Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and cancer susceptibility. Mutations within the FA complementation group C (FAC) gene account for approximately 14% of diagnosed FA cases. Two mutations, one in exon 1 (delG322) and one in exon 4 (IVS4 + 4 A to T), account for 90% of known FAC mutations. The delG322 mutation results in a mild FA phenotype, while the IVS4 + 4 A to T mutation results in severe FA phenotype. To determine the molecular basis for this clinical variability, we analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the delG322 mutation expressed a 50-kD FAC polypeptides, FRP-50 (FAC-related protein), shown to be an amino terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 + 4 A to T mutation lacked FRP-50. Overexpression of a cDNA encoding FRP-50 in an FA(C) cell line resulted in partial correction of mitomycin C sensitivity. In conclusion, expression of an amino terminal truncated FAC protein accounts, at least in part, for the clinical heterogeneity among FA(C) patients.     

Bilateral occurrence of pheochromocytoma in patients with the multiple endocrine neoplasia syndrome type 2A (Sipple's syndrome)

Two kindreds with the multiple endocrine neoplasia type 2A syndrome were studied. Of one of these we examined 150 members, 20 of whom were treated with thyroidectomy for medullary carcinoma and nine with bilateral adrenalectomy for pheochromocytoma. Of the second kindred 59 members were examined, seven of whom were thyroidectomized and seven treated with bilateral adrenalectomy. Pheochromocytomas were invariably found on both sides, even in four cases in which the adrenals on one side appeared to be completely normal, not only at preoperative roentgenologic examination but also on inspection during the operation. The microscopic finding of micronodules and a cluster of abnormal medullary cells identical with those found in pheochromocytomas in one of the apparently normal adrenals represents a first stage in the development of diffuse medullary hyperplasia as well as nodular hyperplasia. This is in accordance with the fact that in the MEN type 2A syndrome pheochromocytomas are always multicentric and multiple in origin. On the basis of these findings we conclude that all patients with the MEN 2A syndrome who show symptoms and signs of active pheochromocytoma should be subjected to bilateral adrenalectomy, even when one or both of the adrenals appear to be normal at roentgenologic investigation.     

Natural killer-like T-cell lymphomas: aggressive lymphomas of T-large granular lymphocytes [see comments]

Natural killer (NK)-like T cells are major histocompatibility complex- unrestricted cytotoxic T cells that are surface CD3-positive, express NK-cell antigens, and rearrange their T-cell receptor. Most neoplasms arising from this T-cell subpopulation have been a chronic lymphoproliferative disease referred to as T-large granular lymphocyte (LGL) leukemia. Only 10 NK-like T-cell lymphomas have been described in detail previously; this study presents the clinicopathologic features of six others and distinguishes these lymphomas from T-LGL leukemia. All patients presented with B-symptoms and often had marked hepatosplenomegaly without significant peripheral lymphadenopathy. Four of the six patients were immunosuppressed. All had CD3, CD8, CD56- positive tumors, presumably of hepatosplenic (n = 3), intestinal (n = 1), pulmonary (n = 1), or nodal (n = 1) origin. Three patients had lymphomatous bone marrow infiltrates, and four had peripheral blood involvement by neoplastic large lymphocytes, some of which had a blastic appearance or resembled virocytes. Azurophilic granules, ultrastructurally corresponding to cytoplasmic dense core and/or double density granules, were seen in all cases. T-cell clonality was shown in five tumors by Southern blot analysis, and three had abnormal karyotypes. Two untreated patients died 20 days after presentation, and three patients who received combination chemotherapy died within 5 months of presentation. One patient remains in complete remission 22 months after treatment. These findings suggest NK-like T-cell lymphomas are aggressive, are clinicopathologically distinct from T-LGL leukemia, and should be in the differential diagnosis of extranodal T-cell lymphoproliferations, including those in immunosuppressed patients. Furthermore, the LGL morphology, phenotype, and tissue distribution of some NK-like T-cell lymphomas suggest they arise from thymic- independent T cells of the hepatic sinusoids and intestinal mucosa.     

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

希—内学习能力测验在中国聋儿中使用的信度和效度

采用经部分修改的希－内学习能力测验（Ｈ－ＮＴＬＡ）量表对全国２１个省、市、自治区１７５８名３－１７岁聋儿逐人测试。样本人群地区分布、家长职业构成与１９９０年全国人口普查资料一致。１７５８名聋儿智商呈现正态分布（ｇ１＝０．０１１Ｐ＞０．０５，ｇ２＝０．０５８Ｐ＞０．０５）。测试员间信度系数０．９８１（Ｎ＝２４），复测信度０．８４１（Ｎ＝１３６），分半信度０．９２７（３－８岁）及０．８５４（９－１７岁）。各分测验得分随年龄增加而增加，小年龄组增加明显，大年龄组增加缓慢。各分测验之间、各分测验和总离差智商之间大多数相关系数有显著统计学意义。智商与学习成绩（语文及数学）相关系数０．２０８（Ｐ＜０．０１Ｎ＝２２４），与教师评语等级相关系数０．４４（Ｐ＜０．０５ｄｆ＝１６），表明经修订的Ｈ－ＮＴＬＡ量表适用于中国听力语言障碍人群进行智力评定。     

创伤病人的手术与焦虑状态调查

采用状态——特质焦虑问卷及１０项躯体性焦虑测试题，对４０例外科创伤病人手术前后的焦虑状态调查显示：术前状态焦虑量表评分显著高于术后；术前躯体性焦虑评分显著高于术后；高特质焦虑评分亚组与低特质焦虑评分亚组术前状态焦虑评分无显著差异，但术后则前者显著高于后者；急诊手术者手术前后状态焦虑评分显著高于择期手术者。     

Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease

The allelic frequency of the gene for the K variant of butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age > 65 years) histopathologically diagnosed Alzheimer's disease (AD), which was higher than the frequencies in 104 elderly control subjects (0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed cases of other dementia (0.10). The association of BCHE-K with late-onset AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E gene (APOE), among whom the presence of BCHE-K gave an odds ratio of confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene for late-onset AD.