Protein C deficiency in a family with thromboembolism and identified gene mutations.

Protein C is the central component of the major anti-thrombotic regulatory system, and individuals with hereditary protein C deficiency tend to have an increased risk of thromboembolism. During the last several years, mutations causing protein C deficiency have been identified. In the present study, we report familial cases with three nucleotide substitutions: One is a missense mutation Arg169Trp, which was previously reported. The other two are C-154T promoter polymorphism (rs1799808 on dbSNP database), the function of which is unknown and Ser99Ser synonymous polymorphism (rs5936). All three mutations were found in a 24-year-old patient with pulmonary thromboembolism and his 54-year-old father who also had pulmonary thromboembolism. C-154T promoter polymorphism (rs1799808 on dbSNP database) and Ser99Ser synonymous polymorphism (rs5936) were found in the patient's mother.

Obstructive sleep apnea-hypopnea syndrome patients with overweight and hypertension in a Japanese workplace.

The objective of this study was to determine the relationship between obstructive sleep apnea-hypopnea syndrome (OSAHS) and overweight combined with hypertension and to examine whether OSAHS in conjunction with overweight and hypertension is associated with daytime sleepiness. In a Japanese workplace of 28,636 employees, 368 men (19-62 yr old), who were anxious regarding their OSAHS symptoms, underwent home pulse oximetry. Of these, 153 men subsequently underwent all-night polysomnography (PSG), and OSAHS was diagnosed in 149. We next classified these 149 men into the following groups: A [Overweight (-)/Hypertension (-), n=41], B [Overweight (-)/Hypertension (+), n=15], C [Overweight (+)/Hypertension (-), n=46], and D [Overweight (+)/Hypertension (+), n=47]. The Epworth Sleepiness Scale (ESS) was used to evaluate daytime sleepiness and the apnea-hypopnea index (AHI) was used to evaluate the severity of OSAHS. The averages of the ESS score and the AHI were compared in each group. Both the average ESS scores and the percentage of ESS scores > or =11 were not significantly different among the groups. The average AHI of group D was the highest among all of the groups and that of group C was significantly higher than those of groups A and B. In all the groups, the OSAHS patients with overweight and hypertension in this study had the highest AHI. The level of daytime sleepiness evaluated by the ESS in this study was almost the same in the OSAHS patients regardless of the degree of overweight or hypertension. These observations suggest that it is necessary to positively recommend PSG to men who are suspected of having OSAHS with overweight and hypertension, even if they do not have daytime sleepiness.

[A case of cT0N2M0 small cell lung cancer with Lambert-Eaton myasthenic syndrome].

We encountered a very rare case of cT0N2M0 small cell lung cancer (SCLC) with Lambert-Eaton myasthenic syndrome (LEMS). A 69-year-old man with a complaint of muscle weakness was admitted to our hospital. Although his chest radiograph on admission showed no abnormal findings, CT scanning detected a mediastinal lymphadenopathy. Also, 2-[18F]-2-fluorodeoxy-D-glucose position emission tomography (FDG-PET) revealed increased accumulation in the same portion in the mediastinum. A diagnosis of LEMS was made from the distinctive electromyogram (EMG) findings (waning and waxing phenomenon in response to low-and high-frequency repetitive stimulation, respectively) in combination with the increased serum level of a P/Q-type anti-voltage-gated calcium channel (VGCC) antibody. Subsequent histopathological diagnosis by mediastinoscopic resection of a paraaortic lymph node was small cell carcinoma. No distant metastasis was detected by MRI of the brain, abdominal CT scan or an FDG-PET. Eight courses of chemotherapy (carboplatin + etoposide) with radiotherapy of the mediastinum (for a total dose of 45 Gy) was performed. A decreased serum level of P/Q-type anti-VGCC antibody titers followed by marked improvement of neurological dysfunction (muscle weakness, gait disturbance and scanning speech) and of an EMG finding (a loss of waning phenomenon) was observed. A close relationship between reduction of the antibody titers and improvement of neurological symptoms after the therapy was noticed. It was suggested that monitoring the level of a P/Q-type anti-VGCC antibody titer in the serum is important for evaluating the efficacy of chemotherapy for LEMS associated with SCLC.

[Recurrence of non-small cell lung cancer after successful treatment with gefitinib--report of three cases].

Gefitinib, a first epidermal growth factor receptor (EGFR) inhibitor has been reported to be effective in chemotherapy-resistant non-small cell lung cancer. Gefitinib was also reported, however, to produce severe adverse effects, such as interstitial lung disease. Thus, clinical evaluation of gefitinib is still controversial and further studies are needed. We present 3 cases of non-small cell lung cancer (stage IV adeno-carcinoma) that showed recurrence after successful gefitinib treatment. Symptoms of all patients ameliorated in a week after the therapy, and radiograph and laboratory data improved. However, all showed recurrence in 3 to 7 months. After recurrence, patient 1 was re-treated with gefitinib at the request of the patient. Patient 2 has been on gefitinib. Patient 3 was treated with gefitinib, which was later replaced by another chemotherapy agent. After recurrence, however, no effective response was obtained in any of the 3 cases. There have been several reports of good response to gefitinib therapy at the first time in patients with advanced non-small cell lung cancer, but few reports of recurrence in patients after successful therapy with this agent. This report is thought to be important for the clinical evaluation of gefitinib and useful in terms of information about the resistance of gefitinib.

[A case of bronchostenosis in the allograft after lung transplantation in pulmonary lymphangioleiomyomatosis].

Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease characterized by hamartomatous proliferation of abnormal smooth muscle cells in the lungs. Recently, severe LAM has been listed as an indicated disease for lung transplantation. A 34-yr-old woman with severe pulmonary cystic changes in a chest CT scan was diagnosed as having an isolated form of pulmonary LAM without genetic disorders. Despite intensive progesterone treatment, her pulmonary functions deteriorated rapidly. In January 2001, a left single-lung transplantation was performed from a cadaveric donor. The total operating time was 8 hours and 47 minutes. Total ischemic time was 5 hours and 59 minutes, which was within the permitted time limit. Except for right pneumothorax, the postoperative course was fairly good without any sign of rejection or infection in the allograft. For about two months after transplantation, bronchostenosis occurred in the left lower lobe bronchus, and necessitated a stent placement. During the following three months, stenosis of the bronchi in the anastomotic and peripheral sites occurred repeatedly, which also necessitated stent placement or balloon dilations on each occasion. Despite all the intensive treatment, the bronchostenosis of the peripheral sites still remains and improvement of her pulmonary functions has been poor. Moreover, a recent chest CT scan revealed a progression of the disease in the native lung. Consequently, we registered her as a candidate for transplantation of the right lung. Bronchostenosis should be kept in mind as a complication of lung transplantation.

Complete genomic sequence and comparative analysis of the tumorigenic poxvirus Yaba monkey tumor virus.

The Yatapoxvirus genus of poxviruses is comprised of Yaba monkey tumor virus (YMTV), Tanapox virus, and Yaba-like disease virus (YLDV), which all have the ability to infect primates, including humans. Unlike other poxviruses, YMTV induces formation of focalized histiocytomas upon infection. To gain a greater understanding of the Yatapoxvirus genus and the unique tumor formation properties of YMTV, we sequenced the 134,721-bp genome of YMTV. The genome of YMTV encodes at least 140 open reading frames, all of which are also found as orthologs in the closely related YLDV. However, 13 open reading frames found in YLDV are completely absent from YMTV. Common to both YLDV and YMTV are the unusually large noncoding regions between many open reading frames. To determine whether any of these noncoding regions might be functionally significant, we carried out a comparative analysis between the putative noncoding regions of YMTV and similar noncoding regions from other poxviruses. This approach identified three new gene poxvirus families, defined as orthologs of YMTV23.5L, YMTV28.5L, and YMTV120.5L, which are highly conserved in virtually all poxvirus species. Furthermore, the comparative analysis also revealed a 40-bp nucleotide sequence at approximately 14,700 bases from the left terminus that was 100% identical in the comparable intergene site within members of the Yatapoxvirus, Suipoxvirus, and Capripoxvirus genera and 95% conserved in the Leporipoxvirus genus. This conserved sequence was shown to function as a poxvirus late promoter element in transfected and infected cells, but other functions, such as an involvement in viral replication or packaging, cannot be excluded. Finally, we summarize the predicted immunomodulatory protein repertoire in the Yatapoxvirus genus as a whole.