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Biomedical subjects

M Abe

Publications and source records attributed to M Abe.

At least 937 records · Page 52Linked to original sources

Regeneration through nerve allografts in the cynomolgus monkey (Macaca fascicularis).

With the use of ulnar nerves of cynomolgus monkeys, the present study examined whether basal laminae of Schwann cells can serve as conduits for regenerating axons in nerve allografts from non-human primates. A segment of ulnar nerve was transected distal to the elbow joint one week before grafting. In Group A, a distal segment of the transected nerve was transplanted, after freezing and thawing, into the ulnar nerve of another monkey, at a level that corresponded to that from which the graft was taken. In Group B (the control group), the segment of nerve was grafted in the same manner but without cryotreatment. Two weeks, five weeks, eight weeks, and five months after grafting, the graft and the host nerve were examined with light and electron microscopy. Within two weeks after grafting in Group A, after degradation of the cellular components of the Schwann cells, the basal laminae of the Schwann cells were intact in the form of tubes. Within five weeks, many regenerating axons grew out into these basal lamina tubes in the three-centimeter-long grafts and extended into the host nerve. As seen at the wrist (seven centimeters from the distal suture) five months after grafting, the axons exhibited fully mature myelination both in the graft and in the host nerve. In contrast, in Group B, in which the Schwann cells had not been disrupted by cryotreatment, cellular components and connective-tissue matrices, including basal laminae, had been degraded and had been replaced by invading cells, which filled the endoneurial spaces of the graft. Five months after grafting, axonal growth had been arrested in the graft one centimeter distal to the proximal suture. The beneficial effect in Group A appears to have been the result of the retention and preservation of intact basal laminae of Schwann cells after rapid removal of killed Schwann cells and myelin debris. Killing of Schwann cells by freezing before grafting may abolish the immune response to the Schwann cells in allografts and lead to fragmentation and disruption of myelin, which facilitates the rapid removal of myelin by macrophages.

Animals↗

[Improved therapeutic effect of sequential immunotherapy with cyclophosphamide, large doses of OK-432 and recombinant interleukin-2 in breast cancer patients with disseminated metastatic liver tumors].

It has been generally agreed that the prognosis of widely spreaded "surgically unresectable" metastatic liver tumor originated from breast cancer is very poor. We reported here the result of clinical efficacy of sequential immunotherapy with intra-tumoral injection of large dose OK-432, after oral administration of cyclophosphamide during 7-10 days, and continuous perfusion of purified human recombinant interleukin-2 (rIL-2) from hepatic artery for the breast cancer patients with unresectable metastatic liver tumors. In all of 3 cases, metastatic liver tumor revealed overwhelming tumor reduction more than 50% of preoperative total tumor burden evaluated by computed tomography. Only 1 day after operation, large doses of OK-432 was injected intratumorally, both activity of Natural Killer (NK) cells and lymphokine activated killer (LAK) cells in peripheral blood lymphocytes were 5-20 folds augmented in all clinical trials. Serum tumor markers, i.e., Carcinoembryonic Antigen (CEA) and CA15-3, were rapidly decreased in all cases, respectively. Our clinical data indicate that intratumoral injection of large dose OK-432 and continuous administration of rIL-2 via hepatic artery, pretreated with cyclophosphamide, were clinically effective immunotherapy for reduction of metastatic liver tumor.

Administration, Oral↗

[Urinary N-acetyl-beta-D-glucosaminidase activity in liver cirrhosis with renal impairment].

The renal tubular damage in liver cirrhosis was evaluated by measurement of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in 32 patients with various stages of liver cirrhosis. The patients were divided to three groups (A, B, and C) according to Child's criterion and urinary NAG activity and renal function parameters were compared in these groups. As a result, urinary NAG activity in group C was significantly higher than group A and group B and slight elevation of serum BUN level and low creatinine clearance value were also observed in group C. In 8 patients who developed the renal failure in their clinical course the level of urinary NAG activity was markedly elevated in the early phase of renal failure. These results suggested that the measurement of urinary NAG activity was useful for early diagnosis of renal impairment in the cirrhotic patients.

Acetylglucosaminidase↗

[Antitumor effect of direct intra-tumor administration of OK-432 on malignant glioma: basic and clinical observations].

In this study, we tried to examine the efficacy of a cytotoxic factor which is induced by periodic, repeated local administration of OK-432 into the tumor cavity of malignant glioma patients. OK-432 was administered intratumorally via a tube to 4 malignant glioma patients on Days 1, 3, 5, 7 and 12 in doses of 0.5 KE, 1 KE, 2 KE, and 3 KE, respectively. Cerebrospinal fluid (CSF) was collected several times during the 24-hour period beginning immediately after the administration on Day 12. The CSF was added to the culture medium of rat glioma cells (GA-1 and C-6) in order to observe the cytotoxic effect morphologically. The clinical efficacy in the patients was evaluated from the changes in tumor size observed by CT. CSF collected from the tumor cavity of 3 patients was bloody. By adding this bloody CSF, a significant morphological cytotoxic effect was observed on both the GA-1 and C-6 glioma cells in culture. The level of cytotoxicity was higher with the bloody fluid collected at 4 to 24 hours after the final administration than with the bloody fluid collected immediately after the final administration. The cytotoxic effect of this fluid was stronger than that of rabbit TNF (tumor necrosis factor) serum induced with P. acnes and LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Platelet factor 4 blocks the binding of basic fibroblast growth factor to the receptor and inhibits the spontaneous migration of vascular endothelial cells.

Platelet factor 4 (PF-4) blocked the binding of basic fibroblast growth factor (bFGF) to the plasma membrane receptor. Five micrograms/ml of PF-4 completely blocked the specific binding of bFGF to the receptor of NIH 3T3 cells. Endogenously produced bFGF regulates the spontaneous migration of bovine aortic endothelial (BAE) cells as an autocrine factor (Sato and Rifkin, 1988). PF-4 inhibited the spontaneous migration of BAE cells in a reversible and dose dependent manner. The inhibition reached maximum at 5 micrograms/ml of PF-4, where the binding of bFGF to the receptor was completely blocked.

Animals↗

Enhanced leukotriene C4 synthase activity in thioglycollate-elicited peritoneal macrophages.

The utilization of LTA4 by peritoneal macrophages (MO) obtained from untreated rats (control) as well as by those elicited from rats was investigated at designated intervals (on days 3, 7, and 14) following the intraperitoneal injection of thioglycollate (TG). On day 7 following the injection the elicited MO converted LTA4 to LTC4 at the highest rate while the resident MO showed the lowest rate. The conversion of LTA4 to LTC4 and LTB4 was next examined by using each MO lysate. The apparent LTC4 synthase activity was significantly higher in the MO lysate both on day 3 and day 7, with the latter being the highest value obtained. The GSH S-transferase activity in each lysate using as the substrate, DNCB was significantly lower on day 3 but significantly higher on day 7 as compared to control values. However, this elevated activity was less variable than that observed with LTC4 synthase. The possible implication for these observations is discussed.

Animals↗

Cloning, sequencing, and transcriptional analysis of the recA gene of Pseudomonas cepacia.

A recombinant plasmid carrying the recA gene of Pseudomonas cepacia complements a recA mutation of Escherichia coli and restores UV and methylmethane sulfonate resistance, as well as recombinational proficiency. The predicted amino acid (aa) sequence of P. cepacia RecA (347 aa; Mr, 37256) is highly homologous to the RecA proteins from Thiobacillus ferrooxidans (74% aa homology), Pseudomonas aeruginosa (72%), E. coli (71%), Anabaena variabilis (61%), and Synechococcus sp. strains PCC7002 (59%). The transcription of the recA gene in P. cepacia and E. coli, which starts at almost the same site, was enhanced slightly by UV irradiation in the former and markedly in the latter bacteria. An SOS box characteristic to LexA-regulated promoters, along with the -10 and -35 consensus sequences, was found in the 5' upstream region of the P. cepacia recA gene.

Amino Acid Sequence↗

[Clinical research on hyperthermia of cancer using microwave heating equipment of lens applicator type].

Ninety cases with 96 tumors were treated by the 430 MHz microwave heating systems, HTS-100, at Tokyo Metropolitan Komagome Hospital, Kyoto University and Aichi Cancer Center. The results of treatment were analyzed, and the following have been clarified. Three cases are demonstrated showing feature of HTS-100. 1) The results of 383 sessions of heating by HTS-100 were analyzed, and it has been clarified that even the larger tumors, more than 5 cm both in size and depth, can be heated satisfactorily to temperatures higher than 42 degrees C. This system is capable of heating remarkably wider areas compared with the conventional microwave heating systems. 2) Hyperthermia by HTS-100 and radiotherapy were combined for treatment. The success rate (total percentage of CR plus PRa) of 89 cases analyzed was as high as 66.3%. Furthermore, local heating was successful for 60.7% of tumors, larger than 5 cm and deeper than 4 cm. 3) Combination of microwave heating and RF wave heating is a new method which is helpful for expansion of indications. 4) The frequencies of side effects of HTS-100 heating were: pain, 15.6%; sensation of heat, 6.3%; burns, 3.6%. Most of side effects were transient and slight. The higher frequency of pain than the conventional microwave heating is attributable to expansion of heating area.

Adenocarcinoma↗

Do thin filaments of smooth muscle contain calponin? A new method for the preparation.

A new method for the preparation of smooth muscle thin filaments which include calponin was established. We found that calponin readily separated from thin filaments in the presence of 10 mM ATP. By preventing thin filament extract from exposing to ATP, we obtained thin filaments which contained actin, tropomyosin, caldesmon and calponin in molar ratios of 7:0.9:0.6:0.7. We studied myosin Mg-ATPase activity by using the thin filaments in comparison with classical thin filaments prepared by the method of Marston and Smith, which contained the same amounts of caldesmon and tropomyosin as our thin filaments but lost almost all calponin. The presence of calponin reduced the Vmax value for thin filament-activated myosin Mg-ATPase activity by 33% without a significant change in Km value. These findings suggest that calponin inhibits myosin Mg-ATPase activity by modulation of a kinetic step as an integral component of smooth muscle thin filaments.

Actin Cytoskeleton↗

[Transcatheter intra-arterial injection of combination drugs in case of advanced uterine cervical cancer].

A total of 10 uterine cervical cancer patients (stage IIb 2, stage IIIb 6, stage IVb 2) were treated two times with selective intra-arterial injection of combined drugs of CDDP, ADR, 5-FU, MMC before operation or radiation therapy. In all patients, the tumor size was reduced macroscopically as well as on MR images. The tumor marker SCC was decreased after TAI. In 7 cases (IIb 2, IIIb 4, IVb 1) surgical treatment was made about 1 month after TAI. Histological examinations revealed that the cancer invasion markedly reduced and no malignant cells found in 3 patients.

Adult↗

The expanded populations of CD4-CD8- T cell receptor alpha/beta+ T cells associated with the lpr and gld mutations are CD2-.

Mice homozygous for either of two autosomal recessive mutations, lpr and gld, develop massive, generalized lymphoproliferation of CD4-CD8- (double negative, DN) T cells associated with a variety of autoantibodies. To determine the origin of these expanded populations of lpr and gld T cells, we examined the expression of CD2 molecules and mRNA transcripts in association with other cell surface phenotypes of these cells and correlated them with subpopulations of DN T cells in the thymus and peripheral lymphoid tissues. The results indicated that both lpr and gld cells are negative for the transcript and product of the CD2 gene. Both lpr and gld DN T cells were CD2-, CD3+, CD4-, CD8-, CD25-, CD45R+, TCR alpha/beta+, TCR gamma/delta-, HSA(J11d)-/+, Thy-1+/-, and Lp-1-/+. Studies of thymocytes in normal mice using three-color flow cytometry analysis showed that there are at least eight phenotypically distinct populations of DN thymocytes, one of which is similar to lpr and gld cells in terms of CD2-, CD3+, TCR alpha/beta+ and CD25- phenotypes, although they did not express CD45R, HSA, or Lp-1. A very minor population of these CD2-CD3+ TCR alpha/beta+ DN T cells were also detected in peripheral T cells from normal mice. These findings may provide insight into not only the origin of the aberrant lpr and gld T cells but also normal T cell development.

Animals↗

Improved survival rate in primary intracranial lymphoma treated by high-dose radiation and systemic vincristine-doxorubicin-cyclophosphamide-prednisolone chemotherapy.

Thirty patients with histologically proven primary intracranial non-Hodgkin's lymphoma were treated at Kyoto University. Ten of them were treated prospectively with a radiation-chemotherapy protocol. All but four specimens were recently reexamined and classified according to the Working Formulation system. The predominant histologic types were diffuse large cell type, large cell immunoblastic type, and diffuse mixed small and large cell type, seen in 38%, 21%, and 21% of cases, respectively. Before 1980, 16 patients were treated with postoperative radiation without definite chemotherapy, and only one has survived more than 5 years. Local recurrence was the most common cause of failure. In 1981, the authors started a protocol in which four to six courses of systemic chemotherapy with vincristine, doxorubicin, cyclophosphamide, and prednisolone (VEPA) was given after whole brain radiation (30-40 Gy) with a local boost up to 50 to 60 Gy. Eight patients completed this protocol, and all of them are alive at 16 to 100 months after diagnosis, with three patients surviving more than 5 years. Only one patient developed recurrence. On the other hand, six patients who did not complete or receive chemotherapy after 1981 are dead or alive with recurrence. Correlation between the Working Formulation subtype and prognosis was not clear because of the variety of treatment. Two patients receiving chemotherapy developed brain necrosis, which was fatal in one case, and the other two patients treated with the protocol are in a poor state without signs of recurrence. Chemotherapy may enhance the radiation effect on normal brain tissue as well as tumor. Combination of radiotherapy and chemotherapy can improve the survival rate, but the optimal dosage needs to be investigated further.

Adolescent↗

The functional site of placental anticoagulant protein: essential histidine residue of placental anticoagulant protein.

Placental anticoagulant protein (PAP) rapidly lost its anticoagulant effect due to photooxidation in the presence of methylene blue at pH 7.9 and 8 degrees C. Photooxidized PAP failed to bind the phospholipid vesicle. It seemed unlikely that the protein underwent a change in molecular size during the photooxidation on the basis of its behavior in electrophoresis and gel filtration. Photooxidized PAP had significantly decreased histidine contents, whereas the contents of other amino acids remained essentially unchanged. The peptide, SHLRKV, was included in the functional site of PAP and still showed an anticoagulant activity. On the other hand, the peptide which substituted histidine by alanine, SALRKV, no longer showed the activity. It was shown that the histidine residue is involved in Ca2+ or the phospholipid binding site of the protein.

Amino Acid Sequence↗

Priming effect of 2,3-dibenzylbutane-1,4-diol (mammalian lignan) on superoxide production in human neutrophils.

We investigated the effect of 2,3-dibenzylbutane-1,4-diol (DBB), a mammalian lignan, on superoxide production and [Ca2+]i mobilization in human neutrophils. DBB did not generate superoxide production by itself, but enhanced the FMLP or A23187-induced superoxide production in a dose dependent manner. DBB did not influence the OAG-induced superoxide production. The priming effect of DBB was inhibited by W-7 or trifluoroperazine, but not by H-7 or staurosporine. And the priming effect of DBB was observed in the presence or absence of extracellular Ca2+. DBB enhanced the low dose FMLP-induced [Ca2+]i mobilization. These results suggest that the priming effect of DBB in human neutrophils may be caused by the activation of the calcium-calmodulin pathway but not the protein kinase pathway.

Alkaloids↗

Radiofrequency thermotherapy for malignant liver tumors.

Inoperable malignant liver tumors have been treated by radiofrequency hyperthermia at Kyoto University Hospital since 1983. In this study, clinical hyperthermia for malignant liver tumor was evaluated for 67 tumors in which we could measure intratumor temperatures. Of the 67 tumors, 41 were hepatocellular carcinomas (HCC), six cholangiocarcinomas, and 20 metastatic tumors. Cholangiocarcinoma and metastatic tumors were more susceptible to this treatment than HCC. Of the three types of HCC, higher intratumor temperatures were achieved in the diffuse type than in the nodular or massive types. The minimum tumor temperature of HCC stayed below 40 degrees C in 46% of cases, especially in larger tumors. The local response rates (complete remission plus partial remission/all) were 28% and 11% for HCC and non-HCC, respectively, for thermochemotherapy; 86% and 33%, for thermoradiotherapy; and 33% and 89%, for thermotherapy with embolization. No apparent relationship was observed between the intratumor temperatures and local response rate.

Adenoma, Bile Duct↗

[Therapy of malignant pheochromocytoma using I-131 metaiodobenzylguanidine--report of a case].

A 67 year-old-female had multiple metastases to her lung, liver and paraaortic lymph nodes from a post-operative malignant pheochromocytoma. She was treated with 3.7 GBq (100 mCi) of I-131 metaiodobenzylguanidine (MIBG). Metastatic nodules in lung and liver almost disappeared and the secretion of catecholamines decreased than baseline rates. However, major but temporary untoward response, such as hypertension and hyperglycemia, was seen after the I-131 MIBG administration.

3-Iodobenzylguanidine↗

[Clinical results of conventional fractionation radiotherapy for glottic and supraglottic laryngeal cancers--the usefulness of hyperfractionation for these cancers].

Ninety patients with glottic and eighteen patients with supraglottic laryngeal cancer (anyN, M0) were treated by conventional fractionation radiotherapy between July, 1963 and August, 1988. Tumor control and cause specific survival were evaluated according to tumor location (glottic or supraglottic) and tumor size (T1, T2, T3, or T4). As a result, the steepness of dose-response curve for the tumor control in T1-2 glottic and T2 supraglottic tumors was more slanting upwards than that in other laryngeal tumors, and the patients whose tumors were irradiated at larger doses had a tendency to survive longer. These results suggested that T1-2 glottic and T2 supraglottic laryngeal tumors can have a good application for hyperfractionation radiotherapy which is a radiation therapy with multiple fractions per day with a small fraction size and with which tumors can receive larger radiation doses than with conventional fractionation radiotherapy. Five patients with glottic or supraglottic tumors treated by hyperfractionation radiotherapy obtained CR, and now show no recurrence. We are going to investigate the usefulness of hyperfractionation radiotherapy after treating more patients with Twice-A-Day fractionation radiotherapy.

Adult↗

Glycine to aspartic acid mutations at codon 13 of the c-Ki-ras gene in human gastrointestinal cancers.

Point mutations of c-ras genes were analyzed in human gastrointestinal cancers. DNA obtained from the tissues was amplified by polymerase chain reaction and then analyzed by dot blot hybridization assay with oligonucleotide probes to detect mutations at codons 12, 13, and 61 of c-Ki-ras, c-Ha-ras, and c-N-ras. In two of 25 cases of stomach cancer point mutations at codon 13 of c-Ki-ras were found. In colorectal cancer, eight of 30 cases showed mutations: four cases of codon 12 and one case at codon 13 of c-Ki-ras and two cases at codon 61 and one case at codon 13 of c-N-ras. These results may indicate involvement of a wide variety of c-ras gene point mutations, in addition to those at codon 12 of c-Ki-ras, in oncogenesis of human gastrointestinal cancers. In all three mutations of c-Ki-ras at codon 13 which had been seldom found in human cancers, glycine to aspartic acid mutations due to identical G to A transition at the second nucleotide were observed.

Aspartic Acid↗