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Daisuke Shimizu

Publications and source records attributed to Daisuke Shimizu.

At least 19 recordsLinked to original sources
PubMed2006

Pulmonary relapse of non-Hodgkin's lymphoma in bilateral upper lobes.

We describe a 68-year-old male patient with diffuse large B-cell lymphoma (DLBCL) who suffered from relapse in bilateral upper lobes of the lung. The patient presented with cough, weakness and fever. A bronchovascular-lymphangitis-like shadow was detected in the bilateral upper lobes on a chest roentgenogram. Although cytological and cytofluorometric examinations revealed no malignant cells in the bronchoalveolar lavage fluid, trans-bronchial lung biopsy (TBLB) showed involvement of DLBCL in the bronchial mucosa. Recurrent lymphoma tends to extend along the bronchovascular bundles, resulting in granulomatous consolidation that may mimic tuberculosis and is likely to involve the lower lobes. Thus, TBLB proved to be essential for the diagnosis of the lung involvement of non-Hodgkin's lymphoma (NHL).

Aged↗
PubMed2006

Functional significance of the microstructural detail of the primate dentino-enamel junction: a possible example of exaptation.

In primate teeth, the dentino-enamel junction (DEJ) exhibits a scalloped appearance, the functional importance of which has been the subject of various suggestions and speculations. Simplified finite-element (FE) models of DEJ microanatomy were created, both in 2D and 3D, and their biomechanical behavior was tested and compared. Consistently, the models with the scalloped DEJ, although having higher maximum tensile stresses than the straight DEJ models, showed discontinuous concentrations of stress. In straight DEJ models, tensile stresses act at the DEJ over continuous areas in a direction, which would push the two tissues apart, thus leading to delamination of the DEJ. Perhaps even more important, in the scallop model, the net-compression towards the DEJ was consistently higher than net-tension away from it. As a consequence, dentine and enamel would be pushed towards each other during loading (i.e., during mastication). These findings suggest that the scalloped nature of the DEJ confers a biomechanical advantage to the integrity of the tooth during mastication. Furthermore, there exists a correlation between pronounced prism decussation and scallop magnitude, suggesting that scallops may have been selected for in response to high bite forces. However, given the equivocal relationship between scallops and presumed bite force across mammalian taxa, we propose that scallops could in fact be exaptations.

Animals↗
PubMed2006

Increasing cyclooxygenase-2 (cox-2) gene expression in the progression of Barrett's esophagus to adenocarcinoma correlates with that of Bcl-2.

Previous studies from our laboratory and others have suggested that increased expression of cox-2 is important in the genesis of esophageal adenocarcinoma. In vitro studies suggest that cox-2 regulates expression of the anti-apoptotic protein bcl-2, thus possibly accounting for reduced apoptosis in carcinogenesis. The aim of this study was to investigate the relationship of these 2 genes in the development of Barrett's-associated adenocarcinoma. Histologic sections from endoscopic biopsies or esophagectomy specimens were classified as non-dysplastic Barrett's (n = 30), intraepithelial neoplasia (n = 12) and adenocarcinoma (n = 48). The desired tissue was isolated by laser capture microdissection and expression levels of cox-2 and bcl-2 were measured by quantitative real-time PCR (Taqman). Gene expression levels were compared to samples of the distal esophageal squamous epithelium (n = 55) and reflux-esophagitis (n = 25), without Barrett's or cancer. Expression of both bcl-2 and cox-2 were increased in non-dysplastic Barrett's (p = 0.0077, p = 0.0037), intraepithelial neoplasia (p = 0.0053, p = 0.0220) and adenocarcinoma (p < 0.0001, p < 0.0001) compared to squamous epithelium or reflux-esophagitis. Furthermore, there is a significant correlation between these two genes, especially in carcinoma (p < 0.0001).

Adenocarcinoma↗
PubMed2006

5-fluorouracil-related gene expression levels in primary colorectal cancer and corresponding liver metastasis.

Gene expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) have been shown to be associated with response to 5-fluorouracil-based therapies. Analyzing these gene expression levels in liver metastases is important to obtain the best prediction of therapy. Our aim was to determine how TS, DPD, TP and OPRT gene expression levels in primary colorectal cancer (CRC) were related to those in liver metastases. Formalin-fixed, paraffin-embedded tumor specimens from 31 pairs of primary CRC and corresponding liver metastases were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse-transcription. Quantitation of target gene and internal reference gene was performed using real-time PCR. No significant difference was seen between median mRNA expression levels of TS, DPD, TP and OPRT in primary cancer and those in corresponding liver metastases (median value: TS 1.48 vs. 1.43; p=0.92, DPD 0.19 vs.0.12; p=0.10, TP 1.20 vs. 0.98; p=0.39, OPRT 1.17 vs. 0.95; p=0.10). When matched tissue sets were compared on an individual basis, there was a significant correlation for TS mRNA expression between primary cancer and corresponding liver metastases (rs=0.52, p=0.0026). However, no correlation was seen between matched sets for DPD, TP or OPRT. Significant correlation was seen between DPD and TP expression levels in both primary CRC (rs=0.38, p=0.03) and liver metastases (rs=0.72, p<0.0001). A good prediction of TS mRNA levels in liver metastases can be obtained by measuring those of primary CRC, although no correlation was seen for DPD, TP and OPRT.

Aged↗
PubMed2006

Predicting 5-fluorouracil chemosensitivity of liver metastases from colorectal cancer using primary tumor specimens: three-gene expression model predicts clinical response.

We identified genes related to 5-fluorouracil (5-FU) sensitivity in colorectal cancer and utilized these genes for predicting the 5-FU sensitivity of liver metastases. Eighty-one candidate genes involved in 5-FU resistance in gastric and colon cancer cell lines were previously identified using a cDNA microarray. In this study, the mRNA expression levels of these 81 selected genes and the genes of 5-FU-related enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT), were measured using real-time quantitative RT-PCR assays of surgically resected materials from primary colorectal tumors in 22 patients. Clinical responses were estimated by evaluating the effects of 5-FU-based hepatic artery injection (HAI) chemotherapy for synchronous liver metastases. Four genes (TNFRSF1B, SLC35F5, NAG-1 and OPRT) had significantly different expression profiles in 5-FU-nonresponding and responding tumors (p < 0.05). A "Response Index" system using three genes (TNFRSF1B, SLC35F5 and OPRT) was then developed using a discriminate analysis; the results were well correlated with the individual chemosensitivities. Among the 11 cases with positive scores in our response index, 9 achieved a reduction in their liver metastases after 5-FU-based chemotherapy, whereas only 1 of the 11 cases with negative scores responded well to chemotherapy. Our "Response Index" system, consisting of TNFRSF1B, SLC35F5 and OPRT, has great potential for predicting the efficacy of 5-FU-based chemotherapy against liver metastases from colorectal cancer.

Aged↗
PubMed2006

Orientational effect of aryl groups on 77Se NMR chemical shifts: experimental and theoretical investigations.

The orientational effect of p-YC6H4 (Ar) on delta(Se) is elucidated for ArSeR, based on experimental and theoretical investigations. The effect is examined in the cases in which Se--CR in ArSeR is either in the Ar plane (pl) or is perpendicular to the plane (pd). 9-(Arylselanyl)anthracenes (1) and 1-(arylselanyl)anthraquionones (2) are employed to establish the effect in pl and pd, respectively. Large upfield shifts are observed for Y=NMe2, OMe, and Me, and large downfield shifts for Y=COOEt, CN, and NO2 in 1, relative to Y=H, as is expected. Large upfield shifts are brought by Y=NMe2, OMe, Me, F, Cl, and Br, and downfield shifts by Y=CN and NO2 in 2, relative to Y=H, with a negligible shift by Y=COOEt. Absolute magnetic shielding tensors of Se (sigma(Se)) are calculated for ArSeR (R=H, Me, and Ph), assuming pl and pd, based on the DFT-GIAO method. Observed characters are well explained by the total sigma(Se). Paramagnetic terms (sigmap(Se)) are governed by (sigmap(Se)xx+sigmap(Se)yy), in which the direction of np(Se) (constructed by 4pz(Se)) is set to the z axis. The main interaction in pl is the np(Se)-pi(C6H4)-pz(Y) type. The Y dependence in pl occurs through admixtures of 4pz(Se) in pi(SeC6H4Y) and pi*(SeC6H4Y), modified by the conjugation, with 4px(Se) and 4py(Se) in sigma(CSeX) and sigma*(CSeX) (X=H or C) under a magnetic field. The main interaction in pd is the sigma(CSeX)-pi(C6H4)-px(Y) type, in which Se-X is nearly on the x axis. The Y dependence in pd mainly arises from admixtures of 4pz(Se) in np(Se) with 4px(Se) and 4py(Se) in modified sigma*(CSeX), since np(Se) is filled with electrons. It is demonstrated that the effect of Y on sigmap(Se) in the pl conformation is the same regardless of whether Y is an electron-donor or electron-acceptor, whereas for pd conformations the effect is greater when Y is an electron donor, as observed in 1 and 2, respectively. Contributions of each molecular orbital and each transition on sigmap(Se) are evaluated, which enables us to recognize and visualize the effect clearly.

Journal Article↗
PubMed2006

Vascular endothelial growth factor messenger RNA expression level is preserved in liver metastases compared with corresponding primary colorectal cancer.

PURPOSE: Increased vascular endothelial growth factor (VEGF) expression is associated with colorectal cancer liver metastases. It is reasonable to expect that measurement of VEGF in liver metastases would provide the best prediction of therapy benefit for VEGF-targeted drugs, such as bevacizumab (Avastin). In this study, we evaluated how VEGF mRNA level in primary colorectal cancer was related to that in corresponding liver metastases. Thirty-one pairs of primary colorectal cancer and corresponding liver metastases were analyzed. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tumor specimens were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse transcription. Quantitation of VEGF and internal reference gene (beta-actin) was done using real-time PCR (Taqman PCR). RESULTS: There was no difference between median VEGF mRNA levels of primary colorectal cancer and liver metastases (median value 3.79 versus 3.97: P = 0.989). On an individual basis, there was a significant correlation in VEGF mRNA expression between primary colorectal cancer and corresponding liver metastases (r(s) = 0.6627, P < 0.0001). In addition, the VEGF mRNA levels of the patients who had two or more liver metastatic tumors were significantly higher than those of the patient who had solitary liver metastatic tumor in both primary cancer (5.02 versus 3.34: P = 0.0483) and liver metastases (4.38 versus 3.25: P = 0.0358). CONCLUSION: Good prediction of VEGF mRNA levels in liver metastases can be obtained by measuring those of primary colorectal cancer. The risk of multiple liver metastatic tumors might be predictable by measuring VEGF mRNA expression in primary colorectal cancer. Further study is required to confirm these preliminary results.

Aged↗
PubMed2006

Molecular determinants in targeted therapy for esophageal adenocarcinoma.

HYPOTHESIS: Cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) are useful biological determinants in targeted therapy for esophageal adenocarcinoma. DESIGN: Prospective analysis. SETTING: University tertiary referral center. PATIENTS: Sixteen patients with squamous mucosa and normal results of a pH study without mucosal injury (control group), 15 with Barrett esophagus (metaplasia group), and 44 with adenocarcinoma (carcinoma group). INTERVENTIONS: Biopsy specimens were obtained 3 cm above the gastroesophageal junction. Dysplastic tissue was additionally isolated from 9 of the patients in the carcinoma group. After laser-capture microdissection, quantitative real-time polymerase chain reaction was used to measure gene expression across the spectrum of the metaplasia-dysplasia-carcinoma sequence. MAIN OUTCOME MEASURES: Expression of COX-2, VEGF, and EGFR in each patient group. RESULTS: Expression of both COX-2 and VEGF was significantly up-regulated in patients with metaplasia, dysplasia, and cancer compared with controls (P<.01). Expression levels of both were significantly higher in cancer than in the metaplasia group (P<.05) and increased sequentially from metaplasia to dysplasia to cancer. Expression of VEGF was significantly higher in the dysplastic tissue than in nondysplastic Barrett epithelium (P<.05). No change in expression levels of EGFR was seen in the histologic progression to esophageal adenocarcinoma. CONCLUSION: Gene expression data suggest that pharmacologic inhibition of COX-2 and VEGF may be useful adjuncts in targeted therapy for esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Antireflux surgery normalizes cyclooxygenase-2 expression in squamous epithelium of the distal esophagus.

BACKGROUND: In some patients GERD presents with heartburn and regurgitation symptoms but a relative paucity of endoscopic and clinical findings, while in others symptoms may be minor or absent yet there is significant mucosal damage on endoscopy including the presence of Barrett's esophagus. The initial injury of gastroesophageal reflux is to the squamous esophageal mucosa, but while substantial research has been devoted to determining which genes are involved in the progression of Barrett's to dysplasia and cancer, little is known about the gene expression alterations in the squamous mucosa of patients with reflux. We hypothesized that the expression of cyclooxygenase-2 (Cox-2) might be increased in the squamous esophageal mucosal of patients with reflux, and might be a molecular indicator of reflux injury. Further, we hypothesized that Cox-2 expression in the squamous mucosa would be reduced following the elimination of reflux with an antireflux operation. METHODS: Biopsies of the distal esophageal squamous mucosa were taken 3 cm above the squamocolumnar junction (SCJ) in 28 GERD patients before and after Nissen fundoplication. Following microdissection and RNA isolation, quantitative real-time PCR was used to measure Cox-2 gene expression in paraffin-embedded (N = 16) and fresh frozen (N = 12) tissue. Biopsies from patients (paraffin N = 15, frozen N = 14) with normal acid exposure and no evidence of mucosal injury were analyzed as controls. RESULTS: Median Cox-2 expression in the squamous epithelium from paraffin embedded biopsies in patients with reflux disease was significantly increased compared to controls (p = 0.04). The presence of esophagitis or Barrett's esophagus did not significantly alter the expression of Cox-2 compared to patients with nonerosive reflux disease (NERD). After antireflux surgery median Cox-2 expression values were significantly reduced (p = 0.0003) and were normalized to levels similar to controls without reflux (p = 0.74). Similar results were observed in the prospectively obtained fresh frozen tissue. CONCLUSIONS: Cox-2 gene expression is increased in the distal esophageal squamous mucosa of most patients with GERD, and the elevation was similar whether there was mucosal injury in the form of esophagitis or Barrett's or no visible mucosal injury. This suggests that increased Cox-2 expression may serve as a molecular marker of reflux disease. The increased Cox-2 expression in patients with reflux was usually normalized following antireflux surgery. These findings demonstrate for the first time that gene expression can be altered by surgical correction of reflux. Thus, in addition to symptom control and improvement in the quality of life, perhaps future studies assessing the efficacy of antireflux therapy should also focus on the impact of the therapy on gene expression in the esophageal squamous mucosa.

Adult↗
PubMed2006

[Two cases of malignant lymphoma with high fever and C-reactive protein (CRP) elevation after treatment with granulocyte colony-stimulating factor (G-CSF)].

We present two cases of malignant lymphoma that developed a high fever that eventually reached an extremely high 38.9 degrees C. The C-reactive protein( CRP) elevation also climbed to a very high 12.2 mg/dl after treatment with granulocyte colony-stimulating factor (G-CSF). In the one case, after stem cells were mobilized with CHASER therapy (cyclophosphamide, cytarabine, etoposide, dexamethasone and rituximab) followed by G-CSF (filgrastim 600 microg/day) subcutaneous daily, the serum CRP level rose to a maximum of 5.6 mg/dl, with a maximum fever elevation of 38.9 degrees C. In the other case, after the subject was given CHASE therapy followed by subcutaneous treatment with G-CSF (filgrastim 75 microg/day) daily, the maximum serum CRP level was 12.2 mg/dl along with a maximum fever of 38.9 degrees C. Although no infection was found in either case, multiple antibacterial agents were ineffective;after discontinuation of G-CSF, fever dissipated and the serum CRP level became negative. G-CSF induces the proliferation and differentiation of neutrophils and also causes the mobilization of mature neutrophils from hematopoietic tissues. With the increasing propensity to G-CSF, we must keep in mind the possibility of such adverse reactions so as to serve the overall best interests of the patient.

Adult↗
PubMed2005

Unusual carbon-sulfur bond cleavage in the reaction of a new type of bulky hexathioether with a zerovalent palladium complex.

The reaction of a bulky hexathioether, TbtS(o-Phen)S(o-Phen)SS(o-Phen)S(o-Phen)STbt (o-Phen = o-phenylene, Tbt = 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl) (1), with 3 molar amounts of Pd(PPh3)4 afforded trinuclear palladium complex bridged by two benzenedithiolato ligands via a three-step palladium insertion reaction into one sulfur-sulfur and two carbon-sulfur bonds of 1.

Carbon↗
PubMed2005

Synthesis and structure of a distorted octahedral palladium(II) complex coordinated with a tetrathioether ligand tethered with bulky substituents.

A new type of an o-phenylene-bridged tetrathioether ligand tethered with extremely bulky substituents, 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl (Tbt) groups, at its terminal sulfur atoms, TbtS[(o-phenylene)S]3Tbt (1), was synthesized by taking advantage of the coupling reaction of thiols with iodobenzenes using Cu2O in 2,4,6-trimethylpyridine. Complexation of 1 with Na2PdCl4 gave the corresponding dichloropalladium(II) complex, [PdCl2(1)] (7). The X-ray structural analysis of 7 indicated that the central palladium metal is in a distorted octahedral environment, where the two inner sulfur atoms of 1 and the two chlorine atoms form a square planar arrangement around the palladium metal and the two terminal sulfur atoms of 1 weakly coordinate to the palladium center at the axial positions. In addition, a phenyl analogue of 1, PhS[(o-phenylene)S]3Ph (2), was synthesized by a method similar to that for 1. Reaction of 2 with Na2PdCl4 gave the corresponding dichloropalladium(II) complex, [PdCl2(2)] (8). X-ray crystallography of 8 showed a type of the structure different from the distorted octahedral structure in 7, i.e., a square planar arrangement around the central palladium atom with the one terminal sulfur atom of 2, its neighboring sulfur atom, and the two chlorine atoms. The results of the NMR studies on 8 in a CDCl3 solution were not consistent with the results of the X-ray crystallography and suggested the coordination of the two inner sulfur atoms of 2 to the palladium metal, although a possibility of the existence of the rapid interconversion among isomers could not be excluded.

Journal Article↗
PubMed2005

Successful endoscopic hemostasis for gastric arterial bleeding due to invasion of malignant lymphoma.

A 75-year-old male with malignant lymphoma (ML) accompanied with gastric lesion was treated with combination chemotherapy. The patient produced tarry stool on the 4th d, and emergency gastroscopy showed arterial bleeding from the lesion. Hemostasis was achieved by injecting pure ethanol and using hemostatic clips. There is only one previous report on endoscopic hemostasis being effective for bleeding due to lymphoma. Since gastric bleeding causes significant mortality, endoscopic hemostasis should be considered as first-line treatment for ML patients who were treated with chemotherapy.

Aged↗
PubMed2005

Pseudomembranous colitis presenting as acute colonic obstruction without diarrhea in a patient with gastric Burkitt lymphoma.

Pseudomembranous colitis (PMC) usually manifests as fever and diarrhea in hospitalized patients treated with systemic antibiotics. We described a case of PMC with intestinal obstruction but without diarrhea. A 60-year-old man was hospitalized for chemotherapy for the treatment of Burkitt lymphoma of the stomach. The patient became febrile and complained of crampy abdominal pain during the post-chemotherapy nadir. Plain abdominal radiography showed some intestinal gas and niveau. Because stool cytotoxin assay for clostridium difficile was positive and colon fiberscopic examination showed a pseudomembrane at the left side of the colon, and a diagnosis of PMC was made. Treatment with intracolonic vancomycin administration by colonoscopy and nasoileus tube was successful. Physicians should take into account the possibility of bowel obstruction due to PMC occurring in patients undergoing chemotherapy and perform emergency colonoscopy examination of suspected cases.

Acute Disease↗
PubMed2005

An additional segment at 1p36 derived from der(18)t(14;18) in patients with diffuse large B-cell lymphomas transformed from follicular lymphoma.

The particular translocation in follicular lymphomas (FLs) is a t(14;18)(q32;q21), recombining the immunoglobulin heavy chain (IgH) gene on chromosome 14 with the B-cell leukemia/lymphoma 2 (BCL2) gene on chromosome 18. Some low-grade FLs are aggressively transformed into diffuse large B-cell lymphomas, presumably by acquisition of secondary chromosomal changes, including chromosomal band 1p36. A common example is add(1)(p36). Because it is difficult to identify the origin of add(1)(p36) even on high-resolution G-banding analysis, we used spectral karyotyping (SKY) and double-color fluorescence in situ hybridization (DC-FISH) to define the t(14;18) and the extra band at 1p36 in two cases of diffuse large B-cell lymphoma (DLBCL). SKY revealed that the extra chromosomal segment on 1p36 was derived from chromosome 18. DC-FISH defined BCL2/IgH fusion signals at 1p36 in addition to t(14;18), suggesting that BCL2/IgH fusion at 1p36 was an evolutionary alteration following the primary BCL2/IgH translocation on der(18) in both cases. Our results indicate that IgH alleles, implicated in chromosomal rearrangement, may themselves frequently be targets for secondary translocations, suggesting that multiple IgH translocations and insertions are associated with the progression of FL.

Chromosome Banding↗
PubMed2005

Effect of prism orientation and loading direction on contact stresses in prismatic enamel of primates: implications for interpreting wear patterns.

The ability of prisms to effectively dissipate contact stress at the surface will influence wear rates in teeth. The aim of this investigation was to begin to quantify the effect of prism orientation on surface stresses. Seven finite element models of enamel microstructure were created, each model differing in the angulation of prism orientation with regard to the wear surface. For validation purposes, the mechanical behavior of the model was compared with published experimental data. In order to test the enamel under lateral loads, a compressed food particle was dragged across the surface from the dentino-enamel junction (DEJ) towards the outer enamel surface (OES). Under these conditions, tensile stresses in the enamel model increased with increases in the coefficient of friction. More importantly, stresses were found to be lowest in models in which the prisms approach the surface at lower angles (i.e., more obliquely cut prisms), and highest when the prisms approached the surface at 60 degrees (i.e., less obliquely cut). Finally, the direction of travel of the simulated food particle was reversed, allowing comparison of the difference in behavior between trailing and leading edge enamels (i.e., when the food particle was dragged either towards or away from the DEJ). Stresses at the trailing edge were usually lower than stresses at the leading edge. Taken together with what is known about prism orientation in primate teeth, such findings imply greater wear resistance at the intercuspal region and less wear resistance at the lateral enamel at midcrown. Such findings appear to be supported by archeological evidence.

Animals↗
PubMed2005

Australopithecus anamensis: a finite-element approach to studying the functional adaptations of extinct hominins.

Australopithecus anamensis is the stem species of all later hominins and exhibits the suite of characters traditionally associated with hominins, i.e., bipedal locomotion when on the ground, canine reduction, and thick-enameled teeth. The functional consequences of its thick enamel are, however, unclear. Without appropriate structural reinforcement, these thick-enameled teeth may be prone to failure. This article investigates the mechanical behavior of A. anamensis enamel and represents the first in a series that will attempt to determine the functional adaptations of hominin teeth. First, the microstructural arrangement of enamel prisms in A. anamensis teeth was reconstructed using recently developed software and was compared with that of extant hominoids. Second, a finite-element model of a block of enamel containing one cycle of prism deviation was reconstructed for Homo, Pan, Gorilla, and A. anamensis and the behavior of these tissues under compressive stress was determined. Despite similarities in enamel microstructure between A. anamensis and the African great apes, the structural arrangement of prismatic enamel in A. anamensis appears to be more effective in load dissipation under these compressive loads. The findings may imply that this hominin species was well adapted to puncture crushing and are in some respects contrary to expectations based on macromorphology of teeth. Taking together, information obtained from both finite-element analyses and dental macroanatomy leads us to suggest that A. anamensis was probably adapted for habitually consuming a hard-tough diet. However, additional tests are needed to understand the functional adaptations of A. anamensis teeth fully.

Adaptation, Physiological↗