Transplanted Murine Long-term Repopulating Hematopoietic Cells Can Differentiate to Osteoblasts in the Marrow Stem Cell Niche

Bone marrow transplantation (BMT) can give rise to donor-derived osteopoiesis in mice and humans; however, the source of this activity, whether a primitive osteoprogenitor or a transplantable marrow cell with dual hematopoietic and osteogenic potential, has eluded detection. To address this issue, we fractionated whole BM from mice according to cell surface immunophenotype and assayed the hematopoietic and osteopoietic potentials of the transplanted cells. Here, we show that a donor marrow cell capable of robust osteopoiesis possesses a surface phenotype of c-Kit⁺ Lin⁻ Sca-1⁺ CD34^−/lo, identical to that of the long-term repopulating hematopoietic stem cell (LTR-HSC). Secondary BMT studies demonstrated that a single marrow cell able to contribute to hematopoietic reconstitution in primary recipients also drives robust osteopoiesis and LT hematopoiesis in secondary recipients. These findings indicate that LTR-HSC can give rise to progeny that differentiate to osteoblasts after BMT, suggesting a mechanism for prompt restoration of the osteoblastic HSC niche following BM injury, such as that induced by clinical BMT preparative regimens. An understanding of the mechanisms that regulate this differentiation potential may lead to novel treatments for disorders of bone as well as methods for preserving the integrity of endosteal hematopoietic niches.     

The Artificial Kidney in Chronic Renal Failure

Hemodialysis has proved valuable in improving and stabilizing patients in terminal chronic uremia.

In this analysis of 71 patients in whom hemodialysis was used, the diagnosis and therapeutic response were definitely correlated. The highest percentage of favorable responses was obtained in cases of polycystic renal disease; none of the patients with subacute glomerulonephritis responded favorably.

The prognosis was worse in chronic glomerulonephritis when hypertension or extensive glomerular destruction was present. Factors such as age, congestive heart failure and active infection were not significant in predicting a response.     

Chaotic and phase-locked responses of the somatosensory cortex to a periodic medial lemniscus stimulation in the anesthetized rat

Field potential responses of the somatosensory cortex to a periodic medial lemniscus (ML) fiber stimulation were investigated in anesthetized rats. Since the field potential responses of the cortex depend on the depth of anesthesia, two criteria were introduced to control the depth of anesthesia. One criterion is that spindle oscillations are caused by a single shock to ML fibers, and the other is that the dominant frequency of spontaneous field potential rhythm is in the frequency range of the delta wave. Phase-lockings and chaotic responses occurred depending on stimulus parameters under the above conditions. Trajectories of the chaotic responses in the two-dimensional phase space (V, dV/dt) reconstruct strange attractors, and stroboscopic cross-sections of each attractor show stretching and folding process. Each one-dimensional strobomap of the chaotic responses is a noninvertible function with an unstable fixed point. This is undoubted evidence for chaotic responses of the somatosensory cortex in vivo. Power spectra well characterize the periodic and the chaotic responses. Positive Lyapunov exponents and low, noninteger correlation dimensions of the chaotic responses are consistent with the above evidence. Consequently, four kinds of chaotic responses were classified. A periodic-chaotic transition sequence was observed at a relatively low stimulus current when the frequency of the stimulation was varied. A cascade of period-doubling bifurcations was also observed on a route from the region of the 1:1 phase-locking to one of the regions of the chaotic responses.     

The efficacy of extracorporeal shock wave lithotripsy on single dense calcified gallstones according to computed tomography

The efficacy and complications of extracorporeal shock wave lithotripsy (ESWL) for single gallstones were compared between 15 patients with a CT-lucent stone and 18 patients with a dense calcified stone. In all of five patients with a stone smaller than 10 mm in diameter, complete or sufficient clearance was observed, regardless of calcification. However, in 28 patients with a stone larger than 11 mm in diameter, the rates of complete or sufficient clearance were lower in those with a dense calcified stone (64%) than in those with a computed tomography (CT) lucent stone (93%). There was no difference in the rate of complications between patients with a CT-lucent stone and those with a dense calcified stone. These results thus suggest that extracorporeal shock wave lithotripsy may be safely employed for patients with a single calcified gallstone.     

Positron emission tomography with 4-[18F]fluoro-L-m-tyrosine in MPTP-induced hemiparkinsonian monkeys

PET imaging studies with 4-[¹⁸F]fluoro-L-m-tyrosine (FMT) in normal macaca monkeys showed selective accumulations of radioactivity in the striatum with time. In monkeys rendered hemiparkinsonian by intracarotid infusion of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP), FMT uptake was eliminated in the lesioned striatum. FMT-PET studies were able to detect dopaminergic terminals in both normal and hemiparkinsonian monkeys, and clearly showed a reduction in aromatic L-amino acid decarboxylase (AAAD) activities in the MPTP-lesioned striatum. These results show that FMT is promising as a PET tracer for the evaluation of central dopaminergic systems in parkinsonism.     

Preventive effect of simultaneously infused lipid emulsion against thrombophlebitis during postoperative peripheral parenteral nutrition

A prospective, randomized study was conducted to determine whether simultaneous infusion of lipid emulsion with an amino acid-dextrose-electrolyte solution would reduce the incidence of thrombophlebitis (TP) during postoperative peripheral parenteral nutrition (PPN). Thirty patients who had undergone gastric resection for adenocarcinoma were randomly divided into two groups according to whether they were infused with 10% lipid emulsion (group A) or 5% glucose solution (group B) simultaneously with the amino acid-glucose solutions. The total osmolarity of the infusion solutions in each group was 853 mOsm/l. The incidence of complications due to TP, namely, redness and/or edema beneath the cannula insertion site and/or pain, was investigated. There were no differences in the background characteristics of the patients in groups A and B, except regarding concurrent resection of other organs (P=0.03). The incidence of edema in group A was significantly lower than in group B on postoperative days 2 and 4, although there was no difference in the incidence of redness and pain between the two groups. These findings suggest that the simultaneous infusion of lipid emulsion has a preventive effect against TP during postoperative PPN, and may be a practical means of providing PPN after gastrointestinal surgery.     

Involvement of α-adrenoceptors in the endothelium-dependent depression of noradrenaline-induced contraction in rat aorta

The involvement of endothelium-derived nitric oxide (NO) in the depressant action of the endothelium on noradrenaline-induced contractions and characterization of the receptor involved in the release of NO were studied using rat aorta. The noradrenaline-induced contraction was significantly potentiated by endothelium removal and in the presence of N^G-nitro-L-arginine (L-NNA) or N^G-monomethyl-L-arginine (L-NMMA). The contraction induced by phenylephrine was also potentiated in the presence of L-NNA. Clonidine could induce contraction only in endothelium-denuded preparations or in the presence of L-NNA. The potentiating action of L-NNA on noradrenaline-induced contractions could also be observed in the presence of yohimbine or rauwolscine, although dose-response curves were shifted to the right. The depression of noradrenaline-induced contractions observed in the presence of the endothelium was increased by repeated stimulation. The depression was prevented by L-NNA and this effect was reversed by L-arginine. These results indicate the possibility that NO can be released through stimulation of α₁- and α₂-adrenoceptors on the endothelium and depresses noradrenaline-induced contractions of smooth muscle, although the contribution of the respective adrenoceptors remains to be investigated. The release of NO was increased when the stimulation was applied repeatedly.     

Renal oncocytomatosis in a long-term hemodialysis patient treated by laparoscopic surgery

A 50-year-old female, who had been on maintenance hemodialysis for 22 years, consulted our clinic because of a left renal mass detected incidentally by ultrasonography. Computed tomography (CT) demonstrated a solid hypervascular mass, suggesting a renal cell carcinoma (RCC), in the left atrophic kidney. Left hand-assisted laparoscopic nephrectomy (HALN) was performed. The histopathological diagnosis was renal oncocytomatosis. Renal oncocytomatosis in a long-term hemodialysis patient is extremely rare. We report the first case of renal oncocytomatosis in a long-term hemodialysis patient treated with hand-assisted laparoscopic nephrectomy.     

Effects of changes in skiing posture on the kinetics of the knee joint

This study was performed to investigate the effects of changes in the skiing posture on mechanical stress across the knee joint. The aim of the present study was to establish a safer form of skiing for the prevention of injury to the anterior cruciate ligament of the knee (ACL). Ten healthy volunteers were placed on a force plate on an artificial slope, and assumed forward and backward bending postures with a single leg by changing their centre of gravity. The knee flexion angles were limited to approximately 30° by orthotics in each posture. Joint moments of the lower extremity were analyzed using a motion analysis system, and the muscle activities of the lower extremity were recorded by EMG and digitised to integrated EMG in each posture. In addition, extrusion of the lower leg by the boot was measured using a force sensor sheet inserted behind the calf. We found that the extension moment of the hip and ankle joints, and muscular activity of the hamstrings were increased in forward bending, whereas the extension moment of the knee and muscular activity of the quadriceps were decreased. Conversely, the muscular activity of the quadriceps, the flexion moment of the hip, extension moment of the knee joint, and pressure of the boot were increased in backward bending, whereas muscular activity of the hamstrings was decreased. The dependency on the hamstrings increased in forward bending in a skiing posture on a slope with slight knee flexion. Therefore, forward bending seemed to be an advantageous posture for the prevention of ACL injury. Conversely, in a backward bending skiing posture, the extension moment of the knee joint produced by muscle contraction of the quadriceps also increased imbalance in the hamstrings. The results of this study suggest that the internal force exerted by the quadriceps, in addition to the passive factor of extrusion of the lower leg by the boot, may contribute to non-contact ACL injury in a backward bending posture while skiing.