Pilot Quasi-Randomized Controlled Study of Herbal Medicine Hochuekkito as an Adjunct to Conventional Treatment for Progressed Pulmonary Mycobacterium avium Complex Disease

Introduction

Hochuekkito, a traditional herbal medicine, is occasionally prescribed in Japan to treat patients with a poor general condition. We aimed to examine whether this medicine was beneficial and tolerable for patients with progressed pulmonary Mycobacterium avium complex (MAC) disease.

Methods

This pilot open-label quasi-randomized controlled trial enrolled 18 patients with progressed pulmonary MAC disease who had initiated antimycobacterial treatment over one year ago but were persistently culture-positive or intolerant. All patients continued their baseline treatment regimens with (n = 9) or without (n = 9) oral Hochuekkito for 24 weeks.

Results

Baseline characteristics were generally similar between the groups. Most patients were elderly (median age 70 years), female, had a low body mass index (<20 kg/m²), and a long-term disease duration (median approximately 8 years). After the 24-week treatment period, no patient achieved sputum conversion. Although the number of colonies in sputum tended to increase in the control group, it generally remained stable in the Hochuekkito group. Radiological disease control was frequently observed in the Hochuekkito group than the control group (8/9 vs. 3/9; p = 0.05). Patients in the Hochuekkito group tended to experience increase in body weight and serum albumin level compared with those in the control group (median body weight change: +0.4 kg vs. −0.8 kg; median albumin change: +0.2 g/dl vs. ±0.0 g/dl). No severe adverse events occurred.

Conclusions

Hochuekkito could be an effective, feasible adjunct to conventional therapy for patients with progressed pulmonary MAC disease. Future study is needed to explore this possibility.

Trial Registration

UMIN Clinical Trials Registry UMIN000009920     

Cloning and chromosome mapping of human and chicken Iroquois (IRX) genes.

Three highly homologous homeobox genes (caupolican, araucan and mirror) have been identified in Drosophila. These genes belong to the novel Iroquois complex, which acts as a pre-pattern molecule in Drosophila neurogenesis. Recently several vertebrate Iroquois homologues (Irx) were isolated and found to be involved in pattern formation of various tissues. Here we report cytogenetic mapping of four human and five chicken Iroquois genes by FISH. Our findings revealed that vertebrate Irx genes are clustered at two different loci.     

Replication of measles virus in Vero cells at elevated temperatures

In one-step growth experiment of measles virus (MV) in Vero cells at 39 C, the appearance of MV infectivity was delayed for 24 hr and the maximum titer was reduced by approximately 1,000-fold, when compared with those at 35 C. MV infectivity was thermolabile at the high temperature. Penetration was rather enhanced at 39 C. By Northern blot hybridization, viral RNAs including 50S genome-sized RNA and mRNAs were first detectable 24 hr post-infection (PI) at 35 C and 36 hr PI at 39 C, respectively. Rapid degradation of viral mRNAs was not observed in the infected cells at 39 C. The synthesis of N, F, and M proteins was relatively reduced at the high temperature and appearance of the other viral protein was delayed, in agreement with the time course of viral RNA synthesis. All these data suggest that less efficient synthesis of viral RNA, restriction of synthesis of N, F, and M proteins at translational level and thermolability of infectivity are all involved in the suppressed MV production in Vero cells at 39 C.     

Efficient production of intersubspecific hybrid mice and embryonic stem cells by intracytoplasmic sperm injection

Recently, mice and embryonic stem (ES) cells with allelic polymorphisms have been used extensively in the field of genetics and developmental biology. In this study, we examined whether intersubspecific hybrid mice and ES cells with these genotypes can be efficiently produced by intracytoplasmic sperm injection (ICSI). Frozen-thawed spermatozoa from wild-derived strains, JF1 (Mus musculus molossinus), MSM (M. m. molossinus), HMI (M. m. castaneus), and SWN (M. m. spp.), were directly injected into mature oocytes from laboratory mice ([C57BL/6 x DBA2]F1; M. m. domesticus). The in vitro and in vivo developmental capacity of F1 embryos was not significantly different among the groups (P > 0.05), and term offspring were efficiently obtained in all groups (27%-34% of transferred embryos). However, the mean body and placental weights of the offspring differed significantly with genotype (P < 5 x 10(-10)), with the HMI hybrid greatest in both body and placental weights. In an application study using these F1 offspring, we analyzed their mitochondrial DNA using intersubspecific polymorphisms and found the consistent disappearance of sperm mitochondrial DNA in the F1 progeny. In a second series of experiments, we generated F1 blastocysts by injecting MSM spermatozoa into C57BL/6 oocytes and used them to generate hybrid ES cell lines. The ES cell lines were established at a high efficiency (9 lines from 20 blastocysts) and their allelic polymorphisms were confirmed. Thus, ICSI using cryopreserved spermatozoa allows the efficient and immediate production of a number of F1 hybrid mice and ES cell lines, which can be used for polymorphic analysis of mouse genetics.     

Duration of static stretching influences muscle force production in hamstring muscles

The purpose of the present study was to investigate whether duration of static stretching could affect the maximal voluntary contraction (MVC). Volunteer male subjects (n = 10) underwent 2 different durations of static stretching of their hamstring muscles in the dominant leg: 30 and 60 seconds. No static stretching condition was used as a control condition. Before and after each stretching trial, hamstring flexibility was measured by a sit and reach test. MVC was then measured using the maximal effort of knee flexion. The hamstring flexibility was significantly increased by 30 and 60 seconds of static stretching (control: 0.5 +/- 1.1 cm; 30 seconds: 2.1 +/- 1.8 cm; 60 seconds: 3.0 +/- 1.6 cm); however, there was no significant difference between 30 and 60 seconds of static stretching conditions. The MVC was significantly lowered with 60 seconds of static stretching compared to the control and 30 seconds of the stretching conditions (control: 287.6 +/- 24.0 N; 30 seconds: 281.8 +/- 24.2 N; 60 seconds: 262.4 +/- 36.2 N). However, there was no significant difference between control and 30 seconds of static stretching conditions. Therefore, it was concluded that the short duration (30 seconds) of static stretching did not have a negative effect on the muscle force production.     

Roles of the DNA binding proteins H-NS and StpA in homologous recombination and repair of bleomycin-induced damage in Escherichia coli

The DNA binding protein H-NS promotes homologous recombination in Escherichia coli, but the role of its paralog StpA in this process remains unclear. Here we show that an hns mutant, but not an stpA mutant, are marginally defective in conjugational recombination and is sensitive to the double-strand-break-inducing agent bleomycin. Interestingly, the hns stpA double mutant is severely defective in homologous recombination and more bleomycin-sensitive than is the hns or stpA single mutant, indicating that the stpA mutation synergistically enhances the defects of homologous recombination and the increased bleomycin-sensitivity in the hns mutant. In addition, the transduction analysis in the hns stpA double mutant indicated that the stpA mutation also enhances the defect of recombination in the hns mutant. These results suggest that H-NS plays an important role in both homologous recombination and repair of bleomycin-induced damage, while StpA can substitute the H-NS function. The recombination analysis of hns single, stpA single, and hns stpA double mutants in the recBC sbcA and recBC sbcBC backgrounds suggested that the reduction of the hns single or hns stpA double mutants may not be due to the defect in a particular recombination pathway, but may be due to the defect in a common process of the pathways. The model for the functions of H-NS and StpA in homologous recombination and double-strand break repair is discussed.