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Biomedical subjects

K Sawada

Publications and source records attributed to K Sawada.

At least 271 records · Page 15Linked to original sources
PubMed1991

Fibrinogen date: congenital hypodysfibrinogenemia associated with decreased binding of tissue-plasminogen activator.

A new case of congenital hypodysfibrinogenemia associated with a thrombotic tendency (thrombosis of the peroneal artery, the pulmonary artery and the deep veins of the lower extremities), is reported. Clotting time using Reptilase was significantly prolonged. The low levels of plasma fibrinogen were demonstrated using both thrombin time (Clauss) method (45.0 mg/ml) and radial immunodiffusion technique (106.1 mg/ml). The fibrinogen is also characterized by a defective polymerization of fibrin monomers. Furthermore, the important functional property of this fibrinogen is that the patient's fibrin adsorbs approximately 31-38% of added tissue-plasminogen activator (t-PA) at the time of fibrin formation, whereas control fibrin can adsorb about 79% of added t-PA. This result could provide an explanation for the thrombotic tendency in this patient. This variant fibrinogen appears to have unique characteristics and has been designated as "Fibrinogen Date," according to the city where the proband has lived.

Afibrinogenemia↗
PubMed1991

Transitional change of colony stimulating factor requirements for erythroid progenitors.

The course of the differentiation and proliferation of the human erythroid burst-forming units (BFU-E) to colony-forming units (CFU-E) was directly investigated using a combination of highly purified BFU-E, a liquid culture system, and the following clonal assay. Highly purified human blood BFU-E with a purity of 45-79% were cultured in liquid medium with recombinant human erythropoietin (rEP) and recombinant human interleukin-3 (rIL-3) to generate more differentiated erythroid progenitors. The cultured cells were collected daily for investigating the morphology, the increment in the number of cells and the clonality. Ninety percent of purified BFU-E required not only rEP but also rIL-3 for clonal development. By 7 days of liquid culture, the total cell number increased 237 +/- 20-fold above the starting cells, while erythroid progenitors increased 156 +/- 74-fold. As the incubation time in liquid culture increased, the cells continuously differentiated in morphology. Replating experiments with rEP combined with or without rIL-3 showed the following: 1) The number of erythroblasts that were part of erythroid colonies decreased with accompanying erythroid progenitor differentiation and proliferation. 2) As the incubation time in liquid culture increased, erythroid progenitors had a graded loss of their dependency on rIL-3 and a complete loss of dependency was observed after 3 days of liquid culture. At that time 85% of the erythroid progenitors gave rise to colonies of more than 100 erythroblasts which were equivalent to mature BFU-E. These studies provide a quantitative assessment of the loss of IL-3 dependency by BFU-E and indicate that the size of the generated erythroid colonies and their IL-3 requirement correlate with the erythroid differentiated state.

Adult↗
PubMed1991

Rapid detection of a point mutation in thyroid-stimulating hormone beta-subunit gene causing congenital isolated thyroid-stimulating hormone deficiency.

Previous study showed that congenital isolated TSH deficiency in Japan is resulted exclusively from a G-A transition at nucleotide 145 in exon 2 of the TSH beta-subunit gene. All reported cases were from the inbred in Shikoku Island. We describe here a 10-year-old boy with hereditary TSH deficiency in the same area. The patient was born with a weight of 3,225 g to non-consanguineous parents. Evaluation at age 2 months revealed typical manifestations of cretinism without goiter. Serum T4, T3, and TSH values were 2.53 micrograms/dl, 107 ng/dl, and 0.5 microU/ml, respectively. A TRH stimulation test showed no increment of serum TSH value. Other anterior pituitary hormone levels were all within the normal range. Two oligonucleotide primers T1a and T1b were synthesized according to the sequence data. Amplified 169 bp nucleotides in exon 2 of the TSH beta gene with this primer set were digested with MaeI. Both the phenotypically normal brother and normal controls showed only the 169 bp fragment, whereas the proband showed 140 and 29 bp fragments and both parents showed three fragments; 169, 140, and 29 bp. These results were consistent with the point mutation of TSH beta gene in Japanese patients with congenital isolated TSH deficiency. Our PCR method with MaeI digestion contributes to the rapid detection of the homozygous patient and the heterozygous carrier.

Child↗
PubMed1991

Architecture of myocardial cells in human cardiac ventricles with concentric and eccentric hypertrophy as demonstrated by quantitative scanning electron microscopy.

Scanning electron microscopy (SEM) was used to compare the shapes, size, and connections of cardiocytes in the midwall myofibers in the left ventricles of 5 normal hearts (266 +/- 16 g), 5 hears with concentric hypertrophy (564 +/- 99 g) and 5 with eccentric hypertrophy (651 +/- 114 g), obtained at autopsy and fixed in formalin. In the myofibers from normal and hypertrophied hearts, intercalated discs demarcated cardiocytes which consisted of a cylindrical trunk and one or more series and/or lateral branches; cell connections at the intercalated discs had 6 common basic patterns. The length (L), width (W) and L/W ratio of the cells and the size and number of the series and lateral branches per cell were measured in 50 cells from each heart and averaged for comparison studies. The cells in the concentrically hypertrophied ventricles were much thicker than normal (33.0 +/- 2.8 vs 18.2 +/- 1.4 microns, P less than 0.01) but not significantly longer (81.2 +/- 9.5 vs 71.2 +/- 9.6 microns, NS), so that the L/W ratio was greatly decreased (2.6 +/- 0.3 vs 4.1 +/- 0.7, P less than 0.01). The cells in the eccentrically hypertrophied ventricles were markedly thickened (25.9 +/- 2.4 microns, P less than 0.01) and elongated (4.2 +/- 0.4, NS) remained the same as in normal hearts. In both types of hypertrophy, series and lateral branches were significantly thicker and longer than in normal hearts; the number of series branches per cell was also significantly increased. The number of lateral branches per cell did not differ between the normal and concentrically hypertrophied hearts (2.2 +/- 0.7 vs 2.3 +/- 0.6, NS), but it was decreased by approximately one-half in the eccentrically hypertrophied hearts (1.2 +/- 0.3, P less than 0.05). The potential significance of these differences in SEM findings of cardiocytes is discussed with special reference to the differences in the cause, anatomy, and pathophysiology of concentric and eccentric hypertrophy in adult human hearts.

Adult↗
PubMed1991

Study of crystallin expression in human lens epithelial cells during differentiation in culture and in non-lenticular tissues.

Crystallin expression in human lens epithelial cells in culture and a number of non-lenticular tissues was studied by the technique of immunoblotting using monoclonal antibodies. The expression of alpha A, beta 5 and beta 6 crystallins per unit number of cells increased with passage number while alpha B appeared to be constant Lentoid bodies derived from cultured human lens epithelial cells not only expressed gamma-crystallin and MP26 as previously demonstrated, but also produced alpha A, alpha B, beta 5 and beta 6 crystallins. In human non-lenticular tissues including ciliary body, vitreous body, neural retina, cultured retinal pigment epithelial cells and scleral fibroblasts, alpha B-crystallin was detected, but was undetectable in cornea and iris. Alpha A was present only in the lens. These studies demonstrate that HLE cells maintain the ability to synthesize crystallins through several passages. Following differentiation, they not only synthesize gamma-crystallin and MP26 but continue to express alpha- and beta-crystallins similar to differentiated lens fiber cells in vivo. Consistent with previous observations, the expression of alpha B-crystallin does not appear to be specific for the lens.

Cell Differentiation↗
PubMed1991

Suppressive effect of wasabi (pungent Japanese spice) on gastric carcinogenesis induced by MNNG in rats.

Dietary habits have been causally implicated in gastric carcinogenesis, whereas minor dietary items may also play a part. Wasabi is a popular pungent spice in Japanese meals. In this study the effect of wasabi on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis was studied in rats. Wistar WKY male rats received drinking water containing 50 micrograms/ml of MNNG or tap water alone and a basal diet (PCE-2) or PCE-2 containing 10% (wt/wt) of wasabi powder for 40 weeks. Thus, three groups were completed as MNNG + PCE-2 (n = 30), MNNG + wasabi (n = 30), and tap water + wasabi (n = 30). At autopsy, nine rats (30%) had seven glandular stomach tumors (2 adenocarcinomas, 2 adenomatous polyps, and 3 adenomatous glandular hyperplasias) and three duodenal adenocarcinomas in the MNNG + PCE-2 group, whereas in the MNNG + wasabi group, two rats (7%) had one forestomach epidermoid cyst and one duodenal carcinosarcoma (corrected chi 2 = 4.63, p less than 0.05 for incidences of glandular stomach tumors between 2 groups). In addition, two rats had microscopic atypical glands in the MNNG + PCE-2 group. There was no tumor in the tap water + wasabi group. These results indicated that glandular stomach carcinogenesis induced by MNNG was suppressed by the administration of wasabi.

Adenocarcinoma↗
PubMed1991

White-spotting mutations affect the regenerative differentiation of testicular germ cells: demonstration by experimental cryptorchidism and its surgical reversal.

The effect of white-spotting (W) mutations on differentiation of testicular germ cells was investigated by using experimental cryptorchidism and its surgical reversal. All mutant mice used in this study (Wv/+, Wsh/+, Wf/+ and Wf/Wf) showed normal fertility and well-ordered spermatogenesis, as in congenic +/+ mice. In the cryptorchid testis, which contains only type A spermatogonia as germ cells, the number and the proliferative activity of type A spermatogonia in mutant mice were comparable to +/+ mice. On the other hand, surgical reversal of the cryptorchid testis in mutants resulted in impaired regenerative differentiation of germ cells. Although complete recovery of spermatogenesis was observed in +/+ mice, testicular weight in Wsh/+, Wf/+ and Wf/Wf mice recovered to approximately 60-70% of intact levels, and some portions of seminiferous epithelium showed incomplete spermatogenesis. In Wv/+ mice, however, ability to recover the weight was completely lost, and only type A spermatogonia existed as germ cells in seminiferous tubules 3 mo after surgical reversal. These results suggest that W mutation affects the differentiation through type A spermatogonia to type B spermatogonia, indicating the functional significance of W (c-kit) in early spermatogenesis.

Animals↗
PubMed1991

Effects of castration and sex steroids on sexually dimorphic development of the mouse submandibular gland.

The aims of this study were to characterize sexual dimorphism in the submandibular glands of young adult mice and to determine how sex differences arise during postnatal development. In the mouse submandibular glands, prominent sexual dimorphism was observed at 30 days of age, when the male gland was superior in both the relative occupied area (ROA) and the mitotic rate of the granular convoluted tubules (GCT) to those of the female. By neonatal castration, this sexual dimorphism was abolished, and the intraglandular structures of castrated males were similar to those of normal females. In castrated mice of both sexes, daily treatment with testosterone and 5 alpha-dihydrotestosterone for 10 days from 20 days induced only the ROA of the GCT to increase to the normal male levels but not those of the other three regions of the glands, the acini, intercalated ducts and excretory striated ducts. Testosterone responsiveness of the glands, considering both the glandular weight gain and the mitotic rate of the GCT, was significantly higher in castrated males than in castrated females. On the other hand, 17 beta-estradiol had no effect on the glands of castrated mice. Therefore, the present study suggests that the testicular hormones are responsible for the masculine development of GCT of the glands, but not the ovarian hormones, and that there is a sex difference in the responsiveness of the glands to testosterone, which is more effective in males than in females.

Animals↗
PubMed1991

Effect of the W mutation, for white belly spot, on testicular germ cell differentiation in mice.

The effect of the mutation for white belly spot controlled by the dominant gene W on spermatogenesis in mice was examined by experimental cryptorchidism and its surgical reversal. The course of spermatogenesis from spermatogonia to spermatid was normal in intact testes of W/+ mice. In cryptorchid testes, there was no difference in the number and activity of Type A spermatogonia between the testes of W/+ and +/+ mice, in mitotic and labelling indices. Although surgical reversal of the cryptorchid testis resulted in regenerative differentiation of germ cells in both genotypes, the recovery of cell differentiation in the W/+ testis was slower than in the +/+ testis. There were fewer germ cells, such as intermediate-Type B spermatogonia or more advanced ones, in W/+ testes. On Day 17 after surgical reversal, cell associations in W/+ testes were abnormal and the numbers of intermediate-Type B spermatogonia, spermatocytes and spermatids were approximately 70, 50 and 15%, respectively, of those in +/+ testes. These results indicate that the W gene affects spermatogenic cell differentiation in adult mice.

Animals↗
PubMed1991

Decreased prolactin level in secretory granules and their increased exocytosis in estrogen-induced pituitary hyperplasia in rats treated with a dopamine agonist.

Treatment with bromocriptine (CB) stimulates the release of secretory granules from human prolactinomas by exocytosis in spite of a remarkable decrease in serum prolactin (PRL) levels. In an attempt to elucidate the reasons for this phenomenon, secretory granules were analyzed in estrogen-induced pituitary hyperplasia in rats which served as a model of human disease. The amount of protein contained in cell fractions rich in secretory granules was the same in CB-treated pituitaries as that in the controls, whereas PRL levels decreased to about a half the level of the controls. Morphometric analysis using point-counting and electron immunocytochemistry revealed that the PRL concentrations in secretory granules decreased to about 50% after CB-treatment. Serum PRL levels estimated by counting the exocytotic secretory granules were remarkably lower in CB-treated rats than in the controls. It was suggested that the composition of secretory granules changed or that nonhormonal constituents in the granules disintegrated more slowly after CB treatment, thus allowing exocytosed granules to be observed more frequently. Additionally CB might also suppress a bypass release of PRL by which PRL is secreted without being packaged into secretory granules.

Animals↗
PubMed1991

Helicobacter pylori is not a co-carcinogen in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis.

Helicobacter pylori was implicated in gastric carcinogenesis through the induction of metaplasia of the gastric mucosa. In this experiment a co-carcinogenic effect of H. pylori on chemically induced gastric carcinogenesis was examined. Wistar WKY male rats received drinking water containing 50 mg/l of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and intragastric administration of 10(6) to 10(8) colony forming unit of H. pylori thrice a week for 40 weeks. Thus, 3 groups were assigned as Group I; MNNG alone, Group II; MNNG + vehicle, and Group III; MNNG + H. pylori (n = 30, each). At autopsy, 9 rats (30%) had 7 glandular stomach and 3 duodenal tumors in Group I, and 10 rats (33%) had 8 glandular stomach and 2 duodenal tumors in Group II, whereas in Group III 4 rats (13%) had 2 glandular stomach and 2 duodenal tumors (chi 2 = 4.257, P < 0.15 for the incidences of glandular stomach tumors among 3 groups). The finding seems to suggest that H. pylori has an ambitendency in the gastritis-metaplasia-carcinogenesis sequence as a promoter for the induction of the predisposing mucosa and as an inhibitor against certain carcinogens.

Animals↗
PubMed1991

[Anesthetic management of caesarean section for the delivery of quadruplets].

Multiple gestation pregnancies are accompanied with risks for both mother and fetuses. Morbidity and mortality of both of them are increased compared with singleton pregnancies. We have presented a case of a 30-year-old parturient with quadruplets. The pregnancy had been complicated by premature labour, anemia, toxemia, coagulopathy, pulmonary congestion and malpresentation. On the 29th week of pregnancy, an elective Caesarean section was scheduled. There is no ideal anesthetic technique for quadruplets. In this case general anesthesia was chosen, because she had coagulopathy. The anesthesia and postoperative course were uneventful. The patient and the four babies had no complication nor sequela on their discharge. The anesthetic considerations for multiple gestation pregnancies were also discussed.

Adult↗
PubMed1991

Rapid improvement in a patient with leukocytoclastic vasculitis with secondary mixed cryoglobulinemia treated with cryofiltration.

A patient with leukocytoclastic vasculitis (LCV) with secondary mixed cryoglobulinemia was treated by cryofiltration in an effort to stop the progression of the disease despite the use of high dose prednisone. Three cryofiltration procedures within one week were performed on this patient. Clinical assessments made through the course of this therapy and the followup period showed excellent response. Peripheral blood mononuclear cell transformation functions (MNC-TF) were evaluated at the pre-1st and post-2nd cryofiltration treatment. MNC-TF pretreatment were significantly suppressed. Post-2nd cryofiltration, MNC-TF were improved. Our study demonstrates that cryofiltration is a safe and effective treatment of a patient with LCV with secondary mixed cryoglobulinemia, without requiring plasma replacement products.

Adolescent↗
PubMed1990

1 Alpha-hydroxyvitamin D3 suppresses colonic tumorigenesis induced by repetitive intrarectal injection of N-methyl-N-nitrosourea in rats.

The effect of 1 alpha-hydroxyvitamin D3 (1 alpha (OH)D3) on colonic tumorigenesis induced by chronic treatment with N-methyl-N-nitrosourea (MNU) was studied in rats. Seventy-four female F344 rats received an intrarectal injection of 1 mg of MNU once a week for 40 weeks. Two-thirds of rats were given concomitant administration of 0.2 ml of medium chain triglyceride (MCT) or MCT containing 0.04 microgram of 1 alpha (OH)D3 through an intragastric route thrice weekly. Numbers of rats bearing colonic tumor were 21 in MNU alone (n = 24), 17 in MNU + MCT (n = 25) and 12 in MNU + 1 alpha (OH)D3 group (n = 25) (uncorrected chi 2 = 8.72). The result indicated that colonic tumorigenesis induced by the chronic treatment with MNU was suppressed by oral supplementation of 1 alpha (OH)D3 and the inhibitory effect of 1 alpha (OH)D3 was partly due to the effect of MCT.

Adenoma↗
PubMed1990

Purification of human blood burst-forming units-erythroid and demonstration of the evolution of erythropoietin receptors.

To facilitate the direct study of the molecular events that control the development of human burst-forming units-erythroid (BFU-E), we have developed a method to purify BFU-E from peripheral blood. Using density centrifugation, rosetting with a mixture of neuraminidase-treated and IgG-coated sheep erythrocytes, positive panning with anti-My10 monoclonal antibody, overnight adherence to plastic dishes, negative panning with monoclonal antibodies, and density centrifugation, human blood BFU-E were purified from 0.04% to 56.6%, a 1,400-fold purification with a 13% yield. More than 90% of purified BFU-E were recombinant interleukin-3 (rIL-3) dependent, which survived for 48 h with rIL-3 in the absence of recombinant erythropoietin (rEP), and 80% gave rise to erythroid bursts of more than 500 hemoglobinized cells. rEP dependency was not evident until after 72 h of incubation in vitro. The purified cells (day 1) were incubated with rIL-3 and rEP in liquid culture for 24 (day 2), 48 (day 3), and 72 (day 4) h and then were transferred into semisolid cultures and incubated until day 15. The size of the erythroid colonies observed in semisolid cultures decreased continuously in association with the incubation time of day 1 purified cells in liquid cultures. The first appearance of colony-forming units-erythroid (CFU-E) that gave rise to colonies of 8 to 49 cells was observed after 72 h of incubation of day 1 cells in the liquid culture. 125I-rEP was incubated for 5 h at 37 degrees C with purified cells (day 1) or with the cells that had been incubated in liquid culture for an additional 24-72 h, and the presence of erythropoietin (EP) receptors was investigated using autoradiography. Specific binding of 125I-rEP was detected in 19 +/- 7% of the initial day 1 BFU-E. The percentage of 125I-rEP-binding to erythroid progenitor cells and the amount of binding continuously increased as day 1 BFU-E matured. 125I-rEP specific binding was observed with all of the erythroid progenitor cells that had been incubated in liquid culture for 72 h. These data demonstrate that primitive BFU-E have a much lower number of EP receptors than CFU-E and develop an increased concentration of EP receptors in association with their maturation and loss of proliferative capacity.

Adult↗
PubMed1990

Erythropoietin: receptors and clinical use in rheumatoid arthritis.

Erythropoietin (Epo) receptors have been delineated using radioiodinated recombinant erythropoietin (rEpo) and highly purified murine and human erythroid colony-forming units (CFU-e). The murine CFU-e had 950 receptors/cell. One-third had a Kd of 0.09 nM while two-thirds had a Kd of 0.57 nM. Human CFU-e had 1,050 receptors/cell. Two hundred had a Kd of 0.10 nM and 850 had a Kd of 0.57 nM. 125I-rEpo was rapidly internalized and degraded by the CFU-e. Cross-linking of 125I-rEpo to human Epo receptors demonstrated two proteins of 100 and 90 kDa and proteolytic peptide mapping of each protein showed identical fragments indicating that they are very similar. rEpo was also used to treat patients with the anemia of rheumatoid arthritis, and one case is presented in which the patient's hematocrit rose from 32.5% to 44% in eight weeks. When the rEpo was discontinued, the hematocrit fell back to 33%.

Aged↗