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Biomedical subjects

T Seki

Publications and source records attributed to T Seki.

At least 487 records · Page 27Linked to original sources

Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues.

The primary structure of rat hepatocyte growth factor (HGF) was elucidated by determining the base sequence of the complementary DNA (cDNA) of HGF. The cDNA for rat HGF was isolated by screening a liver cDNA library with oligonucleotides based on the partial N-terminal amino acid sequence of the beta subunit of purified rat HGF. HGF is encoded in an mRNA of about 6 kilobases. Both alpha and beta subunits of HGF are specified in a single open reading frame for a 728-amino acid protein with a calculated molecular weight of 82,904. The N-terminal part of HGF has a signal sequence and a prosequence with 30 and 25 amino acid residues, respectively. The mature heterodimer structure is derived proteolytically from this single pre-pro precursor polypeptide. The calculated molecular weights of the alpha and beta subunits are 50,664 and 25,883, respectively, and each subunit has two potential N-linked glycosylation sites. The amino acid sequence of HGF is 38% identical with that of plasminogen. The alpha subunit of HGF contains four "kringle" structures, and the beta subunit has 37% amino acid identity with the serine protease domain of plasmin. Northern blot analysis revealed that HGF mRNA was expressed in rat various tissues, including the liver, kidney, lung, and brain.

Amino Acid Sequence↗

Influence of simultaneous bilateral exertion on muscle strength during voluntary submaximal isometric contraction.

The influence of simultaneous bilateral exertion on muscle strength was tested under the conditions in which the same or different levels of strength were exerted by the right and left arm (or hand). Isometric muscle strength of elbow flexion, elbow extension and hand grip was studied. Subjects voluntarily exerted 25%, 50%, and 75% of maximal strength based on their subjective judgement without the feedback of the strength actually exerted. Involuntary decrements of muscle strength were caused by the bilateral exertion. Muscle strength of both sides decreased under the condition where the same level of strength was exerted by the right and the left arm (or hand). When different levels of strength were exerted by each arm (or hand), the strength of the weaker side considerably decreased, while the strength of the stronger side did not decrease.

Adolescent↗

Combination treatment of high-dose pyridoxal phosphate and low-dose ACTH in children with West syndrome and related disorders.

Combination therapy of high-dose pyridoxal phosphate (PAL-P, 40-50 mg/kg/day) and low-dose ACTH beta 1-24-Z (tetracosactide acetate-Zn, Cortrosyn Z, 0.01 mg/kg/day) was instituted in 26 children suffering from West syndrome and related disorders--pretreated without success with high-dose PAL-P alone; 18 with West syndrome (14 with symptomatic and 4 with cryptogenic types), 2 with symptomatic Lennox-Gastaut syndrome, 5 with cerebral palsy with hypsarhythmia or diffuse slow spike-waves and one with myoclonic seizures (secondary generalized epilepsy). Clinical, electroencephalographic and neurochemical investigations were carried out. The results were summarized as follows. 1) Only one of 27 children with West syndrome and related disorders pretreated using high-dose PAL-P alone before ACTH showed a clinically excellent response. 2) Clinical seizures were completely suppressed in 19 of 21 children who initially had seizures (90%) after this combination therapy. 3) Twenty-one of the total 26 children (80%) had disappearance of hypsarhythmia or diffuse slow spike-waves in EEG after this therapy. 4) During PAL-P treatment alone transient increases in liver enzymes occurred in 37 percent. The brain shrinkage of CT and the significant rise in CSF NSE were seen in 95% and 78% after ACTH, respectively. 5) Twenty-three children have been followed for one to 29 months after tapering off of ACTH. No relapses were experienced in 11 of 18 who initially had seizures (61%) and 13 of 23 with hypsarhythmia or diffuse slow spike-waves (57%). 6) Postictal PRL elevations were suppressed during high-dose PAL-P. 7) No significant changes in the CSF levels of HVA and 5-HIAA were seen during this combination therapy. The CSF levels of HVA were significantly lower than the controls. 8) Daily ACTH therapy transiently suppressed the secretion of anterior pituitary hormones (GH, TSH, PRL, LH and FSH) and thyroid hormones (T3 free T3, T4 and free T4). It is recommended that the combination therapy of high-dose PAL-P and low-dose ACTH is a promising new method and should be tried in children with West syndrome and related disorders. The mechanism of action of this combination therapy remains obscure although some information has been obtained from our investigations.

Child, Preschool↗

Interaction between theophylline and mexiletine.

Drugs influencing hepatic microsomal enzyme systems, such as mexiletine, may affect the elimination pattern of theophylline. The three patients reported here had a history of asthma and premature ventricular contractions, and were receiving theophylline therapy. A few days after starting the coadministration of mexiletine and theophylline, theophylline serum concentrations increased about twofold over concentrations during theophylline therapy. In one case, theophylline serum concentrations increased by 2.6 fold, and the patient developed nausea and anorexia. Mexiletine serum concentrations did not change. It seems that with mexiletine therapy, lower doses of theophylline may be required and careful monitoring of serum concentrations is necessary.

Aged↗

Enhanced transdermal delivery of zidovudine in rats and human skin.

Zidovudine (azidothymidine, AZT), a potent antiviral agent acting on acquired immunodeficiency syndrome virus, was examined with regard to permeation through rat and human skin. A steady state plasma concentration of AZT after transdermal application in rats estimated from both pharmacokinetics data after i.v. administration and penetration rate through excised rat skin from 10% oleic acid (OA) aqueous solution shows penetration about 85 times higher compared to that from 10% OA would be needed for therapeutic efficacy. A mixed-solvent system consisted of 5% Sefsol-318 (S-318), 10% OA, 10% N-methyl-2-pyrrolidone (MP), 20% propylene glycol (PG) and water showed promising characteristics as a vehicle in terms of permeability of AZT through excised rat skin. The maximum flux of 0.41 mumol/cm2/h was observed in excised human skin after application of a gel formulation including S-318, OA, MP and PG. The result suggests a possible use of the gel formulation to gain an effective plasma concentration in humans.

Administration, Cutaneous↗

Membrane permeation-controlled transdermal delivery system design. Influence of controlling membrane and adhesive on skin permeation of isosorbide dinitrate.

A membrane permeation-controlled transdermal delivery system (MC-TDS) of isosorbide dinitrate (ISDN), a model drug, was prepared from polyvinyl alcohol aqueous gel containing the drug, a membrane consisting of ethylene-vinyl acetate copolymer membrane and acrylic adhesive (EV-a). The permeability of ISDN through the EV-a membrane was 2.5 times higher than that through excised hairless rat skin. The ratio of plasma concentration of ISDN after application of MC-TDS on stripped (damaged) skin relative to intact skin was lower than that after application of Frandol tape-S, a marketed ISDN TDS, which suggests that the EV-a membrane might work as a control membrane for overall delivery rate of ISDN to the body. When MC-TDS stored at 30 degrees C for 13.5-48h was applied to the damaged skin, however, the initial plasma concentration of ISDN was very much higher than the expected therapeutic level and was not controlled by the EV-a membrane. The initial high plasma concentration of ISDN after application of the stored MC-TDS on the damaged skin was due to migration of ISDN from the reservoir to the adhesive during storage at 30 degrees C. The migration of drugs into the adhesive might be an important problem in developing efficient MC-TDS.

Administration, Cutaneous↗

[Clinical study of penile carcinoma in 38 cases].

We retrospectively reviewed 38 patients with primary penile squamous cell carcinoma (stage 1 in 22, stage 2 in 7 and stage 3 in 9) who were treated in our institution from 1963 through 1987. The incidence of regional nodal metastasis was correlated with tumor category, local infiltration and tumor grade. The incidence rate of nodal metastasis of G2 and G3 tumors was statistically higher than that of G1 tumors. Of 27 patients initially treated by radiotherapy and/or chemotherapy, 11 patients achieved complete response. G1 tumors and T1 to 2 tumors had such high response rates as 58 and 50 per cent, respectively, but 5 patients (45 per cent) had local recurrence at an average of 74 months after initial treatment. The 5-year survival rates of over-all, stage 1, 2 and 3 were 73, 90, 75 and 25 per cent, respectively. Patients with stage 3 disease had a statistical lower survival rate than those with stage 1 or 2 disease. Among 13 patients with regional nodal metastasis, none with G2 tumor survived three years, although 3 patients (60 per cent) of those with G1 tumor survived five years. These results suggest that tumor grade is the most prognostic factor for the regional nodal metastasis, the response of conservative treatment and the survival of metastasized patients.

Adult↗

[Clinical experience of adrenal incidentaloma with particular reference to adrenal cortical function].

The adrenal function mainly cortical one, was evaluated in 16 patients with incidentally discovered adrenal masses. Pathological examination was possible in 15 cases. The finding consisted of adrenocortical adenoma in 9, adrenocortical nodular hyperplasia in 1, adrenal medullary hyperplasia in 1, metastatic tumor in 2 and adrenal cyst in 2. Another case of adrenal cyst was diagnosed by percutaneous puncture. In all cases peripheral levels of plasma cortisol, plasma aldosterone concentration and plasma renin activity were normal. Plasma catecholamine levels were also normal except in a case of adrenal medullary hyperplasia. On the other hand, the cases of adrenocortical adenoma displayed elevation of urinary 17-hydroxycorticosteroids in 6/9 (67%), a loss of plasma cortisol circadian rhythm in 3/7 (43%) and insufficient suppression on dexamethasone (DXM) suppression test in 6/9 (67%). Their adrenal scintigraphy (with 131I-6 beta-iodomethyl-9-nor-cholest-5 (10)-en-3 beta-ol) revealed an increased ipsilateral up-take and insufficient suppression after DXM in all, while a diminished contralateral up-take in 4/9 (44%). These data suggested that a considerable number of adrenal incidentalomas may not be truly "non-functioning". Two patients with cortical adenoma experienced post operative adrenal insufficiency (25%). It was suggested that a pre-operative loss of plasma cortisol circadian rhythm was the most prognosticating of the post operative adrenal insufficiency, rather than insufficient DXM suppression or scintigraphic absence of contralateral up-take. Among the patients with malignancy, differentiation of incidental adrenal adenoma from metastasis by size alone may not be reliable.

Adenoma↗

[Anti-HCV and long-term prognosis in patients with non-A, non-B post-transfusion hepatitis].

Anti-HCV was tested in serial serum samples of 20 patients with non-A, non-B post-transfusion hepatitis (NANB-PTH) who had been followed for more than 3 years after the onset. The rate of chronicity of disease was significantly higher in anti-HCV positive patients (12 out of 14, 85.7%) than in anti-HCV negative patients (group 1) (1 out of 6 patients, 14.3%). Among 14 anti-HCV positive patients, 7 lost anti-HCV during the follow-up period (group 2) and 6 of these 7 patients revealed normalization of liver dysfunction before or after the disappearance of anti-HCV. To the contrary, remaining 7 patients whose anti-HCV sustained positive (group 3) did show persistent abnormal liver function tests. Anti-HCV titer was significantly higher in group 3 than in group 2 at the point of 1 year after PTH. The titration of anti-HCV at 1 year after the onset of PTH was thought to be useful for estimating the prognosis of patients with post-transfusion hepatitis type C.

Adult↗

[Clinical evaluation and problem of intra-arterial infusion chemotherapy of liver metastasis from digestive organ cancer].

Intra-arterial infusion chemotherapy using an implantable reservoir was used for 22 patients with liver metastasis from September 1986 to March 1990. The material consisted of 8 subjects with gastric cancer and 14 with colorectal cancer. One had metastasis in one lobe (H1), 10 had a few scattered metastases in both lobes (H2) and 11 had numerous metastases in both lobes (H3). In 5 cases, a reservoir was implanted to prevent the recurrence after hepatectomy. Infusion catheter was placed in the proper hepatic artery in 5 cases via the gastroduodenal artery at laparotomy and it was carried out subcutaneously via the femoral artery in 17 cases. In all cases intra-arterial infusion of 5-FU was continuously administered followed by intermittent one shot injection of ADM. The clinical effectiveness of the therapy was well evaluated. One-year cumulative survival rate of all cases by Kaplan-Meier method was 55% and that of H2 cases was 78%. No recurrence was noted in post hepatectomy cases. Eight cases (36.3%) showed remarkable complications, which made it impossible to continue intra-arterial infusion chemotherapy: hepatic artery occlusion (3 cases), infection (2 cases), abdominal pain (1 case), hematoma in the implanted site (1 case) and dislocation of the infusion catheter (1 case). From the present study, it is considered that intra-arterial infusion chemotherapy is a useful procedure for the control of liver metastasis. Regimens for improved chemotherapy and the maintenance of more useful and safer catheters should therefore be investigated for further development of the therapeutical estimation.

Colorectal Neoplasms↗

[Report on clinico-pathological examinations in Meikai University (formerly Josai Dental University) Hospital (4)].

This clinico-pathological study was conducted to examine biopsies and surgical specimens for histopathological diagnosis from April 1983 to March 1988 in Meikai University (formerly Josai Dental University) Hospital. The following statistical results were obtained: 1) The total number of the specimens examined was 2705, 2026 from the dental clinic and 679 from the medical clinic. 2) Concerning age distribution, most specimens from the dental clinic were from patients in the 40's age bracket, whereas most from the medical clinic were from those under 10 years of age. With regard to sex distribution, the difference between males and females was not so much in the dental clinic specimens, but the number from the medical clinic was greater for males than for females. 3) Concerning classification of the tumors from the dental clinic, 181 cases were benign; and of them 41 were odontogenic and 140 were non-odontogenic tumors. Among the odontogenic tumors, ameloblastoma, cementoma, and odontoma were the most numerous. Among non-odontogenic tumors, fibroma was the most common, followed by pleomorphic adenoma. Malignant tumors comprised 77 cases. Of them squamous cell carcinoma was the most commonly found, with the grade-2 type being most numerous. Of the medical clinic tumors, nevus was the most common benign tumor observed; and adenocarcinoma, the most common malignant one. 4) Concerning the distribution of main lesions in the dental clinic specimens, most specimens were cysts or cystic lesions, followed by inflammatory lesions and tumors. Among medical clinic specimens, inflammatory lesions were the most common. 5) Regarding the dental clinic specimens, the most frequently observed case was the radicular cyst (301 samples) among the odontogenic cysts (514 samples); and among non-odontogenic cysts (290 samples), the most common was the mucous cyst (159 samples). 5) In terms of the distribution by location, tissue or organ, most tumors from the dental clinic were from the jaws, followed in descending frequency by those from gingiva and alveolar mucosa, maxillary sinus, lip, buccal mucosa, and tongue. Among the medical clinic tumors, the paranasal cavity and tonsils were the most frequent locations.

Adult↗

[An autopsy report of malignant fibrous histiocytoma of the left atrium and a review of the pertinent literature].

A 30-year-old male complaining of fever was admitted to hospital and a diagnosis of a malignant, fibrous histiocytoma (MFH) was established after a biopsy examination. Antitumor chemotherapy and Co60 irradiation was initiated. The patient, however, suddenly died of cardiac arrest 9 months after admission. The autopsy revealed a polypoid, yellow-white tumor (5 cm in diameter) arising from the antero-lateral wall of the left atrium and occupying the chamber. Twenty-two cases of MFH (21 previous reports and 1 current case) arising from the heart are reviewed.

Adult↗

[Changes in thyroid function during ACTH therapy in patients with infantile spasms].

Serum triiodothyronine (T3), free T3, thyroxine (T4) and free T4 levels were measured before and immediately after daily ACTH-Z therapy (0.01 mg/kg/day, 1-2 weeks) for patients with 9 cases of infantile spasms and one case of myoclonus epilepsy. In some of them, serum reverse T3 (rT3) and thyroxine binding globulin (TBG) levels were also measured. All patients became seizure free after ACTH-Z therapy. Before ACTH-Z therapy, all of the hormone levels were within normal limits. Serum T3 and free T3 levels were markedly decreased after daily ACTH-Z therapy, and serum T4, free T4 and TBG levels were moderately decreased after the therapy. 1-6 weeks after the daily treatment, all of these hormone levels returned to pretreatment levels. Serum rT3 levels did not change after ACTH-Z therapy. These results suggest that the effect of long-term daily ACTH-Z therapy is very critical to the immature brain, and conventional ACTH-Z therapy has to be reconsidered.

Adrenocorticotropic Hormone↗