Radioresponse of Thymomas Verified with Histologic Response

Patterns of radiologic response of 10 thymomas treated by preoperative radiotherapy (RT) (18-20 Gy/2 weeks) were determined in conjunction with histologic response. Changes in tumor volume were evaluated with CT scans obtained 5 to 36 days before and 14 to 24 days after the initiation of RT and before surgery. The extent of tumor volume reduction (TR) varied widely (40-78%), while the mean daily volume decrement expressed as a percentage of the pre-RT tumor volume correlated significantly with the pre-RT tumor volume. Histologically, the tumors, all of which were resected 17 to 33 days after RT initiation, generally consisted of predominant fibrous tissues, rare necrotic foci, and few epithelial cells. The TR did not correlate with pre-RT tumor volume, observation period, histologic subtype, or quantity of remaining epithelial cells. The TR of thymomas does not predict RT impact on tumor cells but does reflect the quantity of inherent tumor stroma.     

Presenilin-1 in late-onset depressive disorder

Late-onset depressive disorder (LOD) is thought to be associated with dementia. Allele 1 in the presenilin-1 (PS-1) gene is a risk factor for Alzheimer's disease. An association study on this polymorphism was performed in depressive patients and control subjects. The patients were subdivided into those with early onset and late onset, using 50 years as the cut-off age. There was no statistically significant difference in the age of onset of depressive disorders according to the PS-1 genotype. There was also no association between early/late-onset depressive disorders and the PS-1 genotype. Our results suggest there is no association between the PS-1 allele and LOD.     

Caffeine induces apoptosis of human umbilical vein endothelial cells through the caspase-9 pathway.

Caffeine is known to modulate placental and fetal umbilical circulation. It is demonstrated that apoptosis of human umbilical vein endothelial cells (HUVECs) is associated with placental umbilical vascular diseases. The present study was conducted to investigate the effects of caffeine on apoptosis of HUVECs. Isolated HUVECs were cultured under serum-free conditions for 24 h, and then treated with graded concentrations of caffeine (30, 100 and 300 microM) for additional 24 h and 48 h. The number of viable HUVECs was determined by cell counting. Apoptotic HUVECs were assessed by Hoechst33342 dye staining. The expression of caspase-9, caspase-8, caspase-3 and poly(ADP-ribose) polymerase (PARP) was assessed by Western blot analysis. Caffeine induced a dose- and time-dependent decrease in the number of viable HUVECs. Caffeine at concentrations higher than 100 microM significantly increased the percentage of apoptotic HUVECs. Caffeine at concentrations higher than 100 microM significantly increased cleaved caspase-9, caspase-3 and PARP expression in HUVECs at 24-h treatment compared with untreated cultures, whereas 30 microM caffeine significantly increased only caspase-3 expression at 24 h. Caffeine did not affect cleaved caspase-8 expression at 48 h. These results suggest that high concentrations of caffeine inhibit cell growth of HUVECs and induce apoptosis through the caspase-9 pathway.     

Anti-SARS CoV-2 IgG in COVID-19 Patients with Hematological Diseases: A Single-center,Retrospective Study in Japan

Objective Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the relationship between anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and COVID-19 severity has been reported, information is lacking regarding the seropositivity of patients with particular types of diseases, including hematological diseases. Methods In this single-center, retrospective study, we compared SARS-CoV-2 IgG positivity between patients with hematological diseases and those with non-hematological diseases. Results In total, 77 adult COVID-19 patients were enrolled. Of these, 30 had hematological disorders, and 47 had non-hematological disorders. The IgG antibody against the receptor-binding domain of the spike protein was detected less frequently in patients with hematological diseases (60.0%) than in those with non-hematological diseases (91.5%; p=0.029). Rituximab use was significantly associated with seronegativity (p=0.010). Conclusion Patients with hematological diseases are less likely to develop anti-SARS-CoV-2 antibodies than those with non-hematological diseases, which may explain the poor outcomes of COVID-19 patients in this high-risk group.     

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen‐derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor‐specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1_140–162, which effectively activated TWIST1‐specific CD4⁺ T‐cells. In a short‐term culture system, we detected more TWIST1‐specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1‐reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.     

Association study between catechol-O-methyltransferase polymorphisms and uterine leiomyomas in a Japanese population

PURPOSE: To investigate a possible association between uterine leiomyomas and catechol-O-methyltransferase (COMT) polymorphisms in a Japanese population. METHODS: We compared the allele frequencies and genotype distributions of the exon 4 NlaIII restriction site polymorphism (RSP), the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP in the COMT gene in 250 leiomyoma cases and 182 controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. RESULTS: No significant differences in allele frequencies and genotype distributions of the exon 4 NlaIII RSP, the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP were found between uterine leiomyoma cases and controls. Moreover, no associations were noted between these three polymorphisms in COMT genes and leiomyoma size or a family history of uterine leiomyomas. CONCLUSION: COMT gene polymorphisms are unlikely to be associated with an increased risk of uterine leiomyomas in a Japanese population.     

Safety and usefulness of emergency maternal transport using helicopter

AIM: Japan has a shortage of tertiary medical care facilities for maternal and fetal medicine. Establishment of efficient medical transport systems is needed for pregnant women and fetuses with severe complications. Maternal transport by helicopters is expected to shorten transportation time to advanced facilities, although its feasibility has not yet been evaluated. The aim of the present study was to investigate the status of maternal helicopter transport, and conditions of the pregnant patients and children transferred by helicopter to Kameda Medical Center (KMC). METHODS: Between August 2005 and July 2006, 26 pregnant women were transported by helicopters to KMC. RESULTS: The median net flight time was 24 min (range 15-29 min), and the median of estimation of ground transportation time was 125 min (range 90-180 min). The causes for transfers were preterm labor in eight, preterm premature rupture of the membrane in five, cervical incompetence in five, pre-eclampsia in three and other medical reasons in five. Five of the 26 patients were discharged with restored stability of pregnancy. The remaining 21 patients underwent delivery at KMC. The median gestational age was 26 weeks (range 22-33 weeks) at the time of transfer and 31 weeks (range 22-37 weeks) at delivery. Four of 26 neonates who were born at KMC died after birth due to severe premature or congenital anomaly. Seventeen of the remaining 22 neonates, including 10 twins, received treatment in the neonatal intensive care unit. All of the 22 neonates and all the mothers were discharged in good condition. No patients developed any complications requiring treatment during flights. CONCLUSION: Helicopter transfer is feasible for pregnant patients with severe complications.     

Time-lapse Microscopy and DNA Double-strand Breakage of Chinese Hamster Cells Under Conditions Promoting or Preventing PLD Repair after Irradiation with 60Co γ Rays

Summary

We have confirmed previous time-lapse microscopic observations (Suzuki 1985) using Chinese hamster hai and V79 cells. The proportion of non-dividing to dividing cells was the same under conditions of potentially lethal damage (PLD) repair and non-PLD repair after irradiation with ⁶⁰Co γ-rays. This finding suggested that the radiation-induced damage to cellular DNA was similarly repaired so that cells undergo a first division to the same extent under both sets of conditions. In fact, direct measurement of double-strand breaks (dsb) in DNA from the two cell lines by the neutral elution technique showed no differences either in the initial amount of damage or in the time-course under conditions promoting or preventing PLD repair. These results indicate that PLD repair (i.e. an increase in cell survival) cannot be simply explained by a difference in the repair of dsb, but it can perhaps be explained by assuming that DNA damage is repaired with either fewer or more errors in the presence or absence of PLD repair respectively.     

Effects of traditional “<Emphasis Type="Italic">Juci</Emphasis>” (contralateral acupuncture) on orofacial nociceptive behavior in the rat

Purpose “Juci”, one of the traditional acupuncture techniques, means contralateral acupuncture; i.e., implanting a needle into an acupoint to treat a given disease or disorder, but on the side of the body opposite to the diseased side. The aim of this study was: (1) to assess acupuncture effects on formalin-induced nociceptive behavior in the orofacial region in the rat, and (2) to evaluate the efficacy of Juci in the orofacial formalin test. Methods Forty-four adult male Wistar rats were used in the present study. A 1.0% formalin solution (25 μl s.c., diluted in saline) was injected into the right upper lip. The rats were randomly assigned to five groups. (1) The control group (n = 9), which received formalin injection without acupuncture pretreatment; (2) the ipsilateral Ho-ku (see note below) acupuncture group (n = 10); (3) the contralateral Ho-ku acupuncture group (n = 11); (4) the acupuncture plus naloxone group (n = 9), where intraperitoneal naloxone (1.0 mg·kg⁻¹) was injected immediately before acupuncture pretreatment; and (5) the sham acupuncture group (n = 5). “Ho-ku” is the term used for the “Large Intestine 4” acupoint, located between the first and second metacarpal bones. Results The injection of formalin produced the characteristic biphasic behavioral response. Acupuncture significantly inhibited the response in the early and late phases. Naloxone significantly reversed these effects. There were no statistically significant differences between the ipsilateral and Juci acupuncture groups. Sham acupuncture did not exert any significant effect on the formalin-induced behavior. Conclusion Our results showed that the degree of effectiveness of Juci was similar to that of the ipsilateral acupuncture technique. Therefore, the Juci technique is also useful for the treatment of orofacial pain.     

Surgical treatment for popliteal artery entrapment syndrome

PURPOSE: This study was a retrospective review of 11 limbs of 10 patients with popliteal artery entrapment syndrome (PAES) treated surgically in a 20-yr period. METHODS: The patients were aged 34.7 +/- 17.4 SEM yr. Arteriographic findings varied, showing medial deviation in two limbs, poststenotic dilatation in four limbs and occlusion of the popliteal artery in five limbs. In addition, computed tomographic (CT) scanning showed positive findings of PAES in all the limbs. RESULTS: The surgical procedures consisted of musculotendonous section (MTS) with autogenous saphenous vein (ASV) graft in seven limbs, MTS and ASV patch angioplasty with or without thromboendarterectomy in three limbs, and MTS alone in one limb. All the ASV grafts were found to be patent during the postoperative follow-up period (10.9 +/- 4.0 yr). CONCLUSION: CT scanning was demonstrated to be the most sensitive diagnostic modality for PAES, and MTS with or without ASV grafting method was considered to be the best surgical procedure for PAES.