Impact of Circular Stapler Size on the Risk of Anastomotic Complications in Patients With Left-sided Colorectal Cancer: A Propensity Score-matched Study.

Background/Aim: The present study examined the impact of circular stapler size on anastomotic complications, including leakage and stricture in patients undergoing double-stapling technique (DST) anastomosis for left-sided colon or rectal cancer. Patients and Methods: A total of 403 patients were enrolled in this study, with circular stapler sizes  of 25, 28, and 29 mm. Results: A small circular stapler (25 mm) was used in 170 cases (42.2%), and a medium-sized circular stapler (28/29 mm) was used in 233 cases (57.8%). After propensity score matching, there was no marked difference in the incidence of anastomotic leakage/stricture between the groups (13.9% vs. 10.9%, 3.0% vs. 1.0%, respectively). Conclusion: The size of the circular stapler was not associated with the incidence of anastomotic leakage or stricture in this cohort.

Association of CD8 + T cells expressing nivolumab-free PD-1 with clinical status in a patient with relapsed refractory classical Hodgkin lymphoma.

A 37-year-old man with refractory classical Hodgkin lymphoma (cHL) underwent PD-1 blockade therapy with nivolumab, which resulted in a partial response. However, treatment was discontinued due to immune-related adverse events (irAEs), including myasthenia gravis and myositis. Retreatment with nivolumab resulted in a complete metabolic response and hepatic irAE. Subsequently, nivolumab was administered at extended dosing intervals. Intermittent infusion of ten doses of nivolumab for a total dose of 2400 mg/body helped control the relapsed/refractory cHL over three years. During nivolumab treatment, disease progression and emergence of irAEs were associated with the proportion of CD8 + T cells expressing nivolumab-free PD-1 relative to the total number of CD8 + T cells. The findings in this nivolumab-sensitive patient highlight the clinical utility of monitoring immune cells expressing nivolumab-free PD-1 in patients with cHL who have been treated with nivolumab and have experienced irAEs.

DNA polymerase κ suppresses inflammation and inflammation-induced mutagenesis and carcinogenic potential in the colon of mice.

BACKGROUND: Chronic inflammation induces DNA damage and promotes cell proliferation, thereby increasing the risk of cancer. DNA polymerase κ (Pol κ), involved in translesion DNA synthesis, counteracts mutagenesis induced by inflammation in the colon of mice. In the present study, we examined whether Pol κ suppressed inflammation-induced colon tumorigenesis by treating inactivated Polk knock-in (Polk-/-) mice with dextran sulfate sodium (DSS), an inducer of colon inflammation. RESULTS: Male and female Polk-/- and Polk+/+ mice were administered 2% DSS in drinking water for six consecutive days, succeeded via a recovery period of 16 days, followed by 2% DSS for another two days. DSS treatment strongly induced colitis, and the severity of colitis was higher in Polk-/- mice than in Polk+/+ mice. The mice were sacrificed after 19 weeks from the initiation of the first DSS treatment and subjected to pathological examination and mutation analysis. DSS treatment induced colonic dysplasia, and the multiplicity of dysplasia was higher in Polk-/- mice than in Polk+/+mice. Some of the dysplasias in Polk-/- mice exhibited ß-catenin-stained nucleus and/or cytoplasm. Mutation frequencies in the gpt reporter gene were increased by DSS treatment in Polk-/- mice, and were higher than those in Polk+/+ mice. CONCLUSIONS: Pol κ suppresses inflammation and inflammation-induced dysplasia as well as inflammation-induced mutagenesis. The possible mechanisms by which Pol κ suppresses colitis- and colitis-induced dysplasia are discussed.

Potential use of EGFR-targeted molecular therapies for tumor suppressor CYLD-negative and poor prognosis oral squamous cell carcinoma with chemoresistance.

BACKGROUND: Tumor suppressor CYLD dysfunction by loss of its expression, triggers malignant transformation, especially drug resistance and tumor invasion/metastasis. Although loss of CYLD expression is significantly associated with poor prognosis in a large variety of tumors, no clinically-effective treatment for CYLD-negative cancer patients is available. METHODS: We focused on oral squamous cell carcinoma (OSCC), and sought to develop novel therapeutic agents for CYLD-negative cancer patients with poor prognosis. CYLD-knockdown OSCC cells by using CYLD-specific siRNA, were used to elucidate and determine the efficacy of novel drug candidates by evaluating cell viability and epithelial-mesenchymal transition (EMT)-like change. Therapeutic effects of candidate drug on cell line-derived xenograft (CDX) model and usefulness of CYLD as a novel biomarker using patient-derived xenograft (PDX) model were further investigated. RESULTS: CYLD-knockdown OSCC cells were resistant for all currently-available cytotoxic chemotherapeutic agents for OSCC, such as, cisplatin, 5-FU, carboplatin, docetaxel, and paclitaxel. By using comprehensive proteome analysis approach, we identified epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, played key roles in CYLD-knockdown OSCC cells. Indeed, cell survival rate in the cisplatin-resistant CYLD-knockdown OSCC cells was markedly inhibited by treatment with clinically available EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib. In addition, gefitinib was significantly effective for not only cell survival, but also EMT-like changes through inhibiting transforming growth factor-ß (TGF-ß) signaling in CYLD-knockdown OSCC cells. Thereby, overall survival of CYLD-knockdown CDX models was significantly prolonged by gefitinib treatment. Moreover, we found that CYLD expression was significantly associated with gefitinib response by using PDX models. CONCLUSIONS: Our results first revealed that EGFR-targeted molecular therapies, such as EGFR-TKIs, could have potential to be novel therapeutic agents for the CYLD-negative OSCC patients with poor prognosis.

Age-Stratified Seroprevalence of SARS-CoV-2 Antibodies before and during the Vaccination Era, Japan, February 2020-March 2022.

Japan has reported a relatively small number of COVID-19 cases. Because not all infected persons receive diagnostic tests for COVID-19, the reported number must be lower than the actual number of infections. We assessed SARS-CoV-2 seroprevalence by analyzing >60,000 samples collected in Japan (Tokyo Metropolitan Area and Hokkaido Prefecture) during February 2020-March 2022. The results showed that ≈3.8% of the population had become seropositive by January 2021. The seroprevalence increased with the administration of vaccinations; however, among the elderly, seroprevalence was not as high as the vaccination rate. Among children, who were not eligible for vaccination, infection was spread during the epidemic waves caused by the SARS-CoV-2 Delta and Omicron variants. Nevertheless, seroprevalence for unvaccinated children <5 years of age was as low as 10% as of March 2022. Our study underscores the low incidence of SARS-CoV-2 infection in Japan and the effects of vaccination on immunity at the population level.

Remote-Controlled Drone System through Eye Movements of Patients Who Need Long-Term Care: An Intermediary's Role.

The use of a remote-controlled drone system (RDS) by eye movements was studied to assist patients in psychiatric long-term care (PLTC) to allow them to view the environment outside the hospital, hoping that this will bring them some enjoyment. However, successfully applying this system requires human intermediaries in facilitating the interactions between patients and RDS operators. The aim of the study was to describe the role of nurses as intermediaries in the application of an RDS through eye movements of patients PLTC. This study employed the Intentional Observational Clinical Research Design. Data collection was performed in November 2021 at a psychiatric hospital with selected patients in PLTC. Seventeen patients took part in the indoor experiment, whereas 23 patients took part in the outdoor experiment. Fifteen of the 23 patients in the outdoor experiment were the same patients who took part in the indoor experiment. Most of the patients in the indoor and outdoor test arenas could successfully, delightfully, and safely fly the drone. This study demonstrated that RDS using just eye movements could increase the quality of life in older patients with psychiatric problems in PLTC. For the successful use of this drone system, nurse intermediaries assumed critically significant roles.

o-Aminoazotoluene, 7,12-dimethylbenz[a]anthracene, and N-ethyl-N-nitrosourea, which are mutagenic but not carcinogenic in the colon, rapidly induce colonic tumors in mice with dextran sulfate sodium-induced colitis.

BACKGROUND: Several rodent models with chemically induced colon cancer have been developed. Among these models, dextran sulfate sodium (DSS), a colitis inducer, combined with azoxymethane as a colon mutagenic carcinogen, is commonly used. We previously reported that although benzo [a] pyrene (BP) is mutagenic but not carcinogenic in the colon, it rapidly develops colon tumors at a high incidence/multiplicity after treatment with DSS. In the present study, we examined whether other colon-mutagenic non-carcinogens (CMNCs) induced colon tumors after treatment with DSS. RESULTS: o-Aminoazotoluene, 7,12-dimethylbenz[a]anthracene, and N-ethyl-N-nitrosourea were selected as CMNCs. Male CD2F1 mice were orally administered CMNC for 5 consecutive days. After a 9-day dose-free period, mice were treated with 4% DSS in drinking water for 1 week. Three months after DSS treatment, colon samples were collected for histopathology and ß-catenin immunohistochemistry analyses. All CMNCs in combination with DSS induced colonic adenocarcinomas at a high incidence/multiplicity in the distal and middle parts of the colon, coinciding with the location of colitis. Unlike in normal cells where ß-catenin is exclusively located on the cell membrane, in adenocarcinoma cells, it was translocated to both the nucleus and cytoplasm or only to cytoplasm. The translocation of ß-catenin is closely associated with colon carcinogenesis in rodents and humans. No colonic tumors or dysplastic lesions were found after exposure to either CMNC or DSS alone. CONCLUSION: We provided further evidence clearly showing that CMNCs can rapidly induce colonic tumors in mice with DSS-induced colitis, even if they are not colonic carcinogens.

Very high sensitivity of a rapid influenza diagnostic test in adults and elderly individuals within 48 hours of the onset of illness.

During influenza epidemics, Japanese clinicians routinely perform rapid influenza diagnostic tests (RIDTs) in the examination of patients who have an influenza-like illness, and patients with positive test results, including otherwise healthy individuals, are treated with anti-influenza drugs. However, it was recently reported that the sensitivity of RIDTs was extremely low in adult patients. We examined the sensitivity and specificity of an RIDT that is widely used in Japan, ImunoAce Flu (TAUNS, Shizuoka, Japan), in comparison to reverse transcriptase polymerase chain reaction (RT-PCR). The sensitivity and specificity of the ImunoAce Flu test were 97.1% (95%CI: 93.8-98.9) and 89.2% (95%CI: 84.1-93.1), respectively. The ImunoAce Flu test is designed to not only detect influenza A or B, but also to detect H1N1pdm09 with the use of an additional test kit (Linjudge FluA/pdm). Its sensitivity and specificity for A/H1N1pdm09 were 97.6% (95%CI: 87.4-99.9) and 92.6% (95%CI: 82.1-97.9), respectively. Thus, by consecutively testing patients with the ImunoAce Flu test followed by the Linjudge FluA/pdm test, we are able to diagnose whether a patient has A/H1N1pdm09 or A/H3N2 infection within a short time. The reliability of rapid test results seems to be much higher in Japan than in other countries, because approximately 90% of influenza patients are tested and treated within 48 hours after the onset of illness, when the influenza viral load in the upper respiratory tract is high. From the Japanese experience, RIDTs are sufficiently sensitive and highly useful, if patients are tested within 48 hours after the onset of illness.

Lenvatinib induces death of human hepatocellular carcinoma cells harboring an activated FGF signaling pathway through inhibition of FGFR-MAPK cascades.

Lenvatinib inhibits VEGF- and FGF-driven angiogenesis, and proliferation of tumor cells with activated FGF signaling pathways in preclinical models, and we previously demonstrated antitumor activity in human HCC xenograft tumor models. Here, we examined the inhibitory activity of lenvatinib against FGF-driven survival of human HCC cell lines. First, we conducted a histological analysis of FGF19-overexpressing Hep3B2.1-7 xenograft tumors collected from mice treated with lenvatinib. Second, we examined the effects of pharmacological inhibition on survival of cultured HCC cells with an activated FGF signaling pathway under nutrient-starved culture condition to mimic tumor microenvironments induced by angiogenesis inhibition. In the first analysis, area of histological focal necrosis was greater in Hep3B2.1-7 xenograft tumors with the lenvatinib treatment than that after the treatment with sorafenib, which does not inhibit FGFRs. Lenvatinib and E7090 (a selective FGFR1-3 inhibitor), but not sorafenib, induced death of Hep3B2.1-7, and another FGF19 overexpressing HuH-7 cells. Lenvatinib and E7090 decreased phosphorylation of downstream molecules of the FGF signaling pathway (such as FRS2, Erk, and p38 MAPK), and induced PARP cleavage, even under limited nutrients. PD0325901, MEK inhibitor, caused the same changes in HCC cells as those described above for lenvatinib and E7090. These results reveal that the FGF signaling pathway through MAPK cascades plays an important role in survival of HCC cell lines with an activated FGF signaling pathway under limited nutrients, and FGFR-MAPK cascades likely contribute to survival of HCC cells with an activated FGF signaling pathway under tumor microenvironments with limited nutrients, where tumor angiogenesis is inhibited.

Influenza vaccine showed a good preventive effect against influenza-associated hospitalization among elderly patients, during the 2016/17 season in Japan.

The 2016/17 influenza season in Japan was characterized by a predominance of influenza A (H3N2) activity; with H3N2 accounting for 85% of all detected influenza virus infections. We assessed the vaccine effectiveness (VE) of an inactivated quadrivalent influenza vaccine (IIV4) in adult patients, using a test-negative case-control design study based on the results of a rapid influenza diagnostic test (RIDT). Between November 2016 and March 2017, a total of 1048 adult patients were enrolled: including 363 RIDT positive for influenza A, 9 RIDT-positive for influenza B, and 676 RIDT-negative. During the 2016/17 season, the overall adjusted VE was 28.8% (95% confidence interval [CI]: 6.3-46%). The adjusted VE against influenza A was 27.4% (95%CI: 4.4-45%). The VE against influenza B could not be estimated because of the very low number of influenza B patients. Twenty-nine patients were hospitalized due to influenza-associated illness-during the present study, all of whom were infected with influenza A virus. The adjusted VE, determined using a case-control study, for preventing hospitalization for influenza A infection was 72.6% (95%CI: 30.7-89.1%). In addition, the VE for preventing hospitalization of influenza patients with comorbidities was 78.2% (95%CI: 41.1-92%). Our study showed that, during the 2016/17season, IIV4 was effective for preventing both the onset of influenza and influenza-associated hospitalization.

Histopathologic Characterization of Mifepristone-induced Ovarian Toxicity in Cynomolgus Monkeys.

Mifepristone, which is an orally active synthetic steroid with antiprogesterone activity, is known as an ovarian toxicant. Because the available data regarding the histopathologic characteristics of ovarian toxicity in nonhuman primates are limited, the present study was undertaken in order to investigate detailed histopathologic changes accompanying mifepristone-induced ovarian toxicity and its relationship to changes in menstrual cycle and circulating sex steroid hormone. Twenty mg/kg of mifepristone was orally administered daily to 4 cynomolgus monkeys for 2 months. Mifepristone inhibited the cyclic increases in circulating estradiol-17ß and progesterone levels with associated absence of menstruation. Histopathologically, the ovary in the treated animals showed follicular phase without changes in the percentage of atretic antral follicles, and reduced endometrial thickness was noted in the uterus. These changes indicated that a certain degree of antral follicle development had been retained in spite of the menstrual cycle having been arrested in mifepristone-treated animals. Our investigation suggested that it is important to perform detailed histopathologic examination of reproductive organs with precise knowledge of the characteristics of each menstrual stage to detect ovarian toxicity in nonhuman primates. Monitoring menstrual signs and circulating sex steroid hormone levels provides additional evidence for the investigation of the mechanism of ovarian toxicity.

Influenza vaccine effectiveness in adults based on the rapid influenza diagnostic test results, during the 2015/16 season.

We assessed the influenza vaccine effectiveness (VE) of an inactivated quadrivalent influenza vaccine in adult patients, in our test-negative case-control design study based on the results of a rapid influenza diagnostic test. During the 2015/16 season in Japan, influenza A(H1N1)pdm09 virus and influenza B virus were epidemic. The overall adjusted VE was 44% (95% confidence interval [CI]: 13.6%-63.7%). The adjusted VE was 52.9% (95%CI: 20%-72.3%) against any influenza virus among those < 65 years of age and -5% (95%CI: 136%-53.5%) among the elderly ≧ 65 years of age. The adjusted VE against influenza A was 49.1% (95%CI: 13.9%-69.9%). Although the VE was 55.5% (95%CI: 14.8%-76.8%) among those <65 years of age, it was only 15.3% (95%CI: 120%-67.4%) among the elderly ≧ 65 years of age. The adjusted VE against influenza B was 33.8% (95%CI: 25%-64.8%) among adult patients (≧16 years of age) and 46.8% (95%CI: 13%-75%) among those < 65 years of age, the VE against influenza B could not be estimated in those ≧65 years of age because of the low number of elderly patients with that virus.

[Effectiveness of Influenza Vaccine in Adults Using A Test-negative, Case-control Design ­2013/2014 and 2014/2015 Seasons­].

The influenza vaccine forms the basis of efforts to prevent the occurrence of influenza virus infection. However, vaccine effectiveness (VE) differs every season, which complicates efforts to combat the spread of infection. To develop a robust method to analyse variations in VE, we assessed VE among adult patients with influenza using a test-negative, case-control study design that evaluated vaccination records and the corresponding results of rapid influenza diagnostic tests during the 2013/14 and 2014/15 influenza seasons. During the 2013/14season, the adjusted VEs against influenza A and B viruses were 54.9% (95% confidence interval [CI] = 24.2% - 73.2%) and 56.6% (95% CI = 19.1% - 76.7%), respectively. In contrast, during the 2014/15season, the adjusted VE against the influenza A (H3N2), virus was -2% (95% CI = -66% - 37.5%). Moreover, only a few patients were infected with the influenza B virus, thus, the VE against influenza B could not be assessed. The low VE during the 2014/15 season could be attributed to antigenic drift in the circulating influenza A (H3N2) viruses and mutations in the egg-adapted vaccine strains. Estimation of the VE against the influenza virus using this test-negative, case-control study design was simple and easy, and this study design had a precision similar to that of a randomized control trial. Therefore, this study design could be employed to predict VE through out the influenza season and may be used as the basis of influenza prophylaxis.

Wif1 and Ifitm3 gene expression preferentially altered in the colon mucosa of benzo[a]pyrene pre-treated mice following exposure to dextran sulfate sodium.

Benzo[a]pyrene (BP) is highly mutagenic and yet does not lead to tumor development in the murine colon. We recently reported the generation of colonic tumors one week after treatment with BP followed by dextran sulfate sodium (DSS), a colitis-inducer. In this BP/DSS model, male CD2F1 mice were treated orally with BP at 125 mg/kg/day for 5 days, followed by 4% DSS in drinking water for one week. There has been no report so far on the molecular mechanisms involved in tumor development in this model. In the present study, we performed global gene expression analysis on the colonic mucosae obtained from BP-exposed mice one week after treatment with DSS and those treated with the vehicle, BP, or DSS alone. Global gene expression analysis revealed that there were 563 genes preferentially altered (≥2-fold vs vehicle group) in the colonic mucosae exposed to both BP and DSS. Furthermore, comparative gene expression analysis combined with Ingenuity Pathway Analysis™ identified 2 genes associated with Wnt/ß-catenin signaling pathway that were preferentially up-regulated (≥2-fold vs vehicle group) when BP and DSS were treated in combination in the distal part (site of predilection for tumor induction) of the colonic mucosae, especially in colonic tumors: WNT inhibitory factor 1 (Wif1; 14.6-fold increase) and interferon induced membrane protein 3 (Ifitm3; 5.7-fold increase). In colonic tumors, expression of Wif1 and Ifitm3 proteins were both confirmed by western blot analysis. These findings suggest that these genes are associated with rapid induction of colonic tumors in mice after exposure to BP/DSS, providing insights into the mechanisms of the BP/DSS short-term colon carcinogenesis.

Time course of the incidence/multiplicity and histopathological features of murine colonic dysplasia, adenoma and adenocarcinoma induced by benzo[a]pyrene and dextran sulfate sodium.

Benzo[a]pyrene (BP) is mutagenic but noncarcinogenic in the murine colon. Recently, we reported rapid induction of colonic tumors by treatment of CD2F1 mice with BP (125 mg/kg for 5 days) followed by a colitis inducer, dextran sulfate sodium (DSS) (4% in drinking water for 1 or 2 weeks). However, there are no reports on detailed time course and histopathological features of colonic proliferative lesions in this model. Here, we show the detailed time course of colonic dysplasia, adenoma and adenocarcinoma induced by treatment with BP, DSS, and a combination of the two (BP/DSS). In the colon of mice exposed to BP/DSS, 14.6 dysplastic foci per mouse were present one week after DSS treatment (week 4). The number of dysplastic foci decreased with time to 3.1 at week 9 and thereafter remained almost constant. At week 4, 1.5 adenocarcinomas were also observed, with a marked increase in numbers with time, reaching 29.3 at week 14. In contrast, the number of dysplastic foci induced by DSS alone showed a time course similar to that following BP/DSS treatment; however, only a few tumors appeared. Neither dysplastic foci nor neoplastic lesions were induced by BP only. In mice exposed to BP/DSS, ß-catenin was demonstrated immunohistochemically in the nucleus and/or cytoplasm of the tumor cells, and this translocation from the cell membrane was evident in subsets of dysplastic foci. In dysplastic foci induced by DSS alone, ß-catenin was absent in the nucleus/cytoplasm. These finding suggest that aberrant ß-catenin accumulation in dysplastic foci is associated with tumor progression in this BP/DSS model.

[Acute hepatitis C infection with prolonged intrahepatic cholestasis and remarkable progression of fibrosis mimicking fibrosing cholestatic hepatitis].

We report the case of a 71-year-old woman with acute hepatitis C infection and persistent viremia since 2 years. Her clinical course was characterized by general fatigue and prolonged jaundice with unusually high serum bilirubin levels. Liver histology showed lymphocyte infiltration, marked fibrosis, and severe cholestasis in the periportal zone, findings mimicking fibrosing cholestatic hepatitis (FCH). Fibrosing cholestatic hepatitis is a life-threatening form of recurrent hepatitis C infection that typically occurs in immunosuppressed patients. Here we report the rare case of an immunocompetent patient who developed this condition.

Cytomegalovirus enteritis in immunocompetent subjects: a case report and review of the literature.

Cytomegalovirus (CMV) enteritis (or colitis) is generally diagnosed in immunocompromised patients in association with human immunodeficiency virus infection as well as in recipients of solid organ or hematopoietic stem cell transplant. CMV enteritis has been reported only sporadically in immunocompetent individuals. We encountered a 76-year-old woman who developed CMV enteritis without any previously identified immunocompromised states. An extensive literature review of 33 cases of CMV enteritis or colitis diagnosed in immunocompetent individuals, including the present case, revealed that the median age of the patients was 68, the accompanying symptoms were diarrhea (76%), abdominal pain (52%), and hematochezia or melena (27%), and that the outcome was generally favorable, including resolution without any treatment in 24% of the patients. CMV enteritis should be recognized more widely as a disease entity not only in immunocompromised patients but also in immunocompetent individuals, especially in elderly populations.

Dielectric relaxation for studying molecular dynamics of pullulan in water.

We performed an experiment of broadband dielectric relaxation spectroscopy (BDS) to study the molecular dynamics of an aqueous pullulan solution as a function of pullulan concentration. The frequency range of the BDS experiment is 40 Hz to 50 GHz, and the solution temperature is set at T = 25.0 °C. Two relaxation processes originating from pullulan and water molecules are obtained in the megahertz and gigahertz regions, respectively. Additionally, the electrode polarization and the contribution of dc conductivity are also observed at lower frequencies. The relaxation process at a frequency higher than 10 GHz is associated with the primary process of water (h-process), and that at 100 MHz is attributed to the local chain motion of pullulan (m-process). Impurities in the aqueous solutions, which are practically disregarded in the analysis of polysaccharide solutions, affect the quality of the relaxation spectrum. Thus, the purification of pullulan sample is carried out by methanol precipitation from aqueous pullulan solution. This iterative purification reduces the contributions of electrode polarization and DC conductivity, which enables the clear observation of the relaxation of the m-process. It was found that the relaxation times of the m- and h-processes increase with pullulan concentration. The relaxation strength of the m-process shows increasing behavior with increasing pullulan concentration, whereas the relaxation strength of the h-process decreases with increasing pullulan concentration. It is suggested that the relaxation strength of the m-process is mainly determined by the magnitude of the dipole moment of solvent molecules. The relaxation process of water (h-process) is affected by the interactions of pullulan chains. The interdependence between the h- and m-processes is discussed with respect to the findings of recent dielectric relaxation studies on aqueous polymer solutions.

Granulomatous nephritis consistent with malakoplakia in a cynomolgus monkey.

Malakoplakia is a rare form of chronic granulomatous inflammation in mammals, and usually affects the urinary tract in humans. In this report, we present a case of granulomatous nephritis consistent with malakoplakia in a 4-year-old male cynomolgus monkey. Gross examination showed that the kidney was markedly enlarged and adhered to the surrounding organs. Histology showed that there was diffuse interstitial infiltration of histiocytes with abundant foamy eosinophilic cytoplasm resembling von Hansemann cells, PAS-positive granular cytoplasm and occasional PAS- and iron-positive intracellular small inclusion bodies. Electron microscopy showed that these histiocytes contained abundant lysosomes and phagolysosomes but no obvious Michaelis-Gutmann bodies. Based on these findings, a diagnosis of granulomatous nephritis consistent with early malakoplakia was made. This is the first report in a monkey of a renal lesion consistent with malakoplakia.

Spontaneous gingivitis related to hair penetration in rats.

Maxillary gingivae from male and female Crl:CD(SD) rats at 12, 16, 21, and 34 weeks of age were examined histologically. The incidence of gingivitis was approximately 40%, with no age or sex predilection, and was most frequent between the first and second molar. Lesions were characterized by acute focal neutrophilic infiltration into the gingival mucosa, occasionally with inflammatory exudate. In severe cases, inflammation extended to the periodontal ligament with abscess formation, and adjacent alveolar bone destruction/resorption. The most characteristic finding was the presence of hair shafts associated with the lesion, which was observed in approximately 80% of the rats with gingivitis. These findings suggest that molar gingivitis occurs in rats from an early age and persists thereafter, and that the main cause of gingivitis in rats is hair penetration into the gingiva. It would be prudent to keep these background lesions in mind as potential modifiers in toxicity studies.