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Biomedical subjects

Y Mizutani

Publications and source records attributed to Y Mizutani.

At least 19 recordsLinked to original sources

Do motorcyclists have erectile dysfunction? A preliminary study.

The aim of the present study was to evaluate the relationship between motorcycling and erectile dysfunction (ED). We investigated the relationship between motorcycling and erectile function using the 5-items version of the International Index of Erectile Function (IIEF5) in 234 motorcyclists (response rate 75%) and 752 healthy controls (response rate 66%). In all, 161 (69%) of 234 motorcyclists were diagnosed as ED based on IIEF5. The prevalence of ED in the motorcycle group increased by age as: 58, 63, 76 and 93%, for motorcyclists in 20-29, 30-39, 40-49 and 50-59 years, respectively. There was a significant difference in the prevalence of ED between the motorcycle group and the control group in all age groups. On stepwise logistic regression analysis, motorcycling was the strongest risk factor for ED. Although the severity of ED in motorcyclists was not so severe, motorcycling may be one of risk factors for ED.

Adult↗

Restless legs syndrome in hemodialysis patients: health-related quality of life and laboratory data analysis.

AIMS: To compare clinical data, sleep quality and health-related quality of life (HRQOL) with and without RLS in HD patients. MATERIALS AND METHODS: The international RLS study group diagnosis questionnaire was completed by 228 HD patients. The Pittsburg Sleep Quality Index (PSQI) for the evaluation of sleep quality and the Kidney Disease Quality of Life (KDQOL-SF) for the analysis of HRQOL were also used. RESULTS: 53 (23%) patients were diagnosed as RLS. Age and age at the initiation of HD were significantly younger in the RLS group. Serum calcium concentration (Ca) was significantly higher in the RLS group. Sleep quality evaluated by PSQI was significantly lower in the RLS group. In SF-36 domains of KDQOL-SF, bodily pain, general health perceptions, vitality, role functioning emotional, mental health and mental component score were significantly lower in the RLS group. In kidney targeted scales of KDQOL-SF, symptoms/problems, burden of kidney disease, cognitive function, quality of social interaction, sleep and patient satisfaction were significantly lower in the RLS group. CONCLUSION: High Ca was possibly connected to the pathophysiology of RLS which impaired sleep quality as well as HRQOL including mental health and many kidney disease related scales.

Adult↗

Carbonate-containing hydroxyapatite derived from calcium tripolyphosphate gel with urea.

Carbonate containing hydroxyapatite (CO3HAp) is one of the candidate materials as a bioresorbable bone substitute. In the present work, CO3HAp was efficiently prepared by a hydrothermal treatment of calcium tripolyphosphate gel with urea at 140 degrees C for 24 h. Chemical potential plots of the CO3HAp for estimation of its dissolution behavior suggested that the CO3HAp is more soluble than hydroxyapatite (HAp) and is as soluble as octacalcium phosphate (OCP) and/or beta -tricalcium phosphate (TCP). This material is expected to be applied to bioresorbable materials such as bone fillers.

Absorbable Implants↗

Immunohistochemical and ultrastructural findings related to the blood--brain barrier in the blood vessels of the cerebral white matter in aged dogs.

Immunohistochemical and ultrastructural analysis of canine brain tissue was performed to determine whether cerebral capillaries, which form the blood--brain barrier (BBB), display age-related morphological changes in the white matter (WM). A slight decrease in laminin immunolabelling was detected in the basement membranes (BMs) of capillaries in the WM of old dogs, as compared with that in the brains of young dogs. The Prussian blue DAB post-DAB enhancement method detected iron present in macrophages and astrocytes in the WM. Copper/zinc superoxide dismutase, MT-I and -II and MT-III immunoreactivity was detected mainly in reactive astrocytes in the WM of aged dogs. Ultrastructurally, collagen-like fibrils were detected to a variable degree in the spaces between the BMs of capillary endothelial cells and astrocytes in the WM of some aged dogs. These results suggest that age-related morphological changes in capillaries of the WM are associated with BBB dysfunction, leading to the exudation of serum constituents, including harmful substances (e.g., iron), thereby causing tissue damage by oxidative injury. These factors may play a role in the pathogenesis of severe degenerative changes in the WM of aged dogs.

Aging↗

Can we develop biomarkers that predict response of cancer patients to immunotherapy?

PRIMARY OBJECTIVE: The primary objective is to delineate the potential utility of cancer biomarkers that correlate and predict response to immunotherapy in cancer patients who are refractory to conventional therapeutics. Unlike significant development of biomarkers that predict response to chemotherapy, very few biomarkers have been developed to predict the response to immunotherapy. MAIN OUTCOMES AND RESULTS: This article describes briefly the importance of characterizing and validating biomarkers for immunotherapy. A few examples have been provided, such as the transcription factor NF-kappaB, the transcription repressor Yin-Yang 1 (YY1), the pro-apoptotic gene product (Smac/DIABLO) and the circulating Fas and Fas ligand. These biomarkers have been determined to be of prognostic significance in different cancers. CONCLUSIONS: Immunotherapy is considered as an alternative therapy in the treatment of cancer patients who are refractory to chemotherapy/radiation/hormonal therapies. Cross-resistance to apoptosis develops between cancer cells that are resistant to conventional therapeutics and immunotherapy. Therefore, it is important to develop biomarkers that will determine patient response to immunotherapy.

Animals↗

Severe involvement of cerebral neopallidum in a dog with hepatic encephalopathy.

This report describes a unique distribution of cerebral cortical necrotic lesion, which was diagnosed as hepatic encephalopathy in a 2-year-old Maltese dog. The dog showed splenocaval shunt and small liver with marked hepatocellular fatty degeneration. Histopathologic examination revealed that diffuse laminar cortical necrosis composed of neuronal necrosis, marked infiltration of gitter macrophages, and astrogliosis were found bilaterally in the dorsolateral area of the cerebrum. No necrotic lesions were observed in the cerebral paleopallium and archipallium, the central gray matter, cerebellum, and brain stem. Astrocytes with large and pale nuclei (Alzheimer type II astrocytes) were apparent throughout the brain. Immunohistochemically, a decrease of immunostains for glutamine synthetase and glutamate transporter antibodies was seen in Alzheimer type II astrocytes and neuropil. This is, to our knowledge, the first report of extensive involvement of cerebral neopallidum in canine hepatic encephalopathy.

Amino Acid Transport System X-AG↗

Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus.

We retrospectively investigated the efficacy and feasibility of concurrent chemoradiotherapy for patients with severe dysphagia caused by oesophageal squamous cell carcinoma. Concurrent chemoradiotherapy was performed in 57 patients with T3 or T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU) 400 mg m(-2) 24 h(-1) on days 1-5 and 8-12, combined with 2-h infusion of cisplatin (CDDP) 40 mg m(-2) on days 1 and 8. Radiation treatment at a dose of 30 Gy in 15 fractions of the mediastinum was administered concomitantly with chemotherapy. A course schedule with 3-week treatment and a 1 to 2-week break was applied twice, with a total radiation dose of 60 Gy, followed by two or more courses of 5-FU and CDDP. In all, 24 patients (42%) achieved a complete response, and the 3-year survival rate was 19%. Major toxicities were leukocytopenia and oesophagitis, and there were two (4%) treatment-related deaths. In contrast, 22 patients with T3 disease survived longer than 35 patients with T4 disease (P=0.001); however, the survival rate in 15 patients with M1 LYM disease did not differ significantly from that in 42 patients without M1 LYM disease (P=0.3545). Our results indicate that definitive chemoradiotherapy is potentially curative for locally advanced oesophageal carcinoma with malignant stricture. The efficacy and survival of patients treated with this regimen are related to the T factor.

Adult↗

Significance of dihydropyrimidine dehydrogenase activity in renal cell carcinoma.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the pathway of uracil and thymine catabolism. DPD is also the principal enzyme involved in the degradation of 5-fluorouracil (5-FU), an anticancer chemotherapeutic agent that is used clinically to treat renal cell carcinoma (RCC). Little is known about the significance of DPD activity in human cancers. We investigated the activity of DPD in 68 RCC and the relationship between DPD activity and the sensitivity to 5-FU. The levels of DPD activity in RCC and normal kidney samples were determined by the 5-FU degradation assay. The sensitivity to 5-FU was assessed by the microculture tetrazolium dye assay. The activity of DPD was approximately 2-fold higher in normal kidney compared with RCC. DPD activity in Stage I/II RCC was approximately 2-fold higher than that in Stage III/IV RCC. The levels of DPD activity in Grade 1 and Grade 2 RCC were 3 and 2-fold higher, respectively, than that in the Grade 3 cancers. There was an inverse correlation between DPD activity in RCC cells and their sensitivity to 5-FU. Furthermore, 5-chloro-2,4-dihydroxypyridine (CDHP), a potent DPD inhibitor, enhanced the sensitivity to 5-FU. The current study is the first to demonstrate that the level of DPD activity was inversel correlated with both the progression of the disease and increased grade of RCC, and that DPD activity was inversely associated with the sensitivity of RCC to 5-FU, which was enhanced by a DPD inhibitor. These results suggest that a low DPD activity may be associated with the malignant potential of RCC. In addition, it may be possible to overcome 5-FU resistance by using DPD inhibitors in the treatment protocols of 5-FU-based chemotherapy for RCC.

Adult↗

Nonviral genetic transfer of Fas ligand induced significant growth suppression and apoptotic tumor cell death in prostate cancer in vivo.

To accomplish efficient nonviral gene therapy against prostate cancer (PC), Epstein-Barr virus (EBV)-based plasmid vectors containing EBNA1 gene and oriP were employed and combined with a cationic polymer or cationic lipid. When EBV-plasmid/poly-amidoamine dendrimer complex was injected into PC-3-derived tumors established in severe combined immunodeficiency mice, a considerable expression of marker gene was obtained in the tumors, and the expression level was more than eight-fold higher than that achieved by conventional plasmid vector/dendrimer. Since most PC cells express the apoptotic signal molecule Fas (Apo-1/CD95) on their surface, Fas ligand (FasL) gene was transferred into PC cells to kill the tumor cells. In vitro transfection with pGEG.FasL (an EBV-plasmid with the FasL gene) significantly reduced the viability of PC cells, which subsequently underwent apoptosis. Intratumoral injections of pGEG.FasL into PC induced significant growth suppression of the xenograft tumors, in which typical characteristics of apoptosis were demonstrated by TUNEL staining and electron microscopic observations. When pGEG.FasL transfer was accompanied by systemic administrations of cisplatin, the tumors were inhibited even more remarkably, leading to prolonged survival of the animals. FasL gene transfection by means of EBV-based plasmid/cationic macromolecule complexes may provide a practical therapeutic strategy against PC.

Antineoplastic Agents↗

Resveratrol and cancer: chemoprevention, apoptosis, and chemo-immunosensitizing activities.

The polyphenolic compound Resveratrol is a naturally occurring phytochemical and can be found in many plant species, including grapes, peanuts and various herbs. Several studies have established that Resveratrol can exert anti-oxidant and anti-inflammatory activities. It also has activity in the regulation of multiple cellular events associated with carcinogenesis. This review describes the general properties of Resveratrol including its relationship to estrogen, its effect on lipid metabolism, its cardiovascular effects, and its role on gene expression. Resveratrol has also been examined in several model systems for its potential effect against cancer. Its anti-cancer effects include its role as a chemopreventive agent, its ability to inhibit cell proliferation, its direct effect in cytotoxicity by induction of apoptosis and on its potential therapeutic effect in pre-clinical studies. In addition, Resveratrol has been shown to exert sensitization effects on cancer cells that will result in a synergistic cytotoxic activity when Resveratrol is used in combination with cytotoxic drugs in drug-resistant tumor cells. Clearly, the studies with Resveratrol provide support for the use of Resveratrol in human cancer chemoprevention and combination with chemotherapeutic drugs or cytotoxic factors in the treatment of drug refractory tumor cells.

Animals↗

Potentiation of the sensitivity of renal cell carcinoma cells to TRAIL-mediated apoptosis by subtoxic concentrations of 5-fluorouracil.

Cytotoxic chemotherapy has shown little antitumour activity against renal cell carcinoma (RCC). Although immunotherapy is relatively effective against RCC, the response rate is approximately 20%. Therefore, there is an urgent need to increase this response rate. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo-2L) is one member of the tumour necrosis factor ligand family that selectively induces apoptosis of cancer cells. Since several cytotoxic anticancer drugs including 5-fluorouracil (5-FU) also mediate apoptosis, we reasoned that combined treatment of cancer cells with TRAIL and drugs might result in synergy and overcome the resistance of the cancer cell. This study has examined whether TRAIL can synergise with 5-FU in both cytotoxic and apoptotic assays against drug-resistant RCC cells. Cytotoxicity was determined by an 1-day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis. Treatment of Caki-1 cells with TRAIL in combination with 5-FU resulted in a synergistic cytotoxic effect. Synergy was also achieved in freshly derived RCC cells from 3 patients. The enhanced cytotoxicity was obtained irrespective of the sequence of the treatment, but the highest cytotoxicity was observed when Caki-1 cells were treated with TRAIL and 5-FU simultaneously. The synergy achieved in cytotoxicity with TRAIL and 5-FU was shown to be due to apoptosis. The mechanisms responsible for the synergistic cytotoxicity and apoptosis were examined. Treatment of Caki-1 cells with 5-FU enhanced the expression of p53 and bax, but had no effect on the expression of bcl-2. Incubation of Caki-1 cells with TRAIL enhanced the intracellular accumulation of 5-FU and 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP). Treatment of Caki-1 cells with TRAIL downregulated the expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) modestly, and upregulated the expression of orotate phosphoribosyltransferase (OPRT). However, the expression level of thymidine phosphorylase (TP) was not affected by TRAIL. This study demonstrates that combined treatment of RCC cells with TRAIL and 5-FU overcomes their resistance. The sensitisation obtained with freshly isolated RCC cells required low subtoxic concentrations of 5-FU. These findings support the potential application in vivo of a combination of TRAIL and 5-FU in the treatment of TRAIL/5-FU-resistant RCC.

Antimetabolites, Antineoplastic↗

Significant decrease of the International Index of Erectile Function in male renal failure patients treated with hemodialysis.

In order to evaluate the erectile function in male renal failure patients treated with hemodialysis (HD), we investigated the International Index of Erectile Function (IIEF) in patients and healthy controls. The subjects were 174 male patients treated with HD, of whom 43 had diabetes mellitus (DM) and the remaining 131 patients did not have DM. The controls were 1133 healthy males. We evaluated the prevalence of erectile dysfunction (ED) using the erectile function (EF) score, which is one of the five domains of the IIEF, in each age group (upto 39 y old, 40-49 y old, 50-59 y old, 60-69 y old). The severity of ED was classified into five categories using EF in each age group. The univariate logistic regression analysis and multiple variate analysis of IIEF in HD patients were performed. The prevalence of ED in HD patients was significantly higher than that in the controls in each age group. The severity of ED in HD patients was also significantly higher than that in the controls in each age group. In the logistic regression analysis and multiple variate analysis of IIEF in HD patients, DM and age were significant risk factors on sexual dysfunction. ED was more prevalent in male renal failure patients treated with HD than in the controls. In the patient group, ED was more prevalent in older DM patients.

Adult↗

Erythrocyte aldose reductase correlates with erectile dysfunction in diabetic patients.

Erectile dysfunction (ED) is a common complication of diabetes mellitus. Erythrocyte aldose reductase (AR) has been implicated in a variety of diabetic complications. The subjects were 62 diabetic patients, of whom 25 were treated with hemodialysis (chronic renal failure CRF group) and the remaining 37 did not have chronic renal failure (DM group). The controls were 20 healthy volunteers age-matched to the patients. The level of AR was measured by the quantitative determination kit for AR in all patients and controls. In this study, ED was diagnosed by 5-item version of the International Index of Erectile Function (IIEF-5). The average level of AR in the CRF group was significantly higher than that in the DM group and controls (P<0.001). The average level of AR in the DM group without ED was significantly lower than that in the DM group with ED and controls (P<0.005). These results suggest that the level of AR may be a useful modality for prediction of ED in diabetic patients.

Aged↗

Cisplatin-induced in vivo differentiation of human embryonal carcinoma.

OBJECTIVE: To investigate the differentiation of embryonal carcinoma (EC) by cisplatin, and the underlying mechanism, as untreated metastases of nonseminomatous germ cell tumours rarely consist of fully differentiated mature somatic tissues, but such mature metastases are more common after various treatments, including chemotherapy. MATERIALS AND METHODS: The TTSC-3 human testicular EC line heterotransplanted into nude mice was used as a target. After treating tumour-bearing mice with intraperitoneal injections of varying doses of cisplatin, the histopathology of the tumours was assessed and various gene expressions in the tumours determined by cDNA-array technology. RESULTS: When cisplatin at 1 mg/kg/week was injected intraperitoneally into TTSC-3-bearing mice, there was no effect on tumour growth. However, injecting cisplatin at 5 mg/kg/week induced a marked regression of the tumour. In contrast, cisplatin at 3 mg/kg/week had a modest inhibitory effect on tumour growth and induced tumour dormancy. Histological examination showed that 5 weeks after injecting cisplatin (3 mg/kg/week), primitive mesenchymal-like cells increased, and 10 weeks afterward cartilage and well-developed glands (teratoma) were apparent; at > 15 weeks afterward there were no EC cells visible. cDNA probes from reverse-transcribed mRNAs of TTSC-3 treated with cisplatin or saline for 10 weeks were compared to identify genes differentially expressed in cisplatin-treated TTSC-3. Of 1176 different human cDNA transcripts in cisplatin-treated TTSC-3, three genes (tumour necrosis factor receptor 1, caspase 8 and Apaf1), which are associated with apoptosis, were expressed markedly more than after saline injection. CONCLUSIONS: The intermediate dose of cisplatin inhibited tumour growth of EC by inducing differentiation and enhancing apoptosis-related gene expression. These findings suggest that cisplatin may play a significant role in the differentiation of EC in vivo.

Animals↗

Prognostic significance of thymidylate synthase activity in bladder carcinoma.

BACKGROUND: 5-fluorouracil (5-FU) is an anticancer agent clinically used against various cancers including bladder carcinoma. 5-FU inhibits thymidylate synthase (TS) and blocks DNA synthesis. TS is the key enzyme in the catalysis of the methylation from deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate. Little is known about the significance of TS in bladder carcinoma. The authors investigated the activity of TS in 82 bladder cancers and prognostic significance of the levels of TS and/or activities of dihydropyrimidine dehydrogenase (DPD), an important enzyme in the degradation of 5-FU. METHODS: The levels of TS and DPD activities in nonfixed, fresh, frozen, bladder carcinoma and normal bladder specimens were determined biochemically by the FdUMP binding assay and the 5-FU degradation assay, respectively. RESULTS: The activity of TS was 10-fold higher in bladder carcinoma compared with normal bladder. TS activity in muscle-invasive bladder carcinoma was threefold higher than that in Ta and T1 cancer. In addition, the activity of TS in T1 bladder carcinoma was threefold higher than that in Ta cancer. The level of TS activity in Grade 3 bladder carcinoma was 4.5-fold and 3.5-fold higher than that in Grade 1 and Grade 2 cancers, respectively. Patients with Ta and T1 bladder carcinoma with low TS activity had a longer postoperative tumor-free period than those with high activity in the 2-year follow-up. Patients with Ta and T1 bladder carcinoma with high or low TS activity were divided into four subgroups: high or low DPD activity subgroups. Patients with low TS activity and high DPD activity had the longest postoperative disease-free period among the 4 subgroups during the 2-year follow-up. CONCLUSIONS: To the authors' knowledge, the current study is the first study that demonstrated that the level of TS activity correlates with both the progression of the stage and the increase of the grade of bladder carcinoma and that elevated TS activity predicts early recurrence in Ta and T1 bladder carcinoma. These results suggested that elevated TS activity might have been associated with a higher chance of progression and recurrence of bladder carcinoma in the patients who participated in this study.

Adult↗

Significance of serum soluble Fas ligand in patients with bladder carcinoma.

BACKGROUND: The interaction of Fas and Fas ligand (FasL) plays an important role in cytotoxic T-lymphocyte-mediated and natural killer cell-mediated apoptosis against tumor cells. Circulating soluble FasL (sFasL) has been suggested to provide protection from Fas-mediated apoptosis. The current study examined this possibility in patients with bladder carcinoma. METHODS: The levels of sFasL in the serum of 163 patients with bladder carcinoma were determined using an enzyme-linked immunoadsorbent assay. Antiautologous tumor cytotoxic activity was assessed by the 12-hour chromium isotope ((51)Cr) release assay. RESULTS: The mean serum level of sFasL in patients with bladder carcinoma was 2.5-fold higher than that in healthy donors. The level of serum sFasL in patients with muscle-invasive bladder carcinoma was 2.5-fold higher than that in patients with superficial bladder carcinoma. In addition, serum sFasL levels in patients with T1 and Tis bladder carcinoma was 2-fold and 2.7-fold higher, respectively, than levels in patients with Ta bladder carcinoma. The serum level of patients with sFasL in Grade 3 bladder carcinoma were 2.4-fold and 1.7-fold higher than that in patients with Grade 1 and Grade 2 bladder carcinoma, respectively. Patients with Ta bladder carcinoma with a low level of serum sFasL (less than the median value) had a longer postoperative tumor-free interval than patients with a high sFasL level (greater than the median value) in the 5-year follow-up. There was an apparent inverse correlation between the level of serum sFasL and antiautologous tumor cytotoxic activity. CONCLUSIONS: The results of the current study demonstrated that the level of serum sFasL is correlated with both disease progression and increase in the tumor grade, and that an elevated serum sFasL level predicted early recurrence in patients with Ta bladder carcinoma. These findings suggest that elevated serum sFasL levels might be associated with a greater risk of disease progression and recurrence in patients with bladder carcinoma.

Adult↗

The expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in perinatal mouse.

Recently, pregnane X receptor (PXR) has been described to mediate the genomic effects of several steroid hormones, such as progesterone (P), glucocorticoid (Dex), pregnenolone (Preg), and xenobiotics through the cytochrome P-450 3A gene family (CYP3A), which are monooxygenases, responsible for the oxidative metabolism of some endogenous substrates and xenobiotics. In the present study, we used a transient transfection reporter gene expression assay of COS-7 cells to demonstrate that P, Dex and Preg significantly stimulate PXR-mediated transcription at relatively high concentration comparable with that of progesterone near term pregnancy. In yeast two-hybrid protein interaction assay, PXR interacted with nuclear receptor coactivator proteins, SRC1, RIP140, and SUG1 in a ligand-dependent manner. The expression of PXR mRNA was observed in the liver, intestine, uterus, ovary and placenta. The expressions of PXR mRNA in the liver and ovary increased towards term about fifty-fold compared with that of non-pregnancy and decreased postpartum. Its expression in the placenta was not drastically changed towards term. CYP3A, a target gene of PXR, was also expressed in the liver, ovary, and placenta. The expressions of CYP3A mRNA as well as PXR in the liver and ovary increased about 20-fold during prenatal period. These data suggest that PXR may play certain roles in perinatal period, possibly in the protection of the feto-maternal system from the toxic effect of endogenous steroids and foreign substrates.

Animals↗

Ultrafast dynamics of myoglobin probed by time-resolved resonance Raman spectroscopy.

Recent experimental work carried out in this laboratory on the ultrafast dynamics of myoglobin (Mb) is summarized with a stress on structural and vibrational energy relaxation. Studies on the structural relaxation of Mb following CO photolysis revealed that the structural change of heme itself, caused by CO photodissociation, is completed within the instrumental response time of the time-resolved resonance Raman apparatus used (approximately 2 ps). In contrast, changes in the intensity and frequency of the iron-histidine (Fe-His) stretching mode upon dissociation of the trans ligand were found to occur in the picosecond regime. The Fe-His band is absent for the CO-bound form, and its appearance upon photodissociation was not instantaneous, in contrast with that observed in the vibrational modes of heme, suggesting appreciable time evolution of the Fe displacement from the heme plane. The band position of the Fe-His stretching mode changed with a time constant of about 100 ps, indicating that tertiary structural changes of the protein occurred in a 100-ps range. Temporal changes of the anti-Stokes Raman intensity of the v4 and v7 bands demonstrated immediate generation of vibrationally excited heme upon the photodissociation and decay of the excited populations, whose time constants were 1.1 +/- 0.6 and 1.9 +/- 0.6 ps, respectively. In addition, the development of the time-resolved resonance Raman apparatus and prospects in this research field are described.

Carbon Monoxide↗