Restenosis after successful percutaneous transluminal coronary angioplasty: serial angiographic follow-up of 229 patients

To further understand the temporal mode and mechanisms of coronary restenosis, 229 patients were studied by prospective angiographic follow-up on day 1 and at 1, 3 and 6 months and 1 year after successful percutaneous transluminal coronary angioplasty. Quantitative measurement of coronary stenosis was achieved by cinevideodensitometric analysis. Actuarial restenosis rate was 12.7% at 1 month, 43.0% at 3 months, 49.4% at 6 months and 52.5% at 1 year. In 219 patients followed up for greater than or equal to 3 months, mean stenosis diameter was 1.91 +/- 0.53 mm immediately after coronary angioplasty, 1.72 +/- 0.52 mm on day 1, 1.86 +/- 0.58 mm at 1 month and 1.43 +/- 0.67 mm at 3 months. In 149 patients followed up for greater than or equal to 6 months, mean stenosis diameter was 1.66 +/- 0.58 mm at 3 months and 1.66 +/- 0.62 mm at 6 months. In 73 patients followed up for 1 year, mean stenosis diameter was 1.65 +/- 0.56 mm at 6 months and 1.66 +/- 0.57 mm at 1 year. Thus, stenosis diameter decreased markedly between 1 month and 3 months after coronary angioplasty and reached a plateau thereafter. In conclusion, restenosis is most prevalent between 1 and 3 months and rarely occurs beyond 3 months after coronary angioplasty.     

An autopsied case of Creutzfeldt‐Jakob disease with mutation in the prion protein gene codon 232 and type 1+2 prion protein

A 68‐year‐old Japanese man gradually showed abnormal behavior and gait disturbance with bradykinesia. Slowly progressive dementia, including memory disturbance and disorientation, was also observed. Cerebral cortical hyperintensity on diffusion‐weighted MRI was observed 6 months after onset. The patient progressed to an akinetic mutism state with mild myoclonus, and atypical periodic sharp‐wave complexes were observed by electroencephalogram 13 months after onset. He was clinically suspected of having atypical CJD and died after 19 months total disease duration. The brain weighed 1160 g and showed mild atrophy of the cerebrum and cerebellum with ventricular dilatation. Spongiform changes with varying vacuole size and gliosis was extensive in the cerebral cortex and basal ganglia. Neuron loss in the cerebral cortex, basal ganglia and thalamus was relatively mild. The cerebellum showed mild spongiform changes of the molecular layer and mild neuron loss in the Purkinje cell layer. PrP immunostaining showed mainly coarse‐type combined with diffuse synaptic‐type PrP deposition in the cerebral gray matter. Some perivacuolar‐type PrP deposition was also present. Numerous plaque‐type PrP depositions were observed in the molecular layer of the cerebellum. Analysis of the PrP gene revealed a methionine‐to‐arginine (Met‐to‐Arg) substitution at codon 232 (M232R) with Met homozygosity at codon 129. Western blot analysis of protease‐resistant PrP indicated type 2 dominant PrP combined with type 1. Genetic CJD with M232R substitution in the PrP gene has only been reported in Japan. Although two clinical phenotypes (rapid‐type and slow‐type) were suggested in the M232R CJD cases (despite the presence of the same PrP genotype), the pathological and molecular backgrounds have not been well understood because there have only been a few autopsied case reports. This is the first case report of M232R CJD presenting with 1 + 2 PrP.     

Pathogenic Potential of Eomesodermin-Expressing T-Helper Cells in Neurodegenerative Diseases

Eomesodermin-expressing (Eomes⁺) T-helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes⁺ Th cell frequency was increased in the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by Th cells from such patients was high compared with controls. A high frequency of Eomes⁺ Th cells was observed in the initial (acutely progressive) stage of amyotrophic lateral sclerosis, and a positive correlation between Eomes⁺ Th cell frequency and cognitive decline was observed in Alzheimer's disease patients. Therefore, Eomes⁺ Th cells may be involved in the pathology of amyotrophic lateral sclerosis and Alzheimer's disease. ANN NEUROL 2024;95:1093–1098     

Gerstmann-Sträussler syndrome — A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex

Summary This report presents a variant of Gerstmann-Sträussler syndrome (GSS). A 53-year-old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti- protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS.     

Effect of probucol on repeat revascularization rate after percutaneous transluminal coronary angioplasty (from the Probucol Angioplasty Restenosis Trial [PART])

To address the issue of whether probucol reduces clinical events after percutaneous transluminal coronary angioplasty (PTCA), we surveyed clinical status at 1 year after PTCA of 101 patients who had entered the Probucol Restenosis Angioplasty Trial. Repeat angioplasty at index lesions were required in 5 patients in the probucol group and in 12 in the control group, suggesting that probucol administered beginning 4 weeks before PTCA reduces repeat revascularization rates for 1 year.     

Thymic stromal lymphopoietin plays an adjuvant role in BCG-mediated CD8 cytotoxic T cell responses through dendritic cell activation

Although Bacillus Calmette–Guérin (BCG) has historically emerged as a potent adjuvant in cancer immunization through dendritic cell (DC) activation, the efficacy of its antitumor effect has been limited. Therefore, the strategy of adjuvant therapy using BCG needs to be improved by adding enhancers. Here we found that thymic stromal lymphopoietin (TSLP) acts as an enhancer for the BCG-mediated antitumor effect. While BCG-stimulated DCs induced CD8⁺ T cell production of IFN-γ without strong cell expansion, TSLP-stimulated DCs induced robust CD8⁺ T cell expansion without high quantities of IFN-γ production. Notably, DCs stimulated with both BCG and TSLP induced robust expansion of CD8⁺ T cells that produced a large amount of IFN-γ with a potent cytolytic activity related to granzyme B expression. Our data suggest that TSLP is a good adjuvant to enhance the BCG-mediated cytotoxic T cell effect through DC activation, and provide a functional basis for a novel strategy for antitumor immune-based therapy.     

RhoB enhances migration and MMP1 expression of prostate cancer DU145

Rho family protein regulates variety of cellular functions as cytoskeletal organization, cell proliferation and apoptosis. In the present study, we demonstrate that RhoB-overexpressed prostate cancer cells showed an enhanced cell motility and the administration of the GSK-3 inhibitors inhibited this increase in migration. Among the extracellular matrix and adhesion-related molecules, MMP1 RNA expression was increased in RhoB-overexpressed cells, administration of MMP inhibitor suppressed the collagen gel invasion in these cells. This is the first report evaluating RhoB function and the downstream signaling events in prostate cancer cell. Our results indicate that RhoB promotes cell motility and invasion in a metastatic prostate cancer cell.     

Natural antioxidants may prevent posttraumatic epilepsy: a proposal based on experimental animal studies

Head injury or hemorrhagic cortical infarction results in extravasation of blood and breakdown of red blood cells and hemoglobin. Iron liberated from hemoglobin, and hemoglobin itself, are associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS have been demonstrated to be involved in the mechanism of seizures induced by iron ions in the rat brain, an experimental animal model for posttraumatic epilepsy (PTE). ROS are responsible for the induction for peroxidation of neural lipids, i.e., an injury of neuronal membranes, and also could induce disorders in the excitatory and inhibitory neurotransmitters. Antioxidants, such as a phosphate diester of vitamin E and C (EPC-K1) and antiepileptic zonisamide, have been known to prevent the epileptogenic focus formation, or to attenuate seizure activities in the iron-injected rat brain. Natural antioxidants, such as alpha-tocopherol, and condensed tannins, including (-)-epigallocatechin and (-)-epigallocatechin-3-O-gallate, adenosine and its derivative, melatonin, uyaku (Lindera Strychnifolia), fermented papaya preparations, Gastrodia elata BI., and Guilingji, have been demonstrated to scavenge ROS and/or RNS and to be prophylactic for the occurrence of epileptic discharge in the iron-injected rat brain.