Detection of Merkel cell polyomavirus with a tumour-specific signature in non-small cell lung cancer.

BACKGROUND: We searched for a viral aetiology for non-small cell lung cancer (NSCLC), focusing on Merkel cell polyomavirus (MCPyV). METHODS: We analysed 112 Japanese cases of NSCLC for the presence of the MCPyV genome and the expressions of RNA transcripts and MCPyV-encoded antigen. We also conducted the first analysis of the molecular features of MCPyV in lung cancers. RESULTS: PCR revealed that 9 out of 32 squamous cell carcinomas (SCCs), 9 out of 45 adenocarcinomas (ACs), 1 out of 32 large-cell carcinomas, and 1 out of 3 pleomorphic carcinomas were positive for MCPyV DNA. Some MCPyV DNA-positive cancers expressed large T antigen (LT) RNA transcripts. Immunohistochemistry showed that MCPyV LT antigen was expressed in the tumour cells. The viral integration sites were identified in one SCC and one AC. One had both episomal and integrated/truncated forms. The other carried an integrated MCPyV genome with frameshift mutations in the LT gene. CONCLUSION: We have demonstrated the expression of a viral oncoprotein, the presence of integrated MCPyV, and a truncated LT gene with a preserved retinoblastoma tumour-suppressor protein-binding domain in NSCLCs. Although the viral prevalence was low, the tumour-specific molecular signatures support the possibility that MCPyV is partly associated with the pathogenesis of NSCLC in a subset of patients.

[Senning operation for transposition of great arteries in a premature baby].

A male baby was delivered by emergency cesarean section due to fetal distress at 30 weeks of gestational age with a birth weight of 813 g. By fetal echocardiography, the patient had been diagnosed with transposition of great arteries (type 1). Early two-staged arterial switch operation was planned after 34 gestational age avoiding intracranial hemorrhage under cardiopulmonary bypass. At 19 days of life, vegetation was revealed on the pulmonary valve by echocardiography, so he was diagnosed as infectious endocarditis. Cefotaxime and gamma-globulin were given intravenously for 4 weeks. While waiting for the increase in the body weight, desaturation from chronic respiratory distress syndrome was exacerbated. At 8 months old, urgent Senning operation was performed to improve desaturation. The patient was discharged at 20 post operative day. We conclude that Senning operation can be feasible operation in such a complicated case.

Analysis of T cell receptor Vbeta diversity in peripheral CD4 and CD8 T lymphocytes in patients with autoimmune thyroid diseases.

Autoimmune thyroid diseases are characterized by intrathyroidal infiltration of CD4(+) and CD8(+) T lymphocytes reactive to self-thyroid antigens. Early studies analysing T cell receptor (TCR) Valpha gene usage have shown oligoclonal expansion of intrathyroidal T lymphocytes but not peripheral blood T cells. However, TCR Vbeta diversity of the isolated CD4(+) and CD8(+) T cell compartments in the peripheral blood has not been characterized fully in these patients. We performed complementarity-determining region 3 (CDR3) spectratyping as well as flow cytometric analysis for the TCR Vbeta repertoire in peripheral CD4(+) and CD8(+) T cells from 13 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis. Polyclonal TCR Vbeta repertoire was demonstrated by flow cytometry in both diseases. In contrast, CDR3 spectratyping showed significantly higher skewing of TCR Vbeta in peripheral CD8(+) T cells but not CD4(+) T cells among patients with Hashimoto's thyroiditis compared with healthy adults. We found trends towards a more skewed CDR3 size distribution in those patients having disease longer than 5 years and requiring thyroid hormone replacement. Patients with Graves' disease exhibited no skewing both in CD4(+) and CD8(+) T cells. These findings indicate that clonal expansion of CD8(+) T cells in Hashimoto's thyroiditis can be detected in peripheral blood and may support the role of CD8(+) T cells in cell-mediated autoimmune attacks on the thyroid gland in Hashimoto's thyroiditis.

Relationship of age to prevalence of focal acinar cell dysplasia in the human pancreas.

The prevalence of focal dysplastic lesions of acinar cells in the pancreata of autopsied children and adults was compared. The lesions were recognized in sections stained with hematoxylin and eosin because acinar cells forming islet-sized foci or larger nodules contained one or more of the following cytologic abnormalities: reduced cytoplasmic basophilia, reduced cytoplasm, reduced zymogen, cytoplasmic vacuoles, or nuclear abnormalities. Lesions were found in only 1 patient (age, 7 yr) of 170 patients whose ages ranged from birth to 9 years, whereas 7 of 49 patients 10-19 years old had focal acinar cell dysplasia. The prevalence of such lesions among adults was comparable to that encountered in individuals during the second decade of life and distinctly higher than that found among children during the first decade. Six of the 8 children in whom dysplastic acinar cell foci were found had cancers in other tissues that had been treated by chemotherapy. The data are consistent with the interpretation that dysplastic acinar cell lesions in the pancreas are acquired.

Congestive heart failure and absent femoral pulses in newborns without coarctation of the aorta.

Two infants with thrombosis of the abdominal aorta are discussed. In each case the presentation was indistinguishable from that in coarctation of the aorta, with heart failure and absent femoral pulses. Surgery in one infant successfully relieved the obstruction. The diagnosis may not be suspected from the history. Aggressive management is indicated.

Two patterns of opacity in corneal dystrophy caused by the homozygous BIG-H3 R124H mutation.

PURPOSE: To investigate the opacity pattern in corneas with an Arg124His (R124H) homozygous mutation of the BIG-H3 gene. METHODS: Slit-lamp examination was performed on eight patients with corneal dystrophy resulting from a genetically confirmed BIG-H3 R124H homozygous mutation. The birthplace of each patient also was determined. RESULTS: Slit-lamp examination disclosed two types of opacity patterns in corneas with the BIG-H3 R124H homozygous mutation. Type I (n = 4) is a spot-like opacity present in the anterior stroma in which the lesions are confluent. Type I is the same pattern that previous reports have shown to be caused by the BIG-H3 R124H homozygous mutation. The type II corneal opacity pattern (n = 4) is a reticular opacity in the anterior stroma with round translucent spaces. Type II opacity has not been reported previously in association with any corneal dystrophy. The patients with the type I opacity do not share a common birthplace; however, interestingly, the patients with the type II opacity traced their origin to Tottori prefecture in western Japan. CONCLUSION: The BIG-H3 homozygous R124H mutation induces the development of two distinct patterns of corneal opacity, the recognition of which can establish an accurate diagnosis of corneal dystrophy caused by the homozygous BIG-H3 R124H mutation independent of genetic analysis. In addition, genetic factors or circumstantial influences other than the gene responsible for the corneal dystrophy may influence the pattern of corneal opacity.

Conduction tissue anomalies in absence of the right superior caval vein.

The incidence of electrical instability of the heart is high in patients with absence of the right and persistence of the left superior caval vein when the latter connects to the coronary sinus. It has been suggested that a large coronary sinus may influence the susceptibility to arrhythmias. we studied the conduction tissues of 8 hearts from the cardiopathological collection of Children's Hospital of Pittsburgh. Six of these specimens had a persistent left superior caval vein connecting to the coronary sinus. There were 4 with absence of the right superior caval vein, 3 of which were in the group with persistent left veins. We evaluated the sinus node and the specialized atrioventricular junctional area, comparing them with known normals. The coronary sinus varied in size from through it. The size did not alter the histology of the adjacent conduction tissue. In contrast, the sinus node was abnormal in 3 of the 4 hearts with absent right superior caval vein. This may be the key factor in the development of arrhythmias when the right superior caval vein is absent or abnormal.

Temporal bone histopathologic findings of Waardenburg's syndrome: a case report.

A histopathological study of the temporal bones of a 3-year-old black girl who had bilateral deafness associated with Waardenburg's syndrome type II showed a similar pattern of pathology in both ears. The most striking findings were an absence of pigmentation in the inner ear and cochleosaccular abnormality. This is, to our knowledge, only the third report on human temporal bone histopathology in Waardenburg's syndrome and the first report of such a case with absence of pigment (melanin) in the inner ear. A possible association of hearing loss with absence of inner ear pigment in this case is discussed.

Temporal bone histopathologic findings in Alagille's syndrome.

Six temporal bones obtained from four individuals with Alagille's syndrome, aged 4 months and 3, 6, and 7 years, were studied histopathologically. The external auditory canals and tympanic membranes were normal. Although the stapes, the interossicular joints, and the subarcuate fossae were slightly underdeveloped in the majority of cases, the other structures in the middle ear were almost normal. However, severe anomalies were observed in structures in the inner ear. In all cases, both the bony and membranous structures of the posterior semicircular canal were partially or totally absent, and, in three ears, those of the anterior semicircular canal were also partially absent; the lateral semicircular canal, however, was normal in all cases. The cochlea was observed to be shortened in only one case.

Congenital alopecia, seizures, and psychomotor retardation in three siblings.

Three siblings, devoid of hair at birth, had an unusual autosomal recessive disorder characterized by universal congenital alopecia, microcephaly, seizures, psychomotor retardation, and severe growth failure. Metabolic and chromosome studies were normal. Skin biopsies disclosed immature hair follicles, some of which were filled with keratotic material but had no hair shafts. Neuropathologic features included cerebral cortical hypoplasia, neuronal depletion, and microcalcifications. The familial occurrence of universal congenital alopecia conjoined with nonprogressive central nervous system abnormalities in this and other kindreds defines a nosologic group of neurocutaneous disorders in which congenital alopecia is the solitary cutaneous manifestation.

Polycystic kidneys, pancreatic cysts, and cystadenomatous bile ducts in the oral-facial-digital syndrome type I.

Oral-facial-digital syndrome type I is a group of X-linked dominant conditions, lethal in utero in male individuals. Internal anomalies are less well documented than are external findings. We report a case of typical phenotype and absent family history of kidney disease in a 15-year-old white girl (46,XX) who died of renal failure and massive cerebral hemorrhage. At necropsy, the kidneys were greatly enlarged but of fairly normal shape. The cortex was replaced by thin-walled spherical cysts, 0.5 to 2.0 cm in diameter; the majority of the smaller cysts were located deep in the cortex, and the medulla contained lesser numbers of larger cysts. No distal urinary tract obstruction was present. Microdissection revealed cysts and diverticula located in all segments of the nephrons and collecting ducts. Uninvolved nephrons showed diffuse hypertrophy. These findings were correlated with immunoperoxidase stains using peanut lectin, Lotus tetragonolobus agglutinin, antibodies to cytokeratins, stage-specific embryonic antigen-1, Tamm-Horsfall protein, and epithelial membrane antigen. Other visceral anomalies included biliary cystadenomatous proliferation in the liver and pancreatic cysts. The renal changes are similar to those of autosomal dominant (adult-type) polycystic disease.

Mesenchyme remaining in human temporal bones.

This study was conducted in order to gain basic information about mesenchyme remaining in the middle ear cleft in normal infants. Because no previous report has objectively described the quantity or quality of such postnatal remnants in normal infants, it has not been possible to accurately evaluate the significance of mesenchyme remaining in the middle ears of infants with pathologic conditions, such as otitis media and congenital anomalies. Thus, 53 temporal bones obtained from 41 individuals reported upon here--from 26 weeks' gestation to 8 years of age--will be controls for future studies of pathologic conditions. The children from whom these temporal bones were obtained had no anomalies of the ear (or any other known part of the body); nor did they have any pathologic conditions in the ear. The temporal bones were prepared for histologic study with hematoxylin and eosin staining and were examined under the light microscope. After areas of the mesenchyme in the histologic sections were projected and illustrated for each of 19 portions in the middle ear cleft under the microprojector, those areas were measured by compensating polar planimetry. The findings obtained in this study were as follows: The amount of mesenchyme remaining in the days after birth seemed to gradually decrease in volume with increased maturity and had nearly disappeared within the first year in normal infants. Where mesenchyme was noted in the temporal bones of infants over 1 year of age, it was usually present only in small niches.(ABSTRACT TRUNCATED AT 250 WORDS)

Histopathologic study of otitis media in individuals with head and neck tumors.

Five temporal bones, each including the eustachian tube, were obtained from five adults with advanced malignant tumors of the head and neck. The specimens were from the side on which the tumor had occurred. Otitis media had been detected clinically in two cases, and was detected histopathologically in the other three. We discuss the possibility that otitis media might have been caused by tumor invasion of the paratubal area, by postoperative inflammation in the nasopharynx, or by an inflammatory reaction of tubal structures to radiotherapy, or that these conditions may have coexisted.

Histologic study of eustachian tube cartilage with and without congenital anomalies: a preliminary study.

We investigated histopathologically the development of the eustachian tube (ET) cartilage at a cellular level in individuals with and without congenital anomalies. Fourteen specimens were obtained from 14 individuals ranging in age from 24 weeks' gestation to 3 years who had cleft palate or trisomy 21 (Down) syndrome; the 49 specimens in the nonanomaly (control) group were from 49 individuals ranging from 26 weeks' gestation to 85 years of age. All temporal bone specimens included the ET and its accessory structures, and all were processed and stained with hematoxylin and eosin for histologic study in a routine manner. The number of cartilage cells in the midcartilaginous portion of the ET was determined by light microscopy. In all groups, cartilage cell density of the ET decreased with increasing age. However, cell density tended to be higher at all ages for individuals with cleft palate and microtia versus controls, and tended to be lower at all ages for individuals with Down syndrome.

Histopathology of otitis media in infants with cleft and high-arched palates.

The middle ear and the bony and cartilaginous portions of the eustachian tube (ET) were studied histopathologically in 20 temporal bones from 19 infants, aged 45 minutes to 12 months. Otitis media (OM) was observed in 17 of 20 bones, and 16 bones with OM had an effusion. Otitis media was more severe in the ears of cleft palate infants compared to those with high-arched palates. Inflammation was present in the bony portion of the ET in 15 of 17 temporal bones with OM, but appeared to be less marked than that present in the middle ear. In addition, inflammation of the cartilaginous portion of the ET appeared to be less severe than in its bony portion. Inflammation of the middle ear and the ET appeared to be more pronounced in older infants, particularly in those with cleft palates.

Experimental otitis media evaluated by magnetic resonance imaging: an in vivo model.

The use of magnetic resonance imaging in otitis media research is being explored in our laboratory. In this study, we present a new method for studying changes in the middle ear cleft due to an episode of induced otitis media in the chinchilla model. It uses gadolinium-diethylenetriamine pentaacetic acid, a magnetic resonance imaging contrast agent, to examine the uptake and washout characteristics of middle ear mucosa during an inflammatory episode. Parameters such as the time to maximum intensity of the mucosa and the washout rate of the contrast agent from the mucosa were significantly correlated to the duration of the infection.

A staged laryngotracheal reconstruction using alloplast (Proplast) in the canine model.

Standard laryngotracheal reconstructive procedures are constrained by the availability of grafting materials and the ability to repair large defects. Reconstruction utilizing alloplasts may be ideal, but previous results have generally been poor. We present a two-stage procedure using Proplast to reconstruct large laryngotracheal defects in 6 dogs. A custom-made Proplast implant was inserted into a strap muscle pocket and buccal mucosa was placed in the adjacent peritracheal tissue. The muscle-Proplast composite graft was rotated to repair a large defect (3.25 cm by 2.25 cm). All 6 dogs survived. Endoscopic and histologic studies over 12 months showed continued stabilization and maturation of the implant. We feel that Proplast may be used as an alternative to autograft for reconstructing large laryngotracheal defects when the procedure is staged to allow maximal fibrous ingrowth and the implant is protected from infection.