Occurrence of clinical depression during combination therapy with pegylated interferon alpha or natural human interferon beta plus ribavirin

Aim: The onset of depression symptoms during pegylated interferon α plus ribavirin (PEG‐IFN/RBV) combination therapy has led to treatment discontinuation in some cases. In the present study, we conducted a questionnaire survey during treatment to determine whether natural human interferon β plus ribavirin (IFNβ/RBV) therapy is associated with a lower incidence of depression symptom onset compared with PEG‐IFN/RBV therapy. Methods: Seventy‐seven patients with chronic hepatitis C received PEG‐IFN/RBV (PR) or IFNβ/RBV (FR) therapy. A questionnaire survey was administered at the start of treatment, and at 4 and 12 weeks, using the Beck Depression Inventory II (BDI‐II) and the Pittsburgh Sleep Quality Index (PSQI). Results: BDI‐II scores in the PR group increased at 4 and 12 weeks, but remained unchanged in the FR group. At 12 weeks, the mean BDI‐II score and incidence of abnormalities with a BDI‐II score of ≥14 were significantly lower in the FR group than in the PR group. BDI‐II scores during IFNβ/RBV therapy in 11 patients currently using antidepressants remained unchanged up to 12 weeks. None of these 11 patients required addition or dose increases of antidepressants, and there was no evidence of worsened depression symptoms. Nine PR patients had BDI‐II scores of ≥14 and PSQI scores of ≥11 at 12 weeks. Conclusions: IFNβ/RBV therapy was associated with a lower incidence of depression symptom onset during treatment. In patients already diagnosed with depression, there was no evidence that IFNβ/RBV therapy caused any worsening of symptoms, indicating that IFNβ/RBV therapy is safe for patients with depression.     

Construction of an osteochondral-like tissue graft combining β-tricalcium phosphate block and scaffold-free mesenchymal stem cell sheet

Background

Aiming to construct an osteochondral-like structure, the combination of a β-tricalcium phosphate (βTCP) block with a scaffold-free sheet formed using mesenchymal stem cells (MSCs) was investigated.

Methods

Human bone marrow MSCs in a cell culture insert that was set in a 24-well plate were cultivated using a chondrogenic medium containing dexamethasone, IGF-1, and TGFβ3 for 3 weeks during which a cylindrical βTCP block was put on the sheet at day 1, and the cell sheet construct was harvested. In other experiments, at day 14, the construct was put on a cell sheet that was prepared the day before and cultivated for 3 weeks.

Results

The addition of a βTCP block resulted in a combined osteochondral-like construct and comparable staining intensity by Alcian blue, while the expression levels of the aggrecan and type II collagen genes decreased a little. During the culture with the βTCP block, the expression levels of the aggrecan gene increased monotonically. The increase in the inoculum cell number from 1.86 to 3.72 × 10⁶ cells resulted in marked increases in the thickness of cell sheet parts in the βTCP block and expression levels of the aggrecan and type II collagen genes, while the thickness of cell sheet parts on the βTCP block scarcely changed. On the other hand, the addition of a cell sheet that was prepared a day before to the construct at day 14 resulted in the marked increase in thickness of the cell sheet part on the βTCP block, while the thickness of that in the βTCP block did not increase.

Conclusion

A combined osteochondral-like structure was produced by putting a βTCP block on the sheet of MSC. The thickness of the cell sheet parts in and on the βTCP block could be increased by the increase in inoculum cell number and by providing an additional cell sheet, respectively.     

Oral characteristics of a patient with Ekman-Westborg-Julin trait: a case history

This article presents the case of a Japanese woman who had Ekman-Westborg-Julin trait. She had general macrodontia with multituberculism, evagination of the premolar, single conical roots, shovel-shaped incisors, enamel hypoplasia, impacted tooth, dental crowding, and an open bite. The oral and general characteristics of this patient are described and include the histological and radiographic findings of the mandibular third molars. We suggest that the distinctive oral features with macrodontia of the permanent teeth, multituberculism, evagination, single conical roots, and impaction of the tooth could be defined as the Ekman-Westborg-Julin trait.     

Characteristics of Postoperative Recurrence in Lymph Node-Negative Superficial Esophageal Carcinoma

Background

This study aimed to evaluate the recurrence rates, timings, locations, and risk factors, and survival in patients with lymph node-negative superficial esophageal squamous cell carcinomas (ESCCs).

Methods

We investigated 167 patients with pathological T1 thoracic ESCC who underwent curative esophagectomy with lymphadenectomy between 1986 and 2013. They were classified into lymph node-negative and lymph node-positive groups, each of which included 15 relapsed patients. The recurrence rates, timings, locations, and risk factors, and survival were examined retrospectively.

Results

Significantly better recurrence (12.4 %) and the 5-year overall survival (85.7 %) rates were seen in patients with node-negative superficial ESCC compared with those with node-positive superficial ESCC. Relapsed patients with node-negative superficial ESCC showed a 5-month delay in the time to recurrence compared with relapsed patients with node-positive superficial ESCC, but the recurrence locations were similar. Upper thoracic tumors and the presence of lymph node metastases were independent risk factors for recurrence in superficial ESCC patients, but we did not determine any risk factors in patients who were node negative only. The 5-year overall survival rates did not differ between relapsed node-negative and node-positive patients. Furthermore, the mean times to death and the survival rates from recurrence to death were similar in the node-negative (20.3 months and 9.3 %, respectively) and in the node-positive patients (19.1 months and 13.6 %, respectively) who had relapsed.

Conclusions

Node-negative and node-positive superficial ESCC patients should be followed up similarly, because when recurrences occur, the prognoses and the times to death are similar in node-negative and node-positive superficial ESCC patients.

     

Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas: confirmation of the correlations with histologic subtypes and gene mutations

Although adenocarcinomas of the lung are associated with epidermal growth factor receptor (EGFR) gene mutations and sensitivity to EGFR tyrosine kinase inhibitors, it remains unclear whether bronchioloalveolar carcinoma (BAC) components and/or subtypes affect these associations. We aimed to clarify correlations between EGFR gene mutations and BAC components and to establish the histologic features as reliable predictors for the mutations. We examined 141 non-small cell lung cancers (NSCLCs), including 118 adenocarcinomas, for mutations in exons 19 and 21 of the EGFR gene together with mutations in codon 12 of the K-ras gene using loop-hybrid mobility shift assays, a highly sensitive polymerase chain reaction-based method. Adenocarcinomas were subdivided into subtypes with a nonmucinous or mucinous BAC component and those without BAC components. In NSCLCs, EGFR mutations were detected in 75 cases (53.2%) and were significantly associated with adenocarcinoma, female sex, and never smoking. Among adenocarcinomas, nonmucinous and mucinous BAC components were significantly associated with EGFR and K-ras gene mutations, respectively. Because EGFR mutations were detected even in most pure nonmucinous BACs, ie, lung adenocarcinoma in situ, EGFR mutation is considered a critical event in the pathogenesis of nonmucinous BAC tumors.     

Donors' Quality of Life Evaluated by Short Form-36 Analysis After Living Donor Liver Transplantation in a Single-Center Experience

Background and Purpose

The purpose of this study was to compare the quality of life of donors using the Short Form 36 (SF-36) analysis between the left and right graft periods of living donor liver transplantation.

Patients and Methods

In the left graft period (July 1991 to July 2003), 68 donors were eligible for analysis and 76 were eligible in the right graft period (August 2003 to October 2010). Nine right lobe grafts were included in the left graft period, and 52 right lobe grafts were included in the right graft period. We investigated the risks of donation and evaluated the following: blood loss, operation time, postoperative liver function, and duration of hospitalization. We also assessed quality of life in donors, who were mailed a structured questionnaire and the SF-36.

Results

Ten of the 68 donors in the left graft period and 12 of the 76 in the right graft period had postoperative complications. Most postoperative complications were treated without surgical procedures. There was no donor death in our series. Forty-eight donors in the left graft period and 36 in the right graft period responded to our investigation. Compared with published Japanese norms in SF-36, our donors scored similar or higher than the general population in both groups. Two donors in the left graft period and one in the right graft period regretted their decisions to donate. All donors returned to normalcy.

Conclusions

These results suggested that the donors' quality of life was guaranteed in terms of the SF-36 investigation regardless of the donation period in our series.     

Bradykinin induces NO and PGF2α production via B2 receptor activation from cultured porcine basilar arterial endothelial cells

Our previous in vitro study demonstrated that bradykinin (BK) induced relaxation and contraction of porcine basilar artery (PBA) mediated via activation of endothelial B₂ receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H₂, respectively, but not thromboxane A₂. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH₂ has different functionally active isoforms, including PGD₂, PGE₂, and PGF_2α, we have not yet clarified which of them is responsible for BK-induced contraction. Therefore, we attempted to quantify NO and PG production from cultured porcine basilar arterial endothelial cells (PBAECs) and to identify which of the PGs was involved in this contraction. The cultured PBAECs produced NO spontaneously, and BK enhanced this production in a concentration-dependent manner. The NO synthase inhibitor Nω-nitro-l-arginine (L-NNA) and the B₂ receptor antagonist HOE-140, but not the B₁ receptor antagonist des-Arg⁹, [Leu⁸]-BK, completely abolished it. In a functional study, PGD₂, PGE₂, and PGF_2α induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF_2α?>?PGE₂?>?PGD₂. The cultured PBAECs produced PGD₂, PGE₂, and PGF_2α spontaneously, and BK significantly enhanced the production of PGF_2α, but not that of PGD₂ and PGE₂. The B₂, but not B₁, antagonist completely abolished the BK-enhanced production of PGF_2α. These results suggest that BK induces production of NO and PGF_2α simultaneously from PBAECs via B₂ receptor activation.     

Role of physical therapists and aromatherapy for fall prevention in older people: A narrative review

Falls among older people are usually the result of several causes combined. Identifying all the fall-related factors that apply to a particular individual and providing comprehensive multifactorial intervention is recommended for the prevention of falls among older people. However, the overall net benefit of multifactorial intervention in preventing falls is small, and it does not appear to improve fall-related outcomes, such as the number of fall-related injuries. Therefore, we might require new perspectives to overcome this situation. Here, we raise two novel strategies for fall prevention among older people. One is using physical therapists more actively. The other is using aromatherapy for stabilization of older people. Physical therapists should carry out detailed gait assessment and caregiver education. Aromatherapy is effective in improving balance and mental stability in older people. To overcome refractory geriatric syndrome, there is no choice but to eliminate all preconceived ideas before choosing the best fall prevention strategies. Geriatr Gerontol Int 2021; 21: 445–450 .     

Two types of antibodies inhibiting interleukin-2 production by normal lymphocytes in patients with systemic lupus erythematosus

Decreased interleukin-2 (IL-2) production by lymphocytes in vitro has previously been demonstrated in patients with systemic lupus erythematosus (SLE). In the present study, we examined whether inhibitory factors in SLE patient sera are involved in defective IL-2 production. Our results indicate that purified IgG fractions of some SLE sera inhibit IL-2 production at 2 distinct phases of the IL-1-dependent IL-2 production system in vitro: first, by binding to adherent cells and probably inhibiting IL-1 production by macrophages, similar to the action of anti-HLA-DR antibodies, and second, by binding to T cells and blocking the interaction of IL-1 and T cells.     

Uroporphyrinogen I synthase from human erythrocytes: separation, purification, and properties of isoenzymes.

Uroporphyrinogen I synthase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] from human erythrocytes was separated into two active protein peaks (A and B on DEAE-cellulose, by ammonium sulfate fractionation, on Sephadex G-100, and on DEAE-Sephadex A-50 with a NaCl gradient. The final purification was 613 and 743 times for A and B, respectively. The corresponding yields were 2.2 and 3.4% Fraction A was separated further into two (A1 and A2) active protein bands and fraction B into three (B1, B2, and B3) on analytical polyacrylamide disc gel electrophoresis. Bands A1 and A2 were identical with B1 and B2; B3 represented a third isoenzyme. Molecular weights (mean +/- SEM), measured by gel filtration and sodium dodecyl sulfate/polyacrylamide gel electrophoresis, were 38,000 +/- 1000 for B1 and 40,000 +/- 1000 for B2 and B3. Isoelectric focusing on 4% polyacrylamide gel separated both fractions A and B into three active protein bands. Maximal activity of the enzyme was found in gel cuts (5-mm) at pH 5.6 for both fractions A and B.