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Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 451 records · Page 25Linked to original sources

Association between family history and gastric carcinoma among young adults.

The relationship between family history of gastric carcinoma and gastric carcinoma in Japanese under 40 years of age was analyzed. The subjects were 108 gastric carcinoma patients (86% were diffuse type) at 9 hospitals in the Kanto area of Japan. Firstly, incidence of gastric carcinoma among the parents of the subjects were compared with that in the general population. Observed/expected (O/E) ratios (P-value) were 1.8 (0.06) for all subjects, 1.3 (0.62) for male subjects, 2.1 (0.04) for female subjects, 0.5 (0.41) for early carcinoma, 2.6 (P<0.01) for advanced carcinoma, 2.3 (0.22) for intestinal-type carcinoma and 1.7 (0.13) for diffuse-type carcinoma. Association between gastric carcinoma and parents' history of gastric carcinoma was strong among women and regarding advanced carcinoma, and the difference in O/E ratios between early and advanced carcinoma was remarkable. Secondly, factors related to advanced-stage gastric carcinoma were analyzed. Histological type (diffuse and intestinal types) was not related, but family history of gastric carcinoma among parents and grandparents was related to advanced stage, and the relationship was independent of other factors. The odds ratio (95% confidence interval) was 3.3 (1.1-9.9). Family history may be related to stage of gastric carcinoma through its relationship to the manner or speed of the tumor's progression. We hypothesis that some genetic factor exists which is involved both in progression from early to advanced stage and in occurrence of gastric carcinoma.

Adolescent↗

Overexpression of multidrug resistance protein gene in human cancer cell lines selected for drug resistance to epipodophyllotoxins.

Overexpression of either the multidrug resistance 1 (MDR1) gene or multidrug resistance protein (MRP) gene is involved in acquisition of multidrug-resistant phenotypes in human cancer cells. In this study we examined whether selection for resistance to the epipodophyllotoxins, etoposide/teniposide (VP16/VM26), could induce overexpression of MDR1 or MRP. We have previously isolated two VP16/VM26-resistant KB cell lines. Two VP16/VM26-resistant KB cell lines, KB/VM-1 and KB/ VM-4, which were selected by stepwise exposure to VM26 had decreased accumulation of [3H]VP16 and increased levels of MRP, but no apparent expression of MDR1 gene was observed. Another VP16/VM26-resistant KB cell line, KB/VP-4, which was further isolated from a VP16-resistant KB cell line, KB/VP-2, had decreased accumulation of [3H]VP16 and showed overexpression of MRP gene, but not that of MDR1 gene. We also isolated a VP16-resistant cell line, IN157/VP-1, from a human glioma cell line IN157. IN157/VP-1 cells showed decreased accumulation of [3H]VP16 and overexpression of MRP gene, but not of MDR1. These findings suggest that selection for resistance to VP16/VM26, preferentially induces overexpression of MRP gene.

ATP-Binding Cassette Transporters↗

Mechanisms of veno-occlusion within and outside the canine corpus cavernosum penis using a pressure-flow technique and cavernoso-venography.

BACKGROUND: Physiological erection of the penis requires multiple mechanisms causing an increase in the arterial blood influx into, and decrease in the venous drainage out of the cavernous space. METHODS: We investigated the extent and location of the venous occlusion that occurs with penile erection within (intrinsic mechanism) and outside (extrinsic mechanism) the corpus cavernosum penis, using 15 adult male mongrel dogs. Under controlled flows produced by a combination of aortic ligation and constant infusion of saline into the corpus cavernosum penis, or into the deep dorsal vein, pressures within the cavernous space or deep dorsal vein were measured before and after electrical stimulation of the pelvic splanchnic (pelvic nerve), the hypogastric, and pudendal nerve. An increase in pressure following nerve stimulations represented an increase in outflow resistance due to occlusion of the venous system. Pre-and post-stimulation radiologic evaluations were performed to determine the site(s) of venous occlusion. RESULTS: Unilateral stimulation of the pelvic nerve caused leftward shift of the corporeal pressure-flow curve. Bilateral stimulation of the pudendal nerve caused a marked rise in deep dorsal vein pressure. CONCLUSIONS: Both intrinsic and extrinsic venous occlusion mechanisms exist and that the former is activated primarily by unilateral stimulation of the pelvic nerve and the latter by bilateral stimulation of the pudendal nerve. The occlusion site for the extrinsic mechanism was localized to where the dorsal vein penetrates the muscles at the base of the pelvis, whereas the precise site for the intrinsic mechanism could not be determined.

Animals↗

Transfer function analysis of central arc of aortic baroreceptor reflex in rabbits.

While electrically stimulating the aortic depressor nerve (ADN) pseudorandomly, we recorded renal sympathetic nerve activity (RSNA) and systemic arterial pressure (SAP) in 19 alpha-chloralose-anesthetized rabbits with sinoaortic denervation. From the recorded signals, we determined the transfer functions from ADN stimulation by a pseudorandom binary sequence to RSNA [HCMD.RSNA(f)] and to SAP [HCMD.SAP(f)]. The modulus of HCMD.RSNA(f) was flat over 0.0122-0.8 Hz, whereas the phase lag increased linearly with frequency. Thus the central transduction appeared not to modify the relative amplitude of the signals from the baroreflex afferents but to provide a fixed time delay (approximately 400 ms). In contrast, the modulus of HCMD.SAP(f) decreased precipitously toward high frequencies, and the degree of the phase lag was larger than that of HCMD.RSNA(f). We conclude that 1) the transfer property of the central are does not significantly modify the relative amplitude of the frequency components of the baroreflex afferents but provides a fixed time delay and 2) the frequency independence of the modulus of the transfer property is not preserved when the analysis is extended to SAP.

Animals↗

Nutritional regulation of insulin-like growth factor-I receptor mRNA levels in growing chickens.

Insulin-like growth factor-I (IGF-I) exerts its effect through the IGF-I receptor. To investigate the effects of nutritional status on chicken IGF-I receptor gene expression, a solution hybridization/RNase protection assay for IGF-I receptor mRNA was developed. A cDNA clone corresponding to the carboxyl-terminal region of the IGF-I receptor was obtained by reverse transcription-PCR (RT-PCR). Sequence analysis of the clone showed that this region of the chicken IGF-I receptor is highly divergent from the human IGF-I receptor. IGF-I receptor mRNA was detected in all tissues examined from newly hatched chickens. The rank order of the IGF-I receptor mRNA levels was liver < thigh muscle < stomach < heart < lung < kidney < brain. In 1-week-old chickens, 5 days of starvation caused a 2.5- to 3-fold increase in the mRNA in muscle and kidney. Starvation of 4-week-old chickens for 5 days caused a 1.7 to 2.2-fold increase in IGF-I receptor mRNA levels in kidney, liver, and muscle. In contrast, IGF-I receptor mRNA levels in brain failed to change. The mRNA levels were reduced to the control level by refeeding of the starved chickens for 24h. These data suggest a tissue- and development-specific response of chicken IGF-I receptor gene expression to nutritional status.

Amino Acid Sequence↗

Enhanced cholinergic activity in the medulla oblongata of DOCA-salt hypertensive and renal hypertensive rats.

We previously demonstrated that cholinergic activity in the medulla oblongata is enhanced in adult spontaneously hypertensive rats (SHR), a genetically hypertensive rat model. In this study, we examined possible alterations of medulla oblongata cholinergic mechanisms in nongenetic forms of hypertension, using deoxycorticosterone acetate (DOCA)-salt hypertensive and renal hypertensive rats. At a fully developed stage of hypertension in DOCA-salt hypertensive and renal hypertensive rats, choline acetyl-transferase (CAT) activity in the rostro-ventral medulla oblongata was enhanced, whereas there was no change in the activity of CAT in other parts of the medulla oblongata. There was no alteration of the medulla CAT activity in prehypertensive SHR or at an early stage of renal hypertension. Increases in blood pressure and plasma catecholamine levels induced by physostigmine (0.5 mg/kg, i.p.) were enhanced in DOCA-salt hypertensive and renal hypertensive rats. These findings suggest that cholinergic activities in the medulla oblongata are enhanced and that such activities are involved in enhancement of the sympathetic nervous system in non-genetically hypertensive rats. It seems unlikely that the altered cholinergic activity in the rostral ventrolateral medulla of adult SHR occurs genetically.

Animals↗

Auditory plasticity in cochlear implant patients.

Dynamic range (DR) of cochlear implant electrodes and speech recognition scores (SRS) were chronologically studied in 23 post-lingually deaf subjects over a period of one year. DR significantly increased over one year (ANOVA, p = 0.03). When DR was compared among three groups of electrodes which were located in the inferior, ascending and superior segments of the cochlear basal turn, that in the superior segment showed the largest increase (p = 0.001), followed by those in the ascending and inferior segments. Vowel and consonant recognition scores with auditory cue were best 6 months after operation and were maintained at the level for one year. Although the time course of improvement differed between DR and SRS, a significant positive correlation was observed at 12 months after operation. Improvement of SRS could be a result of a DR increase in the superior segment of the cochlea, which should convey pitch information over the mid-frequency region.

Adolescent↗

[Statistical analysis of recovery from sudden deafness among treatment groups].

This study examined 131 patients with idiopathic sudden deafness in whom the averaged of five frequency hearing levels was greater than 60dB. Since combined pharmacotherapy has been used in the treatment of idiopathic sudden deafness, it is hard to make a quantitative analysis of single-drug efficacy. We used a single-drug treatment in turn to assess the drug efficacy within 30 days after the onset. There was no significant difference among patients treated within 6 days and not less than 7 days after the onset with steroid therapy, PGE1 therapy, and defibrinogenation therapy. Similarly, there was no significant difference among patients treated within 6 days and not less than 7 days after the onset with steroid and defibrinogenation combined therapy, steroid and PGE1 combined therapy, and steroid, defibrinogenation and Lasix-Vitamin combined therapy. In case of no steroid effect, treatment with defibrinogenation, PGE1 and Lasix-Vitamin therapy could achieve hearing improvement.

Adolescent↗

[Three cases of Lermoyez's syndrome and its pathophysiology].

Two cases of bilateral Lermoyez's syndrome and one case of unilateral Lermoyez's syndrome are reported. The patients had recurrent episodes of vertigo with improvement of hearing or tinnitus, which is characteristic is Lermoyez's syndrome. In case 1, a 48-year-old female, dehydration with glycerol or furosemide induced nystagmus and improved bilateral hearing and the gain of the vestibulo-ocular reflex, while overhydration with drinking water impaired bilateral hearing with disappearance of nystagmus. These findings indicate that she had endolymphatic hydrops in both ears, suggesting that simultaneous changes in bilateral cochlear and vestibular function induce Lermoyez's syndrome. In case 3, a 52-year-old female, which we already reported, endolymphatic collapse in both ears may have changed bilateral inner ear function, resulting in Lermoyez's syndrome. On the other hand, patients 2, a 47-year-old male, experienced a vertigo attack with improvement of unilateral hearing after defibrinogenation therapy. In this case, slowly developing insufficiency of the inner ear blood supply may have caused the gradual hearing loss. It seemed that decreasing blood viscosity by defibrinogenation allowed blood to rush into the labyrinth, causing vertigo but at the same time improving hearing. We proposed that there are two types of Lermoyez's syndrome, bilateral (cases 1 and 3) and unilateral (case 2).

Endolymphatic Hydrops↗

[Adjuvant chemotherapy with cyclophosphamide, adriamycin, and CDDP (CAP) for high risk endometrial cancer after complete surgery].

One hundred and six patients with endometrial cancer were treated at Tsukuba University Hospital between 1983 and 1992. Sixteen patients who underwent complete resection were at high risk for recurrence and were given adjuvant platinum-based, multiagent chemotherapy instead of adjuvant radiotherapy. Eligibility criteria included outer-third myometrial invasion (group 1; n = 5), pelvic lymph node metastasis (group 2; n = 3) or both myometrial invasion and lymph node metastasis (group 3; n = 8). Of these three groups at high risk for recurrence, each patient in groups 1 and 2 developed recurrence and died. In group 3 two patients developed recurrence and one patient has died. There was one treatment death due to neutropenic sepsis in group 3. The recurrence sites in all four patients were local and no distant recurrence was noted. In other words, of 15 patients (excluding one treatment death) at high risk for recurrence, three of 12 patients (25%) with deep myometrial invasion and three of 10 patients (30%) with positive pelvic lymph nodes developed recurrence and died. The other 12 patients (include one patient with recurrence; 100 months) have survived for a long interval (range, 45-131 months). The survival rates for stage I, II, III, and IV are 92.6, 89.5, 60.0%, respectively. Patients with stage I in this study had a better survival than those with stage I in the 1984 annual report of the Japan Society of Obstetrics and Gynecology (p < 0.05). The findings of this prospective clinical trial supported those of the randomized trial comparing adjuvant CAP with radiation therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Antitumor effects of angiogenesis inhibitor 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) against murine renal cell carcinoma.

PURPOSE: The effect of 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) on tumor growth and metastasis is investigated. MATERIALS AND METHODS: BALB/c mice were inoculated with Renca murine tumor and graded doses of TNP-470 were given subcutaneously every other day beginning on day 1 and ending on day 9. Tumor angiogenesis was measured quantitatively by a colorimetric assay. RESULTS: TNP-470 inhibited tumor growth and prolonged the life span of Renca-bearing mice in a dose-dependent manner. Body weight-loss was not observed in the mice given less than 30 mg./kg./day. When the treatment was delayed on day 6, TNP-470 did not inhibit tumor growth, pointing to the importance of the timing of drug administration in relation to disease stage. Tumor angiogenesis was inhibited 33 to 62% of the control level by TNP-470. Furthermore, TNP-470 reduced pulmonary and hepatic metastatic foci of intravenously inoculated Renca and of the tumor inoculated in the spleen. CONCLUSION: These data suggest that TNP-470 may be effective as a treatment of renal cell carcinoma, especially when micrometastases are involved.

Animals↗

[Nucleotide sequence and restriction fragment length polymorphism (RFLP) analysis of the long terminal repeat of human T-cell lymphotropic virus type II (HTLV-II)].

Molecular studies have demonstrated the existence of two major subtypes of human T-cell lymphotropic virus type II, HTLV-IIa and HTLV-IIb. In attempts to further classify this family of viruses we have carried out nucleotide sequence and restriction fragment length polymorphism (RFLP) analysis of the long terminal repeat (LTR), a region which has been shown in previous studies to have the greatest intra-and inter-subtype genomic divergence. Analysis of the nucleotide sequences suggested the existence of distinct phylogenetic groups in each subtype, and based on predicted differences in restriction endonuclease sites, RFLP analysis allowed the identification of four groups within the IIa subtype (a1-a4), and six within the IIb subtype (b1-b6). Nucleotide sequence analysis also suggested the possible existence of HTLV-II quasispecies. However this appeared not to be significant, and preliminary studies suggest that these would not be expected to appreciably influence the results of RFLP analysis. The validity of the RFLP method was demonstrated in an analysis of thirty-six randomly chosen samples from the blood donors from the New York City Blood Center where it could be shown that all could be successfully classified. Moreover, the RFLP analysis correctly matched the viruses in donors and recipients of contaminated blood in four situations where HTLV-II was inadvertently transmitted by transfusion. RFLP analysis of the LTR appears to be a rapid and reliable method to identify HTLV-II infection. This should prove useful in studies of the epidemiology and the characterization of viruses present both in non-indigenous in indigenous populations.

Base Sequence↗

[A course of pirarubicin vesical irrigation at thirty mg effectively prevents post-TUR recurrence of superficial bladder cancer].

In order to study its safety and anti-cancer dose-effectiveness in the prevention of cancer recurrence, two groups of patients having superficial bladder cancer (TUR-Bt) had their bladder intravesically irrigated post-surgically with 20 or 30 mg aliquots of (2''R)-4'-0-tetrahydropyranyl-adriamycin (THP). A total of 74 patients with bladder cancer were entered in the study. Four cases proved ineligible, and 30 could not complete the planned treatment. THP vesical irrigation of 14-17 sessions was regarded as a condition for eligibility: Clinical evaluation was feasible with 19 patients of 20 mg and 21 of 30 mg THP. Non-recurrence rates at 1, 2, 3 and 4 years were 89.5, 53.3, and 26.6%, respectively, for the 20 mg group, and 95.2, 84.3, 75.9 and 75.9%, respectively, for the 30 mg THP group. The incidence of side effects appeared slightly greater in the 30 mg THP group than in the 20 mg group, and there were no systemic adverse reactions. Topical reaction of cystitis was noted to be as low as 12.5%. Thus, THP vesical irrigations at 30 mg were found tolerable and effective for the prevention of local recurrence following TUR-Bt.

Administration, Intravesical↗