Search PubMed⌕ Search

Biomedical subjects

T Kusunoki

Publications and source records attributed to T Kusunoki.

At least 73 records · Page 4Linked to original sources

New adipocyte formation in mice during refeeding after long-term deprivation.

Cell kinetic characteristics of the epididymal adipose tissue of mice were examined during refeeding after prolonged food deprivation. Mature mice were given a glucose-electrolyte solution for 20-40 days, and subsequent to a body weight loss of 35%, they were given normal mouse food ad libitum. After refeeding, their body weight and adipose tissue weight returned to the levels before the deprivation. We examined the formation of new adipocytes in the epididymal adipose tissue with [3H]thymidine autoradiography. Flash labeling experiments revealed that cell proliferation was most active on the 6th day after refeeding and decreased thereafter until the 13th day when few labeled cells were seen. Cumulative labeling experiments showed that replicated poorly differentiated mesenchymal cells developed into adipocytes by storing fat droplets. New adipocyte formation was observed in adult mice during refeeding after long-term deprivation.

Adipose Tissue↗

Adipocyte dynamics in hypothalamic obese mice during food deprivation and refeeding.

Effect of hypothalamic lesions on regulation of body weight and fat cell dynamics in obese mice were examined during refeeding after prolonged food deprivation. Obese mice, which were treated with monosodium glutamate for 5 postnatal days and had ventromedial nuclear lesions in the hypothalamus, were used. When adult obese mice were given a glucose electrolyte solution for 20-40 days, the body weight dropped to about 45% of their pre-treatment weight. After reinstituted feeding of normal mouse food ad libitum, their body weight and adipose tissue weight returned to pre-starvation level. Tritiated thymidine autoradiography revealed that cell proliferation occurred in the early stages of refeeding and some fat cells were renewed in the epididymal adipose tissue. Fat cell renewal was found more active in the experimental group than in the control. Thereafter, fat cell size increased gradually via fat storage. These obese mice were found to have the capacity to regulate their body weight and adipose tissue not only through fat storage but also by increasing number of fat cells, in order to replace the cells which were lost during starvation. Therefore, ventromedial nuclear lesion in the hypothalamus does not influence the regulatory mechanism of adipose tissue during starvation and refeeding.

Adipose Tissue↗

[Morphological study of human thyroid papillary carcinoma cells in collagen gel culture].

Human thyroid papillary carcinoma cells (surgical materials) were cultured in a monolayer or a collagen gel system. In the monolayer culture, degeneration and necrosis of cancer cells were observed after 10 days of culture. In the collagen gel culture, degenerative necrosis were observed 14 days culture. In histopathological observation monolayer cells proliferated in pavement-like form without forming any colony. On the contrary, collagen gel culture cells formed branching-type colonies and spheroid-type colonies. Those results suggested that papillary carcinoma cells can be cultured more like in vivo in collagen gel culture than monolayer culture.

Carcinoma, Papillary↗

[The effect of bunazosin hydrochloride on intraocular pressure and aqueous humor dynamics in human].

The effects of bunazosin hydrochloride, a new highly selective alpha 1 adrenergic antagonist, on the intraocular pressure (IOP) and aqueous humor dynamics in healthy human volunteers were studied. Unilateral topical administration of 0.1% bunazosin significantly lowered IOP from 1 to 10 hrs in bunazosin-treated eyes, and from 2 to 8 hrs in contralateral placebo-treated eyes, with its maximum reduction at approximately 3 hrs, when the IOP decreased 5.0 mmHg in treated eyes, and 3.5 mmHg in contralateral eyes from the baseline, respectively. Fluorophotometrically measured aqueous humor flow rates did not change significantly either in treated or contralateral eyes. Bunazosin caused significant reduction of systolic and diastolic blood pressure 5 hr after application. The difference in pupil diameter between treated and contralateral eyes was found to be statistically significant from 1 to 5 hrs. A small but significant increase in anterior chamber depth also was observed from 2 to 6 hrs. Pulse rate and refraction were not substantially altered. There was moderate conjunctival vessel dilation, however, no serious complications were encountered. The results suggest that bunazosin hydrochloride appears to have great clinical potential for ocular hypotensive therapy.

Adrenergic alpha-Antagonists↗

Organization of the primary projections of the lateral line nerves in the lamprey Lampetra japonica.

The lateral line sensory system of Lampetra japonica is innervated by the anterior and posterior lateral line nerves. The anterior lateral line nerve innervates all electroreceptors throughout the body and mechanoreceptors of the head. The posterior lateral line nerve innervates trunk mechanoreceptors. The anterior lateral line nerve consists of two ganglia (anterior lateral line and intracapsular) and four major peripheral branches (superficial ophthalmic, buccal, hyomandibular, and recurrent nerves). The posterior lateral line nerve has one posterior lateral line ganglion and one peripheral branch. The location and central projection patterns of the primary sensory neurons of these branches of the lateral line nerves were studied with the aid of horseradish peroxidase labeling. The ganglion cells of the buccal nerve were found in the rostral half, and those of the hyomandibular nerve were found in the caudal half of the medial part of the anterior lateral line ganglion. The lateral part of the anterior lateral line ganglion contains ganglion cells of the recurrent nerve and the superficial ophthalmic nerve. The rostral half of the intracapsular ganglion contains ganglion cells of the recurrent, hyomandibular, and buccal nerves. The ganglion cells of the posterior lateral line nerve were found in the posterior lateral line ganglion. The buccal nerve afferents terminated mainly in the lateral part of the ipsilateral mechanoreceptive medial nucleus. The peripheral part of the electroreceptive dorsal nucleus also received several afferents. The hyomandibular afferents terminated ipsilaterally in the central part of the medial nucleus and in the dorsolateral part of the dorsal nucleus. Some afferents of the hyomandibular nerve ascended and descended in the descending nucleus of the trigeminal nerve near its dorsal margin. The ventral nucleus, the primary nucleus of the VIIIth nerve, received a few fibers of the buccal and hyomandibular nerves. In the recurrent nerve, the fibers of the lateral part of the anterior lateral line ganglion terminated throughout the entire dorsal nucleus, and the fibers of the intracapsular ganglion projected to the dorsolateral part of the nucleus. The afferents of the posterior lateral line nerve terminated in the medial part of the ipsilateral medial nucleus and in the lateral part of the contralateral medial nucleus. In the cerebellar area, afferents of the anterior lateral line nerve were located laterally to those of the posterior lateral line nerve. Several fibers terminated in some branchiomotor nuclei, the cerebellar crest, and the dorsal gray near the obex level. No efferent cell bodies were found in the place where efferent neurons of the VIIIth nerve have been previously reported.

Afferent Pathways↗

Application of mathematical model to experimental chemotherapy of fatal murine pneumonia.

Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered in an experimental model of murine pneumonia caused by Klebsiella pneumoniae in a way which enabled us to approximate the serum antibiotic concentration time course in humans. Bacterial counts during the experiments were subjected to nonlinear least-squares analyses by using a mathematical model that explained the bacterial killing by the antibiotic concentration time course and other factors associated with antimicrobial potency and bacterial growth. Cefazolin gave a killing curve that changed synchronously with the drug levels in serum; in contrast, cefmenoxime gave a curve that was prolonged as compared with the change in the drug levels in serum. Multiple correlation coefficients were about 0.9, and the model worked well for bacterial count data. Parameters relating to antimicrobial potency of the drugs, bacterial growth rate, and drug distribution into the tissue were estimated numerically.

Animals↗

Effects of undernutrition on the serotonin neuron system in the developing brain: an immunohistochemical study.

The effects of undernutrition during the first 3 weeks of postnatal life on the serotonin neuron system were investigated using a peroxidase-antiperoxidase immunohistochemical method. Undernourishment was induced by increasing the litter size from 6 to 18 mice during the first 3 weeks of postnatal life. At 15 days of age a morphological change (large swelling of serotonin-immunoreactive axons) was noted in various parts of the brain of the undernourished mice with no remarkable changes in dendrites and cell bodies. Quantitative immunohistochemical analysis at 60 days of age showed a significant decrease in serotonin-immunoreactive cell bodies in the nucleus linearis intermedius, the nucleus raphe obscurus, the total raphe system and the subpyramidal region. These results suggest that undernutrition during early postnatal life affected the serotonin neuron system with regional differences.

Animals↗

Afferent and efferent projections of the VIIIth cranial nerve in the lamprey Lampetra japonica.

Anterograde and retrograde transport of horseradish peroxidase was used to examine the afferent and efferent projections of the VIIIth cranial nerve in the lamprey Lampetra japonica. Ganglion cells of the VIIIth nerve are classified into three types on the basis of their morphology. The central processes of these ganglion cells enter the medulla in two groups: the anterior group (mostly thick fibers) and the posterior group (mostly thin fibers). Afferent fibers mainly terminate within the ipsilateral ventral and octavomotor nuclei of the octavolateralis area and within the granular and molecular layer of the cerebellum. Some fibers terminate in the contralateral cerebellum, the medial and dorsal nuclei of the octavolateralis area, the descending nucleus of the trigeminal nerve, some cranial motor nuclei, and the lateral octavus nucleus, which has not been described previously. This small nucleus is located beneath the descending nucleus of the trigeminal nerve near the obex. Within the ventral nucleus, thin fibers occupy the dorsal part and thick fibers occupy the ventral part. The basic projection pattern of the primary afferents of the VIIIth nerve in the lampreys was similar to that of gnathostome fishes that have been studied to date. Cell bodies of the efferent vestibular neurons are located between the ipsilateral trigeminal motor nucleus and the facial motor nucleus. The lateral location of these cell bodies differs from that of all other fish species that have been studied.

Animals↗

Substance P-like immunoreactivity in the trigeminal sensory nuclei of an infrared-sensitive snake, Agkistrodon blomhoffi.

With the peroxidase-antiperoxidase immunohistochemical method we ascertained the presence of substance P-like immunoreactivity (SPLI) in fibers and cell bodies of the trigeminal sensory system of the pit viper, Agkistrodon blomhoffi. There are a few SPLI fibers each in the principal sensory nucleus and the main neuropil of the lateral descending nucleus (i.e., the infrared sensory nucleus); a moderate number in the descending nucleus; and a large number in the caudal subnucleus, the medial edges of the interpolar subnucleus, and the marginal neuropil of the lateral descending nucleus. About 30% of the cell bodies in the ophthalmic and maxillo-mandibular ganglia show SPLI, and of the two craniocervical ganglia, the proximal ganglion has many more cells with SPLI than the distal ganglion. The SPLI distribution in the common trigeminal sensory system is similar to that of mammals, and suggests that the function of this system is also similar. In the infrared that the function of this system is also similar. In the infrared sensory system, the differing distribution in the main and marginal neuropils suggests separate functions for these two structures in the system.

Afferent Pathways↗

Brain energy metabolism in two kinds of total asphyxia: an in vivo phosphorus nuclear magnetic resonance spectroscopic study.

Brain energy metabolism was studied in vivo by means of 31P-NMR spectroscopy in newborn mice during and after 20-minutes exposure to either pure carbon dioxide gas or nitrogen gas. In the N2 group, the brain ATP concentration remained almost normal throughout the experiment, while it showed a 30% reduction in the CO2 group. The brain concentration of phosphocreatine dropped to about 20% of the control value during the asphyxia in both groups, and its recovery was significantly delayed in the CO2 group compared to in the N2 group. Tissue acidosis and Pi accumulation were more remarkable and prolonged in the CO2 group.

Adenosine Triphosphate↗

Morphology and cell dynamics of adipose tissue in hypothalamic obese mice.

Morphological and cell kinetic characteristics of the epididymal adipose tissue of obese mice, induced by monosodium glutamate (MSG), were examined in comparison to those of normal mice. Mice treated with MSG for 5 postnatal days became obese after 8 wk of age; adipocytes of the MSG-treated mice were larger than those of normal mice. Heterogeneity was noted in components of the adipose tissue in the obese mice after 24 wk; various-sized adipocytes appeared, and the connective tissue elements increased; necrosis of adipocytes was observed by 36 wk; and mononuclear cells and macrophages infiltrated around the necrotic adipocytes. Such changes were not seen in normal mice. Autoradiographic study with continuous and pulse labeling with [3H]thymidine showed that half the fat cells were replaced in 150-200 days in normal mice and that the turnover rate of adipocytes was more rapid in the obese mice than in the normal mice. In the obese mice, cell death and cell renewal were found to occur more actively.

Adipose Tissue↗

Development of the epididymal adipose tissue in monosodium glutamate-induced obese mice.

Obesity was induced in neonatal mice by subcutaneous injections of monosodium glutamate (MSG) at an early neonatal stage. The process of adipocyte formation was studied comparatively in the developing epididymal adipose tissue of the MSG-treated mice and in normal mice during the period from the 6th to the 100th postnatal day. Tritiated thymidine autoradiographic studies showed that cell proliferation activity was the highest on the 6th postnatal day both in the MSG-treated and the control mice. In normal mice, however, cell proliferation took place less frequently after 6 days and had almost ceased after 49 days. In the obese mice, as evidenced by relatively high labeling indices, cell proliferation continued to occur even after 49 days. Ultimately there was no difference in the number of adipocytes counted by Hirsch's method in the MSG-treated and the control mice at the 100th postnatal day. The storage of fat droplets became more noticeable in obese mice than in normal mice after 35 days. The mean size of fat droplets of the obese mice was twice as large as that in normal mice on the 49th postnatal day. These results indicate that the MSG-induced obesity is of the hypertrophic type.

Adipose Tissue↗

[A six-day subrenal capsule assay for predictive testing of primary human tumors].

We carried out a total of 36 in vivo chemosensitivity tests in 33 cases of human malignant tumor using the subrenal capsule assay, developed by A.E. Bogden et al. Of the 36 assays, 31 were evaluable. The chemosensitivity of each tumor varied individually. UFT, 5-fluorouracil, mitomycin-C and adriamycin were administered to gastrointestinal cancer patients regularly, but our SRC-assay showed a high sensitivity rate for UFT and 5-fluorouracil but a low sensitivity rate for mitomycin-C and adriamycin. Nine patients had clinically evaluable lesions and a correlation between the assay results and clinical response existed in 6 cases. The true positive rate was 50% (3/6), the true negative rate 100% (3/3), and the overall predictive accuracy 66% (6/9). This study suggested that 6-day SRC assay is useful for selecting effective anti-tumor agents for the treatment of cancer patients.

Animals↗

[Effect of immunosuppressants on the subrenal capsule (SRC) assay as a chemosensitivity test].

Six-day SRC assay as a chemosensitivity test has an advantage of high predictive rate for clinical response. However, it is pointed out that very few viable tumor cells are observed at the end of the assay, so that it may make the assay results unreliable. In this paper, we tested the effect of immunosuppressants on SRC assay using Walker carcinosarcoma originated from Wistar rat xenografted under the renal capsule of BDF1 mice. The changes of tumor size, pathological features and proliferative ability of xenografted tumor under the renal capsule of mice treated with cyclophosphamide, mizolibine or cyclosporin A are examined. Only cyclosporin A treatment could maintain the viable tumor cells and proliferative ability of the tumor grafted under the renal capsule 21 days after transplantation. In order to compare the original 6-day SRC assay developed by Bogden et al, we applied immunosuppressants to the 6-day assay. It is suggested that cyclosporin A and mizolibine amplify the sensitivity of tumor in 6-day SRC assay.

Animals↗

[Clinical evaluation of local infusion chemotherapy in metastatic liver carcinoma].

Twenty patients with metastatic carcinoma of liver were treated with infusion chemotherapy using Port-A-Cath or Infuse-A-Port; canulae were surgically inserted into hepatic artery and/or portal vein, and ports were implanted into subcutaneous pockets. Selection of chemotherapeutic agents was made on the basis of subrenal capsule assay (SRCA) and in vivo chemo-sensitivity test, developed by A. E. Bogden et al., 1987. The results were as follows: 1. Implantation of catheter is beneficial as a maintenance chemotherapy for patients with metastatic liver carcinoma, because of its safety and the improved quality of life. 2. One patient canulated into portal vein, showed partial response. 3. In this prospective study of subrenal capsule assay, true positive rate was 50% (3/6), true negative rate 100% (4/4), and overall predictive accuracy was 70% (7/10). The present study suggested that SRCA is useful for selecting effective anti-tumor agents for treatment of metastatic liver cancer patients.

Adult↗

Organization of sensory and motor nuclei of the trigeminal nerve in lampreys.

Anterograde and retrograde HRP transport were used to elucidate the primary central projections of the trigeminal nerve in a lamprey, Lampetra japonica, by application to the ophthalmic, apical, basilar, suborbital, and mandibular branches of the trigeminal nerve. (1) Most of the trigeminal and a few facial ganglion cells were labeled. The ganglion cells of each nerve were distributed in separate areas within their respective ganglia. (2) Some ipsilateral medullary and spinal dorsal cells were labeled after HRP application to the ophthalmic and apical nerves, but there was no contralateral labeling. (3) Most of the neurons of the trigeminal motor nucleus were labeled, and when the apical or the basilar nerve was labeled, in each case a cluster of small motor neurons was found ventrolateral to the classic motor nucleus. (4) Miscellaneous neurons were found scattered along the course of the descending trigeminal tract and nucleus in all cases except after application to the mandibular branch. The shape, size, and distribution patterns of these neurons were varied, and several characteristics indicated that they were sensory in nature. (5) In the rostral part of the medulla, sensory fibers of each nerve showed restricted localization within the descending trigeminal tract and nucleus. When compared to the distribution of the same fibers in the hagfish Eptatretus burgeri, another member of the cyclostomes, the distribution pattern in the lampreys studied was closer to the type seen in gnathostomes.

Animals↗

Use-dependent blocking action of newly developed lidocaine-analogs on maximum rate of rise of action potentials in guinea pig papillary muscle.

The mode of antiarrhythmic actions of the newly developed antiarrhythmic drugs, tocainide, mexiletine and SUN1165, which bear the N-2,6-dimethylbenzene ring as a common structural unit, were examined by comparing the use-dependent blocking actions on the maximum rate of rise of action potentials (Vmax) in guinea pig ventricular muscle. The time course of the use-dependent reduction of Vmax after stimulation and its recovery after cessation of stimulation were fitted by double exponential curves to avoid the effects of the rapid stimulation (2 Hz) on the level of the membrane diastolic potential. The onset rates constants of the use-dependent block were 0.29 +/- 0.07 per action potential for tocainide (10(-4) M), 0.07 +/- 0.02 (mean +/- SE, n = 5) per action potential for SUN1165 (10(-5) M) and were too rapid to be accurately fitted for mexiletine (10(-5) M). The time constants of the Vmax recovery from the use-dependent block were prolonged to 0.67 +/- 0.32, 0.27 +/- 0.13 and 96 +/- 11 (mean +/- SE, n = 5) sec in the presence of tocainide, mexiletine and SUN1165, respectively. These data indicate that tocainide and mexiletine should be classified as lidocaine-like drugs, while SUN1165 may be a quinidine-like drug which interacts with Na+ channels and has slower kinetics than lidocaine-like drugs.

Action Potentials↗