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Biomedical subjects

N Itoh

Publications and source records attributed to N Itoh.

At least 433 records · Page 24Linked to original sources
PubMed1991

The assessment of bioavailable androgen levels from the serum free testosterone level.

Recently, it has been concluded that measurement of the serum free testosterone level is crucial for evaluating male gonadal function. However, the extent of the decline of serum free testosterone levels with aging and the actual levels in male infertility have not yet been clearly defined. In this study, the clinical significance of serum free testosterone levels was evaluated in a total of 248 subjects, including 120 healthy adult males (54 males aged 20-39, 26 males aged 40-59 and 41 males aged more than 60), 94 infertile males, 28 male hemodialysis patients, and 6 patients with Klinefelter's syndrome. Since the serum free testosterone levels correlate significantly with serum LH and FSH levels among 120 normal adult males, it appears that free testosterone has a biological action on the organ. In the subjects aged over 60, serum free testosterone levels were significantly decreased compared with the decrease of serum total testosterone. Thus, biologically active androgen levels decreased with aging. Serum free testosterone levels tended to decrease significantly from 40 years onwards. In infertile males, serum total testosterone levels were equal to those in normal adult males, but their serum free testosterone levels were significantly lower. This decrease of serum free testosterone may be one of the causes of their hypospermatogenesis. In male hemodialysis patients, serum total and free testosterone levels were not lower than in normal adult males. It is considered that the decline of percentage of serum free testosterone levels in aged males and infertile males was caused by increased serum sex hormone binding globulin (SHBG) levels. Several workers have shown that the production of SHBG is regulated by sex steroid hormones. In this study, however, serum SHBG levels were not correlated with the E2/T ratio. We concluded that measurement of the serum free testosterone level is of value in the endocrinological evaluation of male gonadal function.

Adult↗
PubMed1991

Effects of sex steroids on immunoglobulin M production by Epstein-Barr virus-transformed B-cell line SKW6-CL4.

The effects of estradiol (E2), progesterone (P), and testosterone (T) on the production of immunoglobulin (Ig) M by Epstein-Barr virus-transformed B-cell line, SKW6-CL4, were investigated. Interleukin 6 (IL-6) induced IgM production by SKW6-CL4 cells in a dose-dependent manner without any significant increase in thymidine incorporation. E2 at concentrations ranging from 10(-10) to 10(-9) M enhanced IL-6-induced IgM production by SKW6-CL4 cells, whereas E2 at a high concentration of 10(-7) M inhibited both the IgM production and the growth of SKW6-CL4 cells. Time-course studies revealed that E2 acts in the early phase of differentiation of SKW6-CL4 cells in response to IL-6. On the other hand, P and T at physiological and superphysiological levels did not influence either the IgM production or the proliferation of SKW6-CL4 cells. These findings suggest a direct immunoregulatory effect of E2 on human B lineage cells and support the concept that E2 may have a role in the pathogenesis of some autoimmune diseases.

B-Lymphocytes↗
PubMed1991

Ultrastructure of matriceal changes in chronic phase of Masugi nephritis by quick-freezing and deep-etching method.

The three-dimensional ultrastructure of glomerular sclerosis in the chronic phase of Masugi nephritis was investigated using a quick-freezing and deep-etching method. Newly formed mesangial matrix, which was increased in the axial portions, was composed of fine fibrillar networks similar to those in the lamina densa of the basement membrane. These fibrils were 10-20 nm in diameter and directly attached to the cell membranes of mesangial cells, endothelial cells and podocytes by connecting fibrils. Moreover, thicker fibrils with diameters of 20-30 nm were present in the networks and were connected with cross-bridges. A newly formed matrix of fine fibrillar networks was also seen in the areas of mesangial interposition in the glomerular capillary wall. The border between the matrix and lamina densa was unclear. The fibrils organizing the networks of lamina densa of the glomerular loop were thickened, with some decoration. Connecting fibrils were disrupted in the areas of endothelial detachment. It is suggested that prolonged tissue injury with endothelial detachment might induce mesangial sclerosis composed of fine fibrillar networks. The increase in density of the networks seemingly interfere with the contractile function of mesangial cells, which is followed by alteration of mesangial flow.

Animals↗
PubMed1991

Three-dimensional ultrastructure of glomerular injury in serum sickness nephritis using the quick-freezing and deep-etching method.

The three-dimensional ultrastructure of the glomerulus in serum sickness nephritis has been investigated by the quick-freezing and deep-etching method. Compact granular immune deposits were localized in filamentous networks in the lamina densa and mesangial matrices. These constitutional fibrils with diameters of 8-15 nm, were directly attached to the immune deposits. The filamentous networks became markedly loosened around the deposits. In podocytes, reticular microfilaments with positive decoration by myosin subfragment 1 (S1) were increased in flattened foot processes and directly attached to the cell membranes. Fine filaments with diameters of 4-7 nm were undecorated by S1 and connected with actin filaments as cross-bridges. Intermediate filaments were also increased in the cell bodies and primary processes of podocytes. Connecting fibrils in lamina rara externa were partially disrupted. The immune deposits were primarily detected in the networks of lamina densa and actually destroyed the size barrier composed of filamentous networks. Moreover, the mesangial deposits also disorganized mesangial networks to probably alter mesangial flow through the matrices. Increased actin filaments in foot processes seemingly reinforced the cell membranes and the connecting fibrils in lamina rara externa, which prevented the initial detachment of podocytes from the basement membrane.

Animals↗
PubMed1991

Masking of anionic sites by deposits in lamina rara externa in immune complex nephritis in rats.

Alterations in glomerular basement membrane (GBM) anionic sites associated with immune deposits (ID) were observed using polyethyleneimine (PEI) as a cationic probe in serum sickness nephritis induced by egg albumin (EA). The anionic sites were fewer in number than in other GBM segments and were irregular in distribution in most, but not all, of the segments of the GBM with ID on the epithelial side of the lamina densa (LD). The disappearance of anionic sites was obvious in areas where the internal aspects of the lamina rara externa (LRE) of the GBM were occupied by ID, even if the ID were very small. In contrast, the disappearance of anionic sites was not evident, even though no change in anionic sites was found in some areas, where the ID had departed from the internal aspects of the LRE and a pale band was seen between the ID and the LD. Further, PEI aggregates, showing localization of anionic sites, were seen within the low density ID, but no PEI aggregates were seen within the high density ID. The results suggest that: 1) whether or not ID induce the disappearance of anionic sites is independent of the size of the ID, but is dependent on the density of and the place occupied by the ID, and 2) the ID seem to induce the disappearance of anionic sites by masking rather than destroying them.

Animals↗
PubMed1991

Two types of autoantibodies to adrenal medullary cells in type 1 (insulin-dependent) diabetic patients: prevalence, properties and implications.

Complement-fixing adrenal medullary antibodies were examined in sera from 170 (114 Type 1 and 56 Type 2) diabetic patients and normal subjects by indirect immunofluorescence methods. Two types of antibodies were detected; one showed a homogeneous immunofluorescence pattern (homogeneous-type) and the other a spotty pattern (spotty-type) in the cytoplasm of adrenal medullary cells. Both antibodies were IgG class and adrenal medulla-specific. The prevalence of the homogeneous-type was significantly higher in Type 1 diabetic patients with disease duration under 1 year (36%) than in those with duration of 1 year or more (1.1%), in Type 2 diabetic patients (1.8%) or in normal subjects (0%; P less than 0.01). Conversely, the prevalence of the spotty-type was not significantly different among all subjects examined (3.6-4.5%). The epitope for the homogeneous-type is likely to be a glycoconjugate since binding of this antibody was abolished after periodate oxidation. The epitope for spotty-type antibody is considered to be a peptide since it was trypsin sensitive. Patients who were positive for the homogeneous-type were also positive for islet cell antibodies, although their antibody titers were not correlated. We conclude that (1) adrenal medullary antibodies are of homogeneous-type or spotty-type and the antigenic determinants of these antibodies are different, and (2) the prevalence of the homogeneous-type is significantly higher in newly diagnosed Type 1 diabetic patients and its presence is associated with that of islet cell antibodies.

Adolescent↗
PubMed1991

Expression of cDNA for batroxobin, a thrombin-like snake venom enzyme.

The cloned cDNA for batroxobin has been expressed in E. coli. Batroxobin could only be obtained as intracellular aggregates of fusion proteins, fused with a small peptide. To obtain the mature batroxobin, the recognition sequence for thrombin was inserted between the peptide and the mature batroxobin. This fusion protein accumulated in an insoluble form and could easily be purified. After site-specific cleavage of the fusion protein with thrombin, recombinant batroxobin was isolated by preparative electrophoresis. Batroxobin with enzymatic activity was obtained by the refolding of recombinant batroxobin.

Amino Acid Sequence↗
PubMed1991

Novel plasmid vectors for gene cloning in Pseudomonas.

Novel host-vector systems have been developed for gene cloning in the metabolically versatile bacterial genus Pseudomonas. We found that a new Pseudomonas strain, Pseudomonas flavida IF-4, isolated from soil, carried two small cryptic plasmids, named pNI10 and pNI20. They were multi-copy, but not self-transmissible, and the genome size was 3.7 kb for pNI10 and 2.9 kb for pNI20. Several types of cloning vectors containing a kanamycin or streptomycin resistance (Kmr or Smr) gene were constructed from pNI10 and pNI20. These plasmid vectors were efficiently transformed into several strains of Pseudomonas at a frequency up to 4 x 10(5) transformants per 1 microgram plasmid DNA by the usual competent cell method. The vectors derived from pNI10 replicated not only in Pseudomonas but also in some other Gram-negative enteric bacteria such as Escherichia coli, Enterobacter aerogenes, and Proteus mirabilis.

Blotting, Southern↗
PubMed1991

Augmentation of antiproliferative activity of CPT-11, a new derivative of camptothecin, by tumor necrosis factor against proliferation of gynecologic tumor cell lines.

The co-operative effects of recombinant human tumor necrosis factor (rH-TNF) and CPT-11, a new derivative of camptothecin, against the proliferation of human gynecologic tumor cell lines were examined in vitro. The ishikawa cells were responsive to rH-TNF, the HHUA cells exhibited a minimal degree of responsiveness to rH-TNF, and the HeLa S3 and Caov-3 cells were unresponsive to rH-TNF. The HHUA, Ishikawa and Caov-3 cells were responsive to CPT-11, and the HeLa S3 cells were relatively sensitive to CPT-11 cytotoxicity. In all four cell lines, rH-TNF at clinically achievable concentrations exhibited synergy with CPT-11. The combination therapy of rH-TNF and CPT-11 will be a new approach against gynecologic cancers.

Antineoplastic Agents, Phytogenic↗
PubMed1991

Small cell carcinoma of the gallbladder combined with adenocarcinoma.

A rare case of small cell carcinoma (SCC) of the gallbladder combined with adenocarcinoma is reported. The patient was a 70-year-old Japanese man, who died of the disease shortly after the onset of symptoms. Autopsy disclosed a small tumor (1.0 cm in longest diameter) in the fundus of the gallbladder, with widespread metastasis. Histochemically, the tumor cells showed negative reactions for argyrophilic and argentaffin stainings, a weak immunohistochemical reaction only for neuron-specific enolase, and negative reactions for all of the other neurosecretory markers used, including neurofilament, chromogranin, somatostatin, gastrin and leu-7. However, electron microscopic examination revealed a few typical neurosecretory granules (NSG) in the cytoplasm of some tumor cells. We suggest that: 1. The presence of NSG in the cytoplasm of tumor cells is the most reliable diagnostic criterion for SCC. 2. SCC, at least the combined type, arises from a multipotential stem cell.

Adenocarcinoma↗
PubMed1991

Diffuse malignant peritoneal mesothelioma in a young woman with a high serum level of CA125.

An autopsy case of diffuse malignant peritoneal mesothelioma in a young woman who showed a high serum level of CA125 is reported. Autopsy revealed extensive tumor involvement of the visceral and parietal peritoneum. The liver, spleen and other abdominal viscera were encased by tumor nodules. Histologically, the polygonal tumor cells were arranged mostly in a sheet-like fashion with a few tubular or papillary forms. No PAS reaction-positive mucin was recognized, but there was a strongly positive colloidal iron reaction. The colloidal iron positivity was effaced after combined treatment with hyaluronidase and sialidase. Immunohistochemically the tumor cells showed strongly positive reactions for CA125, epithelial membrane antigen (EMA) and cytokeratin, weak positivity for carcinoembryonic antigen (CEA) and focal positivity for vimentin. Ultrastructurally, the most characteristic feature was the expression of numerous long microvilli projecting from the tumor cell surfaces and abundant long desmosomes between the tumor cells. We consider that pretreatment using a combination of hyaluronidase and sialidase might be useful for the diagnosis of malignant mesothelioma. CA125 staining should be performed routinely in cases where this tumor is suspected.

Adolescent↗
PubMed1991

Peritoneal fluid interleukin-1 beta and tumor necrosis factor in patients with benign gynecologic disease.

The levels of interleukin 1 beta (IL-1 beta) and tumor necrosis factor (TNF) in peritoneal fluid (PF-IL-1 beta and PF-TNF) and production of IL-1 beta and TNF by peritoneal macrophages were determined in patients with benign gynecologic disease. The level of PF-IL-1 beta was elevated in the acute pelvic inflammatory disease (PID) and stages I and II endometriosis (E I/II) groups compared with the normal pelvis group, but not in the myoma of the uterus, ovarian cyst, and postinflammatory pelvic adhesion groups. The level of PF-TNF was elevated in the PID, EI/II and stages III and IV endometriosis (EIII/IV) groups. There was no correlation between the levels of PF-IL-1 beta and PF-TNF. Neither the level of PF-IL-1 beta nor that of PF-TNF was correlated with the concentration of peritoneal macrophages. Peritoneal macrophages produced IL-1 beta and TNF in vitro in the absence of stimulants. The levels of PF-IL-1 beta and PF-TNF are presumably linked to the activation of peritoneal macrophages.

Adult↗
PubMed1991

Interferon-gamma inhibits thyroid-stimulating hormone-induced morphological changes and induces the expression of major histocompatibility complex class II antigen in thyroid follicles in suspension culture.

The effects of interferon-gamma (IFN gamma) on the morphology of thyroid follicles and the expression of major histocompatibility complex (MHC) class II antigens were examined. The thyroid follicles were suspended in RPMI-1640 containing 10% fetal calf serum with or without IFN gamma (200 U/ml). After culture for 5 days, follicles were incubated in the presence of TSH (10 mU/ml) for 1 h and fixed for electron microscopic and immunohistochemical examination. Regardless of the presence of IFN gamma, suspended follicles became inverted within 5 days. However, MHC class II antigens were expressed only in inverted follicles cultured with IFN gamma. In inverted follicles cultured without IFN gamma, TSH stimulation induced remarkable morphological changes, such as elongation of microvilli and an appearance of pseudopods. On the other hand, the follicles cultured with IFN gamma showed poor response to TSH. Thus, IFN gamma induced the expression of MHC class II antigens of cultured thyroid follicles and inhibited TSH-induced morphological changes in the cells.

Animals↗
PubMed1991

Angiotensinogen excretion in rat urine: effects of lipopolysaccharide treatment and sodium balance.

Rat urine was found to contain a component showing cross-reactivity with antibody against rat plasma angiotensinogen. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of rat urine revealed antigenic bands corresponding to the molecular weights of plasma angiotensinogen. The urinary angiotensinogen excretion in 8 rats, determined by direct radioimmunoassay, was 2.70 +/- 0.21 micrograms/day. Induction of acute inflammation in rats by injection of lipopolysaccharide caused about a 7-fold increase of urinary angiotensinogen excretion in the 24 hr after injection, with a concomitant elevation of plasma angiotensinogen. Neither sodium depletion nor loading by a low- or high-sodium diet altered the urinary excretion of angiotensinogen. These results suggest that the angiotensinogen present in rat urine is derived from that in plasma, although the level of excretion is too low to have any influence on the plasma level of angiotensinogen.

Angiotensinogen↗
PubMed1991

[Treatment of newly diagnosed stage D2 prostatic carcinoma with hormonal therapy alone, or chemotherapy agents in combination with hormones].

From June 1984 to March 1988, patients with newly diagnosed stage D2 prostate cancer were treated with protocol 1. This comprised oral hormonal agents either diethylstilbestrol diphosphate (Honvan: 300 mg/day) or estramustine phosphate (Estracyt: 560 mg/day), or chlormadinone acetate (Prostal: 100 mg/day), plus intravenous cyclophosphamide (CPM, 0.5-1 g/m2) every 3-4 weeks. From May 1988, protocol 2 was used in a randomized study of castration alone versus castration plus intravenous methotrexate (MTX, 20 mg/m2) every 2 weeks. Forty-nine of 53 patients who underwent the two protocols were evaluable for the response. The response rates according to the NPCP criteria were 92% (11/12) for Honvan, 100% (9/9) for Estracyt, 78% (7/9) for Prostal and castration plus MTX, and 80% (8/10) for castration alone. There were no significant differences among these treatments. The median response duration and survival time (months) were 16 and 44, respectively, for Honvan, 19 and 37 for Estracyt, 12 and 43 for Prostal, 11 and 15 for castration plus MTX, and 13 and 13 for castration alone. The short survival times of the castration alone and castration plus MTX groups were due to a short follow-up period. There were no statistical differences among the oral hormonal agent plus CPM groups. However, the 2-year survival rate (Kaplan-Meier method) was higher in the CPM and MTX groups than in the castration alone group. Survival was longer in the good performance status (P.S.) group than the poor P.S. group (p less than 0.05 by Wilcoxon test) and in the responders than the non-responders (p less than 0.01). Side effects were not excessive in the chemotherapy groups and patient compliance was good.

Administration, Oral↗
PubMed1991

[Clinical significance and usefulness of measuring nocturnal penile tumescence in children].

Nocturnal penile tumescence (NPT) is a physiological phenomena that is recognized in almost all normal males. This paper presents a study of NPT and the relation of this phenomenon to age, sexual maturation and physical growth in children. In 30 subjects, ranging from 3 to 18 years old, NPT was measured continuously throughout the night. The following results were obtained: 1. The frequency of NPT had a tendency to increase with age with a maximum frequency at 13 or 14 years of age, although the frequency ranged widely. 2. The maximum increase in penile circumference was below 10 mm in all cases below 10 years of age but was greater in children over 12 years old. 3. Tumescence time and percent tumescence time [tumescence time (min.)/sleep period time (min.)] x 100) was greater in children of over 12 years of age. Percent tumescence time showed a positive correlation with serum LH. Percent tumescence time was clearly higher in children with LH pulse, which indicates the onset of puberty, than in those without it. 4. These results suggest that NPT measurement in children can predict the onset of puberty, when coupled with endocrinological findings.

Adolescent↗
PubMed1991

[Therapeutic efficacy of testolactone (aromatase inhibitor) to oligozoospermia with high estradiol/testosterone ratio].

To our knowledge, the action of estradiol which is produced from testosterone by aromatase on human spermatogenesis has not been fully clarified. In oligozoospermia, with high values of E2/T ratio, it is considered that the role of estradiol is suppressive to spermatogenesis. In this study, alteration of spermatogenesis was evaluated when serum estradiol levels were decreased by suppression of aromatase activity. Nine male infertile patients were treated with testolactone (Teslac: 1.0 g/day, for 3 months), one of the aromatase inhibitors. Four of them had an increase in sperm count (more than 10 x 10(6)/ml relative to base line). In endocrinological findings, serum estradiol levels and E2/free T ratio were significantly decreased after treatment. Serum free testosterone levels were significantly increased in all cases, presumably from decreased sex hormone binding globulin (SHBG) levels. These findings suggested the effectiveness of the administrated aromatase inhibitor. In particular four patients whose sperm counts were improved after testolactone treatment had high values of basal serum estradiol levels and E2/free T ratio before treatment, and these values were normalized after treatment. In conclusion we suggest that an aromatase inhibitor may be effective to male infertile patients with high serum estradiol levels.

Adult↗