Biomedical subjects
Publications and source records attributed to T Kudo.
The alpha-amylase gene of a Natronococcus sp. (1,512 bp) contained a signal peptide of 43 amino acids. Haloferax volcanii expressed the gene and cleaved the signal peptide accurately. The signal peptide shared an extremely high amino acid sequence identity with that of a protease from the halophilic archaeon 172P1.
Na+/H+ antiport was studied in alkaliphilic Bacillus sp. strain C-125, its alkali-sensitive mutant 38154, and a transformant (pALK2) with recovered alkaliphily. The transformed was able to maintain an intracellular pH (pHin) that was lower than that of external milieu and contained an electrogenic Na+/H+ antiporter driven only by delta psi (membrane potential, interior negative). The activity of this delta psi-dependent Na+/H+ antiporter was highly dependent on pHin, increasing with increasing pHin, and was found only in cells grown at alkaline pH. On the other hand, the alkali-sensitive mutant, which had lost the ability to grow above pH 9.5, lacked the delta psi-dependent Na+/H+ antiporter and showed defective regulation of pHin at the alkaline pH range. However, this mutant, like the parent strain, still required sodium ions for growth and for an amino acid transport system. Moreover, another Na+/H+ antiporter, driven by the imposed delta pH (pHin > extracellular pHout), was active in this mutant strain, showing that the previously reported delta pH-dependent antiport activity is probably separate from delta psi-dependent antiporter activity. The delta pH-dependent Na+/H+ antiporter was found in cells grown at either pH 7 or pH 9. This latter antiporter was reconstituted into liposomes by using a dilution method. When a transmembrane pH gradient was applied, downhill sodium efflux was accelerated, showing that the antiporter can be reconstituted into liposomes and still retain its activity.
Effect of bioceramic implantation on the intermandibular space along with plating in rostral mandibulectomy was investigated in the dog. In this group, bioceramic beads consisting of a complex of hydroxyapatite and tricalcium phosphate were implanted in the intermandibular space between the lingual surfaces of the fracture ends. In two other groups, the dogs received only plating on the ostectomized end, or they received only rostal mandibulectomy without plating. No difficulty in mastication was observed in the implanted group after surgery. In the dogs which received plating, however, difficulty was noted only in the 4th week when wet food was replaced by dry food, and in the control group in the 6th week after the surgery. From the radiological and microscopical findings, in dogs with only plating or without the fixation there was no bony union in the intermandibular space at 16 weeks, though the increase in fibrous tissue and bony callus in the area was much greater in the plated dogs than in the control group. In the implanted group, on the other hand, the increase in callus formation was considerable compared to the other groups. Moreover, the lingual surfaces of the fracture ends were well ossified at 12 postoperative weeks. This suggests that in canine bilateral rostral mandibulectomy the stabilization of the fracture ends with plates and bioceramic implants filling a gap in the intermandibular space may enhance the ossification between the fracture ends and prevent postoperative difficulty in mastication.
Odontogenic neoplasm was found in the mandibular incisor area of a 3-year-old Japanese black ox. Macroscopically, the cut surface was white and firm with streaks of hard tissue. Histologically, the tumor was composed of enamel organ structures with odontogenic hard tissue in fibromatous areas. It was diagnosed as ameloblastic fibro-odontoma. The absence of the 4th permanent incisor confirmed by radiography and microscopic examination strongly suggests that this tumor has been originated from the tooth germ tissues of the permanent left 4th incisor.
The reduction of experimental humeral fracture in pigeons was performed with intramedullary bone cement (poly (methyl methacrylate): PMMA) and neutralization plate fixation to investigate the effect on bone fracture healing and the recovery of flying ability. As a result, neither plate nor bone cement fixation held for more than 2 weeks, but not refracture was observed in any cases with both plate and bone cement. In the latter group, it was confirmed by flight tests that almost normal flying ability was recovered in 6 weeks. In pathological findings, blood supply to the fractured ends recovered within 2 weeks and no cortical bone necrosis was observed at the time except for a disturbance of endosteal callus formation. The process of fracture healing on the plate side took place slightly later than that on the non-plate side, and when much PMMA remained between the fractured ends of the cortical bone the bone formation became spongioid. In view of the quick recovery of flying ability, however, plate and bone cement fixation is considered appropriate to prevent the displacement of a humeral fracture in the pigeon.
Pulmonary metastatic tumors in two patients with locally well controlled uterine cancer were treated with bronchial arterial infusion chemotherapy. The first patient underwent a radical hysterectomy and pelvic lymphadenectomy for stage IIb cervical cancer. Fifteen months after the operation, pulmonary metastasis was identified. Clinical evidence of tumor was negative after bronchial arterial infusion chemotherapy, systemic chemotherapy and radiotherapy. The patient continues to be healthy without recurrent signs six years after bronchial arterial infusion chemotherapy. The second patient underwent a radical hysterectomy and pelvic lymphadenectomy for stage II endometrial cancer. Fifteen months after the operation, pulmonary metastasis was identified. After bronchial arterial infusion chemotherapy and systemic chemotherapy, regression of the tumors was observed. This patient has also survived for two years since the lung metastases. These results indicate that bronchial arterial infusion chemotherapy is a potent treatment for pulmonary metastases of uterine cancer.
P-glycoprotein is a transmembrane protein which acts as an energy-dependent drug efflux pump for a variety of anti-cancer drugs. The mdr-1 gene which encodes P-glycoprotein was successfully cloned in 1986. To investigate P-glycoprotein expression in diverse ovarian tumors, including benign, low malignant potential and malignant, immunohistochemical study was done using a monoclonal antibody (C 219). Overall, 8 out of the 59 epithelial ovarian tumors (13.6%) expressed P-glycoprotein. It was noted that 5 of the 12 mucinous tumors were found to express P-glycoprotein, while none of the 31 serous tumors were immunohistochemically positive. In 10 malignant ovarian tumors, P-glycoprotein immunostaining was examined both prior to and after chemotherapy. Nine of them did not express any P-glycoprotein before or after chemotherapy. However, one tumor expressed P-glycoprotein after six courses of multidrug resistance-related drug administration. These findings indicate that P-glycoprotein expression is not so common in ovarian tumors, regardless of their malignant potential. Nevertheless, the results suggest a strong association between P-glycoprotein expression and certain histological cell types in epithelial ovarian tumors. It is also possible that P-glycoprotein appears as a result of chemotherapy, but such a phenomenon can not occur unless chemotherapy is administered at high doses for a long period of time.
The effects of epidermal growth factor (EGF) on neonatal intestines were examined in the rat. In 5-day-old rats, sucrase, trehalase, alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) activities in the small intestines were significantly increased after subcutaneous injection of EGF for 3 days (1 microgram/rat/day). gamma-GTP activity was also accelerated after oral EGF administration (2 micrograms/rat/day). Small intestines of 12-day-old rats injected with EGF for 10 days (1 microgram/rat/day) were significantly heavier than those of controls. These results suggest that EGF influences neonatal growth improving enlargement and functional development of their intestines.
A trifluoroacetamide analogue of siastatin B, (3S,4S,5R,6R)-6-(trifluoroacetamido)-4,5-dihydroxy-3-piperidine carboxylic acid has been chemically synthesized. This compound, as well as the previously synthesized analogue, (3R,4R,5R,6R)-6-(trifluoroacetamido)-3,4,5-trihydroxy-3-piperid inecarboxylic acid, showed marked inhibitory activity against beta-glucuronidase and significant inhibition of experimental pulmonary metastasis of the highly metastatic melanoma B16.
Based on our studies on the enzymatic modifications of arbekacin by methicillin-resistant Staphylococcus aureus (MRSA), replacement of the 2''-hydroxyl group by an amino group in arbekacin was designed to synthesize derivatives that would be active against MRSA. 2''-Amino-2''-deoxyarbekacin and five analogs were synthesized starting from dibekacin. Among them, 2''-amino-2''-deoxyarbekacin and the 5-epiamino analog showed excellent antibacterial activities against not only MRSA but also Gram-negative bacteria including Pseudomonas, and lower toxicities than arbekacin.
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We measured plasma aldosterone, cortisol, ACTH and catecholamine concentrations during removal of aldosterone-producing adrenal tumor under sevoflurane anesthesia in four adult patients. Sevoflurane anesthesia alone did not affect the plasma levels of aldosterone, cortisol, ACTH and catecholamine. Plasma aldosterone levels increased significantly with surgical stimulation and reached the peak value before surgical manipulation. Thereafter they declined in magnitude and reached the value below the peanesthetic levels at recovery from anesthesia. Plasma cortisol and ACTH levels increased significantly with surgical stimulation, and plasma ACTH levels reached the peak values after the emergence from anesthesia in the recovery room. Plasma catecholamine levels increased with surgical stimulation, but the increase in plasma epinephrine levels was more striking than that in plasma norepinephrine levels during surgical manipulation of the tumor. Hypertension during manipulation of the tumor was demonstrated to correlate with increase in plasma epinephrine levels but not with plasma aldosterone levels. Sevoflurane gave us no trouble during anesthetic management for removal of aldosterone-producing adrenal tumor. We conclude that sevoflurane anesthesia is a better choice for surgery for primary aldosteronism.
Gene expression of protein phosphatases 1 alpha, 1 gamma 1, 2A alpha, and 2C alpha in 14 rat ascites hepatoma cell lines was studied by Northern blot hybridization. The expression of PP1 alpha and PP2C alpha was increased and decreased, respectively, in all of the ascites hepatoma (AH) cells compared to rat liver, whereas the expression of PP1 gamma 1 and PP2A alpha was increased in about 50% of them. Relative gene expression was affected by several factors, such as harvest time, transplantation rate, percentage of free cells, and sex; the first factor was more important than the others. Relative gene expression of PP1 alpha had a negative correlation with harvest time, whereas gene expression of PP1 gamma 1 and PP2A alpha had a nonlinear (hyperbolic) correlation with harvest time. We suggest that there is a relationship between growth rate and expression of protein phosphatase genes. Our data also suggest that PP1 gamma 1 mRNA is positively controlled by PP2A alpha mRNA.
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We measured plasma catecholamine levels and hemodynamics in 5 patients during surgical removal of pheochromocytoma under sevoflurane anesthesia. Plasma catecholamine levels were unchanged with sevoflurane anesthesia. Plasma epinephrine, norepinephrine and dopamine levels increased 149 folds, 7.8 folds and 2.9 folds respectively as compared with preanesthetic values during surgical manipulation of the tumor, and then declined in magnitude but still remained 15 folds, 2.7 folds and 1.8 folds higher respectively as compared with the preanesthetic levels after removal of the tumor. These catecholamine levels finally reached 180%, 20% and 60% of the preanesthetic values respectively after the emergence from anesthesia in the recovery room. Mean systolic and diastolic arterial blood pressures were 127/82 mmHg before anesthetic induction and increased to 211/71 mmHg during manipulation of the tumor. Then they decreased to 75/52 mmHg immediately after removal of the tumor but recovered up to 126/71 mmHg on recovery from anesthesia. Alpha and beta adrenal blockers were administered if necessary to control hypertension and tachycardia during manipulation of the tumor. Hypotension after removal of the tumor was treated with volume replacement, vasopressor and/or catecholamines. No correlation was found between plasma catecholamine levels and arterial blood pressure in our study except during manipulation of the tumor. No arrhythmias were observed during anesthesia and surgery in our cases even though plasma catecholamines increased extremely with surgical intervention. We conclude that sevoflurane anesthesia is a better choice for surgery for pheochromocytoma.
The need for efficient production of human monoclonal antibodies to tumor-associated antigens is increasing. A study of human monoclonal antibody 904F produced from the regional lymph nodes of a patient with squamous cell carcinoma of the lung was described. By immunohistological study, the 904F antibody has been found to be a new human monoclonal antibody which might be a candidate for clinical application. The second part of the study reports the successful production of human monoclonal antibodies directed to lung cancer by active in vivo immunization of a PBL-SCID mouse (a severe combined immunodeficient mouse grafted with human peripheral blood lymphocytes) with squamous carcinoma cells. These human monoclonal antibodies are promising for the detection and therapy of cancer.
Public health and welfare services were examined in 125 dependent elderly aged 70 to 89 years old from a randomly selected population of 1,249 from 3 different areas (central, residential and suburban) in Wakabayashi-ku, Sendai. Of the 125 dependent elderly, 91 (72.8%) were being cared for at home (the home group), and 34 (27.2%) were in hospitals or nursing homes (the resident group). Multivariate analyses using Hayashi's quantification method II were conducted for a comparison between the home group and the resident group. For the resident group relationships were found to "not having any family members to live with", and to "severe disability in ADL". Of the 91 subjects in the home group, 27 (29.7%) were visited by public health nurses (the visited group), and 64 (70.3%) were not (the not-visited group). Multivariate analyses using Hayashi's quantification method II were conducted for a comparison between the visited group and the not-visited group. For the visited group relation to husbands or wives being caregivers and to severe disability in ADL was found. Of the 91 in the home group, 15 (16.5%) received welfare services (the recipient group), and 76 (83.5%) did not (the non-recipient group). Again, multivariate analyses using Hayashi's quantification method II were conducted for a comparison between the recipient group and the non-recipient group. In the non-recipient group a relationship to not having caregivers or to caregivers being persons other than husbands, wives, children or grandchildren was seen.
It was recently described that the cardiac myxoma produced Interleukin-6 (IL-6) as a kind of cytokines, and the constitutional signs in patients with cardiac myxoma were due to the IL-6 production. We measured the values of plasma IL-6 concentration before and after surgical therapy. It was decreased from 7.2 pg/ml to less than 4.0 pg/ml two months after surgical removal of the myxoma. It is recommended that the measurement of IL-6 is useful for screening of cardiac myxoma and postoperative follow-up.