Tubulointerstitial nephritis complicating IVIG therapy for X-linked agammaglobulinemia

BACKGROUND: Patients with X-linked agammaglobulinemia (XLA) develop immune-complex induced diseases such as nephropathy only rarely, presumably because their immunoglobulin (Ig) G concentration is low. We encountered a patient with XLA who developed tubulointerstitial nephritis during treatment with intravenous immunoglobulin (IVIG). CASE PRESENTATION: A 20-year-old man was diagnosed with XLA 3 months after birth and subsequently received periodic γ-globulin replacement therapy. Renal dysfunction developed at 19 years of age in association with high urinary β2-microglobulin (MG) concentrations. A renal biopsy specimen showed dense CD3-positive lymphocytic infiltration in the tubulointerstitium and tubular atrophy, while no IgG4-bearing cell infiltration was found. Fibrosclerosis and crescent formation were evident in some glomeruli. Fluorescent antibody staining demonstrated deposition of IgG and complement component C3 in tubular basement membranes. After pulse steroid therapy was initiated, urinary β2-MG and serum creatinine concentrations improved. CONCLUSION: Neither drug reactions nor collagen disease were likely causes of tubular interstitial disorder in this patient. Although BK virus was ruled out, IgG in the γ-globulin preparation might have reacted with a pathogen present in the patient to form low-molecular-weight immune complexes that were deposited in the tubular basement membrane

Distribution of Recent Benthic Foraminifera off Western Costa Rica in the Eastern Equatorial Pacific Ocean

Benthic foraminifera provide essential information for paleobathymetric reconstructions. However, the modern distribution of benthic foraminifera, especially at depths below 1000 meters below sea level (mbsl), is still obscure in the offshore regions near Central and South America. To characterize the bathymetric scale in the eastern equatorial Pacific Ocean, we examined the depth distribution of benthic foraminifera using piston core samples taken off the coast of Costa Rica. Foraminiferal assemblages vary according to water depth: 1) U1 (mainly composed of Ammonia beccarii, Cancris sagra, Elphidium tumidum, Hanzawaia concentrica, Pseudononion basispinata, and Planulina exorna) represent inner shelf faunas (shallower than 50 mbsl). 2) U2 (mainly composed of Ammobaculites foliaceus, Bolivina striatula, Cassidulina minuta, Hanzawaia concentrica, Uvigerina incilis, Bulimina denudata, and Cancris sagra) is correlated with mid-shelf depth assemblages, from 50 to 100 mbsl. 3) U3 (mainly composed of Uvigerina incilis, Hanzawaia concentrica, Angulogerina semitrigona, Bolivina acuminata, Bolivina bicostata, and Cibicorbis inflatus) is assigned to outer shelf assemblages from 100 to 200 mbsl. 4) U4 (mainly composed of Bolivina humilis, Bolivina seminuda, Bolivina subadvena, Cassidulina tumida, Epistominella obesa, Angulogerina carinata, and Cibicorbis inflatus) is the upper bathyal faunas (200–600 mbsl). 5) U5 (mainly composed of Brizalina argentea, Uvigerina peregrina, Uvigerina auberiana, Brizalina seminuda, Bulimina striata, Epistominella smithi and Globocassidulina subglobosa) is the mid-bathyal faunas (600–1000 mbsl). 6) U6 (mainly composed of Uvigerina auberiana, Uvigerina peregrina, Brizalina argentea, Bulimina mexicana, Cassidulina carinata, Epistominella smithi, and Lenticulina cushmani) represents the lower bathyal assemblage (1000–2000 mbsl). 7) U7 (mainly composed of Uvigerina auberiana, Brizalina argentea, and Eubuliminella tenuata) represent upper abyssal faunas (2000–3000 mbsl). 8) U8 (mainly composed of Glomospira sp. A, Lagenammina arenulata, Chilostomella oolina, Hoeglundina elegans, Melonis barleeanum, Nonion affine, Oridorsalis umbonatus, Pullenia bulloides, and Uvigerina proboscidea) is characterized by deep-water cosmopolitan faunas (deeper than 3000 mbsl). On the basis of a comparison with several environmental parameters, dissolved oxygen concentrations are likely to be the most effective factor controlling foraminiferal depth distributions in the eastern equatorial Pacific especially below the oxygen minimum zone (OMZ). Around OMZ, nitrate concentration also might be related with the benthic assemblage due to the nitrate respiration

Deconstructing the traditional Japanese medicine “Kampo”: compounds, metabolites and pharmacological profile of maoto, a remedy for flu-like symptoms

Pharmacological activities of the traditional Japanese herbal medicine (Kampo) are putatively mediated by complex interactions between multiple herbal compounds and host factors, which are difficult to characterize via the reductive approach of purifying major bioactive compounds and elucidating their mechanisms by conventional pharmacology. Here, we performed comprehensive compound, pharmacological and metabolomic analyses of maoto, a pharmaceutical-grade Kampo prescribed for flu-like symptoms, in normal and polyI:C-injected rats, the latter suffering from acute inflammation via Toll-like receptor 3 activation. In total, 352 chemical composition-determined compounds (CCDs) were detected in maoto extract by mass spectrometric analysis. After maoto treatment, 113 CCDs were newly detected in rat plasma. Of these CCDs, 19 were present in maoto extract, while 94 were presumed to be metabolites generated from maoto compounds or endogenous substances such as phospholipids. At the phenotypic level, maoto ameliorated the polyI:C-induced decrease in locomotor activity and body weight; however, body weight was not affected by individual maoto components in isolation. In accordance with symptom relief, maoto suppressed TNF-α and IL-1β, increased IL-10, and altered endogenous metabolites related to sympathetic activation and energy expenditure. Furthermore, maoto decreased inflammatory prostaglandins and leukotrienes, and increased anti-inflammatory eicosapentaenoic acid and hydroxyl-eicosapentaenoic acids, suggesting that it has differential effects on eicosanoid metabolic pathways involving cyclooxygenases, lipoxygenases and cytochrome P450s. Collectively, these data indicate that extensive profiling of compounds, metabolites and pharmacological phenotypes is essential for elucidating the mechanisms of herbal medicines, whose vast array of constituents induce a wide range of changes in xenobiotic and endogenous metabolism

Effect of SARS-CoV-2 BNT162b2 mRNA vaccine on thyroid autoimmunity: A twelve-month follow-up study

ObjectivesGraves’ disease (GD) has been highlighted as a possible adverse effect of the respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. However, it is unknown if the SARS-CoV-2 vaccine disrupts thyroid autoimmunity. We aimed to present long-term follow-up of thyroid autoimmunity after the SARS-CoV-2 BNT162b2 mRNA vaccine.MethodsSerum samples collected from seventy Japanese healthcare workers at baseline, 32 weeks after the second dose (pre-third dose), and 4 weeks after the third dose of the vaccine were analyzed. The time courses of anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibody, thyroid-stimulating hormone receptor antibody (TRAb), and thyroid function were evaluated. Anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were additionally evaluated in thirty-three participants.ResultsThe median age was 50 (IQR, 38-54) years and 69% were female. The median anti-spike IgG antibody titer was 17627 (IQR, 10898-24175) U/mL 4 weeks after the third dose. The mean TRAb was significantly increased from 0.81 (SD, 0.05) IU/L at baseline to 0.97 (SD, 0.30) IU/L 4 weeks after the third dose without functional changes. An increase in TRAb was positively associated with female sex (β = 0.32, P = 0.008) and low basal FT4 (β = -0.29, P = 0.02) and FT3 (β = -0.33, P = 0.004). TgAb was increased by the third dose. Increase in TgAb was associated with history of the thyroid diseases (β = 0.55, P <0.001).ConclusionsSARS-CoV-2 BNT162b2 mRNA vaccine can disrupt thyroid autoimmunity. Clinicians should consider the possibility that the SARS-CoV-2 vaccine may disrupt thyroid autoimmunity

〈Cases Reports〉Recurrent focal intestinal perforation in extremely-low-birth-weight infant

[Abstract] In recent years, the incidence of focal intestinal perforation (FIP) has been increasing, as the survival rate of extremely-low-birth-weight(ELBW) infants has been rising. We present a case of an ELBW infant who suffered three recurrences of FIP in a very short period of time. The patient was a female infant who was born at 24 weeks and 2 days of gestation, with a birth weight of 579 g. On her 22^nd day of life, abdominal X-rays revealed free air, which suggested intestinal perforation, and an intraperitoneal drainage tube was placed. Intraperitoneal lavage was performed on day 28 of life,and the drained fluid was turbid with feces, suggesting a recurrence of perforation. On day 30 of life, laparotomy revealed a perforation of approximately 1cm in diameter located at 6 cm from the ileocecum on the oral side. The X-ray taken on day 34 again revealed free air, and, through another laparotomy, a new perforation was found at about 15 cm from the stoma on the oral side. This case provides suggestions that may shed light on our approach to determine the pathogenesis of FIP, especially since no other case of FIP recurring three times has ever been reported

Background Coloration of Squamous Epithelium in Esophago-Pharyngeal Squamous Cell Carcinoma: What Causes the Color Change?

Objectives: This study aims to clarify the cause of background coloration in the epithelia between each dilated intra papillary capillary loop in esophago-pharyngeal squamous cell carcinoma. Design: This is a single center retrospective study including 124 patients with 160 lesions who underwent esophagogastroduodenoscopy in Nagasaki University Hospital from September 2007 to March 2012; a detailed comparison between endoscopic images and pathology was performed. Immunohistological assessment using anti-human hemoglobin antibody (anti-Hb Ab) was performed to verify the presence of hemoglobin (Hb) component in the cancer cells. Real-time polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) on Hb-β mRNA were performed to assess the production of Hb component within the cancer cells. Results: A strong positivity for anti-Hb Ab was observed in the squamous cell carcinoma area, whereas non-cancerous mucosa showed no immunopositivity for Hb. The concordance rate between anti-Hb Ab immunoreactivity and the presence of BC was as high as 80.9%. The amount of Hb-β mRNA expression was three times higher in cancer tissues compared with the surrounding non-cancerous mucosa. ISH images showed that the expression exclusively occurred in cancer cells, indicating that Hb is probably produced within cancer cells. Conclusions: The background coloration observed is partly due to an extravascular component of Hb. RT-PCR and ISH analyses indicate that Hb is produced within cancer cells

Reduction of Cardiovascular Events and Related Healthcare Expenditures through Achieving Population-Level Targets of Dietary Salt Intake in Japan: A Simulation Model Based on the National Health and Nutrition Survey

Reducing population dietary salt intake is expected to help prevent cardiovascular disease and thus constrain increasing national healthcare expenditures in Japan’s super-aged society. We aimed to estimate the impact of achieving global and national salt-reduction targets (8, <6, and <5 grams/day) on cardiovascular events and national healthcare spending in Japan. Using published data including mean salt intake and systolic blood pressure from the 2019 National Health and Nutrition Survey, we developed a Markov model of a closed cohort of adults aged 40–79 years in 2019 (n = 66,955,000) transitioning among six health states based on the disease course of ischemic heart disease (IHD) and stroke. If mean salt intake were to remain at 2019 levels over 10 years, cumulative incident cases in the cohort would be approximately 2.0 million for IHD and 2.6 million for stroke, costing USD 61.6 billion for IHD and USD 104.6 billion for stroke. Compared with the status quo, reducing mean salt intake towards the targets over 10 years would avert 1–3% of IHD and stroke events and save up to 2% of related national healthcare costs. Attaining dietary salt-reduction goals among adults would yield moderate health economic benefits in Japan