Protective properties of a fusion pneumococcal surface protein A (PspA) vaccine against pneumococcal challenge by five different PspA clades in mice

An increase in the appearance of nonvaccine serotypes in both children and adults with invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine represents a limitation of this vaccine. In this study, we generated three recombinant pneumococcal surface protein A (PspA) proteins comprising PspA families 1 and 2, and we examined the reactivity of antisera raised in mice immunized with a PspA fusion protein in combination with CpG oligonucleotides plus aluminum hydroxide gel. The protective effects of immunization with PspA fusion proteins against pneumococcal challenge by strains with five different PspA clades were also examined in mice. Flow cytometry demonstrated that PspA3+2-induced antiserum showed the greatest binding of PspA-specific IgG to all five challenge strains with different clades. PspA2+4- or PspA2+5-induced antiserum showed the lowest binding of PspA-specific IgG to clade 3. Immunization with PspA3+2 afforded significant protection against pneumococcal challenge by five strains with different clades in mice, but immunization with PspA2+4 or PspA2+5 failed to protect mice from pneumococcal challenge by strains with clades 1 and 3. The binding of PspA-specific IgG in antisera raised by three PspA fusion proteins was examined in 68 clinical isolates from adult patients with IPD. Immunization of mice with PspA3+2-induced antiserum with a high binding capacity for clinical isolates expressing clades 1–4, but not clade 5. Our results suggest that the PspA3+2 vaccine has an advantage over the PspA2+4 or PspA2+5 vaccine in terms of a broad range of cross-reactivity with clinical isolates and cross-protection against pneumococcal challenge in mice.     

A biochemical study of the distribution of collagen and its crosslinks in knee ligaments and the patellar tendon

Purpose: The purpose of this study was to investigate biochemical differences in collagen crosslinks from different locations within the ligaments and a tendon of the human knee.

Materials and Methods: The anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), lateral collateral ligament (LCL), and patellar tendon (PT) were obtained from 24 cadavers (13 men and 11 women) whose average age at the time of death was 84.8 years. Ligaments and PT samples were obtained from the femoral and tibial insertions and the midsubstance. Hydroxyproline (Hyp) and collagen crosslinks, including pyridinoline (Pyr) and pentosidine (Pen), were compared among the different sites.

Results: The midsubstance Hyp concentration was greater than at the femoral and tibial insertions in the ACL (p?=?0.00124 and 0.000255, respectively) and PCL (p?=?0.00036 and 0.042, respectively). The Pyr:collagen ratio did not differ among sites in any of the ligaments or PT. The Pen:collagen ratio at the midsubstance was greater than at the femoral and tibial insertions in the ACL (p?=?0.00022 and 0.00025, respectively) and LCL (p?=?0.000081 and 0.000021, respectively) and was greater at the femoral insertion in the MCL (p?=?0.00010).

Conclusions: The mature collagen crosslink Pyr was not different in distribution in knee ligaments and the PT. Pen increased at the midsubstance ligaments and the PT. As increased Pen may represent ligament degeneration, this may indicate that degeneration may progress more rapidly at the midsubstance than at the insertion sites of a ligament.     

Sialolithiasis in two areas of the upper lip

Objective

Minor salivary gland sialolithiasis occurs in ~1 % of all sialolithiasis cases. We report a case of sialolithiasis considered to have occurred in the minor salivary gland in two areas of the upper lip, with special emphasis on the findings from image examinations.

Case report

A 33-year-old male complained of a painless mass on the left upper lip. At the first examination, there was a nodular, hard swelling that involved the left cuspid area of the upper lip. Although a panoramic radiograph revealed no abnormality, an intraoral radiograph showed a small radiopaque body with a laminar pattern. Computed tomography images indicated that a calcified body was present in two areas of the upper lip. On magnetic resonance imaging, the lesion was observed as a lower-signal area than the surrounding soft tissue. The mass had a high signal in the central area in the T2 and short T1 inversion recovery images. The sonogram showed a hypoechoic mass with an echogenic structure in the central area. An excisional biopsy of the left upper lip was performed under local anesthesia. A well-demarcated mass with a calcified body was enucleated. The histopathologic diagnosis was sialoadenitis with sialolithiasis.

Conclusion

Most cases of minor salivary gland sialolithiasis are solitary, with multiple sialolithiasis being extremely rare. Sonograms are useful in the diagnosis of minor salivary gland sialolithiasis. Careful imaging examination is necessary to identify multiple lesions and select appropriate treatments.     

Understanding the immunopathogenesis of COVID-19: Its implication for therapeutic strategy

Although 80% of individuals infected with the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) recover without antiviral treatments, the other 20% progress to severe forms of pulmonary disease, suggesting that the host’s immune response to the virus could influence the outcome of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects alveolar epithelial type 2 cells expressing angiotensin-converting enzyme 2, and these infected epithelial cells recruit dendritic cells, neutrophils and monocytes /macrophages, leading to the activation of CD4+ and CD8+ T cells. These cells launch an antiviral immune response, but are able to completely suppress viral replication or completely eradicate virus in a limited proportion of infected patients. In other patients, viral suppression is incomplete and the numbers of circulating B and T cells are subsequently reduced by as yet unknown mechanisms. Some patients with sustained viral replication progress to a severe condition called cytokine storm. Although antiviral drug(s) should be considered early in infection to prevent progression, there have been no antiviral therapies proven to be effective for significantly inhibiting the viral replication in vivo and suppressing the progression to cytokine storm. Blocking the action of cytokines with dexamethasone or anti-interleukin-6 could have a pivotal role in treatment of those patients. Therapeutic strategy should therefore be based on viral kinetics and the immunopathology of COVID-19.     

Recurrent esophageal carcinoma after esophagectomy with three-field lymph node dissection

To evaluate the effect of the extended lymphadenectomy for thoracic esophageal carcinoma, the pattern of recurrence in the 50 patients with pT3 tumors who underwent esophagectomy with cervical, mediastinal, and abdominal lymph node dissection (3-F) (group A) was compared with that of 100 patients at pT3 who underwent esophagectomy without upper mediastinal and cervical lymphadenectomy (2-F) (group B). The cumulative 5-year survival rate for 115 patients who underwent 3-F was 50.9%. Cumulative 5-year survival rates for patients in groups A and B were 36.8% and 22.0%, respectively. The survival curve for group A was significantly better than group B (P = 0.02332). Lymphatic recurrence was noted less frequently in group A (8/23) than in group B (31/49) (χ² = 5.1149), whereas the rate of hematogenous recurrence was similar. Extension of the field of lymph node dissection reduced the lymph node recurrence in patients with thoracic esophageal carcinoma, which may have positively affected patient survival. © 1996 Wiley-Liss, Inc.     

Tumor necrosis factor and interleukin-1β: suppression of food intake by direct action in the central nervous system

Intracerebroventricular microinfusion of recombinant human tumor necrosis factor (rhTNF) and recombinant human interleukin-1β (rhIL-1β) suppressed food intake in rats. Central infusion of heat-inactivated rhTNF and rhIL-1β, bovine serum albumin, heparin or transforming growth factor-β had no such effect. Central infusion of rhIL-1β did not affect the dipsogenic response to central administration of angiotensin II. Peripheral administration of rhTNF and rhIL-1β in doses equivalent to or higher than those administered centrally had no effect. Electrophoretically applied rhTNF and rhIL-1β specifically suppressed the activity of glucose-sensitive neurons in the lateral hypothalamic area. Glucose-insensitive neurons were little affected. The results suggest that TNF and IL-1β act directly in the central nervous system to suppress feeding, and this effect may be operative during acute and chronic disease.