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Biomedical subjects

H Matsuzaki

Publications and source records attributed to H Matsuzaki.

At least 19 recordsLinked to original sources

Molecular cloning and characterization of a new member of the RAC protein kinase family: association of the pleckstrin homology domain of three types of RAC protein kinase with protein kinase C subspecies and beta gamma subunits of G proteins.

cDNA clones encoding the third member of the RAC protein kinase family, termed RAC-PK gamma, were isolated from a rat brain cDNA library. The deduced amino acid sequence of RAC-PK gamma was highly related to those of previously identified family members, RAC-PK alpha and beta, that have a pleckstrin homology domain and a protein-serine/threonine kinase catalytic domain at the amino- and carboxyl-terminal regions, respectively. Northern blot analysis indicated that RAC-PK gamma was expressed abundantly in brain and testis. Specific activities of RAC-PK alpha, beta, and gamma purified from transfected COS-7 cells were similar when measured by using myelin basic protein as a phosphate acceptor. Analysis using fusion proteins of glutathione S-transferase revealed that the pleckstrin homology domain of the three subtypes of RAC-PK associate with both protein kinase C subspecies and beta gamma subunits of G proteins. These results suggest that the pleckstrin homology domains of RAC protein kinase family could associate more than one protein to regulate the activity and/or intracellular distribution of this enzyme family by different ways.

Amino Acid Sequence

Expression of Fas/Apo-1 (CD95) and apoptosis in tumor cells from patients with plasma cell disorders.

Fas/Apo-1 antigen (CD95) is a cell surface molecule that directly mediates apoptosis. Fas expression was studied in five plasma cell lines, 11 multiple myeloma cases, and three plasma cell leukemia (PCL) cases. Induction of apoptosis by anti-Fas antibody was studied in five plasma cell lines and fresh plasma cells from eight patients. Apoptosis was confirmed by morphologic analysis alone or in combination with DNA electrophoresis analysis. Four of the five cell lines showed Fas expression, three of which showed induction of apoptosis by anti-Fas antibody. One cell line, RPMI 8226, showed the highest sensitivity for Fas-mediated apoptosis. High bcl-2 expression was found in KMS12PE, which showed resistance to Fas-mediated apoptosis despite its Fas expression. Plasma cells from seven fresh cases, including all five cases with high serum lactate dehydrogenase (LDH), showed expression of Fas antigen. Fas-induced apoptosis was found in five cases at various levels, although significant induction of apoptosis was found in only one case. Interestingly, Fas-independent apoptosis was induced during culture without anti-Fas antibody in cases with high serum LDH. These results indicate that plasma cells from aggressive myeloma with high LDH express Fas antigen and undergo apoptosis through either Fas-mediated or Fas-independent pathways. An understanding of the mechanism of apoptosis in malignant plasma cells should contribute to investigations of the pathophysiology of and therapy for myeloma/PCL.

Adult

Serum amino acid disturbance in multiple myeloma with hyperammonemia.

From October 1987 to November 1993 we evaluated the serum levels of ammonia and amino acids in 85 patients with multiple myeloma. Six of the 85 cases of multiple myeloma demonstrated hyperammonemia and none of the known causes of hyperammonemia, such as liver failure, could be identified in these patients. All six patients also showed serum amino acid disturbances and conscious disorders in various degrees. In this study we compared these abnormalities in multiple myeloma with those in chronic liver failure (n = 14), the basic diseases of which were liver cirrhosis in six cases and liver cirrhosis complicated hepatocellular carcinoma in eight cases. There was a marked difference in the levels of individual serum amino acids between these two groups. The level of glycine was significantly higher in the multiple myeloma group (P < 0.001); on the other hand, that of tyrosine was significantly higher in the liver failure group (P < 0.005). The histidine (P < 0.005) and arginine (P < 0.005) levels were lower in the myeloma group. The ratio of glycine to tyrosine (Gly/Tyr) was 16.7 +/- 4.85 in the myeloma group and 1.7 +/- 0.12 in the liver failure group. The ratio of glycine to tyrosine was an important criterion for differential diagnosis.

Adult

Combined dorsal forearm and lateral arm flap.

The free latissimus dorsi musculocutaneous flap and the free groin flap have been used for the coverage of medium- to large-sized soft-tissue defects in the hand. However, these are often too bulky for the hand, requiring secondary operation for thinning. We have used the dorsal forearm flap combined with the lateral arm flap for the coverage of large soft-tissue defects in the hand. This flap is based on the reversed vascular pedicle of the posterior interosseous artery. The posterior radial collateral branch of the profunda brachii artery is then anastomosed to the recipient vessel to augment the vascular supply to the lateral arm flap. We have used this combination flap in two clinical cases and achieved one-stage soft-tissue reconstruction of the hand.

Adult

[Inhibitory effects of menogaril to the proliferation of HTLV-I infected T-cell lines and fresh tumor cells from adult T-cell leukemia patients].

Anti-cancer effect of anthracyclines are well established. In vitro inhibitory effects of a new anthracyclin-derivative drug, menogaril (TUT-7) which is developed for oral administration, on three human T-cell leukemia virus type-I (HTLV-I) infected T-cell lines, a HTLV-I non-infected T cell line, and fresh tumor cells from four adult T-cell leukemia (ATL) cases are evaluated and compared to those of doxorubicin. The inhibitory effects of TUT-7 is almost as much as those of doxorubicin. Both TUT-7 and doxorubicin induced apoptosis to a HTLV-I infected cell line and inhibited proliferation of fresh tumor cells from ATL of chronic, acute and lymphoma type in a dose dependent manner. We have already reported that skin eruption of ATL patient improved by oral administration of TUT-7. This new anthracyclin-derivative would be useful in treating ATL patients even in out-patients clinic keeping a good quality of life.

Apoptosis

[Annual number of Pseudomonas aeruginosa isolated inpatients, and antibacterial activity of various antibiotics against P. aeruginosa isolated from clinical specimens of inpatients].

In recent years, isolation rate of methicillin-resistant Staphylococcus aureus (MRSA) has decreased, while the rate of Pseudomonas aeruginosa has increased. This phenomenon may be a result of regulation of use of antibiotics which belongs to the third cephems and extensive preventive measures against hospital acquired infections due to MRSA. Based on our investigation in which we determined MICs of various antibiotics against P. aeruginosa strains isolated from inpatients, the antibacterial activities of cefclidin (CFCL) was superior to those of other antibiotics. The antibacterial activity of CFCL against P. aeruginosa tested was similar to or stronger than that of tobramycin.

Anti-Bacterial Agents

[Monoclonal antibodies against myeloma cells].

Tumor cells in multiple myeloma are considered to originate from terminally differentiated B-cells e. g. plasma cells. Although it is known that antigens on circulating B-cells, such as CD20, are lost during terminal B-cell differentiation, antigens which are acquired on plasma cells are not well known. Plasma cell specific antibodies would provide useful informations of B-cell differentiation and diagnosis of myeloma. Moreover, therapeutic applications of these antibodies are already reported, especially, in bone marrow transplantation. On the other hand, phenotypic heterogeneity of myeloma cells is investigated by analyzing various antigens on myeloma cells. Monoclonal antibodies against myeloma cells which have appeared in the literature and their clinical applications are summarized.

Antibodies, Monoclonal

Clinical application of the Diapason hook system: a preliminary case report.

A preliminary case report of the clinical application of the Diapason hook system is discussed. The hooks were implanted in six patients for the fixation of the thoracic region (n = 3), the prevention of backout of pedicular screws (n = 3), and repair of the pars interarticularis (n = 1); the patients were followed for more than 6 months after the surgery. Results indicate that in all of the cases the initial purpose of the Diapason hook system was served. The advantages of the Diapason screw and hook system are its titanium alloy material and simplicity in implanting. Although there have been no instrument failures or any other complications, the cases need longer follow-up. In addition, the size of some hooks needs to be improved because they were too large to apply to the short segments.

Adolescent

[An experimental study on preserving the intervertebral discs, in dog--prior to disc allografting].

Disc grafting is a new surgical procedure that may be suitable for preserving mobility of the spine. This experimental study was designed to determine a method of favorably preserving a disc prior to allografting. The lumber vertebrae of adult mongrel dogs were aseptically excised, regarded as the vertebral body-disc unit, and preserved at -80 degrees C, or at 4 degrees C. In the preservation at 4 degrees C, UW solution, Euro-Collins solution, EP-II solution, Ham's F-12, or physiological saline solution was used for preservation. Isotopes were used for determining the activities of the disc cells. In the preservation at -80 degrees C, it was difficult to maintain the activity regardless of the preservation period. There was no difference among these preservative solutions in the preservation at 4 degrees C on the nucleus pulposus, but the 2-day preservation in UW solution provided the best results in terms of the annulus fibrosus. Based on the results of these experiments, at -80 degrees C it was difficult to maintain the activity of disc cells while at 4 degrees C the UW solution was the most effective for preserving the anulus fibrosus. However the period of preservation was very short, and a new method to enable longer periods of preservation should be developed.

Adenosine

[Pharmacokinetic study in biochemical modulation therapy of UFT with leucovorin tablet].

Preoperative oral treatment with UFT and leucovorin tablet was performed. Pharmacokinetics, degree of degeneration in the tumor tissue and side effects were studied in 34 patients with colorectal cancer preoperatively given 400 mg/day of UFT with 20 mg/day of leucovorin tablet or 400 mg/day of UFT alone. Results were as follows; 1) there was no significant difference between UFTL group and UFT group regarding concentration of FdUMP in the tumor tissue. In UFTL group, concentration of FdUMP was higher in the tumor tissue of moderately differentiated adenocarcinoma than that of well differentiated adenocarcinoma. No significant differences regarding concentration of FdUMP were obtained between diploid and aneuploid groups. 2) TS inhibition rate in the tumor tissue was 66.8% in UFTL group and 53.2% in UFT group, and there was a significant difference between these two groups. TS inhibition rate in the tumor tissue was higher than that in the normal tissue either in UFTL group or UFT group. However, there were no significant differences of TS inhibition rates regarding differentiation of tumor tissue or DNA ploidy pattern. 3) Degree of degeneration of more than Grade 2 was not obtained in any patients of either UFTL or UFT group. 4) There was no change in blood laboratory data between before and after medication. Only one patient complained Grade 1 pruritus in UFTL group. These results suggest that oral biochemical modulation therapy of UFT with leucovorin tablet is effective because of pharmacokinetically high anti-tumor effect and minimal side effects.

Adenocarcinoma

Nonanastomotic aneurysm formation in a Dacron arterial graft: report of a case.

Dacron prostheses are the most widely used grafts in replacement procedures for abdominal aortic aneurysms, having been proven as the most reliable substitute for arterial replacement. However, we present herein the rare case of an 82-year-old woman in whom nonanastomotic aneurysm formation occurred in the graft as a complication associated with a Dacron prosthesis. The patient presented with a pulsatile mass in the right inguinal region. She had undergone surgery 13 years earlier for an abdominal aortic aneurysm, at which time an aortobifemoral graft reconstruction had been performed with a double-velour knitted Dacron prosthesis. The pulsatile mass was found to be a nonanastomotic aneurysm of the right limb of the bifurcated graft with an intact distal anastomosis. In this case, the development of the graft aneurysm seemed to result from deterioration of the Dacron prosthesis itself due to mechanical fatigue caused by the inguinal band.

Aged

Simple monitoring system for R-mediated site-specific recombination on chromosomes in Saccharomyces cerevisiae.

A simple measuring system for the frequency of recombinant clones generated by R-protein mediated recombination was constructed. By applying the system, the frequencies of recombinant clones due to site-specific recombination between two loci on one or two different nonhomologous chromosome(s) were monitored during cultivation. Subsequently, it was found that the frequencies increase nearly in proportion to the culture period and are different among the individual two selected loci. Thus, the system is thought to be a candidate for analyzing physicochemical situations, such as folding and localization, of chromosomes in the nucleus.

Bacterial Proteins

Acidic-phospholipid deficiency represses the flagellar master operon through a novel regulatory region in Escherichia coli.

The Escherichia coli pgsA3 mutation, which causes acidic-phospholipid deficiency, was found to repress the flagellar master operon, as assessed by the beta-galactosidase activities of flhD-lacZ fusions. This explained the impairment of flagellar formation and motility by the mutation. A series of deletion analysis indicated that a 40-bp region, at the 5' end of the flhD locus examined, was responsible for the repression of a downstream transcription initiation that was catabolite-repression sensitive. This novel regulatory region was 200 bp upstream of the first possible translation initiation site.

Bacterial Proteins

[Primary plasma cell leukemia complicated with high-output cardiac failure and hyperammonemia].

A 23-year-old male patient with plasma cell leukemia showed characteristic clinical features: accelerating heart failure and consciousness disturbance accompanied with an increase of plasma cells in peripheral blood. Evaluation of cardiac function revealed a hyperdynamic cardiac state with low somatic vascular resistance, indicating high-output cardiac failure. However no disorders causing high-output cardiac failure were found. Consciousness disturbance and hyperammonemia with serum amino acid abnormality of unknown origin were also demonstrated. After intensive combined chemotherapy (MVD + VAD), high-output cardiac failure and hyperammonemia improved with disappearance of plasma cells, suggesting that these symptoms were closely related with progression of plasma cell leukemia.

Adult

Establishment of a CD45-positive immature plasma cell line from an aggressive multiple myeloma with high serum lactate dehydrogenase.

A myeloma cell line (KHM-11) was established from the pleural effusion of a patient with IgA-kappa type aggressive myeloma with high serum lactate dehydrogenase who was extremely resistant to vincristin, adriamycin and dexamethasone combination therapy (VAD). The morphology of fresh tumor cells and KHM-11 was plasmablast according to Greipp's criteria. In addition to the expression of regular plasma cell antigens, CD38 and PCA-1, CD45 was found on both fresh cells and KHM-11. Other T- or B-cells antigens, such as CD2, 4, 8, 19, and 20 were negative. Cytoplasmic immunoglobulin kappa light chain in KHM-11 was found by flowcytometry. Southern blot analysis revealed that fresh sample and KHM-11 shared the same immunoglobulin gene rearrangement. IL-6 was found in the culture supernatant of KHM-11, and this supernatant stimulated the growth of this cell line, indicating an IL-6 autocrine mechanism. These findings indicate that KHM-11 is a CD45-positive immature plasma cell line. As far as we know, there is no report of CD45-positive myeloma cell line. KHM-11 should be a useful tool for understanding not only the pathogenesis of aggressive multiple myeloma with high LDH but also for understanding the mechanism which underlies the terminal differentiation of B-cells.

Antigens, Surface

[Pharmacokinetic studies on continuous intraportal 5-fluorouracil infusion].

Pharmacokinetics of 5-FU administered by continuous intraportal infusion were studied by infusing 5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of 5-FU, respectively, into the ileocecal vein for an hour. Blood samples were collected from portal vein, femoral vein and liver, and small intestine specimens were obtained at proper intervals. The rabbits were sacrificed at 120 minutes from the start of 5-FU infusion. The results were as follows: Extremely high concentrations of 5-FU in the portal vein, femoral vein and liver tissue were observed in the 5-FU group infused with 40 mg/kg. This phenomenon was suggested to rely on the effect by which the 5-FU catabolic enzyme, dihydrouracil dehydrogenase, was saturated with a large inflow of 5-FU. FdUMP concentration of the liver was lower than that of the small intestine in all groups. These results suggest that a large dose of 5-FU infusion is effective to increase the FdUMP concentration in the liver with continuous intraportal 5-FU infusion.

Animals