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Biomedical subjects

K Iwata

Publications and source records attributed to K Iwata.

At least 271 records · Page 15Linked to original sources
PubMed1992

[Primary open angle glaucoma and low tension glaucoma--pathogenesis and mechanism of optic nerve damage].

The etiology, pathogenesis and mechanism of optic nerve damage in primary open angle glaucoma (POAG) and low tension glaucoma (LTG) were investigated by experimental glaucoma in monkey and by follow-up studies of many patients over 15 years, by pathohistological and immunohistochemical analysis. 1) LTG was proved to be a real glaucoma, showing pressure-dependent optic nerve damage. The pathological entity was a primary weakness of the lamina cribrosa (LC), and therefore even normal pressure could deform the LC. Due to backward distortion of LC the channels were disarranged and twisted, inducing mechanical optic nerve damage. There was no active vascular damage or vascular constriction at the site of the optic nerve damage. The filling defects of the advanced glaucomatous optic disc were not the cause of optic nerve damage, but the result of regressive vascular change after axon bundle loss. Splinter hemorrhage of the optic disc might be the result of the same process. 2) The weakness of LC might be induced by the abnormal metabolism of the extracellular matrix of the LC. 3) To arrest the progressive optic nerve damage in LTG, the intraocular pressure (IOP) should be maintained under 12, or ideally, 10 mmHg. 4) The optic nerve damage in POAG was not only pressure-dependent, but also dependent on the weakness of the LC, as in the case of LTG. In the early stage the IOP should be under 19 mmHg, in the advanced stage under 14 mmHg in order to arrest progression for over 15 years. 5) In advanced experimental glaucoma of monkeys, the LC showed reduction of elastin, fragmentation of collagen, and change of proteoglycans. 6) As in the LC, the trabecular meshwork also showed abnormal metabolism and abnormal deposits on the extracellular matrix in POAG, and LTG as well. 7) POAG and LTG might belong to the same family in which common abnormal metabolism of LC and trabecular meshwork induce various clinical features.

Adolescent↗
PubMed1992

Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium.

Degradation of proteoglycans is an initial change in osteoarthritic cartilage. Matrix metalloproteinase-3 (MMP-3; stromelysin) capable of degrading cartilage proteoglycans and type IX collagen was immunolocalized in osteoarthritic and normal cartilage. Immunohistochemical studies showed MMP-3 in chondrocytes of the superficial and transition zones in approximately 90% of osteoarthritic cartilage (60 of 67 samples) and in 31% of those of the superficial zone in some normal cartilage (4 of 13 samples). MMP-3 staining correlated directly with the histological histochemical scores of Mankin and with proteoglycan depletion, up to a certain grade of severity. Chondrocytes in the deep radial zone, clusters, and osteophytes were immunostained only when proteoglycan depletion and fissures affected them. Culture media from osteoarthritic cartilage contained significantly higher levels of metalloproteinase activity that was identified as MMP-3 by immunoblotting and lower amounts of tissue inhibitor of metalloproteinases compared with those in the control samples. MMP-3 was also immunolocalized in the lining cells of most osteoarthritic synovium (20 of 23 specimens, 87%) with a direct correlation with scores of inflammatory cell infiltration in the synovium, but it was not detected in the normal synovium. Light and electron microscopic studies demonstrated that MMP-3 digests proteoglycan aggregates in human articular cartilage. Treatment of normal and osteoarthritic cartilage slices with tumor necrosis factor-alpha and/or interleukin-1 alpha increased the number of MMP-3-immunoreactive chondrocytes and the intensity of the staining. These data suggest that MMP-3 produced by the chondrocytes and synovial lining cells under stimulation with these cytokines may be important in proteoglycan degradation in human ostoearthritic cartilage.

Cartilage Diseases↗
PubMed1992

Sulfated proteoglycans in the human lamina cribrosa.

The sulfated proteoglycans in the normal human lamina cribrosa were studied by electron microscopy after cuprolinic blue dye binding. Within the cores of the laminar plates, three types of cuprolinic blue-positive proteoglycan filaments with different sizes were associated with collagen fibers. These filaments, which were partially sensitive to chondroitinase AC and chondroitinase B, were completely removed by chondroitinase ABC and were identified as chondroitin/dermatan sulfate proteoglycans. In addition, small punctate and filamentous structures that stained with cuprolinic blue were associated with the basal laminae of astrocytes and blood vessels. Enzyme chondroitinase ABC had no effect, but heparinase digested all of these basement membrane-associated structures, indicating that they represented heparan sulfate proteoglycan molecules. Keratanase did not affect any of the cuprolinic blue-positive materials. This investigation illustrates the ultrastructural distribution and morphology of proteoglycans in the human lamina cribrosa and provides baseline information for future studies regarding the roles of proteoglycan molecules in diseases such as glaucoma.

Aged↗
PubMed1991

Microparticle generation during in vitro platelet activation by anti-CD9 murine monoclonal antibodies.

We used flow cytometry and two anti-CD9 murine monoclonal antibodies (NNKY1-19, MALL13) to investigate the glycoprotein composition and the potential functions of microparticles (MP) released by platelets exposed to these antibodies in vitro. NNKY1-19 produced aggregation with characteristics similar to those noted in previous reports. The action of MALL13 on platelets in platelet-rich plasma (PRP), however, differs from that of other anti-CD9 antibodies. The normal fluctuation in the MALL13-induced change in optical density disappeared when complement was present. MALL13-induced effect for platelet in PRP was not inhibited by preincubation with monoclonal anti-GPIIb/IIIa antibody, but was inhibited in washed platelets (WP). Furthermore, following MALL13 stimulation in PRP platelets, the amount of buffer LDH markedly increased and electron microscopy findings showed vacuoles appearing inside the platelets. These results suggest that MALL13 has at least two effects on platelets that differ for PRP platelets and WP. The number of MP released was increased by the addition of anti-CD9 antibodies. MP surfaces were found to be rich in CD9 protein. MALL13 stimulation lead to a significant increase in the binding of C1q and C3 to platelets and caused the production of MP to occur more rapidly than it did the exposure of fibrinogen binding sites in the presence of complement. The analysis of the relationship of MP to anti-CD9 monoclonal antibody may be useful in the investigation of the relationship between platelet function and coagulation regulation.

Antibodies, Monoclonal↗
PubMed1991

Late-infantile type galactosialidosis. Histopathology of the retina and optic nerve.

We studied histopathologic findings from the retina and optic nerve of a patient with the late-infantile type of galactosialidosis and related them to clinical features of the condition. Markedly fewer ganglion cells were evident histopathologically using light microscopy. Results of histochemical studies demonstrated abnormal accumulation of lipid and proteinaceous material in the residual swollen ganglion cells. Marked loss of myelinated nerve fibers and thickening of the pial septum were also observed in the optic nerve. Both retinal ganglion cells and amacrine cells had intracytoplasmic inclusion bodies, but none were found in the optic nerve. These findings suggested that optic atrophy was induced by axonal wallerian degeneration secondary to retinal ganglion cell death. Although the fundus showed advanced optic nerve atrophy, a cherry red spot was not evident, possibly because of the marked decrease in ganglion cells in this case.

Adolescent↗
PubMed1991

Comparisons of the sensation perceived and intradental nerve activity following temperature changes in human teeth.

The relationship between the intradental nerve responses and subjective sensory ratings evoked by thermal stimulation of the teeth was studied in man. Recordings were taken from a total of 12 thermally sensitive units from the inferior dental nerve following thermal tooth stimulation, of which seven responded to both heating and cooling, two were exclusively cold-sensitive and three exclusively heat-sensitive. The early and late sensory responses following both cold and heat stimulation of the tooth were observed. The late sensory responses were more unstable than the early sensory responses. The mean threshold of the early sensory responses to tooth cooling was 13.6 +/- 1.9 degrees C (n = 9) and that to heat stimulation was 48.4 +/- 4.8 degrees C (n = 10). The firing frequency of the heat-sensitive, but not the cold-sensitive, units increased linearly in proportion to the increase in magnitude of the early sensory ratings.

Adult↗
PubMed1991

Immunohistochemical study on tissue inhibitors of metalloproteinases in normal and pathological human livers.

The localization of tissue inhibitor of metalloproteinases (TIMP) in normal and pathological livers was examined by immunohistochemistry using monoclonal antibodies at the light microscopic level. In normal liver, immunoreactive TIMP was detected in smooth muscle cells and endothelial cells of blood vessels, fibroblasts, bile duct cells and Kupffer cells, indicating that TIMP is likely to be a general element of the liver. Immunoreactivity was observed in newly-formed blood vessels, proliferating bile ductules, and fibroblasts in the expanded portal area and fibrous septa of chronic active hepatitis and cirrhosis. TIMP was strongly stained in the capsule of hepatocellular carcinoma. The intensity of the immunoreaction in the capsule was generally greater than that in cirrhotic liver apart from the tumor mass. In three of five cases with hepatocellular carcinoma, endothelial walls in contact with tumor cells were positive.

Antibodies, Monoclonal↗
PubMed1991

New monoclonal anti-human Fc gamma receptor II antibodies induce platelet aggregation.

We developed two new monoclonal antibodies, designated NNKY3-2 and NNKY4-7, that recognized a 40-kD platelet protein. They appeared to be monoclonal anti-Fc gamma receptor II (Fc gamma RII) antibodies from the results of flow cytometric binding inhibition studies using another monoclonal anti-Fc gamma RII antibody (2E1). The addition of NNKY3-2 or NNKY4-7 to platelet-rich plasma (PRP) led to a typical aggregation pattern preceded by a lag phase, but their addition to washed platelets did not induce aggregation. The aggregation of PRP by these antibodies was inhibited by prostaglandin E1 (PGE1) or staurosporine (protein kinase C inhibitor), whereas it was only slightly affected by a monoclonal anti-GPIIb/IIIa antibody or Arg-Gly-Asp-Ser. Furthermore, these antibodies induced the aggregation of washed platelets plus normal serum, but not that of washed platelets plus heat-treated serum (destruction of complement activity). These results suggest that NNKY3-2 or NNKY4-7-induced aggregation involves an unusual pathway independent of fibrinogen, and that the important factor is the participation of complement. NNKY3-2 and NNKY4-7 may be useful to study the relationship between autoantibodies, the Fc receptor, and complement in idiopathic thrombocytopenic purpura.

Adenosine Diphosphate↗
PubMed1991

Trabeculectomy with 5-fluorouracil.

The effect of subconjunctival injection of 5-fluorouracil (5-FU) after trabeculectomy was studied retrospectively in 205 eyes of 168 patients. A life table analysis of the surgical outcome was based on the type of glaucoma and age related differences, and a comparison was made with patients who had trabeculectomy without subconjunctival 5-FU. The success rate at 30 months after trabeculectomy with 5-FU therapy was considerably higher in primary open-angle glaucoma at 93.6% (72.7%), secondary glaucoma at 88.9% (72.4%), and refractory glaucoma at 72.2% (32.5%) with (or without) the use of ocular hypotensive drops when compared with historical control groups treated without 5-FU (60.0% (41.7%), 35.5% (24.0%), and 18.0% (8.0%), respectively). In patients aged over 70 years, no statistically significant improvement could be demonstrated with the use of 5-FU after trabeculectomy in primary open-angle glaucoma. Our study may provide data on the appropriate dosage and indications for the use of this drug after glaucoma surgery.

Aged↗
PubMed1991

Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese.

We studied the prevalence of migraine in low-tension glaucoma (LTG) and primary open-angle glaucoma (POAG). Seventy seven Japanese patients with LTG, 73 with POAG, and 75 normal subjects were randomly selected and tested with a headache questionnaire. The prevalence of headache with or without typical migrainous features (unilateral headache or ocular pain, nausea, vomiting, and visual disturbance before headache) was 51% in LTG, 42% in POAG, and 44% in normal patients. The prevalence of headache with two migrainous features or more (probable migraine) was 17% in LTG, 11% in POAG, and 12% in normal subjects. The prevalence of headache with three migrainous features (classical migraine) was 5% in LTG, 3% in POAG, and 3% in normal subjects. There was no statistically significant difference in the prevalence of any types of migraine between the three groups of patients (p greater than 0.05). These results suggest there is no significant relationship between migraine and LTG or POAG in Japanese patients.

Adult↗
PubMed1991

Reversal of cupping in experimental glaucoma.

We studied the change in the optic disk topography during spontaneous pressure reduction in laser-induced primate glaucoma (7 eyes, follow-up of 20 weeks) using computerized image analysis (vertical and horizontal cup-to-disk ratios CDR(V), CDR(H); neuroretinal rim area/disk area; cup volume/disk area). A significant correlation was found between the percent pressure reduction and the percent reversal in each disk parameter. There was no significant difference in the percent reversal between CDR(V) and CDR(H). These results suggest that reversal of cupping may depend on the percent pressure reduction, and may occur symmetrically in primate glaucoma.

Animals↗
PubMed1991

Adult-form galactosialidosis: ocular findings in three cases.

We reported ocular findings of 3 patients with adult-form galactosialidosis. Diffuse fine opacities in the deep layer of the corneal stroma, an obscure cherry-red spot of the macula and optic nerve atrophy were noted in all cases. Punctate lenticular opacities were observed in 2 cases. Slowly progressive visual disturbance was seen in all cases, and it might be due to secondary optic nerve atrophy caused by retinal ganglion cell death.

Adult↗
PubMed1991

Association between cadmium-induced renal dysfunction and mortality: further evidence.

Our previous follow-up study, carried out from 1979 to 1989, on 256 residents of Sasu, a cadmium (Cd)-polluted area located on Tsushima Island, Nagasaki Prefecture, Japan, showed a significant relationship between urinary beta 2-microglobulin (beta 2-m) excretion and mortality in men. To investigate the association between Cd-induced renal dysfunction and mortality more precisely, 275 residents in the same area aged 40-92 years, who had participated in a health survey conducted in May 1982, were followed to February 1989. The expected number of deaths was calculated on the basis of the sex- and 5-year-age-specific mortality rates for Tsushima Island in 1985. In both men and women with urinary beta 2-m concentrations greater than 1,000 micrograms/g creatinine, observed deaths were greater than the expected. However, the P value of the difference was less than 0.05 only in women. Analysis by the Cox proportional hazards model showed that, in both men and women, serum beta 2-m and creatinine, as well as urinary total protein and beta 2-m were significantly or marginally significantly related to mortality independent of age. In men, serum beta 2-m was more strongly related to mortality than urinary beta 2-m. The results provide further evidence for the causal association between Cd-induced renal dysfunction and mortality. The present report also discusses the role played by decreased glomerular filtration rate in the excess mortality of subjects with Cd-induced renal dysfunction.

Adult↗
PubMed1991

Association between renal tubular dysfunction and mortality among residents in a cadmium-polluted area, Nagasaki, Japan.

A retrospective cohort study was carried out to clarify the effect of exposure to environmental cadmium (Cd) on mortality. A total of 256 residents aged 50 years or older, living in Sasu, a Cd-polluted area in Tsushima Island in Nagasaki Prefecture, Japan, were followed from July 1979 to February 1989. The expected number of deaths calculated was based on the sex- and age- specific mortality rate in Tsushima Island in 1985. In Sasu residents of both sexes with urinary beta 2-microglobulin (beta 2-m) concentration greater than 1,000 microgram/g creatinine in 1979, observed deaths were greater than expected. However, the p value of the difference was less than 0.05 only in men. The relationships of age, mean blood pressure, urinary beta 2-m and urinary Cd concentration to mortality were examined using Cox's proportional hazards model. Urinary beta 2-m was independently and significantly related to mortality in men but not in women. The results suggest an association between Cd-induced renal tubular dysfunction and mortality.

Aged↗
PubMed1991

Screening for unruptured asymptomatic intracranial aneurysms in patients undergoing coronary angiography.

In screening for unruptured asymptomatic intracranial aneurysms, an intracranial intra-arterial digital subtraction angiography (IA-DSA), posteroanterior view, was obtained in 72 consecutive patients who underwent coronary angiography for workup of angina pectoris. In cases where an aneurysm was suspected from IA-DSA, conventional intracranial angiography was obtained. Five asymptomatic unruptured aneurysms were detected in four of these cases. The aneurysms ranged from 4 to 16 mm in diameter. There were no complications associated with the coronary angiography nor with the additional intracranial IA-DSA, which required less than 5 minutes to perform in all cases. The value of performing intracranial IA-DSA in patients undergoing coronary angiography to screen for unruptured asymptomatic aneurysm is discussed, as is the possible racial differences in the frequency of aneurysms.

Aged↗
PubMed1991

[The distribution and characterization of sulfated-proteoglycans in the normal human lamina cribrosa].

The distribution and morphological characterization of the sulfated-proteoglycans in the normal human lamina cribrosa under the electron microscope after staining with cationic-dye (Cuprolinic-Blue) in critical electrolyte condition were studied. Three types of Cuprolinic-Blue positive filaments were identified associated with collagen in the lamina cribrosa according to their size, electro-density and their relation to the collagen fibrils. The thin and short Cuprolinic-Blue positive filaments (referred to as CB-1 filament in this communication) distributed over the collagen fibers in relatively regular fashion. The intermediate-sized Cuprolinic-Blue positive filaments (CB-2) were seen randomly associated with collagen fibers. The clusters of large CB-3 filaments were seen unevenly associated with loosely packed collagen fibers. The higher electron density of CB-2 and CB-3 filaments than those of CB-1 filaments were also demonstrated. Cuprolinic-Blue positive dots and blots as well as various sizes of filaments could be identified in the basal lamina surrounding the collagen beams and in the basement membrane of the blood vessels.

Aged↗