Fibrodysplasia (myositis) ossificans progressiva (FOP)

Clinical Rheumatology -     

脂蛋白（a）和载脂蛋白（a）多态性与女性冠心病的相关性研究

冠心病（ＣＨＤ）在病因、发病年龄等诸多方面存在性别差异。载脂蛋白（ａ）［ａｐｏ（ａ）］多态性与脂蛋白（ａ）［Ｌｐ（ａ）］血浆水平对女性ＣＨＤ影响的资料甚少。我们通过检测３５例女性ＣＨＤ患者和４５例女性正常对照者的ａｐｏ（ａ）多态表型及Ｌｐ（ａ）水平，并与相应的男性组对比分析，发现含有等位基因Ｓ１、Ｓ２、Ｂ的ａｐｏ（ａ）低分子量表型的ＣＨＤ患者，女性占３７．１４％，显著高于对照组，而男性仅占２５．７１％，与对照组比较差异无显著性。在女性中低分子量表型发生ＣＨＤ危险度为对照组的４．７倍，在男性中仅为１．４倍。提示：低分子量表型对女性ＣＨＤ的影响大于男性。Ｌｐ（ａ）水平在两性ＣＨＤ组均明显高于对照组，而两性之间则差异无显著性。     

Erythropoiesis Inhibiting Factor(s) (EIF)

The specificity and toxicity of the urinary erythropoiesis inhibiting factor (EIF) has been tested both in vivo and in vitro. When EIF was given to ESF stimulated erythropoietically suppressed polycythaemic mice and to mice at maximal endogenous erythropoietic stimulation, a reduction of the erythroid bone marrow cells, the erythropoietic ³H-TdR L.I. and the total number of bone marrow cells were observed. No effect was seen on the myelopoietic bone marrow cells. An unspecific toxic effect was unlikely, since addition of EIF did not alter the proliferation of lymphoblastic cells nor change the glucose utilization of bone marrow cells in vitro. Neither did the amount of dead bone marrow cells increase after being incubated with EIF for 72 h. The results indicate that the urinary EIF is a non-toxic, cell specific inhibitor on erythropoiesis.     

Platelet HDL(3) binding sites are not related to integrin alpha(IIb)beta(3) (GPIIb-IIIa)

Early studies considered that fibrinogen receptor (glycoprotein [GP] IIb-IIIa or platelet integrin alpha(IIb)beta(3)) is the binding site for low-density lipoprotein (LDL) and high-density lipoprotein type 3 (HDL(3)). Recent data, however, do not support the hypothesis that the binding of LDL to human intact resting platelets is related to integrin alpha(IIb)beta(3). In this study we present evidence that platelet integrin alpha(IIb)beta(3) is also not involved in the interaction of HDL(3) and human intact resting platelets. Firstly, specific ligands for platelet integrin alpha(IIb)beta(3), such as fibrinogen, vitronectin, von Willebrand factor and fibronectin, were unable to inhibit the binding of HDL(3) to intact resting platelets. Secondly, the HDL(3) binding characteristics (K(d) and B(max) values), the activation of protein kinase C (PKC) and the inhibition of thrombin-induced inositoltriphosphate (IP(3)) formation and calcium (Ca(2+)) mobilization mediated by HDL(3) particles were similar in platelets from control subjects and patients with type I and type II Glanzmann's thrombasthenia, which are characterized by total and partial lack of GPIIb-IIIa and fibrinogen, respectively. In contrast, nitrosylation of tyrosine residues of HDL(3) by tetranitromethane fully abolished both the ability of particles to interact with its specific binding sites and the functional effects. Thirdly, polyclonal antibodies against the GPIIb-IIIa complex (edu-3 and 5B12), human antiserums against platelet alloantigens (anti-Bak(a/B) and anti-PL(A1/2)), anti-integrin subunits (anti-alpha(V) and anti-beta(3)), and a wide panel of monoclonal antibodies (mAbs) against well-known epitopes of GPIIb (M3, M4, M5, M6, M8 and M95-2b) and GPIIIa (P23-7, P33, P37, P40, and P97) did not affect the binding of HDL(3) particles to human intact resting platelets. Overall results show that neither the GPIIb-IIIa complex nor GPIIb or GPIIIa individually are the membrane binding proteins for HDL(3)on intact resting platelets.     

Molecular stability and function of hemoglobins Hasharon (alpha(2)47 (CD5)Asp----His beta 2) and Hasharon (alpha(2)47 (CD5)Asp----His delta 2)

The molecular stability and function of hemoglobin (Hb) Hasharon (alpha 2 H beta 2) and Hb Hasharon2 (alpha 2 H delta 2) were studied and compared to Hbs A, A2 and S. Hb Hasharon and Hb Hasharon2 had slightly lower P50 values than Hb A and Hb A2 but had normal responses to organic phosphates. The molecular stability of Hb Hasharon and Hb Hasharon2 (as measured by mechanical shaking and heat denaturation at 60 degrees C) were less than Hb A and Hb A2 but greater than Hb S in the oxy- and carbonmonoxy-forms. In the met-form, however, Hb Hasharon and Hb Hasharon2 were less stable than hemoglobins S, A and A2. The oxy-form of Hb Hasharon forms methemoglobin at a faster rate than Hb A and Hb S. The mechanical and heat stabilities and the rate of methemoglobin formation of oxy-Hb Hasharon were studied in the presence of sulfisoxazole. This drug increased the rate of methemoglobin formation, thus causing a further decrease in the stability of Hb Hasharon. The relationship between these laboratory findings and previously observed clinical findings associated with Hb Hasharon are discussed.     

Compound heterozygosity of Hb D(Iran) (beta(22) Glu-->Gln) and beta(0)-thalassemia (619 bp-deletion) in India

The present report describes the hematologic and molecular study of the second case of Hb D(Iran) associated with beta(0)-thalassemia (619 bp-deletion) found in India and the first case in which the mutations have been identified at molecular level. The patient showed hypochromic, microcytic red cell picture with reduced red cell indices. The characterization of the hemoglobinopathy was made by electrophoretic and chromatographic techniques and confirmed by sequencing of the beta-globin gene. Both the propositus and her father were found to be carriers of the gene for beta(0)-thalassemia owing to the 619 bp-deletion mutation as seen by the polymerase chain reaction (PCR). Single base substitution GAA > CAA (indicative of Hb D(Iran)) in the heterozygous form was seen in the propositus as well as the mother by sequencing.     

Caudate lobectomy (segmentectomy 1) (with video)

Background

The caudate lobe of the liver is located behind both major lobes and is surrounded by the inferior vena cava, three main hepatic veins, and the hepatic hilum. Despite a hard-to-approach anatomic location, isolated complete removal of the caudate lobe is recommended to improve curability in hepatocellular carcinoma (HCC). This is because most patients with HCC cannot undergo caudate lobectomy (segmentectomy 1) with resection of adjacent liver regions due to their poor liver function.

Methods

We performed an anatomic isolated caudate lobectomy using a high dorsal resection technique in patients with HCC involving the paracaval portion of the liver. In this procedure, the caudate lobe is dissected, the boundary of the caudate lobe is identified using counterstaining and tattooing techniques, and the liver is transected along landmarks. The caudate lobe can be removed completely, without loss of the parenchyma of the major lobes, thereby preserving liver function.

Conclusions

Given that most patients with HCC concurrently have chronic liver disease, those with HCC in the caudate lobe are good candidates for high dorsal resection of the liver, which is safe, potentially curative procedure.     

Obamacare's (3) Day(s) in Court

Before the oral arguments in late March, the vast majority of legal scholars felt confident that the Supreme Court of the United States would uphold the individual mandate against the constitutional challenge that 26 states have levied against it. Since the oral arguments, that confidence has been severely shaken. This article asks why legal scholars were so confident before the argument and what has made us so concerned since the argument. The article posits that certain fundamental characteristics of health insurance, particularly its unusual role in steering health-care consumption decisions, which distinguishes health insurance from standard kinds of indemnity insurance, should make the constitutional question easy, but the Obama Administration's legal team was understandably hesitant to highlight those unique characteristics in its arguments. Because the Supreme Court justices seemed not to understand the uniqueness of health insurance without the government's help and because the justices seemed unusually willing to adopt a new constitutional constraint in this case, the individual mandate appears to be in far greater jeopardy than we legal scholars anticipated.     

Tenofovir (TDF) has stronger antiviral effect than adefovir (ADV) against lamivudine (LAM)-resistant hepatitis B virus (HBV)

Objectives We retrospectively compared the antiviral effect of tenofovir disoproxil fumarate (TDF) with that of adefovir dipivoxil (ADV) for patients with chronic hepatitis B (CHB) who developed resistance to lamivudine (LAM). Materials and methods One hundred nine patients (86 males), all Asian-American except 1 Caucasian male, with LAM resistance received TDF or ADV. HBV DNA levels were measured every 3 months. The HBeAg loss and ALT normalization were assessed at 12 months on therapy. Results Forty-four patients (37 males) received TDF (12 with LAM) and 65 (49 males) received ADV (18 with LAM). Median ages (years) for TDF and ADV were 49 (32–68) and 45 (22–68), respectively. Median duration of therapy was 13 months (6–38) and 17 months (6–34) for the TDF and ADV groups. Baseline HBV DNA levels (log₁₀ copies/ml) were 6.2 ± 1.7 for the TDF and 6.5 ± 1.6 for ADV groups. Baseline ALT (IU/l) levels were 77.0 ± 86.0 and 100 ± 195 for the TDF and ADV (P = 0.46) groups, respectively. At 12 months, mean levels of log₁₀ HBV DNA were 1.5 ± 1.0 and 4.3 ± 2.2 for TDF and ADV (P = 0.01). HBeAg loss and ALT normalization at 12 months showed no differences. Using a single factor, ANOVA (2-tailed P value), 4 groups, TDF (n = 32), TDF + LAM (12), ADV (47), and ADV + LAM (18), were compared. HBV DNA reduction at 12 months was the greatest for TDF + LAM (P < 0.001). Conclusions Our results suggest that for LAM-resistant HBV, TDF, alone or combined with LAM exerts greater viral reduction than ADV. However, no difference in HBeAg loss was observed. It appears that stronger HBV DNA reduction may not necessarily accelerate HBeAg loss. The author (H.W.H.) who has taken part in this study has declared a relationship with the manufacturers of the drugs involved either in the past or present.