Sequencing based typing for genetic polymorphisms in exons 2, 3 and 4 of the MICA gene

We have established a sequencing based typing (SBT) method for detection of genetic polymorphism in the exon 2 to 4 domains of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) and applied it to allele typing of 130 healthy Japanese individuals. A 2.2-kb segment including exons 2, 3 and 4 of the MICA gene was amplified by a pair of generic primers followed by cycle sequencing using exon-specific nested primers. In total, 8 alleles were observed in a Japanese population and the most frequent allele was MICA008 with the gene frequency of 30.8%. MICA009 was the second most frequent (16.5%), while the rarest one was MICA007 (1.2%). MICA alleles displayed strong linkage equilibria with HLA-B antigens (i.e. MICA008 with B7, B48, B60 and B61; MICA009 with B51 and B52; MICA002 with B35, B39, B58 and B67; MICA004 with B44, MICA007 with B13 and B27; MICA010 with B46, B62 and B48, MICA012 with B54, B55, B56 and B59; MICA019 and B70, B71 and B62). Recently, the B48 haplotype has been reported to lack the entire MICA gene by a large-scale deletion in a Japanese population. Among 8 serologically B48 homozygous individuals, 4 were found to represent this MICA null allele as assessed by no polymerase chain reaction (PCR) amplification using MICA-specific primers, while the remaining four possessed the intact MICA gene with MICA008 or MICA010.     

Association study of a polymorphism of nonerythroid alpha-spectrin gene with schizophrenia.

The specificity of cytoarchitectural abnormalities in limbic structures of patients with schizophrenia and their contributions towards the etiology of schizophrenia remain unknown. We have recently reported an increased breakdown of nonerythroid alpha-spectrin (fodrin), a major component of neuronal cytoskeletal proteins, in schizophrenic left superior temporal cortices [Kitamura et al., 1998: Biol Psychiatry 43:254-262], suggesting that polymorphisms of the alpha-spectrin gene might contribute to the vulnerability to schizophrenia. We screened for genetic variations associated with schizophrenia through the C-terminus sequences of the human nonerythroid alpha-spectrin gene (SPTAN1) spanning two EF-hands and also tested a possible contribution of the polymorphism to the development of schizophrenia by an association study. We found a polymorphic region of an intron located in the second EF-hand of SPTAN1 gene. There was no significant difference between patients with schizophrenia and controls in allele frequencies or genotype distribution. There is evidence that the Psh BI SPTAN1 gene polymorphism does not play a major role in the genetic component of schizophrenia.     

Clinical impact of postoperative prognostic nutritional index in colorectal cancer patients undergoing adjuvant chemotherapy

Preoperative Prognostic Nutritional Index (PNI) could be a crucial factor for the prognosis of colorectal cancer (CRC). However, the clinical impact of postoperative PNI is still unclear, and there have been no reports on the significance of postoperative PNI in patients undergoing adjuvant chemotherapy (AC). We retrospectively analysed 227 consecutive patients who underwent AC after radical surgery for high-risk stage II or stage III CRC. PNI value was calculated before radical surgery and before the introduction of AC. In our study, patients with a low PNI value before surgery showed significantly poorer long-term outcomes than those with a high PNI value. Next, we divided the patients into four groups: patients with a high PNI value before surgery and remained after surgery (Group High-High), a high PNI value before surgery but decreased after surgery (Group High-Low), a low PNI value before surgery but recovered after surgery (Group Low-High), and a low PNI value but did not recover after surgery (Group Low-Low). Although the patients in Group Low-Low showed significantly poorer long-term outcomes than those in Group High-High, the prognosis of patients in Group Low-High was the same as that of patients in Group High-High. In addition, in patients with recurrence after AC, those with a high PNI value at the time of recurrence showed a significantly better survival after recurrence than patients with a low PNI value. Postoperative PNI value could be a prognostic biomarker for CRC patients undergoing AC. Even though the PNI value was low before the surgery, recovery of PNI value by the introduction of AC could improve the prognosis of CRC patients.     

Cleft hand in Silver-Russell syndrome

A case of Silver-Russell Syndrome with a typical cleft hand is presented. The association of cleft hand with this syndrome has never been reported before.     

The identification of a rabbit-transmitted cervical toxoplasmosis mimicking malignant lymphoma

A case is presented of acquired cervical toxoplasmosis occurring in a 43-year-old male, which clinically mimicked malignant lymphoma. The histopathology of this case was probable toxoplasmic lymphadenitis. Serologic tests and the use of FITC-labeled antibodies revealed high levels of specific IgG antibodies in the serum and toxoplasmic antigens in paraffin sections of the patient, respectively. During survey of the infection route, it was learned that the patient's pet rabbit and three other rabbits of the same family line had cervicofacial lumps. The pet rabbit had high levels of toxoplasmic antibodies. Immunofluorescence tests on the infraorbital lump also revealed Toxoplasma gondii. Therefore, it was concluded that in this case the rabbit had transmitted Toxoplasma to the patient. The authors know of no other reports of toxoplasmosis transmitted by or through rabbit to human.     

Isochromosome 17q in a case of myelofibrosis with myeloid metaplasia terminating in blastic transformation

A case of myelofibrosis with myeloid metaplasia in a 61-year-old female patient is reported. Cytogenetic studies were performed using short-term culture without phytohemagglutinin. A chromosomal aberration of an isochromosome 17q, [i(17q)], was revealed in 88% of the metaphases of peripheral blood cells in the blastic phase. However, all metaphases of bone marrow cells in the chronic phase showed a normal karyotype. Furthermore, i(17q) was also observed in 10% of the metaphases of spleen cells examined 8 months before blastic transformation. In this case, therefore, the cells with i(17q) were associated with an abnormal clone of blastic transformation, with the abnormal clone originating in the spleen with myeloid metaplasia.     

Mitochondrial abnormalities in selenium-deficient myopathy

We report a man who developed selenium-deficient myopathy during long-term parenteral nutrition. Muscle biopsy showed marked mitochondrial depletion in the deep sarcoplasm and enlarged mitochondria at the periphery mainly in type 2 fibers. Muscle weakness improved gradually after the second course of selenium supplementation. The peculiar mitochondrial abnormalities in muscle fibers appear to play a key role in the pathogenesis of selenium-deficient myopathy. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:637–639, 1998.     

Clinical,pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7 ± 3.1 years (mean ± SD), and loss of ambulance occurred at 38.5 ± 2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca²⁺-binding domain. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1493–1501, 1998