Extensor tendons of the fingers: arrangement and variations--II.

One hundred eighty-one dissected hands were examined to study the pattern of extensor tendons on the dorsum of the hand. Extensor digitorum often had multiple tendons for the middle and ring fingers. Its contribution to the little finger was usually by a bifurcating tendon common with that of the ring finger. The index finger always received a single tendon. Intertendinous connections between the various tendons of the extensor digitorum were variable but were most frequent between ring and middle fingers. Extensor indicis had one tendon in most of the specimens and it was always on the ulnar side of the extensor digitorum tendon. This remained true even when there were multiple tendons. Extensor digiti minimi had two tendons in most cases. It was always linked to extensor digitorum either by receiving one or part of its tendon or by an intertendinous connection. Two accessory muscles were seen, one was extensor indicis brevis replacing the proper muscle. The other, the extensor medii brevis, was distributed to the middle finger.

Progressive myoclonic ataxia without ragged red fibres: Unverricht-Lundborg disease vs Ramsay Hunt syndrome.

We describe eight patients from three families presenting with myoclonus, ataxia, infrequent seizures and minimal intellectual impairment. All were Arabs from different parts of the Arabian peninsula. The new consensus on terminology, genetic and clinical definition of Baltic myoclonus, Ramsay Hunt syndrome and Unverricht-Lundborg disease suggests that our group are best categorised under the term of progressive myoclonic ataxia of the Unverricht-Lundborg type. Moreover, this report reinforces the existence of this syndrome outside Scandinavia.

Identification of sensory neurons supplying receptors in lingual muscles of the rat: histochemical and retrograde labeling study with horseradish peroxidase.

Sensory innervation of lingual musculature was studied in young adult Wistar rats using retrograde labeling by horseradish peroxidase (HRP) and combined silver impregnation and acetylcholinesterase (AchE) methods. Intra-lingual injection of HRP resulted in labeling of neuronal somata in the trigeminal, superior vagal, and second cervical spinal (C2) ganglia. When HRP was directly applied to the proximal stump of severed hypoglossal nerve, labeling occurred only in the cervical and superior vagal ganglia. Morphometric analysis revealed that the labeled neurons were of the small-sized category in all ganglia. However, in the trigeminal and C2 ganglia, labeling occurred also among the medium-sized neurons. Combined silver and AchE preparations from lingual muscles revealed the absence of typical muscle spindles. Instead, there were free and spiral nerve terminals in the interstitium, and epilemmal knob-like or bouton-like endings surrounding non-encapsulated muscle fibers. These terminals showed AchE -ve reaction in contrast to the motor ones. Few ganglionic cells were scattered along the hypoglossal nerve with uniform AchE +ve reaction in their perikarya. This indicates that medium-sized neurons in the trigeminal and C2 ganglia, and probably sensory neurons along the hypoglossal nerve mediate lingual muscle sensibility perceived by atypical sensory terminals.

Rett syndrome: a mitochondrial disease?

Six girls between 2 years 9 months and 15 years of age with Rett syndrome were thoroughly investigated. Blood ammonia levels varied between 42 and 123 mumol/L, and serum lactate concentration was slightly elevated in two girls. Electroencephalograms showed a dysrhythmic pattern during wakefulness; during drowsiness and light sleep, bilateral bursts of spike or multispike-and-wave activity were seen in all but the oldest girl. In one of the younger girls, slight cortical atrophy was found on computed tomographic scan. Muscle biopsy was performed on all girls, and electron microscopy revealed abnormal mitochondria. Physical signs such as somatic hypotrophy with extremely small muscle mass, and unsatisfactory weight gain in spite of good appetite are found in Rett syndrome. These attributes, as well as reports of ornithine carbamoyltransferase deficiency, may support a mitochondrial dysfunction. The mitochondrial changes indicate either a mitochondrial mutation or more probably an X-borne modulator gene mutation. Another genetic possibility discussed is the "metabolic interference" of an X-borne allele. Further delineation of such mitochondrial changes may clarify the causal metabolic defect in Rett syndrome.

Autosomal recessive ataxia, slow eye movements, dementia and extrapyramidal disturbances.

An Arab family with an autosomal recessive form of spinocerebellar degeneration with slow eye movements is reported. Hitherto all the reported cases were either sporadic or of autosomal dominant inheritance. Associated are progressive intellectual impairment and extrapyramidal dysfunction as well as peripheral neuropathy and skeletal abnormalities. Muscle biopsy revealed non-specific mitochondrial abnormalities. The spectrum of eye movement abnormalities is discussed and the literature is reviewed. It is concluded that the hallmark of this syndrome (slow or even absent saccades) is one of a group of oculomotor abnormalities, all being characterized by delayed initiation and slow velocity. The syndrome seems to be related to the olivopontocerebellar degenerations, but differs in that there is in addition selective degeneration of certain tracts and nuclei in the mesencephalon and probably more rostral structures.

Ultrastructural studies on the placentae of streptozotocin induced maternal diabetes in the rat.

Following induction of diabetes by a single injection of (IP) streptozotocin (STZ) to pregnant Wistar rats on days 2, 4 and 6 to 12 of gestation, fetuses and placentae were collected on day 20. The controls were either untreated or vehicle treated; alternatively following STZ injection, 2-6 IU of insulin was administered (sc) daily until term. The placentae were fixed in a glutaraldehyde and paraformaldehyde mixture and ultrathin sections were examined under the electron microscope. The structure of the vehicle treated control resembled that of the untreated control. The insulin control group had pathological changes similar to those of the diabetic group but with considerably less frequency. The giant cells in the basal zone of STZ group were numerous; they had abundant dilated cisternae of rough endoplasmic reticulum, intracytoplasmic fibrinoid and nuclear inclusions. The trophospongial cells presented numerous clear vacuoles, lysosomes and myelin bodies. Enlarged vacuoles often impinged deeply on the nucleus. The glycogen cells disintegrated resulting in cyst formation. In the labyrinthine zone, layer I trophoblast revealed increased number of large pores through which layer II trophoblast projected into the maternal sinusoid. Layer II had abundant glycogen, lipid droplets and lysosomes. Layer III had imbibed much fluid and appeared foamy with swollen organelles. Fibrinoid substance was produced by the giant cells, basophils and the trophoblast bordering the maternal sinusoids. Cyst development was preceded by degeneration of glycogen cells in the basal zone and of the trophoblast in the labyrinthine zone. Pronounced development of gonadotropin/somatotropin granule-like 'secretory granules' and smooth endoplasmic reticulum associated lipid droplets also characterised the labyrinthine trophoblast. The observed placental pathology appears to correlate well with the intrauterine growth retardation and fetal malformations recorded in this animal model.

A boy with the Rett syndrome?

A 13-year-old Kuwaiti boy met all necessary and almost all supportive criteria for the Rett syndrome. Electron microscopy of muscle biopsy specimen revealed abnormal mitochondria, a finding that has recently been reported for girls with the Rett syndrome. The results of other laboratory investigations were normal, besides a blood ammonia level of 100 microM/L. The mitochondrial changes observed in girls may be the consequence of an X-borne gene mutation, in which case only the female zygote survives because of the normal allele on the second X-chromosome. However, another genetic possibility discussed is inheritance according to "metabolic interference" of an X-borne allele, which does not rule out the possibility of a male being affected. We assume that the case reported might be a male variant of the Rett syndrome.

Late onset cerebello-pontomesencephalic degeneration.

Two siblings are presented with late onset, rapidly progressive truncal ataxia, paralysis of down-gaze and loss of up-gaze saccades in association with other oculomotor dysfunctions as well as dementia. Electron microscopic muscle studies revealed abnormal distribution and form of the mitochondria, probably being the ultrastructural basis of the pathologic changes. A neurological syndrome as that described here has not been reported before.

Fine structural study of the spinal cord and spinal ganglia in mice afflicted with a hereditary sensory neuropathy, dystonia musculorum.

Dystonia musculorum in mice is a hereditary autosomal recessive disorder, characterized by a progressive neuromuscular incoordination. This paper describes the ultrastructural changes in the spinal cord and compares and correlates the results with changes in the spinal ganglia in dystonic mice. Ganglion cells exhibited various stages of degeneration and pyknosis. The dorsal roots of the spinal nerves showed severe degeneration and loss of myelinated fibres accompanied by fibrosis, whilst the ventral roots appeared normal. Nerve cells within the dorsal and intermediate grey matter (laminae I to VII) of the spinal cord showed chromatolysis, atrophy, and necrosis. Boutons exhibited glycogen accumulation or an increase in their electron density. Axonal changes consisted of focal swellings, marked accumulation of neurofilaments, membranous and dense bodies, and disintegration of axoplasm. Myelin sheath degeneration of Wallerian type and degenerating axons were prominent in the dorsal, lateral and ventral white columns of the spinal cord. Glial reactions in the spinal cord were limited to mild hypertrophy and hyperplasia of astrocytic processes. The process of phagocytic activity was not intense in spite of the presence of an abundance of degenerating myelin and cell debris. This study showed that the ultrastructural changes in the spinal cord are more severe than those seen with routine light microscopy. The detection of definite neuronal degeneration of the dorsal root ganglia and spinal cord suggests that the defect apparently operates at the level of cell bodies, as well as axons, of the primary and second order sensory neurons.

Abnormal mitochondria in the Rett syndrome.

Two girls with Rett syndrome were investigated including muscle biopsy. The electron microscopy study revealed abnormally swollen and dumb-bell shaped mitochondria. Based on the findings of mitochondrial changes it can be assumed that such changes are due to a mitochondrial mutation steered by an X-borne gene mutation. As a result and because the mitochondrial DNA is maternally inherited, the male zygote may not be implanted or it will proceed to an early embryonal death. The mitochondrial changes with the ensuing effects may be the basic cause of the syndrome.

Ultrastructural study of phagocytic activities of young astrocytes in injured neonatal rat brain following intracerebral injection of colloidal carbon.

The cellular reaction to injury in the mature central nervous system (CNS) has been extensively studied in both man and animals, while a detailed study of the reaction of the immature CNS to injury is lacking in the literature. This study was undertaken to elucidate the response of young astrocytes following injection injury to developing brain. Colloidal carbon was applied because it is a suitable marker for phagocytosis, it is nontoxic, and it is readily identifiable by light and electron microscopy. The cerebral cortex of the neonatal rat was injected with 0.1 microliter of colloidal carbon solution. The animals were allowed to survive from 1 hour to 30 days postoperation. The brains were fixed by vascular perfusion and processed for light and electron microscopy. Carbon particles were ingested in membrane-bound vacuoles and sequestered in lysosomes of young astrocytes. Astrocytes, loaded with carbon particles, were identified after 4 days, and were seen in abundance between 10 to 21 days postoperation. Carbon-laden astrocytes were seen in the immediate vicinity of the site of the injection; in the surrounding, apparently normal, neuropil; and in the perivascular regions. This study demonstrates the ability of young astrocytes to engulf foreign particles injected into the developing brain. The presence of carbon particles in astrocytes located further away from the site of injection is discussed.

Immunohistochemical localization of collagens and fibronectin in human breast neoplasms.

Forty four specimens from neoplastic, hyperplastic and normal human breast tissues were studied for localization of collagens and fibronectin. Affinity purified antihuman type I, III and IV collagens and antifibronectins were utilized by the indirect immunoperoxidase technique on fixed and paraffin-embedded sections. 86% of the cell cytoplasm of infiltrating ductal and 83% of the lobular cancers were positively stained for collagen type I and III. Collagen type IV, however, was detected in 100% of infiltrating ductal and 83% of lobular carcinomas. Focal cytoplasmic staining is a predominant feature for all antigens in the intraduct carcinoma while a diffuse pattern is encountered in the infiltrating types. Intact basement membranes in various lesions always stained for type IV collagen and showed variable staining for type III collagen and fibronectin. Epithelia of normal, benign, hyperplastic breast and most medullary carcinoma were negative for the three collagen types. Our results are in favour of the view that infiltrating breast carcinoma cells produce inappropriately the majority of collagens and inconsistently other proteins such as fibronectin.

Morphological changes in the isolated rat liver perfused in a non-recirculating system: scanning and transmission electron microscopy.

Isolated perfused rat livers have been used for various studies, but detailed investigation into the structural integrity of hepatocytes of this system is lacking. In this study, isolated rat livers were perfused in vitro with oxygenated Krebs-Ringer bicarbonate buffer solution, for 2 minutes and 1, 2, 3, and 4 hour(s) at 37 degrees C, using a non-recirculating perfusion system. The perfused livers were processed for semithin section light microscopy, transmission electron microscopy, and scanning electron microscopy. Sectional areas of cell deaths were measured by a camera-tracing assembly from 1.5 microns thick Araldite sections stained with toluidine blue. Progressive nuclear and cytoplasmic changes, leading to cell death, occurred in the hepatocytes of the centrilobular zone, during the 2nd, 3rd, and 4th hour of the perfusion at a rate of 9.03% +/- 1.5%, 38.7% +/- 2.7%, and 55.1% +/- 5.9% (mean +/- standard deviation) of the total sectional areas respectively. Midzonal hepatocytes showed normal basophilic staining but exhibited loss of glycogen granules, loss of microvilli, development of aqueous vacuoles and formation of blebs. The fine structures of cell organelles, glycogen granules, microvilli and plasma membrane of the cells in the periportal zone were well preserved throughout the experimental period. For further quantitative, metabolic and functional studies using isolated rat liver perfused with Krebs-Ringer solution, it is evident from the present investigation that the periportal zone represents the functional region of the hepatic lobule. Whilst progressive changes, leading to cell death, occurred in the centrilobular zone.

Expression of connective tissue stromal elements in human cholangiocarcinomas. An immunohistochemical and ultrastructural study.

The results of the study of ten cholangiocarcinomas from intrahepatic or extrahepatic origins are reported. Using both light microscopic immunohistochemistry and transmission electron microscopy the scirrhous stroma of the tumour showed clear evidence for the production of its collagenous, elastic and possibly other fibrillar elements by the neoplastic cells. Our findings refute the view that the occasional spindle cells (i.e. fibroblasts, myofibroblasts or even smooth muscle cells) could play a major role in the production of such a voluminous amount of the various connective tissue elements. Therefore, it seems reasonable to suggest that the scirrhous stroma of cholangiocarcinomas is produced by the malignant cells similar to those of the breast, oesophagus, stomach and ureter.

Loss and regeneration of the microvilli of human placental syncytiotrophoblast.

In order to explore the functional role of microvilli of the syncytiotrophoblast of the human full-term placenta, 16 placentas were examined by scanning electron microscopy (SEM). Our results showed that the microvilli projecting from the apical portion of the syncytiotrophoblast appeared to be highly pleomorphic and showed regional variations in their distribution. This has been correlated to the difference in the stage of growth of microvilli following certain obvious examples of loss. Such a process of distortion and renewal or regeneration may suggest a dynamic functional activity of the microvilli on the villous surface.

Patterns of stromal elements in an implanted ureteric transitional cell carcinoma. An immunohistochemical and ultrastructural study.

The results of the study of three implanted ureteric tumors from a primary transitional cell carcinoma of the renal pelvis are reported. Using both light microscopic immunohistochemistry and transmission electron microscopy, the stroma of the tumor showed consistent evidence for the production of at least its collagenous component by the neoplastic cells. Our findings argue with the notion that occasional fibroblasts and other cells of mesenchymal origin could play a major role in this phenomenon. Therefore, it seems plausible to suggest that what is happening in these tumors is similar to the behavior of malignant cells in scirrhous 'infiltrating' carcinoma of the breast and other sites.

Congenital malformations and intrauterine growth retardation in streptozotocin induced diabetes during gestation in the rat.

Diabetes was induced in Wistar rats by single intraperitoneal injections of streptozotocin (STZ) (50 mg/kg, in citrate buffer pH 4.7) at both preimplantation and organogenetic stages. The controls were either buffer treated or, following STZ administration, injected intraperitoneally with 2 to 6 IU of insulin daily until term. Fetuses collected on day 20 were found to have several malformations. Major abnormalities included gastroschisis and evisceration, maxillary hypoplasia and interatrial, and interventricular septal defects. Intrauterine growth retardation was present in most of the diabetic groups. Heavier placentae and shorter umbilical cords were also observed. Malformations and intrauterine growth retardation were numerous and severe in the preimplantation treatment groups. Insulin administration significantly improved the fetal body weight but did not change the malformation rate in the group made diabetic during organogenesis. It appears that the duration of hyperglycemic state plays a crucial role in malformation and growth retardation, and meticulous control of blood sugar from early stages has significant beneficial effects on fetal development.

Distribution and ultrastructural characterization of the stroma in scirrhous 'infiltrating' carcinoma of the human breast.

A combination of light microscopic, histochemical, immunohistochemical and transmission electron microscopic techniques were used to study the distribution and ultrastructural characterization of the stroma of Scirrhous 'infiltrating' carcinoma of the human breast. Both the light and electron microscopic techniques emphasized the presence of regional variations in the distribution of fibrous tissue in this type of tumour. Whilst fibronectin and collagen type III appeared relatively rich in both periductal and diffused regions, there was a clear contrast in the distribution of collagen type I and elastic tissue between the two regions. Collagen type I was more numerous in the diffused regions whereas elastic tissue was more produced in the periductal regions. The present study confirmed the views that Scirrhous carcinoma cells secrete inappropriately the majority of collagen, elastic and possibly other fibrillar elements of the connective tissue stroma. Fibroblasts, myofibroblasts and myoepithelial cells are believed to contribute in a minor way to the production of the various connective tissue elements. Finally, our findings have been discussed in relation to the mechanism of invasiveness of the tumour cells.

Calcium deposition on the maternal surface of the human placenta: a scanning electron microscopic study.

To explore the role of calcium in the materno-foetal relationship we decided to study the surface ultrastructure of the human placenta. Fresh pieces of tissues were obtained from central and peripheral parts of the maternal surface of human full-term placentas, processed and then examined with the Scanning Electron Microscope. Calcium depositions could only be seen at higher magnifications in forms of flecks, plaques, and concretions. They were frequently found in firm association with the tips of microvilli projecting from the apical parts of the syncytiotrophoblasts, which led to the clumping of those tips. Regional variations in the distribution of calcium deposits were apparent. Our findings indicate that placental calcification is a continual process occurring simultaneously in various parts of the placenta to varying degrees. Moreover, it seems possible that the process of placental calcification is of clinical and pathological significance bearing relationship to both maternal and foetal conditions.