Immunohistochemical analysis of 61 pituitary adenomas with a monoclonal antibody to the neuron-specific β-tubulin isotype

Pituitary adenomas surgically resected from 61 consecutive patients and 9 normal pituitary glands were studied by immunohistochemistry to determine the localization of the class III-tubulin isotype (neuron-specific) which is recognized by the monoclonal antibody TUJ1. In normal pituitary glands only a few cells were weakly immunopositive for TUJ1, whereas, in 43(73%) of 61 adenomas, more than 5% of tumor cells were immunopositive. The result may indicate that this neuron-specific -tubulin isotype may be either expressed de novo or enhanced under the transformation of pituitary acinar cells to tumors.Research fellow of the Department of Pathology, Kitasato University School of Medicine where the work was conducted     

Primary infiltrating signet ring carcinoma of the eyelids

A 61-year old man presented with a five-year history of a swelling initially developing in his right lower lid that progressed to involve the lateral canthal skin and eventually the upper lid and anterior orbit. He was discovered to have an infiltrating, poorly differentiated, mucin-producing carcinoma. Systemic work-up failed to disclose a visceral malignancy, and it was concluded that his tumor was primary in the lids, arising from an adnexal sweat gland. Three other reports in the literature also share almost identical clinical and pathologic features, in that all of the earlier reports dealt with middle-aged or elderly men who had diffusely indurated lids. Histopathologically, the tumor cells grow diffusely in a sclerotic stroma, and resemble the "histiocytoid" variant of metastatic breast carcinoma to the lids in women. Ultrastructural studies in our case point toward an apocrine origin, although earlier authors have favored an eccrine origin. Despite its indolent clinical course, the tumor is capable of producing regional and distant metastases on long-term follow-up. Complete local excision, possibly necessitating radical surgery, is probably the preferred method of treatment, but local radiotherapy may have a beneficial effect in retarding spread of the disease.     

Severe hypoaldosteronism due to corticosterone methyl oxidase type II deficiency in two boys: metabolic and gas chromatography-mass spectrometry studies

Infection-triggered, life-threatening salt-loss and hyperkalaemia developed in two male infants with wasting, inappropriately low plasma aldosterone concentrations and elevated plasma renin activity. The presumptive diagnosis of a defective terminal step in aldosterone biosynthesis was made by the presence of large amounts of 11-dehydrotetrahydrocorticosterone and its 18-hydroxylated metabolite (18-OH-THA), free 18-hydroxycorticosterone (18-OH-B) and 18-hydroxytetra-hydrocorticosterone in the urine of both patients. The diagnosis of corticosterone methyl oxidase type II (CMO II) deficiency was confirmed by an elevated urinary 18-OH-THA to tetrahydroaldosterone ratio in one boy and by an elevated plasma 18-OH-B to aldosterone ratio in the other boy. Unknown steroids responsible for the salt-loss were not identified. Sodium supplementation but not short-term high dose oral 9-fluorcortisol (FF) normalized the hyponatraemia in one patient, in whom sodium (Na⁺)/potassium (K⁺) co-transport was decreased. Both patients eventually received long-term FF treatment to prevent impairment of longitudinal growth caused by chronic salt-loss. The diagnosis of CMO II deficiency should always be confirmed by elevated precursor-product ratios in urine or plasma, using radioimmunoassays with prior chromatographic separation. Metabolic studies as the short-term response of serum Na⁺ to high dose FF may not be helpful in differentiating aldosterone biosynthetic defects from endorgan resistance to mineralocorticoids.Dedicated to Professor Dr. Walter Teller, on the occasion of his 60th birthdayPresented in part at the 27th Annual Meeting of the European Society for Paediatric Endocrinology, Copenhagen, Denmark, June 1988     

Dolichol-bound oligosaccharides and the transfer of distal monosaccharides in the synthesis of glycoproteins by normal and tumor mammary epithelial cells

Summary The main dolichol diphosphate-bound oligosaccharides present in primary cultures of both normal and tumor mouse mammary epithelial cells had the same size, yielded the same pattern after acetolysis and paper chromatography, had the same number of mannose residues susceptible to-mannosidase degradation, and were composed of the same monosaccharide residues. This is the first demonstration that normal and tumor mammary cells have dolichol diphosphate-bound oligosaccharides with very similar, if not identical, structures. These compounds are intermediates in the synthesis of asparagine-linked oligosaccharides. On the other hand, normal and tumor cells showed differences in the specific activities of the enzymes involved in the transfer of the distal monosaccharides from the sugar nucleotides to glycoproteins. Sialyl- and fucosyl-transferases were elevated and galactosyl- and N-acetylglucosaminyltransferases were diminished in mammary tumor cells. The intact tumor cells showed an increased fucosylation of glycoproteins of the asparagine-linkage type. Address for reprints: Roberto L. Ceriani, M.D., Ph.D., Bruce Lyon Memorial Research Laboratory, Children's Hospital Medical Center, 51st and Grove Streets, Oakland, CA 94609, USA.     

Treatment of myasthenia gravis

Summary In the treatment of myasthenia gravis (MG) considerable progress has recently been achieved. Our experience is based on the observation of 139 patients with an average follow-up of 3 years and 4 months.A treatment plan and results are presented.Indications for thymectomy: all cases of MG in adult life, apart from ocular myasthenia without radiological thymoma and without electrophysiological and pharmacological signs of generalization; before puberty only cases with radiological thymoma and severely incapacitating or life-threatening signs.Median sternotomy is preferable for thymoma, the transcervical approach with a sternal split for non-neoplastic thymus. Mediastinal radiotherapy is indicated after removal of an invasive or adhesive thymoma.Indications for corticosteroids: 1) before thymectomy: respiratory weakness; 2) soon after thymectomy: life-threatening signs; 3) later after thymectomy: incapacitating or life-threatening signs; 4) as an alternative to thymectomy: when surgery cannot be performed or it is not indicated. Oral Prednisone was nearly always preferred: alternate-day high single dose (75 to 115 mg) has given good results in most cases even if in some cases a small dose was required in the off day; inversely a lower alternate-day or daily dose was often sufficient.Long-term results: following this schedule for adult patients good results were scored in 67% of thymomas, in 94% of hyperplasias, and in 62% of unthymectomized patients: in prepuberal life the few cases of severe MG have all shown a favorable evolution.

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Zusammenfassung Bei der Behandlung der Myasthenie wurden in letzter Zeit beachtliche Fortschritte erzielt. Wir teilen hier unsere Erfahrungen anhand von 139 Patienten mit einer durchschnittlichen Katamnese von 3 Jahren und 4 Monaten mit.Wir betrachten als Indikationen für eine Thymektomie: alle Fälle von Myasthenie beim Erwachsenen mit Ausnahme der rein okulären Formen ohne radiologisch nachweisbares Thymom und ohne elektrophysiologische oder pharmakologische Zeichen einer Generalisierung; bei Kindern vor der Pubertät empfehlen wir die Thymektomie nur in Fällen mit radiologisch nachweisbarem Thymom und mit schwerer Beeinträchtigung oder gar Lebensgefährdung durch die Symptome.Die mediane Sternotomie ist beim Thymom vorzuziehen, der transzervikale Zugang mit Spaltung des Sternums für die nicht neoplastischen Thymusvergrößerungen. Mediastinale Strahlentherapie ist nach Exstirpation eines invasiven Thymoms oder eines Thymoms mit Adhäsionen angezeigt.Als Indikation für die Corticosteroidtherapie betrachten wir: 1. wenn vor der Thymektomie Atemstörungen bestehen; 2. wenn bald nach der Thymektomie lebensbedrohliche Symptome auftreten; 3. wenn später nach Thymektomie nennenswert behindernde oder lebensbedrohliche Symptome in Erscheinung treten; 4. als Alternative zur Thymektomie, wenn diese nicht durchgeführt werden kann oder nicht indiziert ist. Die orale Prednisontherapie wurde fast immer vorgezogen: wir gaben an alternierenden Tagen jeweils hohe Einzeldosen (75–115 mg) mit gutem Erfolg in den meisten Fällen. In gewissen Fällen war eine kleine Dosis an den Tagen zwischen der Hauptdose aber genügend, ebenso in Einzelfällen eine allgemein niedrigere Dosierung. Die Langzeiterfolge mit diesem therapeutischen Vorgehen betrugen 67% gute Ergebnisse bei Thymomen und 94% bei Thymushyperplasie. Unter den nicht thymektomierten Patienten wiesen 62% ein gutes Ergebnis auf. Vor der Pubertät zeigten die allerdings wenigen Fälle schwerer Myasthenie alle ein gutes Ansprechen auf die Therapie.

     

Glutamic acid concentration in human semen--its origin and significance

Glutamic acid content of semen was determined photometrically in over 400 semen specimens. Glutamatic acid content was found to increase proportionately to temperature in the first few hours post ejaculation. The glutamate estimation should therefore be performed on semen at 30 min. after ejaculation. The frequency distribution of glutamic acid concentration with 400 unselected specimens, 50 "normozoospermias" as well as 42 azoospermias is shown. The mean value of normozoospermias was 10.6 mg% (+/- 4.6 mg%) that of azoospermias 7.7 mg% (+/- 4.7 mg%). There was no correlation found between glutamic acid content and pH value. A correlation however, was demonstrated between glutamic acid and following: sperm count, citrate concentration, gamma-GT and carnitine. No correlation to fructose content was detectable. That suggests that glutamate gets to the ejaculate with the secretions from the prostate gland and epididymis whereas the seminal vesicles do not play a role in the level in the total semen.     

Spastic paraplegia associated with addison's disease: Adult variant of adreno-leukodystrophy

Summary Clinical and pathological features of an adult variant of adreno-leukodystrophy (ALD) are presented. A male with clinical and laboratory signs of Addison's disease (AD) developed at age 22 a slowly progressing paraplegia with slight sensory deficits in both legs and bladder and sphincter dysfunctions; he died at age 24 in an AD crisis. Autopsy revealed hyperplasia of lymphatic tissues, lymphocytic infiltrates in various organs including the CNS and adrenocortical atrophy with prominence of large ballooned, sometimes bizarre and occasionally striated cortical cells. CNS lesions consisted in incomplete demyelination of long tracts of brain stem and spinal cord with accentuation in the pyramical tracts; in these areas, perivascular cuffs of epitheloid histiocytic cells contained a strongly PAS-positive non-sudanophilic material. Electron microscopy demonstrated massive storage of leaflet structures in perivascular histiocytes identical to the lamellar profiles previously described as specific for ALD. Some leaflets were found in close contact with compact lamellar arrays and with an electron-dense fingerprint material within astrocytes.In our case, the spastic paraplegia-AD syndrome which has been described previously in several clinical observations could be neuropathologically classified as an adult variant of ALD. Several differences to classical ALD occurring in young boys are stressed: the predominance of the endocrine disorder probably accounting for some of the perivascular lymphocytic infiltrates within the CNS; the absence of both clinical and pathological signs of diffuse cerebral involvement and the peculiar topistic pattern of CNS lesions and the very slow evolution of neurological signs paralleled by the absence of active sudanophilic demyelinating lesions. The possible mechanism of demyelination and the nature of the suggested metabolic defect in ALD are discussed. The ultrastructurally prominent leaflet structures may originate from myelin remnants, thus relating ALD to pathological storage of a myelin degradation product.

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Zusammenfassung Klinische und pathologische Befunde einer adulten Form der Adrenoleukodystrophie (ALD) werden dargestellt. Ein Patient mit klinischem Bild und Laboratoriumsbefunden der Addison-Krankheit (AD) entwickelte im Alter von 22 Jahren eine sehr langsam zunehmende Paraspastik mit geringer Hypaesthesie in beiden Beinen und Blasenund Mastdarmstörungen; er verstarb im Alter von 24 Jahren in einer AD-Krise. Bei der Autopsie fanden sich eine Hyperplasie des lymphatischen Apparats und lymphocytäre Infiltrate in verschiedenen Organen einschließlich des ZNS; beide Nebennieren waren atroph mit Hervortreten großer ballonierter, etwas bizarrer Rindenzellen mit gelegentlicher cytoplasmatischer Streifung. Im ZNS fanden sich pseudosystematische inkomplette Entmarkungen der langen Bahnen in Hirnstamm und Rückenmark mit Betonung der Pyramidenbahn, charakterisiert durch perivasale Manschetten epitheloider histiocytärer Zellen, die ein stark PAS-positives sudannegatives Material enthielten. Elektronenoptisch wurde eine massive Speicherung eines lamellären Materials in perivasalen Histiocyten nachgewiesen, welches mit den als spezifisch für die ALD angesehenen Einschlüssen übereinstimmte. Einige derartige Strukturen zeigten einen engen Zusammenhang mit kompakten Lamellenaggregaten und mit einem elektronendichten fingerprint-Material innerhalb von Astrocyten.In diesem Fall konnte das Paraplegie-AD-Syndrom, welches mehrfach bereits klinisch beschrieben worden war, aufgrund neuropathologischer Befunde als adulte Variante der ALD klassifiziert werden. Die Unterschiede dieser Form zur klassischen ALD, welche üblicherweise Knaben betrifft, werden hervorgehoben: das Überwiegen der endokrinen Symptomatik, was das Auftreten perivasaler Lymphocytensäume im ZNS zum Teil bedingen dürfte; das Fehlen klinischer und pathologischer Hinweise auf diffuse Beteiligung des Großhirns und die spezielle Topik der ZNS-Läsionen und die geringe Progredienz der neurologischen Symptomatik, welche im Einklang mit dem Fehlen florider sudanophiler Entmarkungsvorgänge steht. Der Mechanismus der Entmarkung und die Art der vermuteten metabolischen Störung bei der ALD werden diskutiert. Die elektronenoptisch charakteristischen lamellären Strukturen könnten aus dem Myelinabbau stammen, und damit könnte bei der ALD eine pathologische Speicherung eines Myelinabbauprodukts vorliegen.

     

视网膜与松果体相关关系研究现状

就近年关于对视网膜与松果体在胚胎期的发生与形成、在成年时期的结构与功能等诸多方面的相似性进行了探讨，同时对两者的相互关系与相互影响进行了分析。随着对该领域不断深入的探讨，将有益于对视觉的重新认识和眼科临床的发展。     

Escherichia coli-induced alterations of human spermatozoa. An electron microscopy analysis

This study evaluated if the negative influence of Escherichia coli on the motility of human spermatozoa is a consequence of E. coli-induced ultrastructural alterations. Suspensions of spermatozoa were artificially infected with E. coli from a serotyped, pathogenic strain and incubated at 37 degrees C for 6 h. After incubation, spermatozoa were fixed in glutaraldehyde, stained with osmium tetroxide and ruthenium red and embedded in Spurr(R)-resin followed by ultramicrotomy. The sections were analysed subsequently by use of transmission electron microscopy. Uninfected suspensions of spermatozoa in medium and bacterial suspensions served as controls. Negative contrast technique was performed to facilitate visualization of ultrastructural details of the bacterial capsule after experimental exposure to spermatozoa. Electron microscopic evaluation revealed multiple and profound alterations in the ultrastructure of spermatozoa such as membrane defects and cytoplasmic vacuoles exclusively in spermatozoa of infected samples (> 90%). Morphological alterations involved all superficial structures of spermatozoa, in particular the plasma membrane of the mid-piece and neck as well as the inner and outer acrosomal membrane of the acrosome, indicating that morphological defects account for the immobilization of spermatozoa by E. coli. The results suggest that E. coli infection of ejaculates results in immobilization and impaired acrosomal function in human spermatozoa, findings that support the indication for antimicrobial chemotherapy in symptomatic and silent infections that affect the ejaculate.