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The article discusses into a rare case of microgeodic disease emerging in an elderly woman, marked by redness, swelling, and pain in the fingers, providing insights into its diagnosis and treatment. It mentions that study focused on fostering positive attitudes toward dementia, aiming to identify the factors influencing societal perceptions of dementia and encouraging social participation, emphasizing the need for informed strategies to facilitate inclusion of individuals with dementia.

Corynebacterium striatum occasionally causes nosocomial infections, such as catheter-related bloodstream infection and pneumonia; however, C. striatum- related infective endocarditis or septic arthritis is uncommon. We present the case of an 85-year-old woman with infective endocarditis at the native valve and septic arthritis at the native shoulder joint caused by C. striatum. The patient was admitted for a 10-day history of fever and right shoulder pain. She had no history of artificial device implantation, injury, arthrocentesis, or hospitalization. A physical examination revealed conjunctival petechiae, a systolic heart murmur, and right shoulder joint swelling. C. striatum was observed in two blood culture sets. Transesophageal echocardiography revealed vegetation in the right aortic coronary cusp. Arthrocentesis at the right shoulder aspirated pyogenic fluid and C. striatum was detected in the culture. The patient was diagnosed with infective endocarditis and septic arthritis caused by C. striatum, and ampicillin was administered based on antimicrobial susceptibility test results. The patient's condition was initially stable; however, she developed pulmonary congestion on day 56 and eventually died. An autopsy demonstrated perforation of the aortic left coronary cusp with vegetation. C. striatum may cause native valve endocarditis and native joint septic arthritis. [ABSTRACT FROM AUTHOR]

Elevation of ALP is an abnormal feature in TAFRO syndrome, but the cause is unknown. This article is the first report that histologically showed intrahepatic cholangitis may be the cause of ALP elevation in TAFRO syndrome. [ABSTRACT FROM AUTHOR]

• Ceftriaxone can cause encephalopathy in patients with end-stage renal disease. • Ceftriaxone-associated encephalopathy (CAE) can develop even at a dose of 1 g/day. • A high blood and cerebrospinal fluid ceftriaxone level may be CAE-related. • Estimation of ceftriaxone level may contribute to an accurate diagnosis. Neurotoxicity is a rare and intolerable adverse effect of ceftriaxone therapy. In most cases, it has been diagnosed on the basis of medical history rather than quantitative blood and cerebrospinal fluid testing. We report the case of a woman aged 78 years with ceftriaxone-associated encephalopathy. She regularly underwent hemodialysis. The patient received intravenous ceftriaxone at a dose of 1 g/day for 10 days for a urinary tract infection, and her consciousness level began to deteriorate during the therapy. Five days after ceftriaxone discontinuation, her symptoms rapidly improved. Thus, ceftriaxone-associated encephalopathy was suspected. Ceftriaxone levels in the blood and cerebrospinal fluid were high while the patient had disturbed consciousness. This case showed that ceftriaxone levels were related to ceftriaxone-associated encephalopathy. Therefore, the estimation of ceftriaxone levels may facilitate an accurate diagnosis. [ABSTRACT FROM AUTHOR]

What is known and objective: Daptomycin‐induced creatinine phosphokinase (CPK) elevation is reported to be associated with its trough level (Ctrough; breakpoint of 24.3 μg/mL). However, even with high‐dose treatment (ie, > 8 mg/kg), the safety of daptomycin treatment is widely demonstrated with low or no significant incidence of CPK elevation or other adverse effects, despite the possibility of Ctrough above 24.3 μg/mL. Therefore, we questioned the clinical significance of Ctrough levels of 24.3 μg/mL. In this study, we retrospectively evaluated the significance of Ctrough in the clinical setting, in addition to completing a retrospective safety assessment of daptomycin utilizing electronic health records. Methods: Patients who had received daptomycin treatment for > 4 days from July 2011 to June 2015 were enrolled. Serum daptomycin levels, including Ctrough and peak (Cpeak), were measured by high‐performance liquid chromatography equipped with a photodiode array. To evaluate the safety, patients' characteristics and relevant laboratory test values were reviewed retrospectively using an electronic medical record system. Results and discussion: A total of 52 therapeutic cases for 46 patients were identified; of these, Ctrough and Cpeak levels were measured in 27 and 28 cases, respectively, and 6 patients received multiple courses of daptomycin treatment. The median age of the 52 patients was 68 years (range: 19‐88 years), and 14 patients initially had an estimated creatinine clearance of less than 30 mL/min. Seven cases indicated a Ctrough of above 24.3 μg/mL; however, none of these presented CPK elevation, which meets with the study definition for abnormality. Furthermore, of the two patients with abnormal CPK elevations, only one patient had a measured Ctrough (of 10.9 μg/mL). Their CPK abnormalities were temporal and did not result in treatment discontinuation. The other four patients discontinued daptomycin treatment due to suspicions of adverse effects. Of the discontinued patients, two had measured Ctrough levels; these were 8.6 and 8.1 μg/mL. All patients with abnormal CPK elevation or treatment discontinuation exhibited Ctrough levels lower than 24.3 μg/mL. In this study, two patients receiving high‐dose daptomycin (ie, 9.4 and 10.0 mg/kg) had observed Ctrough levels similar to patients who received doses of daptomycin < 9 mg/kg. What is new and conclusions: The safety of daptomycin treatment was suggested in this study. Ctrough level of 24.3 μg/mL was not suggested as a significant clinical index for the incidence of CPK elevation, adverse effects or treatment discontinuation. Thus, acceptable tolerability towards higher Ctrough levels than 24.3 μg/mL was also suggested, though further studies are required. On the other hand, low levels of daptomycin in blood were unexpectedly observed in two cases, despite the high‐dose treatments. Accordingly, the monitoring of serum daptomycin levels may also be useful to assess cases in which subtherapeutic levels were achieved. [ABSTRACT FROM AUTHOR]

Infections occur more frequently in patients receiving biologics. However, cryptococcal infection is uncommon in patients receiving tocilizumab, an interleukin-6 inhibitor, in contrast to patients receiving tumor necrosis factor-α inhibitors. In this report, we describe a case of disseminated cryptococcosis in a 55-year-old man who was receiving tocilizumab every 2 weeks along with daily prednisolone and cyclosporine for Castleman's disease. He initially developed cellulitis on both upper limbs, and his condition worsened despite antibacterial therapy. Chest X-ray scanning and computed tomography demonstrated bilateral pulmonary infiltration. Cryptococcus neoformans was detected in blood, skin, and sputum cultures. He was diagnosed with disseminated cryptococcosis, and successfully treated with liposomal amphotericin B for a week followed by oral fluconazole for 11 months. The findings of this study indicate that cryptococcosis should be considered during the differential diagnosis of infection in patients receiving tocilizumab, especially in the presence of other risk factors for infections or a short tocilizumab dosing interval. [ABSTRACT FROM AUTHOR]

Wernicke encephalopathy is caused by vitamin B1 deficiency. It presents as a triad consisting of altered mental status, oculomotor dysfunction, and gait ataxia. Early vitamin B1 administration alleviates symptoms. We present a video of gaze‐evoked nystagmus in an elderly patient with Wernicke encephalopathy. It is often difficult to evaluate the mental and ambulatory states of frail elderly patients with dementia. In such cases, nystagmus is the only useful physical finding in the diagnosis of Wernicke encephalopathy. [ABSTRACT FROM AUTHOR]

Rapidly destructive coxarthrosis is a rare entity of unknown etiology that is characterized by rapid hip joint destruction. Blood tests are thought to be non‐specific. However, we herein show a patient with rapidly destructive coxarthrosis, which was accompanied by fluctuating C‐reactive protein level. [ABSTRACT FROM AUTHOR]

Salmonella enterica subsp. arizonae is a bacteria commonly found in the gut of reptiles. In humans, infections caused by this organism are rare. Most cases originate from southwestern United States, where rattlesnake products are often used in traditional medicine. In Asia, only a few cases have been described. This case report documents a case involving a 64-year-old woman with pyelonephritis caused by S. arizonae in Japan. She had no history of contact with reptiles or foreign travel. The likely route of transmission is unclear. She was treated with cephalosporins for 14 days and the pyelonephritis appeared to be resolved; however recurrence occurred twice –after two weeks and then after one month. Prolonged antibiotic therapy with amoxicillin resolved the infection. This case demonstrates that pyelonephritis associated with S. arizonae can be found outside of the typical geographic region and may not be associated with typical animal hosts. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the association between the T 1 ρ and T 2 values and the progression of cartilage degeneration in patients of the same age group. Materials and methods Sagittal T 1 ρ and T 2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T 1 ρ and T 2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T 1 ρ and T 2 values and the degree of patella cartilage degeneration. Results There were no significant differences in age among the four groups. Both the T 1 ρ and T 2 values showed a positive correlation with the degree of OA progression ( ρ = 0.737 and ρ = 0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T 1 ρ mapping, but not in the T 2 mapping. Conclusions Our study confirmed that T 1 ρ and T 2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group. [ABSTRACT FROM AUTHOR]

The article presents a study on articular cartilage degeneration which can develop after anterior cruciate ligament reconstruction (ACLR). It focuses on risk factors in the early postoperative period. The T1ρ spin-lattice relaxation in the rotating frame magnetic resonance imaging is described. The baseline T1ρ value of the medial femoral condyle (MFC) and lateral FC (LFC) was higher in patients with cartilage lesions.

Abstract: Objective: The purpose of this study was to clarify the detectability of the International Cartilage Repair Society (ICRS) grade 1 cartilage lesions in anterior cruciate ligament (ACL)–injured knees using T1ρ and T2 mapping. Materials and Methods: We performed preoperative T1ρ and T2 mapping and 3D gradient–echo with water–selective excitation (WATS) sequences on 37 subjects with ACL injuries. We determined the detectability on 3D WATS based on arthroscopic findings. The T1ρ and T2 values (ms) were measured in the regions of interest that were placed on the weight–bearing cartilage of the femoral condyle. The receiver operating characteristic (ROC) curve based on these values was constructed using the arthroscopic findings as a reference standard. The evaluation of cartilage was carried out only in the weight–bearing cartilage. The cut–off values for determining the presence of a cartilage injury were determined using each ROC curve, and the detectability was calculated for the T1ρ and T2 mapping. Results: The cut–off values for the T1ρ and T2 were 41.6 and 41.2, respectively. The sensitivity and specificity of T1ρ were 91.2% and 89.5%, respectively, while those of T2 were 76.5% and 81.6%, respectively. For the 3D WATS images, the same values were 58.8% and 78.9%, respectively. Conclusions: Our study demonstrated that the T1ρ and T2 values were significantly higher for ICRS grade 1 cartilage lesions than for normal cartilage and that the two mappings were able to non–invasively detect ICRS grade 1 cartilage lesions in the ACL–injured knee with a higher detectability than were 3D WATS images. [Copyright &y& Elsevier]

Abstract: Objective: To study the effects of aging and cartilage degeneration of the proximal tibiofibular- and femorotibial joint (PTFJ, FTJ) on the cartilage of the PTFJ using T 1 ρ and T 2 mapping. Materials and methods: We performed sagittal T 1 ρ and T 2 mapping of the PTFJ and FTJ on 55 subjects with knee disorders. We placed 3 regions of interest (ROIs) on images of the cartilage in the PTFJ, medial femoral condyle (MFC), and medial tibia plateau (MTP). Correlation analysis was performed for the T 1 ρ and T 2 values of each ROI and the patient age and the osteoarthritic grade of the PTFJ and FTJ. Results: The T 1 ρ and T 2 values of the PTFJ were affected neither by aging nor the osteoarthritic grade of the FTJ. Values of the FTJ normalized to PTFJ values were correlated with the osteoarthritic grade of the FTJ in the MFC (r =0.851 and 0.779, respectively) and the MTP (r =0.635 and 0.762, respectively). There was a significant difference in the T 1 ρ but not the T 2 value of the PTFJ and MFC between normal and mildly osteoarthritic cartilage of each joint. Conclusion: We document that the T 1 ρ and T 2 values of PTFJ cartilage were not affected by aging or cartilage degeneration in the FTJ. The T 1 ρ value of the PTFJ may represent a useful internal standard reference for evaluating early degeneration of the FTJ. [Copyright &y& Elsevier]

Capnocytophaga canimorsus is part of normal gingival flora of dogs and cats. The organism can cause septicemia, meningitis, and endocarditis in humans after contact with dogs or cats. In spite of the frequency of gastrointestinal symptoms in C . canimorsus infection patients, specific gastrointestinal disease or clinical images have not been reported. We report a case of C . canimorsus bacteremia presenting with acute cholecystitis in elderly woman. She suffered from general fatigue and right upper abdominal pain. She had leukocytosis and abnormal liver function tests. She showed abnormal findings of the gallbladder by abdominal computed tomography and ultrasonography. She was diagnosed with acute cholecystitis without gallstones and was administered with antibiotics. C. canimorsus was isolated from blood cultures. A history of an insignificant wound secondary to a dog bite was elicited. She recovered completely with antibiotic treatment. This case revealed that C. canimorsus bacteremia can be presented with acute cholecystitis, suggesting that C. canimorsus could cause cholecystitis. And this cholecystitis can be treated with antibiotics without operation. Physicians seeing patients with acute cholecysitis should ask questions regarding animal contact. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Negative myoclonus may present in the early stages of cefepime neurotoxicity. Cefepime neurotoxicity typically presents as reduced consciousness, myoclonus, and seizures; however, negative myoclonus is uncommon. This video shows an older woman with cefepime neurotoxicity that presented as a negative myoclonus of the upper limbs. [ABSTRACT FROM AUTHOR]

This article discusses a case of Immunoglobulin-A vasculitis (IgAV) in an adult patient presenting with edema in the scalp, face, and sternocleidomastoid muscle. IgAV is a small-vessel vasculitis that primarily affects children and is characterized by IgA deposits in the vessel walls. While subcutaneous edema in the scalp and face is rare in adults, it has been occasionally reported in children. Muscle involvement in IgAV is also uncommon and typically occurs in the lower extremities. This case highlights the importance of considering exacerbating IgAV and intensifying treatment when adult patients present with edema in the head and neck. Further research is needed to understand the underlying mechanisms and optimize treatments for similar cases. [Extracted from the article]

The article describes a case of an older male patient with vacuoles, E1 enzyme, X-linked autoinflammatory somatic (VEXAS) syndrome. Topics mentioned include the manifestation of granulomatosis with polyangitis, the management of the syndrome using methotrexate and infliximab, the indication of cytogenetic analysis, and the results of the positron emission tomography scan.

Idiopathic CD4 lymphocytopenia (ICL) is a rare disease characterized by marked loss of CD4 T-cells without human immunodeficiency virus infection. CD4 T-cells play an important role in granuloma formation in cryptococcal infection. Thus far, among ICL patients, it has not been concluded definitely whether granuloma is formed or not. We report the case of a 39-year-old woman with ICL and disseminated cryptococcal infection with granuloma formation. She was referred to our department because of a lung mass, osteolytic lesion, and a subcutaneous mass identified on a computed tomography scan, and an elevated C-reactive protein level. Cryptococcus neoformans was isolated from the tissues. She also had marked CD4 lymphocytopenia (33 cells/μL), without human immunodeficiency virus infection. In a biopsy specimen of the lung mass, granulomas containing CD4 T-cells were observed. The cryptococcosis was treated with liposomal amphotericin B followed by fluconazole and she was found to be cured. The CD4 T-cell count was persistently low. This case showed that granulomas containing CD4 T-cells can be formed in ICL patients with cryptococcal infection despite very low CD4 T-cell counts. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes sometimes causes central nervous system infections. However, rhombencephalitis is a rare form of L. monocytogenes infection. Its clinical symptoms and magnetic resonance imaging (MRI) findings are often similar to those of vertebrobasilar stroke. We present the case of a 79-year-old woman with Listeria rhombencephalitis presenting with rhinorrhea and productive cough. She had giant cell arteritis (GCA) treated with prednisolone and methotrexate. She was admitted for loss of appetite, rhinorrhea, and productive cough. These symptoms were alleviated without specific treatment; however, she suddenly developed multiple cranial nerve palsies, and MRI showed hyperintense signals on diffusion-weighted imaging and hypointense signals on apparent diffusion coefficient in the brainstem. Ischemic stroke due to exacerbation of GCA was suspected, and treatment with intravenous methylprednisolone was initiated; however, seizures occurred, and a lumbar puncture was performed. Cerebrospinal fluid and blood cultures revealed L. monocytogenes , and she was diagnosed with Listeria rhombencephalitis. Although antibiotic treatment was continued, the patient died. Thus, when patients with rhinorrhea or productive cough develop sudden cranial nerve palsy, Listeria rhombencephalitis should be considered as a differential diagnosis, and lumbar puncture should be performed. [ABSTRACT FROM AUTHOR]

The emergence of the Alpha variant of novel coronavirus 2019 (SARS-CoV-2) is a concerning issue but their clinical implications have not been investigated fully. We conducted a nested case-control study to compare severity and mortality caused by the Alpha variant (B.1.1.7) with the one caused by the wild type as a control from December 2020 to March 2021, using whole-genome sequencing. 28-day mortality and other clinically important outcomes were evaluated. Infections caused by the Alpha variant were associated with an increase in the use of oxygen (43.4% vs 26.3%. p = 0.017), high flow nasal cannula (21.2% vs 4.0%, p = 0.0007), mechanical ventilation (16.2% vs 6.1%, p = 0.049), ICU care (30.3% vs 14.1%, p = 0.01) and the length of hospital stay (17 vs 10 days, p = 0.031). More patients with the Alpha variant received medications such as dexamethasone. However, the duration of each modality did not differ between the 2 groups. Likewise, there was no difference in 28-day mortality between the 2 groups (12% vs 8%, p = 0.48), even after multiple sensitivity analyses, including propensity score analysis. The Alpha variant was associated with a severe form of COVID-19, compared with the non-Alpha wild type, but might not be associated with higher mortality. [ABSTRACT FROM AUTHOR]

Background: We experienced a pseudo-outbreak of aspergillosis in a newly constructed COVID-19 ward. Within the first 3 months from the commencement of the ward, six intubated patients of COVID-19 developed probable or possible pulmonary aspergillosis. We suspected an outbreak of pulmonary aspergillosis associated with ward construction and launched air sampling for the investigation of the relationship between these. Methods: The samples were collected at 13 locations in the prefabricated ward and three in the general wards, not under construction, as a control. Results: The results from samples revealed different species of Aspergillus from those detected by the patients. Aspergillus sp. was detected not only from the air samples in the prefabricated ward but also in the general ward. Discussion: In this investigation, we could not find evidence of the outbreak that links the construction of the prefabricated ward with the occurrence of pulmonary aspergillosis. It might suggest that this series of aspergillosis was more likely occurred from fungi that inherently colonized patients, and was associated with patient factors such as severe COVID-19 rather than environmental factors. Once an outbreak originating from building construction is suspected, it is important to conduct an environmental investigation including an air sampling. [ABSTRACT FROM AUTHOR]

Skeletal tuberculosis (TB) accounts for a small percentage of all cases of TB. It is often difficult to diagnose, especially in the hip joint. TB arthritis can be masked by superinfection with other pathogens, leading to a delay in diagnosis and treatment. Trauma or surgery is a reported risk factor of TB arthritis. In contrast, descriptions of TB arthritis after a closed bone fracture are rare. We herein report a case involving an 81-year-old woman with septic arthritis superinfected with methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis . Three months before presentation, she sustained a bone fracture of the left femur and was treated conservatively without surgery. She developed a fever at another hospital and was transferred to our institution. Computed tomography revealed the presence of abnormal fluid around the left hip joint. MRSA was detected from the fluid and blood cultures. The patient was diagnosed with MRSA arthritis and treated with antibiotics and surgical drainage. However, her fever persisted, and the abscess further developed and enlarged around the left hip. It was punctured and cultured again. Three weeks later, Mycobacterium tuberculosis was identified from the abscess culture. The septic arthritis was confirmed to have been caused by MRSA and M . tuberculosis . After the initiation of antituberculosis therapy, her fever subsided and the treatment was continued. This case demonstrates that the diagnosis of TB arthritis can be hindered by the existence of other pathogens and that TB arthritis can occur at a closed fracture site in the hip joint. [ABSTRACT FROM AUTHOR]

Campylobacter jejuni and Campylobacter coli are the leading causes of bacterial intestinal infections worldwide, while Campylobacter fetus subsp. fetus (C. fetus) has been reported to cause extraintestinal infections, including medical device implant infections. However, breast implant infections have rarely been reported. We describe the case of a 64-year-old woman with breast implant infection and vertebral osteomyelitis due to C. fetus. The patient recovered by surgical removal of the infected left implant and was treated with antibiotics for 6 weeks. However, two weeks after the completion of antibiotics, she experienced an infection in the right implant due to C. fetus , which had developed quinolone resistance with a G91T mutation during the treatment course. This case showed that C. fetus can cause breast implant infections, and although the infection may appear to be unilateral initially, the possibility of sequential contralateral infection should be considered. [ABSTRACT FROM AUTHOR]

A 56-year-old man presenting with massive melena and loss of consciousness was diagnosed with an infected thoracoabdominal aneurysm, an aortoduodenal fistula, and Leriche syndrome following an evaluation by computed tomography. Emergency surgery for uncontrolled infection included the reconstruction of the superior mesenteric and bilateral renal arteries using a four-branched graft. The aortoduodenal fistula was resected after omental filling, and an enterostomy was performed for feeding. Intestinal reconstruction was performed in two stages. The patient was discharged on postoperative day 48 and was without evidence of recurrence at 23 months postoperatively. [ABSTRACT FROM AUTHOR]

Objectives: Patients with chronic aortic dissection often require repeat interventions due to enlargement of the pressurized false lumen or disseminated intravascular coagulation even after additional thoracic endovascular aortic repair (TEVAR) to occlude the entry tear. Residual false lumen flow can persist even after performing the candy-plug technique or branched stent-graft placement in some cases. We have devised a new method for false lumen closure. Methods: From December 2010 to May 2017, 5 patients (mean age: 57 [13] years, range: 43-77 years) with chronic dissection at the aortic arch and descending aorta, who underwent initial TEVAR, required additional treatment. Using an open surgical approach, the endograft was fixed with an outer felt under cardiopulmonary bypass after the endograft with stent was expanded by fenestration. The false lumen was closed using this procedure, and the aortotomy was repaired by direct closure in 2 cases and by graft replacement in 3 cases. Results: No major operative complications occurred, such as respiratory failure or paraplegia. Postoperative enhanced computed tomography (CT) images showed that the false lumen flow disappeared in all cases. All patients were discharged under normal conditions. They were all followed up and their CT did not indicate any complications for a mean of 33.6 (20.3) months. Conclusions: Our combined procedure was effective and provided a higher success rate compared with endovascular therapy alone. This staged treatment approach, using a combination of TEVAR and false lumen closure, is less invasive compared with open surgery alone and may represent a valid treatment option for chronic type B dissection. [ABSTRACT FROM AUTHOR]

Necrotizing fasciitis is a rapidly progressing bacterial infection of the superficial fascia and subcutaneous tissue that is associated with a high mortality rate and is caused by a single species of bacteria or polymicrobial organisms. Escherichia coli is rarely isolated from patients with monomicrobial disease. Further, there are few reports of extended-spectrum beta-lactamase (ESBL)-producing E. coli associated with necrotizing fasciitis. We report here our treatment of an 85-year-old man who was admitted because of necrotizing fasciitis of his right thigh. Streptococcus equisimilis was detected as a monomicrobial pathogen, and the infection was cured by amputation of the patient's right leg and the administration of antibiotics. However, 5 days after discontinuing antibiotic therapy, he developed necrotizing fasciitis on his right upper limb and died. ESBL-producing E. coli was the only bacterial species isolated from blood and skin cultures. This case demonstrates that ESBL-producing E. coli can cause monomicrobial necrotizing fasciitis, particularly during hospitalization and that a different bacterial species can cause disease shortly after a previous episode. [ABSTRACT FROM AUTHOR]

• Adenosine deaminase (ADA) in the cerebrospinal fluid (CSF) is not specific for diagnosing tuberculous meningitis in HIV infected patients. • Retroviral rebound syndrome can cause meningitis and can also cause ADA elevation in the CSF. • We have to be aware of retroviral rebound syndrome as a cause of ADA elevation in CSF, to avoid unnecessary anti-tuberculous treatment. Adenosine deaminase (ADA) in cerebrospinal fluid (CSF) is considered to be a useful biomarker in differentiating tuberculous meningitis (TBM) from other meningitis in non-HIV patients. However, its specificity decreases in patients with HIV, and other diseases such as cytomegalovirus encephalitis, toxoplasmosis or meningeal lymphomatosis can also elevate ADA in CSF. We here report a rare case of retroviral rebound syndrome in a HIV patient, whose ADA in CSF was elevated. [ABSTRACT FROM AUTHOR]

Platelet aggregation is mediated by conformational change of integrin αIIbβ3. Tyrosine-phosphorylation of cytoplasmic domain of β3 upon platelet activation has been demonstrated to play a critical role in this process. Recently, the adaptor protein ShcA has been shown to bind to the tyrosine-phosphorylated β3, while it remains open whether ShcA plays any role in platelet aggregation. Here, we show that ShcA bound to tyrosine-phosphorylated β3-tail peptide through its phosphotyrosine-binding domain in vitro. Then, we examined the involvement of ShcA in platelet aggregation by a previously established in vitro assay using platelets permeabilized with streptolysin-O, where exogenous addition of platelet cytosol is required for reconstitution of the Ca2+-induced aggregation. When ShcA was specifically depleted with anti-ShcA antibody from the cytosol, this ShcA-depleted cytosol lost the aggregation-supporting activity, which was rescued by addition of purified recombinant ShcA. Thus, ShcA is essential for the Ca2+-induced platelet aggregation. [Copyright &y& Elsevier]

Platelets store self. agonists such as ADP and serotonin in dense core granules. Although exocytosis of these granules is crucial for hemostasis and thrombosis, the underlying mechanism is not fully understood. Here, we show that incubation of permeabilized platelets with unprenylated active mutant Rab27A-Q78L, wild type Rab27A, and Rab27B inhibited the secretion, whereas inactive mutant Rab27A-T23N and other GTPases had no effects. Furthermore, we affinity-purified a GTPRab27A-binding protein in platelets and identified it as Munc13-4, a homologue of Munc13-1 known as a priming factor for neurotransmitter release. Recombinant Munc13-4 directly bound to GTP-Rab27A and -Rab27B in vitro, but not other GTPases, and enhanced secretion in an in vitro assay. The inhibition of secretion by unprenylated Rab27A was rescued by the addition of Munc13-4, suggesting that Munc13-4 mediates the function of GTP-Rab27. Thus, Rab27 regulates the dense core granule secretion in platelets by employing its binding protein, Munc13-4. [ABSTRACT FROM AUTHOR]

Platelets play critical roles in hemostasis and thrombosis through their aggregation following activation of integrin α[sub IIb]β[sub 3]. However, the molecular mechanism of the integrin activation inside platelets remains largely unknown. Pharmacological experiments have demonstrated that protein kinase C (PKC) plays an important role in platelet aggregation. Because PKC inhibitors can have multiple substrates and given that non-PKC-phorbol ester-binding signaling molecules have been demonstrated to play important roles, the precise involvement of PKC in cellular functions requires re-evaluation. Here, we have established an assay for analyzing the Ca[sup 2+]-induced aggregation of permeabilized platelets. The aggregation of platelets was inhibited by the addition of the arginine-glycine-aspartate-serine peptide, an integrin-binding peptide inhibitor of α[sub IIb]β[sub 3], suggesting that the aggregation was mediated by the integrin. The aggregation was also dependent on exogenous ATP and platelet cytosol, indicating the existence of essential cytosolic factors required for the aggregation. To examine the role of PKC in the aggregation assay, we immunodepleted PKCα and β from the cytosol. The PKC-depleted cytosol lost the aggregation-supporting activity, which was recovered by the addition of purified PKCα. Furthermore, the addition of purified PKCα in the absence of cytosol did not support the aggregation, whereas the cytosol containing less PKC supported it efficiently, suggesting that additional factors besides PKC would also be required. Thus, we directly demonstrated that PKCα is involved in the regulation of Ca[sup 2+]-induced platelet aggregation. [ABSTRACT FROM AUTHOR]