The genetics of tethered cord syndrome

We describe three patients with Malpuech syndrome from two families. Previously, 10 patients from 6 families have been reported. Consanguinity in two families suggests autosomal recessive inheritance. Growth retardation, mental retardation, cleft lip, and/or palate, hypertelorism, urogenital abnormalities, and caudal appendage are the key features. Although the spectrum of the features in the reported patients is variable, we do think this syndrome represents a distinct entity. Chromosomal anomalies should be carefully searched for. We discuss differential diagnosis and possible candidate genes and propose diagnostic criteria for Malpuech syndrome.     

A normal component in rabbit IgG with affinity for mouse tissues

A part of the IgG from normal rabbit serum has been isolated which shows specificity of reactio when compared with the whole of rabbit serum IgG. When it is injected intravenously into mice bearing the L1210 leukaemia it has been found to be fixed in spleens to a much higher degree than is whole IgG. It is also fixed selectively in vitro on the sediments of L1210 cells.

Some of this particular component cross-reacts well with other mouse tissues, while the rest shows an appreciable specificity for the L1210 cells.

     

Acute coronary syndromes occurring while driving: frequency and patient characteristics

Background

Acute coronary syndrome (ACS) may occur during any human activity, including driving. The objectives of this study were to report the frequency of ACS occurring while driving, clarify patient characteristics, and analyze the behavioral patterns of drivers who sustained ACS.

Methods

A single-center, retrospective observational study was conducted using prospectively acquired data. Among 1605 ACS patients admitted between January 2011 and December 2016, 65 (60 men/5 women) patients who sustained ACS while driving were identified. Clinical variables were compared between these 65 patients and 1540 patients who sustained ACS while performing other activities. Furthermore, multivariable regression analysis was performed to identify variables associated with ACS.

Results

The frequency of ACS occurring while driving was 4.0% (65/1605). Compared with patients who sustained ACS while performing other activities, those who sustained ACS while driving were significantly younger (66.2?±?13.0 vs. 57.5?±?12.2 years, p?<?0.001) and more likely to smoke (34.2 vs. 60.0%, p?<?0.001). Multivariable regression analysis showed that age (OR 0.961; 95% CI 0.940–0.982) and current smoking (OR 1.978; 95% CI 1.145–3.417) were associated with ACS. While 55 drivers (85%) who remained conscious after ACS could seek medical attention without causing accidents, the other 10 (15%) who sustained cardiac arrest caused accidents.

Conclusions

The association between current smoking and ACS occurring while driving suggests that smoking cessation is advised for smokers who drive from the standpoint of driving safety. We expect that prospective studies be conducted to verify our findings and identify individuals at risk for ACS while driving.

     

HPMA Copolymer-Conjugated Pirarubicin in Multimodal Treatment of a Patient with Stage IV Prostate Cancer and Extensive Lung and Bone Metastases

Nanomedicine allows achievement of tumor-selective drug delivery because of the enhanced permeability and retention (EPR) effect of solid tumors. We report here the first clinical application of a new agent—HPMA copolymer-conjugated pirarubicin (P-THP)—with a molecular size of about 8 nm, or 38.5 kDa. A patient had advanced prostate cancer with multiple metastases in the lung, pelvis, femur, and perhaps the sacrum. In April 2013, this 60-year-old patient started treatment with leuprorelin and estradiol, which continued until July 2014, but the patient became refractory to this treatment. So the patient underwent proton beam radiotherapy targeted to the primary prostate cancer, and P-THP was administered for numerous metastatic tumor nodules concomitantly with radiotherapy. This combination therapy had remarkable results, with complete remission of multiple metastases in the lung and bone. The prostate-specific antigen (PSA) value was decreased from about 1000 ng/mL on April 30, 2013, to about 100 ng/mL on June 24, 2013, with hormone therapy, but rose again to 964.2 ng/mL and then to 1472 ng/mL in July 2013, during leuprorelin administration. P-THP treatment administered concomitantly with proton beam irradiation was started in August 2013. The PSA value was decreased to 102 ng/mL on August 26, 2013, and then to 0.971 ng/mL on October 8, 2013, and 0.277 ng/mL on January 15, 2015. The P-THP doses ranged from 30 to 75 mg of free THP equivalent/patient every 2–3 weeks without signs of serious toxicity, such as cardiovascular side effects or a reduction in quality of life. No evidence of relapse was found more than 20 months after P-THP administration. This case demonstrates the value of hydrazone-bonded polymeric drugs in multimodal therapy.     

Hemolysis caused by titanium dioxide particles

Washed human erythrocytes were incubated with titanium dioxide (TiO2) particles at 37 degrees C for 1 hr and hemolysis was determined by the percentage of hemoglobin released (optical density at 540 nm; OD540) from the cells. Effects of TiO2 on OD540 were corrected and dose-response curves were analyzed by the Hill plot. Judging from the estimated dose to cause 50% hemolysis, the anatase form of micron-scale (<5000 nm) particles was 73 and 11 times more potent than the amorphous (<50 nm) and rutile (<5000 nm) forms, respectively, whereas it was 1.3 times more potent than the nano-scale (<25 nm) anatase particles. Plasma abolished the hemolysis due to anatase and rutile forms. Thus, hemolytic effects of TiO2 can be greatly different depending on the polymorph but not on the primary size (nano- or micron-scale) of particles. TiO2-induced hemolysis is unlikely to occur in vivo because of the presence of plasma.     

Effects of tanshinone VI on phosphorylation of ERK and Akt in isolated cardiomyocytes and cardiac fibroblasts

Effects of tanshinone VI, a diterpene from Tan-Shen, on humoral factor-induced phosphorylation of ERK and Akt during hypertrophy of cardiomyocytes and fibrosis of cardiac fibroblasts isolated from neonatal rats were examined. Treatment of cultured cardiomyocytes with 10 nM insulin-like growth factor-1 (IGF-1) or 10 nM endothelin-1 resulted in an increase in leucine incorporation into acid-insoluble fraction. Treatment of cultured cardiac fibroblasts with 10 nM IGF-1 or 10 nM angiotensin II increased incorporation of proline. IGF-1 increased phosphorylated extracellular signal-regulated kinase (pERK) and protein kinase B (pAkt) of cardiomyocytes, whereas endothelin-1 increased pERK, but not pAkt. Treatment of cardiac fibroblasts with 10 nM IGF-1 or 10 nM angiotensin II also increased pERK, whereas pAkt was increased by treatment with IGF-1 alone. When the cardiomyocytes were incubated in the presence of 10 μM tanshinone VI, IGF-1- and endothelin-1-induced increases in pERK, but not pAkt, were partially attenuated. Treatment of cardiac fibroblasts with 10 μM tanshinone VI also attenuated IGF-1-induced increases in pERK and pAkt. Tanshinone VI also partially attenuated angiotensin II-induced increase in proline incorporation into cardiac fibroblasts. PD98059, an inhibitor for phosphorylation of extracellular signal-regulated kinase (ERK), but not wortmannin, that for protein kinase B phosphorylation, attenuated an increase in leucine incorporation into cardiomyocytes in the presence of either IGF-1 or endothelin-1. These results suggest that tanshinone VI is a possible agent that can attenuate the humoral factor-induced hypertrophy of cardiomyocytes and fibrosis of cardiac fibroblasts via an attenuation of ERK phosphorylation in these cells.