Time-Resolved Measurement of Interatomic Coulombic Decay Induced by Two-Photon Double Excitation of Ne_{2}.

The hitherto unexplored two-photon doubly excited states [Ne^{*}(2p^{-1}3s)]_{2} were experimentally identified using the seeded, fully coherent, intense extreme ultraviolet free-electron laser FERMI. These states undergo ultrafast interatomic Coulombic decay (ICD), which predominantly produces singly ionized dimers. In order to obtain the rate of ICD, the resulting yield of Ne_{2}^{+} ions was recorded as a function of delay between the extreme ultraviolet pump and UV probe laser pulses. The extracted lifetimes of the long-lived doubly excited states, 390(-130/+450) fs, and of the short-lived ones, less than 150 fs, are in good agreement with ab initio quantum mechanical calculations.

Slow Interatomic Coulombic Decay of Multiply Excited Neon Clusters.

Ne clusters (∼5000 atoms) were resonantly excited (2p→3s) by intense free electron laser (FEL) radiation at FERMI. Such multiply excited clusters can decay nonradiatively via energy exchange between at least two neighboring excited atoms. Benefiting from the precise tunability and narrow bandwidth of seeded FEL radiation, specific sites of the Ne clusters were probed. We found that the relaxation of cluster surface atoms proceeds via a sequence of interatomic or intermolecular Coulombic decay (ICD) processes while ICD of bulk atoms is additionally affected by the surrounding excited medium via inelastic electron scattering. For both cases, cluster excitations relax to atomic states prior to ICD, showing that this kind of ICD is rather slow (picosecond range). Controlling the average number of excitations per cluster via the FEL intensity allows a coarse tuning of the ICD rate.

Towards characterization of photo-excited electron transfer and catalysis in natural and artificial systems using XFELs.

The ultra-bright femtosecond X-ray pulses provided by X-ray Free Electron Lasers (XFELs) open capabilities for studying the structure and dynamics of a wide variety of biological and inorganic systems beyond what is possible at synchrotron sources. Although the structure and chemistry at the catalytic sites have been studied intensively in both biological and inorganic systems, a full understanding of the atomic-scale chemistry requires new approaches beyond the steady state X-ray crystallography and X-ray spectroscopy at cryogenic temperatures. Following the dynamic changes in the geometric and electronic structure at ambient conditions, while overcoming X-ray damage to the redox active catalytic center, is key for deriving reaction mechanisms. Such studies become possible by using the intense and ultra-short femtosecond X-ray pulses from an XFEL, where sample is probed before it is damaged. We have developed methodology for simultaneously collecting X-ray diffraction data and X-ray emission spectra, using an energy dispersive spectrometer, at ambient conditions, and used this approach to study the room temperature structure and intermediate states of the photosynthetic water oxidizing metallo-protein, photosystem II. Moreover, we have also used this setup to simultaneously collect the X-ray emission spectra from multiple metals to follow the ultrafast dynamics of light-induced charge transfer between multiple metal sites. A Mn-Ti containing system was studied at an XFEL to demonstrate the efficacy and potential of this method.

CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation.

CD2 is an intercellular adhesion molecule that has been implicated in T cell activation and differentiation both in humans and mice. Although the ligand for human CD2 has been defined as LFA-3, that for murine CD2 has not been identified yet. To identify the ligand for mouse CD2, we generated a chimeric molecule consisting of the extracellular domain of mouse CD2 and human immunoglobulin (Ig)G1 Fc (mCD2Rg). A hamster monoclonal antibody (mAb), HM48-1, was established by screening mAbs that could block the binding of mCD2Rg to T cell lines at the ligand site. The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein with an apparent molecular mass of 45 kD, which were shared characteristics with human LFA-3. However, its expression was predominantly restricted to hematopoietic cells, unlike human LFA-3. Protein microsequencing analysis for the NH2-terminal 18 amino acid residues of the affinity-purified HM48-1 antigen revealed that it is almost identical with mouse CD48. This identity was further confirmed by the reactivity of HM48-1 with a soluble recombinant CD48 (sCD48) protein and the molecule recognized by a rat mAb raised against sCD48. A rat anti-CD48 mAb blocked the mCD2Rg binding as well as HM48-1. Moreover, sCD48 also inhibited the mCD2Rg binding to the cellular ligand. Finally, like anti-CD2 mAb, HM48-1 inhibited the phytohemagglutinin response and, when crosslinked, augmented the anti-CD3 response of splenic T cells. These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation.

Moths are not silent, but whisper ultrasonic courtship songs.

Ultrasonic hearing is widespread among moths, but very few moth species have been reported to produce ultrasounds for sexual communication. In those that do, the signals are intense and thus well matched for long distance communication. By contrast, males of the Asian corn borer moth (Crambidae) were recently shown to whisper extremely low-intensity ultrasonic courtship songs close to females. Since low sound levels will prevent eavesdropping by predators, parasites and conspecific rivals, we predicted low intensity ultrasound communication to be widespread among moths. Here we tested 13 species of moths including members of the Noctuidae, Arctiidae, Geometridae and Crambidae. Males of nine species, 70%, produced broadband ultrasound close to females. Peak frequencies ranged from 38 to above 100 kHz. All sounds were of low intensity, 43-76 dB SPL at 1 cm [64+/-10 dB peSPL (mean +/- s.d.), N=9 species]. These quiet and/or hyper-frequency ultrasounds are audible to nearby mates, but inaudible to unintended receivers. Although largely unknown because it is so inconspicuous, acoustic communication using low intensity ultrasound appears to be widespread among hearing moths. Thus, acoustic communication may be the norm rather than the exception.

Charge transfer to ground-state ions produces free electrons.

Inner-shell ionization of an isolated atom typically leads to Auger decay. In an environment, for example, a liquid or a van der Waals bonded system, this process will be modified, and becomes part of a complex cascade of relaxation steps. Understanding these steps is important, as they determine the production of slow electrons and singly charged radicals, the most abundant products in radiation chemistry. In this communication, we present experimental evidence for a so-far unobserved, but potentially very important step in such relaxation cascades: Multiply charged ionic states after Auger decay may partially be neutralized by electron transfer, simultaneously evoking the creation of a low-energy free electron (electron transfer-mediated decay). This process is effective even after Auger decay into the dicationic ground state. In our experiment, we observe the decay of Ne2+ produced after Ne 1s photoionization in Ne-Kr mixed clusters.

The role of oval cells in rat hepatocyte transplantation.

BACKGROUND: Oval cells are liver cells capable of differentiating into either hepatocytes or biliary epithelial cells. We compared growth of hepatocytes and biliary epithelial cells between spleens transplanted with oval cell-free and oval cell-enriched rat liver cells. METHODS: Oval cell-enriched liver cells were obtained from livers of adult rats that had undergone treatment with acetylaminofluorene and partial hepatectomy, although oval cell-free liver cells were obtained from livers of untreated rats. Hepatocyte and biliary epithelial cell growth in the spleen was evaluated by counting periodic acid-Schiff-positive cells and cytokeratin 19-positive cells respectively in sections from transplanted spleens. RESULTS: Spleens transplanted with oval cell-free liver cells and spleens transplanted with oval cell-enriched liver cells contained similar numbers of hepatocytes after 2 weeks. Numbers of hepatocytes in spleens transplanted with oval cell-free liver cells decreased markedly at 4 and 8 weeks, then increasing slightly until 32 weeks. In spleens transplanted with oval cell-enriched liver cells, numbers of hepatocytes decreased only slightly at 4 weeks and then increased markedly. At 4, 8, 12, 16, 24, and 32 weeks, numbers of hepatocytes in spleens transplanted with oval cell-enriched liver cells respectively were 2.3, 3.5, 4.5, 6.7, 6.3, and 15.1 times hepatocyte numbers in spleens transplanted with oval cell-free liver cells. Numbers of biliary epithelial cells in spleens receiving oval cell-enriched liver cells showed changes similar to those in spleens transplanted with oval cell-free liver cells, increasing markedly at 4 weeks and then markedly and rapidly decreasing. CONCLUSIONS: Intrasplenic transplantation of oval cell-enriched liver cells enhanced growth of hepatocytes compared with transplantation of oval cell-free liver cells; this was not true for biliary epithelial cells.

Assessment of demented patients by dynamic SPECT of inhaled xenon-133.

We studied the potential for using dynamic single photon emission computed tomography of inhaled xenon-133 (133Xe) gas in the assessment of demented patients. An advanced ring-type single photon emission computed tomography (SPECT) "HEADTOME" with improved spatial resolution [15 mm in full width at half maximum (FWHM)] was used for tomographic measurement of regional cerebral blood flow (rCBF). All 34 patients underwent a detailed psychiatric examination and x-ray computed tomography scan, and matched research criteria for Alzheimer's disease (n = 13), senile dementia of the Alzheimer type (n = 9), or multi-infarct dementia (n = 12). In comparison with a senile control group (n = 7), mean CBF of both the whole brain and the temporo-parietal region was significantly less in the Alzheimer's disease and senile dementia Alzheimer type groups, but no significant difference was seen between the senile control group and multi-infarct dementia group. The correlation was 0.72 (p less than 0.004) between the mean CBF of the whole brain and the score of Hasegawa's Dementia Scale, and 0.94 (p less than 0.0001) between rCBF of the temporo-parietal region and the scale in Alzheimer's disease. In the senile dementia Alzheimer type group, the correlations were 0.77 (p less than 0.01) and 0.83 (p less than 0.004) respectively. No significant correlations were found in the multi-infarct dementia group. A temporo-parietal reduction in the distribution of the rCBF characteristic in the Alzheimer's disease group and a patchy whole brain reduction characteristic in the multi-infarct dementia group was detected. The ability of our improved SPECT to provide both quantitative measurement of rCBF and characteristic rCBF distribution patterns, makes it a promising tool for research or routine examination of demented patients.

Fluorophotometric quantitation of oxidative stress in the retina in vivo.

PURPOSE: To establish a new fluorophotometric method to quantitate oxidative stress in the retina in vivo with a hydrogen peroxide (H2O2)-sensitive fluorescent dye. METHODS: For in vitro fluorophotometric study, nonfluorescent 2',7'-dichlorofluorescein (DCFH) was incubated with H2O2 (10 pM to 100 nM), and the production of fluorescent 2',7'-dichlorofluorescein (DCF) was measured with fluorophotometric analysis. The inhibitory effect of catalase was also examined. For in vivo fluorophotometric study, rabbit eyes received vitrectomy and were perfused with 5 microM 2',7'-dichlorofluorescein diacetate (DCF-DA) or 2',7'-dichlorofluorescein diacetate (DCFH-DA). For oxidative stress, 300 microM H2O2 was infused after perfusion of DCFH-DA. Fluorophotometric measurements of the chorioretinal peak were performed. The eyes were enucleated for fluorescent microscopic examination to determine the localization of DCF fluorescence. RESULTS: H2O2 converted DCFH to DCF in a dose-dependent manner, which was inhibited by catalase dose dependently. In vivo fluorophotometric study showed DCF-DA and DCFH-DA caused production of 2006 +/- 274 picomole/ml (mean +/- SD, n = 5) and 8.35 +/- 1.11 picomole/ml (n = 5), respectively, in the chorioretinal peak. DCFH-DA with stimulation by H2O2 induced 30.7 +/- 13.1 (n = 4) picomole/ml DCF. Fluorescent microscopy showed DCF production in the retina was significant in the eye treated with DCF-DA and minimal in the eye treated with DCFH-DA. Moderate DCF production in the nerve fiber layer was observed in the eye treated with DCFH-DA and H2O2. CONCLUSIONS: This new fluorophotometric method with DCFH-DA may be useful in quantitatively evaluating oxidative stress in the retina in vivo.

In vivo quantitation of peroxides in the vitreous humor by fluorophotometry.

PURPOSE: To detect intravitreal peroxides in vivo by a new fluorophotometric method with a hydrogen peroxide (H2O2)-sensitive fluorescent dye. METHODS: The authors used a 2',7'-dichlorofluorescin (DCFH) assay to measure oxidative status in the rabbit vitreous. In the presence of H2O2 and lipid hydroperoxides, nonfluorescent DCFH in the vitreous is oxidized to highly fluorescent 2',7'-dichlorofluorescein (DCF; excitation, 495 nm; emission, 520 nm) that is detectable by fluorophotometry. Reactions of DCFH with various concentrations of H2O2 were investigated in vitro and in vivo. An inhibitory effect of catalase also was monitored. Vitreous fluorophotometry with DCFH was performed immediately and at 3, 7, and 28 days after constant light exposure to the retina (1800 lux, 24 hours) as an oxidative stress. RESULTS: In vitro study revealed that H2O2 oxidized DCFH to DCF in a dose-dependent manner, ranging from 0.1 to 100 mmol/1 in concentration. Catalase inhibited DCF production. Vitreous fluorophotometry demonstrated that H2O2 oxidized DCFH to DCF in vivo in a dose-dependent manner, ranging from 0.06 to 60 mmol/1 in concentration. DCF production in the vitreous significantly increased immediately (P = 0.03) and at 3 days (P = 0.01) and 7 days (P = 0.01) after light exposure, and it returned to the pretreatment level by day 28. CONCLUSIONS: The results suggest that this fluorophotometric method quantitatively can detect intravitreal peroxides in vivo. This method will be helpful to study the oxidative status in some experimental pathologic conditions.

Fluorophotometric detection of intravitreal peroxides after panretinal laser photocoagulation.

PURPOSE: To develop a highly sensitive method for in vivo quantitation of intravitreal peroxides by vitreous fluorophotometry with 2',7'-dichlorofluorescin (DCFH), a hydrogen peroxide (H2O2)-sensitive fluorescent dye, and to measure peroxides in the vitreous humor after panretinal laser photocoagulation (PRP). METHODS: In the presence of H2O2 and lipid hydroperoxides, nonfluorescent DCFH was oxidized to highly fluorescent 2',7'-dichlorofluorescein (DCF; excitation, 495 nm; emission, 520 nm), which is detectable by vitreous fluorophotometry. Reactions of DCFH, including hematin with various concentrations of H2O2, were investigated in vivo. Fluorophotometry with DCFH was performed 1, 7, 14, and 28 days and 2 months after argon laser PRP. Untreated eyes served as the controls. RESULTS: Exogenously applied H2O2 oxidized DCFH to DCF in a dose-dependent manner, ranging from 6 x 10(-8) mol/l to 6 x 10(-5) mol/l in concentration in vivo. Intravitreal DCF concentration was 83.7 +/- 6.8 nmol/l in control eyes. A significant increase of DCF was detected 1 day after PRP (330.7 +/- 123.8 nmol/l, P < 0.002). The increase peaked on day 7 (352.4 +/- 239.5 nmol/l, P < 0.002) and remained elevated at 2 months after PRP (161.8 +/- 51.4 nmol/l, P < 0.01). CONCLUSIONS: This method allowed a highly sensitive quantitation of intravitreal peroxides in vivo. The authors' findings indicated that PRP induces increased production of peroxides in rabbit vitreous for 2 months. The data suggested that persistently high levels of peroxides in the vitreous humor affect the development of vitreous liquefaction after PRP.

Quantitative analysis of lens changes after vitrectomy by fluorophotometry.

We measured the amount of autofluorescence in the lens to evaluate quantitatively lens changes after vitrectomy. Thirteen phakic patients, ranging in age from 12 to 75 years, were studied after unilateral vitrectomy, with a follow-up period of more than two years (range, 26 to 55 months). Autofluorescence in the lens was measured at the center along the ocular axis by fluorophotometry. Lens autofluorescence in the eyes that underwent vitrectomy was significantly higher than in the contralateral eyes that were not operated on (P = .0003). The increase of autofluorescence was correlated significantly with the age at time of vitrectomy (P = .0008). There was no correlation between the increase in autofluorescence and the length of postoperative follow-up or the use of air during vitrectomy. Based on these results, we believe that oxidation of lens proteins intraoperatively may be one of the causes of development of nuclear cataract after vitrectomy.

Granulomatous myositis: pathologic re-evaluation by immunohistochemical analysis of infiltrating mononuclear cells.

To characterize the non-caseating granuloma formation in granulomatous myositis, we analyzed infiltrating mononuclear cells in 7 patients including 2 sarcoid patients, using monoclonal antibodies with a modified immunoperoxidase method. All granulomas consisting of epithelioid, infiltrating mononuclear cells and multinucleated giant cells had markedly increased numbers of CD45Ro-positive cells. The infiltrating inflammatory cells were mostly T lymphocytes and macrophages. The majority of T lymphocytes behaved as T helper/inducer subtype, expressing CD4 positivity. Although the ratio of CD4- to CD8-positive cells in the granuloma in muscle biopsies was not significantly different from that in other organs seen in systemic sarcoidosis, T helper/inducer and T suppressor/cytotoxic cells showed some characteristic distributions: CD4-positive cells accumulated in the center of, and CD8-positive cells at the periphery of, the granuloma. The distribution of infiltrating cells did not differ between muscle biopsies from patients with and without systemic sarcoidosis, suggesting that both groups share the same pathogenetic mechanism in granuloma formation.

Expression of a bioactive bovine interleukin-12 using baculovirus.

Recombinant baculoviruses that express recombinant bovine interleukin-12 (rboIL-12) subunits, p35 and p40 subunits were constructed. A recombinant virus containing the p40 subunit gene expressed the p40 subunit as a 40kDa monomer and an 80kDa disulfide-linked homodimer in the infected insect cells and in the culture supernatant. The p35 subunit was expressed in a 30kDa monomer in the infected cells but not in the supernatant. Superinfection of both recombinant viruses into the cells in a spinner flask resulted in the formation of a 70kDa disulfide-bonded heterodimer detected in the supernatant by immunoblotting using anti-p40 and anti-p35 subunits antibodies. The superinfected culture supernatant showed induction of IFNgamma mRNA synthesis and IFNgamma production in bovine peripheral blood mononuclear cells. Thus, the bioactive rboIL-12 was produced in large scale using a baculovirus expression system.

Biodegradable polymeric device for sustained intravitreal release of ganciclovir in rabbits.

PURPOSE: A scleral plug made of biodegradable polymer implanted at the pars plana was evaluated to determine its ability to control the intravitreal release of ganciclovir. METHODS: Scleral plugs containing 25% ganciclovir were prepared with poly(lactic-glycolic acid) (molecular weight, 121 kDa). The release of ganciclovir was evaluated in vitro by spectrophotometry. In vivo intravitreal ganciclovir concentrations were measured by high performance liquid chromatography following plug implantation in pigmented rabbits. The biocompatibility of the device was determined by indirect ophthalmoscopy, electroretinography, and light and electron microscopy. RESULTS: The in vitro study showed that the plug released ganciclovir throughout a 10-week period. The in vivo study demonstrated that the plugs maintained the drug concentration in the vitreous in a therapeutic range adequate to treat cytomegalovirus (CMV) retinitis for 12 weeks. No significant retinal toxicity was observed. CONCLUSIONS: This study demonstrated that this drug delivery system can potentially be useful to treat CMV retinitis.

Implantable biodegradable polymeric device in the treatment of experimental proliferative vitreoretinopathy.

We investigated the use of a scleral plug of biodegradable polymer implanted at the pars plana to create a controlled drug-delivery system in the vitreous. We evaluated the efficacy of a plug containing doxorubicin hydrochloride to treat experimental proliferative vitreoretinopathy (PVR) in pigmented rabbits. An implantable device on the sclera, which imitates a scleral plug, containing 1% doxorubicin, was prepared with poly(lactic acid) (molecular weight, 20,000). The release of doxorubicin in phosphate-buffered saline was evaluated by spectro-photometry. After pars plana vitrectomy and plug implantation, concentrations of doxorubicin in the vitreous humor of the rabbits were measured by high performance liquid chromatography. The release profiles were evaluated during 5 weeks in vitro and 4 weeks in vivo. Cultured homologous fibroblasts were injected into the vitreous space to induce experimental PVR after gas compression of the vitreous. The scleral plugs were implanted at the pars plana in treatment animals (n = 11). Control rabbits (n = 11) were followed up without implantation after PVR induction. All eyes of the control group developed tractional retinal detachment at day 28, while the incidence of retinal detachment was decreased to 64% in the treated eyes. (P = 0.002). The implantation of the scleral plug effectively inhibited intravitreous proliferation of fibroblasts. This study demonstrated that the scleral plug of biodegradable polymers may have potential as a treatment modality for PVR.

Inhibition by an angiogenesis inhibitor, TNP-470, of the growth of a human hepatoblastoma heterotransplanted into nude mice.

BACKGROUND/PURPOSE: The effect of TNP-470, an angiogenesis inhibitor, on the growth of a hepatoblastoma transplanted into nude mice was examined. METHODS: A hepatoblastoma obtained from a 3-year-old girl was serially transplanted into nude mice subcutaneously, and the transplant tumors of the seventh and eighth generations were used for experiments. Expression of various markers in the tumors was examined immunohistochemically. TNP-470 was injected subcutaneously every other day into tumor-bearing mice from 3 weeks after tumor transplantation. The proliferation of tumor cells and endothelial cells was estimated by means of the bromodeoxyuridine labeling index. RESULTS: The original hepatoblastoma showed the histology of the epithelial type, consisting of both the fetal and embryonal subtypes and was positively stained with anti-alpha-fetoprotein (AFP), anti-cytokeratin-19 and polyclonal anticarcinoembryonic antigen antibodies, and an antihuman hepatocyte antibody (hepatocyte paraffin 1). The transplant tumors consisted of solid nests of tumor cells with numerous vascular lakes of various sizes, and showed positive staining with all antibodies that reacted positively with the original hepatoblastoma. Injections of TNP-470 at the doses of 15 mg and 30 mg/kg body weight suppressed the tumor growth and the increase in the serum level of AFP dose dependently. Injections of TNP-470 also suppressed the proliferation of tumor cells and endothelial cells in the tumors. CONCLUSIONS: Hepatoblastomas maintained in nude mice retained the immunohistochemical characteristics of the original hepatoblastoma, and TNP-470 suppressed the growth of hepatoblastomas transplanted into nude mice. TNP-470 may be worth investigating further as to its usefulness as a therapy for hepatoblastomas.

Three-dimensional vectorcardiography (3-D VCG) by computer graphics in old myocardial infarction.

By using computer graphics we rotated the vector loop and three coordinate axes to find the viewpoint where the infarctional changes are maximally exposed and demonstrated the advantage of the "3-D VCG" over the conventional VCG by defining the quantitative "MI index." The orthogonal electrocardiogram recorded by the Frank lead system was digitally measured and processed by a microcomputer. The loops and axes were rotated about the X axis (X-rot) and the Y axis (Y-rot). The spatial vector loop and orthogonal coordinates can be presented as viewed from any spheric direction. Eight quadrants were illustrated with four colors and red circles. The subjects consisted of 30 patients with old anterior myocardial infarction (MI) and 15 patients with old inferior MI. We measured the area of "Bite" in anterior MI and superior displacement in inferior MI. The MI index was defined and averaged in 361 directions. In anterior MI, the maximum mean index was obtained when X-rot is +90 degrees and Y-rot -40 degrees, viewed from upward and leftward, whereas in inferior MI it was obtained when X-rot is -50 degrees and Y-rot -80 degrees, viewed from downward and leftward. These values were significantly higher than those in conventional VCG projections, substantiating superior diagnostic sensitivity of 3-D VCG.

Long-term prognosis of extracapsular cataract extraction and intraocular lens implantation in diabetic patients.

Although cataract extraction with intraocular lens implantation (IOL) is being used for increasing numbers of patients, there is still insufficient information regarding the long-term outcome for these patients. In this retrospective study of 140 eyes of 102 patients, 97 eyes (69%) achieved a best visual acuity of 20/40 or better. After a minimum 6-month postoperative period, 26 eyes (19%) had developed retinopathy: eight eyes progressed from nonproliferative to proliferative retinopathy. Glycosylated hemoglobin levels and fasting blood glucose were significantly higher at time of surgery in the eight that progressed than in those who did not (P = 0.002, P = 0.034). There were 65 unilateral IOL implantations; in 10 (15%) of these eyes, retinopathy progressed. Retinopathy also progressed in 70% of the fellow eyes of these patients. In patients whose retinopathy did not progress, 95% of the fellow eyes also showed no progression. Also, patients with progression in the pseudophakic eye frequently had progression in the fellow unoperated eye. Postoperative progression was symmetrical (P = 0.0001). Our analysis suggests that progression of diabetic retinopathy following IOL implantation can be correlated to diabetic control at the time of surgery.

[Free amino acids and activities of folate-derivative converting enzymes in nervous system of rats administered with beta, beta'-iminodipropionitrile].

Swelling of proximal axon is a morphological similarity between patients with amyotrophic lateral sclerosis (ALS) and beta, beta'-iminodipropionitrile (IDPN)-injected animals. In order to investigate whether these two states have something in common biochemically with each other, we measured free amino acids (FAAs) and activities of folate-derivative converting enzymes which participate in the metabolic turnover of the folate cycle. Thirty male Wistar rats weighing about 125 g were administered intraperitoneally with 2 g/kg of IDPN. These rats and 10 control rats injected with physiological saline were sacrificed 1, 3 and 6 weeks after injection. Subsequently organs were immediately removed and stored at -80 degrees C until analyzed. FAAs were quantitated by a JLC-6AH amino acid analyzer, and activities of the enzymes were measured by established methods. Changes in FAAs were detected not only in the central and peripheral nervous systems, but also in the other tissues examined, suggesting diverse action of IDPN. Among the various changes, elevation of taurine content in the cerebrum and spinal cord seems to be important, because the same alteration has been reported in the central nervous system (CNS) of ALS patients. In relation to the increase in taurine, metabolic slowing-down of the folate cycle which has been reported in ALS was suggested from reduced activity of N5,N10-methylenetetrahydrofolate reductase (MTR), one of the three enzymes of this metabolic cycle.(ABSTRACT TRUNCATED AT 250 WORDS)