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Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 649 records · Page 36Linked to original sources

A rapid synthesis of a DNA fragment using an unprotected nucleoside and a phosphine derivative.

A rapid synthesis of DNA fragment from unprotected nucleoside and phosphine derivative, morpholinophosphordichloridite, has been studied, demonstrating a d(T-T) and its amino-phosphonate derivative syntheses. A high selectivity of this reagent eliminates the protection of nucleoside hydroxyl groups. The P-N bond in the resulting dinucleoside phosphite can readily be converted to a phosphite triester with alcohol and to the corresponding aminophosphonate by a non-aqueous oxidation with m-chlorobenzoic acid. The P-N bond in the phosphate link is very stable and so provides a protection for the phosphoryl group which has many potential uses. Deprotection can be achieved by a simple treatment with NH2OH.

DNA↗

Little sleep-promoting effect of three sleep substances diurnally infused in unrestrained rats.

Delta-sleep-inducing peptide (2.5 nmol), prostaglandin D2 (0.36 nmol) and uridine (10 pmol) were intraventricularly infused for 10 h at daytime in otherwise saline-infused freely moving male rats. In contrast to a nocturnal infusion which may result in marked sleep-promoting effects, such a diurnal infusion brought about almost no change in sleep parameters. It is postulated that the requirement of sleep in rats might be fully achieved at the environmental light period to cancel the effect of the exogenously administered sleep substances. It is proposed that an endogenous sleep substance should be characterized by a property not to cause excessive sleep at the time when sleep is physiologically saturated.

Animals↗

Uridine as an active component of sleep-promoting substance: its effects on nocturnal sleep in rats.

A 10-h intraventricular infusion of 10 pmol of uridine from 19.00 to 05.00 h resulted in significant increases in sleep in otherwise saline-infused male rats (n = 8) during the environmental dark period (20.00-08.00 h). Increments of slow wave sleep (SWS) and paradoxical sleep (PS) were 21.0% and 68.1%, respectively, of the baseline value. This was due to increases in the frequencies of both SWS and PS episodes but not to their durations. Similar increases occurred the first recovery night under saline infusion, but sleep amounts returned to the baseline levels the second night. Brain temperature was not affected by uridine administration. A small dose of uridine (1 pmol/10 h) exerted no effect (n = 6) while larger doses (100 and 1000 pmol/10 h, each n = 5) resulted in slight but insignificant increases in SWS and PS. The 1000-pmol uridine administration seemed to be non-physiological since it brought about irregularities in locomotor activity and sleep-waking rhythms. Thus, authentic uridine exhibited the same sleep-enhancing effects as a naturally occurring active component of sleep-promoting substance, which was recently identified with uridine.

Animals↗

Differential sleep-promoting effects of five sleep substances nocturnally infused in unrestrained rats.

Sleep-inducing and sleep-maintaining effects of five different putative sleep substances were compared by the same nocturnal 10-hr intracerebroventricular infusion technique in otherwise saline-infused, freely moving male rats. Delta-sleep-inducing peptide (2.5 nmol), which induces electroencephalogram delta (slow)-wave patterns, was rapidly effective in increasing both slow-wave sleep and paradoxical sleep but the effects were not long-lasting. Muramyl dipeptide (2 nmol) induced excessive slow-wave sleep in the middle of the infusion period, accompanying a simultaneous elevation of brain temperature. However, paradoxical sleep was not affected. Component B of sleep-promoting substance (2 brainstem equivalents), a partially purified extract from rats deprived of sleep for 24-hr, was markedly effective in inducing and maintaining both kinds of sleep. Prostaglandin D2 (0.36 nmol) was more effective in enhancing sleep at the later period of the infusion period. Uridine (10 pmol) caused a mild but long-lasting increase in sleep, especially in paradoxical sleep. Thus, each substance exhibited compound-specific sleep-modulating properties.

Acetylmuramyl-Alanyl-Isoglutamine↗

Spinal pathway of the milk-ejection reflex in the rat.

The effects of lesions of the spinal cord on the milk-ejection reflex evoked by suckling were studied in urethane-anesthetized lactating rats. All lesions were made between C6 and C7 vertebrae and milk ejection was monitored by recording intramammary pressure. In the first experiment on the rats with bilateral lesions, a 3-h suckling test with 5 pups on each side was performed. Eleven (84.6%) of 13 rats with the section of the dorsal funiculus (Group 2), and 12 (85.7%) of 14 rats with the combined section of the dorsal and ventral funiculi (Group 4) displayed regular milk ejection. The incidence of milk ejection in both groups was not significantly different from 81.8% (9 rats) of the 11 sham-operated rats (Group 1). In contrast, none of the 12 rats with bilateral section of the lateral funiculus (Group 3) displayed milk ejection and the incidence of milk ejection was significantly lower than that in Group 1. In the second experiment on the rats with unilateral section of the lateral funiculus, bilateral suckling with 10 pups (5 pups on each side) and unilateral suckling (both ipsilateral and contralateral to the lesion) with 5 pups were consecutively performed in the 10 rats. Milk ejection was induced in 50% by contralateral suckling and in 100% by bilateral suckling, and the incidence was significantly higher than that (0%) observed during ipsilateral suckling. A significant difference in the incidence of milk ejection was also observed between contralateral and bilateral sucklings.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

New sulfamoylphenethylamines, potent alpha 1-adrenoceptor antagonists.

The (+)-isomer of amosulalol, a combined alpha- and beta-adrenoceptor antagonist, was one log unit order more potent and less potent than the (-)-isomer in blocking alpha 1- and beta 1-adrenoceptors, respectively, in anaesthetized rats. Nine newly synthesized desoxy compounds derived from amosulalol and its analogues were found to possess potent alpha 1-adrenoceptor blocking activity and to be practically devoid of beta 1-adrenoceptor blocking activity. Among the desoxy derivatives, YM-12617 was more potent than prazosin in blocking alpha 1-adrenoceptors in anaesthetized rats and in reducing blood pressure, total peripheral resistance and left ventricular work in anaesthetized dogs.

Adrenergic alpha-Antagonists↗

Laryngeal muscles and articulatory control.

The present study continues earlier work on laryngeal control in speech with particular reference to adjustments in Swedish voiceless consonants and consonant cluster. Electromyographic recordings were obtained from four intrinsic laryngeal muscles together with simultaneous transillumination and acoustic signals. Results indicate that the vocalis and lateral cricoarytenoid muscles participate in the control of both articulation and phonation (F0). The interarytenoid muscle appeared to be involved only in articulatory adjustments. Activity in the cricothyroid was mostly related F0 change; however, this muscle also showed an increase in activity for voiceless sounds. In addition, the vocalis muscle appeared to participate in glottal adduction without complete closure in voiceless clusters with the lateral cricoarytenoid and the interarytenoid playing no particular roles. The results suggest the need of studying laryngeal behavior in speech within a general systems famework for movement control.

Electromyography↗

Bronchial and intercostal angiography with ioxaglate and diatrizoate in man. A comparative investigation.

A low osmolality contrast medium, ioxaglate, was compared with diatrizoate of high osmolality in selective bronchial and intercostal angiography. The frequency and degree of pain, heat sensation, cough and involuntary movement were significantly lower with ioxaglate. In addition haemodynamics recorded in 17 cases of bronchial angiography revealed that ioxaglate induced significantly less effect on systemic blood pressure and heart rate.

Aged↗

Experimental studies in total artificial heart replacement.

Twenty-seven calves were operated on in our institute for total artificial heart replacement. Thomasu hearts (made by the Thomasu Technical Company, Japan) were used in 21 calves from February 1980 to May 1983. Utah Jarvik 7 hearts were used for the first five calves and the 17th calf. The air-driven Thomasu heart, made of segmented polyurethane, has 95 ml and 85 ml of stroke volume in its left and right sides respectively and showed recognizable function curves in mock circulation systems. There were no satisfactory results in the first 19 cases but the 20th calf survived for 28 days. In 1982, we adopted a new surgical method in which, instead of suturing, a sutureless artificial graft with a stainless steel ring was inserted into the aorta and pulmonary truncus. Since then two out of six calves have survived for more than one month; one of these survived for 66 days. The causes of death after the Thomasu heart replacements were varied. Ten (48%) out of 21 cases had heart trouble and four calves (19%) died through thrombus formation at the inflow and outflow valves. Three calves (14%) died because of mechanical failure of the driving system, two (10%) due to surgical failure, one because of pneumonia, and one due to an abnormal reaction after donor blood transfusion. Our longest surviving calf died after 66 days, because of a broken left blood diaphram though, it remained in excellent condition until its death. There was no thrombus formation in either ventricle, no fibrin net formation and no calcium deposit on the surface of the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of drug sensitivity among tumor cells within a tumor, between primary tumor and metastases, and between different metastases in the human tumor colony-forming assay.

The human tumor colony-forming assay was used to compare chemosensitivity among tumor cells within a primary tumor, between primary tumor and metastases, and between different metastases. No significant differences in cloning efficiency were found in any of the three comparison studies. However, considerable differences in chemosensitivities were observed between different parts of the same tumor and between the primary tumor and metastases. Two different parts of the same tumor were comparably assayed for nine primary tumors. In nine paired samples which allowed in vitro drug sensitivity testing, there was no satisfactory correlation of sensitivity to cytostatic drugs. Cell suspensions were prepared from 28 primary tumors and from metastases taken from the same patient. In 14 paired samples which formed sufficient colonies for determination of drug effect, the data showed no satisfactory correlation of chemosensitivity between a primary tumor and its metastases. Both tumor samples from different metastatic sites of the same patient formed sufficient colonies in seven of eight instances. In the seven paired samples, there was strong association of chemosensitivity (p less than 0.005). The results indicate that the reported discrepancies of in vitro and in vivo results in clinical trials using the tumor colony-forming assay for predicting resistance or sensitivity to cytostatic drugs may be due to therapeutic heterogeneity among tumor colony-forming units within a primary tumor and between a primary tumor and its metastases.

Antineoplastic Agents↗

[A case of multicentric early carcinoma of the stomach--preoperative diagnosis].

A 59-year-old man was admitted complaining of substernal pain and anorexia. Upper GI series revealed a benign gastric ulcer in the posterior wall, and gastrofiberscopy was done. Besides the benign lesion, two early carcinomas of type IIc were found. Biopsy specimens of both lesions showed malignancy and gastrectomy was performed. Histological investigation revealed poorly differentiated adenocarcinoma in the anterior wall and well differentiated tubular adenocarcinoma in the posterior wall. Both lesions were absolutely independent and isolated. In most instances, multicentric or multiple early gastric carcinomas manifest similar histological features, but in our case, the lesions were of different types.

Adenocarcinoma↗

[Local administration of anti-cancer drugs].

Anti-cancer drugs in the forms of an emulsion, a microsphere, and of conjugates with high molecular dextran have been developed in our laboratories, namely a fat emulsion of anticancer drug, MMC-microsphere, or MMC-dextran conjugates. The main advantages of these forms of pharmaceutical preparation are that they give prolongation of pharmacological actions by slow release and that they are applicable for topical use because of their reduced toxicities to local tissue yet maintaining local therapeutic potency. In this study we found that the rate of sustained release of drugs and antitumor effects were enhanced when used in such modified forms of drugs for topical injections. Results of clinical trials of those drugs have been promising. However, the number of trials has been limited so far. Further studies would be required for evaluating on of their clinical utilities.

Adult↗