Formation and evolution of carbonaceous asteroid Ryugu: Direct evidence from returned samples.

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide-bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu's parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of <1 (by mass). Less altered fragments contain olivine, pyroxene, amorphous silicates, calcite, and phosphide. Numerical simulations, based on the mineralogical and physical properties of the samples, indicate that Ryugu's parent body formed ~2 million years after the beginning of Solar System formation.

Impactor material records the ancient lunar magnetic field in antipodal anomalies.

The Moon presently has no dynamo, but magnetic fields have been detected over numerous portions of its crust. Most of these regions are located antipodal to large basins, leading to the hypothesis that lunar rock ejected during basin-forming impacts accumulated at the basin antipode and recorded the ambient magnetic field. However, a major problem with this hypothesis is that lunar materials have low iron content and cannot become strongly magnetized. Here we simulate oblique impacts of 100-km-diameter impactors at high resolution and show that an ~700 m thick deposit of potentially iron-rich impactor material accumulates at the basin antipode. The material is shock-heated above the Curie temperature and therefore may efficiently record the ambient magnetic field after deposition. These results explain a substantial fraction of the Moon's crustal magnetism, and are consistent with a dynamo field strength of at least several tens of microtesla during the basin-forming epoch.

A non-acromegalic case of multiple endocrine neoplasia type 1 accompanied by a growth hormone-releasing hormone-producing pancreatic tumor.

Cases of acromegaly due to GHRHproducing pancreatic endocrine tumors have been reported. Here we present a case of a 31-yr-old nonacromegalic man with hyperparathyroidism and elevated serum IGF-I with normal serum GH levels. Serum GH was not suppressed below 1 ng/ml by the glucose tolerance test and increased in response to TR H and GHRH administration. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia and an abdominal computed tomography (CT ) scan showed a tumor in the pancreatic tail. Plasma concentration of GHRH was elevated. Based on these clinical data, multiple endocrine neoplasia (MEN) type 1 was suspected. Three enlarged parathyroid glands were removed and a distal pancreatectomy was performed. Pathological examination of the parathyroid glands and pancreatic tumor showed nodular hyperplasia and a well-differentiated endocrine tumor, respectively, both compatible with MEN features. Immunohistochemistry revealed positive immunoreactivity for GHRH, SS , insulin, glucagon, chromogranin A, and pancreatic polypeptide in the pancreatic tumor. After pancreatic surgery, elevated levels of GHRH and IGF-I were normalized and pituitary hyperplasia definitely decreased in size. In cases of pituitary hyperplasia with elevated IGF-I, ectopic GHRH syndrome must be considered even if physical features of acromegaly are absent. It is also important to measure plasma GHRH concentrations in order to give a diagnosis.

Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia.

We conducted a comprehensive analysis of 28 recurrently mutated genes in acute myeloid leukemia (AML) in 271 patients with de novo AML. Co-mutations were frequently detected in the intermediate cytogenetic risk group, at an average of 2.76 co-mutations per patient. When assessing the prognostic impact of these co-mutations in the intermediate cytogenetic risk group, overall survival (OS) was found to be significantly shorter (P=0.0006) and cumulative incidence of relapse (CIR) significantly higher (P=0.0052) in patients with complex molecular genetic abnormalities (CMGAs) involving three or more mutations. This trend was marked even among patients aged ⩽65 years who were also FLT3-ITD (FMS-like tyrosine kinase 3 internal tandem duplications)-negative (OS: P=0.0010; CIR: P=0.1800). Moreover, the multivariate analysis revealed that CMGA positivity was an independent prognostic factor associated with OS (P=0.0007). In stratification based on FLT3-ITD and CEBPA status and 'simplified analysis of co-mutations' using seven genes that featured frequently in CMGAs, CMGA positivity retained its prognostic value in transplantation-aged patients of the intermediate cytogenetic risk group (OS: P=0.0002. CIR: P<0.0001). In conclusion, CMGAs in AML were found to be strong independent adverse prognostic factors and simplified co-mutation analysis to have clinical usefulness and applicability.

The Tokyo Metropolitan Home Vision Screening Program for amblyopia in 3-year-old children.

In August 1989, the Tokyo Metropolitan Government officially began a vision screening program for children aged 3 years 1 month. A 1988 pilot study of 1,303 children this age disclosed five cases (0.38%) of amblyopia. The home vision test, which uses picture cards of familiar figures, proved to be an efficient and inexpensive method of screening when incorporated into the existing health-check program for 3-year-old children. In the initial eight months of the program, 21,906 children were screened. Of these, 419 children (1.9%) were referred to an ophthalmologist for follow-up, and amblyopia was detected in 41 children (0.19%).

Scalp localization using a simple algorithm.

We have developed a simple algorithm for scalp localization for craniotomy. Using a series of CT/MRI data, the point on the scalp closest to the center of the lesion (T) is determined by our program. A plane (plane R) is defined by three points: bilateral auditory meati and T. Point S is the intersection of three planes: the plane R, the scalp surface and the midsagittal plane. The distance from either S or the ipsilateral external auditory meatus to T is measured along the scalp surface on the plane R. The distance from the nasion to S along the scalp surface on the midsagittal plane is also measured. To determine the craniotomy site, these distances are measured directly on a patient's scalp in the operating room. This simple and accurate method for scalp localization could be used by installing our program in conventional CT/MR scanners.

Haloperidol-induced blockade of induction of long-term potentiation in perforant path-dentate gyrus pathway in chronically prepared rabbits.

We investigated the effects of the representative neuroleptic and dopamine receptor antagonist haloperidol (HPD) on the induction of long-term potentiation (LTP) or on the previously induced LTP in the perforant path-dentate gyrus pathway in chronically prepared rabbits. The IP HPD injection of 0.8 mg/kg blocked the induction of LTP when it was given before LTP-inducing tetanic stimulations, although this dose showed virtually no effect on the baseline control responses in the perforant path-dentate gyrus pathway to single shocks. However, neither 0.8-mg/kg nor 1.6-mg/kg HPD doses affected the previously induced LTP. The possible mechanisms underlying these results, notably the HPD-induced blockade of LTP induction, are discussed, especially in association with the inhibitory action of HPD on calmodulin-mediated events rather than dopaminergic function.

Chemonucleolysis with calpain I in rabbits.

Calpain I is a calcium-dependent cysteine proteinase that has been recently shown to degrade proteoglycan in vitro. The authors injected calpain I, which was purified from human red blood cells, into the intervertebral discs of rabbits. Roentgenograms showed disc space narrowing 1 week after the injection. Histologically, proteoglycan of the nucleus pulposus and anulus fibrosus decreased and notochordal cells in the nucleus pulposus almost disappeared. Biochemical data of the nucleus pulposus showed that the amounts of smaller proteoglycans increased 1 and 4 weeks after the injection. Eight weeks after the injection, histologic and biochemical data showed recovery compared with the data 1 week after injection. These findings show that calpain I is as potent an enzyme as chondroitinase ABC and has milder chemonucleolytic action than chymopapain. Regarding its possible clinical application, autogenous calpain I as purified from the patient's own red blood cells may have advantages over chymopapain and chondroitinase ABC in that it will prevent anaphylactic reaction.

Surgical correction of cryptotia with superiorly based superficial mastoid fascia and skin paddle.

An approach for the correction of cryptotia using a superiorly based superficial mastoid fascial flap and a skin paddle is introduced. The buried portion of the auricle was exposed through an incision made along the upper part of the helix, followed by an appropriate correction of the deformed cartilage. Protrusion of the upper portion of the auricle was accomplished using anchoring sutures. A small skin paddle was elevated from the caudal portion of the auricular sulcus with the superiorly based superficial mastoid fascia as the nutrient pedicle and transferred to the temporal skin defect. The procedure was performed in eight auricles in a total of seven patients with cryptotia. A satisfactory contour and protrusion of the auricle were maintained postoperatively, leaving the scar within the auricular sulcus.

Effect of recirculation of 99mTc-Sn colloid in estimating mean transit time of soft-tissue vascular anomalies by direct puncture scintigraphy: a simulation analysis.

We have reported direct puncture scintigraphy, a novel method to estimate mean transit time (MTT) of soft-tissue vascular anomaly. In the examination, 99mTc-Sn colloid is infused percutaneously into the lesion, and MTT is calculated using the time-activity curve for the lesion. Recirculation of 99mTc-Sn colloid is neglected in computing MTT, and this may cause error. The aim of this study was to assess this error by simulation analysis. Data simulating direct puncture scintigraphy were produced for lesions with various blood volumes and various blood flows, considering recirculation and blood clearance of 99mTc-Sn colloid, and MTT was estimated by the same method used in the patient examination. Although MTT was overestimated in large lesions with intermediate or long MTT, the error was small except in extremely large lesions. It was suggested that recirculation of 99mTc-Sn colloid does not cause a serious problem in the clinical use of direct puncture scintigraphy.

Use of whole-body imaging using Tc-99m RBC in patients with soft-tissue vascular lesions.

We investigated the usefulness of whole-body imaging as an adjunct to spot imaging in soft-tissue vascular lesions, such as hemangiomas and vascular malformations. Spot imaging of the known lesion and whole-body imaging were performed 1-3 hours after the injection of Tc-99m RBC in 42 patients with soft-tissue vascular lesions. Whole-body imaging was considered to be useful in only two patients, who had multiple distant occult lesions in addition to large known lesions. It was suggested that the routine addition of whole-body imaging is not cost effective in patients with soft-tissue vascular lesions, although it may be beneficial for detecting occult lesions in patients with hemangiomas.

[Efficacy of immunized milk for preventing viral infection].

This paper investigated the efficacy of passive protection provided by milk (immunized milk) against enterovirus infection in mice experimentally infected with enterovirus. Milk with a high antibody titer against six enterovirus serotypes was prepared from hyperimmunized goat. In vivo and in vitro experiments were performed and the results showed that immunized milk has an antiviral activity against enterovirus infection. Further observation was performed using Coxsackie B 3 virus (CVB 3). When immunized milk was orally applied to mice prior to oral inoculation with CVB 3, preventive effects against viral infection such as reduction of histopathological changes in the heart and reduced detection of the virus genome in the organs were seen. The antiviral effect was also indicated by the increase of CD4+T cells proportion in the i-IEL. The proportion of virus specific CD4+T cells was increased in mice treated with immunized milk, whereas no such increase was detected in control mice. These results suggest that oral application of immunized milk is not only capable of preventing viral infection but also induces specific immunological responses. These phenomena may play an important role in host defense mechanisms.

Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia.

Gene mutations were found in acute myeloid leukemia (AML) and their importance has been noted. To clarify the importance and stability of mutations, we examined gene mutations in paired samples at diagnosis and relapse of 34 adult AML patients. Five acquired gene mutations were detected at relapse. Of the 45 gene mutations at diagnosis, 11 of them were lost at relapse. The acquired mutations at relapse were all class I mutations as Fms-like tyrosine kinase 3 (FLT3) and rat sarcoma viral oncogene homolog (RAS) mutations. The disappeared mutations at relapse were 3 of 11 internal tandem duplications of FLT3 (FLT3-ITD) (27.3%), 3 of 3 FLT3 tyrosine kinase domain (FLT3-TKD) (100%), 3 of 13 Nucleophosmin 1 (23.1%) and 2 of 5 CCAAT/enhancer-binding protein-α (40%) mutations. However, epigenetics-modifying gene (DNMT3a, TET2 and IDH1/2) mutations had no change between diagnosis and relapse samples, and may become minimal residual disease marker. The frequency of FLT3-ITD at relapse in patients with DNMT3a mutation at diagnosis is significantly higher than those in patients without them (P=0.001). Moreover, the high frequency of FLT3-ITD at relapse is also seen in AML cases that initially present with any epigenetics-modifying gene mutations (P<0.001). Our results indicate that epigenetics-modifying gene mutations may cause genetic instability and induce FLT3-ITD, leading to resistance to therapy and relapse.

Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia.

Recently, c-kit mutations have been reported as a novel adverse prognostic factor of acute myeloid leukemia with t(8;21)(q22;q22) translocation (t(8;21) AML). However, much remains unclear about its clinical significance. In this study, we developed a highly sensitive mutation detection method known as mutation-biased PCR (MB-PCR) and investigated the relationship between c-kit mutations and prognosis. When c-kit mutations were analyzed for 26 cases of t(8;21) AML using the direct sequence (DS) and MB-PCR, the latter had a much higher detection rate of c-kit mutations at initial presentation (DS 5/26(19.2%) vs MB-PCR 12/26(46.2%)). Interestingly for the three cases, in which c-kit mutations were observed only at relapse with the DS, c-kit mutations were detected at initial presentation using the MB-PCR. This result suggests that a minor leukemia clone with c-kit mutations have resistance to treatment and are involved in relapse. In univariate analyses, the presence of a c-kit mutation using DS was not an adverse prognostic factor (P = 0.355), but was a factor when using MB-PCR (P = 0.014). The presence of c-kit mutations with MB-PCR was also an independent adverse prognostic factor by multivariate analyses (P = 0.006). We conclude that sensitivity of c-kit mutation detection method is important to predict prognosis for t(8;21) AML.

Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats.

Phosphorus directly controls parathyroid hormone (PTH) synthesis and secretion. Serum levels of the novel phosphate-regulating hormone, fibroblast growth factor 23 (FGF23), are positively correlated with hyperphosphatemia in patients with chronic renal insufficiency (CRI). We proposed that changes in serum PTH and FGF23 levels might be associated with changes in serum phosphorus levels caused by the phosphate binder sevelamer hydrochloride (sevelamer, i.e. crosslinked poly[allylamine hydrochloride]). Rats were fed a diet containing adenine for 4 weeks to establish CRI. Animals were then offered either a normal diet or a diet containing 1 or 3% sevelamer for 8 weeks continuously, or intermittently with sevelamer diet or a normal diet offered for alternating 2-week periods. Changes in the serum levels of phosphorus, calcium, PTH, FGF23, and 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) were monitored over time. Adenine-treated rats developed severe CRI, with markedly elevated serum levels of phosphorus, PTH and FGF23, and reduced levels of serum 1,25(OH)(2)D(3). Continuous treatment with sevelamer suppressed these increases throughout the study period. Serum phosphorus, PTH, and FGF23 levels decreased rapidly when sevelamer treatments commenced and recovered rapidly once they were discontinued. However, the changes in serum FGF23 levels began after the onset of changes in serum phosphorus and PTH levels. In conclusion, circulating PTH, and FGF23 levels can be promptly manipulated through the control of serum phosphorus levels. Moreover, phosphate-binder treatment can effectively inhibit the elevation of serum FGF23 levels, as well as PTH levels, under conditions of CRI.

Friedrich's disease: a case report.

An eight-year-old girl was presented with painful swelling of the sternoclavicular joint. Radiological and scintigraphic examinations lead to a diagnosis of Friedrich's disease, aseptic necrosis of the sternal end of the clavicle. It is a rare condition which is to be differentiated from osteomyelitis, arthritis, or tumor. Because it is a self-resolving, benign condition, awareness of this disease will save the patient from unnecessary surgery.

Paradoxical GABAergic facilitation on seizure development observed from bicuculline-induced effects on visual cortical kindling at short interstimulus intervals in chronically prepared rabbits.

To investigate the influence of GABAergic function on seizure development, the effects of bicuculline, a GABAa receptor antagonist, on visual cortical and hippocampal kindling were examined in chronically prepared rabbits. Kindling-inducing stimulations were repeated at 5-min intervals. The changes in afterdischarge (AD) durations were compared before and 30 min after a low (2 mg/kg) and high dose (5 mg/kg) i.p. injection of bicuculline solution. In the visual cortical kindling group, the AD durations were markedly shortened after the low dose bicuculline injection, while bicuculline produced a prolongation of the AD durations in the visual cortical with the high dose injection and hippocampal kindling groups. The low dose bicuculline-induced inhibition of visual cortical kindling suggests facilitative GABAergic action on seizure development, while the drug-induced enhancement in the other groups reflects the well-known inhibitory GABAergic action.

Diagnosis by ultrasound of congenital dislocation of the hip joint.

Two hundred thirty-four hips of 117 babies from one day to 18 months of age were examined ultrasonographically for congenital dislocation of the hip joint. Ten hips in eight babies were dislocated or subluxated and there were 11 hip dysplasias in seven babies. In the normal hip, the adaptation between the acetabulum and the femoral head is well demonstrated, and there is no apparent interposition of the limbus between the acetabular roof and the cartilaginous head. In the dislocated hip, the protrusion of the acetabular rim is not so clear as that of the normal hip, and the limbus is seen to be interpositioned between the acetabular roof and the cartilaginous head. In severe cases, the acetabular rim is hidden under the shade of the femoral head. Ultrasonography is an effective method of determining the incidence of dislocation and of diagnosing hip subluxation as well as dysplasia and does not have the hazards of x-ray examination.

Comparison of the incidence of intracranial hemorrhage following conventional mechanical ventilation and high frequency oscillation in beagle puppies.

Controversy exists as to whether high frequency oscillation (HFO) increases the risk of intraventricular hemorrhage (IVH) compared with conventional mechanical ventilation (CMV). We compared the risk of intracranial hemorrhage after phenylephrine-induced hypertension, combined with a hypovolemic, hypotensive insult followed by rapid volume replacement in two groups of newborn beagle puppies (one group on a piston pump HFO and the other on CMV). A total of 12 beagle puppies (6 on HFO and 6 on CMV) survived the protocol. Arterial blood gas analysis and arterial blood pressures through the study were of the same magnitude in both groups. The length of time for which the puppies remained hypertensive and hypotensive also did not vary significantly between the groups. Intraventricular hemorrhages were observed in two of six CMV puppies and two of six HFO puppies. One animal in each group had a white matter hemorrhage. Subarachnoid hemorrhages were seen in 4 animals on CMV and 3 on HFO. This study indicated that HFO does not increase the risk of any kind of intracranial hemorrhage, including IVH, in beagle puppies.