Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma.

Somatic G17V RHOA mutations were found in 50-70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high-throughput screening. We found that binding of G17V RHOA to VAV1 augmented its adaptor function through phosphorylation of 174Tyr, resulting in acceleration of T-cell receptor (TCR) signaling. Enrichment of cytokine and chemokine-related pathways was also evident by the expression of G17V RHOA. We further identified VAV1 mutations and a new translocation, VAV1-STAP2, in seven of the 85 RHOA mutation-negative samples (8.2%), whereas none of the 41 RHOA mutation-positive samples exhibited VAV1 mutations. Augmentation of 174Tyr phosphorylation was also demonstrated in VAV1-STAP2. Dasatinib, a multikinase inhibitor, efficiently blocked the accelerated VAV1 phosphorylation and the associating TCR signaling by both G17V RHOA and VAV1-STAP2 expression. Phospho-VAV1 staining was demonstrated in the clinical specimens harboring G17V RHOA and VAV1 mutations at a higher frequency than those without. Our findings indicate that the G17V RHOA-VAV1 axis may provide a new therapeutic target in AITL.

Pituitary Macroadenoma and Visual Impairment: Postoperative Outcome Prediction with Contrast-Enhanced FIESTA.

BACKGROUND AND PURPOSE: Contrast-enhanced FIESTA can depict anterior optic pathways in patients with large suprasellar tumors. We assessed whether the degree of kink in the optic nerve at the optic canal orifice on contrast-enhanced FIESTA correlates with the postoperative improvement of visual impairment in patients with pituitary macroadenoma. MATERIALS AND METHODS: Thirty-one patients with pituitary macroadenoma who underwent preoperative MR imaging and an operation were evaluated. We measured the optic nerve kinking angle on sagittal oblique contrast-enhanced FIESTA parallel to the optic nerve; the optic nerve kinking angle was defined as the angle between a line parallel to the planum sphenoidale and a line parallel to the intracranial optic nerve at the optic canal orifice. We used logistic regression analyses to determine whether the clinical (sex, age, and duration of symptoms) and imaging (tumor height, chiasmal compression severity, hyperintense optic nerve on T2WI, and optic nerve kinking angle) characteristics were associated with the postoperative improvement (good-versus-little improvement) of visual acuity disturbance and visual field defect. RESULTS: There were 53 impaired sides before the operation: 2 sides with visual acuity disturbance alone, 25 with visual field defect alone, and 26 with both. After the operation, good improvement was found in 17 of the 28 sides with visual acuity disturbance and in 32 of the 51 sides with visual field defects. Only the optic nerve kinking angle was significantly associated with good improvement of the visual acuity disturbance (P = .011) and visual field defect (P = .002). CONCLUSIONS: The degree of the optic nerve kinking angle was an independent predictor of postoperative improvement, indicating that irreversible damage to the optic nerve may be associated with its kinking at the optic canal orifice.

Production of three-dimensional tissue-engineered cartilage through mutual fusion of chondrocyte pellets.

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds.

Tumor consistency of pituitary macroadenomas: predictive analysis on the basis of imaging features with contrast-enhanced 3D FIESTA at 3T.

BACKGROUND AND PURPOSE: Preoperative evaluation of pituitary macroadenoma tumor consistency is important for neurosurgery. Thus, we aimed to retrospectively assess the role of contrast-enhanced FIESTA in predicting the tumor consistency of pituitary macroadenomas. MATERIALS AND METHODS: Twenty-nine patients with pituitary macroadenomas underwent conventional MR imaging sequences and contrast-enhanced FIESTA before surgery. Two neuroradiologists assessed the contrast-enhanced FIESTA, contrast-enhanced T1WI, and T2WI. On the basis of surgical findings, the macroadenomas were classified by the neurosurgeons as either soft or hard. Finally, Fisher exact probability tests and unpaired t tests were used to compare predictions on the basis of the MR imaging findings with the tumor consistency, collagen content, and postoperative tumor size. RESULTS: The 29 pituitary macroadenomas were classified as either solid or mosaic types. Solid type was characterized by a homogeneous pattern of tumor signal intensity without intratumoral hyperintense dots, whereas the mosaic type was characterized by many intratumoral hyperintense dots on each MR image. Statistical analyses revealed a significant correlation between tumor consistency and contrast-enhanced FIESTA findings. Sensitivity and specificity were higher for contrast-enhanced FIESTA (1.00 and 0.88-0.92, respectively) than for contrast-enhanced T1WI (0.80 and 0.25-0.33, respectively) and T2WI (0.60 and 0.38-0.54, respectively). Compared with mosaic-type adenomas, solid-type adenomas tended to have a hard tumor consistency as well as a significantly higher collagen content and lower postoperative tumor size. CONCLUSIONS: Contrast-enhanced FIESTA may provide preoperative information regarding the consistency of macroadenomas that appears to be related to the tumor collagen content.

Levels of the oxidative stress marker γ-glutamyltranspeptidase at different stages of nonalcoholic fatty liver disease.

OBJECTIVES: This study investigated oxidative stress in the liver, by determining hepatic expression and serum levels of γ-glutamyltranspeptidase (GGT) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in different stages of nonalcoholic fatty liver disease (NAFLD), and assessed whether GGT can differentiate between the various stages of NAFLD. METHODS: Expression of GGT and 8-OHdG was examined in biopsy specimens by immunohistochemistry, and serum GGT and 8-OHdG levels were measured by enzyme-linked immuno sorbent assays in patients with simple fatty liver (n = 10), nonalcoholic steatohepatitis (NASH; n = 10) and, as a control, in alcoholic liver disease (ALD; n = 10). RESULTS: Hepatic tissue expression of GGT and 8-OHdG was seen in ALD, NASH and fatty liver patients. The percentage of hepatocytes positive for 8-OHdG expression and serum 8-OHdG levels was significantly higher in patients with NASH than simple fatty liver. Serum GGT levels were increased in all cases with ALD, NASH and fatty liver, and correlated significantly with serum levels of 8-OHdG in ALD and NASH, but not in simple fatty liver. CONCLUSIONS: Levels of GGT in fatty liver patients may compensate for mild oxidative stress by repressing 8-OHdG levels and preventing progression to NASH; however further oxidative stress leads to increased levels of 8-OHdG and the development of NASH.

Physiological uptake of 18F-fluorodeoxyglucose in uterine endometrium and myometrium: correlation with uterine motility evaluated by cine magnetic resonance imaging.

BACKGROUND: Accumulation of (18)F-fluorodeoxyglucose ((18)F-FDG) in the uterine endometrium and uterine motility are dependent on menstrual cycle. However, the relationship between them remains unknown. PURPOSE: To investigate the relationship between radiometabolic activity of (18)F-FDG in the uterus and uterine motility observed by cine magnetic resonance imaging (MRI). MATERIAL AND METHODS: The study population consisted of 65 healthy, fertile women, selected from 229 women who underwent positron emission tomography (PET), computed tomography (CT), and MRI for cancer screening at our facility. They were divided into three groups according to their menstrual cycle phases: menstrual, follicular-periovulatory, and luteal. Regions of interest (ROIs) were placed over the endometrium and myometrium to calculate the standardized uptake value (SUV). Uterine peristalsis and contraction shown by cine MR imaging were evaluated visually, and the correlation between FDG uptake and uterine movements was assessed. RESULTS: After excluding nine patients due to inadequate images, 56 patients (19 follicular-periovulatory, 27 luteal, and 10 menstrual) were analyzed. FDG uptake of the endometrium, frequency of peristalsis, and the presence of sustained contraction varied according to the menstruation cycle, with a tendency toward greater uptake in the menstrual phase, but there was little relationship between the frequency of uterine peristalsis and FDG accumulation in the uterus. Significantly higher FDG accumulation in the endometrium was observed in patients with sustained contractions (3.32+/-1.47) than in those without contractions (2.45+/-0.66). CONCLUSION: Our preliminary data suggest that FDG accumulation in the endometrium tends to be higher in patients with uterine contraction, although there was no significant correlation between uterine peristalsis and FDG uptake in the uterine myometrium or endometrium.

Neural activity of the globus pallidus interna and its anatomical relations to the optic tract in Parkinson's disease.

BACKGROUND: To reveal landmarks for placing the globus pallidus interna (GPi) target on MR images, visual evoked potentials (VEPs) of the optic tract (OT) and neural activities of the GPi were studied retrospectively. METHODS: The dorsal and lateral border of the OT were determined by VEPs of the OT, and neural activity in the pallidal region was recorded with a semimicro-electrode in 20 patients. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess the condition of each patient before and 6 months and 12 months after surgery. FINDINGS: The location of trajectories relative to the lateral border of the OT were 3 mm medial (-3) in 6, 2 mm medial (-2) in 7, 1 mm medial (-1) in 8, at the lateral border (0) in 6, 1 mm lateral (+1) in 5, 2 mm lateral (+2) in 6, and 3 mm lateral (+3) in 5. The mean amplitudes along trajectories -3 and -2 mm were significantly higher than the others (post-hoc, p<0.01). In dorsoventral relations, the amplitudes from 5.1 mm to 6.8 mm of the medial trajectories (-3 to 0 mm) were significantly higher than others (post-hoc, p<0.01). The lesions placed medial to the lateral border of the OT located just above the lateral border of the OT on postoperative MR images (n=12) and brought better surgical benefits of total motor score, rigidity and bradykinesia than those placed lateral to the OT (n=8). INTERPRETATION: Our data indicate that hyperactive cells of the GPi are located medial to the lateral border of the OT and at least 5.1 mm above its dorsal surface, and this corresponds to the area just above the lateral border of the OT on MR images.

Significance of absent prohormone convertase 1/3 in inducing clinically silent corticotroph pituitary adenoma of subtype I--immunohistochemical study.

Biologically inactive ACTH-producing pituitary adenoma is known as clinically silent corticotroph adenoma. To search for the mechanism causing clinically silent corticotroph adenoma, we immunohistochemically examined the expression of prohormone convertase 1/3 (PC1/3) in this type of adenoma and compared our results with those obtained for Cushing's disease. All of the Cushing's disease specimens exhibited strongly positive PC1/3 exhibition. On the contrary, the expression of PC1/3 was very weak in the clinically silent corticotroph adenoma specimens. The absence of PC1/3 in clinically silent corticotroph adenoma indicates that silent corticotroph adenomas arise in a different cell type sharing the prohormone pro-opiomelanocortin (POMC), but processing it differently, accounting for the lack of clinical symptoms due to ACTH excess.

Assessment of cerebral hemodynamics before and after revascularization in patients with occlusive cerebrovascular disease by means of quantitative IMP-SPECT with double-injection protocol.

UNLABELLED: The purpose of this study was to validate a double-injection (DI) method with N-isopropyl-[123I]p-iodoamphetamine (IMP) to measure regional cerebral blood flow (rCBF) twice in a single session of dynamic SPECT and to elucidate a possible role of this method to identify patients with occlusive disease of major cerebral arteries, who might benefit from cerebral revascularization procedures (CR). MATERIALS AND METHODS: Fourteen patients with occlusion or severe stenosis of the internal carotid or middle cerebral artery were studied before and after CR to assess hemodynamic changes after revascularization treatment. We quantitatively measured rCBF before and after acetazolamide (ACZ) challenge along with cerebrovascular reserve capacity (CVR) with two injections of IMP in a single session of dynamic SPECT scans (DI method). The reliability and reproducibility of the DI method were validated by means of a simulation study and in eight patients who were examined without ACZ challenge to measure baseline rCBF twice. RESULTS: The analysis of simulated noisy data with realistic noise levels showed that the errors of the estimates for the first and the second rCBF and for the increase in rCBF were 2.6%, 8.1% and 10.4%, respectively. In the 8 patients examined by the DI method to measure baseline rCBF twice, the mean and the SD of percentage differences between the two consecutive measurements in rCBF were -1.3% and 5.5%, respectively. Eight out of 14 patients with occlusive disease had at least one region with a CVR less than 10%. They showed a significant increase in resting rCBF after CR, not only in the ipsilateral hemisphere (from 26.1 +/- 6.4 to 33.4 +/- 4.7) but also in the contralateral one (from 28.3 +/- 7.0 to 34.7 +/- 4.7) with a recovery of the ipsilateral CVR from 9.3 +/- 17.2 to 41.2 +/- 20.1%. The remaining six patients with good-moderate CVR did not show an increase in rCBF after CR (from 28.0 +/- 2.7 to 28.3 +/- 3.4). The three of them with a moderate CVR (10-25%) before CR showed normalization of CVR after CR. CONCLUSION: Patients with decreased rCBF and reduced CVR benefited from CR in terms of an increase in rCBF and recovery of CVR. The quantitative double-injection IMP-SPECT has the ability to identify those patients who may benefit from CR.

Cdc6 expression as a marker of proliferative activity in brain tumors.

Antibodies against human proteins that regulate DNA replication such as Cdc6 and Mcm5 became available as a new marker of proliferation. We performed immunohistochemical analysis with MIB-1 and antibody against Cdc6 on 35 brain tumors, including tumors of neuroepithelial tissue, vestibular schwannomas, meningiomas, and pituitary adenomas. Median reactivity for MIB-1 was 8.8%, and that for Cdc6 was 55%. Reactivity in most brain tumors was significantly higher for Cdc6 than for MIB-1, but reactivity of Cdc6 was independent of tumor grade. Detection of Cdc6 expression might be useful for the estimation of proliferative activity in brain tumors.

Incidentally identified syringomyelia associated with Chiari I malformations: is early interventional surgery necessary?

OBJECTIVE: The purpose of this study was to analyze clinical data and magnetic resonance imaging (MRI) findings for patients with asymptomatic, incidentally identified syringomyelia associated with Chiari I malformations who were monitored for more than 10 years, and to clarify the natural history of these lesions. METHODS: The clinical records of nine patients who had not been surgically treated and were regularly subjected to neurological and MRI examinations were analyzed. In MRI studies, the axial diameter of the syrinx at the widest level, the longitudinal extent of the syrinx, and the extent of tonsillar herniation into the spinal canal were analyzed. As a control, MRI findings for 11 patients with symptomatic syringomyelia associated with Chiari I malformations who had been surgically treated were also analyzed, and these MRI parameters were statistically compared between the asymptomatic and symptomatic groups. RESULTS: One patient underwent surgery, because of neurological changes, 7 years after the first visit. None of the remaining patients demonstrated any neurological change during the follow-up period (11.2+/-0.7 yr), and all of them have been faring well without surgery. No statistically significant differences in MRI findings between the asymptomatic and symptomatic groups were observed. CONCLUSION: The long-term clinical courses of patients with asymptomatic, incidentally identified syringomyelia associated with Chiari I malformations were observed to be benign. MRI parameters did not provide predictable values to recommend interventional surgery. Unless changes in neurological or MRI findings are detected, early interventional surgery is not necessary.

Acute effects of stereotactic radiosurgery on the kinetics of glucose metabolism in metastatic brain tumors: FDG PET study.

UNLABELLED: Hyperacute changes in the expression of glycolysis-associate gene products as well as FDG uptake in tumor cells after high-dose irradiation reflect response of the cells to noxious intervention and may be a potential indicator of the outcome of treatment. To understand acute effects on the kinetics of glucose metabolism of tumors in vivo after high-dose irradiation, we analyzed dynamic FDG PET data in patients with metastatic brain tumors receiving stereotactic radiosurgery. MATERIALS AND METHODS: We studied 5 patients with metastatic brain tumors by means of dynamic FDG PET before and 4 hours after stereotactic radiosurgery. Rate constants of glucose metabolism (K1*- k3*) were determined in a total of 13 tumors by a non-linear least squares fitting method for dynamic PET and arterial blood sampling data. Rate constants after radiosurgery were compared with those before radiosurgery. Changes in the rate constants induced by the therapy were also correlated with changes in tumor size evaluated by CT and/or MRI 6 months later. RESULTS: Four hours after radiosurgery, the phosphorylation rate indicated by k3* was significantly higher (0.080 +/- 0.058) than that before radiosurgery (0.049 +/- 0.023) (p < 0.05, paired t test), but there was no significant change in the membrane transport rates indicated by K1* and k2*. Although increases in the net influx rate constant K* (= K1*k3*/(k2* + k3*)) were correlated with increases in k3*, K* after radiosurgery (0.027 +/- 0.011) was not significantly different from that before the therapy (0.024 +/- 0.012). The reduction in the tumor size was correlated with k3* after radiosurgery. CONCLUSION: Acceleration of the phosphorylation process was demonstrated in vivo in metastatic brain tumors as early as 4 hours after stereotactic radiosurgery, as shown experimentally in vitro in a previous report. The phenomenon may be a sensitive indicator of cell damage.

Prevention of postoperative complications in skull base surgery for nasal or paranasal sinus carcinoma invading the skull base.

With recent technical advances in skull base surgery, radical resection of a nasal or paranasal sinus carcinoma invading the skull base can now be achieved. To assure a satisfactory surgical result, it is essential to prevent postoperative infection. In our series of 14 cases, serious postoperative infections occurred in the earliest 10 cases, and only 2 of these patients are still alive. The vascularised abdominal muscle flap for skull base reconstruction was fixed with fibrin glue, but was not adequate to fill the dead space, resulting in cerebrospinal fluid leakage and subsequent meningitis. Once the infection occurred, a free bone flap became the focus of infection. Based on these earlier experiences, we used a ROC fastener system to completely fill the dead space with an abdominal muscle flap, and bone flap was primarily craniectomised in the four most recent cases. With this technique, there were no postoperative infections.

Diagnostic and surgical strategies for intractable spontaneous intracranial hypotension. Case report.

The authors present the case of a 55-year-old man suffering from intractable spontaneous intracranial hypotension, in whom conservative treatment with 19 weeks of bed rest was not effective. In this period the patient twice underwent surgery for bilateral chronic subdural hematoma, a complication of spontaneous intracranial hypotension. Conventional radionuclide cisternography, magnetic resonance imaging, and computerized tomography myelography did not demonstrate cerebrospinal fluid (CSF) leakage. Repeated radionuclide cisternography with the patient in an upright position revealed leakage of the tracer at upper cervical levels. Computerized tomography myelography with breath holding also showed CSF leakage of the contrast medium bilaterally at upper cervical levels. The patient underwent surgery, and bilateral C-2 and C-3 spinal nerve root pouches were sealed off from the subarachnoid space with oxidized cellulose cotton and fibrin glue. Epiarachnoid spaces around the root sleeves were also sealed to ensure complete resolution of the CSF leakage. After the surgery, the patient was completely free of the disease. In the case of intractable persistent spontaneous intracranial hypotension, surgical treatment is preferable to long-term conservative management. To identify CSF leakage, radionuclide cisternography with the patient in the upright position is useful. When obvious leakage is encountered, surgical sealing of the lesion should be performed via a subarachnoid approach.

Coexistence of thyrotropin-producing pituitary adenoma with papillary adenocarcinoma of the thyroid--a case report and surgical strategy.

We report a very rare case of thyrotropin (thyroxin stimulating hormone, TSH)-producing pituitary adenoma coexisting with a papillary adenocarcinoma of the thyroid. A 45-year-old woman presented with hyperhidrosis and a nodule in the left thyroid that was first noticed one year earlier. An endocrinological examination showed elevated serum levels of free triiodothyronine (T3) and free throxin (T4) without inhibition of TSH, suggesting the presence of syndromes of inappropriate secretion of TSH. A specimen obtained by needle aspiration of the thyroid nodule revealed the presence of papillary adenocarcinoma. Magnetic resonance images demonstrated a pituitary macroadenoma. The patient was diagnosed as having a TSH-producing pituitary adenoma coexisting with a papillary adenocarcinoma of the thyroid. The patient underwent a total thyroidectomy with resection of the neighboring lymph nodes. Two weeks after this surgery, the pituitary adenoma was totally removed via a pterional approach. Histological and immunohistochemical examinations of the surgical specimens confirmed the lesion as a papillary adenocarcinoma of the thyroid and a TSH-producing pituitary adenoma. Serum TSH levels decreased to undetectable levels immediately after the surgery for the pituitary adenoma. Prolonged stimulation of the thyroid gland by TSH may be involved in the growth of thyroid carcinoma. In cases with a TSH-producing pituitary adenoma, the possible coexistence of thyroid carcinoma should be carefully ruled out. In such cases, a total thyroidectomy followed by TSH level normalization should be performed. Incomplete removal of the thyroid might enable the carcinoma to re-grow if TSH level can not be normalized after the pituitary adenomectomy.

Intracerebral hemorrhage from a ruptured pseudoaneurysm after STA-MCA anastomosis--case report.

A 43-year-old hypertensive male developed a pseudoaneurysm at the site of a superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis, causing massive intracerebral hemorrhage 5 years after the operation. He first experienced repeated transient ischemic attacks, and cerebral angiography disclosed complete occlusion in the cervical portion of the left internal carotid artery. STA-MCA anastomosis was performed, and the ischemic attacks stopped. Postoperative angiography confirmed patency of the anastomosis and good filling of the cortical branches of the left MCA. Five years after surgery, the patient suffered sudden onset of generalized convulsions and consciousness disturbance. Computed tomography disclosed a massive intracerebral hemorrhage in the left frontoparietal region, and angiography revealed an aneurysmal dilatation at the site of the anastomosis that was not seen before. Emergency evacuation of the hematoma and clipping of the aneurysmal dilatation were performed. The patient recovered well and became ambulatory. Histological examination of the surgical specimen showed collagen tissue, indicating a pseudoaneurysm. Patients who undergo STA-MCA anastomosis, especially hypertensive patients, should be followed up by repeated magnetic resonance angiography to confirm the patency of the anastomosis and cerebral perfusion, and to detect the formation of pseudoaneurysms at the anastomosis site, which can cause fatal bleeding.

[The vanishing testis: diagnosis and histological findings].

PURPOSE: Controversy exists on how to diagnose the vanishing testis and the degree of investigation required. In this series, we reviewed anatomical and histological findings in vanishing testes and investigated the effectiveness of diagnostic laparoscopy and imaging studies. MATERIALS AND METHODS: Between 1974 and March 1999, 107 boys with nonpalpable testis underwent surgery. Of the total, 52 had spermatic vessels, vas deferens, and/or nubbin, and as a result the diagnosis of vanishing testis was made. RESULTS: The affected side of vanishing testis was left 41, right 9 and bilateral 2.35 nubbins were found and the lengths of 24 nubbins were 5 mm or less. Histological examinations were performed in 43 cases including 27 nubbins. From that total, 31 had vas deferens and 11 had epididymis. Only two nubbins had seminiferous tubules but they included no germ cells. The two nubbins were greater than 5 mm long. Laparoscopic surgery was undertaken in 12 separate cases of the vanishing testis and as a result hypoplastic spermatic vessels were present in 7 of the 12 cases. CONCLUSION: The incidence of viable testicular tissue in vanishing testes was 4.7% in our series and it ranges from 0-16% in other series. We submit that one can diagnose the inguinal vanishing testis with preoperative imaging and laparoscopy, and that the nubbin seldom contains testicular tissue. Our results do not support the necessity to remove nubbins.

[Prolactinoma in a child showing high MIB-1 labeling index: a case report].

We report a very rare case of a prolactin secreting pituitary tumor (prolactinoma) which occurred in a 12-year-old boy. The tumor showed an extremely high MIB-1 index. The clinical implication in the postoperative management of childhood prolactinoma is discussed. The patient showed right third nerve palsy, and MRI revealed a pituitary tumor invading the right cavernous sinus. Preoperative hormonal evaluation showed a very high prolactin level (2800 ng/ml). The patient underwent transsphenoidal surgery, and the third nerve palsy disappeared just after the procedure. MIB-1 index obtained by using immunostaining was 18.9%. Postoperative prolactin level remained high (2200 ng/ml), and the patient was treated with 10 mg/day of bromocriptine. Prolactinomas in children with high MIB-1 index show resistance to treatment with bromocriptine. In the postoperative management of a childhood prolactinoma, it should be considered how to control sufficiently high serum prolactin level to expect sexual development while preserving other normal residual pituitary functions. If control with bromocriptine, fails radiation treatment should be adopted with careful observation of the increase in height and the progress of sexual development of the patient.

The complete nucleotide sequence of the mitochondrial genome of sugar beet (Beta vulgaris L.) reveals a novel gene for tRNA(Cys)(GCA).

We determined the complete nucleotide sequence of the mitochondrial genome of an angiosperm, sugar beet (Beta vulgaris cv TK81-O). The 368 799 bp genome contains 29 protein, five rRNA and 25 tRNA genes, most of which are also shared by the mitochondrial genome of Arabidopsis thaliana, the only other completely sequenced angiosperm mitochondrial genome. However, four genes identified here (namely rps13, trnF-GAA, ccb577 and trnC2-GCA) are missing in Arabidopsis mitochondria. In addition, four genes found in Arabidopsis (ccb228, rpl2, rpl16 and trnY2-GUA) are entirely absent in sugar beet or present only in severely truncated form. Introns, duplicated sequences, additional reading frames and inserted foreign sequences (chloroplast, nuclear and plasmid DNA sequences) contribute significantly to the overall size of the sugar beet mitochondrial genome. Nevertheless, 55.6% of the genome has no obvious features of information. We identified a novel tRNA(Cys) gene (trnC2-GCA) which shows no sequence homology with any tRNA(Cys) genes reported so far in higher plants. Intriguingly, this tRNA gene is actually transcribed into a mature tRNA, whereas the native tRNA(Cys) gene (trnC1-GCA) is most likely a pseudogene.