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Biomedical subjects

Y Hirooka

Publications and source records attributed to Y Hirooka.

At least 19 recordsLinked to original sources
PubMed2003

Heparanase gene expression and its correlation with spontaneous apoptosis in hepatocytes of cirrhotic liver and carcinoma.

Heparanase (hep) degrades heparan sulphate proteoglycans (HSPGs), which are the main components of the extracellular matrix. This process has been considered as the first step of tumour invasion or metastasis. However, HSPGs play an important role in signal transduction. Thus, the degradation of HSPGs by hep may suppress tumour cell growth. In the present study, we investigated the clinicopathological importance of enhanced hep mRNA expression in 48 hepatocellular carcinomas (HCCs) and in 48 non-cancerous liver samples obtained from the same patients by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Spontaneous apoptosis in the hepatocytes was evaluated by immunohistochemistry. The relative hep mRNA expression levels were described as hep/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios. The hep mRNA levels of HCCs were significantly lower than those of non-cancerous livers (P<0.001). Hep mRNA levels decreased with increasing liver fibrosis. A significant positive correlation between hep gene expression and spontaneous apoptosis was detected. Hep expression in the tumours did not correlate with tumour differentiation or with tumour stage. However, low hep gene expression was associated with a poor disease-free survival of the patients. Thus, hep gene expression may play an important role in programmed cell death and this gene expression may be lost during the malignant transformation of hepatocytes.

Adult↗
PubMed2003

Urinary excretion of aquaporin-2 and inappropriate secretion of vasopressin in hyponatremic patients after cerebral infarction.

Aquaporin-2, a water-channel protein, is known to increase water permeability due to vasopressin binding to V2 receptors at the renal collecting duct and is excreted into the urine. It is still unclear whether a hyponatremic state is caused by vasopressin-dependent aquaporin-2 in patients clinically diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone. To determine this, we measured urinary aquaporin-2 and vasopressin by radioimmunoassay in normonatremic or hyponatremic patients after cerebral infarction and in healthy controls. In the normonatremia group, urinary aquaporin-2 and plasma AVP levels were higher than in controls. In the hyponatremia group, plasma AVP was relatively high despite low plasma osmolality in each patient. However, urinary aquaporin-2 in hyponatremia was significantly increased when compared with the other two groups. In conclusion, AQP-2 increment does not directly reflect non-osmotic AVP secretion in a hyponatremic state. This result indicates that the urinary excretion of AQP-2 is not only AVP-dependent in hyponatremic states.

Aged↗
PubMed2003

Contrast-enhanced transabdominal ultrasonography in the diagnosis of pancreatic mass lesions.

PURPOSE: In this study, we evaluated the diagnostic usefulness of contrast-enhanced transabdominal ultrasonography (CE-US) in pancreatic mass lesions that could be detected by US. MATERIAL AND METHODS: CE-US was performed in 37 patients with various pancreatic mass lesions to evaluate the characteristic vascular findings. RESULTS: Pancreatic tubular adenocarcinoma showed negative enhancement pattern in 16 cases and a slight spotty enhancement pattern in 5 cases. Poorly differentiated adenocarcinoma showed slight homogeneous enhancement pattern in 1 case and acinar cell carcinoma was expressed as a heterogeneous enhancement pattern in 3 cases on CE-US. Endocrine cell tumor had a strong homogeneous enhancement pattern in 3 cases, a strong central enhancement in 1 case and a strong peripheral enhancement in 2 cases. Pseudotumorous pancreatitis showed an iso-enhancement pattern in 6 cases. CONCLUSION: CE-US is useful in evaluating the vascularity of the lesions in various pancreatic mass lesions in real-time images, and may be useful for the differential diagnosis of pancreatic mass lesions.

Abdomen↗
PubMed2002

Serum lipid profiles in Japanese women and men during consumption of walnuts.

OBJECTIVE: To determine the serum cholesterol, apolipoproteins and LDL oxidizability in young Japanese women and men during walnut consumption and to evaluate its active principle. DESIGN: Experimental study with a randomized design. SUBJECTS: Twenty healthy women and 20 healthy men. INTERVENTIONS: Subjects were randomly assigned to consume each of two mixed natural diets for 4 weeks in a cross-over design. Reference and walnut diets were designed and the walnut diet had 12.5% of the energy derived from walnuts (44-58 g/day). RESULTS: The total cholesterol and serum apolipoprotein B concentrations, and the ratio of LDL cholesterol to HDL cholesterol was significantly lowered in women and men when fed on the walnut diet, than when on the reference diet (P<or=0.05). The LDL cholesterol concentration was significantly lowered in women on the walnut diet (0.22 mmol/l, P=0.0008), whereas this decrease was not significant in men (0.18 mmol/l, P=0.078). The most prominent change in the fatty acid composition of the cholesteryl esters from serum after the walnut diet was an elevation of alpha-linolenic acid in women (76%, P<0.001) and men (107%, P<0.001). This elevation was negatively correlated to the change in LDL cholesterol in women (r=0.496, P=0.019) and men (r=0.326, P=0.138). The LDL oxidizability in women was not influenced by the diets (P=0.19). CONCLUSIONS: alpha-Linolenic acid in the walnut diet appears to be responsible for the lowering of LDL cholesterol in women. SPONSORSHIP: Kyushu University (Fukuoka, Japan) and the California Walnut Commission (California, USA).

Adult↗
PubMed2002

Central mechanisms underlying short- and long-term regulation of the cardiovascular system.

1. Sympathetic vasomotor nerves play a major role in determining the level of arterial blood pressure and the distribution of cardiac output. The present review will discuss briefly the central regulatory mechanisms that control the sympathetic outflow to the cardiovascular system in the short and long term. 2. In the short term, the sympathetic vasomotor outflow is regulated by: (i) homeostatic feedback mechanisms, such as the baroreceptor or chemoreceptor reflexes; or (ii) feed-forward mechanisms that evoke cardiovascular changes as part of more complex behavioural responses. 3. The essential central pathways that subserve the baroreceptor reflex and, to a lesser extent, other cardiovascular reflexes, have been identified by studies in both anaesthetized and conscious animals. A critical component of these pathways is a group of neurons in the rostral ventrolateral medulla that project directly to the spinal sympathetic outflow and that receive inputs from both peripheral receptors and higher centres in the brain. 4. Much less is known about the central pathways subserving feed-forward or 'central command' responses, such as the cardiovascular changes that occur during exercise or that are evoked by a threatening or alerting stimulus. However, recent evidence indicates that the dorsomedial hypothalamic nucleus is a critical component of the pathways mediating the cardiovascular response to an acute alerting stimulus. 5. Long-term sustained changes in sympathetic vasomotor activity occur under both physiological conditions (e.g. a change in salt intake) and pathophysiological conditions (e.g. heart failure). There is evidence that the paraventricular nucleus in the hypothalamus is a critical component of the pathways mediating these changes. 6. Understanding the central mechanisms involved in the long-term regulation of sympathetic activity and blood pressure is a major challenge for the future. As a working hypothesis, a model is presented of the postulated central mechanisms that result in sustained changes in sympathetic vasomotor activity that are evoked by different types of chronic stimulation.

Animals↗
PubMed2001

Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans.

Rho-kinase plays an important role in modulating Ca(2+) sensitivity of vascular smooth muscle and has been suggested to be involved in the increased systemic vascular resistance in hypertensive animals. However, it remains to be examined whether this is also the case in patients with essential hypertension. Recently, it has been shown that fasudil is a specific Rho-kinase inhibitor. The aim of this study was to examine whether Rho-kinase is involved in the pathogenesis of hypertension in humans by using this Rho-kinase inhibitor. Studies were performed in hypertensive patients (HT group, n=14) and age-matched normotensive subjects (NT group, n=12). Forearm blood flow was measured by a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil (3.2, 6.4, 12.8, and 25.6 microg/min) or sodium nitroprusside (0.4, 0.8, 1.6, and 3.2 microg/min). Resting forearm vascular resistance was significantly higher in the HT group than in the NT group (22+/-4 versus 17+/-5 U, respectively; P<0.05). The extent of the increase in forearm blood flow evoked by fasudil was significantly greater in the HT group than in the NT group (12.3+/-1.4 versus 6.0+/-0.6 mL. min(-1). 100 mL(-1), respectively; P<0.01). The percent decrease in forearm vascular resistance was significantly greater in the HT group than in the NT group (63.6+/-4.7% versus 29.6+/-3.9%, respectively; P<0.01). By contrast, forearm vasodilator response evoked by sodium nitroprusside was comparable between the 2 groups. These results provide the first evidence that Rho-kinase may be involved in the pathogenesis of the increased peripheral vascular resistance in hypertension in humans.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Octreotide-induced suppression of the hyperglycemic response to neostigmine or bombesin: relationship to hypothalamic noradrenergic drive.

Neostigmine (cholinesterase inhibitor) or bombesin, when injected into the third cerebral ventricle of awake rat, dose-dependently increased serum glucose with the simultaneous rise in hypothalamic noradrenergic neuronal activity (NAA). Co-administration of octreotide with neostigmine or bombesin suppressed the hypothalamic NNA response with the simultaneous inhibition of the hyperglycemic response. There was a close relationship between hypothalamic NNA and serum glucose in these studies. On the basis of the concept that hypothalamic noradrenergic drive plays an important role in mediating the hyperglycemic response to stressful stimuli, the present findings suggest that the hyperglycemic response to neostigmine or bombesin is mediated via the interaction with hypothalamic noradrenergic neurons.

Animals↗
PubMed2001

Central suppressive effect of octreotide on the hyperglycemic response to 2-deoxy-D-glucose injection or cold-swim stress in awake rats: possible mediation role of hypothalamic noradrenergic drive.

Somatostatin (SRIH) and its analog have been reported to act within the central nervous system to suppress the hyperglycemic response to a variety of neural stimuli. On the other hand, the hyperglycemic response to 2-deoxy-D-glucose (2-DG) injection or cold-swim stress is well demonstrated to be closely associated with an increase in hypothalamic noradrenergic neuronal activity (NNA). To evaluate whether the suppression of the hypothalamic NNA response could be involved in the central mechanism whereby a SRIH analog inhibits the hyperglycemic response, octreotide, a clinically used long-acting octapeptide SRIH analog, was administered into the third cerebral ventricle of awake rats prior to the intraperitoneal injection of 2-DG or cold-swim stress. Hypothalamic noradrenaline (NA) and its neuronal metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG), were analyzed, and the ratio of DHPG to NA was used as an index of NNA. Intracerebroventricular (i.c.v.) pretreatment with octreotide suppressed the 2-DG-induced increase in hypothalamic NNA, accompanied by the inhibition of the serum glucose, NA and adrenaline responses. This suppressive effect of octreotide was dose-dependent. Similarly, i.c.v. pretreatment with octreotide prevented the hypothalamic NNA response to cold-swim stress, accompanied by a blockade of the increases in serum glucose, NA and adrenaline. A close relationship between hypothalamic NNA and serum glucose emerged from these studies. Intraperitoneal pretreatment with octreotide had no significant effect on the hyperglycemic or hypothalamic NNA response to 2-DG injection. These findings suggest that the inhibitory effect of octreotide on the hypothalamic NNA response to 2-DG injection or cold-swim stress is associated with the simultaneous suppression of the hyperglycemic response. Supporting the concept that hypothalamic NNA contributes to the modulation of blood glucose in stressful conditions, it is suggested that the suppression of the hypothalamic NNA response is, at least in part, involved in the central mechanism by which octreotide inhibits the hyperglycemic response to 2-DG injection or cold-swim stress.

Animals↗
PubMed2001

Interferon alpha inhibits intrahepatic recurrence in hepatocellular carcinoma with chronic hepatitis C: a pilot study.

The aim of the present study is to evaluate whether interferon alpha (IFNalpha) therapy can inhibit intrahepatic recurrence after the curative treatment of small HCC with underlying chronic hepatitis C. Forty patients were enrolled in this study. They had solitary, small HCC</=3 cm in diameter, underlying chronic hepatitis C, and were </=70 years old. Of the patients, 18 were treated with IFNalpha for 6 months after the treatment of HCC, and 22 patients who did not receive IFNalpha therapy were used as controls. Six (33%) patients in the IFN group showed sustained response. The incidence of local recurrence was not different in the IFN and non-IFN groups (6 vs. 9%). The cumulative incidences of distant recurrence in the non-IFN and IFN groups were 9 and 6% at 1 year, 27 and 11% at 2 years, 63 and 18% at 3 years, 76 and 28% at 4 years, and 82 and 28% at 5 years; they were significantly different (P<0.01). Six (27%) patients in the non-IFN group died from the progression of HCC, but all IFN-treated patients were alive (P<0.05). The pilot study demonstrates that IFNalpha therapy after the curative treatment of small HCC can inhibit intrahepatic recurrence in the remnant liver and improve the prognosis of hepatitis C virus-related HCC.

Journal Article↗
PubMed2001

Intraoperative ultrasonography by high-resolution annular array transducer for intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: Intraductal papillary mucinous tumors of the pancreas (IPMT) spread along the main pancreatic duct (MPD) or branch duct, or both. It is important to intraoperatively determine the extent of IPMT lesions in the MPD to perform a successful operation. METHODS: This study included 27 consecutive patients with IPMT who were referred for operation and who had undergone endoscopic ultrasonography, endoscopic retrograde pancreatography, and computed tomography as a diagnostic examination. Intraoperative ultrasonography with a 7.5-MHz annular array transducer and a 7. 5-MHz conventional transducer was performed. All patients underwent operation, and the pathology was confirmed. Endoscopic ultrasonography, endoscopic retrograde pancreatography, intraoperative conventional ultrasonography, and intraoperative annular array ultrasonography results were correlated with those from a pathologic examination of the resected specimens. The diagnostic accuracy of these 4 modalities in the detection of IPMT lesions in the MPD and the branch duct was confirmed. RESULTS: The diagnostic criterion of IPMT lesions by intraoperative annular array ultrasonography was the presence of echogenic masses with irregular margins in the MPD or branch duct, or both. An IPMT lesion in the MPD was found in 22 of the 27 patients. Intraoperative annular array ultrasonography detected 5 cases of IPMT lesions in the MPD that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. In 3 of 5 patients, pancreatic resection was extended to remove IPMT lesions. Intraoperative annular array ultrasonography detected 3 multifocal lesions that could not be detected by preoperative examinations. For the diagnosis of IPMT lesions in the MPD, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 86%, 100%, and 89%; the respective values were 50%, 100%, and 59% for endoscopic retrograde pancreatography; 59%, 100%, and 67% for endoscopic ultrasonography, and 32%, 100%, and 44% for intraoperative conventional ultrasonography. For the diagnosis of IPMT lesions in the branch duct, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 95%, 100%, and 96%. CONCLUSIONS: Intraoperative annular array ultrasonography is suitable for longitudinal scanning of the MPD, useful for accurate diagnosis of the extent of IPMT in the pancreas, and valuable for planning surgical strategy and successful operations for IPMT.

Adenocarcinoma, Mucinous↗
PubMed2001

Asymptomatic inflammatory bowel disease with special reference to ulcerative colitis in apparently healthy persons.

OBJECTIVE: We examined cases of asymptomatic inflammatory bowel diseases, particularly asymptomatic ulcerative colitis, which were found in apparently healthy Japanese persons who underwent general health screening. METHODS: Patients with positive immunological fecal occult blood test (IFOBT) among approximately 236,000 persons participating in the health screening program at the Aichi Prefectural Center for Health Care for the past 9 yr underwent total colonoscopy. In patients with ulcerative colitis, we investigated the sex and age distributions, extent of lesion, endoscopic activity, incidence rate, and clinical course. RESULTS: In all, 35 cases of inflammatory bowel disease were detected, and 274 cases of colorectal cancer (not discussed here) were detected in the same population. The 35 cases of inflammatory bowel disease consisted of 19 cases of ulcerative colitis (12 of asymptomatic and minimally symptomatic ulcerative colitis, and seven of symptomatic or with past history of ulcerative colitis); five of intestinal tuberculosis; two of Crohn's disease; two of amebic colitis; and seven of endoscopic colitis. The 12 patients with asymptomatic and minimally symptomatic ulcerative colitis consisted of 11 men and one woman aged 36-63 yr (mean 46.2 yr). We classified these cases into three grades of severity according to endoscopic findings: four cases were mild, eight moderate, and none severe. Of these 12 cases, three were found endoscopically because of positive IFOBT, although barium enema was normal. Anatomic types of colitis cases included three of total colitis, three left-sided colitis, two proctitis, and four right-sided or segmental colitis. In one case, the disease extended proximally during the course of observation. CONCLUSIONS: We found 35 cases of inflammatory bowel disease because of positive IFOBT performed as part of a general health screening. Of these, 19 cases were ulcerative colitis. These included many asymptomatic and minimally symptomatic cases, which could be very important in helping to elucidate the natural history of ulcerative colitis; thus, long-term follow up is necessary.

Adult↗
PubMed2001

Adenovirus-mediated gene transfer into the NTS in conscious rats. A new approach to examining the central control of cardiovascular regulation.

The nucleus tractus solitarii (NTS) is an important site for the regulation of sympathetic nerve activity. It receives the signals through afferent fibers from arterial baroreceptors, chemoreceptors, cardiopulmonary receptors, and other visceral receptors. Many studies have examined the role of nitric oxide (NO) in the NTS in cardiovascular regulation. However, most of these studies were conducted in an acute state with anesthesia. We have developed a novel technique of endothelial nitric oxide synthase (eNOS) gene transfer into the NTS in vivo. Adenovirus vectors encoding either the beta-galactosidase gene (Ad beta gal) or the endothelial nitric oxide synthase gene (AdeNOS) gene were transfected into the NTS. In the Ad beta gal-treated rats, the local expression of beta-galactosidase was confirmed by X-Gal staining, and beta-galactosidase activity was quantified using a colorimetric assay. In the AdeNOS-treated rats, the local expression of eNOS protein was confirmed by immunohistochemistry, and eNOS production was measured by in vivo microdialysis. Blood pressure and heart rate were monitored by a radiotelemetry system in a conscious state. The expression of each gene was observed from day 5 to day 10 after the gene transfer. In the AdeNOS-treated rats, blood pressure and heart rate significantly decreased from day 5 to day 10, and then thereafter gradually recovered over time. Our method may be useful in examining the local effect of a particular substance produced by a specific gene in the brain on cardiovascular function.

Adenoviridae↗
PubMed2001

Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo.

Nitric oxide (NO) in the nucleus tractus solitarii (NTS) plays an important role in regulating sympathetic nerve activity. The aims of this study were to determine whether the activation of N-methyl-D-aspartate (NMDA) receptors in the NTS facilitates the release of L-glutamate (Glu) via NO production, and, if so, to determine whether this mechanism is involved in the depressor and bradycardic responses evoked by NMDA. We measured the production of NO in the NTS as NO2- and NO3- (NO(x)) or Glu levels by in vivo microdialysis before, during, and after infusion of NMDA in anesthetized rats. We also examined effects of N(omega)-nitro-L-arginine methyl ester (L-NAME) on the changes in these levels. NMDA elicited depressor and bradycardic responses and increased the levels of NO(x) and Glu. L-NAME abolished the increases in the levels of NO(x) and Glu and attenuated cardiovascular responses evoked by NMDA. These results suggest that NMDA receptor activation in the NTS induces Glu release through NO synthesis and that Glu released via NO enhances depressor and bradycardic responses.

Animals↗
PubMed2001

Endogenous angiotensin II in the NTS contributes to sympathetic activation in rats with aortocaval shunt.

Recent studies have suggested that the central nervous system is responsible for activation of sympathetic nerve activity (SNA) and the renin-angiotensin system in heart failure (HF). The aim of this study was to determine whether activation of the renin-angiotensin system within the nucleus of the solitary tract (NTS) plays a role in enhanced SNA in HF. High-output HF was induced by an aortocaval (A-V) shunt with some modifications in the rat. These rats exhibited a left ventricular dilatation and hemodynamic signs of high-output HF. Urinary catecholamine excretion and maximal renal SNA (RSNA) were greater in the A-V shunted rats than in the control rats. Microinjection of an angiotensin II type 1-receptor antagonist, CV11974, into the NTS was performed. The arterial pressure and RSNA were reduced by CV11974 to a greater degree in the A-V shunted rats than in the control rats. The expression of angiotensin-converting enzyme mRNA in the medulla was greater in the A-V shunted rats than in the control rats. These results suggest that activation of the renin-angiotensin system within the NTS contributes to an enhanced SNA in this model.

Angiotensin II↗
PubMed2001

Noise-enhanced heart rate and sympathetic nerve responses to oscillatory lower body negative pressure in humans.

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as "stochastic resonance." It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately -10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.

Adult↗
PubMed2001

Role of nitric oxide in central sympathetic outflow.

The gaseous molecule nitric oxide (NO) plays an important role in cardiovascular homeostasis. It plays this role by its action on both the central and peripheral autonomic nervous systems. In this review, the central role of NO in the regulation of sympathetic outflow and subsequent cardiovascular control is examined. After a brief introduction concerning the location of NO synthase (NOS) containing neurons in the central nervous system (CNS), studies that demonstrate the central effect of NO by systemic administration of NO modulators will be presented. The central effects of NO as assessed by intracerebroventricular, intracisternal, or direct injection within the specific central areas is also discussed. Our studies demonstrating specific medullary and hypothalamic sites involved in sympathetic outflow are summarized. The review will be concluded with a discussion of the role of central NO mechanisms in the altered sympathetic outflow in disease states such as hypertension and heart failure.

Animals↗
PubMed2001

Stimulatory effect of endothelin-1 on neurons in the nucleus tractus solitarii is mediated by non-N-methyl-D-aspartate receptors.

We previously demonstrated that endothlin-1 (ET-1) augments and ETA receptor antagonist attenuates excitatory neuronal response to glutamate (Glu) in brainstem slices from normotensive rats. The aim of this study was to determine which type of Glu receptor is responsible for the stimulatory effects of ET-1 on neurons of the nucleus tractus solitarii (NTS). Single unit discharges were recorded extracellularly from rat brainstem slice preparations. Seven NTS neurons that were excited by solitary tract (ST) stimulation responded to iontophoretically applied ET-1 with neuronal activity. An N-methyl-D-aspartate (NMDA) receptor antagonist, non-NMDA, 6-cyano-7-nitro-quinoxaline-2, 3-dione (CNQX), or DL-2-amino-5-phosphonovaleric acid (AP-5) was perfused over the slices with Kreb's-Ringer solution. The increase in neuronal activity evoked by iontophoretically applied ET-1 was nearly abolished by CNQX but not by AP-5. CNQX but not AP-5 decreased the basal spontaneous neuronal activity of NTS neurons. These results suggest that non-NMDA receptors play a role in mediating the stimulatory effect of ET-1 on neuronal activity in the NTS.

2-Amino-5-phosphonovalerate↗