Long-term follow-up results of 175 patients with malignant glioma: Importance of radical tumour resection and postoperative adjuvant therapy with interferon,ACNU and radiation

Summary We analysed long-term follow-up results of 175 patients with malignant glioma (110 glioblastoma and 65 anaplastic astrocytoma) treated under five different regimes during the past two decades. The factors of age (less than 40), histology (anaplastic astrocytoma) and type of adjuvant therapy (radiation and chemotherapy) contributed to long survival. The other important factor was the response to adjuvant therapy.Cases of gross total removal or complete response (CR) of a residual tumour to an adjuvant therapy showed a better prognosis. The three and five year survival rate was 42% and 24%, respectively. The highest CR ratio (23%) was seen in patients treated by intravenous injection of interferon and ACNU in addition to radiotherapy (IAR therapy).     

Three TNFalpha single nucleotide polymorphisms in the Japanese population

BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) is an essential regulator of immune responses and is implicated to relate to several types of disease susceptibilities. Population information on polymorphisms is essential for the study of genetic diseases. AIM: To obtain accurate information about single nucleotide polymorphisms (SNPs) in the TNFalpha gene in the Japanese population. SUBJECTS AND METHODS: The entire TNFalpha gene was screened for SNPs by directly sequencing 48 chromosomes derived from 24 unrelated Japanese individuals. Allele frequencies of each polymorphism were determined and compared with those previously reported in other populations. RESULTS: Three SNPs, -308G/A at nt -308, IVS1 + 125G/A at nt 492 and IVS3 + 104G/A at nt 1359 were observed, of which one (IVS3 + 104G/A at nt 1359) was novel. In addition, allele frequencies of -308G/A were remarkably different from those presented in the NCBI dbSNP, indicating a significant ethnic difference. CONCLUSIONS: The polymorphisms and allele frequencies obtained in this study will be useful for genetic studies of common diseases such as osteoporosis and rheumatoid arthritis in the Japanese population.     

Expression profiles of the duplicated matrix metalloproteinase-9 genes suggest their different roles in apoptosis of larval intestinal epithelial cells during Xenopus laevis metamorphosis.

Matrix metalloproteinases (MMPs) play a pivotal role in development and/or pathogenesis through degrading extracellular matrix (ECM) components. We have previously shown that Xenopus MMP-9 gene is duplicated. To assess possible roles of MMP-9 and MMP-9TH in X. laevis intestinal remodeling, we here analyzed their expression profiles by in situ hybridization and show that their expression is transiently up-regulated during thyroid hormone-dependent metamorphosis. Of interest, MMP-9TH mRNA is strictly localized in the connective tissue and most highly expressed just beneath the larval epithelium that begins to undergo apoptosis. On the other hand, cells expressing MMP-9 mRNA become first detectable in the connective tissue and then, after the start of epithelial apoptosis, also in the larval epithelium. These results strongly suggest that MMP-9TH is responsible in the larval epithelial apoptosis through degrading ECM components in the basal lamina, whereas MMP-9 is involved in the removal of dying epithelial cells during amphibian intestinal remodeling.     

Novel single nucleotide polymorphisms of the human nuclear factor kappa-B 2 gene identified by sequencing the entire gene

The nuclear factor kappa-B 2 (NFKB2) gene is a member of the NFKB/Rel gene family, which is known to be a pivotal regulator of the acute phase of the inflammatory response and of immune responses. We identified three novel single nucleotide polymorphisms (SNPs) and determined their allelic frequencies, as determined by the sequencing of 48 alleles of the entire gene in a Japanese population sample. Two of the three polymorphisms were identified at nucleotide (nt) position 1837 (T/C) and nt position, 1867 (GG/G) in the upstream region of the gene. The other polymorphism was identified at nt position 2584 (G/T) within intron 1. These polymorphisms will be useful in genetic studies of the processes involved in inflammatory responses and in bone differentiation. Received: October 17, 2000 / Accepted: October 23, 2000     

ADRENOCORTICAL CARCINOMA IN INFANCY

A case of adrenocortical carcinoma associated with congenital heart defect in a 6-month-old Japanese girl is reported. A fist-sized tumor was incidentally noted in the right hypochondrium upon admission for cardiac surgery. No clinical endocrinopathy was evident in this case. The resected tumor was encapsulated with smooth surface and no invasion to adjacent tissues or organs was observed. Histologically, the tumor was composed of small cells with granular or clear cytoplasm, and occasional giant cells with single or multiple nuclei. By electron microscopy, the tumor cells showed various nuclear contours with distinct nucleoli and had a moderate amount of cytoplasm containing abundant rough endoplasmic reticulum and mitochondria with variable-sized electron-dense granules. Intercellular desmosome-llke junctions were observed in some tumor cells. Immunohistochemlcally, the tumor cells contained granules positive for estriol, progesterone and Cortisol. These morphological findings including electron microscopic features suggested that the tumor cells had a malignant character.     

Cardiomyopathy characterized by abnormal accumulation of desmin-type intermediate filaments in cardiac muscle fibers. A case report and review of the literature

A 42-year-old Japanese male, who had been suffering from congestive heart failure and electrocardiographic abnormalities (A-V block, intraventricular conduction disturbance, ventricular tachycardia), died after a clinical course of 2 years and 1 month. Macroscopic investigation revealed dilation of the left ventricle and thickening of the right ventricular wall. The unique finding in this case was a circumferential fibrous scar in the median circular layer and outer oblique layer of the left ventricular wall. Biopsy and autopsy materials revealed diffuse loss of myofibrils in the central zone of cardiac muscle fibers, and replacement with aniline blue-positive homogeneous material (17-35% of the area of one muscle fiber). Electron microscopy revealed abnormal accumulation of fine filamentous material (7.5-25 nm in diameter), which was immunohistochemically proved to be desmin-type intermediate filament. Moreover, sarcoplasmic reticulum-like material was detected in the degenerated area. At autopsy, degeneration was detected all over the heart. The ventricular muscle fibers were more severely affected than the atrial muscle fibers. The conduction system was also affected, in some parts more severely than the surrounding ordinary muscle fibers. The pathogenesis of this disorder remains to be clarified.     

Adrenocortical carcinoma in infancy. Report of a case with immunohistochemical and ultrastructural studies

A case of adrenocortical carcinoma associated with congenital heart defect in a 6-month-old Japanese girl is reported. A fist-sized tumor was incidentally noted in the right hypochondrium upon admission for cardiac surgery. No clinical endocrinopathy was evident in this case. The resected tumor was encapsulated with smooth surface and no invasion to adjacent tissues or organs was observed. Histologically, the tumor was composed of small cells with granular or clear cytoplasm, and occasional giant cells with single or multiple nuclei. By electron microscopy, the tumor cells showed various nuclear contours with distinct nucleoli and had a moderate amount of cytoplasm containing abundant rough endoplasmic reticulum and mitochondria with variable-sized electron-dense granules. Intercellular desmosome-like junctions were observed in some tumor cells. Immunohistochemically, the tumor cells contained granules positive for estriol, progesterone and cortisol. These morphological findings including electron microscopic features suggested that the tumor cells had a malignant character.     

Association of genetic variation of the RIL gene,encoding a PDZ-LIM domain protein and localized in 5q31.1, with low bone mineral density in adult Japanese women

Twin and family studies had shown that genetic factors are important determinants of bone mass. Multiple genes might be involved. One candidate gene, the reversion-induced LIM gene (RIL), is a PDZ and LIM-domain-containing protein and has been localized within the cytokine cluster of chromosome 5 (5q31.1). In a genetic study of 370 adult Japanese women, we investigated the correlation between radial bone mineral density (BMD) and a genetic variation (−3333T→C) of the 5'-flanking region of RIL gene. A significant association was identified between the RIL variation −3333T→C and radial BMD (r=0.15, P=0.003). The variation of the RIL locus may be an important determinant of osteoporosis.     

ABNORMAL INTRACRANIAL VASCULAR NETWORKS ("MOYAMOYA" DISEASE), POSSIBLY DUE TO OCCLUSION OF BILATERAL INTERNAL CAROTID ARTERIES — A CASE REPORT WITH HISTOMETRICAL ANALYSIS —

An autopsy case of abnormal Intracranial vascular networks at the base of the brain corresponding to so-called rete mirabile, associated with occlusion of bilateral internal carotid arteries was reported. This patient was a 62 year-old female who died about two months after sudden onset of subarachnoid hemorrhage. At autopsy, abnormal vascular networks termed as rete mirabile were observed to be collateral blood supplies among the cerebral regions with flow of the anterior, middle, and posterior cerebral arteries, caused by long-stading obstruction of bilateral internal carotid arteries at the syphon level. Morphometrical analysis was done by measuring the length of internal elastic membrane of the internal carotid arteries in cross section, and comparing it with those of controlled persons of the same sex and age without any intracranial disorders and hypertensive histories. The result that no significant difference was observed between the former and the latter values suggested that the unusual cerebro-vascular disorder of this case developed not on the base of congenital anomaly including hypoplasia of internal carotid arteries or arteriovenous malformation but as an acquired lesion established for a long time.     

Clinical results of arthroscopic rotator cuff repair in diabetic and non-diabetic patients

BackgroundAlthough the clinical outcomes of arthroscopic rotator cuff repair (ARCR) have been reported, few studies have focused on diabetic patients. We investigated and compared the clinical results of ARCR in patients with and without diabetes.MethodsThis retrospective study involved 195 consecutive patients who underwent ARCR from 2015 to 2018 in our hospital. Twenty-seven and 168 shoulders were assigned to diabetes and non-diabetes groups, respectively. Diabetic patients with poor control were preoperatively hospitalized for perioperative diabetic control. We evaluated range of motion (ROM), Japanese Orthopaedic Association shoulder (JOA) score, Constant Shoulder Score, and University of California, Los Angeles (UCLA) score preoperatively and at 6 months and 1 year post-ARCR. Rates of rotator cuff retear 1 year post-ARCR and preoperative and postoperative stiff shoulder were also evaluated. We compared the results between groups and analyzed them statistically. A p-value of <0.05 was considered statistically significant.ResultsPreoperative ROM, JOA score, Constant Shoulder Score and UCLA scores showed significant improvement at post-ARCR in both groups (p < 0.05). On comparing the groups, although preoperative JOA score and Constant Shoulder Score were significantly lower in diabetes group than in non-diabetes group (diabetic/non-diabetic group; 60.0/65.3 for JOA score; p = 0.003, 59.7/64.2 for Constant Shoulder Score; p = 0.003), there was no significant difference postoperatively (6 months post-ARCR; 88.0/89.7 for JOA score; p = 0.783, 88.1/88.6 for Constant Shoulder Score; p = 0.597, 1 year post-ARCR; 96.7/95.4 for JOA score; p = 0.238, 96.6/95.4 for Constant Shoulder Score; p = 0.248). Furthermore, preoperative and postoperative stiff shoulder and retear rates were not significantly different between groups (p = 0.152, p = 0.344, p = 0.347, and p = 0.563, respectively).ConclusionDiabetic patients showed comparable clinical results with non-diabetic patients post-ARCR. Perioperative diabetic control may be recommended for preoperatively uncontrolled diabetic patients.