Atypical skin conditions of the neck and back as a dermal manifestation of anti-HMGCR antibody-positive myopathy.

BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is an idiopathic inflammatory myopathy (IIM). Though patients with IMNM were not considered to show skin rash, several reports have showed atypical skin conditions in patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive IMNM (HMGCR-IMNM). The incidence and phenotype of skin conditions in patients with HMGCR-IMNM are not fully known. RESULTS: Among the 100 IIM patients diagnosed from April 2015 through August 2022, 34 (34%) presented some form of skin condition, with 27 having typical skin rashes; this included 13 patients with dermatomyositis (DM), 8 with anti-synthetase syndrome (ASS), and 6 with IMNM. Meanwhile, 8 of 19 patients with HMGCR-IMNM (42%) presented atypical skin lesions, but no patients with other IIMs did (p < 0.001). Skin eruption with ash-like scales was observed in four HMGCR-IMNM patients, and non-scaly red patches and lumps in the other four patients; accordingly, their skin manifestations were considered as other dermal diseases except for IIM. However, skin and muscle biopsies revealed the atypical skin conditions of patients with HMGCR-IMNM to have the same pathological background, formed by Bcl-2-positive lymphocyte infiltrations. CONCLUSIONS: HMGCR-IMNM patients frequently have atypical skin conditions of the neck and back. Skin biopsy specimens from these lesions showed the same Bcl-2-positive lymphocytic infiltrations as muscle biopsy specimens regardless of the different gross dermal findings. Thus, such atypical skin conditions may be suggestive for HMGCR-IMNM.

Giant cell arteritis with myeloperoxidase anti-neutrophil cytoplasmic antibody seropositivity in a patient with systemic sclerosis.

To the best of our knowledge, systemic sclerosis with overlapping characteristics of both microscopic polyangiitis and giant cell arteritis (i.e. microscopic polyangiitis involving the superficial temporal artery or giant cell arteritis with myeloperoxidase anti-neutrophil cytoplasmic antibody seropositivity) has not been reported previously. An 82-year-old woman with diffuse cutaneous systemic sclerosis experienced dyspnoea on exertion and fever. No signs of infection were observed on computed tomography. Her fever persisted despite antibiotic treatment for occult bacterial infection and secondary Clostridioides difficile-associated diarrhoea. Microscopic polyangiitis was suspected because of myeloperoxidase anti-neutrophil cytoplasmic antibody seropositivity, and giant cell arteritis was suspected as a differential diagnosis due to swelling of the superficial temporal artery. Arterial biopsy revealed inflammatory cell infiltration with granuloma formation. Based on the presence of granulomatous inflammation in the superficial temporal artery, we concluded that giant cell arteritis with myeloperoxidase anti-neutrophil cytoplasmic antibody seropositivity occurred as a complication. After glucocorticoid therapy, her fever and dyspnoea on exertion improved with a gradual decline in the serum myeloperoxidase anti-neutrophil cytoplasmic antibody levels. It is possible that vasculitis occurs as a complication in patients with systemic sclerosis in cases where the fever persists and cannot be explained by systemic sclerosis itself, infectious disease, or malignancy. Clinicians must be careful not to prematurely diagnose microscopic polyangiitis based on myeloperoxidase anti-neutrophil cytoplasmic antibody seropositivity or giant cell arteritis based on the swelling of the superficial temporal artery. Careful evaluation of the presence of granulomatous inflammation in an arterial biopsy specimen is essential to differentiate between microscopic polyangiitis and giant cell arteritis.

Outcomes of pediatric obesity-related lifestyle disease screenings in Kumamoto.

BACKGROUND: Obesity is an important issue causing both health hazards and socioeconomic loss to those affected. Kumamoto City regularly performs obesity-related lifestyle disease screenings for fourth grade children with obesity, including physical examinations, blood tests, and special examination referrals. We retrospectively analyzed the outcomes of the screenings conducted from 2011 to 2020. METHODS: The percentage of overweight was calculated using data from the Lifestyle Disease Screening Board of Kumamoto City from 2011 to 2020. The percentage of overweight, abdominal circumference, blood pressure, and laboratory test outcomes of the Secondary Lifestyle Disease Test were evaluated. RESULTS: The proportion of children with obesity in grades 1-4 in Kumamoto was higher than the national average, while that in grades 5-6 was lower than the national average. Among the fourth graders screened, 6521 were eligible for the Secondary Lifestyle Disease Tests, of which 3291 children underwent the test. In the testing, 22.3% of the boys and 29.1% of the girls were nonobese. Moreover, 25.9% of the boys and 19.2% of the girls, including nonobese children, required further examination and intervention. Notably, 62.1% of the boys and 46.2% of the girls who were nonobese and required special examination had a waist circumference of ≥75 cm or waist-to-height ratios of ≥0.5. CONCLUSIONS: Obesity-related lifestyle disease screenings contributed to preventing obesity progression. Abdominal circumference measurements may be useful in determining nonobese children at a risk of lifestyle diseases.

Endometrial and vaginal microbiomes influence assisted reproductive technology outcomes.

OBJECTIVE: The role of Lactobacillus-dominant microbiota in the endometrium in reproductive function is unclear. We therefore aimed to explore the impact of the balance of Lactobacillus and pathological bacteria in the endometrial and vaginal microbiomes on the pregnancy outcomes of women treated with assisted reproductive technology (ART). METHODS: This study included 35 women with infertility submitted to good-quality embryo transfers. The cutoff values for abundance of Lactobacillus species (spp.) and pathological bacteria in the endometrium and vagina were calculated. Women with Lactobacillus spp. and pathological bacteria abundance above the cutoff values were categorized in the high-abundance group, whereas those with abundance below cutoff values were categorized in the low abundance group. We divided the patients into four groups based on the combination of high/low abundance of Lactobacillus spp. and pathological bacteria. RESULTS: The 35 cases of good-quality embryo transfer resulted in 21 pregnancies. Pregnant women were present in significantly higher proportions in the high Lactobacillus spp. abundance and low pathological bacteria abundance group, whereas the opposite combination (i.e., low Lactobacillus spp. abundance and high pathological bacteria abundance) saw a significantly higher proportion of nonpregnant women (p=0.022). CONCLUSIONS: The balance between Lactobacillus and pathological bacterial abundance in the endometrial and vaginal microbiomes is associated with pregnancy from ART.

Resection of an intrapulmonary solitary fibrous tumor in the center of the middle lobe: a case report.

A 75-year-old female patient was referred to our hospital due to an abnormal shadow detected by chest X-ray. Computed tomography scans revealed a well-circumscribed nodule measuring 28 mm between B4 and B5 in the right middle lobe. Because the tumor was in the center of right middle lobe, a middle lobe resection was performed. The tumor was located within the lung and there were no obvious pleural surface changes. Postoperative histological findings showed 34-mm firm and round tumor, and well circumscribed without involving the visceral pleura. The pathologic examination revealed proliferating spindle-shaped cells with a random fascicular arrangement with continuity to the pulmonary interstitium. Not much cellular atypia was observed. Immunohistochemical staining indicated that the tumor was positive for STAT6, CD34. The final diagnosis was an intrapulmonary benign solitary fibrous tumor (SFT). Even benign intrapulmonary SFTs that have been completely resected may later become malignant and recur, and careful follow-up is necessary.

Concurrent coronavirus disease 2019 and primary syphilis in a young man: A rare case report.

INTRODUCTION: The global rise of syphilis infections and the ongoing coronavirus disease 2019 (COVID-19) pandemic are causes for concern. We herein report a rare case of concurrent primary syphilis and COVID-19. CASE REPORT: A 29-year-old man was admitted with a diagnosis of COVID-19. Although COVID-19 pneumonia appeared during ciclesonide and favipiravir treatment, his symptoms improved without developing severe hypoxemia. A small, red ulcer on the left-side of his glans penis was noted and left inguinal lymph node swellings were detected on computed tomography (CT). He reported that his last engagement in sexual intercourse had been 3 months previously, and that his partner had subsequently been diagnosed with syphilis. Although both serum Treponema pallidum (TP) antibody and rapid plasma reagin (RPR) quantitative tests were negative on the day of admission, we clinically diagnosed a suspected case of primary syphilis and started treatment with amoxicillin (1500 mg/day). We subsequently learned that the TP antibody and RPR quantitative tests had been positive 4 days before starting syphilis treatment. Amoxicillin treatment was continued for 61 days, and the ulcer gradually improved. One year later, the RPR quantitative test was negative, and CT revealed a reduction in size of the inguinal lymph nodes and no residual signs of COVID-19 pneumonia. CONCLUSION: The prevalence of syphilis has been increasing even during the COVID-19 pandemic, and the incidence of concurrent syphilis and COVID-19 might be higher than is recognized. Asking patients with COVID-19 about high-risk sexual behavior and genital lesions could help with early diagnosis of syphilis.

Microbiome analysis in women with endometriosis: Does a microbiome exist in peritoneal fluid and ovarian cystic fluid?

Purpose: To investigate the relationship between the microbiome of the female genital tract and endometriosis. Methods: This prospective cohort study included 36 women who underwent laparoscopic surgery for ovarian tumor from July 2019 to April 2020. Of them, 18 had endometriosis, and 18 did not have endometriosis. Vaginal secretions, endometrial fluid, peritoneal fluid, and ovarian cystic fluid were collected during surgery. Next-generation sequencing of bacterial 16S rRNA was performed to characterize the microbiome. Results: Specific microbiomes were not detected in either peritoneal fluid or ovarian cystic fluid regardless of the presence or absence of endometriosis and the type of cyst. When the cutoff value of infectious bacterial abundance in the vagina was set as 64.3%, there were many cases more than a cutoff value in the endometriosis group significantly (p = 0.01). When the cutoff value of infectious bacterial abundance in the endometrium was set as 18.6%, there were many cases more than a cutoff level in the endometriosis cases significantly (p = 0.02). Conclusion: Peritoneal fluid and ovarian cystic fluid are almost sterile, although dysbiosis may occur in the vaginal and endometrial microbiome in women with endometriosis.

Relationship between compliance with management target values and renal prognosis in multidisciplinary care for outpatients with chronic kidney disease.

BACKGROUND: Although multidisciplinary care (MDC) is necessary for controlling chronic kidney disease (CKD), its impact on compliance with management target values in the CKD guidelines remains unclear. This study was designed to clarify the relationship between compliance with management target values and renal prognosis in CKD outpatients who received MDC. METHODS: There were 255 outpatients with pre-dialysis CKD who received MDC. Achievement rates of systolic, and diastolic blood pressure, hemoglobin, uric acid, low-density lipoprotein cholesterol, and hemoglobin A1c values determined according to CKD guidelines were compared before and 12 months after MDC. In addition, after dividing achievement rates of the target values at 12 months after MDC into four groups (A < 30% ≤ B < 60% ≤ C < 80% ≤ D), dialysis initiation and renal survival rates were compared. RESULTS: There was a significant increase in the overall achievement rate from 62.8 to 69.1% (p < 0.001). The higher the achievement rate after MDC, the lower the dialysis initiation rate (A 72.7%, B 35.3%, C 20.5%, D 8.2%, p < 0.001). There was also a significantly higher renal survival rate (p < 0.001). These findings suggest that MDC for CKD raised awareness of health literacy, and improved the achievement rate of target values. Furthermore, the higher the achievement rate, the later the initiation of dialysis, which led to improvement of renal survival. CONCLUSIONS: MDC can improve compliance with management target values for CKD, suggesting that it may improve renal prognosis.

Development of a skin microbiome diagnostic method to assess skin condition in healthy individuals: Application of research on skin microbiomes and skin condition.

OBJECTIVE: Skin microbiomes vary across individuals. They are known to play essential roles in maintaining homeostasis and preventing infectious pathogens. In recent years, cosmetic product development has begun to focus on the relationship between skin microbiomes and skin conditions. However, the statistical methods used in many studies include the standard t-test and small-scale correlation analysis, which do not take into account the internal correlation structure in data on skin microbiomes and skin features. In this study, we aimed to understand the relationship between skin microbiomes and skin features by analysing complex microbiomes and skin data. METHODS: We obtained data on 19 skin characteristics and skin microbiomes based on 16s ribosomal RNA (16S rRNA) gene analysis of 276 healthy Japanese women. We then performed the principal component analysis (PCA), a method that takes into account the internal correlation structure, on 234 panels of them that did not contain outliers or missing values. We confirmed the relationship between skin microbiomes and skin features with principal component regression analysis and hierarchical clustering analysis (HCA). RESULTS: The principal component regression analysis showed strong relationships between skin microbiomes and sebum-related skin characteristics and skin pH. In the HCA, the female panel was classified into two major groups based on the skin microbiome. Furthermore, there were significant differences in sebum-related skin characteristics and the way skin condition changes with ageing between those groups, suggesting the possibility of measuring skin condition and age-related skin risk based on microbiome data. In addition, sebum-related characteristics differed significantly among middle-aged participants, suggesting a strong relationship between skin microbiomes and sebum-related characteristics. CONCLUSION: Analysis of skin condition and skin microbiome in Japanese women, taking into account the correlation between variables, showed that skin microbiome was significantly related to the number of pores and the amount of sebum. Furthermore, it was suggested that the skin condition and the way the skin condition changes with ageing may differ depending on the type of skin microbiome. The finding of a relationship between skin condition and skin microbiome suggests the possibility of proposing a new beauty method focusing on the skin microbiome in the future.

OBJECTIF: Les microbiomes de la peau varient selon les individus. Ils sont connus pour jouer des rôles essentiels dans le maintien de l'homéostasie et la prévention des agents pathogènes infectieux. Ces dernières années, le développement de produits cosmétiques a commencé à se concentrer sur la relation entre les microbiomes cutanés et les conditions de la peau. Cependant, les méthodes statistiques utilisées dans de nombreuses études comprennent le t-test standard et l'analyse de corrélation à petite échelle, qui ne tiennent pas compte de la structure de corrélation interne dans les données sur les microbiomes cutanés et les caractéristiques de la peau. Dans cette étude, nous avons cherché à comprendre la relation entre les microbiomes cutanés et les caractéristiques de la peau en analysant des données complexes sur les microbiomes et la peau. MÉTHODES: Nous avons obtenu des données sur 19 caractéristiques de la peau et sur les microbiomes cutanés à partir de l'analyse du gène de l'ARNr 16S (16S rRNA) de 276 femmes japonaises en bonne santé. Nous avons ensuite effectué l'analyse en composantes principales (PCA: principal component analysis), une méthode qui prend en compte la structure de corrélation interne, sur 234 d'entre elles qui ne contenaient pas de valeurs aberrantes ou manquantes. Nous avons confirmé la relation entre les microbiomes cutanés et les caractéristiques de la peau à l'aide d'une analyse de régression en composantes principales et d'une analyse de regroupement hiérarchique (HCA: hierarchical clustering analysis). RÉSULTATS: L'analyse de régression en composantes principales a montré des relations fortes entre les microbiomes cutanés et les caractéristiques de la peau liées au sébum et au pH de la peau. Dans l'étude HCA, le panel de femmes a été classé en deux grands groupes sur la base du microbiome cutané. En outre, il y avait des différences significatives dans les caractéristiques de la peau liées au sébum et dans la façon dont l'état de la peau change avec l'âge entre ces groupes, ce qui suggère la possibilité de mesurer l'état de la peau et le risque cutané lié à l'âge à partir des données du microbiome. En outre, les caractéristiques liées au sébum différaient de manière significative chez les participants d'âge moyen, ce qui suggère une forte relation entre les microbiomes cutanés et les caractéristiques liées au sébum. CONCLUSION: L'analyse de l'état de la peau et du microbiome cutané chez les femmes japonaises, en tenant compte de la corrélation entre les variables, a montré que le microbiome cutané était significativement lié au nombre de pores et à la quantité de sébum. En outre, il a été suggéré que l'état de la peau et la façon dont l'état de la peau évolue avec le vieillissement peuvent différer en fonction du type de microbiome cutané. La découverte d'une relation entre l'état de la peau et le microbiome cutané suggère la possibilité de proposer à l'avenir une nouvelle méthode de beauté axée sur le microbiome cutané.

Two cases of polycystic ovary syndrome with onset of severe ovarian hyperstimulation syndrome following controlled ovarian stimulation with aromatase inhibitors for fertility preservation before breast cancer treatment.

OBJECTIVE: The risks of ovarian hyperstimulation syndrome (OHSS) involve high estrogen (E2) levels. We report two breast cancer patients with polycystic ovarian syndrome who underwent fertility preservation and had severe OHSS; their E2 levels were lowered using aromatase inhibitors (AI). CASE REPORTS: A 36-year-old woman underwent controlled ovarian stimulation (COS) with AI and cryopreserved 10 blastocysts. She was hospitalized with OHSS (E2 = 139.1 pg/mL). She improved with infusion alone. A 31-year-old woman underwent COS with AI and cryopreserved 8 blastocysts. She was hospitalized for OHSS (E2: 429 pg/mL). Her vascular endothelial growth factor (VEGF) levels were high (62 pg/mL) at 8 days after the procedure. She needed hospitalization for 9 days. The planned adjuvant therapy was delayed for a week in both cases. CONCLUSION: Elevated VEGF levels should be considered as a risk factor of OHSS even if E2 levels are low with AI treatment.

Live birth outcomes from IVF treatments in younger patients with low AMH.

OBJECTIVE: Anti-Müllerian hormone (AMH) is used to predict in vitro fertilization outcomes. However, predicting live birth is difficult in younger patients with low AMH. Thus, this study aimed to determine the live birth rates from younger patients with low anti-Müllerian hormone levels. METHODS: A total of 296 infertile patients with AMH measured (younger group, aged 25-38 years; older group, aged 39-42 years) were included in this study. In vitro fertilization outcomes between patients with AMH levels of <1.0ng/mL and ≥1.0ng/mL were compared. RESULTS: Younger patients with AMH levels <1.0ng/mL (younger low AMH group) exhibited lower number of oocytes retrieved than patients with AMH levels ≥1.0ng/mL (younger normal AMH group). However, there were no significant differences in cumulative pregnancy or cumulative live birth rates between groups. Older patients with AMH levels ≥1.0ng/mL (older normal AMH group) had significantly better outcomes as per mean number of oocytes, cumulative pregnancy rate, and cumulative live birth rate than older patients with AMH levels <1.0ng/mL (older low AMH group). In the younger low AMH group, the frequency of oocyte retrieval was significantly higher in patients who achieved live birth. In addition, the blastocyst transfer rate was significantly higher in individuals with live births versus subjects with non-live births. CONCLUSIONS: AMH is a predictor of live birth among older, but not younger, women. Our report suggests that younger women may become pregnant even with low AMH levels when they obtain blastocysts from frequent oocyte retrievals.

Prediction of future wrinkles for middle-aged women: A 7-year longitudinal study on the progression of wrinkles in Japanese women.

BACKGROUND: It is commonly believed that there is serious heterogeneity in the rate of wrinkle progression among individuals. Although several skin characteristics have been shown to influence wrinkle progression, the ability to predict which individuals with skin characteristics are likely to develop wrinkles is still limited. OBJECTIVES: The purpose of this study is to develop and validate an effective prediction model for longitudinal changes in wrinkles. METHODS: We collected annual wrinkle scores and multiple skin physiological characteristics in 48 Japanese women over a period of 7 years. We developed a multivariable prediction model for predicting future wrinkle status based on the various skin physiological characteristics using a linear mixed-effects model. RESULTS: After variable selection by backwards, the final wrinkle prediction model included age, sebum volume, redness of skin color, lightness of skin color, and an interaction term between sebum volume and redness of skin color. The developed prediction model showed favorable prediction accuracy (R2  = 87.92%, 95% confidence interval 84.27%-90.68%). CONCLUSIONS: The developed model accurately predicted levels of wrinkles in Japanese women aged 22-60 years. The prediction model is based on age and three practical skin characteristics, which might implicate an essential insight to prevent wrinkle progression in individuals.

Effect of multidisciplinary care of dialysis initiation for outpatients with chronic kidney disease.

BACKGROUND: The aim of comprehensive multidisciplinary care (MDC) by the chronic kidney disease (CKD) team is not only to prevent worsening renal function, but also provide education on the selection of renal replacement therapy (RRT) by shared decision making (SDM). The purpose of this study was to examine the effects of MDC for predialysis outpatients on dialysis therapy, especially with regard to peritoneal dialysis (PD). METHODS: This study evaluated 112 CKD patients who underwent dialysis at our hospital starting from 2012, with 53 outpatients receiving MDC from the CKD team and 59 outpatients not receiving MDC. Annual decreases in the estimated glomerular filtration rates (ΔeGFR), the duration from the time of intervention to dialysis initiation, the urgent dialysis rate using a temporary catheter, and the PD selection rate were compared and examined between the two groups. The ΔeGFR, the duration from intervention to PD initiation, and the PD retention rate were compared between 18 PD patients in the MDC group and 10 PD patients in the non-MDC group. RESULTS: The MDC group had a significantly lower ΔeGFR, significantly longer duration, and a significantly lower urgent dialysis initiation rate versus the non-MDC group. Moreover, there was a significantly higher PD selection rate, significantly prolonged duration, and significantly higher PD retention rate. CONCLUSIONS: Multidisciplinary CKD team care for outpatients is effective in delaying the progression of CKD and avoiding the initiation of urgent dialysis; contributing to improved PD selectivity and continuity by SDM.

Sex ratio of infants born through in vitro fertilization and embryo transfer: Results of a single-institution study and literature review.

OBJECTIVE: The possible effects of Assisted Reproductive Technology (ART) on sex ratio at birth are extremely significant. This study aimed to determine whether ART affects the sex ratio of infants born through in vitro fertilization and embryo transfer (IVF-ET). MATERIALS AND METHODS: We ran this retrospective study on 290 singleton infants born following IVF-ET from February 2014 to August 2018 at a single institution. We compared the sex ratios of these infants with respect to insemination versus intracytoplasmic sperm injection (ICSI), early-cleavage embryo versus blastocyst transfer, fresh versus frozen-thawed embryo transfer and normal sperm versus asthenospermia. RESULTS: There were no significant differences in the sex ratio with respect to the fertilization method, transfer time, fresh embryo or frozen-thawed embryo transfer. In addition, the multiple logistic regression analysis revealed that these factors did not significantly affect the sex ratio. CONCLUSIONS: Our study indicated that the differences in the fertilization method transfer time and sperm motility rate did not affect the sex ratio of IVF live births. However, with increasing numbers of ICSI and blastocyst transfer cycles, factors possibly affecting the sex ratio need to be further investigated.

Impact of the one-carbon metabolism on oocyte maturation, fertilization, embryo quality, and subsequent pregnancy.

PURPOSE: To investigate impact of the one-carbon metabolism (OCM) on oocyte maturity and embryo development. METHODS: This prospective study analyzed 18 women who agreed to participate. We measured the OCM biomarkers' concentrations including Vitamin B12 (VB12), folic acid (FA), and homocysteine (Hcy) in serum and follicular fluid (FF), and assessed their correlation. We also evaluated the influence of such OCM biomarker concentrations in mono-FF on oocyte maturation, fertilization, embryo quality, and consequent pregnancy after embryo transfers. RESULTS: All biomarkers showed a high concentration variability in different follicles of each woman, but their mean levels correlated with the serum levels. Among the 106 collected oocytes, 92 were mature, 59 were fertilized, and 16 yielded good-quality embryos. We performed 26 single embryo transfers, and 7 patients achieved clinical pregnancies. VB12 concentration (FF) was significantly lower in fertilized than unfertilized oocytes by univariate analysis. In multivariate logistic analysis, a significant correlation was found between FA concentration (FF) <14.25 ng/mL and good-quality embryos and between Hcy concentration (FF) <4.9 nmol/mL and clinical pregnancy. CONCLUSION: OCM in FF may affect fertilization, embryo quality, and clinical pregnancy.

Threatened uterine rupture following laparoscopic surgery in interstitial tubal pregnancy.

Contraception is recommended for a certain period following a hysterotomy; however, no consensus exists on the required duration of contraception. A 21-year-old female was brought to the emergency room in a state of shock due to intraperitoneal bleeding. An emergency laparoscopic cornuostomy indicated for ruptured interstitial pregnancy was performed. Despite contraception, the patient got pregnant 1.5 months after surgery. At 16 weeks of gestation, threatened uterine rupture was suspected, as magnetic resonance imaging (MRI) revealed hematogenous amniotic fluid and a subchorionic hematoma near the interstitial portion of the fallopian tube. An MRI at 21 weeks showed hematoma shrinkage and disappearance of the hematogenous amniotic fluid. At 37 weeks, an elective cesarean section was performed, which resulted in a live birth. Pregnancy shortly after surgery is a risk factor for uterine rupture. In such cases, MRI could be useful in the evaluation of threatened uterine ruptures.

Phenylalanine ammonia-lyase and phenolic compounds are related to hybrid lethality in the cross Nicotiana suaveolens×N. tabacum.

Hybrid lethality observed in hybrid seedlings between Nicotiana suaveolens and N. tabacum is characterized by browning, initially of the hypocotyls and eventually of entire seedlings. We investigated the mechanism underlying this browning of tissues. A phenylalanine ammonia-lyase (PAL) gene codes an enzyme involved in a pathway producing phenolic compounds related to the browning of plant tissues. The expression of PAL rapidly increased with the induction of hybrid lethality. Phenolic compounds were observed to be accumulated in whole parts of hybrid seedlings. Treatment of hybrid seedlings with L-2-aminooxy-3-phenylpropionic acid (AOPP), an inhibitor for PAL, suppressed browning and decreased the phenolic content of hybrid seedlings. Although programmed cell death (PCD) was involved in hybrid lethality, AOPP treatment also suppressed cell death and enhanced the growth of hybrid seedlings. These results indicated that PAL is involved in hybrid lethality, and phenolic compounds could be the cause of hybrid lethality-associated tissue browning.