Multivalency drives interactions of alpha-synuclein fibrils with tau.

Age-related neurodegenerative disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by deposits of protein aggregates, or amyloid, in various regions of the brain. Historically, aggregation of a single protein was observed to be correlated with these different pathologies: tau in AD and α-synuclein (αS) in PD. However, there is increasing evidence that the pathologies of these two diseases overlap, and the individual proteins may even promote each other's aggregation.

Synthesis of 7-Aminocoumarins from 7-Hydroxycoumarins via Amide Smiles Rearrangement.

N-Substituted 7-aminocoumarins can be synthesized from readily available 7-hydroxycoumarins via alkylation with α-bromoacetamides and subsequent tandem O → N Smiles rearrangement-amide hydrolysis. The key rearrangement sequence proceeds under mild conditions to provide convenient access to various -alkyl and -aryl products in moderate to high yields. The process is operationally simple, inexpensive, transition-metal-free, and can be telescoped into a one-pot process.

[N-isopropyl-p-[I123] iodoamphetamine single photon emission computed tomography (I123-IMP SPECT) and child neurology].

We studied the clinical usefulness of I123-IMP SPECT in 50 pediatric patients with CNS disorders, which were categorized into the convulsive disorder group (n = 20), the cerebrovascular disorder group (n = 10), the acute encephalopathy or CNS infection group (n = 10), the metabolic or degenerative disorder group (n = 6), the congenital abnormality group (n = 2) and the migraine group (n = 2). The findings obtained were compared with those of cranial CT. I123-IMP SPECT revealed abnormal findings in 45 out of the 50 patients (90%), although cranial CT showed abnormal findings in only 24 patients (48%).

Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients.

The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL by in vitro additional OK432, interleukin 2 or gamma-interferon were remarkable in the patients given IT-OK432.

[The expression of NCC-ST-439, a tumor marker, in human breast cancer patients].

The expression and serum level of NCC-ST-439, a tumor marker, has been investigated in 20 primary and 28 recurrent breast cancer patients, and the positive rate was found to amount to 21.1% in primary cases and 42.9% in recurrent cases, respectively, thereby indicating a positive correlation between the expression of NCC-ST-439 and the progression of the diseases.

Prospective randomized controlled study on bestatin in resectable gastric cancer--third report.

The efficacy of Bestatin as adjuvant immunochemotherapy for patients with resectable gastric cancer was investigated. Ninety-six patients with similar background factors were randomized into two groups; a control group and an experimental group, the patients in the experimental group receiving a daily oral dose of 60 mg Bestatin over a long period. All 96 patients were treated with a bolus intravenous injection of mitomycin C (MMC) plus oral administration of tegafur (FT-207, FT).

Interference of the induction of suppressor cells by a streptococcal preparation, OK-432 through the blocking of suppressor inducer T-cells.

The effect of OK-432 on suppressor inducer T cells in the generation of suppressor cells was investigated to determine its mechanism of action as an immunopotentiating agent. Suppressor cell activities induced by sera from patients with advanced cancer (stage III, IV or recurrence) were found to be as high as those induced by Con-A. Suppressor activity induced by Con-A or serum from cancer patients resided in CD8+ T cells, although CD4+ T-cells were required for the induction of suppressor cells.

[Clinical efficacy of intratumoral administration of BRM in advanced cancer and their mechanism of actions].

The clinical efficacy of intratumoral (IT) administration of BRM in 157 patients with unresectable or recurrent tumors was investigated, and the infiltration of lymphocyte subsets into tumor tissues after IT administration of BRM was immunohistologically examined, to analyse its action mechanism. BRMs used in this study were OK-432, tumor necrosing factor (TNF), whole peptide glucagon (WPG), interferon (IFN)-alpha, IFN-beta, IFN-gamma and interleukin-2 (IL-2). Among them, one hundred thirty-one patients were evaluable for clinical effects, and the therapeutic response rate (CR + PR) was determined in 11/131 (8.

Chemosensitivity tests in colorectal cancer patients.

In order to assess the usefulness of chemosensitivity tests in the treatment of colorectal cancer, 71 tumor specimens were tested for chemosensitivity in the following assays: nude mouse isotope assay (NMIA), subrenal capsule assay (SRCA), human tumor clonogenic assay (HTCA) and adenosine triphosphate inhibition assay (ATPA). The agents examined were: mitomycin C (MMC), 5-fluorouracil (5-FU), cyclophosphamide (CPM), adriamycin (ADM) and cis-diamminedichloroplatinum (CDDP). The evaluability rates were 90.

The histological assessment and evaluation of a 4 day subrenal capsule assay by the percentage inhibition of DNA/protein.

A four day subrenal capsule assay was investigated in order to determine its ability to clinically predict tumor chemosensitivity. To establish more objective and accurate evaluation criteria, a histological assessment and measurement of the DNA and protein content of excised tumor implants was conducted in ddY mice. The histological studies provided qualitative results concerning the percentage of cancer cells in the xenograft, the number of mitoses, the amount of necrosis, and the extent of lymphocytic infiltration.

[Evaluation and problems of second-look operations in resectable gastric cancer].

During the period from June 1973 to December 1985, one thousand and ninety-seven patients with primary gastric cancer have been operated on in our Dept. of Surgery. Of the 1097 gastric cancer patients, 59 were reoperated and evaluated for chemotherapeutic effects.

[Surgical stress and immunosuppression in cancer patients].

The immunosuppression caused by surgical stress in cancer therapy may affect the prognosis of patients by enhancing the residual tumors. An investigation of changes of lymphocyte subsets and suppressor cell activity during the postoperative course was performed for the analysis of the immunosuppression caused by the surgical stress in patients with gastrointestinal cancer. In patients undergoing the surgical stress of total gastrectomy or esophageal resection, CD4+2H4- (helper T) and CD8+CD11-(cytotoxic T) cells significantly depressed on day 1 after operation and remained until day 7.

[Combination chemotherapy of CPM-MTX-5-FU in non-resectable and recurrent cancer patients].

Fifty-two non-resectable and recurrent cancer patients with prior treatment, were entered in this study; 1 esophageal, 33 gastric, 1 duodenal, 4 colorectal, 2 pancreatic, 2 bile duct, and 9 breast cancer. The protocol of this therapy was as follows: On day 1, 500 mg/body cyclophosphamide (CPM) was administered by drip infusion, and on day 2, 200 mg/m2 methotrexate (MTX) was infused intravenously for 30 min; immediately after, 500 mg/body 5-fluorouracil (5-FU) was injected by bolus infusion for 5-10 min. On day 3, 24 hours after MTX administration, leucovorin rescue was added.

Blocking of lymphocyte surface binding sites for the soluble suppressor factor by protein-bound polysaccharide, PSK.

The ability of protein-bound polysaccharide (PSK) to block the suppressive activity of soluble suppressor factor (SSF) was investigated. The suppressive activity of SSF derived from U-937 cells on phytohemagglutinin (PHA)-induced lymphocyte proliferative (LP) response was significantly reduced in the presence of PSK. The release of SSF was not inhibited by the treatment of U-937 cells with PSK.

The regulation of natural killer cell activity by splenic nonspecific suppressor cells and its modification in cancer patients.

Spleen cells (SC), splenic venous blood lymphocytes (SVL) and peripheral blood lymphocytes (PBL) from gastric and esophageal cancer patients were simultaneously tested for natural killer (NK) and nonspecific suppressor (Ts) cell activities. Furthermore, the influence of Ts activity on the augmentation of NK activity by a biological response modifier (BRM) was also investigated. Positive Ts activities were frequently detected in the SC, SVL and PBL of advanced cancer patients.

[Hoarseness after removing a cervical schwannoma--a case report].

A 54-year-old man complained of asymptomatic lump in the right parotid gland region. The lump was well movable and had no fixation to the adjacent tissue. The lump was surgically extirpated and histological sections of the lump revealed benign schwannoma.

Relationship of the distribution of Leu-2+ cells with suppressor cell activities in the spleen and lymph-nodes from gastric cancer.

Tissue distributions of Leu-2+ cells in the spleen and draining lymph-nodes in cases of clinical gastric cancer were investigated, with special reference to suppressor cell function. Significantly higher Concanavalin-A (Con-A) induced suppressor cell activities were evident in spleen cells (SCs), as compared with peripheral blood lymphocytes (PBLs). As for the tissue distribution, the proportion of Leu-2+ (cytotoxic/suppressor) cells within Leu-1+ cells was higher in the spleen than in the lymph-nodes without metastasis.

Reduction of suppressor cell activities of human peripheral blood lymphocytes by a streptococcal preparation, OK-432.

The effect of a streptococcal preparation, OK-432 on suppressor cell activities of peripheral blood lymphocytes was investigated. Suppressor cell activities were significantly reduced when they were generated in vitro by concanavalin A (Con A) in the presence of OK-432. However, the reduction of suppressor cell activities was not observed when OK-432 was added in the effector phase.

[Microangiopathic hemolytic anemia associated with gastric cancer].

A case of advanced gastric cancer associated with metastatic carcinomatosis of the bone marrow, microangiopathic hemolytic anemia (MAHA) and disseminated intravascular coagulation (DIC) was reported. A 71-year-old woman complained of lumbago and general fatigue. At the time of admission, besides anemia, jaundice and a tendency to bleeding, the laboratory data showed, hyperbilirubinemia, elevated FDP and hemolytic anemia with fragmented red cells.

[Immune reactivities of lymphocytes from peripheral blood, regional lymph nodes and tumor-infiltrating lymphocytes in breast cancer].

Immune reactivities in 174 breast cancer patients were investigated. Immune reactivities were assessed by lymphocyte responsiveness to phytohemagglutinin (PHA), suppressor cell activities, sera-induced suppressor cell activities, NK activities and autologous tumor-killing activities. Low responsiveness of peripheral blood lymphocytes (PBL) to PHA mitogen and an increase in the inductive activity of suppressor cells by sera were observed in breast cancer patients as compared with normal volunteers or patients with benign breast diseases.

[Development of cancer immunotherapy by a combination of biological response modifiers on the basis of their mechanism of action].

The enhancement of antitumor effects by combination of biological response modifiers (BRM) was investigated on the basis of their action mechanisms. Experimentally, significant inhibition of tumor growth by combination treatment with BRM, which eliminated immune suppressive mechanisms and in turn enhanced immune responses, was observed. Furthermore, inhibition of tumor growth was observed under conditions of uniform biorhythm in mice and the effect of modification of biorhythm was enhanced by combination with BRM.

Autologous tumor killing and natural cytotoxic activity of tumor-associated macrophages in cancer patients.

Tumor-associated macrophages (TAM) isolated from pleural effusions and ascites fluids of cancer patients were tested for cytotoxicity against freshly isolated autologous tumor cells and K562 in a 4-h 51Cr-release assay, and in vitro effects of OK432 (a streptococcal preparation) and partially purified human leukocyte interferon (IFN) on their cytotoxicities were examined. Positive cytotoxicities against K562 were recorded for TAM samples from 2 of 23 pleural effusions and 3 of 10 ascites specimens. Tumor-associated macrophages were not cytotoxic to autologous tumor cells, while low but significant lysis was observed with tumor-associated lymphocytes (TAL) samples from 2 of 13 pleural effusions and 1 of 6 ascites specimens.