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T Hirose

Publications and source records attributed to T Hirose.

At least 271 records · Page 15Linked to original sources

[A case report of dysembryoplastic neuroepithelial tumor associated with neurofibromatosis type 1].

Dysembryoplastic neuroepithelial tumor (DNT) in a newly proposed mixed neuroglial tumor in the cerebral cortex. However, DNT associated with phacomatosis has mostly been considered exceptional. In this paper, a case of DNT associated with neurofibromatosis type 1 is reported. A 23-year-old male was admitted to our hospital complaining of intractable complex-partial seizure. He had a history of neurofibromatosis type 1 (NF - 1) and pituitary dwarfism. On general physiological examination, many cafe au lait spots and freckling could be noted, showing that the case was neurofibromatosis type 1. In addition, neurological examination showed no abnormal findings. MR images revealed a small area of abnormal intensity on the right temporal. This region showed high intensity on T2 weighted image and low intensity without enhancement on T1 weighted image. On electroencephalography (EEG), an epileptic spike focus was demonstrated in the right temporal lobe. So, lobectomy was performed for control of epilepsy. Postoperative course was uneventful and without seizure. On histological examination, the tumor was composed of three different components : specific glioneural element, foci of oligodendrocyte-like cell, and cortical dysplasia. All of these findings were consistent with the definition of DNT by Daumas-Duport et al, except for the association with NF - 1. Although reported cases of DNT associated with FN - 1 are exceptionally rare, both DNT and NF - 1 originate from maldevelopment of the fetal central nervous system. It is very interesting that our case indicated the possibility of co-existence of both diseases.

Adult↗

[Present status and future on automated PCR testing for microorganisms].

PCR is a continually evolving technology. In the years since in inception, there have been many improvements made to the assay, and also to the automation. Some of the early developmental highlights in PCR are listed as follows; 1) The amplification process was automated with the introduction of thermocyclers. 2) False-positive results from carryover of amplification products have been largely eliminated by the incorporation of dUTP into amplification reactions and the subsequent restriction of dU-containing amplicons with UNG (AmpErase). 3) A combined RT-PCR assay for the amplification of RNA that utilizes a single thermoactive enzyme (Tth DNA polymerase) was recently developed. This assay eliminates the need to change buffer/enzymes between the RT and PCR steps. 4) The methods for detecting amplicons has been made simpler and faster. The use of radioactivity and electrophoresis have been eliminated. The development of microwell plate assays provides users with a familiar format (similar to EIAs) and makes use of reagents that are readily available. Based on the above developments and clinical requirements, the developments of the automated PCR testing are progressed. The recent introduction of the COBAS AMPLICOR represents a major advance in PCR instrumentation. With the COBAS AMPLICORE, both the amplification and detection process are automated. This greatly reduces the hand-on time required to carry out PCR assays and further improves assay reproducibility. Further developments for full automation are on going, i.e., kinetic PCR, 5' exonuclease assay, etc.

Automation↗

[Home oxygen therapy (HOT) in patients with pulmonary tuberculosis sequelae--comparison between patients medically treated and those surgically treated].

In Japan there are about 40,000 patients under home oxygen therapy (HOT), of whom about 30 to 40% are pulmonary tuberculosis sequelae (TBS). These patients can be divided into three groups depending on the treatments they had, Group 1: those who had medical treatments only, Group 2: those who had artificial pneumothorax, and Group 3: those who had thoracoplasties or other surgical treatments. The purpose of this study was to observe the distributions and possible differences in the survival rates among these groups. The study included 1537 patients with TBS under HOT followed at National Hospitals and Sanatoriums nationwide in Japan. In 819 patients the treatments were specified and of those 354 were in Group 1, 29 in Group 2, and 436 in Group 3, so that the proportion of surgically treated patients in PTS was estimated between 28.4% (436/ 1537) to 53.2% (436/819). The ages at the onset of tuberculosis, at the start of HOT and the intervals in between were 36.6, 66.2 and 29.8 in Group 1, and 26.8, 65.5, and 38.1 in Group 3 respectively. Though the ages at the start of HOT were the same, those at the onset of tuberculosis were about ten years younger in Group 3 than in Group 1. Comparing Group 1 and 3, the survival rates after the initiation of HOT (Kaplan-Meier method) was better in Group 2 (surgically treated) than in Group 1 (medically treated). It is speculated that the reason could be a better preservation of the function of the remaining lung in the surgically treated and a higher incidence of obstructive impairments in the medically treated patients.

Adolescent↗

[Diagnosis of pleural dissemination lung cancer by thin-section CT--a prospective study].

In this prospective study, thin-section CT was used to diagnose pleural dissemination in patients with pulmonary adenocarcinomas in which the primary lesion was found to be adjacent to the pleural surface by conventional CT. The subjects were 32 patients (25) who had undergone resection and 7 who had not with pulmonary adenocarcinoma without pleural effusion from among the 136 patients with pulmonary adenocarcinoma examined at our institution over 3 years. Thin-section CT images of three regions were obtained, and these included the pleural surface adjacent to the lesion, the minor fissure, and the diaphragmatic dome. Histopathological examination revealed pleural dissemination in 12 patients (5 who had undergone resection and who had not), in 2 of whom a diagnosis could not be made preoperatively. Pleural dissemination was diagnosed by CT in 12 patients; there were 2 false positives. In 6 patients who did not undergo resection, cancerous cells were found in fluid obtained by percutaneous pleural lavage, and mediastinal lymph node metastases or distant metastases were also detected. The diagnostic rate of CT was as follows interlobar space. 100% (7/7); mediastinum, 75% (3/4); diaphragm, 71% (5/7); and chest wall, 57% (4/7). In the patients who underwent resection, sensitivity was 100% for the interlobar space, but it was 0% to 33% for other pleural surfaces.

Adenocarcinoma↗

[Evaluation of ultrasound hyperthermia system with a phantom model].

Ultrasound (US) hyperthermia is a local heating method that has recently been introduced into clinical practice. A prototype and modified version of this system using a phantom model (agar with bone inserted) were evaluated. The prototype system consists of a power delivery unit (0.5 MHz frequency) with a circulating cooled water bolus. This system heats a shallow area irrespective of power output, but has a tendency to overheat the phantom surface. We incorporated three modifications into the prototype. The modified type has three frequency applicators (0.5, 1.0, 1.5MHz) and a secondary bolus. Aluminum-urethane shields were used to cover the phantom surface located over bone preventing overheating of bone. By changing the applicator's US frequency, we could change the depth of the heating area. Overheating of the phantom surface and bone thus was avoided. These results suggest that our modified US hyperthermia system with multiple frequency applicators, a secondary bolus and aluminum-urethane shields provided a good heating pattern.

Hyperthermia, Induced↗

[Clinical evaluation of ultrasound hyperthermia system].

We studied clinically ultrasound (US) hyperthermia system developed in Japan. The prototype system consists of a power delivery unit (0.5MHz frequency) and a coolded water bolus. The modified type has three frequency applicators (0.5, 1.0, 1.5MHz) with a secondary bolus. Thirty-four patients with recurrent or metastatic tumors located in the shallow tissues were treated. Fourteen patients (Group I) were treated with the prototype system and 20 patients (Group II) with the modified type. In 13 of the Group II patients, aluminum-urethane shields were used to protect nearby bone from overheating. The heating goal was 42.0 degrees C for at least 30 minutes in the tumor's center. The temperature was raised to 42.0 degrees C in 7 of 14 cases (50%) and in 17 of 41 sessions (41.5%) in Group I. In Group II the temperature was raised in 19 of 20 cases (95.0%) and in 67 of 80 sessions (83.7%). Response rates were 50.0% and 75.0% respectively in Groups I and II. The incidence of side effects including burn and ostalgia were 100% and 20% respectively in Groups I and II. These results suggest that the modified US hyperthermia system was valuable in clinical use.

Aged↗

Cloning of the gene encoding the murine orphan receptor TAK1 and cell-type-specific expression in testis.

We have cloned the gene encoding the mouse homologue of the orphan receptor, TAK1, a member of the nuclear receptor superfamily, from a mouse testis cDNA library. The amino acid sequence of mouse TAK1 (mTAK1) is highly homologous to that of human TAK1, with an overall identity of 98%. Northern blot analysis using RNA from different testicular cell types showed that the mTAK1 transcript is predominantly expressed in pachytene spermatocytes at a low level in round spermatids, but not in germ cells at earlier phases of spermatogenesis or in Sertoli cells. Southern analysis using genomic DNA prepared from a panel of hamster/human and mouse/human hybrid cell lines indicated that the TAK1 gene is located on human chromosome 3.

Amino Acid Sequence↗

Prognostic implication of the p53 protein and Ki-67 antigen immunohistochemistry in malignant fibrous histiocytoma.

BACKGROUND: Mounting evidence indicates that p53 regulates cell growth and abnormal p53 immunophenotypic expression is associated with an unfavorable prognosis for patients with some types of carcinoma. The prognostic significance of p53 overexpression in malignant fibrous histiocytomas (MFHs) of soft tissue has not yet been elucidated. METHODS: Expressions of p53 protein and Ki-67 antigen in 54 primary MFHs of soft tissue were investigated immunohistochemically and indexed quantitatively by counting the number of immunoreactive nuclei versus the total neoplastic nuclei in the representative fields of each tumor to evaluate their prognostic implications and interrelations with other clinicopathologic parameters. RESULTS: The percentages (labeling indices [LIs]) of p53 and Ki-67-immunoreactive nuclei versus the total neoplastic nuclei were 0.1-93.2% (mean +/- standard deviation [SD], 40.6% +/- 21.8%) and 5.3-90.8% (mean +/- SD, 42.7% +/- 29.4%), respectively. The Ki-67 LI correlated with histologic grade (P = 0.01498), primary tumor size (P = 0.04985), disease free interval (reverse correlation, P = 0.00776), and recurrence and metastasis (P = 0.00360). The p53 LI correlated with primary tumor size (P = 0.00431) but did not show any significant correlation with histologic grade, Ki-67 LI, primary tumor size, disease free interval, or recurrence and metastasis. Other significant correlations included histologic grade and disease free interval (P = 0.00010), primary tumor size and disease free interval (reverse correlation, P = 0.00869), histologic grade and recurrence (P = 0.02714), and primary tumor size and primary tumor location (P = 0.00028). In the grouped survival analysis, patients with recurrence or metastasis or with tumors of larger size (> or = 7 cm), high histologic grade, or higher Ki-67 LI (> or = 25%) had a significantly reduced survival (P < 0.05). The different p53 immunohistochemical expression and the different histologic types did not reflect different cumulative survival (P > 0.05). Regression analysis revealed that the primary tumor size and histologic grade, but not Ki-67 or p53 LIs, were independent statistical variables for prognostication. CONCLUSIONS: These results indicate that (1) primary tumor size and histologic grade are two important prognostic factors, (2) Ki-67 LI should be used in adjunct with other main prognostic factors for patients with MFHs, and (3) nuclear p53 overexpression in MFHs of soft tissue is a comparatively common event that has no prognostic implication.

Adult↗

Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study.

BACKGROUND: Olfactory neuroblastoma is an uncommon neuroectodermal tumor of the upper nasal cavity, microscopic features of which are not always homogeneous. No morphologic features have been found to correlate reliably with prognosis. METHODS: Twenty-six olfactory neuroblastomas occurring in 14 females and 12 males, ages 18-78 years, were studied by immunohistochemistry, electron microscopy, and DNA flow cytometry. Survival rates were statistically analyzed relative to several variables. RESULTS: Microscopically, 22 tumors formed a morphologic spectrum intermediate between paraganglioma (PG) and neuroblastoma (NB). Others included two ganglioneuroblastomas (GNB), one lesion exhibited biphasic (neuronal and epithelial) differentiation, and one tumor showed predominantly epithelial features. Immunoreactivity for neuronal and neuroendocrine markers included synaptophysin in 77%, neurofilament protein in 38%, class III beta-tubulin in 81%, and chromogranin A in 77%. In 88% of cases, elongated S-100 protein-positive cells surrounded tumor lobules. Cytokeratin and epithelial membrane antigen immunoreactivity were noted in six (23%) and two (8%) tumors, respectively. Aberrant p53 expression was detected in 16 tumors (62%). The Ki-67 labeling index (LI) varied from 0%-43.8% (mean, 7.4%). Ultrastructurally, 80-230 nm dense core granules were noted within perikarya and as in microtubule-containing processes in all of the 11 tumors studied by electromicroscopy. Lobules of seven tumors were surrounded by electron-dense sustentacular cells. Epithelial tumors exhibited obviously epithelial features in addition to neuronal differentiation. DNA flow cytometry demonstrated a high incidence of polyploidy and aneuploidy (78%) and a wide range of percent S phase fractions (1.5%-21.8%; mean, 9.0%). The study showed that longer survival rates are related significantly to (1) the occurrence of metastases which was linked to tumor subtype, (2) to a higher incidence of S-100 protein-positive cells, and (3) to a low (< 10%) Ki-67 labeling index. CONCLUSIONS: The present study indicates that (1) although typical olfactory neuroblastomas exhibit PG/NB differentiation, they more closely resemble PG, (2) occasional tumors show GNB and/or epithelial differentiation, and (3) survival rates may correlate with S-100 protein immunoreactivity and Ki-67 LI. Cancer 1995; 76:4-19.

Adult↗

The orphan receptor TAK1 acts as a repressor of RAR-, RXR- and T3R-mediated signaling pathways.

Recently, we reported the cloning and characterization of the novel orphan receptor TAK1. In this study, we analyze the interaction of TAK1 with a variety of response elements (RE's) and demonstrate that TAK1 binds effectively to RE's composed of the core motif PuGGTCA configured in direct repeats spaced by one or more nucleotides. TAK1 bound poorly to palindromic or inverted palindromic motifs and was unable to bind to a single core motif, suggesting that a dimeric site is required for binding. Transfection experiments with CV-1 cells revealed that TAK1 is able to repress retinoid- and thyroid-hormone-induced transactivation through a subset of retinoid and thyroid hormone RE's. Our studies indicate that the antagonism of RAR-mediated transactivation does not involve the formation of heterodimers between TAK1 and RAR or RXR but is due to the competition of TAK1 homodimers with RAR-RXR heterodimers and RXR homodimers for binding to RARE and RXRE, respectively. Our results suggest that the orphan receptor TAK1 can be a negative modulator of the regulation of gene expression mediated by retinoid and thyroid hormone signaling pathways.

Animals↗

Direct cellular communications between CD45R0 and CD45RA T cell subsets via CD27/CD70.

The engagement of CD27 with its ligand CD70 is considered to play an important role in T cell costimulation. In the present study, we investigated both the kinetics of CD70 expression and the contribution of its interaction with CD27 in T cell immune responses. CD70 was found to be expressed almost equally on both activated CD4 and CD8 T cells. On subsets of CD4 T cells, however, CD70 expression was induced preferentially on the CD45R0 T cell population after activation, whereas its expression was not noted on CD45RA T cells for almost 2 wk following activation. In long-term culture with media containing T cell growth factor (TCGF) and rIL-2, the expression of CD70 was increased markedly on CD45R0 T cells and minimally expressed on CD45RA T cells. In addition, strong surface expression of CD70 was observed on T cell clones originally derived from CD45R0+ CD4 T cells, whereas T cell clones originally derived from CD45RA+ CD4 T cells showed lower levels of expression. The addition of irradiated, activated CD45R0 T cells to CD45RA T cells caused a down-regulation of CD27 expression and an up-regulation of CD25 expression. These changes were blocked by addition of the anti-CD70 mAb, suggesting that direct contact between CD45R0 T cells and CD45RA T cells via CD27/CD70 occurred, leading to the activation of CD45RA T cells as measured by CD25 expression. These observations strongly support the notion that the engagement of CD27 plays an important regulatory role in the communication of subsets of CD45R0 and CD45RA T cells.

Antigens, CD↗

Role of Thr-252 in cytochrome P450cam: a study with unnatural amino acid mutagenesis.

Replacement of Thr-252 in the active center of cytochrome P450cam with a non-hydroxy amino acid residue such as Ala and Val by conventional site-directed mutagenesis converted this monooxygenase to an NADH oxidase (Imai, M. et al. Proc. Natl. Sci. U. S. A. 86, 7823-7827, 1989). In this study, a mutant enzyme with a methoxy group in place of the hydroxy group of Thr-252 (OMe-mutant) was synthesized by the method of unnatural amino acid mutagenesis (Noren, C. J. et al., Science 244, 182-188, 1989). Unlike other site-directed mutants without a hydroxy group at the position, the OMe-mutant retained a considerably high monooxygenase activity, yielding a stoichiometric amount of 5-exo-hydroxycamphor to that of the oxygen consumed. Thus a free hydroxy group at this position is not an indispensable requisite for the monooxygenase to cleave the O-O bond of molecular O2 as previously proposed.

Alanine↗

Cellular schwannoma. A clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 patients.

BACKGROUND: A clinicopathologic study of 70 cases of cellular schwannoma was performed to assess their distribution, response to therapy, and rate of recurrence relative to modern prognostic indicators. METHODS: Seventy-one cellular schwannomas from 70 patients were retrieved from the files of the Mayo Clinic Tissue Registry. The significance of mitotic index, proliferative marker staining (proliferating cell nuclear antigen and MIB1), immunochemical p53 expression, and DNA ploidy were assessed relative to tumor behavior, particularly recurrence. All parameters were subject to statistical analysis (Student's t test). RESULTS: Cellular schwannomas represented 4.6% of benign peripheral nerve tumors operated on at the Mayo Clinic. In 15% of the cases, an initial diagnosis of malignancy had been made. The median patient age was 47.7 years (range, 15-80 years) and the female-to-male ratio was 1.6:1. The principle tumor locations were the para- and intraspinal regions, including the sacrum (64%), extremities (25%), and intracranial space (8%). All tumors consisted primarily of hypercellular, compact, Antoni A tissue. Mitoses (< or = 4/10 hPF]) were observed in 71% of the cases. Foci of necrosis were noted in 11% of cases. Ultrastructural studies and immunohistochemistry clearly demonstrated features of schwannian differentiation. Surgery was the treatment in all cases. Excision was intralesional to gross total in the majority; total resection with wide margins was undertaken in three tumors, each of which had initially been considered malignant. Follow-up in 47 patients (67%) ranged from 1 to 29 years (mean, 7.7 years) and revealed recurrences in 11 patients (23.4%): no patient experienced metastasis or died of tumor. Although no correlation existed between recurrence and DNA ploidy, percent S-phase determinations, proliferation marker (PCNA, MIB1) staining, or the frequency of p53 immunoreactivity, a statistically significant correlation (P < 0.001) was observed, however, between recurrence and mitotic indices. CONCLUSION: Proliferation indices, as defined by immunochemical analysis, are not useful predictors of recurrence in cellular schwannoma. In lesions not completely resected, tumor recurrence is significantly correlated with mitotic count. The significant overall frequency of recurrence in this series is attributable to a high proportion of intraspinal and intracranial tumors. Our study confirms the benign nature of cellular schwannoma and underscores the necessity of distinguishing them from malignant peripheral nerve sheath tumors, lesions that often require adjuvant therapy.

Adolescent↗

RTR: a new member of the nuclear receptor superfamily that is highly expressed in murine testis.

We have identified and cloned a novel member of the nuclear receptor superfamily from murine testis, referred to as retinoid receptor-related testis-associated receptor or RTR. Degenerate PCR primers homologous to two conserved regions of the DNA-binding domain of members of this superfamily were employed to identify this gene. The amino-acid sequence of RTR is most closely related to that of the mouse RXRs with an overall identity of 32-34%; the highest similarity (61%) is observed in the DNA-binding domain. Northern blot analysis using RNA from multiple tissues showed that RTR is predominantly expressed in the testis. Northern blot analysis using RNA from different testicular cell types showed that RTR mRNA is not expressed in early germ cells or Sertoli cells but is most abundant in round spermatids. Our observations suggest that this putative transcription factor plays a role in the regulation of gene expression particularly during the post-meiotic phase of spermatogenesis.

Amino Acid Sequence↗

GSH-independent denitration of the nitrate ester of a dihydropyridine derivative in rabbit hepatic cytosol.

The denitration of a dihydropyridine derivative having two nitrate ester groups, 2-nitroxypropyl 3-nitrooxypropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate (NND), by rabbit hepatic cytosol was investigated. Sephadex G-150 chromatography of ammonium sulfate precipitate (30-60%) from the cytosol demonstrated the presence of two distinct activities (peak I and peak II) responsible for denitration of [14C]-NND. The first peak, peak I, was observed in the presence of dithiothreitol (DTT), but not in the presence of glutathione (GSH). Moreover, the denitration activity of peak I was not inhibited by S-hexyl GSH, an inhibitor of GSH S-transferase (GST), indicating that peak I possessed no GST activity. In contrast, the denitration activity of peak II, having GST activity, required GSH and was inhibited by S-hexyl GSH. These results strongly suggest that the GSH-independent enzyme system(s), in addition to GST, is responsible for denitration of nitrate esters of NND.

Animals↗

Identification of a transposon-related RNA down-regulated by retinoic acid in embryonal carcinoma and embryonic stem cells.

The differential display polymerase chain reaction was employed to identify changes in mRNA expression during retinoic acid-induced differentiation in embryonal carcinoma PCC4.aza1R cells. In this study, we report on one cDNA, EC1, that was identified by this method. EC-1 encodes a 0.6-kb mRNA that is present in PCC4.aza1R cells and down-regulated by retinoic acid. Sequence analysis revealed that EC-1 exhibits a 47% identity with the early transposon RNA ETn and does not contain a long open reading frame. EC-1 mRNA expression was reduced by 50% after 24 h of treatment with 10 nM retinoic acid and was undetectable after 48 h. Down-regulation of EC-1 mRNA was observed at retinoic acid concentrations as low as 0.1 nM. EC-1 was found to be expressed in several other embryonal carcinoma cell lines as well as in embryonic stem cells but was undetectable in differentiated cell types obtained after RA treatment. Northern blot analysis using RNA from multiple mouse tissues demonstrated that the expression of EC-1 is restricted to the testis. Treatment of PCC4.aza1R cells with an RAR-selective agonist also repressed the expression of EC-1 mRNA while treatment with an RXR-selective agonist reduced EC-1 expression slightly. The RAR alpha-specific antagonist Ro 41-5253 had little effect on the down-regulation of EC-1 by retinoic acid. Our observations indicate that the repression of EC-1 is associated with the induction of differentiation in embryonal carcinoma and embryonic stem cells and involves an RAR-activated signaling pathway.

Animals↗

Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study.

The cellular nature of the giant eosinophilic cells of tuber and of the cells comprising subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis (TS) remains unclear. To assess the characteristics of these lesions, 13 tubers and 6 SEGA were immunohistochemically studied with glial and neuron-associated antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were subjected to immunoelectron microscopic study for glial fibrillary acidic protein (GFAP) and somatostatin. Eosinophilic giant cells of tubers were positive for vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also found to a various extent to be reactive for neuron-associated antigens, including neurofilament (NF) proteins (38%) or class III beta-tubulin (77%). SEGA also showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF epitopes, class III beta-tubulin, and calbindin 28-kD were expressed in 2 (33%), 5 (83%) and 4 (67%) cases, respectively. Cytoplasmic staining for somatostatin (50%), met-enkephalin (50%), 5-hydroxytryptamine (33%), beta-endorphin (33%) and neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the giant cells of tubers and the cells of SEGA contained numerous intermediate filaments, frequent lysosomes and occasional rectangular or rhomboid membrane-bound crystalloids exhibiting lamellar periodicity and structural transition to lysosomes. Some SEGA cells showed features suggestive of neuronal differentiation, including stacks of rough endoplasmic reticulum, occasional microtubules and a few dense-core granules. Furthermore, in one case of tuber, a process of a single large cell was seen to be engaged in synapse formation. Intermediate filaments within a few cells of both lesions were decorated by gold particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non-membrane-bound, electron-lucent areas often contained somatostatin-immunoreactive particles, whereas the latter could not be detected in tuber. The present study provides further evidence of divergent glioneuronal differentiation, both in the giant cells of tubers and the cells of SEGA. The findings of similar cells at different sites, including the subependymal zone, white matter ("heterotopias"), and cortex indirectly supports the idea that these lesions of TS result from a migration abnormality.

Adolescent↗