Accumulation of L-[2-(F-18)]fluorophenylalanine in peri-infarct area in a patient with acute cerebral infarction

We studied the brain uptake of amino acid in a patient with acute cerebral infarction with L-[2-(F-18)] fluorophenylalanine and positron emission tomography. The increased accumulation of the ligand was specifically found in the peri-infarct area where oxygen metabolism was still maintained but decreased later in the 72-day follow-up period. The kinetic analysis revealed that increased accumulation was not due to increased transport from the blood to the brain but to delayed washout from the brain to the blood. Although the mechanism is still unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict delayed neuronal changes after ischemic insults of the brain.     

Microdissection and microcloning of chromosomal alterations in human breast cancer

Summary The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5–8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band-or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10–13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.Presented by Jeffrey M. Trent at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, USA, November 4, 1993; Minisymposium on Molecular Genetics in Breast Cancer.     

Assessment of borderzone ischemia with a combined MR imaging-MR angiography-MR spectroscopy protocol

We attempted to assess whether magnetic resonance imaging (MRI)-MR angiography (MRA)-MR spectroscopy (MRS) measurements can be used in the differentiation of patients in whom severe carotid lesions result in chronically hypoperfused regions and in whom the collateral capacity is sufficient to maintain a normal cerebral blood flow. Sixty-six patients with severe stenosis of the internal carotid artery (ICA) and 19 control subjects underwent MRI, 1H MRS, and MRA. Anaerobic metabolic changes in the middle cerebral artery (MCA) territory were studied by assessing N-acetyl-L-aspartate (NAA)/choline and lactate/ NAA ratios. Quantitative flow was measured in the ICA, in the basilar artery, and in the MCA. Thirty-four patients had borderzone infarcts, 16 patients had territory infarcts, and 16 patients had no infarcts on MRI. Patients with border-zone infarcts had significantly reduced flow in the ICA (P < 0.001) and in the MCA (P < 0.05) and decreased NAA/ choline ratios (P < 0.001) in non-infarcted regions compared with control subjects (P < 0.001) but also compared with patients with territory infarcts (P < 0.05) and patients without infarcts (P < 0.05). Flow measurements in the ICA and MCA and metabolic measurements in the MCA territory can be applied to select patients in whom cerebral perfusion pressure is insufficient to maintain normal cellular integrity.     

A case of ABO-incompatible renal transplant patient with non-insulin-dependent diabetes mellitus; long-standing observation of serial glomerular change by protocol biopsy

A 41-yr-old patient with non-insulin-dependent diabetes mellitus (NIDDM), before and after ABO-incompatible renal transplant, is reviewed using serial protocol biopsy. Although she recovered from delayed hyperacute rejection (DHAR) immediately post-transplantation, her graft function deteriorated gradually. A mild acute transplant glomerulitis, noted at the 155th day post-transplantation, progressed to pronounced chronic transplant glomerulopathy over 5 yr. In the specimen of the last biopsy, at 5 yr post-transplantation, glomeruli demonstrated an exudative hyaline lesion, which was characteristic of diabetic nephropathy in addition to chronic transplant glomerulopathy. Therefore, we made a diagnosis of this glomerular lesion as chronic transplant glomerulopathy complicated by diabetic glomerulopathy. Considering the result of this case, the protocol biopsy is a useful procedure to diagnose an accurate cause of graft dysfunction in individual cases. It is concluded that the protocol biopsy is apparently useful for the detection of various pathological processes occurring in allograft and may contribute to a strategy for improvement of graft survival.     

Differential motion hyperacuity under conditions of common image motion

Sensitivity to horizontal shearing motion in random dots was measured as a function of common image motion amplitude. Without common image motion, thresholds for differential motion are comparable or better than vernier acuity. Above about 2 arc min of common image motion there is a proportionate increase in motion parallax thresholds such that for 20 arc min of common image motion, differential motion thresholds have risen by an order of magnitude. This differs from a comparable lack of threshold elevation for vernier acuity targets under similar conditions of movement (Westheimer and McKee, 1975). By varying movement duration, it can be shown that common image motion amplitude rather than common image velocity is the primary determinant of the effect. Furthermore this degradation of performance is not affected by changes in random dot size. Under favorable circumstances the phenomenon can also be seen with differentially moving vernier lines. The effect shows directional selectivity such that common motion directions closest to the horizontal leads to the greatest interference. The results add weight to the view that differential motion hyperacuity is mediated by a separate mechanism than differential position hyperacuity.     

A new mutation in the POU3F4 gene in a japanese family with x-linked mixed deafness (DFN3)

Objective: The molecular defect in patients with X-linked mixed deafness showing a perilymphatic gusher at stapedectomy (DFN3) has been attributed to mutations in the POU3F4 gene. This study aimed to clarify an allelic variant of this gene. Study Design: This was a genetic study of a single Japanese family with DFN3. Methods: Products of a polymerase chain reaction (PCR) were subjected to single-strand conformation polymorphism (SSCP) analysis. Direct sequencing of PCR products from patients and carriers showing SSCP variants was performed using the fluorescent dideoxy termination method and a sequencer. Results: Sequencing of the PCR product revealed a 6-base deletion (TTCAAA) at nucleotides 601 to 606, resulting in a two-amino-acid deletion in the POU3F4 protein, (phenylalanine and lysine at amino acid residues 201 and 202). The deletion was adjacent to the site of a nonsense mutation previously described. Conclusion: Microdeletions at a previously undescribed location account for some clinically important POU3F4 mutations. Laryngoscope, 108:1544–1547, 1998     

Tumor-specific Activation of Mitogen-activated Protein Kinase in Human Colorectal and Gastric Carcinoma Tissues

To search for the signaling events in colorectal carcinoma relevant to its tumorigenesis, we investigated the activity of mitogen-activated protein kinase (MAPK) in human colorectal carcinoma tissues and paired normal tissues. Of 64 cases examined, approximately 75% (48 cases) showed tumor-specific activation of MAPK by in situ kinase renaturation assay, as well as in vitro kinase assay with immunoprecipitated MAPK. In addition, tumor-specific activation of MAPK was associated with the activation of MAPK kinase in the cases we examined. However, no clear correlation of MAPK activation with lymph node involvement, metastatic rate, stage, histological classification, age or sex was observed. These results suggest that the MAPK pathway is involved in colorectal tumor development, but its activation alone is not sufficient for malignant conversion. In contrast to colorectal carcinoma, gastric carcinoma tissues showed a lower rate of MAPK activation, suggesting that the signaling pathway activated in colorectal carcinoma tissues may differ in part from that of gastric carcinoma.