Neuropathology of progressive multifocal leukoencephalopathy]

Progressive multifocal leukoencephalopathy (PML) is caused by opportunistic infection of JC virus which belongs to Papovavirus, and presents with progressive demyelinating lesion in the central nervous system. PML was originally reported as a rare complication of hematologic disorders, but later greatly increased in number in association with acquired immunodeficeincy syndrome (AIDS). Original neuropathological features of PML consist of demyelination lacking inflammatory reaction or necrosis, accompanying oligodendroglial nuclear inclusions in the periphery of demyelination. The lesion is preferentially localized to gray-white junction of the cerebral hemisphere and manifests as characteristic demyelinating lesion, called scallopping. Detection of JC virus is essential for the final diagnosis of PML and is achieved via immunohistochemical detection of JC virus with antibodies raised against their components, ultrastructural demonstration of virions characteristic of JC virus, or detection with in-situ hybridization of the genome of JC virus. JC virus can replicate only in oligodendroglial cells, but astrocytes are frequently infected by the virus. The resume of immunological function through therapeutic intervention develops new pathology in PML, exhibiting severe inflammatory reaction with edema and necrosis. This new pathological feature is called immune reconstruction syndrome and clinically presents with severe progression in symptoms of the central nervous system. Nevertheless, treatment of PML is directed for the elimination of the viruses by host immune system. The modification of the above immune reconstruction syndrome is essential for successful outcome of such therapeutic trial.     

Conditions of Alzheimer-type dementia in the old-old and oldest-old patients with special reference to extreme conditions of brain aging

A neuropathological study on 1540 consecutive autopsy brains ranging from 60 to 107 years of age revealed the following points. (1) Of the of the demented cases of the plaque-predominant type, 93% were complicated with multiple tiny cortical infarcts. They showed a tendency for dementia to develop before or after the appearance or worsening of a systemic disorder such as cardiovascular disease, respiratory infection and cancer. However, there was no case showing Alzheimer-type dementia (ATD). (2) The plaque-predominant type might be an extreme condition of brain aging in terms of senile plaques (SP). It is likely that although the pathological appearance of SP alone is not responsible for dementia, its coexistence with multiple cortical infarcts could be the cause of dementia. Therefore, this type should be distinguished from ATD. (3) Primary hippocampal degeneration could also be an extreme condition of brain aging in terms of neurofibrillary tangles. This condition was different pathologically from the hippocampal lesion in ATD. (4) Several characteristics of old-old and oldest-old patients were clarified.     

Treatment strategies for hepatic metastasis from colorectal cancer

Hepatic micrometastases of the parenchyma adjacent to a macroscopic lesion were detected in 17 of 31 resected liver metastases. Fifty-nine micrometastatic lesions were detected in total; 26 lesions were situated in the portal vein (PV), 22 in the central vein (CV), 5 in the bile duct (BD), and 6 in the sinusoid (SS). A histological study confirmed the direct invasion of the macrometastatic cancer cells into the adjacent PV, CV, BD, and SS. According to the tumor doubling time, the mean diameter of the macrometastases in 19 remnant livers was calculated to have been 0.57±0.87 cm at the time of the primary resection. The calculated diameter of 3 of these 19 macrometastases was found to be less than 0.01 cm, the minimum implantable size, indicating that the cancer recurrence in these specimens may have developed from macroscopic metastatic lesions as a satellite, and not from the primary tumor. In 13 patients who received doses of 5250 mg or more of 5 fluorouracil (FU) via the hepatic artery, the cumulative disease-free rate 2 years postoperatively was 100%; this value was 47.6% in 11 patients who received less than 5250 mg of 5 FU via the hepatic artery, and 0% in 39 patients who received no chemotherapy (P<0.005). These results suggest that anatomical hepatic resection for satellite lesions, combined with prophylactic hepatic arterial chemotherapy for micrometastases, decreases the recurrence rate of hepatic metastases in the remnant liver.     

Fibrolamellar hepatocellular carcinoma coexistent with a hepatocellular carcinoma of common type: Report of a case

A case of small fibrolamellar hepatocellular carcinoma (HCC) coexistent with a HCC of common type is herein reported. A 56-year-old man was diagnosed as having multi-nodular type HCC with liver cirrhosis. The serum alpha-fetoprotein (AFP) level was slightly increased. The patient underwent a partial caudate lobectomy and lateral segmentectomy. Histologically, both resected tumors were small HCCs measuring less than 2 cm in diameter. One was a fibrolamellar type located in the caudate lobe, while the other was the common type in the lateral segment of the liver. Positive immunohistochemical staining for AFP was observed in the tumor cells of the HCC of common type but was not observed in the fibrolamellar HCC. We also reviewed previously reported cases of fibrolamellar HCC in Japan, and discussed the clinicopathologic implications of this disease.     

Nasotracheal intubation using fiberoptic bronchoscopy in infants and children

Journal of Anesthesia -     

Protodioscin isolated from fenugreek (Trigonella foenumgraecum L.) induces cell death and morphological change indicative of apoptosis in leukemic cell line H-60, but not in gastric cancer cell line KATO III

Protodioscin (PD) was purified from fenugreek (Trigonella foenumgraecum L.) and identified by Mass, and 1H- and 13C-NMR. The effects of PD on cell viability in human leukemia HL-60 and human stomach cancer KATO III cells were investigated. PD displayed strong growth inhibitory effect against HL-60 cells, but weak growth inhibitory effect on KATO III cells. Morphological change showing apoptotic bodies was observed in the HL-60 cells treated with PD, but not in KATO III cells treated with PD. Flow cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were increased to 75.2, 96.3, and 100% after a 3-day treatment with 2.5, 5, and 10 microM PD, respectively. The fragmentation by PD of DNA to oligonucleosomal-sized fragments, that is a characteristic of apoptosis, was observed to be both concentration- and time-dependent in the HL-60 cells. These findings suggest that growth inhibition by PD of HL-60 cells results from the induction of apoptosis by this compound in HL-60 cells.     

The distinction between Burkitt lymphoma and diffuse large B-Cell lymphoma with c-myc rearrangement.

To compare immunophenotypic and molecular features between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) with c-myc rearrangements (c-mycR DLBCL), we analyzed 18 cases of B-cell non-Hodgkin's lymphoma with c-mycR that were confirmed by chromosomal and/or Southern blotting analyses. The cases were histologically classified into 10 BLs and five DLBCLs. The remaining three cases could not be classified because of suboptimal quality of the surgical materials. BLs were from five adults and five children, whereas all DLBCLs were from adults. BLs were positive for CD20 (10/10 cases examined), CD10 (9/10), Bcl-2 (1/9), and Bcl-6 (10/10), whereas they were negative for CD3 (0/10) and EBV (0/8), by Epstein-Barr virus (EBV) EBER-1 RNA in situ hybridization. c-MycR DLBCLs were positive for CD20 (5/5), CD10 (2/5), Bcl-2 (3/4), and Bcl-6 (4/4), whereas none of them were positive for CD3 and EBV. A mean of MIB-1 index (MIB-1+ cells/neoplastic cells, %) of BLs (98.1%) was higher than that of c-mycR DLBCLs (66.3%; P <.0001). Somatic mutation of immunoglobulin heavy-chain gene variable region (VH gene) in BLs (four cases) ranged from 0.7 to 4.9% with an average value of 2.3%, whereas those in DLBCLs (three cases) from 8.2 to 32.0% with an average value of 17.0%. It is, therefore, concluded that a growth fraction of nearly 100%, as well as a monotonous proliferation of medium-sized cells and c-myc(R), should be of value in the diagnosis of BL, which is probably different from c-myc(R) DLBCL. In addition, CD10+, Bcl-2-, and low frequency of mutation of the VH gene could be helpful for the histologic distinction of BL from (c-mycR) DLBCL.     

Detection of Balamuthia mitochondrial 16S rRNA gene DNA in clinical specimens by PCR

Balamuthia mandrillaris is a free-living ameba that causes granulomatous amebic encephalitis in both immunocompromised and immunocompetent individuals. Because of a lack of pathognomonic symptoms and the difficulty in recognizing amebas in biopsied tissues, most cases are not diagnosed or effectively treated, leading to a >95% mortality. We report here on five cases of balamuthiasis that were diagnosed by indirect immunofluorescence (IIF) staining of serum for anti-Balamuthia antibodies (titer > or = 1:128) and confirmed by IIF of unstained brain tissue sections and/or detection of amebas in hematoxylin-eosin-stained slides. Additionally, we have used the PCR for the detection of mitochondrial 16S rRNA gene DNA from the ameba in clinical specimens such as brain tissue and cerebrospinal fluid (CSF) from individuals with Balamuthia encephalitis. Balamuthia DNA was successfully detected by the PCR in clinical samples from all five individuals. It was detected in brain tissue from three cases, in CSF from three cases, and in one of two samples of lung tissue from two individuals, but not in two samples of kidney tissue tested. One sample of unfixed brain tissue was culture positive for Balamuthia. In order to test the sensitivity of the PCR for detection of Balamuthia DNA, CSF specimens from two individuals negative for amebic infection were spiked with Balamuthia amebas. We found that it was possible to detect Balamuthia DNA in the PCR mixtures containing mitochondrial DNA from 1 to as little as 0.2 ameba per reaction mixture. A single Balamuthia ameba contains multiple mitochondrial targets; thus, 0.2 ameba represents multiple targets for amplification and is not equivalent to 0.2 of an ameba as a target.     

Granulocytic sarcoma presenting with lymph node infarction at disease onset

A completely infarcted lymph node is an unusual event. However, lymph node infarction should alert the pathologist to the considerable likelihood of malignant lymphoma. We report two unusual cases of acute myeloid leukemia presenting with granulocytic sarcoma at disease onset with a lymph node lesion exhibiting extensive lymph node infarction. The infarcted tissue contained numerous eosinophilic cell ghosts. There were some islands of degenerated, pyknotic medium-sized nuclei resembling lymphoblasts present in the necrotic area. By immunohistochemistry, these medium sized cells were CD3-, CD20-, CD34+, CD43+, CD45RO-, CD68-, CD79a- and myeloperoxidase+ in both cases. Differentiation of granulocytic sarcoma from malignant lymphomas is important for adequate therapy. The present cases indicate that granulocytic sarcoma should be added to the list of differential diagnoses for lymph node infarction.     

NMDA antagonist MK-801 does not interfere with the use of spatial representation in a familiar environment

There is disagreement among researchers concerning whether glutamatergic N-methyl-D-aspartate (NMDA) receptors play a role in constructing spatial representations. Therefore, the authors reexamined the effects of the NMDA antagonist on a spatial discrimination task using rats in a water pool. The authors confirmed that MK-801 impaired acquisition of the spatial discrimination task (Experiment 1). When rats were pretrained before drug treatment, MK-801 induced learning deficits in the novel environment but not in the familiar environment (Experiment 2). Moreover, in a familiar environment, MK-801 did not impair spatial learning, even when the task was completely novel for the rats (Experiment 3). These results suggest that NMDA receptors play an important role in the construction of spatial representations but not in the use of them.