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Biomedical subjects

K Iwata

Publications and source records attributed to K Iwata.

At least 235 records · Page 13Linked to original sources

Multiple effects of morphine on facial scratching in monkeys.

The medullary dorsal horn (MDH), the medullary homolog of the spinal dorsal horn, is a site where opioid-receptor agonists can act at opioid receptors to produce pronounced facial scratching, the behavioral correlate of pruritus. In the present study, after a 10-min baseline period, morphine (5.0 micrograms) was micro-injected into the MDH of monkeys. Behavior was videotaped and facial scratches were counted by two independent raters. Morphine greatly increased facial scratching behavior, which is consistent with previous findings where mu-opioid receptor agonists microinjected into the MDH have been to induce dose-dependent, naloxone-reversible facial scratching in monkeys. In the current research, intramuscular (IM) administration of the opioid-receptor antagonist, naloxone (0.5 mg/kg), reversed this MDH morphine-induced scratching. Additionally, IM morphine (1.0 mg/kg) produced a substantial reduction in facial scratching behavior. Scratching behavior continued at a high rate after injection of saline (0.1 mL/kg, IM). These findings support the hypothesis that morphine has both pruragenic and antipruragenic activity, depending on the site of action.

Animals↗

Immunohistochemical study of hemangioblastoma with special reference to its cytogenesis.

The cytogenesis of so-called hemangioblastoma arising in the central nervous system was investigated using the immunoreactivity to various proteins in cerebellar hemangioblastomas, extracerebellar hemangioblastomas, cerebral hemangiopericytomas, and hemangioendotheliomas, as well as a variety of meningiomas. The antisera used included vimentin, glial fibrillary acidic protein, epithelial membrane antigen, factor VIII-related antigen, and cytokeratin. Lipid-laden cells often encountered in partially degenerated meningiomas revealed almost identical reactivity patterns as the lipid-laden cells, i.e., so-called stroma cells, of hemangioblastomas. The results indicate that the so-called hemangioblastoma of the central nervous system is derived from arachnoid cells in meningotheliomatous meningiomas by way of cellular degeneration.

Adult↗

Age-related changes of sulfated proteoglycans in the human lamina cribrosa.

Sulfated proteoglycans in the lamina cribrosa of the optic nerve head from individuals aged 2 months, 18 months, and 23, 35, 44, 55, 67, 74, and 88 years were studied by electron microscopy after cuprolinic blue dye binding. Within the cores of the laminar plates, cuprolinic blue-positive chondroitin/dermatan sulfate proteoglycan filaments of different sizes were found associated with collagen fibers. In addition, small punctate and filamentous structures that represented heparan sulfate proteoglycan molecules were associated with the basal laminae of astrocytes and blood vessels. In the eyes of older individuals, the chondroitin/dermatan sulfate and heparan sulfate proteoglycan filaments were found to be shorter than those in younger persons. A mild decline with aging in the diameter of the filaments was also noted. Our findings illustrate the age-related changes in the proteoglycans in the human lamina cribrosa, which may help explain why the optic nerve head is more susceptible to damage with aging.

Adult↗

[Fertility after treatment for testicular tumor].

Thirty-four patients with stage 1 or stage 2A testicular tumor all survived 5 years after the treatment, whereas eighteen patients with stage 2B or 3 testicular tumor, including only nonseminomatous tumor, had a 5-year survival rate of less than 50%. Spermatogenesis returned to normal in 3 patients surviving 22 months after chemotherapy. Five patients who had undergone retroperitoneal lymph node dissection with division of the inferior mesenteric artery developed impaired ejaculation, whereas 3 patients who had undergone the operation without division of the inferior mesenteric artery had normal ejaculation. In 17 patients with right testicular tumor metastases were found in the para-aortic, paracaval and interaortocaval lymph nodes. On the other hand, in 4 patients with left testicular tumor metastases were limited to the para-aortic nodes. These results indicate that impaired spermatogenesis by conventional chemotherapy is reversible in patients with stage 1 or 2 testicular tumor, and patients with stage 1 tumor or stage 2 tumor with localized para-aortic metastases, not involving the inferior mesenteric artery, should undergo retroperitoneal lymph node dissection without division of the inferior mesenteric artery to preserve postoperative fertility.

Adolescent↗

[A case of gastric cancer with multiple liver metastasis treated with low dose CDDP therapy on an outpatient basis after palliative gastrectomy].

A 59-year-old-male with advanced gastric cancer and multiple liver metastasis was treated by intravenous administration of MMC (30 mg/body) and oral administration of HCFU (400mg/body/day) initially after palliative gastrectomy. CT scan revealed that liver metastatic lesions were undetectable at three months after operation. Seven months later, administration of HCFU was discontinued because liver metastatic lesions were observed again. Intravenous administration of MMC (10mg/body)+ACR (20mg/body) was performed four times weekly, but liver metastatic lesions were increasing in size. From 15 months after operation intravenous administration of CDDP (25mg/body/week) was started on an outpatient basis. After administration of CDDP 6 times, liver metastatic lesions were diminished in size. By CT scan the maximum percent reduction of liver metastatic lesions was 97% and duration of partial response was seven months. Eight months later, liver metastatic lesions regrew. At 28 months after operation, the patient died of liver metastatic lesions. This low dose regimen of CDDP on an outpatient basis is potentially useful in the treatment of advanced gastric cancer with multiple liver metastasis.

Ambulatory Care↗

[Expression of proliferating cell nuclear antigen following filtration surgery in rabbits].

We evaluated cell replication in wound healing following experimental filtration surgery. Cell replication was measured via immunohistochemistry for proliferating cell nuclear antigen, which is a marker of cell proliferation. Trabeculectomy was performed on albino rabbit eyes, with the filtering site harvested on postoperative days 1, 4, 7, and 14. Samples were fixed with 10% buffered formalin and prepared for paraffin section, and proliferating cell nuclear antigen was detected in filtering site tissue using the labeled streptavidin-biotin method. The number of immunoreactive cells increased at days 4 to 7 and was markedly decreased at day 14; the filtering site was obstructed at days 7 to 14. These findings may have clinical implications for the administration of antiproliferative agents after filtration surgery. Evaluation of cell replication following filtration surgery by detecting proliferating cell nuclear antigen is a simpler technique than autoradiography.

Animals↗

Effects of the novel thyrotropin-releasing hormone analogue Na -((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L-prol ina mide monohydrate on the central nervous system in mice and rats.

The central nervous system (CNS) effects of a novel thyrotropin-releasing hormone (TRH) analogue, JTP-2942 (Na-alpha- ((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L-pro linamide monohydrate, CAS 131404-34-7) were investigated and compared with those of TRH. When administrated subcutaneously, JTP-2942 was about 80 times more potent than TRH in the antagonization of reserpine-induced hypothermia, and when administrated intravenously it was about 16 times more potent than TRH in the potentiation of flexor reflexes. Furthermore, oral administration of JTP-2942 was able to antagonize a chlorpromazine-induced reduction in locomotor activity, while TRH was far less effective. In tests on the recovery from pentobarbital-induced sleep and disturbance of consciousness induced by concussive head trauma, JTP-2942 was about 30 and 3 times more potent than TRH, respectively. Thus, JTP-2942 had a far stronger and more persistent action compared with TRH in regard to these effects. However, JTP-2942 had a 3-fold lower effect on thyroid stimulating hormone (TSH) release than TRH. These results suggest that the stimulatory effects of JTP-2942 are selective for the CNS and that this TRH analogue may be applicable to clinical use.

Animals↗

[Fluorescein angiographic findings regarding the optic disc in cases of low-tension glaucoma and the chronic stage of anterior ischemic optic neuropathy].

The optic disc was studied by stereofluorescein angiography in 7 cases of the chronic stage of anterior ischemic optic neuropathy (AION) and 20 cases of low-tension glaucoma (LTG), to clarify the difference in vasculature. In the LTG patients, a selective and well-defined decrease of laminar and prelaminar capillaries in the upper and (or) lower temporal area of the optic disc was found in 38 (95%) of 40 eyes in the 20 cases. In the AION patients, a decrease of laminar and prelaminar capillaries was also found in 3 (43%) of 7 eyes in the 7 unilateral cases, but the specific area and form of vascular reduction were not found. These results show that the angiographic picture of the optic disc in LTG is clearly different from that in AION.

Adult↗

Electroretinogram and visual evoked potential in two siblings with adult form galactosialidosis.

We recorded flash electroretinograms (ERGs), flash visual evoked potentials (VEPs), pattern ERGs and pattern VEPs in two siblings with adult form galactosialidosis. The amplitude of b-wave was decreased in flash ERGs. The peak latency of flash VEPs was within normal range. The pattern ERGs and VEPs were nonrecordable. These results suggested the damage of retinal ganglion cell and inner nuclear layer in these cases.

Adult↗

The medullary dorsal horn. A site of action of morphine in producing facial scratching in monkeys.

BACKGROUND: Pruritus is a common side effect of epidural and intrathecal morphine administration in humans. This naloxone-reversible pruritus is typically present on the trunk, but is often severe around the eyes and nose, of the patients. The brain stem has been proposed as the site where opioids act to produce this effect. The authors studied the effect of morphine administered into the medullary dorsal horn (MDH), the brain stem homologue of the spinal dorsal horn, on facial-scratching behavior in monkeys. METHODS: Morphine was unilaterally microinjected into the MDH of rhesus monkeys. Systemic injections of the opioid-receptor antagonist naloxone (0.5 mg/kg intramuscularly) were also made in combination with morphine microinjection. Systemic injections of the antihistamine chlorcyclizine (1.0 and 2.5 mg/kg intramuscularly) were also made to determine if facial scratching was mediated through histamine release. The monkeys were videotaped for 10-15 min before and 1-2 h after opioid microinjection, and the number and location of scratches were counted. RESULTS: A dose-response curve was established for the mu/delta-opioid-receptor agonist morphine (0.5, 1.0, 2.5, and 5.0 micrograms). Specificity of the site of action within the MDH was examined by systematically changing the microinjection site, and examining the area of the face that the monkeys scratched. Morphine produced large dose-dependent increases in facial scratching ipsilateral to the microinjection. Increases in facial scratching were also observed contralateral to the microinjections. These effects were reversed by naloxone. The facial area scratched after microinjection of morphine was directly related to the injection site, with 1-mm changes in the location of the microinjection resulting in pronounced changes in the area of the face that the monkeys scratched. Systemic injection of chlorcyclizine produced only a small, transient attenuation of morphine's effect. CONCLUSIONS: Data from this study demonstrate that the MDH is a site where morphine acts to produce facial scratching in monkeys by acting at opioid receptors. It is also likely that the MDH is a site where centrally administered opioids act in producing facial pruritus in humans. The effects of morphine on facial-scratching behavior were only modestly attenuated with chlorcyclizine, indicating a minor involvement of a histamine-dependent mechanism of action.

Animals↗

[Optic disc measurements for cup depth with computerized image analysis in normal subjects and case of ocular hypertension and glaucoma].

Computerized image analysis was performed in 46 normals subjects and in 47 cases of ocular hypertension and 48 cases of early glaucoma for optic disc cup depth and optic disc parameters (rim area, cup area, cup volume and cup/disc ratio). The optic disc cup depth was 369.6 +/- 18.2 microns (M +/- SEM) in normal subject, 538.3 +/- 24.0 microns in ocular hypertension cases, 675.0 +/- 24.7 microns in glaucoma cases. The cup depth was significantly different among the three groups. The quotient of horizontal to vertical cup/disc ratio was also significantly different among the groups (1.84 +/- 0.17 in normal subjects, 1.28 +/- 0.05 in ocular hypertension cases, and 1.120 +/- 0.03 in glaucoma cases.) These results demonstrate that the optic disc cup enlarges three-dimensionally in early glaucoma.

Adult↗

[Histopathology of corneal plaque in vernal keratoconjunctivitis].

The author reported 2 cases of vernal keratoconjunctivitis with corneal plaque showing a white board-like appearance. Conventional medications were not effective in both cases and during the course of the disease corneal ulcer developed followed by formation of corneal plaque. After the plaque spontaneously peeled off, or were surgically removed, the ulcers of both cases healed. The histological specimens from the 2 cases were examined by light and electron microscopy. The plaques showed lamellae-like structures, and formed alternate accumulation of hyaline-like material and another amorphous material. No cell components, such as corneal epithelial cells, keratocytes, or fibroblasts, were found either on the surface of and within the plaques. The corneal epithelial cells and/or eosinophils, however, were found at the edge of the plaque. These findings may suggest that these corneal plaques were formed by repeated episodes of deposition and that corneal epithelial cells and eosinophils may have been involved.

Adolescent↗

[Proteoglycan abnormality in a nanophthalmos sclera].

We examined a scleral specimen obtained from a nanophthalmos eye with uveal effusion at the surgery, using cuprolinic blue (CB) dye binding and electron microscopy. The nanophthalmic sclera was separated into two areas electron microscopically. One was an area composed of tightly packed collagen fibers, the other with irregularly arranged collagen fibers. In irregular areas, several abnormal findings, such as twisting or fraying, were detected in collagen fibers, which were surrounded by fine fibrous materials. Furthermore, CB-positive materials were fewer in number and less in size and electron density around the collagen fibers and in fine fibrous materials than in the normal eye. Since the nanophthalmic sclera in this study showed some abnormalities both in collagen fibers and in proteoglycans, we suggest that the function and/or interaction of both of these were abnormal, which might be related to the onset of uveal effusion.

Adult↗

Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties.

Matrix metalloproteinase 9 (MMP-9) has been purified as an inactive zymogen of M(r) 92,000 (proMMP-9) from the culture medium of HT 1080 human fibrosarcoma cells. The NH2-terminal sequence of proMMP-9 is Ala-Pro-Arg-Gln-Arg-Gln-Ser-Thr-Leu-Val-Leu-Phe-Pro, which is identical to that of the 92-kDa type IV collagenase/gelatinase. The zymogen can be activated by 4-aminophenylmercuric acetate, yielding an intermediate form of M(r) 83,000 and an active species of M(r) 67,000, the second of which has a new NH2 terminus of Met-Arg-Thr-Pro-Arg-(Cys)-Gly-Val-Pro-Asp-Leu-Gly-Arg-Phe-Gln-Thr- Phe-Glu. Immunoblot analyses demonstrate that this activation process is achieved by sequential processing of both NH2- and COOH-terminal peptides. TIMP-1 complexed with proMMP-9 inhibits the conversion of the intermediate form to the active species of M(r) 67,000. The proenzyme is fully activated by cathepsin G, trypsin, alpha-chymotrypsin, and MMP-3 (stromelysin 1) but not by plasmin, leukocyte elastase, plasma kallikrein, thrombin, or MMP-1 (tissue collagenase). During the activation by MMP-3, proMMP-9 is converted to an active species of M(r) 64,000 that lacks both NH2- and COOH-terminal peptides. In addition, HOCl partially activates the zymogen by reacting with an intermediate species of M(r) 83,000. The enzyme degrades type I gelatin rapidly and also cleaves native collagens including alpha 2 chain of type I collagen, collagen types III, IV, and V at undenaturing temperatures. These results indicate that MMP-9 has different activation mechanisms and substrate specificity from those of MMP-2 (72-kDa gelatinase/type IV collagenase).

Amino Acid Sequence↗

A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 3 (stromelysin-1) using monoclonal antibodies.

A one-step sandwich enzyme immunoassay (EIA) for matrix metalloproteinase 3 (MMP-3; stromelysin-1) was developed. The assay system used two simultaneous immunoreactions using a solid phase monoclonal antibody and a horseradish peroxidase-labeled monoclonal antibody (Fab'). The sensitivity of the assay system was 20 micrograms/l and linearity was obtained between 31 and 500 micrograms/l. The EIA system was capable of measuring both precursor and active forms of MMP-3 as well as the forms of MMP-3 complexed with tissue inhibitors of metalloproteinases. MMP-3 levels as measured by this assay are significantly higher in the sera of patients with rheumatoid arthritis as compared to those of healthy subjects and patients with osteoarthritis. Immunoblot analyses showed that in the sera and synovial fluids of patients with rheumatoid arthritis, MMP-3 is present in the 59- and 57-kDa precursor forms.

Animals↗

Concentration of serum laminin and type IV collagen in liver diseases assayed by a sandwich enzyme-immunoassay using monoclonal antibodies.

Serum laminin (P1 fragment) and type IV collagen levels were determined in patients with hepatic disorders. The method was based on a sandwich enzyme-immunoassay using two monoclonal antibodies that recognize different epitopes of either laminin or type IV collagen molecule. Laminin and type IV collagen levels in the serum of patients with chronic hepatic disorders were higher as compared with those in healthy control subjects, with the increment of serum type IV collagen being far greater than that of laminin. Since type IV collagen and laminin are major basement membrane components, it is suggested that the higher levels of these peptides may reflect a so-called capillarization of the perisinusoidal wall encountered in hepatic fibrogenesis. The assay system used in this experiment is simple and sensitive and can be applied to clinical evaluation of hepatic fibrosis.

Adolescent↗

Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer.

BACKGROUND: The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy using lymphokine-activated killer (LAK) cells generated from tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) was investigated. METHODS: TIL, RLNL, and PBL derived from 39 patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of recombinant interleukin-2. To one group, solid-phase 10 micrograms/ml OKT3 was added during the initial culture period (day 2 or 4). Cytotoxicity against K562 cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of effector cells generated after culturing for 2-3 weeks were studied. RESULTS: Proliferative responses were significantly increased by OKT3 in each type of effector cell (P less than 0.01); in particular, TIL expanded more by OKT3 than PBL and RLNL (P less than 0.01). The population of CD8+ CD11b- cytotoxic T-cells in OKT3-stimulated groups was significantly larger than that in unstimulated groups (P less than 0.01), whereas no differences were observed with CD4+ cells (helper/inducer T-cells) and CD8+ CD11b+ cells (suppressor T-cells). OKT3 enhanced the NK-like activity of TIL and PBL but did not affect their LAK activity. OKT3 suppressed the NK and LAK activity of RLNL. CONCLUSIONS: OKT3 stimulation did not significantly enhance the LAK activity, but the authors propose that OKT3 could be an effective addition to adoptive immunotherapy using TIL due to an increased proliferation and generation of a large cytotoxic T-cell population.

Aged↗

Diencephalic projections from the superficial and deep laminae of the medullary dorsal horn in the rat.

An important function of the medullary dorsal horn (MDH) is the relay of nociceptive information from the face and mouth to higher centers of the central nervous system. We studied the central projection pattern of axons arising from the MDH by examining the axonal transport of Phaseolus vulgaris-leucoagglutinin (PHA-L). Labeled axon and axon terminal distributions arising from the MDH were analyzed at the light microscopic level. After large injections of PHA-L into both superficial and deep laminae of the MDH in the rat, labeled axons were observed in the nucleus submedius of the thalamus (SUB), ventroposterior thalamic nucleus medialis (VPM), ventroposterior thalamic nucleus parvicellularis (VPPC), posterior thalamic nuclei (PO), zona incerta (ZI), lateral hypothalamic nucleus (LH), and posterior hypothalamic nucleus (PH). Restriction of PHA-L into only the superficial laminae resulted in heavy axon and varicosity labeling in the SUB, VPM, PO, and VPPC and light labeling in LH. In contrast, after injections into deep laminae, labeled axons were mainly distributed in ZI and PH; some were also in VPM and LH, and fewer still in PO and SUB. Varicosities in VPM, SUB, and PO were significantly larger than those in VPPC, ZI, LH, and PH. Varicosity density was highest in SUB and lowest in the VPPC. We concluded that there are two distinct nociceptive pathways, one originating from the superficial MDH and terminating primarily in the dorsal diencephalon and the second originating from deep laminae of the MDH and terminating primarily in the ventral diencephalon. We propose that in the rat, input from the deeper laminae is primarily involved in the motivational-affective component of pain, whereas input from the superficial MDH is related to both the sensory-discriminative and motivational-affective component of pain.

Animals↗