Subjacent Lamina Research Articles

Characteristics of Hirayama Disease in Young South Korean Soldiers.

The purpose of this study was to describe the clinical presentation and features in electrodiagnostic and imaging investigations of young South Korean males diagnosed with Hirayama disease (HD). We reviewed the electronic medical records of South Korean enlisted soldiers who were diagnosed with HD and discharged from military service during 2011-2021. We investigated the clinical characteristics and results of electrodiagnostic and magnetic resonance imaging (MRI) investigations. We analyzed laterality and identified the involved muscles using needle electromyography (EMG). Loss of lordosis, localized cervical cord atrophy, loss of attachment between the posterior dura and subjacent lamina, asymmetric flattening of the cord, crescent-shaped mass in the posterior epidural space, and noncompressive intramedullary T2-weighted high signal intensity were investigated using neutral- or flexion-position MRI. Forty-two male patients aged 20.2±0.8 years (mean±standard deviation) were identified. All patients complained of hand weakness, and 10 complained of hand tremor (23.8%). Four patients (9.5%) had symptoms in both upper limbs, and five (11.9%) had sensory disturbances. Needle EMG revealed that muscles in the C7-T1 myotome were commonly involved, and C5-C6 involvement of the deltoid (10.5%) and biceps brachii (12.5%) was also observed. In cervical MRI, localized cord atrophy (90.0%) was the most characteristic finding, and cord atrophy was most severe at the C5-C6 level (58.3%). This is the first description of a large number of patients with HD in South Korea. The clinical presentation and features found in electrodiagnostic and imaging investigations will improve the understanding of HD in the young South Korean male population.

Clinical profile and dynamic magnetic resonance imaging in Hirayama disease: a single-centered cross-sectional study in Nepal.

Eighteen patients were assessed for clinical and radiological Hirayama disease. Clinical criteria included insidious onset nonprogressive chronic upper limb weakness and atrophy in teens or early twenties without sensory deficits and coarse tremors. MRI was done in a neutral position followed by neck flexion to evaluate cord atrophy and flattening, abnormal cervical curvature, loss of attachment between the posterior dural sac and subjacent lamina, anterior shifting of the posterior wall of the cervical dural canal, posterior epidural flow voids, and an enhancing epidural component with its dorsal extension. The mean age was 20.33 years, and the majority, 17 (94.4%), were male. Neutral-position MRI revealed loss of cervical lordosis in 5 (27.8%) patients, cord flattening in all patients with asymmetry in 10 (55.5%), and cord atrophy was observed in 13 (72.2%) patients with localized cervical cord atrophy in only 2 (11.1%) and extension of atrophy to dorsal cord in 11 (61.1%) patients. Intramedullary cord signal change was seen in 7 (38.9%) patients. Loss of attachment of posterior dura and subjacent lamina and anterior displacement of dorsal dura was seen in all patients. A crescent-shaped epidural intense enhancement was noted along the posterior aspect of the distal cervical canal in all patients, with dorsal level extension in 16 (88.89%) patients. The mean thickness of this epidural space was 4.38±2.26 (mean±2SD), and the mean extension was 5.5±4.6 vertebral levels (mean±2SD). The high degree of clinical suspicion can guide additional contrast studies in flexion as a set MRI protocol for early detection and avoiding false negative diagnoses of HD.

Update on the Pathogenesis, Clinical Diagnosis, and Treatment of Hirayama Disease.

Hirayama disease (HD) is characterized by the juvenile onset of unilateral or asymmetric weakness and amyotrophy of the hand and ulnar forearm and is most common in males in Asia. A perception of compliance with previous standards of diagnosis and treatment appears to be challenged, so the review is to update on HD. First, based on existing theory, the factors related to HD includes, (1) cervical cord compression during cervical flexion, (2) immunological factors, and (3) other musculoskeletal dynamic factors. Then, we review the clinical manifestations: typically, (1) distal weakness and wasting in one or both upper extremities, (2) insidious onset and initial progression for 3–5 years, (3) coarse tremors in the fingers, (4) cold paralysis, and (5) absence of objective sensory loss; and atypically, (1) positive pyramidal signs, (2) atrophy of the muscles of the proximal upper extremity, (3) long progression, and (4) sensory deficits. Next, updated manifestations of imaging are reviewed, (1) asymmetric spinal cord flattening, and localized lower cervical spinal cord atrophy, (2) loss of attachment between the posterior dural sac and the subjacent lamina, (3) forward displacement of the posterior wall of the cervical dural sac, (4) intramedullary high signal intensity in the anterior horn cells on T2-weighted imaging, and (5) straight alignment or kyphosis of cervical spine. Thus, the main manifestations of eletrophysiological examinations in HD include segmental neurogenic damages of anterior horn cells or anterior roots of the spinal nerve located in the lower cervical spinal cord, without disorder of the sensory nerves. In addition, definite HD needs three-dimensional diagnostic framework above, while probable HD needs to exclude other diseases via “clinical manifestations” and “electrophysiological examinations”. Finally, the main purpose of treatment is to avoid neck flexion. Cervical collar is the first-line treatment for HD, while several surgical methods are available and have achieved satisfactory results. This review aimed to improve the awareness of HD in clinicians to enable early diagnosis and treatment, which will enable patients to achieve a better prognosis.

Hirayama Disease: Magnetic Resonance Imaging Manifestations and Single Centre Experience

Purpose: A retrospective study to evaluate various MR imaging spectrums of clinically diagnosed cases of Hirayama disease. Materials and Method: This study included a review of images of 13 patients on the hospital information system who underwent imaging evaluation for suspected Hirayama disease on 3 Tesla MRI scanner in postcontrast neutral and flexion positions. Images were evaluated for the following findings: Localised lower cervical cord atrophy, asymmetric cord flattening, Abnormal cervical curvature, an Increased signal on T2WS, Loss of attachment between posterior dura and lamina, presence of flow void with enhancement. Observations: Lower cervical cord atrophy, anterior dural shift with flexion, and postcontrast enhancement of epidural component was found in thirteen out of thirteen patients (100%), followed by the hyperintense signal in T2WS in the cord which was found in 11 patients. Loss of attachment of posterior dura and subjacent lamina and abnormal curvature of the spine was found in 9 out of thirteen patients (91.3%), prominent epidural flow void was found in eight out of thirteen patients (61.5%), the thoracic extension of enhancing epidural component was found in five patients (38.4%).

PROXIMAL BRACHIAL MONOMELIC AMYOTROPHY OR HIRAYAMA DISEASE: NO LONGER AN ALIAS? (case report)

Background. Brachial Monomelic Amyotrophy (BMMA) has been called as Hirayama disease (HD) when it is characterized by unilateral distal upper limb weakness and atrophy that shows progression for a limited period and is associated with typical features on MRI of cervical spine in flexion.
 Objective was to explore the differences when BMMA affects the proximal upper limb muscles with the help of case report.
 Methods. A case report of BMMA in an adult Indian male is represented.
 Results. A 30-year-old man presented to us with a history of weakness in the proximal aspect of his left upper limb that began four years ago. The weakness was progressive up until 6 months prior to his presentation since when the weakness had neither worsened nor improved. Cervical spine contrast enhanced MRI revealed mild loss of cervical lordosis, but no features of HD like localized cord atrophy, loss of attachment of dura from subjacent lamina on neutral position axial T2WI MRI, nor any presence of posterior epidural crescentic enhancing mass on flexion contrast sagittal T1WI MRI. The patient was managed with supportive therapy and has been under regular follow up ever since. His clinical status has been stable.
 Conclusions. We support the suggestion to consider proximal Brachial Monomelic Amyotrophy to be a separate entity and to be distinguished from Hirayama disease that should be reserved for patients with distal upper limb involvement with cervical MRI findings on flexion studies.

A Highly Divergent Picornavirus Infecting the Gut Epithelia of Zebrafish (Danio rerio) in Research Institutions Worldwide.

Zebrafish have been extensively used as a model system for research in vertebrate development and pathogen-host interactions. We describe the complete genome of a novel picornavirus identified during a viral metagenomics analysis of zebrafish gut tissue. The closest relatives of this virus showed identity of <20% in their P1 capsids and <36% in their RdRp qualifying zebrafish picornavirus-1 (ZfPV-1) as member of a novel genus with a proposed name of Cyprivirus. Reverse transcription (RT)-PCR testing of zebrafish from North America, Europe, and Asia showed ZfPV-1 to be globally distributed, being detected in 23 of 41 (56%) institutions tested. In situ hybridization of whole zebrafish showed viral RNA was restricted to a subset of enterocytes and cells in the subjacent lamina propria of the intestine and the intestinal mucosa. This naturally occurring and apparently asymptomatic infection (in wild-type zebrafish lineage AB) provides a natural infection system to study picornavirus-host interactions in an advanced vertebrate model organism. Whether ZfPV-1 infection affects any immunological, developmental, or other biological processes in wild-type or mutant zebrafish lineages remains to be determined.

Hirayama disease: An uncommon cause of distal upper extremity deficit

Hirayama disease is a myelopathy related to flexion movements of the neck that produce ischemic damage in the anterior horn of the cervical cord. The disease affects young people and is characterized by a distal upper extremity deficit that develops gradually. The diagnosis is confirmed by cervical magnetic resonance imaging (MRI) in flexion demonstrating a forward shift of the posterior dural sac and spinal cord compression. On radiology, there should be suggestive signs in neutral position such as cord atrophy, intramedullary bilateral high signal intensity on T2-weighted images, straightening of the cervical spine, and loss of attachment between the posterior dural sac and subjacent lamina. Exploration should be completed by an MR study in neck flexion. We report here on two typical cases of the disease and also include a review of the literature.

Waterskier’s Hirayama syndrome

Hirayama disease is a segmental inferior cervical myelopathy. Presentation is usually in young males with unilateral or asymmetrical upper limb weakness and atrophy. The clinical features can be similar to the initial presentation of amyotrophic lateral sclerosis, but Hirayama syndrome has a benign course and is typically limited to distal muscles of the upper limbs. The typical teenage onset of the syndrome corresponds with juvenile growth spurt. The disproportionate growth of the vertebral column compared to the spinal cord resulting in the relative shortening of the dorsal roots and the loss of attachment between the posterior dural sac and the subjacent lamina are considered to be contributing factors [1]. Several reports document antecedent events including repetitive movements, competitive sport or strenuous physical work. Jeannet et al. [2] documented the case of a 10-year-old girl who had a nocturnal rhythmic movement disorder, leading to prolonged repetitive neck flexion at night time. Huang et al. [3] reported that 37.5% of their patients with Hirayama disease frequently participated in vigorous sports or physical activity for at least 6 months before the onset of symptoms. These activities included basketball, baseball, martial arts, body-building, strenuous farm work or military training. We describe the case of a competitive waterskier who presented with the typical clinical features of Hirayama syndrome. A 55-year-old international waterski champion presented with a 2-year history of progressive left hand weakness. His symptoms developed following an intensive season of waterskiing. His waterskiing activities include travelling up to speeds of 80 kph prior to jumps, with violent passive neck flexion when landing. On examination he had marked wasting of C8 and T1 innervated muscles with striking preservation of the proximal forearm musculature (Fig. 1). Sensory examination was normal as was remainder of his neurological examination. Concentric needle EMG examination revealed fibrillation potentials and positive sharp waves in the left dorsal interosseous and abductor pollicis brevis. Large amplitude long duration polyphasic motor unit activation potentials with reduced recruitment were present in the remaining C7-T1 innervated muscles on the left. Sensory nerve action potentials were normal. No abnormalities were detected in the remaining limbs. A priority of the diagnostic work up was to rule out multifocal motor neuropathy (MMN). There was no evidence of conduction block on repeated conduction studies and anti GM1 ganglioside antibody titers were negative. CSF examination was normal. Standard, axial and sagittal cervical spine MR imaging in a neutral position showed moderate spondylotic changes, in which the vertebral bodies formed an uneven posterior surface. There was no evidence of cord or nerve root compression. Axial imaging in neck flexion demonstrated cord flattening with marked anterior shifting of the posterior wall of the cervical dural canal Fig. 2. P. Bede (&) A. L. W. Bokde S. C. Byrne M. Elamin O. Hardiman Trinity College Dublin, Dublin, Ireland e-mail: bedepeter@hotmail.com

Imaging features in Hirayama disease

To evaluate the MR findings in clinically suspected cases of Hirayama disease. The pre and post contrast neutral and flexion position cervical MR images of eight patients of clinically suspected Hirayama disease were evaluated for the following findings: localized lower cervical cord atrophy, asymmetric cord flattening, abnormal cervical curvature, loss of attachment between the posterior dural sac and subjacent lamina, anterior shifting of the posterior wall of the cervical dural canal and enhancing epidural component with flow voids. The distribution of the above features in our patient population was noted and correlated with their clinical presentation and electromyography findings. Although lower cervical cord atrophy was noted in all eight cases of suspected Hirayama disease, the rest of the findings were variably distributed with asymmetric cord flattening, abnormal cervical curvature, anterior shifting of the posterior wall of the cervical dural canal and enhancing epidural component seen in six out of eight (75%) cases. An additional finding of thoracic extension of the enhancing epidural component was also noted in five out of eight cases. Dynamic post contrast MRI evaluation of cervicothoracic spine is an accurate method for the diagnosis of Hirayama disease.

Morphology of the air-breathing stomach of the catfish Hypostomus plecostomus.

Histological and ultrastructural investigations of the stomach of the catfish Hypostomus plecostomus show that its structure is different from that typical of the stomachs of other teleostean fishes: the wall is thin and transparent, while the mucosal layer is smooth and devoid of folds. The epithelium lining the whole internal surface of the stomach consists of several types of cells, the most prominent being flattened respiratory epithelial cells. There are also two types of gastric gland cells, three types of endocrine cells (EC), and basal cells. The epithelial layer is underlain by capillaries of a diameter ranging from 6.1-13.1 microm. Capillaries are more numerous in the anterior part of the stomach, where the mean number of capillary sections per 100 microm of epithelium length is 4, compared with 3 in the posterior part. The cytoplasm of the epithelial cells, apart from its typical organelles, contains electron-dense and lamellar bodies at different stages of maturation, which form the sites of accumulation of surfactant. Small, electron-dense vesicles containing acidic mucopolysaccharides are found in the apical parts of some respiratory epithelial cells. Numerous gastric glands (2 glands per 100 microm of epithelium length), composed of two types of pyramidal cells, extend from the surface epithelium into the subjacent lamina propria. The gland outlets, as well as the apical cytoplasm of the cells are Alcian blue-positive, indicating the presence of acidic mucopolysaccharides. Zymogen granules have not been found, but the apical parts of cells contain vesicles of variable electron density. The cytoplasm of the gastric gland cells also contains numerous electron-dense and lamellar bodies. Gastric gland cells with electron-dense cytoplasm and tubulovesicular system are probably involved in the production of hydrochloric acid. Fixation with tannic acid as well as with ruthenium red revealed a thin layer of phospholipids and glycosaminoglycans covering the entire inner surface of the stomach. In regions of the epithelium where the capillaries are covered by the thin cytoplasmic sheets of the respiratory epithelial cells, a thin air-blood barrier (0.25-2.02 microm) is formed, thus enabling gaseous exchange. Relatively numerous pores closed by diaphragms are seen in the endothelium lining the apical and lateral parts of the capillaries. Between gastric gland cells, solitary, noninnervated endocrine cells (EC) of three types were found. EC are characterized by lighter cytoplasm than the surrounding cells and they contain dense core vesicles (DCV) with a halo between the electron-dense core and the limiting membrane. EC of type I are the most abundant. They are of an open type, reaching the stomach lumen. The round DCV of this type, with a diameter from 92-194 nm, have a centrally located core surrounded by a narrow halo. EC of type II are rarely observed and are of a closed type. They possess two kinds of DCV with a very narrow halo. The majority of them are round, with a diameter ranging from 88-177 nm, while elongated ones, 159-389 nm long, are rare. EC of type III are numerous and also closed. The whole cytoplasm is filled with large DCV: round, with a diameter from 123-283 nm, and oval, 230-371 nm long, both with a core of irregular shape and a wide, irregular halo. EC are involved in the regulation of digestion and probably local gas exchange. In conclusion, the thin-walled stomach of Hypostomus plecostomus, with its rich network of capillaries, has a morphology suggesting it is an efficient organ for air breathing.

Binding of Clostridium difficile surface layer proteins to gastrointestinal tissues.

Clostridium difficile is the etiological agent of antibiotic-associated diarrhea, a potentially serious condition frequently affecting elderly hospitalized patients. While tissue damage is primarily induced by two toxins, the mechanism of gut colonization, and particularly the role of bacterial adherence to the mucosa, remains to be clarified. Previous studies have shown binding of C. difficile whole cells to cultured cell lines and suggested the existence of multiple adhesins, only one of which has been molecularly characterized. In this paper, we have investigated tissue binding of C. difficile surface layer proteins (SLPs), which are the predominant outer surface components and are encoded by the slpA gene. The adherence of C. difficile to HEp-2 cells was studied by enzyme-linked immunosorbent assay and fluorescence-activated cell sorter analysis, which showed that antibodies to the high-molecular-weight (MW) SLP inhibited adherence. Immunohistochemical analysis of human gastrointestinal tissue sections revealed strong binding both to the surface epithelium lining the digestive cavities and to the subjacent lamina propria, while glands were negative. A similar pattern was observed in the mouse. By using purified recombinant SLPs, we show that binding is largely mediated by the high-MW SLP. By Western blotting analysis, we have identified two potential ligands of the C. difficile SLPs, one of which may be specific to the gut. By using purified extracellular matrix components immobilized on nitrocellulose, we also show SLP binding to collagen I, thrombospondin, and vitronectin, but not to collagen IV, fibronectin, or laminin. These results raise the possibility that the SLPs play a role both in the initial colonization of the gut by C. difficile and in the subsequent inflammatory reaction.

A Retrospective Histopathological Survey of Capillariasis in Raccoons from the Eastern United States

A 7-yr retrospective survey (1986-1993) of 193 raccoons (Procyon lotor) from 4 different geographic locations (South Carolina, Virginia, and 2 sites in Pennsylvania) in the eastern United States was conducted by histopathological examination of various tissues. Lesions indicative of capillariasis were observed in raccoons at all locations. An overall prevalence of 45% was recorded. Highest prevalence of nematodes in tissues (71%) was seen in the rural Pennsylvania site. Nematodes were confined to the mucosa of the anterior alimentary tract (mouth, tongue, esophagus) or urinary system (bladder, urethra) without significant inflammation except for a single raccoon in which Capillaria sp. were present in the tracheal mucosa and within the subjacent lamina propria, with moderate inflammatory cellular infiltrate.

Isolation of mature olfactory neurones using retrograde labelling and flow cytometry

Currently we can observe an increasing interest for epithelial olfactory neurones. Several laboratories are involved in elucidation of the odorant-molecule recognition process and transduction cascade which brings information to the olfactory bulb. Others use this model, unique in mammals, to accumulate new knowledge on the neurogenesis phenomenon. Here we describe a simple and efficient method to purify mature olfactory neurone populations extracted from the nasal cavity. The approach relies on retrograde axonal tracing followed by flow cytometry sorting. For this purpose we inject a fluorescent dye (Fast Blue or diI C 18(3)) in the olfactory bulb of adult rats. Seven days later, we extract the nasal turbinates and separate the mucosa from the subjacent lamina propria. The tissue is enzymatically dissociated and the labelled cells are sorted with a flow cytometer. Purification of the mature olfactory neurones varies from 80 to 99%.

Parvalbumin‐immunoreactive structures of the adult human entorhinal and transentorhinal region

Parvalbumin-immunoreactive structures in the entorhinal and transentorhinal region of the adult human brain were studied using the avidin-biotin-peroxidase technique. Parvalbumin-immunoreactive neurons and fibers (axons) were present in all layers (layer nomenclature according to Rose, 1927). The density of fibers was high in the islands of the superficial cell layer pre-alpha and in layer pre-beta and still heavier in pre-gamma. In the subjacent lamina dissecans it diminished abruptly and remained low in all layers of the internal principal stratum (layers pri-alpha, -beta, -gamma). This low density of fibers facilitated recognition of axon cartridges in layers pri-alpha and pri-gamma. Axon cartridges were also present within layers pre-beta and pre-gamma but were obscured by the dense fiber network there. Parvalbumin immunoreactivity was observed in the nerve cell soma and throughout the dendritic tree allowing the distinction of numerous nerve cell types. All parvalbumin-immunoreactive neurons belonged to the class of nonpyramidal neurons. Their lipofuscin pigment patterns differed distinctly from that of the pyramidal and modified pyramidal neurons. Based on their location, soma size, and dendritic arborization, they were grouped as large, medium-sized, and small neurons either of the multipolar or bipolar (vertical or horizontal) type. One type could be identified as an axo-axonic neuron, more specifically as a chandelier neuron generating axon cartridges. The dense fiber net within layer pre-gamma suggested the existence of another neuronal type, probably a neuron with an extended axonal ramification. The identified neurons were compared to neuronal types described in the literature from Golgi studies.

The topographic distribution of lymphocytic gastritis in gastrectomy specimens

Forty-eight entire gastrectomy specimens received consecutively at this Department were cut into blocks for histologic examination. Focal or more extended areas of chronic gastritis (i.e. superficial or atrophic with or without intestinal metaplasia) were present in all 48 specimens. In addition, two of the 48 specimens had a large number of lymphocytes in the surface and foveolar epithelium of the mucosa. In the literature the latter is regarded as "lymphocytic gastritis". Lymphocytic gastritis was found in all 156 sections obtained from the two specimens. This lympho-epithelial phenomenon was present even in areas lacking chronic inflammation in the subjacent lamina propria mucosae. From our results it would appear that while chronic gastritis has a focal or a regional topographic distribution, lymphocytic gastritis includes the entire surface-foveolar epithelium of the gastric mucosa.

New information on the location of Capillaria procyonis (Nematoda: Trichuroidea) in the tongue of a raccoon (Procyon lotor).

Histologic examination of the tongue of one juvenile male raccoon demonstrated the presence of adults and unembryonated eggs of the nematode Capillaria procyonis within parasite-induced tunnels in the stratified squamous epithelium. There was no inflammatory infiltrate within the epithelium or the subjacent lamina propria. The shape of tunnels approximated that of the resident nematodes and were lined by flattened and attenuated epithelial cells. Therefore, the site of infection of C. procyonis in the raccoon includes the oral, lingual and pharyngeal epithelium in addition to the esophagus.

Ultrastructural characteristics of sustentacular cells in control and odorant-treated olfactory mucosae of the salamander.

The ultrastructural characteristics of five morphologically distinct regions of sustentacular cells in the salamander olfactory mucosa are described. 1) The apical region was characterized by a microvillar surface that lay below the level of the olfactory knob of olfactory receptor neurons and contained endosome-like vesicles and a filamentous array at the level of the zonula adherens. 2) The supranuclear region contained rough and smooth endoplasmic reticulum, a Golgi complex, and secretory vesicles. Few sustentacular cells showed morphological signs of secretion, suggesting a low rate of baseline secretory activity. 3) The nuclear region contained the cylindrical nucleus surrounded by a thin band of cytoplasm containing bundles of filaments. 4) The central stalk contained filamentous arrays, Golgi-like cisternae, multivesicular bodies, and peroxisomes. Cytoplasmic veils that extended from the central stalk contained filamentous aggregates. 5) The basilar expansion had a complex series of lateral and basal folds. The lateral folds enveloped extracellular material and nonmyelinated axons of the receptor neurons. The basal folds formed complex interdigitations with the basal lamina, particularly in regions occupied by blood vessels and the acini of Bowman's glands in the subjacent lamina propria. These characteristics, and the presence of endosome-like vesicles and mitochondria, suggest that the basilar expansion is metabolically active and participates in cellular transport of material. Treatment with the odorant 2-isobutyl-3-methoxypyrazine caused ultrastructural changes in the apical and supranuclear regions that were associated with secretion and in the basilar expansion region that were indicative of an increase in metabolic and transport activity.

Histological and ultrastructural characteristics of the periodontal syndrome in the rice rat. IV. The effects of dietary antibiotics on the histological and ultrastructural characteristics of periodontal syndrome susceptible rats.

In this paper on the periodontal syndrome in the rice rat, the effects of dietary penicillin and tetracycline on the progressive inflammatory and degenerative changes (as seen in rice rats fed diet 700 alone) were noted at the light and electron microscopic level. Throughout the observation period (0–14 weeks postweaning), animals fed diet 700 with penicillin or diet 700 with tetracycline showed no evidence of bacterial colonization, a minimal PMN infiltrate restricted to the gingival epithelium and subjacent lamina propria, and no marked degenerative changes within cells that normally inhabited the periodontium (viz. epithelial cells, fibroblasts, osteoblasts). Marked osteoblastic or osteoclastic activity was rarely noted along the alveolar crest in this group of animals.These results give added support to the concept of a single microbial agent or group of microbial agents, as the primary etiology of this disease.

Lymphocyte infiltration of gut epithelium in fetal and neonatal rabbits.

Lymphocytes infiltrate the epithelium of small intestinal villi of fetal rabbits as early as day 28 of gestation. They appear within the lateral spaces between the columnar absorptive cells. At this time, the epithelial cells transport compounds, such as injected horseradish peroxidase, through these intercellular spaces to the subjacent lamina propria. The possibility for in utero interaction between intraepithelial lymphocytes and antigen in swallowed amniotic fluid is discussed. There is an increase in the number of intraepithelial lymphocytes from 1 per 500 epithelial cells on day 1 to 16 per 500 epithelial cells on day 21 of postnatal life. Each segment, duodenum, jejunum and ileum, shows an increase in the number of lymphocytes during this period.

Canine histiocytic ulcerative colitis. An ultrastructural study of the early mucosal lesion.

Canine histiocytic ulcerative colitis (CHUC) is a chronic debilitating disease of boxer dogs. Study of this disorder may provide information essential to the understanding of pathogenic mechanisms that result in progressive large bowel ulceration. In this study, large intestinal mucosal biopsy specimens from seven affected boxers and four normal dogs were examined by light and electron microscopy. The earliest morphologic change discernible was focal, acute inflammation and epithelial cell degeneration at the luminal surface of the large bowel. These latter changes were nonspecific in nature. The basement membrane of affected epithelium consistently was effaced and intercellular spaces were dilated. Neutrophils were found between intact, degenerating epithelial cells and within the subjacent lamina propria. Convincing evidence for an infectious cause of CHUC was not found. Observed microorganisms probably were secondary invaders since they were present only in lesions exhibiting actual epithelial disruption. The PAS-positive macrophages, which are pathognomonic for the disease, were engorged with numerous digestive vacuoles that mainly contained phospholipid membranes. A developmental sequence was observed which suggested that these PAS-positive cells arose from the actively phagocytic, normal-appearing macrophages found in the surface-oriented mucosal lesions.