A novel t(2;6)(p12;q23) appearing during transformation of follicular lymphoma with t(18;22)(q21;q11) to diffuse large cell lymphoma

Follicular lymphoma is characterized genetically by t(14;18)(q32;q21), whereas t(18;22)(q21;q11), a rare variant form of t(14;18), has been preferentially observed in chronic lymphocytic leukemia (CLL). We describe here an unusual case of follicular lymphoma with a t(18;22)(q21;q11), that progressed to diffuse large cell lymphoma with a novel t(2;6)(p12;q23). Spectral karyotyping revealed that add(2)(p12) and add(6)(q23) were derived from a t(2;6)(p12;q23). Fluorescence in situ hybridization analysis confirmed rearrangements of the BCL2 gene at 18q21 and the BCL6 gene at 3q27. Our results indicate that a reciprocal translocation involving 6q23 could be implicated in the progression of follicular lymphoma and that t(18;22) may have a specific role in the pathogenesis of follicular lymphoma as well as CLL.     

PATHOLOGICAL STUDY ON AMYLOIDOSIS —RELATIONSHIP OF AMYLOID DEPOSITS IN THE AORTA TO AGING—

Senile aortic amyloidosis in 224 autopsy cases over 40 years was investigated comparing cardiac and pancreatic amyloidosis in them. A total of 176 cases of aortic amyloidosis was found for an average incidence of 79%. Under the 5th decade the incidence was 51% and it rose sharply with age and reached 95% in over the 8th decade. The incidence of cardiac amyloidosis also increased with age, but it was always higher in the aorta. Aortic and cardiac amyloid were both positive in the DMAB method for tryptophan. The major part exposed to amyloidosis in the aorta was the media. The medial amyloid consisted of numerous minute deposits and had no relation to atherosclerosis. Some comments about the pathogenesis of senile amyloidosis were also mentioned.     

A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia

Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia.     

GATA3 abnormalities and the phenotypic spectrum of HDR syndrome

We report on GATA3 analysis and the phenotypic spectrum in nine Japanese families with the HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) (MIM 146255). Fluorescence in situ hybridisation and microsatellite analyses showed heterozygous gross deletions including GATA3 in four families. Sequence analysis showed heterozygous novel mutations in three families: a missense mutation within the first zinc finger domain at exon 4 (T823A, W275R), an unusual mutation at exon 4 (900insAA plus 901insCCT or C901AACCCT) resulting in a premature stop at codon 357 with loss of the second zinc finger domain, and a nonsense mutation at exon 6 (C1099T, R367X). No GATA3 abnormalities were identified in the remaining two families. The triad of HDR syndrome was variably manifested by patients with GATA3 abnormalities. The results suggest that HDR syndrome is primarily caused by GATA3 haploinsufficiency and is associated with a wide phenotypic spectrum.


Keywords: GATA3; HDR syndrome; phenotypic spectrum; mutation analysis     

Comparison of blood-free medium (cyclodextrin solid medium) with Bordet-Gengou medium for clinical isolation of Bordetella pertussis.

Cyclodextrin solid medium (CSM) developed by us was evaluated to be a suitable synthetic medium for the clinical isolation of Bordetella pertussis when compared with Bordet-Gengou (BG) medium. The addition of 5 micrograms of cephalexin (CEX) per ml to CSM not only supported the good growth of B. pertussis but also sufficiently suppressed the growth of nasopharyngeal flora. During period 1 of this study, nasopharyngeal specimens from 60 patients with clinical pertussis were inoculated on CSM supplemented with 5 micrograms of CEX per ml. The isolation rate was 70% (42 of 60). To confirm the efficacy of CSM, another study was performed. During period 2 of this study, nasopharyngeal specimens were cultured on both CSM and BG medium, each with 5 micrograms of CEX per ml. The comparative isolation rates were 100% (40 of 40 specimens from 29 patients) on CSM with 5 micrograms of CEX and 65% (26 out of 40) on BG medium with 5 micrograms of CEX. The excellent efficacy of CSM as measured by the isolation rate was thought to be due to the poor nutrition of this medium for the growth of nasopharyngeal bacteria. CSM retained its efficacy in clinical isolations even after 3 months of storage in a refrigerator. These data led us to conclude that CSM with 5 micrograms of CEX was much better than BG medium with 5 micrograms of CEX, determined by both the isolation rate and preservativity considerations, and that CSM with 5 micrograms of CEX per ml can be successfully used instead of BG medium as a medium for the clinical isolation of B. pertussis.     

ULTRASTRUCTURE OF AN ANAPLASTIC GIANT-CELL CARCINOMA FOUND 8 YEARS AFTER OPERATION ON A PAPILLARY CARCINOMA OF THE THYROID

Light and electron microscopic studies have been made on an anaplastic giant-cell tumor that developed in a woman 8 years after an operation on the thyroid for papillary carcinoma. Many giant cells were observed in the anaplastic tumor tissue, but no follicles. Numerous tightly-packed mitochondria and abundant ribosomes were present, but there were no desmosomes. The basement membrane was not distinct.     

Agarose for a bioartificial pancreas.

Islets were encapsulated into 5% concentration agarose microbeads. The effect of microencapsulation on islet allograft survivals was determined using a streptozotocin-induced diabetic (STZ) mouse and a nonobese diabetic (NOD) mouse as recipients. All five STZ BALB/c mice receiving microencapsulated islets (C57BL/6) maintained normoglycemia indefinitely. When NOD mice were used as recipients of the bioartificial pancreas, four of five grafts (islets from C3H/He) functioned for more than 80 d. Two of five NOD mice maintained normoglycemia until animals were sacrificed at 102 and 192 postoperative d. Microbeads made of commercially available agarose can effectively prolong alloislets functioning in the STZ-diabetic mouse and even in the NOD mouse (animal model of human type I diabetes) without the use of any immunosuppressive drug.     

The course ofAngiostrongylus cantonensis infection in athymic nude and neonatally thymectomized mice

BALB/c athymic nude and thymus-reconstituted nude mice and neonatally thymectomized BALB/c mice were infected with stage 3 larvae ofAngiostrongylus cantonensis and the worm burdens of the mice were determined at various times after infection. When the nude and thymectomized mice were exposed to the parasite, some worms were found to migrate from the brain to lungs but died there without reaching maturity. This pulmonary arterial migration of the worms in the nude mice did not occur following thymic reconstitution. These data suggest that the inability of murine intracranial worms to migrate to the lungs is at least in part due to thymus-dependent mechanisms, and also that the failure of worm maturation in mouse lungs might be due to thymus-independent immune mechanisms and/or nonimmunological mechanisms.     

Morphological and immunohistochemical studies of the lungs and bronchus-associated lymphoid tissue in a rat model of chronic pulmonary infection with Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most frequently encountered bacterial pathogens in patients with chronic pulmonary infections, including cystic fibrosis and diffuse panbronchiolitis. Bronchus-associated lymphoid tissue (BALT), noted frequently in patients with cystic fibrosis and diffuse panbronchiolitis, is considered to play an important role in the local immunologic defense mechanisms in the respiratory tract. To investigate the role of BALT in chronic pulmonary infections, we developed an animal model for chronic pulmonary infection and studied the morphological and immunohistochemical characteristics of BALT. Experimental pneumonia was produced in rats by intratracheal inoculation of P. aeruginosa enmeshed in agar beads. The histological changes corresponded to those occurring in chronic bronchiolitis. Immunohistochemically, surface immunoglobulin M-positive (sIgM+) cells and sIgA+ cells were recognized in the inflamed bronchial walls from day 4, and sIgG+ cells were recognized from day 14, W3/25+ cells exceeded OX8+ cells in number until day 14. In the BALT, there was a massive accumulation of lymphocytes in the lymphatics and high endothelial venules. The development of germinal centers was accompanied by increased numbers of sIgM+ and sIgA+ cells. W3/25+ cells exceeded OX8+ cells in number in the BALT until day 14. On the other hand, OX8+ cells were predominant in comparison with W3/25+ cells at day 21, and then both sIgM+ and sIgA+ cells and inflammatory changes in the lung decreased at day 28. These findings suggest that BALT regulates the local immune responses against chronic pulmonary infection due to P. aeruginosa.