A Clinicopathologic Case Report of Inflammatory Pseudotumors Involving the Conjunctiva and Lung

Background Inflammatory pseudotumors are characterized histopathologically by aggregates of inflammatory lymphocytes, plasma cells, neutrophils, and fibroblasts. We report a rare case of inflammatory pseudotumor involving both the conjunctiva and lung.Case A 58-year-old man with a 6-year history of pulmonary inflammatory pseudotumor was referred to our hospital for evaluation of conjunctival swelling in the left eye and bilateral iritis.Observations The subconjunctival tumor enlarged slowly, but regressed spontaneously. After partial resection of the subconjunctival and lung tumors, the presence was confirmed of aggregates of chronic inflammatory cells (lymphocytes, plasma cells, neutrophils, fibroblasts) without noncaseating epithelioid granuloma formation. Gene rearrangement testing ruled out malignancy. The patient was treated with oral corticosteroids for fever and primary biliary hepatic cirrhosis. Iritis signs subsided slightly in response to corticosteroids, but persisted. The temporal subconjunctival pseudotumor resolved without recurrence.Conclusions This case was compatible histopathologically with inflammatory pseudotumor, and is a rare case of simultaneous occurrence in the lung and conjunctiva. Jpn J Ophthalmol 2004;48:573–577 © Japanese Ophthalmological Society 2004     

Gender and age differences in lifestyle factors related to hypertension in middle-aged civil service employees

The aim of this study is to identify lifestyle factors related to hypertension in man and woman workers, and to investigate age and gender differences in the relationships of the factors. From 6,000 civil service employees (4,937 men and 1,063 women) aged 40-69 years, information on lifestyle-related factors such as stress, exercise habits, preference for salty taste, alcohol drinking and smoking habits, and body mass index, as well as age and family history of hypertension was obtained through self-administered questionnaires in 1997. Hypertension was defined as either a systolic blood pressure > or = 140 mmHg, a diastolic blood pressure > or = 90 mmHg, or undergoing treatment for hypertension, and was present by 37.0% in men and 19.6% in women. Only body mass index was a significant lifestyle-related risk factor common to both genders with an odds ratio and its 95% confidence interval in parentheses of 2.2 (2.0-2.5) for men and 3.2 (2.3-4.6) for women. Men and women who preferred salty taste showed multivariate adjusted odds ratios of 0.9 (0.8-1.1) and 1.5 (1.1-2.2) for hypertension, respectively. In the stratified subanalysis, women aged 50 years and over had a significant odds ratio of 2.7 (1.5-4.9), whereas women aged 40-49 years and men of all age classes failed to show significant relationships. Salt intake was suggested to be a key factor for hypertension particularly for women after menopause.     

Rhabdomyolysis Caused by Gefitinib Overdose

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are common therapeutic agents for EGFR mutation-positive advanced non-small-cell lung cancer. There has been no report of rhabdomyolysis caused by an overdose of EGFR-TKIs. We herein review the existing literature on the subject and report a rare case of rhabdomyolysis due to an overdose of gefitinib, an EGFR-TKI.     

Combined effect of sesamin and α-lipoic acid on hepatic fatty acid metabolism in rats

Purpose

Dietary sesamin (1:1 mixture of sesamin and episesamin) decreases fatty acid synthesis but increases fatty acid oxidation in rat liver. Dietary α-lipoic acid lowers hepatic fatty acid synthesis. These changes can account for the serum lipid-lowering effect of sesamin and α-lipoic acid. It is expected that the combination of these compounds in the diet potentially ameliorates lipid metabolism more than the individual compounds. We therefore studied the combined effect of sesamin and α-lipoic acid on lipid metabolism in rats.

Methods

Male Sprague–Dawley rats were fed diets supplemented with 0 or 2 g/kg sesamin and containing 0 or 2.5 g/kg α-lipoic acid for 22 days.

Results and conclusions

Sesamin and α-lipoic acid decreased serum lipid concentrations and the combination of these compounds further decreased the parameters in an additive fashion. These compounds reduced the hepatic concentration of triacylglycerol, the lignan being less effective in decreasing this value. The combination failed to cause a stronger decrease in hepatic triacylglycerol concentration. The combination of sesamin and α-lipoic acid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Sesamin strongly increased the parameters of hepatic fatty acid oxidation enzymes. α-Lipoic acid antagonized the stimulating effect of sesamin of fatty acid oxidation through reductions in the activity of some fatty acid oxidation enzymes and carnitine concentration in the liver. This may account for the failure to observe strong reductions in hepatic triacylglycerol concentration in rats given a diet containing both sesamin and α-lipoic acid.     

Safe Concurrent Use of Anti-tuberculosis Drugs and Pembrolizumab in a Patient with Non-small-cell Lung Cancer Who Was Infected with Mycobacterium tuberculosis

A 68-year-old Japanese man was diagnosed with lung adenocarcinoma stage IVB. We introduced a first-line chemotherapy of four cycles of carboplatin and pemetrexed and pembrolizumab, followed by pemetrexed and pembrolizumab maintenance therapy. Approximately four months after anticancer therapy, a small nodule appeared in the right peripheral S3 lesion. After five months, the nodule was confirmed as a Mycobacterium tuberculosis (TB) nodule. We initiated anti-TB therapy without stopping pembrolizumab, and the right S3 nodule shrank immediately. This report supports the concurrent use of anti-TB treatment with an immune checkpoint inhibitor when the TB infection area is limited.     

Endoscopic ultrasound-guided transmural drainage for pancreatic fistula or pancreatic duct dilation after pancreatic surgery

Background

Endoscopic ultrasound (EUS)-guided drainage is widely used to manage pancreatic pseudocysts. Several studies have reported the use of EUS-guided drainage for pancreatic fistula and stasis of pancreatic juice caused by stricture of the pancreatic duct after pancreatic resection.

Methods

At the authors’ hospital, 262 patients underwent surgery involving pancreatic resection from April 2005 to March 2010. In 90 of these patients (34%), a grade B or C postoperative pancreatic fistula developed that required additional treatment. The authors performed EUS-guided transmural drainage (EUS-TD) for six patients (2.1%) with a pancreatic fistula or dilation of the main pancreatic duct visible by EUS. Percutaneous drainage was provided for 18 patients (6.8%). The success rates for EUS-TD and percutaneous drainage were compared in a retrospective analysis.

Results

In all six cases, EUS-TD was performed successfully without complications. Five of the six patients were successfully treated with only one trial of EUS-TD. The final technical success rate was 100% for both EUS-TD and percutaneous drainage. Both the short- and long-term clinical success rates for EUS-TD were 100% and those for percutaneous drainage were 61.1 and 83%, respectively. The differences in these rates were not significant (short-term success, P?=?0.091 vs. long-term success, P?=?0.403). However, the time to clinical success was significantly shorter with EUS-TD (5.8?days) than with percutaneous drainage (30.4?days; P?=?0.0013) in the current series.

Conclusions

The EUS-TD approach appears to be a safe and technically feasible alternative to percutaneous drainage and may be considered as first-line therapy for pancreatic fistulas visible by EUS.     

Severe Post-COVID-19 Organizing Pneumonia during Cancer Immunochemotherapy

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.     

Maternal GABAergic and GnRH/corazonin pathway modulates egg diapause phenotype of the silkworm Bombyx mori

Diapause represents a major developmental switch in insects and is a seasonal adaptation that evolved as a specific subtype of dormancy in most insect species to ensure survival under unfavorable environmental conditions and synchronize populations. However, the hierarchical relationship of the molecular mechanisms involved in the perception of environmental signals to integration in morphological, physiological, behavioral, and reproductive responses remains unclear. In the bivoltine strain of the silkworm Bombyx mori, embryonic diapause is induced transgenerationally as a maternal effect. Progeny diapause is determined by the environmental temperature during embryonic development of the mother. Here, we show that the hierarchical pathway consists of a γ-aminobutyric acid (GABA)ergic and corazonin signaling system modulating progeny diapause induction via diapause hormone release, which may be finely tuned by the temperature-dependent expression of plasma membrane GABA transporter. Furthermore, this signaling pathway possesses similar features to the gonadotropin-releasing hormone (GnRH) signaling system for seasonal reproductive plasticity in vertebrates.

To ensure survival under unfavorable environmental conditions and synchronize populations, most insect species enter diapause, which is a seasonal adaptation that evolved as a specific subtype of dormancy (1, 2). Diapause is not a passive response to changing conditions but rather an actively induced state that precedes adverse natural situations. Therefore, this diapause phenotype is accompanied by changes in energy metabolism or storage to improve cold/stress tolerance in later life stages, or progeny via reproductive switch (3). Although it has been generally suggested that brain/neuroendocrine systems are associated with this seasonal reproductive plasticity in both vertebrates and invertebrates (3, 4), the hierarchical relationship of the molecular mechanisms involved in the perception of environmental signals to integration into morphological, physiological, behavioral, and reproductive responses, known as the diapause syndrome, remains unclear (3).The silkworm Bombyx mori is a typical insect that arrests normal development during early embryogenesis, which is accompanied by metabolic changes in diapause (5, 6). The development of diapause-destined embryos is arrested during the G2 cell cycle stage immediately after the formation of the cephalic lobe and telson and sequential segmentation of the mesoderm (7). The bivoltine strain of B. mori has two generations per year, and progeny diapause is transgenerationally induced as a maternal effect and is determined by the environmental temperature, photoperiod, and nutrient conditions during embryonic and larval development of the mother (5, 6). The temperature signal during the mother’s embryonic development predominantly affects diapause determination, even if silkworms of the bivoltine Kosetsu strain are exposed to all cases of photoperiods during embryonic and larval development. In the Kosetsu strain, when eggs are incubated at 25 °C under continuous darkness, the resultant female moths (25DD) lay diapause eggs in almost all cases. In contrast, incubation of eggs at 15 °C in dark condition results in moths (15DD) that lay nondiapause eggs in almost all cases (6).Embryonic diapause is induced by the diapause hormone (DH) signaling pathway, which consists of highly sensitive and specific interactions between a neuropeptide, DH, and DH receptor (DHR) (6, 8). DH is exclusively synthesized in seven pairs of neurosecretory cells (DH-PBAN–producing neurosecretory cells [DHPCs]) located within the subesophageal ganglion (SG) in the mother’s generation (6). DH is released into the hemolymph during pupal–adult development and acts on the DHR, which belongs to the G protein-coupled receptors (GPCRs) (9). DH levels in the hemolymph are higher in the 25DD than 15DD pupae in the middle of pupal–adult development when the developing ovaries are sensitive to DH (6). Furthermore, the embryonic Bombyx TRPA1 ortholog (BmTRPA1) acts as a thermosensitive channel that is activated at temperatures above ∼21 °C and affects diapause induction through DH release (10). However, there remain questions about the thermal information that is received by BmTRPA1 and linked to DH signaling to induce diapause.From the 1950s, it has been suggested that the DH release was controlled by signals derived from certain region(s) in the brain based on surgical experiments, such as midsagittal bisection or transection (11–13). Especially, the operation in nondiapause producers changed them to diapause producers while transection of the protocerebrum had no effect on the diapause producers. These surgical results suggested the involvement of the protocerebrum in the inhibitory control of DH secretion (12, 14). Furthermore, the accumulation of the ovarian 3-hydroxykynurenine (3-OHK) pigment that accompanies the diapause syndrome was affected by injection with γ-aminobutyric acid (GABA) and the plant alkaloid picrotoxin (PTX), which is a widely used ionotropic GABA and glycine receptor antagonist (15, 16), and the selective ionotropic GABA receptor (GABAR) antagonist bicuculline. This suggests that a GABAergic neurotransmission via ionotropic GABAR is involved in DH secretion, which may be active in nondiapause producers but inactive in diapause producers throughout the pupal–adult development (14, 17). In general, ionotropic GABAR is composed of homo- or hetero-pentameric subunits. All known GABAR subunits display a similar structural scheme, with a large N-terminal extracellular domain involved in the formation of a ligand-binding pocket and a pore domain made of four transmembrane alpha-helices (TM1–TM4) (16, 18). Four homologous sequences of the ionotropic GABAR subunit genes were identified as RDL, LCCH3, GRD, and a GRD-like sequence named 8916 in various insects (19). However, the in vivo physiological roles of both signals derived from the brain and the GABAergic pathway in diapause induction have not been previously investigated.Corazonin (Crz) is an undecapeptide neurohormone sharing a highly conserved amino acid (a.a.) sequence across insect lineages and is involved in different physiological functions, such as heart contraction (20), stress response (21, 22), various metabolic activities (23–25), female fecundity (26), melanization of locust cuticles (27), regulation of ecdysis (28, 29), and control of caste identity (30). Moreover, Crz belongs to the gonadotropin-releasing hormone (GnRH) superfamily alongside adipokinetic hormone (AKH) and AKH/Crz-related peptide (ACP). Duplicates of an ancestral GnRH/Crz signaling system occurred in a common ancestor of protostomes and deuterostomes through coevolution of the ligand receptor (31, 32).Herein, we demonstrated that the hierarchical pathway consists of a GABAergic and Crz signaling system modulating progeny diapause induction by acting on DH release. We propose that the PTX-sensitive GABAergic signal may act to chronically suppress Crz release in dorsolateral Crz neurons (under nondiapause conditions) and that diapause conditions (or PTX injection) inhibits GABAergic signaling, resulting in accelerated Crz release, which in turn induces DH release. GABA signaling may be finely tuned by the temperature-dependent expression of the plasma membrane GABA transporter (GAT), which differs between the 25DD and 15DD conditions. Furthermore, this signaling pathway possesses similar features to the GnRH signaling system with respect to seasonal reproductive plasticity in vertebrates.