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Biomedical subjects

R Doi

Publications and source records attributed to R Doi.

At least 19 recordsLinked to original sources
PubMed2006

Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion.

AIMS/HYPOTHESIS: G protein-coupled receptor 40 (GPR40) is abundantly expressed in pancreatic beta cells in rodents, where it facilitates glucose-induced insulin secretion in response to mid- to long-chain fatty acids in vitro. However, GPR40 gene expression in humans has not been fully investigated, and little is known about the physiological and pathophysiological roles of GPR40 in humans. The aim of this study, therefore, was to examine GPR40 expression and its clinical implications in humans. METHODS: GPR40 mRNA expression in the human pancreas, pancreatic islets and islet cell tumours was analysed using TaqMan PCR. RESULTS: GPR40 mRNA was detected in all human pancreases collected intraoperatively. It was enriched approximately 20-fold in isolated islets freshly prepared from the pancreases of the same individuals. The estimated mRNA copy number for the GPR40 gene in pancreatic islets was comparable to those for genes encoding sulfonylurea receptor 1, glucagon-like peptide 1 receptor and somatostatin receptors, all of which are known to be expressed abundantly in the human pancreatic islet. A large amount of GPR40 mRNA was detected in insulinoma tissues, whereas mRNA expression was undetectable in glucagonoma or gastrinoma. The GPR40 mRNA level in the pancreas correlated with the insulinogenic index, which reflects beta cell function (r=0.82, p=0.044), but not with glucose levels during the OGTT, the insulin area under the OGTT curve or the index for the homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSIONS/INTERPRETATION: The present study provides evidence for GPR40 gene expression in pancreatic beta cells and implicates GPR40 in insulin secretion in humans.

Adult↗
PubMed2005

Morphological imaging in the localization of neuroendocrine gastroenteropancreatic tumors found by somatostatin receptor scintigraphy.

PURPOSE: To evaluate the necessity of morphological images (MI) in reading somatostatin receptor scintigraphy (SRS) in patients with suspected neuroendocrine gastroenteropancreatic (GEP) tumors. MATERIAL AND METHODS: A Japanese multicenter clinical trial of SRS was conducted in 40 patients with suspected GEP tumors. Three experienced radiologists interpreted the images in three separate sessions in a blinded manner (1: SRS images alone, 2: MI alone, 3: SRS and MI analyzed simultaneously), and the reading results of each session were compared. In addition, the diagnostic abilities of SRS, MI and SRS alone and simultaneous SRS and MI readings were compared for patients where final diagnosis was obtained. RESULTS: SRS detected more suspected lesions (positive or inconclusive uptake) than morphological images did (51 vs 27 lesions), but included many physiological uptakes detected as positive or inconclusive uptakes. Combined reading of SRS and morphological images helped to correctly recognize these physiological uptakes, and also helped in determining the anatomical localization of the abnormal uptakes. Combined reading of SRS and morphological images gave the highest diagnostic impact. CONCLUSION: The sensitivity of SRS with regard to GEP is high. However the specificity is very low. Morphologic imaging is necessary for the exclusion of physiological uptake and correct anatomic location of an abnormal tracer uptake. The combined reading of SRS and morphologic imaging studies gives the highest diagnostic impact.

Adenocarcinoma↗
PubMed2003

Hand-assisted laparoscopic resection of serous cystadenoma of the pancreas.

It is difficult to exclude the possibility of malignancy of pancreatic cystic tumors because a biopsy of the pancreas is hard to obtain. The indication of open surgery for those cystic tumors without evidence of malignancy is controversial. Therefore, laparoscopic or laparoscopically assisted procedure would be an adequate choice of treatment for cystic tumors of the pancreas. Hand-assisted laparoscopic distal pancreatectomy with preservation of the spleen and the splenic artery and vein was performed for two cases of pancreatic cystic tumors. Three ports and one hand port were used. After careful dissection and accurate hemostasis between the pancreas and splenic vessels, laparoscopic distal pancreatectomy was carried out using an endoscopic linear stapler. There were no perioperative complications. The pathological diagnoses were oligocystic serous cystadenoma and solitary cystic serous cystadenoma, respectively. Hand-assisted, spleen-preserving laparoscopic distal pancreatectomy with preservation of the splenic artery and vein is a feasible procedure for the treatment of benign or borderline-malignant cystic lesions of the distal pancreas.

Adult↗
PubMed2002

Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells.

Somatostatin analogues have been developed as antiproliferative agents, but their administration as general antitumour agents is limited, mainly because of the wide distribution of somatostatin receptors throughout the human body. TT-232, a new somatostatin structural analogue, was reported to have tumour-selective antiproliferative activity without an antisecretory action. We examined whether TT-232 had antiproliferative activity in human pancreatic cancer cell lines, and compared its antiproliferative activity with that of RC-160 and other TT-232 derivatives. TT-232 inhibited the growth of all of the cell lines used in this study and induced apoptotic cell death. RC-160 showed no such growth inhibition. TT-232 also inhibited tumour formation in a xenograft model. A competitive binding assay was performed using the cell membrane fraction and 111In-DTPA-TT-232 in order to show the existence of a specific binding site on the cells. A specific binding site was detected in MIAPaCa-2 cells. It has been shown that the activation of protein tyrosine phosphatase (PTPase) is one of the main intracellular pathways responsible for somatostatinergic inhibition of cell growth. We found a significant PTPase stimulation after TT-232 administration using an immunoblot analysis assessing the level of protein tyrosine phosphorylation, and also a direct measurement of the PTPase activity. We also demonstrated that PTPase stimulation by TT-232 was involved in its antiproliferative activity as this activity was reversed by the addition of sodium orthovanadate, a PTPase inhibitor. Our results indicate that TT-232 could be a potentially useful therapeutic agent if these data are translated into clinical practice.

Antineoplastic Agents↗
PubMed2002

Indirect conductimetric assay of antibacterial activities.

The applicability of indirect conductimetric assays for evaluation of antibacterial activity was examined. The minimal inhibitory concentration (MIC) obtained by the indirect method was consistent with that by the direct conductimetric assay and the turbidity method. The indirect assay allows use of growth media, which cannot be used in the direct conductimetric assay, making it possible to evaluate the antibacterial activity of insoluble or slightly soluble materials with high turbidity, such as antibacterial ceramic powders.

Anti-Bacterial Agents↗
PubMed2001

Human gastrinoma cells express calcium-sensing receptor.

The intravenous calcium injection test has been reported to be useful for the diagnosis of gastrinoma. However, the mechanism underlying calcium-evoked gastrin release is not fully understood. We investigated the mechanism of calcium-stimulated gastrin release from gastrinoma cells in vitro with a particular focus on the calcium-sensing receptor (CaR). Human gastrinoma cells were taken from mechanically minced gastrinoma tissues obtained at surgery. In the perifusion system, high [Ca2+]o induced gastrin release from gastrinoma cells. As [Ca2+]o increased, [Ca2+]i rapidly increased, as monitored by fluorometry. The response was not inhibited by nifedipine, a blocker of the voltage-dependent calcium channel. Reverse transcriptase-polymerase chain reaction and subsequent Southern blot hybridization revealed the presence of the CaR gene in human gastrinoma tissues. Moreover, the expression of CaR in gastrinoma tissues was confirmed by immunohistochemistry. Our results demonstrated that CaR was expressed in human gastrinoma cells and could be involved in the mechanism of calcium-evoked gastrin release.

Blotting, Southern↗
PubMed2001

A novel synthetic Arg-Gly-Asp-containing peptide cyclo(-RGDf==V-) is the potent inhibitor of angiogenesis.

Arg-Gly-Asp (RGD)-containing peptide is a ligand for integrin alpha(V)beta3 and acts as an angiogenic inhibitor. A novel cyclic RGD peptide, cyclo(-RGDf==V-) (f==V), was synthesized and its biological activities were characterized and compared with its analogs, cyclo(-RGDfV-) (fV) and cyclo(-RGDf-MeV-) (fMeV). It bound to integrin alpha(V)beta3 with almost the same affinity as the fV and fMeV analogs. All three compounds inhibited the adhesion and growth of HUVEC cells in a dose-dependent manner in vitro. Out of three, fMeV had the strongest effect, f==V was almost as strong as fMeV, and fV had the least effect. However, in vivo, f==V significantly decreased the intratumoral microvessel density (MVD) in the DLD-1 (human colon cancer cell) inoculated mice, while fMeV had little effect. These results suggest the potential usefulness of the cyclo(-RGDf==V-) as an antiangiogenic agent for clinical use in the future.

Animals↗
PubMed2001

Wide use of skin-lightening soap may cause mercury poisoning in Kenya.

In a previous study, we speculated that some of the high mercury levels observed in head hair from a total of 14 subjects who resided around Lake Victoria, Tanzania, might be attributable to the habitual use of toilet soap containing considerable amounts of mercury (Harada et al. Sci Total Environ 1999;227:249-256). In August 1998, the current study was conducted to investigate if such mercury-containing soap was also available in the surroundings of Lake Victoria, Kenya, and if so, its toxic effects. A total of nine goldminers, 44 fishermen and their families, and 12 residents of Kisumu City, Kenya, volunteered for the study. Fourteen types of toilet soap were collected in Kisumu. Total mercury content was very significantly higher than in European-made soap (0.47-1.7%, as mercury iodide) compared with Kenya-made soap (0.41 x 10(-4)-6.2 x 10(-4)%). Indeed, all the subjects with a high hair mercury level (> 36.1 ppm) had made habitual use of European-made soap, accompanied by various symptoms, such as tremor, lassitude, vertigo, neurosthenia, and black and white blots, suggesting inorganic-mercury poisoning. On the other hand, any subject who had used soap other than the European-made soap, did not exceed a mercury level of 10 ppm in hair that is well within normal limits (Harada et al. Sci Total Environ 1999:227:249-256). The findings obtained suggest that the mercury-containing soap must be barred from circulation without delay, and that the residents' health in addition to the environmental pollution in Lake Victoria (Kenya as well as Tanzania) should be kept under close observation.

Adult↗
PubMed2001

Electrochemical and ferromagnetic couplings in 4,4',4' '-(1,3,5-benzenetriyl)tris(phenoxyl) radical formation.

4,4',4' '-(1,3,5-Benzenetriyl)tris(2,6-di-tert-butylphenol) was prepared by the cross-coupling of 1,3,5-tribromobenzene and [4-(trimethylsiloxy)phenyl]magnesium bromide. X-ray analysis of the single crystal showed a propeller-like structure with a mean dihedral angle of 39 degrees between the hydroxyphenyl and the core benzene. The phenoxyl mono-, di-, and triradicals were generated by the electrochemical oxidation of the trianion. A stepwise radical formation was revealed by a differential pulse voltammogram, electrolytic ESR spectroscopy, and a comproportionation reaction between the radicals, which was discussed as an effect of the pi-conjugated but non-Kekulé-type coupler. The quartet and triplet ground state for the tri- and diradical, respectively, were confirmed by a SQUID measurement.

Journal Article↗
PubMed2001

Renin angiotensin system-dependent hypertrophy as a contributor to heart failure in hypertensive rats: different characteristics from renin angiotensin system-independent hypertrophy.

OBJECTIVES: This study aimed to characterize the difference between renin angiotensin system (RAS)-dependent and RAS-independent hypertrophy and their differential contribution to the transition to heart failure. BACKGROUND: Hypertensive left ventricular (LV) hypertrophy develops with RAS activation in the heart; however, LV hypertrophy develops even without RAS activation. METHODS: Left ventricular geometry and function were assessed in Dahl salt-sensitive rats placed on an 8% NaCl diet from seven weeks old (hypertensive rats) and in those placed on an 0.3% NaCl diet (control rats, n = 8). The hypertensive rats were randomized to no treatment (n = 8) or treatment with the angiotensin type 1 receptor (AT1R) antagonist candesartan (1 mg/kg per day, n = 10) after the baseline echocardiography study. RESULTS: From 7 to 13 weeks, AT1R blockade at a subdepressor dose did not restrain the development of LV hypertrophy but prevented narrowing of LV diastolic dimension, leading to the normalization of abnormally decreased end-systolic wall stress in the untreated rats. Progressive development of LV hypertrophy in spite of lower than normal end-systolic wall stress (excessive hypertrophy) after 13 weeks was suppressed by the AT1R blockade. Elevation of LV end-diastolic pressure and prolongation of Tau were associated with histological evidence of myocyte hypertrophy and massive interstitial fibrosis in the untreated rats, and none of these was evident in the treated rats. CONCLUSIONS: Renin-angiotensin system activation and AT1R signaling may be dispensable for the development of early adaptive LV hypertrophy and closely linked to the transition to heart failure.

Animals↗
PubMed2001

[Mercury concentration of fish in Tokyo Bay and the surrounding sea area].

Total mercury in the muscles of three fish species was analyzed in fish caught in Tokyo Bay and the surrounding sea areas, Sagami Bay and Choshi. Tokyo Bay is a semi-closed sea area surrounded by Tokyo, Kanagawa and Chiba prefectures. Sagami Bay and Choshi are open to the Pacific Ocean. A total of 412 fish consisting of northern whiting (Sillago japonica), flatfish (Limanda yokohamae) and sardine (Sardinops melanosticta) were caught in these areas over a 6 months period from November 1998 to April 1999. Total mercury concentration ranged from 0.008-0.092 microgram/g (wet wt.) in northern whiting, 0.006-0.065 microgram/g in flatfish and 0.001-0.045 microgram/g in sardine. All concentrations were below the restriction limit of fish mercury in Japan, 0.4 microgram/g of total mercury concentration. A significant correlation was found between mercury concentrations and body length or body weight in northern whiting and flatfish, irrespective of the sea area. A correlation was also found between mercury concentration in fish and their feeding habits: among the 3 species caught in the same area, crustacean feeding northern whiting had the highest, polychaete feeding flatfish moderate, and plankton feeding sardine had the lowest mercury concentration. In a comparison of mercury concentration in the same species caught in different sea areas, a higher concentration was noted in fish caught in the semi-closed sea area of Tokyo Bay, than in fish caught in the open sea areas of Sagami Bay and Choshi. This difference was most marked in fish caught at the bottom of Tokyo Bay and we considered that the mercury concentration of seawater and sediment in these areas was the cause of mercury accumulation in fish. These findings suggest that improved water quality control and environmental monitoring is necessary in semi-closed sea areas such as Tokyo Bay.

Animals↗
PubMed2001

Expression of METH-1 and METH-2 in pancreatic cancer.

PURPOSE: METH-1/hADAMTS-1 and METH-2/hADAMTS-8 are recently identified genes that inhibit angiogenesis, and the murine homologue, ADAMTS-1, shows metalloproteinase function. Because the significance of METH-1 and METH-2 has not been determined in solid tumors, we examined the mRNA expressions of these molecules in pancreatic cancer and hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: METH-1 and METH-2 mRNA expressions were identified in six pancreatic cancer cell lines and were quantified by TaqMan reverse transcription-PCR in 18 paired samples of pancreatic cancer and surrounding noncancerous pancreas, and in 14 samples of pancreatic cancer. METH-1 mRNA expression was also examined in 16 pairs of HCC and cirrhotic liver. Vascularity was estimated by CD34 staining. The correlation between clinicopathological factors and METH-1 expression was additionally analyzed. RESULTS: Four of six pancreatic cancer cell lines expressed METH-1, and 1/6 expressed METH-2. METH-1 was substantially expressed in both pancreatic cancer and noncancerous pancreas, but METH-2 was not. METH-1 expression in pancreatic cancer tissue was significantly lower than that in noncancerous pancreas (P = 0.002), and a similar result was obtained between HCC and cirrhotic liver (P = 0.003). METH-1 expression did not show a significant correlation with vascularity in pancreatic cancer or in HCC. However, pancreatic cancer with higher expression of METH-1 showed significantly severe lymph node metastasis or retroperitoneal invasion (P = 0.033 and P = 0.018, respectively) and worse prognosis (P = 0.038). CONCLUSIONS: METH-1, which was initially reported to have a potent antiangiogenic effect, does not seem to be a predominant determinant of tumor vascularity in pancreatic cancer. Rather, METH-1 seems to be involved in progression of pancreatic cancer through local invasion and lymph node metastasis.

ADAM Proteins↗
PubMed2000

Delayed (18)F-fluoro-2-deoxy-D-glucose positron emission tomography scan for differentiation between malignant and benign lesions in the pancreas.

BACKGROUND: Positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG) has been used for the evaluation of various tumors, but accumulation in inflammatory lesions makes it a controversial modality. The aim of this study was to investigate the usefulness of delayed scanning in differentiation between malignant and benign lesions in the pancreas. METHODS: Forty-seven patients with suspected pancreatic carcinoma were studied by FDG-PET. All patients received approximately 370 megabequerels of FDG after a transmission scan, and an emission scan was performed 1 hour and 2 hours later for all patients. A subset of 19 patients was also scanned at 3 hours postinjection. The standardized uptake value (SUV) was determined, and the retention index was calculated by dividing the increase in the SUV between 1 hour and 2 hours postinjection by the SUV at 1 hour postinjection. RESULTS: Of 27 malignant lesions, the SUVs of 22 lesions increased at 2 hours postinjection, whereas the FDG uptake in 17 of 20 benign lesions decreased. The SUVs at 3 hours postinjection were higher than those at 2 hours postinjection in 9 of 14 malignant lesions and in 2 of 5 benign lesions. Malignant lesions showed a higher retention index than benign lesions (mean +/- standard deviation: 12. 36 +/- 13.37 and -7.05 +/- 17.28, respectively; P < 0.0001). Applying an SUV of 2.5 at 1 hour postinjection with the cut-off value for the differentiation between malignant and benign lesions caused one false negative result and seven false positive results, with a diagnostic accuracy of 83.0% (39 of 47 patients). However, combining the retention index with the SUV obtained at 2 hours postinjection provided a higher diagnostic accuracy (91.5%; 43 or 47 patients) than the SUV alone. The false negative rate remained constant when the retention index was taken into account. Images at 3 hours postinjection usually were unhelpful in differentiating further between malignant lesions and benign lesions. CONCLUSIONS: The current data suggest that delayed FDG-PET scanning at 2 hours postinjection may contribute to differentiation between malignant and benign lesions in the pancreas.

Adult↗
PubMed2000

Inhibition of pRb phosphorylation and cell cycle progression by an antennapedia-p16(INK4A) fusion peptide in pancreatic cancer cells.

In this study, we examined whether or not a small peptide derived from p16(INK4A) protein with the antennapedia carrier sequence could inhibit the growth of pancreatic cancer cells through the inhibition of cell cycle progression. Growth inhibition by the p16-derived peptide was observed in a time- and dose-dependent manner in AsPC-1 and BxPC-3 cells (p16-negative and pRb-positive), whereas Saos-2 cells (p16-positive and pRb-negative) showed no inhibitory effect. In AsPC-1 and BxPC-3 cells, the proportion of cells in the G(1) phase markedly increased 48 h after treatment with 20 microM p16-derived peptide. Cell-cycle analysis of Saos-2 cells showed little change during the entire period of treatment. Immunoblot analysis showed inhibition of pRb phosphorylation after treatment of BxPC-3 with 10 microM p16 peptide. Furthermore, the p16 peptide caused a decrease in cyclin A at later times of treatment. These results demonstrate that the p16-derived peptide can inhibit the growth of p16-negative and pRb-positive pancreatic cancer cells by means of G(1) phase cell cycle arrest resulting from the inhibition of pRb phosphorylation. Restoration of p16/pRb tumor-suppressive pathway by re-expression of p16(INK4A) may play a therapeutic role in the treatment of pancreatic cancer.

Amino Acid Sequence↗
PubMed2000

Curative resection of microgastrinomas based on the intraoperative secretin test.

The intravenous secretin injection test (secretin test) has been used for the differential diagnosis of gastrinoma. In this study we report that the intraoperative secretin test (IOS test) is also useful for determining the extent of curability in patients with Zollinger-Ellison syndrome (ZES). Twelve patients with ZES underwent surgical exploration and the IOS test. The results of the IOS test were obtained by rapid radioimmunoassay of the serum gastrin level (IRG) within 60 minutes. The test was diagnosed as negative when the maximum increase of serum IRG was less than 80 pg/ml and also less than 20% of the basal serum IRG level. Three of the twelve patients underwent pancreatoduodenectomy (PD), and two patients underwent distal pancreatectomy. Extirpation of duodenal tumors with dissection of regional lymph nodes was performed in seven patients. In two of the seven patients the IOS test remained positive after extirpation of the duodenal tumors and the dissection of regional lymph nodes. In one patient PD was performed on the basis of the positive results, and the IOS test became negative after PD. In the other patient, two tiny metastatic liver tumors were identified and were resected, but the IOS test did not become negative. We closed the abdomen in 11 patients when we obtained negative results from the IOS test. The results of the IOS test were almost identical to the data obtained by the standard assay postoperatively. The serum IRG levels of all but one patient fell to the normal level, and the secretin test became negative postoperatively. The IOS test is thus useful and indispensable for curative resection of microgastrinomas in patients with ZES.

Adult↗
PubMed2000

Pancreatic lesions in von Hippel-Lindau syndrome: the coexistence of metastatic tumors from renal cell carcinoma and multiple cysts.

Multiple cysts and benign cystadenomas of the pancreas have been documented occasionally in von Hippel-Lindau syndrome (HLS); however, the malignant involvement of the pancreas in HLS is very rare. We report a case of HLS in which metastatic tumors from renal cell carcinoma (RCC) coexisted with multiple cysts in the pancreas. A 22-year-old woman with a history of HLS had undergone a partial resection of the left kidney for RCC 3 years earlier, at which time a solid mass in the pancreatic tail and multiple pancreatic cysts were also incidentally detected by computed tomography. Over the following 3 years, the mass enlarged slightly, thus raising suspicions that it might be a primary neoplasm of the pancreas. She was referred to the Department of Surgery and Surgical Basic Science to undergo surgery. In addition to the tumor in the pancreatic tail, however, further tumors in the pancreatic head were also disclosed by preoperative celiac arteriography and intraoperative palpation and ultrasonography. A distal pancreatectomy was performed, because the enucleation of all the tumors in the pancreatic head was technically impossible and because the patient declined a total pancreatectomy. A histologic examination of the mass in the pancreatic tail revealed metastatic RCC. This case emphasizes that metastatic disease should be included in the differential diagnosis when evaluating the pancreas in a patient with HLS.

Adult↗
PubMed2000

Local neurohumoral regulation in the transition to isolated diastolic heart failure in hypertensive heart disease: absence of AT1 receptor downregulation and 'overdrive' of the endothelin system.

OBJECTIVE: Although isolated diastolic heart failure with preserved left ventricular (LV) systolic function frequently occurs, regulation of local neurohumoral factors in the transition from diastolic dysfunction without signs of heart failure to diastolic failure, a target for therapeutic strategy, remains to be clarified, partly because of a lack of animal models. Our laboratory recently demonstrated that Dahl-Iwai salt-sensitive (Dahl-S) rats fed on a high-salt diet since 7 weeks of age develop hypertension followed by compensated LV hypertrophy at 13 weeks and transition to isolated diastolic heart failure at 19 weeks. METHODS: Gene expression of the components of the renin-angiotensin system, endothelin (ET) system and natriuretic peptide system in the left ventricle was investigated in the transition to isolated diastolic heart failure in this model. RESULTS: The compensated ventricular hypertrophy was associated with slight increases in angiotensin-converting enzyme (ACE) and angiotensin II type-1a (AT1a) receptor mRNA levels. Although preproET-1 (ppET-1) and ET-converting enzyme-1 (ECE-1) mRNA levels were not increased, mRNA levels of ET type-A (ETA) and ET type-B (ETB) receptors were increased. Atrial natriuretic peptide (ANP) mRNA level increased, but not brain natriuretic peptide (BNP) mRNA level. At the decompensated failing stage (at 19 weeks), ACE mRNA level further increased without downregulation of ATla receptor mRNA level. The mRNA levels of ppET-1 and ECE-1 increased with persistent upregulation of mRNA levels of ETA and ETB receptors, and immunohistochemical staining for ET-1 was found at endothelial cells and myocytes. BNP mRNA level increased with a further increase in ANP mRNA level. CONCLUSIONS: The transition to isolated diastolic heart failure in hypertrophied hearts was associated with preserved gene expression of the renin-angiotensin system and 'overdrive' of gene expression of the ET system. BNP gene expression is likely to be activated by the progression of diastolic failure rather than by LV hypertrophy alone.

Analysis of Variance↗