Distribution of cervical intraepithelial neoplasia is closely associated with HPV status and uterine position.

Although cervical intraepithelial neoplasia (CIN) lesions are considered to be not randomly distributed across the cervix, but predominantly in the anterior wall, the clinicopathological etiology remains unknown. Herein, we aimed to elucidate the relationship between quantitatively measured area of CIN2/3 and cervical cancer associated factors by retrospective cohort study. We analyzed 235 consecutive therapeutic conization specimens dissected as a single intact section to determine CIN2/3 area and its correlation with both clinical risk factors including human papillomavirus (HPV) status (single or multiple infection) and uterine position defined by transvaginal ultrasound. Cervical wall was classified into three groups: anterior: (11, 12, 1, and 2 o'clock), posterior (5, 6, 7, and 8 o'clock) and lateral (3, 4, 9, and 10 o'clock). Multiple regression revealed that younger age and HPV16 status were significantly correlated with CIN2/3 area (p = 0.0224 and p = 0.0075, respectively). The Jonckheere-Terpstra test showed a significant trend: CIN2/3 area was highest in the single HPV16 group, followed by the multiple HPV16 group and the non-HPV16 group (p < 0.0001). CIN2/3 area in the anterior wall was statistically significantly larger than the posterior and lateral wall (p = 0.0059 and p = 0.0107, respectively). CIN2/3 area in the anterior wall was significantly greater with anteversion-anteflexion than retroversion-retroflexion (p = 0.0485), whereas CIN2/3 area in the posterior wall was significantly larger with retroversion-retroflexion than anteversion-anteflexion (p = 0.0394). In conclusion, the topographical distribution of CIN2/3 area is closely associated with patient age, high-risk HPV status, especially single HPV16 infection and uterine position.

Perinatal Management in a Pregnant Woman with Ureteropelvic Junction Obstruction: Case Report and Literature Review.

Although giant hydronephrosis (GH) associated with ureteropelvic junction obstruction (UPJO) is extremely rarely detected in pregnant women, diagnostic methods, therapeutic approaches, and perinatal management have not been established. A 31-year-old Japanese primipara had a 15 cm × 12 cm multi-cystic mass in the right abdomen detected by transabdominal ultrasound at gestational week 26. Magnetic resonance imaging revealed that the mass was right renal GH. She underwent serial ultrasound-guided transretroperitoneal drainage as conservative treatment. She delivered vaginally at gestational week 36. Since she had flank pain and a documented non-functional right kidney, laparoscopic nephrectomy was conducted 22 months after delivery. UPJO with fewer smooth muscle cells and fibrosis was histologically diagnosed in the surgical specimen. Her postpartum and postoperative courses were uneventful for 10 months. We performed a literature review of diagnostic methods, clinical characteristics, and perinatal management in pregnant women with GH due to UPJO.

Progression of cervical intraepithelial neoplasia grade 2 lesions among Japanese women harboring different genotype categories of high-risk human papillomaviruses.

Background: This study aimed to examine whether genotype categories of high-risk human papillomaviruses (HR-HPVs), when divided into HPV16/18, HPV 31/33/45/52/58, and HPV35/39/51/56/59/68, had an effect on the time required for and the proportion of cases that progressed to cervical intraepithelial neoplasia (CIN) grade 3 among women with CIN2. Patients: A total of 160 women aged 20-49 years and having CIN2 were recruited between January 2008 and June 2018. The time required for progression to CIN3 was determined by Kaplan-Meier time-to-event analysis. HPV genotypes were determined using the Linear Array HPV genotyping test. Results: During an average follow-up time of 22 months, 62 (39%) women with CIN2 progressed to CIN3, whereas 34 (21%) eliminated HR-HPVs and became cytologically normal. The majority (63%) of the women harboring HPV16/18 progressed to CIN3 with a 50% progression time of 11 months, whereas 26% of those harboring HPV31/33/45/52/58 progressed to CIN3 with a 50% progression time of 70 months. Conclusion: For every patient diagnosed with CIN2, genotyping to distinguish HPV16/18 from other HR-HPVs should be performed. Therefore, electing a surgical treatment, such as conization, should be considered as the primary option for women who are positive for HPV16/18, particularly when they are likely to be lost for follow-up or are 40 years old or older. In contrast, follow-up cytology should be repeated every 12 months for women harboring non-16/18 HR-HPVs. Those who tested negative for HR-HPV may be followed at the maximum interval of 24 months.

Reduction in HPV 16/18 prevalence among young women following HPV vaccine introduction in a highly vaccinated district, Japan, 2008-2017.

Objective: Human papillomavirus (HPV) vaccination was introduced in Japan in April 2013, as a national immunization program for girls aged 12-16 years, after an initial introduction in 2010 as a public-aid program for girls aged 13-16 years. The Yuri-Honjo district had the highest vaccine coverage among women aged 17-51 years in 2017, due to the original public-aid program. The aim of this study was to evaluate the differences in the vaccine types of HPV16/18 infections between 2008-2012 (pre-vaccine era) and 2013-2017 (vaccine era). Materials and Methods: We evaluated whether HPV vaccination was associated with a decrease in the prevalence of HPV16/18 and high-risk HPV and the incidence of HPV-associated cervical lesions. A total of 1,342 women aged 18-49 years, covering both the pre-vaccine and vaccine eras, who visited Yuri Kumiai General Hospital and underwent HPV genotype tests from June 2008 to December 2017 were compared. Results: Among women aged 18-24 years with higher vaccine coverage (68.2%), the prevalence of HPV16/18 and high-risk HPV decreased from 36.7% and 69.4%, respectively, in the pre-vaccine era to 5.8% and 50.0%, respectively, in the vaccine era (p=0.00013 and p=0.047, respectively). Among those with cervical intraepithelial neoplasia grade 2- and grade 2+, HPV16/18 prevalence decreased from 30.0% to 2.7% (p=0.0018) and from 81.8% to 36.4% (p=0.030), respectively. In this age group, the rate of HPV16/18 positivity decreased significantly. Among age groups with lower vaccine coverage, HPV prevalence did not significantly differ between the two eras. Conclusion: The prevalence of HPV16/18 and high-risk HPV significantly decreased in women aged 18-24 years, most of whom were vaccinated. HPV vaccination effectively reduced the prevalence of HPV16/18 infections in the Yuri-Honjo district.

ACTH-Dependent Cyclic Cushing Syndrome Triggered by Glucocorticoid Excess Through a Positive-Feedback Mechanism.

CONTEXT: Cyclic Cushing syndrome is a rare variant of Cushing syndrome that demonstrates periodic cortisol excess. It has been thought that inhibition of a glucocorticoid positive-feedback loop is associated with remission of hypercortisolism in ACTH-dependent cyclic Cushing syndrome. However, the underlying mechanism that triggers the development of the hypercortisolism is still unknown. We observed a case of ACTH-dependent cyclic Cushing syndrome that was developed by exogenous glucocorticoids, possibly through a glucocorticoid positive-feedback loop. CASE DESCRIPTION: A 75-year-old woman had experienced cyclic ACTH and cortisol elevations six times in the previous 4 years. Her diagnosis was cyclic Cushing syndrome. During the hypercortisolemic phase, neither low-dose nor high-dose dexamethasone suppressed her plasma ACTH and cortisol levels. Daily metyrapone therapy decreased her plasma cortisol and ACTH levels during every hypercortisolemic phase. After the sixth remission of a hypercortisolemic phase, she took 25 mg of hydrocortisone for 4 weeks and developed ACTH-dependent hypercortisolemia. Treatment with 1 mg of dexamethasone gradually increased both plasma ACTH and cortisol levels over 2 weeks, resulting in the eighth hypercortisolemic phase. Treatment using a combination of dexamethasone and metyrapone did not increase plasma ACTH or cortisol level and successfully prevented development of ACTH-dependent hypercortisolism. CONCLUSION: We present an interesting case of cyclic Cushing syndrome in which ACTH-dependent hypercortisolemic phases relapsed during exogenous glucocorticoid treatment. A glucocorticoid positive-feedback loop and endogenous glucocorticoid synthesis may play key roles in the periodicity of hypercortisolism in cyclic Cushing syndrome.

Interstitial fluid shifts to plasma compartment during blood donation.

BACKGROUND: A vasovagal reaction (VVR) occurs in 0.8% to 0.9% of voluntary blood donors in Japan. However, they generally tolerate the acute loss of 400 mL of whole blood rather well, perhaps because several circulatory defense mechanisms compensate for the loss. This study aimed to determine the extent to which an interstitial fluid shift contributes to the development of a VVR. STUDY DESIGN AND METHODS: Blood hemoglobin (Hb) was measured upon admission, at venipuncture, and immediately after collecting 400 mL of whole blood from 736 donors. Shifted fluid volume was calculated using a formula that included Hb levels and estimated total blood volume. RESULTS: By the end of blood collection, 188 ± 80 and 211 ± 82 mL of fluid, which is equivalent to almost half of the total amount of withdrawn blood, had entered the intravascular space in male and female donors, respectively. The difference between the sexes was significant despite the lower body weight and circulating blood volume of the female donors. Body weight increased, whereas age decreased the volume of shifted fluid in female donors. CONCLUSION: Blood loss after donation is quickly compensated by an interstitial fluid shift into the intravascular space and may not be the only direct cause of VVR in the setting of a whole blood donation of 400 mL.

Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: structure elucidation, gene identification and role in drug resistance.

We demonstrated that the rox gene of Nocardia farcinica encodes a rifampicin monooxygenase capable of converting rifampicin to a new compound 2'-N-hydroxy-4-oxo-rifampicin with a markedly lowered antibiotic activity. The deletion mutation (Deltarox) of the rox gene gave no significant influence to the rifampicin resistance of N. farcinica. However, transformation with a plasmid containing an overexpressing the rox gene markedly raised the rifampicin resistance in the strain with the deletion mutation of the rpoB2 gene as the principal rifampicin resistance determinant. On the other hand, rifampicin was decolorized by the wild-type strain, whereas it remained intact when incubated with the Deltarox strain. Based on these results, it will be conclusive that the rox gene is capable of initiating rifampicin degradation with a new metabolite formation at the first step and having a role as the secondary rifampicin resistance factor in N. farcinica.

Trends of arbekacin-resistant MRSA strains in Japanese hospitals (1979 to 2000).

A total of 472 clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated in Japan between 1979 and 2000 were investigated for resistance to 8 aminoglycosides, 4 aminoglycoside-modifying enzyme gene profiles, and AluI-restriction fragment length polymorphism of the coagulase gene determined by polymerase chain reaction assay. The majority of MRSA strains tested belonged to 4 groups based on coa-RFLP: L21, L22, L31, and M22. About 90% of recent isolates belonged to type L21, indicating the spread of a specific type of MRSA in Japan. Of the type L21 strains, 41.9% included the aac(6')/aph(2") gene, which was one of the risk factors of arbekacin (ABK) resistance, but only 5.5% were resistant to ABK. In contrast, all of the type M22 strains carried aac(6')/aph(2") and 70.1% showed ABK resistance. Among the other types, less than 20% of strains showed ABK resistance. These results suggested that ABK has maintained potent activity. If the predominance of type L21 continues, there will be no progression to ABK resistance in MRSA. However, it may be necessary to monitor the trends in type M22 continuously.

cDNA cloning, genomic structure and chromosomal mapping of the mouse glucuronyltransferase-S involved in the biosynthesis of the HNK-1 carbohydrate epitope.

The HNK-1 carbohydrate epitope is expressed on a series of cell adhesion molecules and some glycolipids in the nervous system. Two glucuronyltransferases (GlcAT-P and GlcAT-S) are involved in the biosynthesis of the HNK-1 carbohydrate epitope. In this study, we isolated cDNA and genomic clones encoding the mouse glucuronyltransferase-S involved in the biosynthesis of the HNK-1 carbohydrate epitope and determined the structural organization of the gene. The deduced amino acid sequence of mouse GlcAT-S consists of 324 amino acids and has a type II membrane topology. The predicted amino acid sequence of mouse GlcAT-S is 98.1% identical to that of rat GlcAT-S. Northern blot analysis revealed that the mouse GlcAT-S transcript is specifically expressed in the nervous system. Moreover, the mouse GlcAT-S gene is composed of four exons spanning over more than 25 kilobase pairs. Southern blot analysis and chromosomal mapping indicated that the mouse GlcAT-S gene is a single copy gene and it was mapped to the A4-B region of mouse chromosome 1.