Human Th1 responses driven by IL-12 are associated with enhanced expression of CD40 ligand

IL- 12 is the prominent inducer of Th1 responses in humans and in the mouse. CD40 ligand (CD40L) plays important roles in regulation of immune responses, including T cell-dependent activation of B cells and cytokine production by monocytes and dendritic cells. The present study examined the influences of IL-12 on the CD40L expression of activated human CD4⁺ T cells. IL-12 enhanced CD40L expression on CD4⁺ T cells stimulated with immobilized anti-CD3 in the complete absence of accessory cells, whereas IL-4 and IL-10 decreased it. Exogenous interferon-gamma (IFN-γ) did not increase CD40L expression on immobilized anti-CD3 stimulated CD4⁺ T cells at any time up to 168 h of culture. The IL-12-induced enhancement of CD40L expression on anti-CD3 activated CD4⁺ T cells was not influenced in the presence of a metalloproteinase inhibitor KB8301, which up-regulated CD40L expression by preventing the processing of membrane-bound CD40L, or B cells, which down-regulated CD40L expression by receptor-mediated endocytosis. These results indicate that IL-12 enhances the CD40L expression of activated CD4⁺ T cells independently of the IFN-γ production. The data thus suggest that Th1 responses induced by IL-12 might play an important role in the regulation of humoral immune responses through up-regulated CD40L expression.     

Five Cases with Ectopic Esophageal Sebaceous Glands

Abstract: Sebaceous glands in the esophagus are considered to be rare and are of particular interest because of their as yet unknown origin. Six postmortem and 48 antemortem cases with this condition have been reported. We report herein five cases diagnosed by endoscopy and biopsy, with a review of the pertinent literature. The hypotheses that gastroesophageal reflux disease (GERD), alcohol consumption, smoking, and hyperlipidemia play roles in the pathogenesis of ectopic sebaceous glands of the esophagus are not supported by current evidence. Given the gradual increase in reports of adult cases with ectopic esophageal sebaceous glands, we suspect that these lesions may not be as rare as generally assumed.     

Efficacy of a Novel Prophylactic Barbiturate Therapy for Severe Traumatic Brain Injuries: Step-down Infusion of a Barbiturate with Normothermia

This study aimed to examine the beneficial effects of a novel prophylactic barbiturate therapy, step-down infusion of barbiturates, using thiamylal with normothermia (NOR+sdB), on the poor outcome in the patients with severe traumatic brain injuries (sTBI), in comparison with mild hypothermia (MD-HYPO). From January 2000 to March 2019, 4133 patients with TBI were admitted to our hospital. The inclusion criteria were: a Glasgow coma scale (GCS) score of ≤8 on admission, age between 20 and 80 years, intracranial hematoma requiring surgical evacuation of the hematoma with craniotomy and/or external decompression, and patients who underwent management of body temperature and assessed their outcome at 6–12 months. Finally, 43 patients were included in the MD-HYPO (n = 29) and NOR+sdB (n = 14) groups. sdB was initiated intraoperatively or immediately after the surgical treatment. There were no significant differences in patient characteristics, including age, sex, past medical history, GCS on admission, type of intracranial hematoma, and length of hospitalization between the two groups. Although NOR+sdB could not improve the patient’s poor outcome either at discharge from the intensive care unit (ICU) or at 6–12 months after admission, the treatment inhibited composite death at discharge from the ICU. The mean value of the maximum intracranial pressure (ICP) in the NOR+sdB group was <20 mmHg throughout the first 120 h. NOR+sdB prevented composite death in the ICU in patients with sTBI, and we may obtain novel insights into the beneficial role of prophylactic barbiturate therapy from suppression of the elevated ICP during the first 120 h.     

Treatment of Pituitary Carcinomas and Atypical Pituitary Adenomas: A Review

Atypical pituitary adenomas (APAs) are aggressive tumors, harboring a Ki-67 (MIB-1) staining index of 3% or more, and positive immunohistochemical staining for p53 protein, according to the World Health Organization (WHO) classification in 2004. Pituitary carcinomas (PC) usually develop from progressive APAs and predominantly consist of hormone-generating tumors, defined by the presence of disseminations in the cerebrospinal system or systemic metastases. Most of the cases with these malignant pituitary adenomas underwent surgeries, irradiations and adjuvant medical treatments, nevertheless, the therapies are mainly palliative. Recently, the efficacy of temozolomide (TMZ), an orally administered alkylating agent, has been reported as an alternative medical treatment. However, some recent studies have demonstrated a significant recurrence rate after effective response to TMZ. Further clinical and pathological researches of malignant pituitary adenomas will be required to improve the outcome of patients with these tumors.     

A case control study of female systemic lupus erythematosus in Japan

In a multi-institutional case-control study, we investigatedrisk factors for systemic lupus erythematosus (SLE) in 151 Japanesewomen treated for SLE during the period September 1988 to August1990. We used two control groups: sisters of SLE patients andsisters of female patients with another disease. Informationwas obtained by a self-administered questionnaire. Our findingssuggest that having a history of operations and blood transfusionsand working in a cold environment may be risk factors for SLE.Viral infections, psychological stress, and pet ownership werenot risk factors for SLE in our study. In addition, smokingwas not protective for SLE. Skin sensitivity to sunlight andcold feet, which may be symptoms of SLE that occurred beforethe diagnosis, were also positively associated with SLE.     

Factors Associated with Rapidly Deteriorating Myelopathy in Patients with Spinal Arteriovenous Shunts

Spinal arteriovenous (AV) shunts are rare conditions that sometimes present with myelopathy symptoms. The progression of the symptoms is usually gradual; however, some cases show rapid deterioration. We retrospectively investigated the factors that induced the rapid deterioration of myelopathy symptoms in patients with spinal AV shunts. We treated 33 patients with myelopathy with spinal AV shunts at our institutions, eight of whom experienced rapid deterioration (within 24 hours: 24.2%). Of these, three were related to the body movement or particular postures associated with playing golf, 30 minutes of Japanese straight sitting, and massage care. One patient showed deterioration after embolization for a tracheal aneurysm. The remaining four patients received steroid pulse therapy (high-dose steroid infusion) shortly before the rapid deterioration. These symptoms stopped progressing after cessation of steroid use. While positional or physical factors contributing to myelopathy deterioration might exist, we could not identify specific factors in this study. Nevertheless, rapid deterioration was frequently observed after high-dose steroid use. We must take care not to administer high-dose steroids for myelopathy caused by spinal AV shunt disease.