Axonal dystrophy in the posterior column nuclei of young adult epileptics with chronic phenytoin intoxication

Axonal spheroids in the posterior column nuclei of phenytoin-intoxicated epileptics were classified according to their predominant subcellular components into six types, and their incidences were compared with those in controls. Spheroids from phenytoin-intoxicated epileptics showed significantly higher proportions of the tubulomembranous (TM) and layered membrane loop (LML) types in the gracile nucleus, appearance of the same types in the cuneate nucleus, and a significant decrease of the neurofilamentous (NF) type in both nuclei. The incidences of the complex body (CB) and granular material types and of the homogeneous dense-body (HDB) type, which appeared only in the gracile nucleus, showed no difference between the intoxicated patients and the controls. The NF, CB and HDB types were therefore considered to be nonspecific. It was thought that chronic phenytoin intoxication might induce dystrophic changes, such as those characterized by the presence of the TM and LML types, in the axon terminals of the gracile and cuneate nuclei, possibly due to some abnormalities of the axoplasmic transport system.     

PFK inhibition test for cancer detection: clinical applications and mechanisms of PFK inhibition

A newly established cancer marker, the PFK inhibition test, has been further examined for its capacity to detect malignant neoplasms irrespective of the organs in which cancer cells start proliferating. We tested 1,160 sera from cancer patients and compared them with 756 normal sera, using histograms and normal paper for analysis of accumulated frequency. PFK activity through the influence of normal sera showed normal distribution, and cancerous sera shifted to the inhibitory site with an irregular shape. From these analyses, the patients were classified into the following types: normal range: PFK greater than SD (standard deviation of PFK activity in normal sera); suspicious range: SD greater than PFK greater than 2SD, must be given the PFK test again; and dangerous range: PFK less than 2SD, further examination must be carried out to detect cancer. Fifty percent of the sera from all the cancer patients inhibited PFK beyond 2 SD of normal sera. We also analyzed organ-associated PFK distribution, eg, gastric, colorectal, and mammary cancer. In gastric cancer, PFK inhibition was stronger in accordance with how far a particular stage of cancer had progressed. However, 50% of sera from stage I gastric cancer patients was positive beyond the cut-off line of 2 SD. We examined 104 sera from patients diagnosed as benign prostatic hypertrophy and found malignant cells in 10 patients whose sera tended to be positive in PFK inhibition. The PFK inhibitory factor in the body fluids of cancer patients was fractionated by Sephadex G-75 gel filtration and DEAE ion exchange chromatography. The approximate molecular weight of this factor was 13,000 daltons. The factor was resistant to heat and acid (0.1 N HCl and H2SO4) and was sensitive to 0.1 N NaOH and phosphate buffer. Diluted sulfuric acid and ammonium sulfate made an inactive NaOH-treated sample active when lyophilized following dialysis against distilled water. PFK inhibition by cancerous sera was eliminated by fructose-2,6-bisphosphate (the strongest activator of PFK) in a dose-dependent manner. PFK attached to agarose beads was found to be reversible even after being inhibited by cancerous body fluids and ATP water solution. Although PFK is apt to decay in a low pH range, the established procedure did not destroy PFK, but induced a direct inhibition of PFK by ATP through the ATP inhibition site on the PFK molecule. The PFK inhibitor may possibly function as a proton carrier and release protons to activate the ATP inhibition site.(ABSTRACT TRUNCATED AT 400 WORDS)     

An immunohistochemical study of MAP2 and clathrin in gerbil hippocampus after cerebral ischemia

Changes in MAP2 and clathrin immunoreactivity were studied in gerbil hippocampus after transient cerebral ischemia. MAP2 immuno-reactivity decreased significantly by 1 h in the subiculum-CA1 and CA2 areas which correspond to reactive change, while no decrease was observed in CA1 until day 4. Before the initiation of delayed neuronal death, MAP2 immunoreactivity was not changed in CA1. On the other hand clathrin immunoreactivity increased in the pyramidal cell layer of CA1 by 3 h after ischemia and remained high for 2 days. Clathrin immunoreactivity in the pyramidal cell layer of CA1 diminished after delayed neuronal death. The transient change of clathrin was noted especially in CA1 in the period prior to delayed neuronal death. These results imply an abnormal change in clathrin turnover after ischemia, which may participate in the pathogenesis of delayed neuronal death.     

Qualitative abnormalities of choline acetyltransferase in Alzheimer type dementia

The maximum activity of choline acetyltransferase (ChAT), the affinity for choline or acetyl-CoA and the isozyme pattern in the cerebral cortex of 5 cases of Alzheimer type dementia (ATD) and 6 age-matched control subjects were examined post-mortem. Maximum activities of ChAT were estimated in 5 cerebral cortical areas of Brodmann: 4, 7, 10, 17 and 22. A significant reduction in maximum activities of ChAT was found in all cortical areas for the cases of ATD. The affinity for choline or acetyl-CoA was measured in the frontal cortex (Brodmann's areas 4 and 6) and in the temporal cortex (Brodmann's areas 21 and 22). The affinity was significantly decreased in both cortices of demented patients. A significant correlation was observed between maximum activity of ChAT and the affinity for choline or acetyl-CoA. The isozyme pattern obtained by column chromatography on Sephadex G-200 was similar to that obtained by centrifugation on a sucrose density gradient. The isozyme pattern of ATD was different from that of the control subjects. These results suggest qualitative as well as quantitative abnormalities in the ChAT in autopsied brains of ATD.     

Suppressive effect of LD78 on the proliferation of human hemopoietic progenitors.

LD78 is a cDNA newly isolated from human stimulated tonsillar lymphocytes. The expression of LD78 is related to inflammatory responses and its structure has a homology with macrophage inflammatory protein 1-alpha, which is known to have an inhibitory effect on murine CFU-S. Using a colony assay technique, we examined the effects of LD78 on human hemopoietic progenitors. The addition of doses of 100 ng/ml or more of LD78 suppressed the colony formation of KMT-2, a factor-dependent myelomonocytic cell line established from cord blood cells; this suppressive activity was neutralized by the addition of antibody against LD78. The same doses of LD78 suppressed the formation of neutrophil, macrophage, and megakaryocytic colonies which were supported by human interleukin-3 and erythropoietin; however, LD78 did not affect colony formation by either non-phagocytic mononuclear cells or sorted CD34+ cells. The conditioned medium of KMT-2 cells or peripheral blood mononuclear cells cultured with LD78 suppressed colony formation by CD34+ cells. From these findings, it is suggested that LD78 affects phagocytic cells and induces factors that are inhibitory for hemopoiesis. We consider LD78 to be a new cytokine that plays an inhibitory role in hemopoiesis.     

Report of a patient of primary Sj?gren syndrome, IgA nephropathy and chronic idiopathic thrombocytopenic purpura]

We describe the case of a 61-year-old woman diagnosed with primary Sj?gren's syndrome (SS) after an 8-year history of IgA nephropathy and a 3-year history of recurrent purpuric rashes. Her two daughters had previously been diagnosed with other autoimmune diseases. One daughter had Graves' disease and the other had Hashimoto's disease and systemic lupus erythematosus. The diagnosis of SS was made based on dryness of mucous membranes, Shirmer test, and parotid sialography. Thrombocytopenia, high platelet-aggregated IgG (PA-IgG) level, and normal megakaryocytes count in bone marrow suggested that her recurrent purpuric rashes were due to idiopathic thrombocytopenic purpura (ITP). Patients with SS may develop other autoimmune diseases. This case aids understanding of the immune pathogenesis and genetic background of SS.     

Squamous cell carcinoma of the thymus

A 68-year-old woman was admitted with cough and dyspnea. Her chest X-ray showed right pleural effusion and a mediastinal tumor. She underwent mediastinotomy following a preoperative diagnosis of invasive thymoma. A tumor originating from the thymus had invaded the right middle lobe and pericardium, and multiple pleural dissemination was also found. Therefore, considering the patient's age and pulmonary function, we performed only subtotal resection of the tumor. The pathological diagnosis was poorly differentiated squamous cell carcinoma. The patient received irradiation and chemotherapy including Cisplatin after surgery, but she died 1 year later because of rapid progression of distant metastases.