Biomedical subjects

K Niimi

Publications and source records attributed to K Niimi.

At least 55 records · Page 3Linked to original sources

PubMed1987

Thalamic projections to the hippocampal and entorhinal areas in the cat.

The thalamic projections to the hippocampal formation and to the subicular and entorhinal areas in the cat have been studied with retrograde transport of horseradish peroxidase (HRP) or wheat germ agglutinin conjugated to HRP (WGA-HRP) and anterograde transport of WGA-HRP. Retrograde transport tracers injected in various parts of these cortices resulted in labeled cells in the midline, anterior, and lateral dorsal nuclei. Injections into the hippocampal formation or the subiculum led to retrograde labeling of cells in the reuniens nucleus of the ipsilateral thalamus throughout its rostrocaudal extent, whereas the restricted injections into the dentate gyrus and the inferior region of the hippocampus led to no labeling. Following an injection into the pre- and parasubiculum, a large number of labeled cells were seen not only in the reuniens nucleus but in other midline nuclei. In addition, a substantial number of labeled cells were also detected in the anterior and lateral dorsal nuclei, particularly in the anterodorsal nucleus, which contained densely arranged labeled cells throughout almost the entire rostrocaudal extent. An injection into the medial entorhinal area labeled a number of cells in the anterior nuclei and in the reuniens nucleus, particularly its dorsal part. Injections into various subdivisions of the lateral entorhinal area yielded different patterns of distribution of labeled cells in the thalamic nuclei. An injection into the ventromedial division (VMEA) led to abundant labeling of cells in the paraventricular and reuniens nuclei. After an injection into the ventral division (VLEA), numerous labeled cells were detected in the reuniens nucleus and a lesser number in the paraventricular nucleus at anterior levels. When an injection was made into the dorsal division (DLEA), a large number of labeled cells were detected in the reuniens nucleus, and less numerous labeled cells were found in the central medial nucleus. There appears to be a topographic arrangement of cortical projections of the reuniens nucleus. The pre- and parasubiculum receive projections from the most medial part of the reuniens nucleus near the midline, and the DLEA receives projections from the medial part of the nucleus. The cells projecting to the VLEA and MEA are distributed in the central part of the reuniens nucleus, and those to the VMEA are distributed in the lateral part. Anterograde experiments were also performed; injections of WGA-HRP into the reuniens nucleus resulted in terminal labeling in the superficial layers of the subicular area and the neighboring hippocampus and in the entorhinal area.

Afferent Pathways↗

PubMed1987

Clinical studies on a new screening assay for anticancer agents using nude mice and isotopic evaluation.

A new screening assay for anticancer agents was established using an in vivo nude mouse model. Assessment of the chemosensitivity of individual human tumors was determined by [3H]thymidine incorporation by the treated tumors. Three hundred and thirty tumors derived from cancer patients were transplanted into nude mice s.c. and treated with anticancer agents. Mitomycin C, 5-fluorouracil, cyclophosphamide, and doxorubicin were used in the present studies. In 270 of 330 cancers, chemosensitivity was evaluated by this method (evaluable rate, 81.8%). The rate of positive sensitivity against all tumors was 21.9% in mitomycin C, 12.2% in 5-fluorouracil, 27.4% in cyclophosphamide, and 23.6% in doxorubicin, respectively. The tumor sensitivity to anticancer agents varied according to the type of cancer. Retrospective and prospective clinical studies were performed to determine the usefulness of the nude mouse-isotope assay for the prediction of tumor sensitivity. The 24-month survival rates of 24 gastric cancer patients treated with tumor-sensitive agents was significantly higher than that of 28 patients treated with tumor-resistant agents. The end results after chemotherapy in far-advanced and inoperable terminal cases of gastrointestinal cancers was also investigated, prospectively. Out of 19 cases, the 50% survival time of 11 patients treated with tumor-sensitive agents was longer than that of eight patients treated with tumor-resistant agents. From prospective correlative studies carried out on 25 patients, this assay correlated with clinical responses (overall agreement, 76.0%; P less than 0.05) with specific agreements of sensitivity and resistance of 37.5 and 94.1%, respectively. From these results, it seems reasonable to conclude that nude mouse-isotope assay is a screening assay to identify appropriate agents for the treatment of patients with cancer. However, there is still a need to develop a better protocol in this assay, especially for antimetabolites, and to continue research in order to find more sufficient assays to predict clinical sensitivity to anticancer agents.

Animals↗

PubMed1987

Experimental studies on the combined effects of alpha and gamma interferons against human tumor xenografts transplanted into nude mice.

The antitumor activities, resulting from the combined treatment of leukocyte interferon (IFN-alpha), with recombinant human immune interferon (IFN-gamma), against human tumor xenografts in nude mice, were studied. Nine human tumor xenografts, (7 from gastric carcinoma, 1 from gallbladder carcinoma and 1 from breast carcinoma), were serially transplanted into nude mice for the purpose of this experiment. Each human tumor xenograft was inoculated subcutaneously into BALB/c nu/nu nude mice and treatment was started after the estimated tumor had reached 100-300 mg. IFN was administered intramuscularly at a schedule of qd X 14. Treatment with either IFN-alpha or IFN-gamma alone, did not produce any antitumor effect against the various human tumor xenografts, however the combination of IFN-alpha with IFN-gamma resulted in achieving significant antitumor effects against the various human tumors. Inhibition of tumor growth was observed in 7 of the 9 tumors (77.8 per cent), and regression of the tumor was noted in 5 of the 9 tumors (55.6 per cent).

Adenocarcinoma↗

PubMed1987

Effect of oxygen tension on the antitumor activity of mitomycin C assayed by human tumor clonogenic assay.

The effects of oxygen tensions on the antitumor activity of mitomycin-C (MMC) were surveyed using the human tumor clonogenic assay technique. Six human tumor xenografts (4 gastric cancers, and 2 colon cancers) were used in this study. Tumor cells were continuously exposed to MMC during the experimental period at various oxygen tensions, such as 2 per cent, which is considered to be hypoxic oxygen tension, 5 per cent which is considered as the physiological oxygen tension, and 20 per cent which is the conventional in vitro culture condition. The antitumor activities of MMC on the 6 human tumor xenografts increased when the oxygen tension was lowered from 20 per cent to 5 per cent. However, no further increases of the antitumor activities of MMC were observed by lowering the oxygen tension from 5 to 2 per cent. Additionally, the in vitro antitumor activities of MMC at various oxygen tensions were compared with the in vivo chemosensitivities evaluated in nude mice. In five of the 6 human tumor xenografts, in vitro chemosensitivities assayed at 2 or 5 per cent oxygen tension were concordant with in vivo chemosensitivities, although in vitro chemosensitivities assayed at 20 per cent were concordant with in vivo chemosensitivities in 3 of the 6 tested tumors.

Animals↗

PubMed1987

Comparative studies on in vitro human tumor clonogenic assay (HTCA) and in vivo nude mouse-isotope assay (NM-IA).

Comparative studies between the in vitro human tumor clonogenic assay (HTCA) and nude mouse-isotope assay (NM-IA), in which the final evaluation was made with 3H-thymidine incorporations of tumor cells transplanted into nude mice, were performed simultaneously on 60 fresh human tumors. Tissues used included 27 gastric cancers, 10 breast cancers, 7 colorectal cancers, 4 gallbladder cancers, 4 sarcomas, 3 lymphomas, and 5 other tumors. Mitomycin C (MMC), 5-fluorouracil (5-FU), cyclophosphamide (CPM) and adriamycin (ADM) were tested. The overall evaluable rate was 66.7 per cent in HTCA and 83.3 per cent in NM-IA, respectively. When the per cent survival in HTCA and the per cent inhibition in NM-IA less than 50 per cent was defined as drug sensitive, the drug sensitive rates of MMC, 5-FU, CPM, and ADM were 23.1, 16.7, 11.8, and 27.8 per cent in HTCA and 17.6, 18.4, 22.4, and 25.5 per cent in NM-IA, respectively. Although statistically significant correlations between the results of HTCA and those of NM-IA were obtained for MMC and ADM, no correlation was observed for 5-FU and CPM. The overall predictive accuracy rate of clinical response was 83.3 per cent (true positive rate 50 per cent and true negative rate 92.9 per cent) in HTCA and 76.0 per cent (true positive rate 37.5 per cent and true negative rate 93.8 per cent) in NM-IA, respectively.

Animals↗

PubMed1987

Antitumor activities of KW-2152, a new isoquinon agent, against human tumor xenografts transplanted into nude mice.

The antitumor activities of KW-2152, a new isoquinon derivative, were examined in thirteen human tumor xenografts, transplanted into nude mice. KW-2152 was administered intravenously at a schedule of q4d X 3, in daily doses of 7.3 mg/kg and 3.6 mg/kg, and q2d X 6 with a daily doses of 7.3 mg/kg, respectively. KW-2152 displayed significant antitumor activities against the human tumor xenografts in 3 out of 13 strains (23.1 per cent) at the schedule of q4d X 3, with a daily dose of 7.3 mg/kg. Depending on the schedule of administration, tumor activity was observed in 8 out of 13 strains (61.5 per cent) at a schedule of q2d X 6, with a daily dose of 7.3 mg/kg. SH-2 and SH-9 gastric tumors were sensitive to KW-2152 and growth was completely inhibited with the schedule of q4d X 3, and a daily dose of 7.3 mg/kg. Thus, KW-2152 seems to have a wide antitumor spectrum, and the possible antitumor effects for clinical use, warrant attention.

Animals↗

PubMed1987

Thalamic posterior ventral neurons with bifurcating axons to the first and second somatosensory areas in the cat, demonstrated by the fluorescent retrograde double labeling technique.

The thalamic posterior ventral neurons with bifurcating axons to both the first and second somatosensory cortical areas (SI and SII) in the cat were examined by the fluorescent retrograde double labeling technique. After injection of Evans blue (EB) into the SI, and of 4',6-diamidino-2-phenylindol.2HCl (DAPI) into the SII of the same hemisphere, EB- and DAPI-labeled cells were observed predominantly in both the posterolateral ventral and the posteromedial ventral nuclei of the thalamus. Although EB single-labeled and DAPI single-labeled cells tended to occupy separate regions within the posterior ventral nuclei, a small number of cells double-labeled with both EB and DAPI were detected in the border zone between two single-labeled cell groups. These observations indicate that some cells in the posteromedial and posterolateral ventral nuclei project both to the SI and SII by bifurcating axons.

Animals↗

PubMed1987

Thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat.

The topical organization of thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat has been studied using the technique of retrograde axonal transport of horseradish peroxidase. The projections of the posterolateral and posteromedial ventral nuclei (VPL, VPM) to the second somesthetic area (SII) are organized somatotopically. The posterior portion of SII (hindlimb area) receives fibers mainly from the dorsolateral part of VPL, the middle portion of SII (forelimb area) from the ventromedial part of VPL, and the anterior portion of SII (face area) from VPM. These topical projections are more loosely organized and less densely arranged than those to the first somesthetic area. The SII receives a few fibers from the medial geniculate nucleus, particularly its magnocellular and dorsal principal parts, and from the suprageniculate nucleus. The posterior part of SII lying near the secondary auditory area receives many fibers from the medial geniculate and suprageniculate nuclei, and only a few fibers from the lateral central and paracentral nuclei. The fourth somesthetic area (SIV), located in the dorsal bank of the anterior ectosylvian sulcus, receives fibers mainly from the dorsal principal and magnocellular parts of the medial geniculate nucleus, and from the suprageniculate nucleus. The SIV receives a fair number of fibers from VPL and VPM roughly in a somatotopical manner. The posterior portion of SIV receives fibers chiefly from the dorsolateral part of VPL, the middle portion of SIV from the ventromedial part of VPL, and the anterior portion from VPM. In addition, SIV receives a few fibers from the lateral central, paracentral, ventral lateral and ventral medial nuclei. The SIV, together with the most posterior part of SII, forms an auditory area, receiving many fibers from the medial geniculate and suprageniculate nuclei, and a few fibers from the intralaminar nuclei.

Animals↗

PubMed1987

[In vivo chemosensitivity test for UFT and FT-207. I--Subrenal capsule assay].

A chemosensitivity test for UFT and FT-207, which are used in long-term administration clinically, was investigated for prediction of clinical response. Five transplantation-established human tumor xenograft systems were examined using subrenal capsule assay. Both anticancer agents showed antiproliferative effects according to the total administered dose. Two of 5 tumors were determined to be sensitive to UFT using microscopic measurements following intragastric administration of 1/2 of the LD50 value, while they were shown to be resistant to 5-FU. In these two cases, prolongation of life span by long-term administration of UFT was shown clinically. All these experiments could be performed on condition that the loss of body weight in mice was less than 20%. These results suggest that in the 4-day subrenal capsule assay, clinical responses to long-term administration of UFT or FT-207 are predictable using intragastric high-dose administration which does not induce more than 20% body weight loss in experimental mice.

Adenocarcinoma↗

PubMed1987

[In vivo chemosensitivity test for UFT and FT-207. II. Chemosensitivity test on human tumor xenografts transplanted in nude mice].

The present study was designed to predict the clinical effect of UFT and FT-207 in short-term administration using a nude mouse-xenograft system. Five human tumor xenografts transplanted into nude mice were used. UFT and FT-207 were administered with the LD10 doses orally for seven consecutive days. Tumor size was measured on day 7, 14 and 21 after the administrations. No significant differences in antiproliferative effects were observed between the measurements of tumor size made on day 7 and day 21. UFT inhibited significantly the tumor growth of CH-I established from colon cancer in which the prolongation of life span has been obtained by clinical long-term administration of UFT. These results suggest that this chemosensitivity test system using nude mice is useful for prediction of clinical response at 7 days after final administration of UFT and FT-207.

Adenocarcinoma↗

PubMed1987

[Clinical trials of the subrenal capsule assay].

Clinical trials of 4-day subrenal capsule assay (SRC assay) were carried out. One hundred and forty-one cases were investigated in order to evaluate the clinical utility of the assay. A total evaluability rate of 81.0% and a response rate of 36.5% were obtained in the SRC assay. The overall predictive accuracy between the tumor sensitivity of the assay and the clinical response was 82.1%. The percentage inhibition of %DNA/protein content of the implanted tumor, as a new predictor of the tumor growth inhibition, also indicated a good prediction rate for the assay. Correlation between the sensitivity test and the end results after chemotherapy in cases of inoperable gastric cancer classified as stage IV was investigated, retrospectively. Comparison of the survival curves between the patients treated with sensitive agents and those with insensitive agents exhibited a significant advantage for the former (p less than 0.01). These results suggest the utility of the SRC assay for clinical use, but histological studies exhibited certain limitations of this assay due to the existence of early host rejection of the implanted tumor. The utility of the SRC assay should be finally evaluated using more histological assessments and clinical trials.

Animals↗

PubMed1986

Second hepatic resection for recurrent hepatocellular carcinoma.

During the last 5 years, radical hepatic resection was performed in 91 patients with hepatocellular carcinoma (HCC). Thirty-one of them had tumour recurrence in the remaining liver during the follow-up period. Second hepatic resection was carried out on nine of them 4-38 months after the first hepatectomy. The ages of these patients ranged from 39 to 65 years with an average of 53.7. There were six men and three women. Eight patients had underlying cirrhosis of the liver and one chronic active hepatitis. Six patients are alive, four being free of HCC and two with disease, for 15-45 months after the first operation. Two patients died of systemic cancer dissemination. The remaining patient had tumour recurrence in the liver again and died of hepatic failure after the third laparotomy. The survival rate of these nine patients was significantly better than that of twenty-two patients who were treated by other palliative methods. The present result shows that a second hepatic resection is a possible and meaningful method of treatment for the patients with recurrent HCCs in the liver remnant.

Adult↗

PubMed1986

Thalamic projections to the motor and premotor areas in the cat traced with horseradish peroxidase.

The thalamic afferents to cortical areas 4 and 6 in the cat have been studied using retrograde axonal transport of horseradish peroxidase. Areas 4 and 6 receive projections mostly from the ventral lateral (VL) and ventral anterior nuclei. Area 4 gamma receives fibers from the central, ventral and ventrolateral parts of the VL, area 4 delta from the lateral part, area 4sfu from the dorsal and dorsolateral parts, and area 4fu from the dorsal and dorsomedial parts. Area 6a beta receives fibers from the ventromedial part of the VL, area 6a alpha from the medial part, and area 6iffu from the dorsomedial part. Thus, the VL projects to areas 4 and 6 in a topical manner. The ventrodorsal axis of the VL is projected along the anteroposterior axis of areas 4 and 6. In addition, the VL projects topically to these areas also in the mediolateral direction. A considerable number of neurons in the ventral anterior nucleus (VA) send axons to areas 4 and 6. Area 4 receives fibers from the ventrolateral part of the VA, while area 6 receives fibers from its dorsomedial part. These projections are organized topically; the ventrodorsal axis of the VA is represented by the anteroposterior axis of areas 4 and 6. In addition to the VL and VA, areas 4 and 6 receive a fair number of fibers from the lateral central nucleus, and a few fibers from the paracentral, parafascicular and medial central nuclei and from the dorsolateral part of the posteromedial ventral nucleus. Area 4 receives only few fibers from the centre median and limitans nuclei. Area 6 receives a few fibers from the submedial and ventral medial nuclei.

Animals↗

PubMed1986

Clinical experience with 118 hepatic resections for hepatocellular carcinoma.

During the recent 5 2/3 years, hepatic resection was performed on 118 patients with hepatocellular carcinoma. Ages ranged from 17 to 78 years with an average of 57 years. There were 101 males and 17 females. Underlying cirrhosis of the liver was found in 101 cases, and chronic hepatitis was found in 16 cases. Before surgery 62 patients had 71 associated conditions such as esophageal varices, diabetes mellitus, cholelithiasis, or peptic ulcer. Operations for the varices and cholelithiasis were performed simultaneously with hepatic resection in 15 and six patients, respectively. The operative mortality rate within 1 month was 7.6%, and the overall in-hospital death rate was 14.4%. In 94 patients with curative resection, the 2-year survival rate was 81.2% in patients without cirrhosis and 55.4% in patients with cirrhosis. The 4-year survival rate was 81.2% in the former and 34.8% in the latter group. The prognosis was significantly better in patients without cirrhosis than in those with cirrhosis. On the contrary, 21 of 24 patients with palliative resection died within 2 years despite extensive chemotherapy. The present results may indicate that the resectability rate of hepatocellular carcinoma is currently increasing, even in the presence of cirrhosis of the liver due to early detection of the tumor by current advances in diagnostic methods and also that major hepatic resection is possible in selected patients with cirrhosis.

Adolescent↗

PubMed1986

Afferent projections to the thalamic mediodorsal nucleus in the cat studied by retrograde and anterograde axonal transport of horseradish peroxidase.

The afferent pathways to the thalamic mediodorsal nucleus (MD) in the cat were studied using the methods of anterograde and retrograde axonal transport of horseradish peroxidase (HRP) and wheat germ agglutinin conjugated to HRP (WGA-HRP). The MD receives fibers from the prefrontal cortex in a topically organized manner in accordance with the thalamocortical projections. The medial or ventral portion of the MD receives afferents from the islands of Calleja of the olfactory tubercle, the nucleus of the diagonal band, the amygdala and the claustrum. The lateral hypothalamic nucleus sends a moderate number of fibers to the medial MD, but other hypothalamic nuclei send only a few fibers to the MD. The lateral or dorsal portion of the MD receives fibers from the nucleus of the diagonal band, the ventral pallidum and the entopeduncular nucleus, but only few from the olfactory tubercle and the amygdala. The thalamic reticular nucleus sends many fibers to the MD without showing any topography. The MD, particularly its lateral part, receives afferents from brainstem structures, such as the substantia nigra, superior colliculus, reticular formation, raphe nuclei and nucleus loci coerulei. Only the interpeduncular nucleus sends fibers mainly to the medial part of the MD. The cerebellar nuclei send only a few fibers to the lateral part of the MD at posterior levels.

Afferent Pathways↗

PubMed1986

[Studies on long-term survival and prognostic factors after surgical treatment of breast cancer].

Two hundred twenty-nine patients with primary breast cancer seen from 1970 through 1983 were investigated in terms of the survival rate and factors relevant to the prognosis. The operative methods were as follows: so-called radical in 191, modified radical in 24, super radical in eight, and other limited operations in six. Fifty-four patients had Stage I, 128 had Stage II, 45 had Stage III, and four had Stage IV diseases. The curabilities of these operations were absolute curative in 190, relative curative in 26, and non-curative in 13 cases. The overall cumulative survival rate was 80.9% and 78.2% at five and 10 years, respectively.

Adult↗

PubMed1985

Thalamic projections to the hippocampal formation in the cat.

The thalamo-hippocampal projections in the cat were studied by anterograde and retrograde tracing methods. Injections of horseradish peroxidase (HRP) into the hippocampus and dentate gyrus led to retrograde labeling of cells in the nucleus reuniens of the ipsilateral thalamus throughout almost its entire anteroposterior extent. The labeled cells were found mostly in the parvocellular ventral part, but a few cells were labeled in the dorsal part at anterior levels. Anterograde transport following injections of wheat germ agglutinin conjugated to HRP into the nucleus reuniens resulted in terminal labeling in the subicular area, the neighboring parts of the hippocampus (CA1) and the border zone of the dentate gyrus with the hippocampus.

Animals↗

PubMed1985

Direct projections of the hypothalamic nuclei to the thalamic mediodorsal nucleus in the cat.

Direct projections of the hypothalamic nuclei to the thalamic mediodorsal nucleus (MD) were studied using retrograde and anterograde transport of horseradish peroxidase (HRP) and wheat germ agglutinin (WGA)-HRP. HRP and WGA-HRP were injected into the MD, thalamic paraventricular, lateral habenular and hypothalamic nuclei. The results indicate that the MD, particularly its medial part, receives a moderate amount of hypothalamic afferents, and that most of these afferents originate in the medial part of the lateral hypothalamic nucleus at anterior levels, while a limited number are derived from the dorsal, dorsomedial, ventromedial and anterior hypothalamic and lateral preoptic nuclei.

Animals↗