Because posterior cruciate ligament (PCL) resection makes flexion
gaps wider in total knee replacement (TKR), preserving or sacrificing
a PCL affects the gap equivalence; however, there are no criteria
for the PCL resection that consider gap situations of each knee.
This study aims to investigate gap characteristics of knees and
to consider the criteria for PCL resection.
The extension and flexion gaps were measured, first with the
PCL preserved and subsequently with the PCL removed (in cases in
which posterior substitute components were selected). The PCL preservation
or sacrifice was solely determined by the gap measurement results,
without considering other functions of the PCL such as ‘roll back.’
Wide variations were observed in the extension and flexion gaps.
The flexion gaps were significantly larger than the extension gaps.
Cases with 18 mm or more flexion gap and with larger flexion than
extension gap were implanted with cruciate retaining component.
A posterior substitute component was implanted with the other cases.
In order to make adequate gaps, it is important to decide whether
to preserve the PCL based on the intra-operative gap measurements
made with the PCL intact.
Cite this article: Bone Joint Res 2014;3:95–100.
Knee; Arthroplasty; Posterior cruciate ligament; Gap
A bioinformatic and phylogenetic study has been performed on a family of
penicillin–binding proteins including D–aminopeptidases, D–amino acid
amidases, DD–carboxypeptidases, and β –lactamases. Significant homology
between D–aminopeptidase from Ochrobactrum anthropi and other members
of the family has been shown and a number of conserved residues identified as S62, K65, Y153,
N155, H287, and G289. Three of those (Ser62, Lys65, and Tyr153) form a catalytic triangle
– the proton relay system that activates the generalized nucleophile in the course of
catalysis. Molecular modeling has indicated the conserved residue Lys65 to have an unusually
low pKa value, which has been confirmed experimentally by a study of the pH–profile of
D–aminopeptidase catalytic activity. The resulting data have been used to elucidate the
role of Lys65 in the catalytic mechanism of D–aminopeptidase as a general base for proton
transfer from catalytic Ser62 to Tyr153, and vice versa, during the
formation and hydrolysis of the acyl – enzyme intermediate.
D-aminopeptidase; penicillin-binding protein family; bioinformatic analysis; catalytic mechanism
Objective: To assess the role of intravenous myocardial contrast echocardiography (MCE) in predicting functional recovery and regional or global left ventricular (LV) remodelling after acute myocardial infarction (AMI) compared with low dose dobutamine stress echocardiography (LDSE).
Methods: 21 patients with anterior AMI and successful primary angioplasty underwent MCE and LDSE during the subacute stage (2–4 weeks after AMI). Myocardial perfusion and contractile reserve were assessed in each segment (12 segment model) with MCE and LDSE. The 118 dyssynergic segments in the subacute stage were classified as recovered, unchanged, or remodelled according to wall motion at six months’ follow up. Percentage increase in LV end diastolic volume (%ΔEDV) was also calculated.
Results: The presence of perfusion was less accurate than the presence of contractile reserve in predicting regional recovery (55% v 81%, p < 0.0001). However, the absence of perfusion was more accurate than the absence of contractile reserve in predicting regional remodelling (83% v 48%, p < 0.0001). The number of segments without perfusion was an independent predictor of %ΔEDV, whereas the number of segments without contractile reserve was not. The area under the receiver operating characteristic curve showed that the number of segments without perfusion predicted substantial LV dilatation (%ΔEDV > 20%) more accurately than did the number of segments without contractile reserve (0.88 v 0.72).
Conclusion: In successfully revascularised patients with AMI, myocardial perfusion assessed by MCE is predictive of regional and global LV remodelling rather than of functional recovery, whereas contractile reserve assessed by LDSE is predictive of functional recovery rather than of LV remodelling.
contrast echocardiography; dobutamine echocardiography; myocardial infarction; functional recovery; ventricular remodelling
coronary disease; mitral regurgitation; dobutamine; echocardiography
Images in cardiology
Methods: Adult male Sprague-Dawley rats were given 0.3 mg/kg BLM intratracheally. Two days earlier they had received 10 mg/kg/day of the AT1 antagonist candesartan cilexetil mixed in the drinking water. AT1 expression in the lungs was examined by immunohistochemistry and immunoblot methods. The effect of the AT1 antagonist on pulmonary fibrosis was studied by analysis of bronchoalveolar lavage (BAL) fluid, histopathology, and hydroxyproline assay.
Results: Immunohistochemical studies showed overexpression of AT1 in inflammatory immune cells, alveolar type II cells, and fibroblasts. A quantitative assay for AT1 showed that AT1 expression was significantly upregulated in cells from BAL fluid after day 3 and in the lung homogenates after day 21. Candesartan cilexetil significantly inhibited the increase in total protein and albumin, as well as the increase in total cells and neutrophils in BAL fluid. On day 21 candesartan cilexetil also ameliorated morphological changes and an increased amount of hydroxyproline in lung homogenates. In addition, BLM increased the expression of transforming growth factor (TGF)-ß1 in BAL fluid on day 7; this increase was significantly reduced by candesartan cilexetil.
Conclusion: AT1 expression is upregulated in fibrotic lungs. Angiotensin II promotes lung fibrosis via AT1 and, presumably, in part via TGF-ß1.
1. The responses of coeliac ganglion neurones of the guinea-pig to electrical stimulation of the mesenteric nerves and applications of tachykinin receptor agonists were investigated by use of intracellular recording techniques. 2. Ganglion neurones were classified into three groups based on firing patterns in response to a depolarizing current pulse: phasic (38% of the population), tonic (39%) and atypical (23%). In the majority of phasic neurones (91%) a long after-hyperpolarization (LAH) lasting 5-8 s followed action potentials induced by a train of depolarizing current pulses. In contrast, LAH was rarely observed in tonic neurones (5%). 3. In most of tonic neurones (90%) slow excitatory post-synaptic potentials (e.p.s.ps) lasting 3-10 min were evoked by repetitive electrical stimulation of the mesenteric nerves. Prolonged depolarizations were also evoked in most tonic neurones by applications of substance P (SP), neurokinin A (NKA) or senktide, a tachykinin NK3 receptor agonist. 4. In most of phasic neurones (73%), mesenteric nerve stimulation did not induce an obvious depolarization but induced a prolonged inhibition of LAH lasting 3-10 min. Bath-applied tachykinin receptor agonists similarly induced an inhibition of LAH without causing depolarization in most of the phasic neurones. 5. GR 71251 (5 microM), a tachykinin NK1 receptor antagonist, partially depressed the nerve-evoked slow e.p.s.ps in tonic neurones and the nerve-evoked LAH inhibition in phasic neurones. 6. Capsaicin (0.1-5 microM) induced a prolonged depolarization in tonic neurones and an inhibition of LAH in phasic neurones. 7. A mixture of peptidase inhibitors potentiated the depolarization and the LAH inhibition evoked by nerve stimulation, SP and NKA, but not those evoked by senktide. 8. It is concluded that tonic neurones respond to repetitive mesenteric nerve stimulation preferentially with slow e.p.s.ps and that phasic neurones respond preferentially with LAH inhibition. The present study further suggests that SP and NKA, released from axon collaterals of primary afferent neurones, produce slow e.p.s.ps in tonic neurones and the LAH inhibition in phasic neurones via NK1 receptors.
We have developed a fluorescent DNA probe, oxazole yellow (YO)-linked oligonucleotide complementary to a target DNA/RNA, which can enhance the fluorescence on hybridizing with a target nucleotide. We demonstrated the applicability of the YO-linked oligonucleotide probe to real-time monitoring of the in vitro transcription process of a plasmid DNA constructed containing the 5'-terminus non-coded region of hepatitis C virus RNA. In the process of in vitro transcription in the presence of YO-linked complementary oligonucleotide, the fluorescence of the reaction mixture showed a time-dependent linear increase corresponding to the generated target RNA product.
1. Intracellular recording techniques were used to investigate the characteristics of tachykinin receptors and their subtypes in tonic and phasic neurones, which constituted two major neuronal populations in the coeliac ganglion of the guinea-pig. 2. In 95% of phasic neurones a long-lasting after-hyperpolarization (LAH), 5-8 s in duration and 10-20 mV in amplitude, was observed following action potentials evoked by passing a train of depolarizing current pulses into the neurones. In contrast, LAH was observed in only 4% of tonic neurones. 3. In most tonic neurones, substance P (SP), neurokinin A (NKA) and senktide induced depolarizations, whereas in phasic neurones they usually inhibited LAH but rarely induced depolarization. 4. Tonic and phasic neurones were further classified into three groups based on their responses (depolarization for tonic neurones and LAH inhibition for phasic neurones) to these tachykinin receptor agonists: (1) neurones responsive to SP, NKA and senktide (71-78%); (2) those responsive to senktide but not to SP and NKA (12-23%) and (3) those not responsive to any of the three agonists (7-11%). 5. GR71251 (5 microM), an NK1-selective tachykinin receptor antagonist, depressed the depolarization in tonic neurones and the LAH inhibition in phasic neurones induced by SP and NKA, but not those induced by senktide. 6. Selective NK2 receptor agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, were without effect in both tonic and phasic neurones. Furthermore, an NK2 receptor antagonist, L659,877, did not inhibit the depolarization induced by NKA, SP or senktide in tonic neurones.(ABSTRACT TRUNCATED AT 250 WORDS)
1. The pharmacological characteristics of RP 67580, a non-peptide tachykinin NK1 receptor antagonist, and its effects on a reflex response evoked by stimulation of primary afferent fibres, were examined in isolated neonatal spinal cord preparations of the rat. Potentials were recorded extracellularly from a lumbar ventral root and drugs were bath-applied in normal artificial cerebrospinal fluid (CSF) or in the presence of tetrodotoxin (TTX). 2. In normal artificial CSF, RP 67580 (0.1-0.3 microM) caused rightward shifts of the concentration-response curves for substance P (SP), neurokinin A (NKA) and substance P methyl ester (SPOMe), an NK1-selective agonist, with pA2 values of 7.25, 7.47 and 7.49, respectively. 3. In the presence of TTX (0.3 microM), RP 67580 also caused rightward shifts of the concentration-response curves for SPOMe and NKA. The pA2 value of RP 67580 against SPOMe (6.75) was significantly lower than that against NKA (7.22). RP 67580 (0.3-1 microM) did not cause a clear parallel shift of the concentration-response curves for SP, and it depressed the depolarizations induced by low concentrations of SP, but slightly potentiated those induced by high concentrations of SP. 4. RP 67580 (1 microM) did not depress the depolarizing responses to bombesin, L--glutamate, gamma-aminobutyric acid (GABA), thyrotropin-releasing hormone and muscarine. RP 67580 (1 microM), however, depressed the response to acetylcholine in the presence of atropine and the response to nicotine. RP 68651 (1 microM), the enantiomer of RP 67580 devoid of activity at tachykinin NK1 receptors, also depressed the response to acetylcholine in the presence of atropine.(ABSTRACT TRUNCATED AT 250 WORDS)
1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
1. The pharmacological profile of GR71251, a new tachykinin receptor antagonist, and its effect on the responses evoked by stimulation of primary afferent fibres were studied in isolated spinal cord preparations of neonatal rats. Potential changes were recorded extracellularly from a lumbar ventral root (L3-L5). 2. Bath-application of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) at 0.01-3 microM to the spinal cord induced depolarization of the ventral root in normal artificial cerebrospinal fluid (CSF). The NK1 agonist, acetyl-Arg6-septide, and the NK3 agonist, senktide, at 0.01-3 microM, also had potent depolarizing actions whereas two NK2 agonists, beta-Ala8NKA4-10 and Nle10NKA4-10, showed little depolarizing effects at 1 microM. 3. GR71251 (0.3-3 microM) caused a rightward shift of the concentration-response curves for SP, acetyl-Arg6-septide and NKA with pA2 values of 6.14, 6.75 or 6.70, respectively. The effects of GR71251 were readily reversible within 15-30 min after its removal. By contrast, GR71251 (1-5 microM) had little effect on the depolarizing responses to NKB and senktide. 4. GR71251 (1-3 microM) did not depress the depolarizing responses to bombesin, neuromedin B and gastrin-releasing peptide in normal artificial CSF. 5. Application of capsaicin to the spinal cord induced a depolarizing response, which was partially depressed by GR71251 (3-10 microM). 6. In the isolated spinal cord preparation, intense electrical stimulation of a dorsal root evoked a slow depolarizing response of the contralateral ventral root of the same segment.(ABSTRACT TRUNCATED AT 250 WORDS)
Striatal blood flow, glucose metabolism and 18F-Dopa uptake were studied with positron emission tomography (PET) in eight non-demented patients with idiopathic Parkinson's disease and eight with atypical Parkinsonism. Patients with atypical Parkinsonism had no specific cause for the Parkinsonian symptoms and were clinically different from Parkinson's disease with lack of resting tremor and a poor response to dopaminergic drugs. Decreased 18F-Dopa uptake in the putamen was observed in patients with Parkinson's disease and atypical Parkinsonism compared with normal controls. 18F-Dopa uptake in the head of the caudate was also significantly reduced in both conditions but relatively less in Parkinson's disease. Decreased blood flow and glucose metabolism in the striatum associated with a global cerebral decrease were also observed in patients with atypical Parkinsonism compared with controls, while they were preserved in patients with Parkinson's disease, indicating affected neurons not only in the striatum but also in the cerebrum in patients with atypical Parkinsonism compared with patients with Parkinson's disease. The differences in the caudate 18F-Dopa uptake, and blood flow and glucose metabolism in the cerebrum including the striatum between Parkinson's disease and atypical Parkinsonism assessed by PET may be due to the differences in the pathophysiological mechanism between Parkinson's disease and atypical Parkinsonism.
1. The pharmacological profile of a tachykinin antagonist, [D-Arg1, D-Trp7,9, Leu11] substance P (spantide), was studied on motoneurones of the isolated spinal cord of the newborn rat. For this purpose, potentials were recorded from a lumbar ventral root extracellularly and drugs were bath-applied in the presence of tetrodotoxin (TTX). 2. Neurokinin A (NKA), a NK2-receptor selective agonist, induced concentration-dependent depolarizations, which were antagonized by spantide. Analyses of concentration-response curves suggested a competitive type antagonism with a pA2 of 6.5. 3. Depolarizations induced by acetyl-Arg6-septide, a NK1-receptor selective agonist, were also antagonized by spantide with a pA2 of 6.5. 4. Spantide (0.5-16 microM) had no depolarizing action on the ventral root in the presence of TTX. 5. Spantide antagonized the depolarizing action of substance P (SP) when SP was applied at low concentrations (0.1-0.3 microM) or by short duration pulses in artificial cerebrospinal fluid containing TTX, but much higher concentrations of spantide (4-10 microM) were needed to exert an antagonistic action against SP than against acetyl-Arg6-septide or NKA. 6. Thyrotrophin-releasing hormone, L-glutamate, GABA, and noradrenaline, also induced depolarizations of the ventral root in the presence of TTX but the responses to these agonists were not depressed by spantide (16 microM). 7. These results suggest that there is a subtype of tachykinin receptors on neonatal rat spinal motoneurones to which NKA, acetyl-Arg6-septide and spantide bind competitively with high affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
1. An isolated spinal cord-peripheral nerve preparation of the newborn rat was developed. In this preparation it is possible to record spinal reflexes from a lumbar ventral root in response to stimulation of the ipsilateral saphenous or obturator nerve. 2. Single shock, weak intensity stimulation of the saphenous nerve induced a fast conducted compound action potential in the L3 dorsal root and a fast depolarizing response in the ipsilateral L3 ventral root. As a stronger stimulus was applied to the saphenous nerve, a slowly conducted compound action potential appeared in the dorsal root and a slow depolarizing ventral root potential (v.r.p.) in the L3 ventral root. 3. Single shock stimulation of the obturator nerve induced a rapidly conducted compound action potential in the L3 dorsal root and monosynaptic and polysynaptic reflexes, with a fast time course, in the ipsilateral L3 ventral root. 4. The slow v.r.p. evoked by saphenous nerve stimulation was depressed by the tachykinin antagonist, [D-Arg1, D-Trp7,9, Leu11] substance P (spantide), 4-16 microM. The response recovered its original shape and size 30-60 min after the removal of this antagonist. 5. The saphenous nerve-evoked slow v.r.p. was depressed by [Met5] enkephalin (0.1-1 microM), dynorphin (1-13)(0.2 microM) and morphine (1-2 microM), and these effects were reversed by naloxone (1 microM). 6. Two endogenous peptides, galanin (1-2 microM) and somatostatin (1-2.5 microM), inhibited the slow v.r.p. evoked by saphenous nerve stimulation, whereas another endogenous peptide, calcitonin gene-related peptide (0.1-0.5 microM), potentiated the slow v.r.p. The slow v.r.p. was also inhibited by gamma-aminobutyric acid (GABA, 20 microM) and muscimol (0.2 microM), and their effects were antagonized by bicuculline (1 microM). 7. The present results suggest that substance P and neurokinin A are involved in the saphenous nerve-evoked C-fibre response in the spinal cord of the newborn rat.
In order to reveal the spinal reflexes involving the transmitter action of substance P (SP), the effects of capsaicin and an SP antagonist on the isolated spinal cord of the neonatal rat studied. When a single shock stimulus was given to a dorsal root (L3-L5) or a sciatic nerve, depolarizing responses of various time courses were recorded extracellularly from both ipsi- and contra-lateral ventral roots of the corresponding segments. The reflex response recorded from the contralateral ventral root consisted of fast and slow components, which will be referred to as contralateral fast and slow ventral root potentials (v.r.ps). The latter contralateral slow v.r.p. had a time-to-peak of 2-5 s and lasted 10-30 s. The threshold for the contralateral slow v.r.p. was about two times higher than that for the monosynaptic reflex, and it coincided with the threshold for activating the slow-conducting afferent fibres. The contralateral slow v.r.p. was abolished after the spinal cord was treated with capsaicin (1 microM for 30 min) in vitro. The contralateral slow v.r.p. was absent in the spinal cord derived from 4-day-old rats that had received capsaicin (50 mg kg-1, s.c.) on the 2nd day of life. The contralateral fast v.r.p. and other reflexes of fast time courses remained unaltered after treatment with capsaicin in vitro or in vivo. Administration of an SP antagonist, [D-Arg1, D-Pro2, D-Trp7,9 Leu11]-SP in concentrations of 5-16 microM depressed the contralateral slow v.r.p., but did not affect the monosynaptic reflex, the dorsal root potential and the contralateral fast v.r.p. [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP (5 microM) markedly depressed the SP-induced depolarizing response recorded from the ventral root whereas the responses to noradrenaline, 5-hydroxytryptamine, neurotensin and thyrotrophin releasing hormone (TRH) were unaffected by the SP antagonist. The response of the ventral root to acetylcholine was slightly depressed by the antagonist. The SP antagonist at 5-10 microM did not exert any agonist action on the motoneurones. The present results in conjunction with those of previous studies support the hypothesis that SP released from certain primary afferent fibres acts as a neurotransmitter, producing in dorsal horn neurones slow excitatory postsynaptic potentials which lead to the generation of the contralateral slow v.r.p.
We have designed and synthesized a series of novel DNA photocleaving agents which break DNA with high sequence specificity. These compounds contain the non-diffusible photoactive p-nitrobenzoyl group covalently linked via a dimethylene (or tetramethylene) spacer to thiazole analogues of the DNA binding portion of the antibiotic bleomycin A2. By using a variety of 5' or 3' 32P-end labeled restriction fragments from plasmid pBR322 as substrate, we have shown that photoactive bithiazole compounds bind DNA at the consensus sequence 5'-AAAT-3' and induce DNA cleavage 3' of the site. Analysis of cleavage sites on the complementary DNA strand and inhibition of DNA breakage by distamycin A indicates these bithiazole derivatives bind and attack the minor groove of DNA. A photoactive unithiazole compound was less specific inducing DNA breakage at the degenerate site 5'-(A/T)(AA/TT)TPu(A/T)-3'. DNA sequence recognition of these derivatives appears to be determined by the thiazole moiety rather than the p-nitrobenzoyl group: use of a tetramethylene group in place of a dimethylene spacer shifted the position of DNA breakage by one base pair. Moreover, much less specific DNA photocleavage was observed for a compound in which p-nitrobenzoyl was linked to the intercalator acridine via a sequence-neutral hexamethylene spacer. The 5'-AAAT-3' specificity of photoactive bithiazole derivatives contrasts with that of bleomycin A2 which cleaves DNA most frequently at 5'-GPy-3' sequences. These results suggest that the cleavage specificity exhibited by bleomycin is not simply determined by its bithiazole/sulphonium terminus, and the contributions from other features, e.g. its metal-chelating domain, must be considered. The novel thiazole-based DNA cleavage agents described here should prove useful as reagents for probing DNA structure and for elucidating the molecular basis of DNA recognition by bleomycin and other ligands.