Passive terminal extension causes anterior tibial translation in some anterior cruciate ligament-deficient knees

The purpose of the present study was to accurately measure anterior tibial translation during passive terminal extension (ATT-PTE) in anterior cruciate ligament (ACL)-deficient knees, and to investigate correlations between various characteristics of such knees and the magnitude of ATT-PTE. The subjects were 79 patients with unilateral ACL-deficient knees and little flexion contracture. All patients were confirmed to have ACL injury of one knee by arthroscopy. Lateral radiographs of the bilateral knees in passive terminal extension were compared, and ATT-PTE was measured using an original superimposition method. The inter-observer and intra-observer reproducibility of measurement was significantly greater for this method than for the method without superimposition. In 42 of the 79 patients (53%), ATT-PTE was greater than 1 mm, while it was greater than 4 mm in 15 patients (19%). ATT-PTE was significantly larger in patients with a large anterior displacement difference (as measured with the KT-1000 arthrometer) (ATT-KT), a long period since injury, a history of reinjury, injury to the meniscus, and the presence of gross pivot shift. On the other hand, ATT-KT was equal to or greater than 2.5 mm in all 79 patients and showed no significant correlation with the time since initial injury, history of reinjury, on injury to the meniscus. Received for publication on March 29, 1999; accepted on Oct. 7, 1999     

Distal arch replacement for aortic aneurysm associated with pseudocoarctation through the L-incision approach

We report the case of a 16-year-old boy in whom we successfully repaired a distal aortic arch aneurysm associated with pseudocoarctation using double aortic cannulation and antegrade selective cerebral perfusion through the L-incision approach. This approach provided excellent exposure from the ascending aorta to the descending aorta, which enabled total body perfusion. We avoided cardiac arrest and hypothermic circulatory arrest during the surgery. The L-incision approach could be a better alternative for aortic arch surgery in adolescents.     

Issue of Waist Circumference for the Diagnosis of Metabolic Syndrome Regarding Arterial Stiffness: Possible Utility of a Body Shape Index in Middle-Aged Nonobese Japanese Urban Residents Receiving Health Screening

IntroductionAbdominal obesity as a risk factor for diagnosing metabolic syndrome (MetS) is evaluated using waist circumference (WC), although WC does not necessarily reflect visceral adiposity. This cross-sectional study aimed to clarify whether replacing WC with “A Body Shape Index (ABSI),” an abdominal obesity index, in MetS diagnosis detects individuals with arterial stiffening assessed by cardio-ankle vascular index (CAVI).MethodsA retrospective cross-sectional study was conducted in 46,872 Japanese urban residents (median age 40 years) who underwent health screening. Exclusion criteria were current treatments and a past history of cardiovascular disease (CVD). The Japanese, International Diabetes Federation, and NCEP-ATPIII criteria were used to diagnose MetS. High CAVI was defined as CAVI ≥9.0.ResultsCAVI correlated positively with ABSI (β = 0.127), but negatively with WC (β = −0.186), independent of age, sex, systolic blood pressure, fasting plasma glucose, and high-density lipoprotein–cholesterol. Receiver operating characteristic (ROC) analysis showed that ABSI had a stronger contribution to high CAVI (area under the ROC curve [AUC] = 0.730) than WC (AUC = 0.595) and body mass index (AUC = 0.520). ABSI ≥0.080 was defined as abdominal obesity based on the results of ROC analysis for high CAVI and estimated glomerular filtration rate <60 mL/min/1.73 m². Logistic regression analysis revealed that replacing high WC with ABSI ≥0.080 in MetS diagnosis enhanced the detection of subjects with high CAVI.Discussion/ConclusionUse of ABSI can detect subjects with arterial stiffening, which may lead to efficient stratification of CVD risk. Further studies are needed to confirm whether MetS diagnosis using ABSI predicts CVD morbidity and mortality.     

Arg506Gln mutation of the coagulation factor V gene not detected in Japanese pulmonary thromboembolism

Summary The incidence of pulmonary thromboembolism (PTE) is lower in Japanese than in Caucasians. The basis for the different incidence has not been clarified. A poor anticoagulant response to activated protein C based on a single point mutation of the factor V gene (Arg506Gln) was found to be a pathogenetic factor for venous thrombosis and PTE in North America and Europe. We investigated whether the Arg506Gln mutation of factor V is responsible for the occurrence of PTE among Japanese. We analyzed genomic DNA prepared from fresh peripheral blood of 25 patients with PTE of unknown etiology (12 of acute type and 13 of chronic type) and that of 110 controls without respiratory or circulatory disorders. To detect the Arg506Gln mutation, 267bp DNA fragments of the factor V gene including the Arg506Gln region were amplified by PCR, digested byMnlI and electrophoresed. After digestion of PCR products withMnlI, DNA fragments of 163bp length, but not DNA fragments of 200bp length, were identified in all samples, indicating the absence of the Arg506Gln mutation in the patients with PTE and control subjects. These results suggest that the Arg506Gln mutation is absent or very rare and not an important pathogenetic factor for PTE in Japanese.     

Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption

Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-kappaB ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption, but also accelerates bone formation. We examined whether bone formation is coupled with bone resorption in OPG-deficient (OPG-/-) mice using risedronate, an inhibitor of bone resorption. Histomorphometric analysis showed that bone formation-related parameters (e.g. mineral apposition rate and osteoblast surface/bone surface) in OPG-/- mice sharply decreased with suppression of bone resorption by daily injection of risedronate for 30 d. OPG-/- mice exhibited high serum alkaline phosphatase activity and osteocalcin concentration, both of which were decreased to the levels in wild-type mice by the risedronate injection. Serum levels of RANKL were markedly elevated in OPG-/- mice, but were unaffected by risedronate. The ectopic bone formation induced by bone morphogenetic protein-2 implantation into OPG-/- mice was not accelerated even with a high turnover rate of bone, but attenuation of mineral density from the ectopic bone was more pronounced than that in wild-type mice. These results suggest that bone formation is coupled with bone resorption at local sites in OPG-/- mice, and that serum RANKL levels do not reflect this coupling.     

Neuropathological and molecular studies of spinocerebellar ataxia type 6 (SCA6)

SCA6 is an autosomal dominant spinocerebellar ataxia (SCA) caused by a small CAG repeat expansion of the gene encoding an α-1a-voltage-dependent Ca channel gene subunit on chromosome 19p13. A Japanese woman with SCA6, with a 7-year history of progressive pure cerebellar ataxia, died of malignant lymphoma. Systematic neuropathological examination showed that neuronal degeneration was confined to the cerebellar Purkinje cells and, to a lesser degree, the granular cells, without any involvement of other central nervous system structures. Such pathological selectivity correlates with the localized expression of the responsible gene, and coincides with the neurological manifestation. These findings might contribute to establishing the phenotype of the SCA6 via comparison with other dominant ataxias. Received: 7 July 1997 / Revised, accepted: 14 August 1997     

Human melanoma invasion and metastasis enhancement by high expression of aminopeptidase N/CD13

Aminopeptidase N/CD13 is a Zn²⁺-dependent exoprotease present on the cell surface as a transmembrane protein. Our previous studies using aminopeptidase inhibitors and antibodies demonstrated that aminopeptidase N is involved in the degradation and invasion of the extracellular matrix (ECM) by metastatic tumor cells. In the present study we transfected human A375M melanoma cells with eukaryotic plasmid expression vectors that contained full length cDNA of aminopeptidase N/CD13 and examined their characteristics. The transfectants that expressed extremely high levels of aminopeptidase N/CD13 degraded type IV collagen and invaded ECM more actively than the parental and control vector-transfected cells. Furthermore, the aminopeptidase N/CD13-transfected A375M cells had significantly augmented lung colonizing potential in nude mice. The results show that the aminopeptidase N/CD13 plays an active role in degradation and invasion of ECM and may be involved in the molecular mechanisms of blood-borne metastasis.     

High juvenile hormone titre and abdominal activation of JH signalling may induce reproduction of termite neotenics

Termite castes are a key example of polyphenism, in which reproductive division of labour is clearly seen in colonies. The reproductive castes in termites include primary and neotenic reproductives; primary reproductives found a new colony whereas neotenics succeed them in the reproductive role when the primary reproductives die or become senescent. Neotenics usually differentiate from nymphs or workers by developing functional gonads while retaining juvenile characteristics; however, the developmental mechanism during neotenic differentiation remains poorly understood. Juvenile hormone (JH) mediates a number of aspects of developmental regulation in caste differentiation in termites. In the present study we quantified JH titres in neotenic reproductives of Reticulitermes speratus, and compared these with other developmental stages. In addition, expression changes in JH signalling gene homologues (Methoprene‐tolerant [Met], Krüppel‐homolog1, Broad‐Complex) in the head, thorax and abdomen were investigated during neotenic differentiation. Finally, we examined the function of Met in reproduction of neotenics by RNA interference (RNAi). Our results showed that the JH titres of neotenics were significantly higher than those of nymphs and workers. JH signalling genes were highly expressed in neotenic abdomens, compared with those in workers and nymphs. Met RNAi resulted in the inhibition of vitellogenin gene expression in newly moulted neotenics. These results suggest that the fertility of neotenics might be controlled by a large increase of JH titres and body‐part‐specific activation of JH signalling pathways.     

L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

The purpose of this investigation was to determine whether a nutritionally essential amino acid, l-lysine, acts like a serotonin receptor 4 (5-HT4) antagonist, and if l-lysine is beneficial in animal models of serotonin (5-HT)-induced anxiety, diarrhea, ileum contractions, and tachycardia and in stress-induced fecal excretion. The radioligand-binding assay was used to test the binding of l-lysine to various 5-HT receptors. The effects of l-lysine on 5-HT-induced contractions of isolated guinea pig ileum were studied in vitro. The effects of oral administration of l-lysine on diarrhea, stress-induced fecal excretion, and 5-HT-induced corticosterone release, tachycardia, and anxiety (an elevated plus maze paradigm) were studied in rats in vivo. l-Lysine (0.8 mmol/dl) inhibited (9.17%) binding of 5-HT to the 5-HT4 receptor, without any effect on 5-HT1A,2A,2B,2C,3 binding. l-Lysine (0.07 and 0.7 mmol/dl) blocked 5-HT-induced contractions of an isolated guinea pig ileum in vitro (P < 0.05 and P < 0.01). Orally applied l-lysine (1 g/kg of body weight) inhibited (P < 0.12) diarrhea triggered by coadministration of restraint stress and 5-hydroxytryptophane (10 mg/kg of body weight), and significantly blocked anxiety induced by the 5-HT4 receptor agonist (3.0 mmol/liter) in rats in vivo. No effects of l-lysine or the 5-HT4 receptor agonist on plasma corticosterone and heart rate were recorded. l-Lysine may be a partial 5-HT4 receptor antagonist and suppresses 5-HT4 receptor-mediated intestinal pathologies and anxiety in rats. An increase in nutritional load of l-lysine might be a useful tool in treating stress-induced anxiety and 5-HT-related diarrhea-type intestinal dysfunctions.