On-chip temporal focusing of elastic waves in a phononic crystal waveguide.

The ability to manipulate acoustic and elastic waveforms in continuous media has attracted significant research interest and is crucial for practical applications ranging from biological imaging to material characterization. Although several spatial focusing techniques have been developed, these systems require sophisticated resonant structures with narrow bandwidth, which limit their practical applications. Here we demonstrate temporal pulse manipulation in a dispersive one-dimensional phononic crystal waveguide, which enables the temporal control of ultrasonic wave propagation. On-chip pulse focusing is realized at a desired time and position with chirped input pulses that agree perfectly with the theoretical prediction. Moreover, traveling four-wave mixing experiments are implemented, providing a platform on which to realize novel nonlinear phenomena in the system. Incorporating this dispersive pulse engineering scheme into nonlinear phononic crystal architecture opens up the possibility of investigating novel phenomena such as phononic solitons.

Highly diastereofacial anti-aldol reaction: practical synthesis of optically active anti-2-alkyl-3-hydroxycarboxylic acid ester units.

A variety of esters derived from commercially available norephedrine were used in diastereoselective anti-aldol reactions. The aldol reaction of designed 2-(N-2-methylbenzyl-N-2,4,6-trimethylbenzyl)amino-1-phenylpropanol esters 4a-d with aldehydes furnished anti-2-alkyl-3-hydroxycarboxylic acid esters in excellent diastereomeric ratios (>98:2) when LDA-Cp2ZrCl2 (0.3 equiv) was used for enolization, followed by transmetalation into the zirconium enolate for aldolization. The novel auxiliary 3 for the anti-aldol reaction does not exhibit the ordinary basicity of tertiary amines; 3 can be extracted from acidic media with organic solvents. Its use is, therefore, very advantageous not only for extraction of the aldol products from the acidic water solutions, but also for recovering the chiral auxiliary 3 after the reductive cleavage. Treatment of aldol or 3-protected aldol products with DIBAL-H or LiAlH4 affords the versatile synthons, 2-alkyl-propane-1,3-diols or those 3-protected diols in >98% ee's together with 3 in nearly quantitative recovery.

Immunotactoid glomerulopathy characterized by steroid-responsive massive subendothelial deposition.

We report a case of immunotactoid glomerulopathy with unique histologic findings in serial biopsies. A 73-year-old man complained of developing general edema. Laboratory data on admission presented moderate renal dysfunction with nephrotic syndrome. There was no evidence of systemic disease that might cause secondary glomerulopathy. Light microscopy of the renal specimen revealed lobulation of glomerular tufts and massive endothelial deposition of hyaline-like periodic acid-Schiff-positive substance with neutrophilic infiltration. The deposits were positive for immunoglobulin by immunohistochemical stains but negative for Congo red stain. Electron microscopy disclosed the deposition of microtubular structure (60 nm in diameter) predominantly in the subendothelial area and to some extent in the subepithelial and mesangial areas. Some of the tubules were extremely large (100 to 130 nm in diameter) and displayed a unique scroll structure in cross-section. The patient was treated with two sessions of plasma exchange and subsequent oral prednisolone (30 mg/d). Proteinuria and renal dysfunction improved significantly in the following 2 months. Second and third renal biopsies revealed disappearance of the deposit along with the improvement of proteinuria and renal dysfunction. Because similar microtubular structures were found in neutrophils in the glomerulus as well as in the urinary sediment, phagocytosis was suggested as a possible mechanism for removal of the deposit.

[High PTHrP level induced hypercalcemia and acute renal failure in a multiple myeloma patient].

Multiple myeloma causes various renal injuries by direct invasion of myeloma cells, AL amyloidosis and hypercalcemia. Hypercalcemia induced by myeloma has been thought to be a result of local osteolysis. Recently, however, it was noted that no significant difference existed in the degree of bone-destruction between hypercalcemic and normocalcemic multiple myeloma. The exact mechanisms of hypercalcemia induced by multiple myeloma remain unconfirmed. In the present study, we report a 70-year-old man, suffering from acute renal failure due to multiple myeloma and severe hypercalcemia. While the serum PTH level was low, PTHrP was markedly increased. Bone scintigraphy implied systemic increase in bone turnover in addition to cold spots corresponding to punched out lesions on bone Xp. After the intravenous administration of bisphosphonate, hypercalcemia and hot accumulation on bone scintigraphy were improved while the PTHrp level and bone destruction by myeloma cells were not improved. The present case suggests involvement of PTHrP in hypercalcemia of multiple myeloma.

[Factors related to the QT prolongation in chronic renal failure].

QT prolongation, a risk factor for arrhythmia and cardiac death, is observed in uremic patients. Though hypocalcemia, autonomic nerve dysfunction and cardiac hypertrophy are assumed to cause the uremic QT prolongation, the exact mechanism remains unspecified. We therefore examined factors related to the QT interval in chronic renal failure (CRF). Corrected QT interval (QTc) was significantly prolonged in CRF just before the induction of dialysis therapy (group A) compared with nephrotic syndrome with the intact or mildly impaired renal function (group B). QTc was also prolonged in acute renal failure (group C). Cardio-thoracic ratio, serum albumin and Ca correlated with QTc in group A, but not in B or C. A single HD session in group A failed to shorten QTc, despite a significant increase in serum Ca++. Autonomic dysfunction did not appear to be a major determinant of QT prolongation, since QTc was not different between diabetics and non-diabetics in group A and in chronic HD patients (group D). In group D, QTc did not correlate with SV1 + RV5 on ECG or left ventricular wall thickness (LVWT) on echocardiography. In another group of chronic HD patients (group E), there was no significant correlation between QTc and the parameters of left ventricular mass, plasma brain natriuretic peptide (BNP). However, in the patients subjected to repeated echocardiography in group D, QTc and LVWT changed in parallel. In a retrospective analysis of QTc in group D, QTc was maximally prolonged at the time of starting HD therapy, and gradually improved in the following 1-5 years in both diabetics and non-diabetics. In contrast, chronic CAPD patients (group F) revealed no improvement of QTc. Thus, uremic QT prolongation cannot be explained simply by any of the previously assumed factors, but appears to be affected by multiple factors, which are partially correctable by chronic HD therapy.

Improved total synthesis and structure-activity relationship of arenastatin A, a potent cytotoxic spongean depsipeptide.

An efficient asymmetric synthesis of a cyclic depsipeptide arenastatis A (1) is described. 1, isolated from the marine sponge Dysidea arenaria, exhibited extremely potent cytotoxicity with IC50 of pg/ml for KB cells, and in this context the structure-activity relationship among several stereoisomers of 1 and allied compounds has also been examined.

Marine natural products. XXXIV. Trisindoline, a new antibiotic indole trimer, produced by a bacterium of Vibrio sp. separated from the marine sponge Hyrtios altum.

A new antibiotic indole trimer named trisindoline (1) was isolated, together with a known dioxopiperazine brevianamide F (2), from the culture of a bacterium of Vibrio sp., which was separated from the Okinawan marine sponge Hyrtios altum. The structure of trisindoline (1) has been determined on the bases of physicochemical evidence and chemical synthesis.

[Allosterism of acidic alcohol dehydrogenase (class III ADH) of mouse liver and its role in alcohol metabolism].

Two major ADH isozymes of mouse liver, basic ADH (Class I) and acidic ADH (Class III) were purified and the effects of various hydrophobic substances (t-butanol, butyramide, trifluoroethanol, trichloroacetic acid, stearic acid, oleamide, phenylalanine and norleucine) on their activities were investigated. All these hydrophobic substances activated acidic ADH with a range of from 15 to 560%, and reversely inactivated basic ADH activity with a range of from 10 to 100%, when 150 mmol/l ethanol was used as a substrate. Among these substances, t-butanol, which was the most potent activator of acidic ADH, enhanced the activity by 560% and completely inactivated basic ADH at a concentration of 1.0 mol/l. Kinetics studies demonstrated that the activation of acidic ADH by the hydrophobic substances was due to marked decreases of Km for ethanol in spite of decreases of Vmax, suggesting these substances were positive allosteric effectors for the isozyme. The inactivation of basic ADH by the hydrophobic substances was due to a decrease of Vmax without changing Km for ethanol. These results indicate that the activities of two ADH isozymes are regulated reversely by the hydrophobicity of the reaction environment which changes their kinetics constants. The ELISA method using the isozyme-specific antibody demonstrated that the content of acidic ADH in mouse liver was about 7 times larger than that of basic ADH (5.3 +/- 0.86 vs 0.72 +/- 0.06 mg/g-liver). In the light of the hydrophobic regulation of ADH isozyme activities and their liver contents, the role of acidic ADH on alcohol metabolism may be more predominant than basic ADH in the liver under hydrophobic condition.

Effects of chronic ethanol intoxication on aldehyde dehydrogenase in mouse liver.

Effects of chronic ethanol treatment with liquid diet (ethanol constituted 28% of the calories) on hepatic aldehyde dehydrogenase (ALDH) isozymes were studied in mice. One week of ethanol feeding caused 66% loss of mitochondrial low Km ALDH activity and 80% loss of mitochondrial high Km ALDH activity, compared with the control-fed group. However, these decreases recovered after 4 weeks of ethanol feeding. The cytosolic ALDH activity increased up to 140% after 10 weeks of ethanol feeding, compared with the control-fed group. Effects of acute ethanol injection on ALDH activity after prolonged ethanol feeding were studied. The severe acute ethanol injection (4.5 g/kg body wt) after 4 weeks of ethanol feeding caused a drastic decrease of the mitochondrial low Km ALDH activity; however, that did not affect the ethanol-fed group. After 10 weeks of ethanol feeding, acute ethanol injection (4.5 g/kg body wt) caused about twofold increase in mitochondrial low Km ALDH activity. From the agarose IEF study, it was found that ethanol intoxication does not affect the number and pI value of ALDH isozymes.

[Death investigation system in the United States].

In light of recent developments and public interest on the issue of organ transplant and the definition of death by neurological function ("brain death"). A more expansive role of medicolegal investigation of deaths may be needed. This article was presented for the purpose of understanding the medicolegal investigative system in the United States. The traditional coroner system in the United States was taken from the English system and was established as an elected coroner system during a colonial period. The coroner system became more politically involved and the coroner was elected by popular votes. The political aspect was the main driving force and the medicolegal aspect was ignored, thus, the Commonwealth of Massachusetts was the first state to adopt the medical examiner system. In 1991, 41 out of 50 states have adopted the medical examiner system, either state-wide or on a local option. One of the principal differences between coroner and medical examiner systems is the qualification of the head of the agency. The coroner is an elected individual who acts as an administrator and conducts quasi-judicial function of the department. The medical function is delegated to a physician who performs his duty often on a part-time basis. The medical examiner's office is headed by a Board certified Forensic Pathologist who acts as an administrator and directs all functions including medical and scientific investigation. He is a public employee and is protected under the civil service rules, thus, his decision would be less likely influenced by political pressure. The jurisdiction of the coroner and medical examiner is generally the same by law, however a medical examiner's approach and decision-making is more medically oriented and tends to be more expansive and ready to adopt to the needs in medicolegal issues arising from scientific progress.(ABSTRACT TRUNCATED AT 250 WORDS)

Fixed human tissues: a resource for the identification of individuals.

Polymorphic genetic loci of the deoxyribonucleic acid (DNA) present in formalin-fixed, paraffin-embedded tissues were successfully analyzed by utilizing the polymerase chain reaction. Using this analysis, with three different polymorphic loci [human leucocyte antigen (HLA) DQ alpha, low-density lipoprotein receptor, and parathyroid hormone], fixed tissues representing 14 different individuals were genotyped and could be distinguished from each other. The techniques were further applied to the fixed autopsy tissues of a man in which a question of paternity arose postmortem. Since many individuals have surgical procedures or autopsy, these readily available fixed tissues represent an additional resource for the identification of individuals.

Effects of acute ethanol intoxication on aldehyde dehydrogenase in mouse liver.

To elucidate the effects of acute ethanol intoxication on hepatic aldehyde dehydrogenase (ALDH), the activities of these isozymes were measured after acute ethanol injection at the doses of 1, 3 or 5 g/Kg body weight in mice. At the same time, blood ethanol and acetaldehyde levels were measured to consider their correlation to the changes in ALDH activities. In the cytosolic fraction, acute ethanol injection caused no effects on high Km ALDH. However, low Km ALDH activity decreased significantly after 0.5 and 12 hr at the dose of 5 g/Kg body weight. In the granule fraction, acute ethanol injection caused more than 50% loss of low Km ALDH activity after 2 to 8 hr at the dose of 1 g/Kg and after 0.5 to 8 hr at the dose of 3 or 5 g/Kg body weight, in comparison with the untreated group. However, high Km ALDH activity decreased only after 4 hr at the dose of 3 or 5 g/Kg body weight. The elimination rate of blood ethanol was 158.0 mumol/min/1 and 125.6 mumol/min/1 after 0.5 to 4 hr of ethanol injection at the dose of 3 or 5 g/Kg body weight, respectively. However, these elimination rates decreased drastically after 4 to 8 hr following ethanol injection. The elimination rate of blood acetaldehyde was 116.6 nmol/min/1 after 1 to 2 hr, and the rate decreased to 6.9 nmol/min/1 after 2 to 8 hr following ethanol injection at the dose of 5 g/Kg body weight. These drastic decreases in acetaldehyde elimination rate appear to be caused by reduction of the granule low Km ALDH activity.