Immunoreactive beta-endorphin and adrenocorticotropin in human cerebrospinal fluid.

To elucidate the significance of beta-endorphin in human cerebrospinal fluid (CSF), CSF levels of beta-endorphin-like immunoreactivity (beta-EP-LI) in various diseases were determined by a specific radioimmunoassay and compared with simultaneously determined ACTH-like immunoreactivity (ACTH-LI) levels in CSF. CSF beta-EP-LI and ACTH-LI in the control group, consisting of 5 normal subjects and 19 patients with nonendocrine diseases, were 22.2+/-1.3 and 14.6+/-0.4 fmol/ml, respectively. CSF levels of these peptides in patients with schizophrenia (n = 19) and acromegaly (n = 10) were not significantly different from those in the control group. Patients with Cushing's disease (n = 7) had significantly lower CSF beta-EP-LI and ACTH-LI levels than those in the control group. Four of them showed a parallel increase in CSF beta-EP-LI and CSF ACTH-LI levels after the complete removal of pituitary microadenomas (P < 0.05). Gel chromatography of CSF beta-EP-LI from a normal volunteer, a control patient, and one patient each with catatonia, Nelson's syndrome, Cushing's syndrome (adrenal adenoma), and acromegaly gave similar patterns consisting of three peaks with the elution positions comparable to those of authentic beta-endorphin, beta-lipotropin, and possibly their precursor molecule. Gel chromatographic patterns of CSF beta-EP-LI and ACTH-LI were compared in a normal volunteer. The first peaks of beta-EP-LI and ACTH-LI eluted at the same position and the second peak of ACTH-LI coincided with the elution position of authentic ACTH.CSF beta-EP-LI and ACTH-LI levels determined every 5 min over a period of 80 min in three normal volunteers did not show moment-to-moment variability.A significant correlation (r = 0.75, P < 0.001) was seen between CSF beta-EP-LI and ACTH-LI levels in normal subjects and patients studied (n = 73). This suggests that beta-endorphin and ACTH in human CSF share the common regulatory mechanism in normal and pathologic conditions.

Weight loss is associated with plasma free amino acid alterations in subjects with metabolic syndrome.

OBJECTIVES: The prevalence of metabolic syndrome is increasing worldwide, especially in Asian populations. Early detection and effective intervention are vital. Plasma free amino acid profile is a potential biomarker for the early detection for lifestyle-related diseases. However, little is known about whether the altered plasma free amino acid profiles in subjects with metabolic syndrome are related to the effectiveness of dietary and exercise interventions. METHODS: Eighty-five Japanese subjects who fulfilled the Japanese diagnostic criteria for metabolic syndrome were enrolled in a 3-month diet and exercise intervention. The plasma free amino acid concentrations and metabolic variables were measured, and the relationships between plasma free amino acid profiles, metabolic variables and the extent of body weight reduction were investigated. Those who lost more than 3% of body weight were compared with those who lost less than 3%. RESULTS: Baseline levels of most amino acids in the subset that went on to lose <3% body weight were markedly lower compared with the counterpart, although both groups showed similar proportional pattern of plasma amino acid profiles. The weight loss induced by the diet and exercise intervention normalized plasma free amino acid profiles. For those with a high degree of weight loss, those changes were also associated with improvement in blood pressure, triglyceride and hemoglobin A1c levels. CONCLUSIONS: These data suggest that among Japanese adults meeting the criteria for metabolic syndrome, baseline plasma free amino acid profiles may differ in ways that predict who will be more vs less beneficially responsive to a standard diet and exercise program. Plasma free amino acid profiles may also be useful as markers for monitoring the risks of developing lifestyle-related diseases and measuring improvement in physiological states.

Anterior pituitary function after transsphenoidal selective adenomectomy in patients with Cushing's disease.

The anterior pituitary function in 25 patients with Cushing's disease was assessed before and after transsphenoidal adenomectomy. Pituitary adenoma was detected and removed in 24 cases, resulting in clinical remission in 22. Postoperative hypoadrenocorticism was observed in all of the cases with remission, necessitating substitution of glucocorticoid. One case had a recurrence after a year in remission. Plasma ACTH and cortisol rapidly decreased after surgery and remained at subnormal levels. However, diurnal rhythmicity of ACTH and cortisol appeared in 5 of 9 cases within 6 months after surgery and exhibited normal suppressibility in response to low dose dexamethasone. The impaired ACTH response to hypoglycemia was restored after surgery. The GH response to hypoglycemia and the TSH response to TRH were improved by correction of hypercorticism and became evident over time. These results suggest that preoperative impairment of anterior pituitary hormone secretion is secondary to hyperadrenocorticism and that ACTH hypersecretion by a primary pituitary adenoma is the primary etiology in Cushing's disease. We conclude that transphenoidal pituitary exploration should be considered as a first choice of treatment of Cushing's disease because of its high clinical remission rate in association with normalization of other endocrine functions.

Pituitary adenomas in acromegalic patients: an immunohistochemical and endocrinological study with special reference to prolactin-secreting adenoma.

To establish a functional classification of purification of pituitary adenomas in acromegalic patients, we used immunoperoxidase-staining techniques specific for GH and PRL. Surgical specimens from 55 acromegalic patients were studied. GH was demonstrated in all adenomas and PRL was found in 25 of them (45.5%). Immunohistologically, GH- and PRL-containing adenomas could be divided into 3 types. In type 1 (11 patients), immunoreactive PRL was present in single cells surrounded by immunoreactive GH cells. In type 2 (6 patients), immunoreactive PRL cells formed clusters. In Type 3 (8 patients), immunoreactive PRL and GH cells demonstrated a mosaic pattern, and it was difficult to determine which were in the majority. A double immunostaining method revealed 15 adenomas in which individual cells contained both GH and PRL. Hyperprolactinemia was present in 21 patients, 15 of these had immunoreactive PRL cells (type 1, 4 patients; type 2, 3 patients; type 3, 8 patients). There was no correlation between the size of the adenoma and its type. Endocrinologically, all patients with type 2 and 3 adenomas had an abnormal serum GH response to TRH administration; all type 3 patients had a substantial serum PRL response to TRH administration. Type 3 is considered to be an actively PRL-secreting adenoma, resulting in hyperprolactinemia.

Concomitant secretion of adrenocorticotropin, beta-endorphin, and gamma-melanotropin from perfused pituitary tumor cells of Cushing's disease: effects of lysine vasopressin, rat median eminence extracts, thyrotropin-releasing hormone, and luteinizing hormone-releasing hormone.

Regulation of secretion of ACTH-, beta-endorphin-, and gamma-melanotropin-like immunoreactivities (ACTH-LI, beta-EP-LI, and gamma-MSH-LI, respectively) was studied by using a perfused Sephadex column containing dispersed pituitary tumor cells obtained from three patients with Cushing's disease. Serial dilution of the perfusion medium gave lines parallel to the standard curve in each RIA for ACTH, beta-EP and gamma-MSH, suggesting that immunoreactive materials in the medium are immunologically indistinguishable from the authentic peptides. Gel exclusion chromatography of the medium revealed the existence of ACTH, beta-lipotropin (beta-LPH), beta-EP, and their possible precursor protein. gamma-MSH-LI consists of a major peak of big gamma-MSH eluted near the elution position of beta-LPH, suggesting the entire or nearly entire N-terminal portion of the precursor molecule. The addition of lysine vasopressin and rat median eminence extracts (MEE) to the perfusion system concomitantly enhanced the release of ACTH-LI, beta-EP-LI, and gamma-MSH-LI, although the dose-response relationship was clear-cut only in the case of MEE. TRH and LRH also elicited the concomitant release of these peptides in one patient, in whom combined administration of TRH and LRH significantly augmented plasma cortisol levels when studied preoperatively. The molar ratio of ACTH-LI to beta-EP-LI was approximately 1.0, whereas gamma-MSH-LI was about one fourth of ACTH-LI when compared on a weight basis. These results indicate that 1) ACTH-producing human pituitary adenomas concomitantly secrete ACTH, beta-LPH, beta-EP, and big gamma-MSH, and 2) lysine vasopressin, MEE, TRH, and LRH act directly on pituitary cells to stimulate the release of these peptides.

Pituitary adenomas that caused Cushing's disease or Nelson's syndrome are not responsive to ovine corticotropin-releasing factor in vitro.

The response of pituitary adenomas obtained surgically from patients with Cushing's disease of Nelson's syndrome to synthetic ovine corticotropin-releasing factor (CRF), vasopressins, somatostatin-28, dexamethasone, 3-isobutylmethylxanthine or high [K+] was examined in vitro by measuring the amount of pro-opiomelanocortin (POMC)-derived peptides secreted into the culture medium. CRF did not stimulate the secretion of adrenocorticotropin-, beta-endorphin-, or gamma 3-melanotropin-like peptides from the pituitary adenomas at concentrations ranging from 1 x 10(-13) M to 1 x 10(-7) M whereas vasopressins, 3-isobutyrl-methylxanthine and high [K+] increased, while somatostatin-28 and dexamethasone suppressed, the secretion of these POMC-derived peptides. These findings suggest that either the pituitary ACTH-producing tumors have lost their receptors to CRF or their post-receptor mechanism to CRF is not functional.

Development of bone canaliculi during bone repair.

We recently found that silver impregnation staining with protargol (silver protein), that is, a modified Bodian method, is useful for histologically identifying the details of bone canaliculi structure, using thin sections of decalcified bone tissues. With this staining method, we conducted the present study to assess the development of bone canaliculi during the process of intramembranous ossification using a fracture-like stimulation model of the rat femur. After making a drill-hole in the cortex of the rat femur, decalcified thin sections were obtained after 3, 5, 7, and 14 days by the standard paraffin-embedding procedure. Silver staining for bone canaliculi was performed using our previously reported technique. The results showed that woven bone covered the fracture surface of the cortex after 5 days, then immature lamellar bone attached to the woven bone after 7 days, and finally the lamellar bone matured and became thick with appositional growth after 14 days. The osteocytes in the woven bone appeared at an early stage of bone repair and developed a few canaliculi that were short and irregularly distributed in the osteoid matrix, while the osteocytes in the lamellar bone at a late stage formed many bone canaliculi that were long and regularly distributed in mature bone matrix. Therefore, we concluded that woven bone osteocytes may be necessary for induction of the lamellar bone osteocytes followed by active appositional growth of the lamellar bone at the early stage of bone repair, and also that both bone tissues could be clearly distinguished from one another based on the pattern of development of bone canaliculi by the osteocytes, as seen with the use of our sensitive staining method.

Molecular cloning and characterization of two zebrafish alpha(1,3)fucosyltransferase genes developmentally regulated in embryogenesis.

Some alpha(1,3)fucosylated oligosaccharides serve as counter receptors to lectin-like adhesion proteins or are expressed with temporal precision during embryogenesis, and alpha(1, 3)fucosyltransferase is a key enzyme in the production of these oligosaccharides. Two alpha(1,3)-fucosyltransferase genes, designated zFT1 and zFT2, were cloned from zebrafish. Sequence comparisons with other genes indicated that zFT1 and zFT2 share about 30% amino acid sequence identity with human alpha(1, 3)fucosyltransferases. Although the alpha(1,3)fucosyltransferases cloned so far can be classified into three types-myeloid, Lewis, and leukocyte-by virtue of their amino acid sequences, phylogenetic analysis indicated that neither zFT1 nor zFT2 belongs to any of these categories. The expression of zFT1 or zFT2 in mammalian cells induces alpha(1,3)fucosyltransferase activity to synthesize the Lewis x structure from pyridylaminated lacto-N-neotetraose; however, lacto-N-tetraose does not serve as a substrate. Reverse transcriptase-polymerase chain reaction analysis revealed that zFT1 is transcribed during a restricted period before hatching, whereas the mRNA for zFT2 was detected only after hatching.

Regional distribution of dopamine and norepinephrine in canine cerebral arteries--effect of pre- or postganglionic sympathetic denervation.

The regional distribution of dopamine (DA) and norepinephrine (NE) was investigated in dog cerebral arteries using high performance liquid chromatography with electrochemical detection. The distribution patterns of these two amines differed and there was a wide fluctuation in the ratio between the amounts of DA and NE. The ratios of DA to NE in the anterior cerebral artery and the anterior inferior cerebellar artery were 2-4 times higher than in the basilar or middle cerebral arteries, thereby suggesting that DA plays a role other than that of precursor of NE. The concentrations of both amines following pre- or postganglionic sympathetic denervation (superior cervical ganglion) were investigated. After preganglionic denervation (decentralization), neither amine showed significant changes in concentration. Postganglionic denervation one week prior to sacrifice resulted in a reduction in the concentrations of both amines; however, decrease in the former was less. These results suggest that the origin of dopamine in the cerebral arteries differs from that of the sympathetic nerves, via the superior cervical ganglion.

Superior sagittal sinus thrombosis associated with Evans' syndrome of haemolytic anaemia.

A case of superior sagittal sinus thrombosis associated with Evans' syndrome of immune haemolytic anaemia is reported. The neurological symptoms and signs were headaches, right quadrant hemianopia, dyslexia without agraphia, motor aphasia, numbness in and weakness of the right upper extremity, papilloedema and coma. The cerebral venous sinus thrombosis, involving cerebral veins, superior sagittal sinus and straight sinus, was diagnosed by cerebral angiography. It is noteworthy that the superior sagittal sinus thrombosis occurred during a haematological recovery period, with rapid responses to treatment with 6-mercaptopurine and high doses of adrenocorticosteroids. Following a reduction in the doses of these drugs, the symptoms and signs related to the superior sagittal sinus thrombosis gradually subsided, and the haematological pictures remained in remission.

Cerebrovascular occlusion by catheterization and embolization: clinical experience.

Intravascular occlusion by various catheterization techniques was used to treat 27 cases of carotid-cavernous fistula, giant intracavernous aneurysm, and cerebral or dural arteriovenous malformation. Several case reports are presented. The detachable balloon technique proved valuable in the treatment of traumatic carotid-cavernous fistula and giant aneurysm. Calibrated-leak balloon catheterization with fluid embolization was used to treat cerebral arteriovenous malformation. Selection of embolic material is discussed.

Pineal Tumors: clinical diagnosis, with special emphasis on the significance of pineal calcification.

The clinical presentations, findings of neuroradiological examinations, laboratory findings, pathological diagnoses, methods of treatment, and results of follow-up of 43 cases of pineal tumor collected at the Nagoya University Hospital from 1958 to 1979 are reviewed. The definitions of calcification of the pineal body and of pineal tumor are given. There is a significant difference in the incidence of calcification of the pineal body between pineal teratomas and pineal germinomas. Although there is a 100% rate of calcification of the pineal body in cases of pineal germinoma, the rate is very low in cases of pineal teratoma; calcification appears in only a small percentage of the cases of teratoma mixed with germinoma or embryonal carcinoma, or both. In male patients with suprasellar germinoma, there is a high frequency of an associated pineal calcification. No pineal calcification is seen in cases of basal ganglia germinoma. The computed tomographic (CT) findings of pineal teratoma and germinoma are characteristic. CT scanning is superior for early diagnosis of suprasellar and basal ganglia germinomas.

Trigeminal sensory evoked potentials in patients with trigeminal neurinoma: report of two cases.

The trigeminal sensory evoked potentials (TEPs) in two patients with trigeminal neurinoma are reported. In contrast to the two cases previously reported by others, in which the preoperative TEPs were normal, the two cases reported herein showed significant changes on the affected side: the sensory thresholds were greater and the peak latencies of P19 and N28 were longer on the affected side than those on the normal side. Our results confirm that a TEP measurement is very useful in a preoperative examination of patients with trigeminal neurinoma, when the function of the trigeminal nerve should be evaluated objectively.

Long term results of transsphenoidal adenomectomy in patients with Cushing's disease.

As part of an ongoing series, 100 patients with Cushing's disease underwent transsphenoidal operations. Pituitary adenomas were confirmed in 93 patients, and initial remission was achieved in 86 (92%) of them. Hypercortisolemia was not corrected in 7 patients, and in 4 this was due to invasive adenomas. These patients were subjected to irradiation, medical treatment, or both after operation. Only 7 of the 100 patients had no pituitary adenoma found at operation, and they obtained no clinical remission even after partial or subtotal hypophysectomy. Follow-up review, with an emphasis on endocrinological studies, was performed on these patients for a mean period of 38 months. Seventy-eight patients were in long term remission after operation and had restoration of noncorticotropic hormone secretion as well as pituitary-adrenal function. Recurrence was noted in 8 patients after 19 to 82 months in remission. In all of these patients, pituitary adenomas were verified by reoperation and no case of corticotrophic cell hyperplasia was noted. We conclude that late recurrence of Cushing's disease may occur after adenoma removal and is due to the regrowth of adenoma cells left behind in the peritumoral tissue at the first operation. In view of the overall remission rate, transsphenoidal adenomectomy is considered a highly effective treatment for Cushing's disease.

Early operation for ruptured intracranial aneurysms: comparative study with computed tomography.

The relationship between the results of early operation for ruptured intracranial aneurysms (72 cases) and the preoperative computed tomographic (CT) findings was studied. There was a correlation among the surgical results, the development of symptomatic vasospasm, and high density on the preoperative CT scan, particularly the presence of a localized, thick layer in the subarachnoid space. However, no relationship was found between the occurrence of ventricular enlargement and the preoperative CT findings. Cisternal or ventricular drainage might contribute to an uncomplicated postoperative course for patients with severe subarachnoid clot shown on the preoperative CT scan.

Microsurgical anatomy of the pineal region.

Thirty cadaver brains were examined under X 6 to 16 magnification in order to define the microsurgical anatomy of the pineal region, particularly the relationship of the pineal body, posterior cerebral artery, superior cerebellar artery, vein of Galen, basal vein of Rosenthal, internal cerebral vein, straight sinus, bridging vein, the size of the tentorial notch, and the third and the fourth cranial nerves. The infratentorial and supratentorial approaches to the pineal region are compared from the viewpoint of microsurgical anatomy.

Moyamoya disease in monovular twins: case report.

The first reported instance of identical twins with moyamoya disease is presented. The involved portions of the main intracranial arteries were similar, but the formation of the moyamoya vessels was somewhat different. The cause fo obstructive changes in large intracranial arteries remains obscure, but the frequent familial occurrence suggests that the initial stages of this disease and the formation of the moyamoya vessels occur in the prenatal period.

Internal irradiation for cystic craniopharyngioma.

The authors report the results of internal irradiation with labeled chromic phosphate (32P) and gold-198 (198Au) colloid in eight cases of cystic craniopharyngiomas. They used a newly developed dosimetric formula, by which the radiation dose at the cyst wall and at any point far from the radioactive source can be calculated. Ten courses of irradiation in eight patients were carried out by injection of either 32P or 198Au colloid into the cyst through an Ommaya drainage system that had been placed at craniotomy. Follow-up studies ranging from 13 to 156 months revealed that all cysts were effectively treated, with elimination of fluid or collapse of the cyst. This was confirmed by Conray cystography and/or computerized tomography. Not only the dose delivered to the wall but also the thickness of the cyst wall and the location of the cyst are important factors in planning internal irradiation. A safe and adequate dose to the cyst wall could range between 9000 to 30,000 rads for craniopharyngioma. This treatment is suitable for large cysts that are thought to be difficult to remove radically, recurrent cysts resistant to previous treatment, or multiple cysts. Internal irradiation may also be applicable in other cystic intracranial tumors if dosimetry is calculated accurately.

Symptomatic Rathke's cleft cyst. Morphological study with light and electron microscopy and tissue culture.

A rare case is reported in which a symptomatic Rathke's cleft cyst was studied by light and electron microscopy and tissue culture. The findings are compared with those of a craniopharyngioma studied in the same way. The patient was a 26-year-old woman presenting with headache, chiasmatic syndrome, and hypopituitarism. A cyst containing a mural nodule was partially removed and an Ommaya reservoir placed in the operative site for further treatment. The cyst wall was composed of connective tissue and three kinds of epithelial cells: non-ciliated squamous, ciliated columnar, and mucous-secreting cells. The morphology of these cells in vitro was similar to prickle cells seen in craniopharyngioma and the epidermis. It is concluded that both Rathke's left cyst and craniopharyngioma originate in remnants of Rathke's pouch, but at times may show some histological differences.

Neurological manifestations of pediatric achondroplasia.

The neurological and neuroradiological manifestations of pediatric achondroplasia are analyzed on the basis of 10 cases. In addition to the classical symptomatology of an enlarging head, with or without increased intracranial pressure, several patients presented symptoms related to a small foramen magnum. Respiratory problems and quadriparesis were also observed in these patients. Six patients who were treated by foramen magnum decompression showed remarkable improvement. Neuroradiological evaluation revealed a significant number of patients with dilated cortical sulci and basal cisterns, and mild dilatation of the ventricles on computerized tomography (CT) and/or ventriculography. Two patients showed signs of obstruction at the fourth ventricle outlets. Some exhibited anomalous dilatation of cerebral veins and dural sinuses, narrowing of the sinuses at the jugular foramen, and enlarged emissary veins. Ventriculoperitoneal or ventriculoatrial shunts were placed in three patients. In the other children with a large head and dilated ventricles, head growth curves paralleled the normal slope, and there was no significant clinical evidence of increased intracranial pressure or enlarging ventricles on follow-up CT scan.