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Objective Chlamydia pneumoniae and Mycoplasma pneumoniae are both common causes of atypical pneumonia. We conducted an annual national survey of Japanese children to screen them for C. pneumoniae infections during the M. pneumoniae epidemic season. Methods Nasopharyngeal swab specimens were collected from children aged 0–15 years with suspected acute lower respiratory tract infection due to atypical pathogens, at 85 medical facilities in Japan from June 2008 to March 2018. Specimens were tested for infection using real-time polymerase chain reaction assays. Results Of 5002 specimens tested, 1822 (36.5%) were positive for M. pneumoniae alone, 42 (0.8%) were positive for C. pneumoniae alone, and 20 (0.4%) were positive for both organisms. In children with C. pneumoniae infection, the median C. pneumoniae DNA copy number was higher in those with single infections than in those with M. pneumoniae coinfection (p = 0.08); however it did not differ significantly according to whether the children had received antibiotics prior to sample collection (p = 0.34). Conclusions The prevalence of C. pneumoniae infection was substantially lower than that of M. pneumoniae infection during the study period. The change in prevalence of C. pneumoniae was not influenced by that of M. pneumoniae. Children with single C. pneumoniae infection are likely to have had C. pneumoniae infection, while those with coinfection are likely to have been C. pneumoniae carriers.

BACKGROUND Infants ≤90 days old exhibit nonspecific signs of infection, even in cases of serious bacterial infection (SBI). METHODS This prospective study included infants aged ≤90 days hospitalized for fever from June 2017 to August 2019. Nasopharyngeal swabs were tested using multiplex real-time PCR, and 16S ribosomal RNA analysis of whole blood was performed to determine causative microorganisms. Data pertaining to inflammatory markers, maximum body temperature (BT), and respiratory symptoms of infants and their cohabiting families were collected at admission. RESULTS A total of 110 infants were enrolled (age range: 9-90 days), 17 (15.5%) of whom presented with SBIs. White blood cell count (WBC) and absolute neutrophil count (ANC) were significantly higher in patients with SBIs than in those without, although maximum BT did not significantly differ between the SBI and non-SBI groups (n=93). One or more viruses were detected in 82 (74.5%) infants. Viruses were detected more frequently in infants with respiratory symptoms than in those without respiratory (P=0.038), and patients with SBIs experienced significantly less respiratory symptoms than those with non-SBI (P=0.049). Moreover, viruses were more often detected in infants from cohabiting families with respiratory symptoms than in those whose family members did not exhibit respiratory symptoms (P=0.0018). CONCLUSION WBC, and ANC were significantly higher, and experienced respiratory symptoms were less in infants ≤90 days old with SBIs than in those without. Detection of microorganisms from nasopharyngeal by multiplex real-time PCR swabs could not be judged as SBI or non-SBI.

Although febrile neutropenia (FN) is one of the most common adverse events produced by chemotherapy, its microbiological etiology is determined for only 15% to 30% of cases.We investigated the rate of viremia with common DNA viruses in patients with FN.From June 2012 to April 2014, 72 blood samples from 24 patients receiving chemotherapy, who experienced FN episodes, were examined for the presence of herpes viruses and other DNA viruses. We used real-time polymerase chain reaction assays to detect herpes simplex virus type 1 and 2, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, human herpes virus types 6 and 7, BK virus and human parvovirus B19 (B19).Viruses were identified in 14 of 72 samples (19.4%). The detected etiological agents were BK virus (5 episodes), human herpes virus type 6 (4 episodes), B19 (4 episodes), Epstein-Barr virus (2 episodes), and cytomegalovirus (1 episode).Our results indicate that viral infections are common causes in patients with FN. Therefore, viruses may be responsible for FN in a large proportion of patients in whom a causative microorganism could not be identified, and this viral etiology may explain their poor response to antibiotic therapy.

This randomized phase II trial compared tegafur–uracil/leucovorin (UFT/LV) plus oxaliplatin (TEGAFOX) to UFT/LV as adjuvant chemotherapy for patients with high-risk stage II/III colorectal cancer. From 2010 to April 2015, 159 patients who underwent curative resection were randomly assigned to receive TEGAFOX (85 mg/m2 oxaliplatin on days 1 and 15, 300 mg/m2/day UFT and 75 mg/day LV on days 1–28, every 35 days for five cycles) or UFT/LV. The primary study endpoint was disease-free survival. The 3-year disease-free survival rate was 84.2% in the TEGAFOX arm, versus 62.1% for UFT/LV. The stratified hazard ratio for disease-free survival for TEGAFOX compared to UFT/LV was 0.338 (P < 0.01). The incidence of any-grade adverse events was significantly higher in the TEGAFOX arm (96.1%) than in the UFT/LV arm (76.6%; P < 0.01). The rates of any-grade neutropenia, thrombocytopenia, aspartate aminotransferase/alanine aminotransferase elevation, and peripheral sensory neuropathy were higher in the TEGAFOX group, whereas the incidence of grade ≥ 3 adverse events did not differ between the groups. TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer. UMIN ID: 000007696, date of registration: April 10, 2012

This randomized phase II trial compared tegafur-uracil/leucovorin (UFT/LV) plus oxaliplatin (TEGAFOX) to UFT/LV as adjuvant chemotherapy for patients with high-risk stage II/III colorectal cancer.From 2010 to April 2015, 159 patients who underwent curative resection were randomly assigned to receive TEGAFOX (85 mg/mThe 3-year disease-free survival rate was 84.2% in the TEGAFOX arm, versus 62.1% for UFT/LV. The stratified hazard ratio for disease-free survival for TEGAFOX compared to UFT/LV was 0.338 (P0.01). The incidence of any-grade adverse events was significantly higher in the TEGAFOX arm (96.1%) than in the UFT/LV arm (76.6%; P0.01). The rates of any-grade neutropenia, thrombocytopenia, aspartate aminotransferase/alanine aminotransferase elevation, and peripheral sensory neuropathy were higher in the TEGAFOX group, whereas the incidence of grade ≥ 3 adverse events did not differ between the groups.TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer.UMIN ID: 000007696, date of registration: April 10, 2012.

Introduction The features of pneumonia in children with neurologic impairment (NI) resemble those of healthcare-associated pneumonia is defined as pneumonia occurring in the community associated with healthcare risk factors. There are currently no guidelines for the treatment of pneumonia in children with NI. Here, we assessed whether the guidelines applicable for treating pneumonia in adults could be applied to children with NI. Methods Between 2008 and 2019, we enrolled children with NI who developed pneumonia and were treated in the pediatric ward of Kawasaki Medical School Hospital. We evaluated patient characteristics, the frequency of isolation of multidrug-resistant (MDR) pathogens, and clinical outcomes. Results MDR pathogens were more frequently isolated from patients receiving tube feeding (TF) and/or with tracheostomy than from patients without these risk factors. Other risk factors, including a history of antibiotic therapy and methicillin-resistant Staphylococcus aureus isolation, recent hospitalization, residence in a nursing home or extended care facility, and low-dose, long-term macrolide therapy, did not significantly affect the frequency of MDR pathogen isolation. In patients receiving TF and/or with tracheostomy, treatment success was achieved in all cases treated with broad-spectrum antibiotics and 72.2% of cases treated with non-broad-spectrum antibiotics (P = 0.007). Conversely, among patients without these risk factors, no such difference was observed. Conclusions Our findings indicate that the guideline to select antibiotics for treating pneumonia in children with NI should be simpler and more useful than the current guidelines for adult pneumonia, based on risk factor assessment for MDR pathogens.

We evaluated isolates obtained from children with Mycoplasma pneumoniae infection throughout Japan during 2008–2015. The highest prevalence of macrolide-resistant M. pneumoniae was 81.6% in 2012, followed by 59.3% in 2014 and 43.6% in 2015. The prevalence of macrolide-resistant M. pneumoniae among children in Japan has decreased.

We compared the antimicrobial susceptibility of Mycoplasma pneumoniae isolates from pediatric patients in Japan in 2011–2012 and 2015–2016, when epidemics occurred. The antimicrobial activity of macrolides and tetracyclines against M. pneumoniae infection tended to be restored in 2015–2016.

We compared the antimicrobial susceptibility of Mycoplasma pneumoniae isolates from pediatric patients in Japan in 2011–2012 and 2015–2016, when epidemics occurred. The antimicrobial activity of macrolides and tetracyclines against M. pneumoniae infection tended to be restored in 2015–2016., We compared the antimicrobial susceptibility of Mycoplasma pneumoniae isolates from pediatric patients in Japan in 2011–2012 and 2015–2016, when epidemics occurred. The antimicrobial activity of macrolides and tetracyclines against M. pneumoniae infection tended to be restored in 2015–2016. There was no change in the antimicrobial activity of quinolones against M. pneumoniae infection.

Ni–Al layered double hydroxide (Ni–Al LDH) and Co–Al LDH were prepared using a coprecipitation method. Ni–Al LDH and Co–Al LDH were found to remove Cr(VI) from aqueous solution through anion exchange of Cr 2 O 7 2− with Cl − intercalated in the interlayer of the LDHs. Ni–Al LDH and Co–Al LDH were both found to be superior to Mg–Al LDH for removal of Cr(VI). This excellent behavior is attributed to the buffering effect of Ni–Al LDH and Co–Al LDH that results in a lower amount of OH − in solution and allows Cr 2 O 7 2− to be more easily intercalated in the LDH interlayer. The Cr(VI) removal process was consistent with a Langmuir-type adsorption, indicating that the removal of Cr(VI) proceeded via chemical adsorption involving the anion exchange of Cr 2 O 7 2− with intercalated Cl − . The maximum adsorption and equilibrium adsorption constant values were 2.0 mmol g −1 and 2.4, respectively, for Ni–Al LDH, and 1.9 mmol g −1 and 1.5, respectively, for Co–Al LDH. The kinetics of Cr(VI) removal by Ni–Al LDH and Co–Al LDH were consistent with a pseudo-second-order reaction, and the rate-determining step for Cr(VI) removal was found to be the anion exchange. The apparent rate constants at 10, 30, and 60 °C for Ni–Al LDH were 2.2 × 10 −3 , 2.4 × 10 −3 , and 3.2 × 10 −3 g mmol −1 min −1 , respectively. The apparent rate constants at 10, 30, and 60 °C for Co–Al LDH were 1.2 × 10 −3 , 1.6 × 10 −3 , and 1.9 × 10 −3 g mmol −1 min −1 , respectively. The Arrhenius plot of the rate constants yielded apparent activation energies of 6.1 and 6.6 kJ mol −1 for Ni–Al LDH and Co–Al LDH, respectively.

Mg–Al layered double hydroxides (Mg–Al LDHs) doped with Fe 2+ adsorbed As(V) ( As O 4 3 − ) and Sb(V) ( Sb ( OH ) 6 − ) from an aqueous solution through anion exchange with Cl − intercalated in the LDH interlayer. Fe 2+ -doped Mg–Al LDH exhibited superior As(V) removal compared with Mg–Al LDH. The oxidation of Fe 2+ doped in the Mg–Al LDH host layer to Fe 3+ increased the positive layer charge of the LDH, thus increasing the anion-uptake capacity owing to stronger electrostatic attractive force between the positively charged layer and the anion. However, Fe 2+ -doped Mg–Al LDH was not superior to Mg–Al LDH in terms of Sb(V) removal. This was attributed to the preferential intercalation of OH − over Sb ( OH ) 6 − . The As(V) and Sb(V) removal by LDH followed Langmuir-type adsorption, which proceeded via a pseudo-first-order reaction. The equilibrium and kinetics studies confirm that the adsorption of As(V) and Sb(V) by Fe 2+ -doped Mg–Al LDH was the result of chemical adsorption, involving the anion exchange of As O 4 3 − and Sb ( OH ) 6 − with the intercalated Cl − .

Mg–Al layered double hydroxide (Mg–Al LDH) doped with Fe2+ was prepared by dropwise addition of a mixed solution of MgCl2, FeCl2, and AlCl3 to NaOH solution at a constant pH. The Fe2+-doped LDH was found to be able to remove Cr(VI) from an aqueous solution through the anion exchange of Cr 2 O 7 2 - with the intercalated Cl−, the production of Cr(OH)3, and the adsorption of Cr 2 O 7 2 - on the surface of the produced FeO(OH). The excellent performance of this LDH for Cr(VI) removal is caused by both the anion exchange properties of Mg–Al LDH and the reducing activity of the Fe2+ doped into the Mg–Al LDH. This process can be considered to occur through Langmuir-type adsorption, and the maximum adsorption amount and equilibrium adsorption constant are 12.5 mmol g−1 and 242.1, respectively.

Mg–Al layered double hydroxide (Mg–Al LDH) doped with Fe2+ was found to be superior to undoped Mg–Al LDH in the removal of Se(VI) from aqueous solutions. For both systems, Se(VI) as SeO42− was removed through anion exchange with intercalated Cl−. In the Fe2+-doped Mg–Al LDH, however, some of the Se(VI) was reduced to Se(IV) upon oxidation of Fe2+ to Fe3+ in the LDH host layer to produce SeO32−, which was also adsorbed by the Fe2+-doped Mg–Al LDH through anion exchange. The reduction of Se(VI) to Se(IV) is advantageous for Se(VI) removal by Fe2+-doped Mg–Al LDH due to the larger charge density of SeO32−. The Fe2+-doped Mg–Al LDH effectively removed Se(VI) from an aqueous solution because of the anion exchange properties of Mg–Al LDH and activity of Fe2+ as a reducing agent. Se(VI) removal occurs through Langmuir-type adsorption, where the maximum adsorption and equilibrium adsorption constant were 1.4 mmol g−1 and 1.6, respectively. Se(VI) removal is well expressed as a pseudo second-order reaction. The apparent rate constants at 10, 30, and 60 °C were 1.2 × 10−3, 1.5 × 10−3, and 2.2 × 10−3 g mmol−1 min−1, respectively, and the apparent activation energy was 10.0 kJ mol−1. The rate-determining step is chemical adsorption through anion exchange of SeO42− and SeO32− with intercalated Cl−.

The removal of Cr(VI) from aqueous solution by a Mg–Al layered double hydroxide (Mg–Al LDH) doped with Fe 2+ increased with time and temperature. Cr(VI) removal could not be described by first-order reaction kinetics, but it was well represented as a pseudo second-order reaction. The apparent rate constants at 10, 30, and 60 °C were 0.9 × 10 −3 , 1.2 × 10 −3 , and 2.2 × 10 −3 g mmol −1 min −1 , respectively, and the apparent activation energy was 14.5 kJ mol −1 . This value confirms that the rate-determining step for Cr(VI) removal is chemical adsorption involving the anion exchange of Cr 2 O 7 2− with intercalated Cl − and the adsorption of Cr 2 O 7 2− on the surface of the produced FeO(OH).

The importance of macrolide-resistant (MR) Mycoplasma pneumoniae has become much more apparent in the past decade. We investigated differences in the therapeutic efficacies of macrolides, minocycline, and tosufloxacin against MR M. pneumoniae . A total of 188 children with M. pneumoniae pneumonia confirmed by culture and PCR were analyzed. Of these, 150 patients had a strain with an MR gene and 134 had one with an A-to-G mutation at position 2063 of M. pneumoniae 23S rRNA domain V. Azithromycin ( n = 27), clarithromycin ( n = 23), tosufloxacin ( n = 62), or minocycline ( n = 38) was used for definitive treatment of patients with MR M. pneumoniae . Defervescence within 48 h after the initiation of antibiotic therapy was observed in 41% of the patients in the azithromycin group, 48% of those in the clarithromycin group, 69% of those in the tosufloxacin group, and 87% of those in the minocycline group. The average number of days of fever after the administration of antibiotic treatment was lower in the minocycline and tosufloxacin groups than in the macrolide groups. The decrease in the M. pneumoniae burden, as estimated by the number of DNA copies, after 48 to 96 h of treatment was more rapid in patients receiving minocycline ( P = 0.016) than in those receiving tosufloxacin ( P = 0.049), azithromycin ( P = 0.273), or clarithromycin ( P = 0.107). We found that the clinical and bacteriological efficacies of macrolides against MR M. pneumoniae pneumonia was low. Our results indicated that minocycline rather than tosufloxacin can be considered the first-choice drug for the treatment of M. pneumoniae pneumonia in children aged ≥8 years.

Isolated hypoaldosteronism is a rare and occasionally life-threatening cause of salt wasting in infancy. A 2-month-old Japanese boy of unrelated parents was examined for failure to thrive and poor weight gain. Laboratory findings were hyponatremia, hyperkalemia, high plasma renin and low aldosterone levels. Spot urine analysis by gas chromatography-mass spectrometry (GC-MS) showed that urinary excretion of corticosterone metabolites was elevated. Whereas excretion of 18-hydroxycortricosterone metabolites was within the normal range, excretion of aldosterone metabolites was undetectable. The patient was therefore suspected to have aldosterone synthase deficiency type 1. Sequence analysis of CYP11B2, the gene encoding aldosterone synthase (CYP11B2), showed that the patient was a compound heterozygote for c.168G>A, p.W56X in exon 1 and c.1149C>T, p.R384X in exon 7. p.W56X was inherited from his mother and p.R384X was from his father. Since both alleles contain nonsense mutations, a lack of CYP11B2 activity was speculated to cause his condition. To our knowledge, this is the first Japanese patient in which the molecular basis of aldosterone synthase deficiency type 1 has been clarified. This case also indicates that spot urinary steroid analysis is useful for diagnosis.

The efficacy of ramelteon, a sleep agent thought to induce natural sleep through its actions on the melatonin receptors 1 and 2, was evaluated during electroencephalography (EEG).We retrospectively analyzed the data from 862 EEG sessions in the electronic medical records of 523 patients (mean age, 8.9 ± 6.4 years; range, 0-38 years) who underwent EEGs in the Department of Pediatrics of Kawasaki Medical School Hospital. We compared the sleep induction statuses of patients not treated with hypnotics and those treated with the following hypnotics: ramelteon, triclofos sodium, and/or chloral hydrate.The success rates of sleep induction in the different groups were as follows: 440/513 (85.7%) in the hypnotic-free, 60/63 (95.2%) in the ramelteon, 209/217 (96.3%) in the triclofos sodium, 36/37 (97.3%) in the chloral hydrate, and 29/32 (90.6%) in the triclofos sodium plus chloral hydrate group. The incidence of adverse reactions was 0/63 (0%) in the ramelteon, 104/199 (52.2%) in the triclofos sodium, 12/31 (38.7%) in the chloral hydrate, and 20/30 (66.7%) in the triclofos sodium plus chloral hydrate group. The mean sleep latency in the ramelteon group was 22.3 ± 12.8 min (range, 5-60 min).Ramelteon induced sleep significantly more compared to the control group. The incidence of adverse reactions after treatment with ramelteon was significantly lower than after treatment with any of the other hypnotics. These results suggest that ramelteon is useful as a hypnotic during EEG.

鼠径ヘルニアの手術術式はtension free法が報告されてから，そのメッシュの素材・形状・配置する位置などの変遷を経て進化し続けている．最近Lichtenstein法のためのセルフグリップメッシュであるParietex ProGrip（Covidien）が発表された．ProGripの評価を行う目的で，当院での鼠径ヘルニア手術症例におけるProGrip，Mesh Plug，Direct Kugelの使用とその結果についてretrospectiveに比較検討した．手術時間はProGrip群39.9分，Mesh Plug群50.1分，Direct Kugel群55.3分とProGrip群で有意に短く，合併症については有意差を認めなかった．ProGripについての報告は本邦では初めてであり，その使用は手術時間の短縮が可能であり，鼠径ヘルニア手術において有用であると考えられた．

症例は65歳の男性で，上腹部不快感を主訴に近医で胃内視鏡検査を施行，胃体下部後壁に潰瘍が認められ生検で印環細胞癌と診断され当院紹介となった．CT，超音波にて肺・肝転移，リンパ節腫大認めず，早期胃癌の診断にて腹腔鏡下胃切除（D1＋β）を施行した．病理組織学的診断はpT1（m）pN0であった．術後CEA上昇を認め，腹部CTにて指摘された傍脊椎（Th1～L1）腫瘍に対する針生検にて転移性腺癌の診断となったため，化学療法を施行した．抗癌剤開始後1年5か月後にふらつき，感情鈍麻が出現，髄液検査にて髄膜癌腫症と診断され，その後急速に病状が悪化して死亡した．胃粘膜癌でも，腫瘍マーカーの上昇や脳神経症状を認めた場合には髄膜癌腫症を考慮して精査が必要であると考えられた．

症例は, 77歳の男性.排尿障害で泌尿器科を受診,骨盤内の腫瘤を指摘された.下腹部と右ソケイ部に腫瘤を触知し,両下肢の浮腫を認めた. CT, MRIでは,骨盤内を占拠する主腫瘍と,右ソケイ部に娘腫瘍を認めた.注腸検査では,直腸の圧排所見を認めた.術前の画像検査では,確定診断には至らなかったが,骨盤内悪性腫瘍を疑い手術を施行した.骨盤内を占拠する巨大な腫瘍を認め,直腸壁とは剥離不能で合併切除としハルトマン術式を施行した.腫瘤は嚢胞性で内壁にコーヒー残渣様の隆起を認めた.病理組織診断は,陳旧性血腫の診断であった. 30年前に,骨盤内の手術歴があり, 6年前に, 5cmの骨盤内の腫瘤を指摘されていた. 30年前の手術が血腫の契機で,ゆっくり骨盤内で巨大化し各種の症状を呈したと推測された.慢性拡張性血腫 (chronic expanding hemangioma) の診断であった.

症例は72歳の女性,嘔吐,食指不振とめまいを繰り返し受診し,血液検査で小球性低血色素性貧血と低タンパクを認めた.患者は椎間板ヘルニアで, 24年間のNSAIDの服用,座薬の使用歴があった.腹部レントゲン, CTで腸閉塞の所見を認め,小腸イレウスの診断で小腸造影を施行したところ,分節,球状に拡張した小腸を認めた.流出小腸液の潜血反応を調べたところ陽性であった.以上の結果より小腸イレウスと出血の診断で小腸部分切除術を行った.切除標本では小腸に多数の隔膜様の輪状狭窄を認め,狭窄が軽度の部位には浅い潰瘍を伴っていた.病理では狭窄部位での粘膜の薄化と粘膜筋板の肥厚と軽度の炎症細胞浸潤を認めた.本症例は,多発する回腸の隔膜様の輪状狭窄が原因であり, 1968年に岡部らが非特異性小腸潰瘍として報告した症例と本症例は病態が類似していたが,発症年齢や狭窄の形状所見,狭窄の原因となる潰瘍病変の有無などが異なっていた. NSAIDの長期使用歴があり, NSAIDの長期使用に起因し,小腸に稀に生じる“diaphragm-like disease”隔膜様狭窄症と考えられた.

Background We investigated whether impaired preoperative natural killer (NK) cell activity correlates with asynchronous distant metastasis after curative surgery for rectal cancers. In addition, we examined if preoperative chemoradiotherapy for rectal cancers impairs NK cell activity and contributes to the induction of distant metastasis. Study design Preoperative NK cell activity was examined in 174 rectal cancer patients. All patients were enrolled in this study and followed until asynchronous distant metastasis occurred. Results The mean NK activity in patients with stage IV disease (n = 20) was significantly lower than seen in other stages. There were no differences among stage I to stage III patients. In stage III patients, the cumulative distant metastasis-free rate after curative surgery was significantly lower in cases with NK activity of 25% or less than those with more than 25%. Preoperative chemoradiotherapy for stage I to III patients significantly impaired NK cell activity (n = 39), and the metastasis-positive ratio significantly increased among patients with stage II or stage III diseases (n = 30). Multivariate analysis indicated that dichotomized NK cell activity was a significant risk factor that is associated with distant metastasis as well as nodal involvement. Conclusions In primary rectal cancers, NK cell activity is not necessarily impaired in accordance with the disease progression. It is considered an important background factor for developing asynchronous distant metastases in stage III rectal cancers. Neoadjuvant chemoradiotherapy impaired NK cell activity in selected patients, suggesting the necessity of concurrent immunotherapy for better outcomes.

Recombination-activating gene (RAG) 1 and 2 are essential for the gene rearrangement of antigen receptors of both T and B cells. To investigate RAG gene expression in peripheral lymphoid organs other than the thymus and bone marrow, we established mice in which a green fluorescent protein (GFP) gene is knocked-in the RAG2 gene locus (RAG2-GFP mice). In the thymus and bone marrow of heterozygous RAG2-GFP mice, as expected, GFP expression was detected in the appropriate stages of developing T and B cells. Interestingly, only a fraction of Thy-1.2(+) cells in the Peyer's patch were found to be GFP(+) amongst the peripheral lymphoid organs. The GFP(+) cells expressed high levels of surface TCRbeta and CD3, suggesting mature T cells with rearranged TCRalphabeta. However, they showed activated/memory phenotypes, i.e. CD45RB(low), CD69(high), CD44(high) and CD62L(low), and belonged to a CD4(+)CD8(+) population expressing c-kit, IL-7R and pTalpha characteristic of immature developing lymphocytes. Moreover, RAG(+) Peyer's patch T cells seem to be of thymic origin as judged by their expression of CD8alphabeta. These results show that there exists a fraction of mature T cells expressing RAG genes in the Peyer's patch, implying a potential for a secondary rearrangement of TCR in extrathymic tissues.

It has been suggested that cytokines are associated with refractory Mycoplasma pneumoniae pneumonia, and steroid administration is reported to be effective in this situation. In order to elucidate the characteristics of refractory M. pneumoniae pneumonia, we analyzed five pediatric patients with refractory M. pneumoniae pneumonia, which was defined as showing prolonged fever and deterioration of clinical and radiological findings despite administration of appropriate antibiotics, compared with 15 pediatric patients with M. pneumoniae pneumonia who responded to treatment promptly (control group). Serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin (IL)-18 levels were significantly higher in the refractory group than in the control group at the initiation of corticosteroid use (LDH: 571 vs 292 IU/L, p = 0.0129; ALT: 25 vs 11 IU/L, p = 0.0143; AST: 41 vs 26 IU/L, p = 0.0404; IL-18: 579 vs 365 pg/mL, p = 0.0402). Significant correlation was found between serum values of IL-18 and LDH (r(2) = 0.504, p = 0.0433). The administration of corticosteroids to patients in the refractory group resulted in the rapid improvement of symptoms and decrease in serum LDH levels in all patients. A serum LDH level of ≥410 IU/L, which was calculated from receiver operating characteristic curve analysis, seemed to be an appropriate criterion for the initiation of steroid therapy. In conclusion, serum IL-18 and LDH levels can be used as parameters to determine which patients are candidates for corticosteroid therapy. In addition, serum LDH levels seem to be a useful marker for the evaluation of therapeutic efficacy in refractory M. pneumoniae pneumonia.

A novel lymphoid lineage, NK T cells, was recently found. The NK T cells are the major population in the periphery comprising 5% of splenic T cells and 40% of bone marrow T cells. They express a unique TCR composed of invariant Vα14Jα281 and Vβ8.2 together with NK receptor (NKRPI). Surprisingly, the invariant Vα14 + TCR is exclusively expressed on NK T cells but not on conventional T cells. As the selective decrease in Vα14 + NK T cell population in the periphery is tightly correlated with autoimmune disease development, Vα14 + NK T cells control development of autoimmune diseases. We also found that Vα14 TCR gene rearrangement and transcripts were detected at an early embryogenesis (d9.5) before the thymus formation. Therefore NK T cells are in the distinct category from conventional T cells. The target of NK T cells is found to be CD1 (class 1b, monomorphic class I MHC-like molecule) present on bone marrow–derived cells and is killed by Fas-FasL interaction or perforin-mediated mechanisms. These results indicate that NK T cells consist of an immunoregulatory system different from defense system in terms of homogeneous repertoire, extrathymic development in early stage of gestation, and their regulatory functional role. (J Allergy Clin Immunol 1996;98:S263-9)

Colon gas volume analysis using abdominal radiographs is an objective and reproducible method for evaluating functional bowel disorders. The aim of this study was to clarify the relevance of colon gas distribution and transit time in rectosigmoid cancer patients after surgery.Segmental colon gas volume score was calculated using plain abdominal radiography and evaluated in 40 patients who had undergone sphincter-saving resection. Segmental colonic transit time was analysed using radiopaque markers in the same patients.Transit times in the right colon (RCT) were 15.3 +/- 1.1 h and in the left colon (LCT) 11.2 +/- 1.1 h. Gas volume scores in the RCS and LCS were 1.10 +/- 0.13% and 1.06 +/- 0.14%, respectively. Neither colonic transit time nor colon gas volume score correlated with the operation methods for rectosigmoid colon cancer. A positive correlation of RCS and a negative correlation of LCS/RCS with ageing were noted in male patients but not in female patients. There was no correlation between RCT and RCS (r = 0.028); however, LCT correlated with LCS (r = 0.318, P0.05). The ratio of colonic transit time (LCT/RCT) was 0.84 +/- 0.10, while that of colon gas volume score (LCS/RCS) was 1.29 +/- 0.21. There was a significant correlation between LCT/RCT and LCS/RCS (r = 0.541, P0.001).Analysis of colon gas volume is useful for evaluating colonic transit time in rectosigmoid cancer patients after sphincter-saving surgery.

Background/Aims: To determine whether preoperative natural killer (NK) cell activity has any prognostic significance in colon cancer patients. Methods: The study population consisted of 140 patients with colon cancer. NK cell activity was determined within 2 weeks before surgery in 128 patients and at the time of diagnosis in the remaining 12 patients who either did not undergo surgery or who underwent palliative surgery only. Disease progression and postoperative prognosis were examined in relation to NK cell activity. Results: Decreases in NK cell activity did not necessarily correspond to tumor stage. In curatively operated stage I–III diseases, preoperative NK cell activity of 20% or less correlated with poor survival. Lower activity was also associated with metachronous distant metastases but not with local recurrences. In particular, more than half the stage III patients with attenuated NK cell activity developed metastases. Multivariate analysis indicated that attenuated NK cell activity was a significant parameter for predicting distant metastasis following curative surgery for colon cancer. Conclusion: Preoperative NK cell activity has a significant prognostic value in curatively operated colon cancer, particularly for the development of metachronous distant metastasis in stage III patients.

The immunological mechanisms that regulate abortion are largely unknown. Here, we found that a distinct subset of lymphocytes, Valpha14 NKT cells expressing an invariant antigen receptor encoded by Valpha14/Jalpha281 and Vbeta7 segments, accumulated in the decidua during pregnancy and provoked abortion upon stimulation with alpha-galactosylceramide (alpha-GalCer), a specific ligand for Valpha14 NKT cells. The alpha-GalCer-mediated abortion was not observed in Valpha14 NKT-, IFN-gamma-, tumor necrosis factor alpha-, or perforin-knock-out mice and appeared to be due to the degeneration of embryonic trophoblasts mediated by the activated Valpha14 NKT cells whose perforin-dependent killing and production of IFN-gamma and tumor necrosis factor alpha were essential. The possible role of the decidual Valpha14 NKT cells in the pathogenesis of abortion is discussed.

We have recently identified alpha-galactosylceramide (alpha-GalCer) as a specific ligand for an invariant Valpha14/Vbeta8.2 T cell receptor exclusively expressed on the majority of Valpha14 NKT cells, a novel subset of lymphocytes. Here, we report that alpha-GalCer selectively activates Valpha14 NKT cells resulting in prevention of tumor metastasis. The effector mechanisms of the ligand-activated Valpha14 NKT cells seem to be mediated by natural killer (NK)-like nonspecific cytotoxicity. Indeed, the cytotoxic index obtained by alpha-GalCer-activated Valpha14 NKT cells was reduced by the addition of cold target tumor cells or by treatment with concanamycin A, which inhibits activation and secretion of perforin, but not by mAbs against molecules involved in the NKT cell recognition and conventional cytotoxicity, such as CD1d, Vbeta8, NK1. 1, Ly49C, Fas, or Fas ligand. These results suggest that the ligand-activated Valpha14 NKT cells kill tumor cells directly through a CD1d/Valpha14 T cell receptor-independent, NK-like mechanism.

Natural killer T (NKT) lymphocytes express an invariant T cell antigen receptor (TCR) encoded by the Vα14 and Jα281 gene segments. A glycosylceramide-containing α-anomeric sugar with a longer fatty acyl chain (C26) and sphingosine base (C18) was identified as a ligand for this TCR. Glycosylceramide-mediated proliferative responses of Vα14 NKT cells were abrogated by treatment with chloroquine–concanamycin A or by monoclonal antibodies against CD1d/Vβ8, CD40/CD40L, or B7/CTLA-4/CD28, but not by interference with the function of a transporter-associated protein. Thus, this lymphocyte shares distinct recognition systems with either T or NK cells.

A lymphocyte subpopulation, the Vα14 natural killer T (NKT) cells, expresses both NK1.1 and a single invariant T cell receptor encoded by the Vα14 and Jα281 gene segments. Mice with a deletion of the Jα281 gene segment were found to exclusively lack this subpopulation. The Vα14 NKT cell–deficient mice could no longer mediate the interleukin-12 (IL-12)–induced rejection of tumors. Although the antitumor effect of IL-12 was thought to be mediated through natural killer cells and T cells, Vα14 NKT cells were found to be an essential target of IL-12, and they mediated their cytotoxicity by an NK-like effector mechanism after activation with IL-12.

NK1.1+ T [natural killer (NK) T] cells express an invariant T cell antigen receptor alpha chain (TCR alpha) encoded by V alpha 14 and J alpha 281 segments in association with a limited number of V betas, predominantly V beta 8.2. Expression of the invariant V alpha 14/J alpha 281, but not V alpha 1, TCR in transgenic mice lacking endogenous TCR alpha expression blocks the development of conventional T alpha beta cells and leads to the preferential development of V alpha 14 NK T cells, suggesting a prerequisite role of invariant V alpha 14 TCR in NK T cell development. In V beta 8.2 but not B beta 3 transgenic mice, two NK T cells with different CD3 epsilon expressions, CD3 epsilon(dim) and CD3 epsilon(high), can be identified. CD3 epsilon(high) NK T cells express surface V alpha 14/V beta 8 TCR, indicating a mature cell type, whereas CD3 epsilon(dim) NK T cells express V beta 8 without V alpha 14 TCR and no significant CD3 epsilon expression (CD3 epsilon(dim)) on the cell surface. However, the latter are positive for recombination activating gene (RAG-1 and RAG-2) mRNA, which are only expressed in the precursor or immature T cell lineage, and also possess CD3 epsilon mRNA in their cytoplasm, suggesting that CD3 epsilon(dim) NK T cells are the precursor of V alpha 14 NK T cells.