[On the 10th Examination for Specialties by the Japanese Society of Ophthalmology].
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Educational Measurement↗
Biomedical subjects
H Matsuda
Publications and source records attributed to H Matsuda.
[Histopathological examination of transurethral electrovaporization of the prostate].
Transurethral electrovaporization of the prostate (TVP) has been devised to eliminate prostatic tissue by electric vaporization and to create a dry coagulation layer beneath to minimize bleeding from the site of TVP. However, vaporization induces degeneration due to thermal coagulation deep in the tissue beneath the vaporized layer, and local tissue damage is thus greater than that caused by the standard transurethral resection of prostate (TURP) loop. Since this results in difficulty with histopathological examination, the percentages of tissue-diagnosable area were determined in sections resected using various vaporization electrodes (Roller Loop, Band & Wedge Loop). The percentage of tissue-diagnosable area was 92.0 +/- 3.3% with the standard TUR loop, 2.4 +/- 0.9% with the Roller Loop, 42.7 +/- 21.1% with the Band Loop, and 39.7 +/- 24.4% with the Wedge Loop. Concerning speed of resection, the best vaporization effect was obtained when the speed of operation was 1/2 or 1/3 that with the standard TUR loop. Since the region in which tissue diagnosis was smaller with the vaporization electrode than with standard TURP, more careful examination was required for diagnosis of incidental cancers. Therefore, postoperative observation by PSA measurement appeared to be important.
Aged↗
[Cardiac disorders associated with progressive systemic sclerosis].
This study investigated cardiac disorders in 25 patients with diagnoses of progressive systemic sclerosis based on the criteria of the American College of Rheumatology. All were women, and the mean age was 59 +/- 11 (range 41-80) years old. The duration of the disease was 11 +/- 9 (range 3-40) years. The following complications were seen; Raynaud's phenomenon in all, esophageal disorders in 11, pulmonary fibrosis in 9, diabetes mellitus in 3, high blood pressure in 6, hyperlipidemia in 7, and positive anticardiolipin antibody in 8. Electrocardiography (ECG) and echocardiography were performed to assess the cardiac disorders. Abnormal ECG was seen in 11 patients (44%) and abnormal echocardiograms in 16 patients (64%). ECG abnormalities included incomplete right bundle branch block in 8 (32%), low voltage in 3 (12%), supraventricular arrhythmia in 3 (12%), ventricular arrhythmia in 1 (4%) and septal myocardial infarction pattern in 1 (4%). Echocardiographic abnormalities included valvular diseases in 13 (52%) and pericardial thickening in 7 (28%). No relationship was found between ECG and echocardiographic abnormalities. Echocardiographic abnormalities were more frequently observed in patients with positive anticardiolipin antibody (7/8, 88%) than in those with negative anticardiolipin antibody (9/17, 53%). Especially, pericardial thickening was seen in 63% (5/8) of positive patients, in comparison to 12% (2/17) of the negative patients (p < 0.05). Patients with progressive systemic sclerosis may have several cardiac disorders including conduction disturbances, low voltage ECG, valvular diseases and pericardial thickening. Pericardial thickening has a close relationship with positive anticardiolipin antibody.
Adult↗
Computer-assisted skull identification system using video superimposition.
This system consists of two main units, namely a video superimposition system and a computer-assisted skull identification system. The video superimposition system is comprised of the following five parts: a skull-positioning box having a monochrome CCD camera, a photo-stand having a color CCD camera, a video image mixing device, a TV monitor and a videotape recorder. The computer-assisted skull identification system is composed of a host computer including our original application software, a film recorder and a color printer. After the determination of the orientation and size of the skull to those of the facial photograph using the video superimposition system, the skull and facial photograph images are digitized and stored within the computer, and then both digitized images are superimposed on the monitor. For the assessment of anatomical consistency between the digitized skull and face, the distance between the landmarks and the thickness of soft tissue of the anthropometrical points are semi-automatically measured on the monitor. The wipe images facilitates the comparison of positional relationships between the digitized skull and face. The software includes the polynomial functions and Fourier harmonic analysis for evaluating the match of the outline such as the forehead and mandibular line in both the digitized images.
Adult↗
p16INK4, pRB, p53 and cyclin D1 expression and hypermethylation of CDKN2 gene in thymoma and thymic carcinoma.
There have been few reports on genetic alterations in thymomas. To investigate the expression of p16INK4A, RB, p53 and cyclin D1 in thymomas, we first examined 36 thymomas (non-invasive type, 16 cases; invasive type, 20 cases) and 3 thymic carcinomas, using immunohistochemistry. Abnormal expression of p16INK4A, RB, p53 and cyclin D1 was observed in 18, 8, 10 and 7 cases, respectively. Only a subgroup of invasive thymomas and thymic carcinomas showed an inverse correlation between p16INK4A and RB expression. Subsequently, we examined the 36 thymomas and 4 thymic carcinomas for mutations in p53 and CDKN2 genes, using PCR-SSCP and direct-sequencing analyses. No mutation of these genes was detected in the thymomas and thymic carcinomas examined. A polymorphism in the 3' untranslated region of exon 3 of CDKN2 was detected in 5 cases of thymoma. We searched for hypermethylation in the promoter region of CDKN2, observing it in 4 thymomas and 1 thymic carcinoma. Our data suggest that, unlike other more common cancers, alteration of the p53 gene may not play a significant role in the tumorigenesis of thymoma. However, inactivation of p16INK4A and RB may play a role in the progression of thymoma and thymic carcinoma.
Blotting, Southern↗
Lumbar spinal canal stenosis examined electrophysiologically in a rat model of chronic cauda equina compression.
STUDY DESIGN: A model of chronic cauda equina compression with conductive stress was studied electrophysiologically. OBJECTIVE: To analyze the pathophysiology arising from chronic compression electrophysiologically. SUMMARY OF BACKGROUND DATA: This rat model of cauda equina compression that is chronic, not acute, has been reported elsewhere. METHODS: A stainless steel wire and plate were fastened to the spine at L5 of 8 rats 3 weeks old. One year later, the ascending and descending nerve action potentials were recorded and the conduction velocities (CVs) were measured. Electrophysiologic changes after high-frequency stimulation (HFS) were observed. RESULTS: The waveform of the ascending cauda equina action potential at the cauda equina had three peaks, and that at the conus medullaris had a peak followed by a broad wave. The waveform of the descending nerve action potential had two peaks. The mean ascending and descending CVs of the treated rats were slower (P < 0.001) than those of the control rats. In the control rats, the mean CV and mean amplitude after HFS decreased slightly and returned to normal within 30 seconds, and the waveform was unchanged. In treated rats, the mean CV decreased after HFS but returned to normal within 10 minutes. The mean amplitude decreased after HFS and did not return to normal within 10 minutes. The waveform was unchanged. CONCLUSIONS: Because the differences between treated and control rats in amplitude (and CVs) were greater before HFS than after HFS, we concluded that treated rats had disturbance of the blood flow in vessels around the nerves of the cauda equina with histologic damage. In human patients, such disturbance may be one cause of intermittent claudication.
Action Potentials↗
C-Myc expression and its role in patients with chronic aortic regurgitation.
BACKGROUND: Proto-oncogenes have been implicated in the pathogenesis of gene-mediated myocardial remodeling. In the human heart, however, it has not been clarified whether these proto-oncogenes are related to contractile impairment and structural alteration of the myocardium. The present study is designed to investigate the relationship between the c-Myc protein expression in the myocardium and the myocardial contractile dysfunction in patients with chronic aortic regurgitation who underwent indicated for aortic valve replacement. METHODS AND RESULTS: Twelve patients (11 males and one female) with an average age of 55 years who underwent aortic valve replacement for isolated chronic aortic regurgitation were studied. The preoperative New York Heart Association class was II in four patients and III in eight. Ejection fraction, end-systolic volume index, end-systolic stress (Mirsky's form), and mass index of the left ventricle before surgery were 47+/-13%, 93+/-37 mL/m2, 223.2+/-44.4 Kdyn/cm2, and 210+/-38 g/m2, respectively. A left ventricular endomyocardial biopsy was performed to assess the myocardial cell diameter, fibrous content, and c-Myc protein expression in the myocardium. Cell diameter and fibrous content were significantly higher than those in five normal controls. C-Myc was detected in 9 of 12 present patients but in none of the normal controls. The degree of c-Myc expression had significant positive correlations with ejection fraction (r=0.93; P<.01) and end-systolic stress/end-systolic volume index (r=0.96; P<.01) and significant negative correlations with end-systolic volume index (r=-0.90; P<.01), cell diameter (r=-0.97; P<.01), and fibrous content (r=-0.92; P<.01), which suggested that the degree of c-Myc expression may have a significant negative correlation with myocardial contractility and myocardial hypertrophy. CONCLUSIONS: C-Myc expression may be related to the pathogenesis of myocardial remodeling in patients with chronic aortic regurgitation.
Adult↗
Developmental differences in cytosolic calcium accumulation associated with global ischemia: evidence for differential intracellular calcium channel receptor activity.
BACKGROUND: Cytosolic calcium ([Ca2+]i) accumulation during global ischemia is increased 30% more in the aged compared with the mature heart and is associated with decreased functional recovery. Recently, we have shown that [Ca2+]i accumulation occurs via the ryanodinc sensitive (RyR) and the inositol (1,4,5) triphosphate calcium channels (IP3) but not the Na+/Ca2+ exchanger in both the mature and aged heart, suggesting that the increase in [Ca2+]i accumulation in the aged heart may result from either alteration of intracellular Ca2+ channel receptor activity or abundance. METHODS: [3H]-Ryanodine and [3H]-Inositol (1,4,5) triphosphate binding was determined in mature (MAT; 15 to 20 weeks) and aged (AGE; >130 weeks) rabbit hearts perfused for 60 minutes (control) or perfused for 30 minutes then subjected to 30 minutes of global ischemia (global ischemia). RESULTS: RyR and IP3R activities in control were decreased significantly (P<.05) in aged compared with mature hearts. Global ischemia significantly decreased RyR activity in MAT but not in AGE. IP3R was significantly increased (P<.05) during global ischemia in AGE but not in MAT. Northern and Western blot analysis indicated that there were no differences in RyR or IP3R mRNA or protein levels between MAT and AGE. CONCLUSIONS: Aging alters intracellular Ca2+ channel activity. Ca2+ channel activity is decreased during global ischemia in mature but increased in the aged heart resulting in increased [Ca2+]i accumulation. Differences in RyR and IP3R activities were shown not to be the result of a decrease in receptor mRNA or protein levels in the aged compared with the mature heart.
Animals↗
A novel strategy for myocardial protection using in vivo transfection of cis element 'decoy' against NFkappaB binding site: evidence for a role of NFkappaB in ischemia-reperfusion injury.
BACKGROUND: NFkappaB, an important transcriptional factor, has been reported to play a significant role in the coordinated transcription of cytokine and adhesion molecule genes. Therefore, blocking the NFkappaB may attenuate ischemia reperfusion injury in the myocardium. For blocking transcriptional factors, gene therapy, such as cis element "decoy," appears to be an innovative and useful therapy. This study aimed to prove the efficacy of cis element decoy against NFkappaB binding site for myocardial protection. METHODS AND RESULTS: Rat hearts were transfected with fluorescence isothiocyanate-labeled cis element decoy against NFkappaB (NF)-binding site (NF group, n=6) and scrambled decoy (SD) group (n=6) by coronary infusion of hemagglutinating virus of Japan (HVJ)-liposome during cardioplegic arrest. Both the NF and SD groups showed marked FITC-staining in the nuclei of myocytes, demonstrating the efficacy of gene transfer into the nuclei of cardiac myocytes as compared with the control group transfected with empty liposomes. After 3 days of transfection, the NF group showed significantly higher percentages of recovery of left ventricular developed pressure (NF versus SD, 87+/-11 versus 54+/-12%) and coronary flow (97+/-16 versus 61+/-15%) than did the control hearts when exposed to ischemia (30 minutes, 37 degrees C) and reperfusion (30 minutes, 37 degrees C). The NF group showed a significantly lower percentage of neutrophil adherence to endothelial cells (38+/-6 versus 81+/-3%) and a lower tissue level of interleukin-8 (109+/-48 versus 210+/-55 ng/mg) than did the SD group. CONCLUSION: The hearts transfected with cis element decoy against NFkappaB binding site showed significant improvement in tolerance against ischemia-reperfusion injury in association with the inhibition of neutrophil adherence and tissue IL-8 production. This suggests that NFkappaB plays a significant role in ischemia-reperfusion injury. This method, using in vivo gene transfection of cis element decoy against NFkappaB binding site, appears to be a novel and future strategy for myocardial protection.
Animals↗
Involvement of transcription factor encoded by the mouse mi locus (MITF) in expression of p75 receptor of nerve growth factor in cultured mast cells of mice.
The mi locus of mice encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Cultured mast cells (CMCs) of mi/mi genotype showed a poor response to nerve growth factor (NGF). Addition of NGF to the suboptimal dose of interleukin-3 (IL-3) increased the plating efficiency of normal (+/+) CMCs but not mi/mi CMCs. Although +/+ CMCs were berberine sulfate-negative when cultured with IL-3, +/+ CMCs became berberine sulfate-positive when cultured in the presence of both IL-3 and NGF, which suggested increased heparin content. In contrast, NGF did not influence the phenotype of mi/mi CMCs. The poor response of mi/mi CMCs to NGF was attributed to the deficient expression of p75 NGF receptor. The purpose of the present study is to examine the effect of MITF on p75 gene transcription. Overexpression of +-MITF or mi-MITF was observed in mi/mi CMCs to which cDNA encoding each type of MITF had been introduced using the retroviral vector. Overexpression of +-MITF but not of mi-MITF normalized the expression of p75 and the above-mentioned poor responses of mi/mi CMCs to NGF, indicating the involvement of +-MITF in p75 gene transactivation. Then, we analyzed the promoter of the p75 gene. Two CANNTG motifs recognized by bHLH-Zip-type transcription factors were conserved between the mouse and rat p75 promoters. One of these two CANNTG motifs was specifically bound by +-MITF. When the luciferase gene under the control of the p75 promoter was cotransfected into NIH/3T3 fibroblasts with cDNA encoding +-MITF or mi-MITF, luciferase activity increased significantly only when +-MITF cDNA was cotransfected. The mutation of this CANNTG motif abolished the transactivation effect of +-MITF, indicating that +-MITF transactivated the p75 gene, at least in part, through direct binding.
3T3 Cells↗
Donor-specific tolerance by perioperative intrathymic injection of bone marrow cells in the rat cardiac allograft model: use of FK506 can shorten the necessary duration of pretransplant intrathymic conditioning.
BACKGROUND: Many strategies of tolerance induction by intrathymic (IT) injection of donor alloantigens have been reported to date; however, the timing of IT injection is usually 1-3 weeks before transplantation. METHODS: To apply IT injection to cadaveric organ transplantation, 1 x 10(8) fully allogeneic bone marrow cells (BMC) of Buffalo (BUF; RT1b) rats were intrathymically injected into Wistar Furth (WF; RT1u) rats at the time of BUF cardiac allografting with short-course therapy of antilymphocyte serum (ALS) and FK506 in our experimental model. RESULTS: Allogeneic IT injection of BUF BMC with ALS and FK506 indefinitely prolonged graft survival (mean survival time > 210 days) in all WF rats. On day 130 after grafting, tolerant WF rats accepted donor BUF skin grafts (> 120 days) but not third-party Lewis skin grafts. In control groups, syngeneic IT injection of WF BMC or intravenous injection of donor BUF BMC in combination with ALS/FK506 therapy failed to induce tolerance. In vivo testing was performed during induction (1 month) or during maintenance (6 months of tolerance. In the mixed lymphocyte reaction (MLR), spleen T cells of tolerant rats at 1 month after grafting displayed hyporesponsiveness after stimulation with donor cells. The addition of interleukin (IL)-2 to MLR culture did not restore T-cell responsiveness. Tolerant rats had a significantly decreased frequency of T cytotoxic cell precursors (fTcp) of 1:4,926, and frequency of IL-2-producing T helper cell precursors (fThp) of 1:23,925, compared with naive rats (1: 2,158 and 1:4,266, respectively). By 6 months after grafting, however, the anti-donor MLR proliferative responses of tolerant rats had been restored to the levels of naive splenic T cells. These tolerant rats displayed restoration of the (fTcp) of 1:2,842 and of the (fThp) of 1:5,630, which were comparable frequencies of naive rats. Suppressor T cells did not contribute in this model. In cardiac grafts of tolerant rats induced by IT injection, expression of both Th1 (interferon-gamma and IL-2) and Th2 (IL-4 and IL-10) cytokines was detected in the early phase; thereafter, expression was completely inhibited, except for interferon-gamma in the chronic phase. CONCLUSIONS: Perfect donor-specific tolerance was obtained by IT injection of donor BMC at the time of transplantation, while alloimmune responses were maintained at levels similar to those of naive rats.
Adoptive Transfer↗
Significant downregulation of the major swine xenoantigen by N-acetylglucosaminyltransferase III gene transfection.
Introduction of the beta-D-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene into swine endothelial cells (SEC) reduced their susceptibility to normal human serum (NHS) in complement-mediated cell lysis and also suppressed the antigenicity to human natural antibodies as evidenced by flow cytometric analysis, as well as Griffonia simplicifolia 1 isolectin (1B4 lectin) binding to the Gal alpha1-3 Gal beta 1-4 GlcNAc-R (the alpha-galactosyl epitope). Western blot analysis indicated that proteins smaller than 66 kDa had diminished reactivity to NHS and 1B4 lectin. GnT-III, a key enzyme involved in branch formation of N-linked sugars, was found to downregulate the expression of xenoantigen, suggesting that this approach may be of value in clinical xenotransplantation in the future.
Animals↗
In vivo gene transfection with heat shock protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat.
Heat shock protein 70 (HSP70) has been reported to be involved in the myocardial self-preservation system. To obtain the evidence that HSP70 plays a direct role in the protection from myocardial ischemia-reperfusion injury, rat hearts were transfected with human HSP70 gene by intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome containing human HSP70 gene. The control hearts were infused with HVJ-liposome without the HSP70 gene. The hearts from whole-body heat-stressed or nontreated rats were also examined. Western blot and immunohistochemical analysis showed that apparent overexpression of HSP70 occurred in the gene transfected hearts and that gene transfection might be more effective for HSP70 induction than heat stress. In Langendorff perfusion, better functional recovery as well as less creatine phosphokinase leakage after ischemia were obtained in the gene transfected hearts with HSP70 than in the control or nontreated hearts. Furthermore, the gene transfected hearts showed better functional recovery than the heat-stressed hearts. These results indicated that overexpressed HSP70 plays a protective role in myocardial injury, suggesting the possibility that gene transfection with HSP70 may become a novel method for myocardial protection through enforcing the self-preservation systems.
Animals↗
Human platelets can initiate T cell-dependent contact sensitivity through local serotonin release mediated by IgE antibodies.
To investigate the role of human platelets in initiating Ag-specific contact sensitivity (CS), a mouse model employing human platelets was used. Intravenous injection of immune lymphoid cells containing Ag-specific CS-effector Thy1+ B220- T cells that were depleted of CS-initiating Thy1+, B220+ cells together with human platelets presensitized in vitro with Ag-specific IgE mAb led to elicitation of CS responses in recipient mice. The fact that this response was blocked by preincubation of platelets with an irrelevant IgE or with a mixture of anti-Fc epsilonRI alpha mAb and anti-Fc epsilonRII mAb suggested that IgE Fc epsilonR on platelets were involved. When platelets that were presensitized with Ag-specific IgE mAb were incubated in vitro with specific Ag in the presence of fresh mouse serum, a significant net release of [3H]serotonin (5-hydroxytryptamine, 5-HT) was observed. Furthermore, in vitro depletion of 5-HT from platelets or in vivo pretreatment of recipients with a 5-HT2A receptor antagonist (ketanserin) abolished the IgE-dependent CS initiation mediated by platelets. These results show that human platelets can initiate T cell-dependent CS responses through IgE mAb, and this CS initiation is mediated by 5-HT released from the platelets in an Ag-specific manner.
Animals↗
Inwardly rectifying potassium channels expressed by gene transfection into the green Monkey kidney cell line COS-1.
1. cDNA encoding a functional inwardly rectifying K+ (IRK1) channel was transfected into COS-1 cells (a Green Monkey kidney cell line) using the liposome method, and voltage clamp experiments were done after 48-72 h. 2. Transfected cells showed inward rectification under whole-cell recording. The unitary current-voltage relationships in the inside-out configuration were almost linear in the absence of internal Mg2+ and polyamines, and the channel conductance averaged 34.1 +/- 2.0 pS (n = 15) at 23-26 degrees C. 3. Internal Mg2+ (2-10 microM) induced sublevels in the outward current with one-third and two-thirds of the unitary amplitude as in native channels. 4. To determine the subunit stoichiometry, we constructed tandem multimeric cDNAs consisting of the coding sequences of the IRK1 gene linked in a head-to-tail fashion. Cells transfected with tandem homomultimers up to octamers showed similar inwardly rectifying K+ channels. 5. A mutation (E138Q) eliminated the ionic conductance of the channel. Channels expressed by dimeric constructs containing a single mutant have a conductance ranging between 5 and 35 pS. 6. The E138Q mutant cotransfected with a wild-type dimeric, trimeric or tetrameric construct did not alter the channel conductance. The results do not support the notion that IRK1 channel proteins consist of four subunits.
Animals↗
Nerve growth factor promotes giant-cell transformation of mouse trophoblast cells in vitro.
We examined the effects of NGF on the TGC (trophoblastic giant cell) transformation of the ectoplacental cone (EPC) cells derived from the mouse pregnant uteri on day 7.5 p.c. The addition of NGF strongly accelerated the rate of the TGC transformation of EPC cells in a dose-dependent manner. The promoting action of NGF was abolished by the addition of anti-NGF MAb. Histochemical staining with succinyl wheat germ agglutinin (s-WGA), an in situ marker for the TGCs on day 10.5 p.c., revealed that NGF induced the expression of s-WGA-binding glycoproteins in TGCs in vitro. RNA analysis revealed that NGF mRNA was expressed in the pregnant uterus on day 7.5 p.c., mainly in the decidua, but it could not be detected in the EPC. p75NGFR mRNA was expressed in the EPCs, whereas TrkA mRNA was not detected in the placental tissues throughout day 7.5 to 10.5 p.c. We therefore conclude that maternally derived NGF may play a role in mouse placentation by promoting the giant-cell transformation of trophoblast cells through p75NGFR.
Animals↗
Usefulness of myocardial velocity gradient derived from two-dimensional tissue Doppler imaging as an indicator of regional myocardial contraction independent of translational motion assessed in atrial septal defect.
Independence of myocardial velocity gradient from translational motion of the heart was tested by comparing normal subjects and patients with atrial septal defect. Myocardial velocity gradient obtained from patients fit within the normal range, even though the translation of the left ventricle was exaggerated in patients, demonstrating the translation independence of myocardial velocity gradient in clinical settings.
Adolescent↗
Simultaneous observation of endocrine and exocrine functions of the pancreas responding to somatostatin in man.
Six patients who underwent segmental autotransplantation of the caudal pancreas (SAT) following total pancreatectomy for pancreatic cancer were investigated. The graft was transplanted to the left groin, and pancreatic juice was diverted outside through a polyethylene tube indwelled into the main pancreatic duct. In these SAT patients, the responses of insulin (IRIS) in terms of plasma levels and pancreatic secretion to subcutaneous injections of somatostatin octreotide (Sandostatin: SMS201-995) were simultaneously observed. Four doses (0.039, 0.156, 0.625 and 2.5 micrograms/kg) of SMS201-995 were given on separate days. As a control, saline was injected subcutaneously. Standard liquid test meal was given 1 h after the subcutaneous injection. The basal plasma IRI were significantly decreased with doses greater than 0.156 microgram/kg. The postprandial responses of IRI was also significantly suppressed with the same doses. On the other hand, the basal pancreatic exocrine secretion was significantly suppressed with doses greater than 0.625 microgram/kg. The postprandial pancreatic exocrine secretion was also significantly suppressed with doses greater than 0.625 microgram/kg. Those suppressions were dose-dependent. The postprandial CCK secretion was also significantly suppressed in dose-dependent manner with SMS201-995. The CCK suppression was significantly correlated with the suppression of pancreatic exocrine secretion. This clinical study under the setting of SAT demonstrated not only the direct inhibitory effect of somatostatin on both the islet and acinar cells but also, probably, the indirect inhibitory effect on the acinal cells via suppression of CCK release in humans.
Aged↗