN in these tumors. Furthermore, although a further detailed analysis of a larger number of cases is still necessary, the present results suggest that PTEN expression may be a useful indicator of cell proliferation in patients with STS.     

Usefulness of skin prick test using bifurcated needle for the diagnosis of food allergy among infantile atopic dermatitis--1st report. In the case of egg allergy

OBJECTIVE: We investigated the usefulness of skin prick test (SPT) for the diagnosis of egg white (EW) allergy in infants with atopic dermatitis who showed negative to EW CAPRAST, and followed up the EW-CAPRAST in this study. SUBJECTS AND METHODS: Data of negative SPT using Bifurcated needle (BN) were analyzed from the data of 202 atopic dermatitis infants, who had received SPT from January in 2001 to April in 2005. From the negative SPT value (average and standard deviation) positive SPT value was obtained. Among 202 cases, 89 suspected-egg allergy infants with negative IgE CAPRAST against EW at the time of first visit were recruited to examine the usefulness of SPT. Positive conversion of EW-CAPRAST was checked in 78 cases (65: egg allergy+, 13: egg allergy(-)) who had been followed up in our outpatient clinic. RESULTS: Range of negative SPT control value (mean+2SD) using BF among infants could be set as less than 2 mm for wheal and/or 5 mm for erythema. Among 89 suspected-egg allergy infants with negative EW-CAPRAST, 72 infants (80.9%) were diagnosed as egg allergy by the combination of elimination and provocation test, interestingly 39 infants (54.2%) showed positive SPT results. In the follow up study of 78 negative EW-CAPRAST cases, 47 EW-CAPRAST out of 65 egg-allergy cases turned positive later infantile period (mean EW-CAPRAST: 9.6+/-16.7 Ua/ml at 9.9+/-5.6 months old). EW-CAPRAST of 7 cases in 13 non-egg allergies also turned positive in the follow up, however EW-CAPRAST titer was relatively lower compared to that of egg allergies (1.1+/-1.5 Ua/ml at 13.3+/-2.6 months old). CONCLUSIONS: We experienced fairly number of atopic infants with negative EW-CAPRAST at the first outpatient visit, who were later diagnosed as egg allergy. In about half of these cases, SPT egg-allergy infants, three quarter of EW-CAPRAST turned positive around 10 months old. EW-CAPRAST of atopic infants without egg allergy also turned transiently and slightly positive. In the conclusions, SPT seemed to be more useful than EW-CAPRAST for the diagnosis of egg allergy in early infantile period, however provocation test should be required for the definitive diagnosis in suspected-egg allergy infants without any proof of egg-sensitization.     

Association between childhood oral allergy syndrome and sensitization against four major pollens (Japanese cedar, orchard grass, short ragweed, alder)]

BACKGROUND/AIM: Although OAS (oral allergy syndrome) during childhood is believed to be rare, it seems to be increasing these days. METHODS, SUBJECTS: We here report 16 cases of childhood OAS, which were diagnosed, in our division. In addition to these reports, we investigated the rate of sensitization against four major pollens (Japanese cedar, orchard grass, short ragweed, alder) among 1067 pediatric patients with allergic diseases (median age: 4 years old) in our division. The sensitization was examined by IgE CAPRAST and above class 2 was judged as positive sensitization. RESULTS: OAS in childhood differs from that in adulthood in some ways. One is that childhood OAS does not always accompany with pollinosis. The most frequent allergen in our study was kiwi fruits followed by tomato, orange and melon among these patients. The sensitization rate against alder was equivalent as that against orchard grass and short ragweed, but less than that against Japanese cedar. CONCLUSION: Childhood OAS may have different mechanisms from adulthood OAS which almost always accompanies with pollinosis or latex allergy.     

Novel mutations in TNFRSF1A in patients with typical tumor necrosis factor receptor-associated periodic syndrome and with systemic lupus erythematosus in Japanese

Molecular defects of TNFRSF1A was investigated in members of a family presenting with typical phenotypes of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and in patients with the autoimmune disorders, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Genomic DNA from the members of a family with typical TRAPS, as well as from 100 patients with SLE, 100 patients with RA and 100 healthy individuals, was studied for mutations in exons 2, 3 and 4 of the TNFRSF1A gene. All individuals were Japanese. Three novel missense mutations were identified in the TNFRSF1A. The C70G mutation was identified in family members with typical TRAPS, which was the second case in eastern Asian population. In addition, the T61I and R104Q mutations were each identified in 2 of the 100 SLE patients. The T61I mutation was identified in one of the 100 healthy individuals. No mutations were identified in the 100 RA patients. Functional analysis revealed that PMA-induced shedding of TNFRSF1A from PBMCs was impaired in a patient carrying T61I. A larger scale of study will clarify whether these two mutations, T61I and R104Q, are associated with chronic inflammatory disorders, such as SLE, or not.     

A histologic study on "surgical landmarks" of the specialized conduction system, with particular reference to the adjacent structure

The conduction system in 29 cardiac specimens was histologically investigated as to the course and its surgical landmarks. The course varied individually, but was relatively inherent to the type of ventricular septal defect (VSD) (classification by Soto, et al.). The His bundle distributed as reported hitherto. Interesting features were noted in the relationship between the right bundle branch (RBB) and its adjacent papillary muscles. Our definition used for certain papillary muscles is merely to point the topographic site. The RBB ran beneath or slightly anterior to upper accessory papillary muscles (AcPMs) or uppermost AcPM, regardless of the type of perimembranous VSD. It ran posterior to the medial papillary muscle (MPM), with wider variation. In tetralogy of Fallot (TOF), it ran beneath or slightly anterior to the MPM. Relationships described above may be unitarily expressed as below, providing that Van Mierop's embryologic hypothesis on the conus defect anomaly (i.e.,: the uppermost AcPM being often morphologically interpreted as the MPM) is valid: -"The RBB runs beneath or slightly anterior to the upper(most) AcPM, regardless of the type of VSD. Such an arrangement was often observed in other anomalies too. The relationship between the RBB and upper or uppermost AcPM was modified by the attitude of the trabecula septomarginalis. Informations thus obtained have significantly lowered conduction disturbances in our experience.     

Differences in gut integrity following abdominal surgery according to the magnitude of the surgical stress

BACKGROUND: An increase in serum diamine oxidase (DAO) activity reflects intestinal mucosal damage. This was used to estimate the effect of surgical stress after elective abdominal surgery on gut integrity. METHODS: Patients with gastrointestinal tract cancers were placed in either group T (transthoracic esophagectomy for esophageal cancer, n = 9) or group L (laparotomy, n = 10). The serum DAO activity was measured pre-operatively, and on postoperative days 1, 3, and 8. RESULTS: Transthoracic esophagectomy was associated with a more extensive stress than the operations in group L, as measured by the intra-operative blood loss, the amount of blood transfused, and the operative time (P = 0.007, P = 0.0002, P = 0.0011, respectively). Following surgery, the serum DAO activity was decreased markedly in all patients in group T. In contrast, the activity was unchanged in group L (P = 0.04). CONCLUSIONS: The severity of the surgical insult plays a significant role in the decrease in serum DAO activity. These results suggest that surgical stress influences gut integrity following elective abdominal surgery.     

Oral styletted intubation under video control in a patient with a large mobile glottic tumour and a difficult airway

PURPOSE: With fibreoptic intubation, advancement of the endotracheal tube (ETT) through the glottis is blind. Thus, in patients with a laryngeal tumour, there is a potential for damage to the tumour. Previously, we proposed the use of a fibreoptic bronchoscope (FOB)-video camera system to permit visualization of tube passage. We used this technique successfully in a patient with a known difficult airway and a large glottic tumour. CLINICAL FEATURES: A 61-yr-old man with a known history of difficult laryngoscopic intubation underwent laryngeal microsurgery for recurrence of a glottic tumour. As preoperative indirect laryngoscopy revealed a large, mobile, and pedunculated glottic lesion obstructing the glottic opening, we planned a conventional awake fibreoptic intubation. Endoscopy showed that the tumour partially obstructed the glottis and the space between the tumour and the glottic opening was very narrow. To avoid damage to the tumour, we changed to an alternative fibreoptic intubation technique. The FOB attached to a video camera was passed nasally and a jaw thrust manoeuver was applied, providing an excellent view of the larynx. An anesthesiologist inserted the ETT with a curved stylet orally, and carefully advanced the tube tip into the space between the tumour and the glottic opening under video control. Absence of damage to the tumour and passage of the tube between the cords were confirmed visually. CONCLUSION: This alternative intubation technique, providing a view of the tube passage into the glottis, was a reasonable method to avoid potential damage to the glottic tumour by blind tube passage during conventional fibreoptic intubation.     

Ruptured aneurysm at an anastomotic artery extending from the vertebral artery to the posterior inferior cerebellar artery: a case report

A 51-year-old hypertensive man presented with subarachnoid haemorrhage. He had a past history of cerebellar infarction due to occlusion of the right posterior inferior cerebellar artery (PICA) 4 years earlier. Digital subtraction angiography showed a saccular aneurysm above an arterial loop extending from the vertebral artery to the distal part of the PICA, reminiscent of peripheral PICA branches. We performed aneurysmal neck clipping with excellent outcome. Aneurysms at anastomotic arteries are extremely rare and can result from increased haemodynamic stress. We report the first case of a ruptured aneurysm at an anastomotic artery in the posterior circulation territory.