Long-term follow-up of 5 patients with intracranial germinoma initially treated by chemotherapy alone.

BACKGROUND: High rates of overall- and event-free survival have been reported in patients with intracranial germinoma treated by radiotherapy. We report the long-term results after treatment initially with chemotherapy, but without radiation. PATIENTS AND METHOD: Five patients with an intracranial germinoma were treated with 2 cycles of etoposide and cisplatin, without radiotherapy. All achieved complete remission; 3 suffered recurrence within 2 years and were again treated with 2 cycles of etoposide and cisplatin followed by radiotherapy. RESULTS: At long-term follow-up, each of the 5 patients was in complete remission without further recurrence. Each patient with a neurohypophyseal germinoma who presented with endocrinopathy had initially recovered endocrinological function. CONCLUSION: In a patient with a germinoma chemotherapy, and restriction of radiation to those with recurrence may allow restoration of hypophyseal function damaged by the intracranial germinoma without compromising long term survivial.

A novel heterozygous missense mutation in the vasopressin moiety is identified in a Japanese person with neurohypophyseal diabetes insipidus.

The autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by diverse mutations in one allele of the gene that encodes the arginine vasopressin (AVP) precursor protein, AVP-neurophysin II (AVP-NP II). Most of the mutations identified so far are located in either the signal peptide or NP II moiety. Two recently published mutations in the AVP gene identified in kindreds with adFNDI predict a substitution of histidine for tyrosine at position 2 and a deletion of phenylalanine at position 3 in AVP. They are unique among adFNDI mutations in that they are the only adFNDI mutations that affect amino acid residues in the AVP moiety of the pro-hormone. Here, we report a novel heterozygous missense mutation in the AVP moiety of the AVP-NP II gene in a Japanese person with neurohypophyseal diabetes insipidus (DI). This mutation occurs at position 2 in AVP and predicts a substitution of serine for tyrosine (Y21S). It is expected to interfere with normal binding of AVP with NP II, and thus result in misfolding of the precursor proteins. The data of this study support the notion that mutations affecting the AVP moiety can result in the initiation of the pathological processes.

Konjak mosaic virus: the complete nucleotide sequence of the genomic RNA and its comparison with other potyviruses.

Konjak mosaic virus (KoMV) belongs to the genus Potyvirus, family Potyviridae. The complete nucleotide sequence of KoMV F isolate (KoMV F) was determined. The genome is 9,544 nucleotides long excluding the 3' terminal poly A tail and encodes a typical potyviral 350-kDa polyprotein of 3,087 amino acids. Phylogenetic analysis using known potyvirus polyproteins shows that KoMV constitutes a branch with yam mosaic virus, close to another branch including Japanese yam mosaic virus, turnip mosaic virus, scallion mosaic virus and lettuce mosaic virus. The 3' terminal 1,842 nucleotides of a different isolate of KoMV, K-2, was also determined, covering the C-terminal 292 amino acids of the nuclear inclusion protein b (NIb), coat protein (CP), and the 3' untranslated region. The amino acid sequences of the KoMV F CP and the nucleotide sequences of the KoMV F 3' untranslated region showed 92.5 and 90.5% identity to the corresponding genes of K-2, 88.7-96.8 and 92.7-94.4% to those of Zantedeschia mosaic virus (ZaMV) isolates, 87.5-89.7% and 85.5-90.3% to those of Japanese hornwort mosaic virus (JHMV) isolates. These results showed that KoMV is a distinct potyvirus and that KoMV, ZaMV, and JHMV are members of the same potyvirus species. Considering that KoMV was the first of these to be described, ZaMV and JHMV may be considered isolates of KoMV.

Magnetic resonance imaging of the hypothalamic-neurohypophyseal system.

Magnetic resonance imaging (MRI) is a revolutionary advance in diagnostic imaging of the hypothalamic-neurohypophyseal system (HNS). The detailed anatomy of the sellar and parasellar region is clearly visible using MRI, because it has no bony artifacts and multidirectional capability. The posterior lobe of the pituitary gland displays a characteristic bright signal on the MR T1-weighted image (T1WI), and is distinctly separated from the anterior lobe. The bright signal is absent in patients with central diabetes insipidus, and is thought to reflect normal vasopressin storage in the posterior lobe. The signal intensity ratio of the posterior lobe to the pons on T1WI is strongly correlated with vasopressin content in the posterior lobe. In addition to the morphological evaluation, MRI provides unique information concerning the function of the HNS. The MRI findings of the HNS (normal condition, central diabetes insipidus, a depleted posterior lobe, an ectopic posterior lobe, and a damming-up phenomenon of the neurosecretory vesicles in the pituitary stalk) are demonstrated in this article.

Evaluation of pituitary adenomas by multidirectional multislice dynamic CT.

PURPOSE: Multidetector-row CT is a new technology with a short scanning time. Multislice dynamic CT (MSDCT) in various directions can be obtained using the multidetector-row CT with multiplanar reformatting (MPR) technique. MATERIAL AND METHODS: We evaluated the initial results of sagittal and coronal MSDCT images reconstructed by MPR (MSDCT-MPR) in 3 pituitary adenoma patients with a pacemaker. RESULTS: In a patient with microadenoma, the maximum contrast between the normal anterior pituitary gland and the adenoma occurred approximately 50 s after the start of the contrast medium injection. A microadenoma was depicted as a less enhanced area relative to normal pituitary tissue. The macroadenomas were depicted as a less enhanced mass with cavernous sinus invasion in 1 patient and as a non-uniformly enhanced mass in another patient. Bone destruction and incomplete opening of the sellar floor during previous surgery were clearly detected in 2 patients with macroadenomas. These pituitary adenomas were removed via the transnasal route based on information from the MSDCT-MPR images only. The findings were verified surgically. CONCLUSION: The MSDCT-MPR provided the information needed for surgery with good image quality in the 3 patients with pacemakers. MSDCT-MPR appears to be a useful technique for patients with a pituitary adenoma in whom MR imaging is not available. This is the first report, to our knowledge, of the MSDCT-MPR technique being used to demonstrate pituitary disorders.

Replication of Tomato spotted wilt virus After Ingestion by Adult Thrips setosus is Restricted to Midgut Epithelial Cells.

ABSTRACT If acquisition access feeding (AAF) is first given after adult eclosion, none of the nine thrips species able to serve as tospovirus vectors can become infective. The previous cellular investigations of this phenomenon, carried out only in Frankliniella occidentalis, suggested that infectivity was prevented because the type member of the tospoviruses, Tomato spotted wilt virus (TSWV), was unable to enter the midgut of adult thrips. The present study extends a cellular view of tospovirus-thrips interactions to a species other than the western flower thrips, F. occidentalis. Our findings show that TSWV enters and replicates within the midgut of adult Thrips setosus, but does not infect cells beyond the midgut epithelia. After AAF as adult, TSWV replicated in T. setosus midgut cells as indicated by significant increases in nucleocapsid (N) protein detected by double-antibody sandwich enzyme-linked immunosorbent assay, and the presence of inclusions containing the S RNA-encoded nonstructural and N proteins revealed by microscopic observations. Electron microscopic observations of adult insects showed that no infection occurred in cells beyond the midgut epithelia, and insects subsampled from the same cohorts could not transmit TSWV. In contrast, electron microscopy observations of larval T. setosus revealed that TSWV infected the midgut and muscle cells, and adult insects developing from these cohorts had infected salivary glands and were able to transmit TSWV. Mature virions were observed only in the salivary glands of adults developing from infected larvae. Our findings suggest that the barrier to infectivity in T. setosus adults differs from that shown for F. occidentalis adults.

An archetypical extradiol-cleaving catecholic dioxygenase: the crystal structure of catechol 2,3-dioxygenase (metapyrocatechase) from Ppseudomonas putida mt-2.

BACKGROUND: Catechol dioxygenases catalyze the ring cleavage of catechol and its derivatives in either an intradiol or extradiol manner. These enzymes have a key role in the degradation of aromatic molecules in the environment by soil bacteria. Catechol 2, 3-dioxygenase catalyzes the incorporation of dioxygen into catechol and the extradiol ring cleavage to form 2-hydroxymuconate semialdehyde. Catechol 2,3-dioxygenase (metapyrocatechase, MPC) from Pseudomonas putida mt-2 was the first extradiol dioxygenase to be obtained in a pure form and has been studied extensively. The lack of an MPC structure has hampered the understanding of the general mechanism of extradiol dioxygenases. RESULTS: The three-dimensional structure of MPC has been determined at 2.8 A resolution by the multiple isomorphous replacement method. The enzyme is a homotetramer with each subunit folded into two similar domains. The structure of the MPC subunit resembles that of 2,3-dihydroxybiphenyl 1,2-dioxygenase, although there is low amino acid sequence identity between these enzymes. The active-site structure reveals a distorted tetrahedral Fe(II) site with three endogenous ligands (His153, His214 and Glu265), and an additional molecule that is most probably acetone. CONCLUSIONS: The present structure of MPC, combined with those of two 2,3-dihydroxybiphenyl 1,2-dioxygenases, reveals a conserved core region of the active site comprising three Fe(II) ligands (His153, His214 and Glu265), one tyrosine (Tyr255) and two histidine (His199 and His246) residues. The results suggest that extradiol dioxygenases employ a common mechanism to recognize the catechol ring moiety of various substrates and to activate dioxygen. One of the conserved histidine residues (His199) seems to have important roles in the catalytic cycle.

Posterior lobe of the pituitary gland: correlation between signal intensity on T1-weighted MR images and vasopressin concentration.

PURPOSE: To correlate the signal intensity on magnetic resonance (MR) images in the posterior lobe of the pituitary gland with the vasopressin content. MATERIALS AND METHODS: Fourteen rabbits were studied: 12 water-deprived rabbits (two each at 48, 74, 96, 120, 144, or 168 hours of deprivation) and two control rabbits. Sagittal T1-weighted MR images were obtained before and after water deprivation. The signal intensity ratio of the posterior lobe to the pons was correlated with the vasopressin content in the posterior lobe, which was measured by means of radioimmunoassay. RESULTS: Before water deprivation, high signal intensity in the posterior lobe was demonstrated clearly in all rabbits. The signal intensity ratio and vasopressin content in the posterior lobe gradually decreased with water deprivation. The signal intensity ratio correlated strongly with the vasopressin content in the posterior lobe (Pearson correlation coefficient, .809; P < .001). CONCLUSION: The signal intensity ratio on T1-weighted MR images may be used as an indicator for the quantitative evaluation of the vasopressin content in the posterior lobe. The results strongly suggest that the origin of the high signal intensity in the posterior lobe on T1-weighted MR images is the vasopressin-neurophysin II-copeptin complex.

Supra- and extrasellar pituitary microadenoma as a cause of Cushing's disease.

There has been accumulating evidence that pituitary adenomas which cause Cushing's disease are located not only in sella turcica but also in various extrasellar and intracranial regions. We describe a case of Cushing's disease caused by a supra- and extrasellar ACTH-producing microadenoma, which originated in the anterior pituitary and extended upward without connecting to the stalk. The pituitary microadenoma was identified and removed by transsphenoidal microsurgery. After the surgery the patient experienced complete remission. This type of pituitary microadenoma is considered to be rare, but in order to accomplish successful surgical treatment, it is necessary to consider that pituitary adenomas which cause Cushing's disease may be located in such an unusual position.

Plasma and neurohypophyseal content of vasopressin in diabetes mellitus.

Vasopressin (VP) hypersecretion is known to occur in diabetes mellitus. Using magnetic resonance (MR) imaging, we evaluated the VP content of the posterior lobe of the pituitary gland in 22 patients with uncontrolled noninsulin-dependent diabetes mellitus. The mean VP level and hemoglobin A1c value were elevated; 6.8 +/- 6.8 pg/mL (normal, 0.3-3.5) and 11.7 +/- 2.1% (normal, < 6%). The signal intensity ratio of the posterior lobe to the pons was calculated on a MR T1-weighted image where the signal intensity reflects VP content and the posterior lobe has a characteristic hyperintense signal under normal conditions. The mean signal intensity ratio (1.34 +/- 0.22) was lower than that in 20 healthy subjects (1.56 +/- 0.13; P < 0.01). In 7 cases, the signal intensity ration was markedly decreased, and the hyperintense signal was absent. The hyperintense signal appeared after diabetic control in all 6 subjects who underwent follow-up MR examinations within 1-2 months. The VP content in the posterior lobe was decreased in patients with uncontrolled diabetes mellitus, which was thought to be caused by persistent VP hypersecretion. The persistent elevation of plasma VP might have some role in the initiation and progression of diabetic complications.

[Highly effective preoperative intraarterial infusion chemotherapy with CDDP for progressive uterine corpus cancer with a Sister Mary Joseph's nodule].

A 57-year-old female patient complained of atypical genital bleeding and a noxious emanation from her navel. A histological examination of the uterine body and the navel area confirmed a diagnosis of adenocarcinoma. We diagnosed it as IVb stage of uterine corpus cancer with a Sister Mary Joseph's nodule. We selectively administered intraarterial injection chemotherapy (Cisplatin 120 mg, Pirarubicin 40 mg) in the uterus and navel area (three times, once every three weeks) prior to surgery. The isolated uterus showed that the cancerous tissue had been eradicated, and we judged the cancer to be grade 3 following histopathological effective grading standards. The metastasis exhibited extreme shrinkage, but affirmed changes in the tumor quality. Currently, the patient is receiving maintenance therapy of 600 mg of Hysron H, and 600 mg of UFT. There are no indications of recurrence, and the patient is progressing well.

[A case of sacral neuroblastoma in an adult successfully treated with combination chemotherapy].

A 35-year-old woman was admitted with complaints of severe posterior femoral pain and was diagnosed as having sacral neuroblastoma by tumor open biopsy. After admission, combination chemotherapy consisting of CDDP, etoposide, CPA, and THP was started intra-arterially and intravenously. After 2 courses of chemotherapy, her symptoms markedly improved and the tumor size was reduced. Now, after completion of 16 courses of chemotherapy, she is in a state of partial remission. Hereafter, we intend to reconsider the treatment strategy including surgical therapy.

[Huge leiomyosarcoma of the mesentery: a case report].

A patient, a 63 year-old-man, was admitted suffering from discomfort in the left abdominal area; this proved to be a case of leiomyosarcoma of the mesentery. An upper gastrointestinal series revealed stenosis in the 3rd portion of the duodenum, and shift of the entire intestine to the right side. Computed tomography showed a giant mass lesion with a central necrosis. Selective arterial angiography showed a heterogeneous tumor stain with several feeders and drainage veins. A partial resection of the intestine around the Treitz's ligament and left hemicolectomy was required due to the tumor's invasion of the intestinal wall and transverse colon. The operation was successfully performed supported by the angiographic findings. The resected tumor was 23 cm in diameter, 2330 g in weight, and was filled with blood. The histological diagnosis was leiomyosarcoma of the mesentery. The patient has been doing well during the 6 months postoperative period.

Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus.

BACKGROUND: Central diabetes insipidus may be familial, secondary to hypothalamic or pituitary disorders, or idiopathic. Idiopathic central diabetes insipidus is characterized by selective hypofunction of the hypothalamic-neurohypophysial system, but its cause is unknown. METHODS: We studied 17 patients with idiopathic diabetes insipidus, in whom the duration of the disorder ranged from 2 months to 20 years. Only four patients had been treated with vasopressin before the study began. All the patients underwent endocrinologic studies and magnetic resonance imaging (MRI) with a 1.5-T superconducting unit, and two patients had biopsies of the neurohypophysis or the pituitary stalk. RESULTS: Nine of the 17 patients had thickening of the pituitary stalk, enlargement of the neurohypophysis, or both and lacked the hyperintense signal of the normal neurohypophysis. In the remaining eight patients, the pituitary stalk and the neurohypophysis were normal, although the hyperintense signal was absent. The abnormalities of thickening and enlargement were seen on MRI only in the patients who had had diabetes insipidus for less than two years, and the abnormalities disappeared during follow-up, suggesting a self-limited process. In addition to vasopressin deficiency, two patients had mild hyperprolactinemia and nine had impaired secretory responses of growth hormone to insulin-induced hypoglycemia. The two biopsies revealed chronic inflammation, with infiltration of lymphocytes (mainly T lymphocytes) and plasma cells. CONCLUSIONS: Diabetes insipidus can be caused by lymphocytic infundibuloneurohypophysitis, which can be detected by MRI. The natural course of the disorder is self-limited.

Acquired growth hormone deficiency due to pituitary stalk transection after head trauma in childhood.

Two patients are reported with growth hormone deficiency due to head trauma in childhood. Although their injuries were outwardly only slight and there was no loss of consciousness and no subsequent neurological deficits, they exhibited gradual growth retardation from the time of the trauma. Provocative endocrinological tests showed growth hormone deficiency and MRI showed transection of the pituitary stalk. These findings suggest that ordinary head trauma, as well as perinatal insult and congenital abnormalities, could be a cause of growth hormone deficiency.

Radiation therapy for juvenile pilocytic astrocytoma of the pituitary stalk. Case report.

A case of juvenile pilocytic astrocytoma of the pituitary stalk is reported. The patient presented with diabetes insipidus and growth retardation. Magnetic resonance (MR) imaging was useful in diagnosing the lesion. Although the tumor could not be completely removed by surgery, radiotherapy was effective and the residual tumor disappeared 6 months after irradiation. The patient's condition has remained stable and no recurrence has been observed by MR imaging in the 4 years since radiation therapy.

Magnetic resonance imaging of neurohypophyseal germinomas.

The authors reviewed magnetic resonance (MR) images in seven cases of germinoma in the hypothalamoneurohypophyseal axis (HNA). The intrasellar portions were clearly identified in six germinomas. Two small germinomas of these six were located only in the neurohypophysis. The major parts of the four large germinomas were located below the optic chiasm, and the large intrasellar portions were demonstrated. The remaining one small germinoma was localized from the pituitary stalk to the third ventricular floor. These findings strongly suggest that the primary site of germinomas in the HNA is the neurohypophysis. In the four large germinomas, the tumor shape was similar to that of pituitary adenoma. The authors believe that age (limited to first three decades), symptoms (diabetes insipidus), MR findings (absence of normal hyperintense signal of the posterior pituitary on T1-weighted (T1WI) images, and homogeneous hypointensity to the pons on T1WI images/isointensity on T2-weighted images are important in differential diagnosis.