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Biomedical subjects

K Hirokawa

Publications and source records attributed to K Hirokawa.

At least 163 records · Page 9Linked to original sources
PubMed1990

Up-regulation of thrombomodulin in human umbilical vein endothelial cells in vitro.

Previous studies have shown that thrombomodulin (TM) on endothelial cells is down-regulated by endotoxin, interleukin-1 beta (IL-1 beta), and tumor necrosis factor (TNF). This loss of anti-coagulant potential is thought to be related to the hypercoagulable state in sepsis, inflammation, and cancer. The current studies describe up-regulation of TM in human umbilical vein endothelial cells (HUVECs) by several compounds as judged by increased surface cofactor activity, surface TM antigen, and TM mRNA levels. Surface TM activity was increased by active phorbol esters (10(-8) M, 24-48 h), analogs of cAMP (1-10 mM, 4 h), and forskolin (10(-5) M, 24-48 h). Up-regulation of TM in HUVECs by 4 beta-phorbol 12-myristate 13-acetate (PMA) and dibutyryl cAMP (dBcAMP) was due to de novo synthesis of TM protein resulting from increased TM mRNA levels. The results suggest that protein kinase C and protein kinase A may be involved in cellular regulatory mechanisms for TM expression. In addition, PMA effects on surface TM activity are biphasic, with an initial reduction followed by a significant enhancement. Hence, we propose that compounds capable of increasing intracellular cAMP concentrations in HUVECs may be useful in preventing thrombosis by increasing the anti-thrombotic properties of endothelial cells.

Antibodies, Monoclonal↗
PubMed1990

Immunopathological study of neuropeptide expression in human salivary gland neoplasms.

The immunoreactivity of anti-neuron-specific enolase (NSE) and anti-Leu-7 on formalin-fixed sections of human salivary gland neoplasms was determined by the avidin-biotin-peroxidase complex method. In addition, neuropeptides, such as vasoactive intestinal polypeptide, somatostatin, and substance P, in human salivary gland neoplasms were expressed, whereas other polypeptides, including glucagon, cholecystokinin, leu-enkephalin and calcitonin, were absent. When 182 paraffin-embedded examples of human salivary gland tumors, including 112 benign and 70 malignant neoplasms, were examined immunohistochemically, positive immunoreactivity was observed in: 51 cases with NSE (59%) and 46 cases with Leu-7 (54%) of 86 pleomorphic adenomas; 11 cases with Leu-7 (61%) of 18 Warthin's tumors; 7 cases with Leu-7 (58%) of 12 acinic cell carcinomas; 5 cases with NSE (31%) of 16 adenoid cystic carcinomas; 5 cases with NSE (42%) and 4 cases with Leu-7 (33%) of 12 adenocarcinomas; 4 cases with NSE (25%) and 6 cases with Leu-7 (38%) of 16 undifferentiated carcinomas. The other tumors, such as oxyphilic adenomas, basal cell adenomas, epidermoid carcinomas, and mucoepidermoid carcinomas, were nonreactive. Neuropeptides were observed in the neoplastic epithelial cells of certain tumors such as Warthin's tumors, acinic cell carcinomas, adenocarcinomas and undifferentiated carcinomas. These findings suggest the possibility that cells of neuroendocrine origin, present in certain neoplastic salivary gland epithelia may play a significant role in the histogenesis of human salivary gland neoplasms.

Adenoma↗
PubMed1990

Immunopathological analysis of interstitial renal lesions in elderly people.

The incidence of focal lymphoid infiltrates in the renal interstitium was examined in autopsy cases of young and old subjects, and the infiltrating lymphocytes were immunohistologically characterized by a panel of monoclonal antibodies. Histologically, 198 and 227 autopsy cases over 60 years of age (87.2%) were shown to have mononuclear cell infiltrates of varying degree in the renal interstitium, whether or not these were accompanied by progressive arteriosclerotic changes. Above all, severely infiltrating foci in the renal interstitium were frequently found in the elderly over 70 years of age overlapping arterio-artherolosclerotic changes. In contrast, in the 54 younger control subjects under 49 years of age, the incidence of such a lesion was less (5.6%). An immunohistologic study revealed that the infiltrating mononuclear cells were predominantly composed of CD4+ cells, whereas CD22+ B cells were apparently lesser in number. Moreover, a considerable proportion of T cells was activated as judged by IL-2 receptor expression. From these findings, we now propose that susceptibility to the development of interstitial renal lesions in the elderly involves the cellular immune response, and may be related to an age-associated disturbance in regulatory T-cell function.

Aged↗
PubMed1990

Increased gamma-aminobutyrate aminotransferase activity in brain of patients with Alzheimer's disease.

In order to search for more proximal factors in the pathogenesis of Alzheimer's disease, we studied the activities of various enzyme in the brains of patients, as well as control cases, by postmortem autopsy. In addition to the findings already known, such as the increase in prolyl endopeptidase (post-proline cleaving enzyme, PPCE) activity and the decrease in kallikrein activity, we found, anew, an increase in aminobutyrate aminotransferase (GABA-T) activity in the Alzheimer brain. This may be an important impetus for the reduction of gamma-aminobutyric acid (GABA) in the brain, one of the neurotransmitters. It has to be determined whether the former two abnormalities offer a background for such an abnormality of the neurotransmitter.

4-Aminobutyrate Transaminase↗
PubMed1990

Increase in aminobutyrate aminotransferase and cholineacetyltransferase in cerebrum of aged rats.

We previously reported an increase in aminobutyrate aminotransferase (GABA-T) activity in the cerebrum of Alzheimer patients. In the present study, we investigated whether such findings are common in the usual aging process as well. We examined the activity of various enzymes, which were examined in the previous study, in the cerebrum of Wistar-Kyoto rats and spontaneously hypertensive rats. In the two strains, we compared the enzyme activities between the two groups of animals, 5 weeks and 13 weeks of age. In both strains, the older animals had significantly higher activities of GABA-T and choline acetyltransferase (ChAc-T). In spite of other enzymatic changes coexisting, the above two enzymes were suggested by discriminant function analysis to be playing a major role in the multiple enzymatic changes in the cerebrum of the animals.

4-Aminobutyrate Transaminase↗
PubMed1990

[Immunohistologic study on focal lymphocytic infiltration in the liver of the elderly autopsy cases].

Immunologic and immunohistologic analyses were performed on lymphocytic infiltration in periportal areas of the liver obtained from 105 autopsy cases over 60 years of age and 63 cases under 60 years of age, all cases showing no symptoms of overt liver diseases. Lymphocytic infiltration in the periportal areas began to be found in the livers of young autopsy cases in the 4th decade, with an incidence of more than 60%. The incidence reached 100% in cases of 6th decade and over, accompanied by increased severity. The infiltrating lymphocytes consisted mainly of T cells, (approximately 85%), regardless of sex, age and underlying diseases. In terms of T cell subsets composing the infiltrating lymphocytes, there were 3 types; A:CD4+ cells greater than CD8+ cells. B:CD4+ cells = CD8+ cells. C:CD4+ cells greater than CD8+ cells. Type A was seen in 60/105 cases (57%), type B in 10/105 (9%) and type C in 35/105 (34%). The presence of cases with predominant CD8+ cells appeared to be characteristic of lymphocytic infiltration lesions in the liver, and was different from lesions in other organs. It was suggested that lesion of lymphocytic infiltration in the periportal areas of the liver might be of an autoimmune nature, gradually advancing with age.

Aged↗
PubMed1990

Effects of intracameral injection of viscoelastic solutions on corneal endothelium in dogs.

Contact in vivo wide-field specular microscopy was performed on right eyes of 20 healthy dogs after sodium hyaluronate (1%, n = 5), sodium chondroitin sulfate (4%) and sodium hyaluronate (3%, n = 5), hydroxypropyl methylcellulose (2%, n = 5), or balanced salt solution (control, n = 5) was injected into the anterior chamber. Using computerized morphometric analysis and pachymetry, changes in endothelial cell density, cell morphologic features, and corneal thickness from baseline values were evaluated at postinjection hour (PIH) 72 and PIH 168. Changes were not seen in endothelial cell density or cell morphologic features in any treated eye. The mean corneal thickness of all treated eyes at PIH 72 increased 6%, significantly greater than that of the nontreated eyes (P = 0.03). Mean corneal thickness of treated and nontreated eyes was similar at baseline and PIH 168 in all treatment groups.

Animals↗
PubMed1990

[Supervised daily mouth-rinsing with a 0.023% weak acid NaF solution. Results of a school-based program started at the age of four].

The principal means of preventing dental caries in Japan are dietary control and tooth-brushing. However, these measures in public health have not been conducive to a definite reduction of dental caries, while the use of fluorides has led to a remarkable and rapid decrease in caries prevalence. Fluoride mouth-rinsing are usually incorporated into the school-based programs. Many trials were carried out in the elementary schools and a 30-50% reduction in caries increment was reported. To provide greater benefits to the permanent teeth, therefore, it is suggested that fluoride mouth-rinsing should be started earlier in the age. However, fluoride mouth-rinsing is not recommended generally for preschool children who cannot rinse out their mouths well. Among the solutions for mouth-rinsing, there are some different types in the fluoride used, the fluoride content and the frequency of application. The most commonly used fluoride mouth-rinsing solution for daily use is 0.05-0.1% NaF in neutral or weak acid solution. The present study was conducted to confirm the fluoride mouth-rinsing with a lower content of fluoride solution would have an additional cariostatic effect if it is started at the age of four. Participants rinsed with a weak acid (pH 5.0) NaF solution (100 ppm F) for 30 seconds 5 times a week. After all, they were received benefits from fluoride before eruption of the permanent teeth. In the present study, it was demonstrated that the effect of dental caries inhibition was greater than those in the previous study. Especially, many lower first molars were free from dental caries. After 7 years, the caries reduction rates were about 48% in DMFT and 54% in DMFS respectively. So far as 4 first molars, the caries reduction rate was about 41% in DMFT, and this figure was almost the same as all DMFT. It was recommended that the fluoride mouth-rinsing program with a lower fluoride content solution should be started at the age of four.

Child↗
PubMed1989

Changes in serum levels of Forssman-like antibody in patients with gastric cancer.

Because Forssman antigen, one of the most well-known heteroantigens, has been noted in certain cancerous tissues, it would seem that the serum levels of the Forssman antibody of patients with these cancers would be low, owing to the absorption of the naturally occurring antibody by the Forssman antigen-containing cancerous tissues. This hypothesis was tested by researchers assessing the serum hemolysin titers of 174 patients with cancer (gastric cancer, 100; colonic cancer, 40; and other cancers, 45) and of 856 age-matched, sex-matched, and blood type-matched healthy individuals against the serum levels of sheep red blood cells. Serum levels of the hemolysin of patients with gastric cancer tend to be lower than those of patients with other types of cancer and also lower than those of age-matched and sex-matched controls. The decrease was especially prominent in patients with moderately differentiated adenocarcinoma of the stomach. Preoperative and postoperative serum samples of 40 patients with gastric cancer were analyzed therefore to determine the effect of surgically removing the cancer on the serum level of the hemolysin. The results showed that the serum levels of the hemolysin antibody increased in all 40 patients after the successful surgical removal of the cancer. However, in patients with recurrence of the cancer, the serum levels of hemolysin decreased again in 11 of 11 patients. These results indicate that the serum levels of the Forssman-like hemolysin could be used as an index of recurrence in patients with gastric cancer after surgical removal of the cancer.

Adenocarcinoma↗
PubMed1989

Tolerance induction in the organ-cultured thymus lobes upon intimate contact with allogeneic thymus lobes.

In an organ-cultured murine fetus thymus, precursor cytotoxic T lymphocytes (pCTL) specific for alloantigens developed successfully but those reactive with self antigens were eliminated. In attempting to dissect the mechanism of self tolerance, intrathymic chimera was made by culturing two genetically disparate thymuses in close contact with each other (parabiosis of thymuses). This maneuver resulted in the induction of specific and mutual CTL tolerance. It seems that CTL tolerance was induced by clonal deletion but not by active suppression. Since 2'-deoxyguanosine treatment abolished the tolerogenic capability of the thymus, hemopoietic cells capable of migrating to and fro in the parabiotic thymuses are thought to be responsible for tolerance induction. Induction of CTL tolerance was dependent on the maturation stages of T cells in the thymus: T cells in 5-day-, but not in 7-day-cultured thymuses were susceptible to tolerance induction, indicating that T cells expressing T cell receptors at low density are susceptible to tolerance induction.

Age Factors↗
PubMed1989

Establishment of a monoclonal antibody against senile plaques and its application for immunohistological and immunoelectron microscopical studies in the brain of the elderly.

A monoclonal antibody (Am-3) was produced against senile plaques in the brain of a patient with Alzheimer's disease. Am-3 was reactive with senile plaques of typical, primitive and diffuse type not only in the brain used as immunogen, but also those in the brain of 15 out of 25 autopsy cases of the aged people. Moreover, Am-3 was also reactive with granular materials of various sizes scattered in the 1st, 3rd and 4th layers of the cerebral cortices of the cases with severe dementia. Am-3 was also reactive with vessel wall of the congophilic angiopathy. By immunoelectron microscopic examination, Am-3 was positive with amyloid fibril in the core and crown of senile plaques, and in the congophilic angiopathy.

Aged↗
PubMed1989

Immunohistological analysis of immigration of thymocyte-precursors into the thymus: evidence for immigration of peripheral T cells into the thymic medulla.

The immigration route of thymocyte precursors into the thymic microenvironment was examined in various experiments using two strains of mice (B10.Thy-1.1 and C57BL/6) that were identical in H-2 and different in Thy-1 locus. The experiment of thymus grafting revealed that there were two types of thymocyte precursors; one immigrated into the cortex and vigorously proliferated and the other directly immigrated into the medulla. Such a direct immigration of host-type cells into the medulla of the grafted thymus was not observed, when thymus was grafted into young adult nude mice having no T cells. When bone marrow cells were iv injected into intact mice, the direct immigration of donor-type cells was observed only in the cortex, not in the medulla. In parabiotic mice, the immigration of partner's cells into the medulla was observed independently before the proliferation of partner's cell in the cortex. These findings taken together indicate that peripheral T cells directly immigrate into and recirculate through the thymic medulla.

Animals↗
PubMed1989

Hypertrophy of the thymus and restoration of immune functions in mice and rats by gonadectomy.

Hypertrophy of the thymus was observed in aging C57BL/6 mice, ranging in age from 4 to 20 months, which had been gonadectomized 2 months before the sacrifice, and the magnitude of thymic regeneration was more pronounced in male than in female. However, enhancement of anti-SRBC antibody response was observed only in female, but not in male mice regardless of age. Gonadectomy brought about not only thymic hypertrophy but also an increase in T cells and B cells in the spleen. An increase in T cell subpopulations was proportional in female mice, but disproportional in male. The disproportional increase of T cell subpopulations could account for the failure to enhance the anti-SRBC antibody response in male mice. Gonadectomy also resulted in the thymic hypertrophy in male and female young Wistar rats, but not in those which had been previously hypophysectomized.

Aging↗
PubMed1989

Combined grafting of bone marrow and thymus, and sequential multiple thymus graftings in various strains of mice. The effect on immune functions and life span.

The combined grafting of young bone marrow and newborn thymus performed in old mice was effective in restoring the impaired immune functions, but the same treatment performed in middle-aged adult mice had no effect on the life span of C3H/MTV female mice. Sequential multiple newborn thymus graftings starting at young adult age were effective in enhancing immunological functions, delaying the onset of tumor and extending the survival rate to certain degree in the first half of the experimental course in both C3H/MTV as well as C57BL/6 mice, but these effects were not observed in the latter half of the experimental course. It was suggested that multiple newborn thymuses sequentially implanted into the peritoneal cavity underwent atrophy and these atrophic thymuses had a suppressive effect on the host immune system. In autoimmune prone B/WF1 mice, however, the combined grafting of young bone marrow and newborn thymus resulted in suppression of antibody formation to SRBC, and single grafting of either young bone marrow or newborn thymus resulted in a trend of increase in the antibody formation to SRBC. The sequential multiple newborn thymus graftings in B/WF1 mice brought about aggravation of kidney diseases and shortening of the mean life span. On the contrary, administration of thymosin in B/WF1 mice resulted in amelioration of kidney disease and elongation of the mean life span.

Animals↗
PubMed1989

Age-associated changes in renal glomeruli of mice.

To investigate age-associated changes in renal glomeruli of C57BL/6 female mice, we used a single radial immunodiffusion method to measure albumin excretion. Up to 100 mg/dl in urine samples was regarded as microalbuminuria. The mean amount of urinary albumin increased from 14.0 mg/dl at 6 months to 151.1 mg/dl at 24 months of age. Microalbuminuria occurred in 64.6% of tested mice by the time they were 24 months old, and 10% of the mice had marked albuminuria (more than 100 mg/dl) at that time. Parallel morphological study showed that renal mesangial changes were also age-dependent. Mesangial cell proliferation and spike lesions in glomerular capillary walls appeared in aged mice with microalbuminuria, and were then followed by diffuse glomerular sclerosis accompanied by marked albuminuria. Histological scores on damage in the renal mesangium with changes of glomerular basement membrane increased significantly with age from a mean score of 0 at 6 months to 3.24 at 24 months of age. Immunofluorescent study showed a marked deposition of IgG and IgM, but no complement component C3 in enlarged mesangium. Electron microscopic examination of diffuse sclerotic glomeruli in aged mice revealed amyloid substances. These results suggest that assays of albuminuria could be a useful method for early detection of age-associated renal deterioration.

Aging↗