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Biomedical subjects

K Iwasa

Publications and source records attributed to K Iwasa.

At least 55 records · Page 3Linked to original sources

Gamma aminobutyric acid immunoreactivity in the mouse adrenal gland during postnatal development.

To understand the developing processes of gamma-aminobutyric acid (GABA)-containing chromaffin cells and nerve fibers in the mouse adrenal gland, we examined the tissues in various postnatal stages by immunohistochemistry using a GABA antibody. From birth until postnatal week 1, GABA-immunoreactivity was seen in very few nerve fibers, and in none of the chromaffin cells. At postnatal week 2, GABA-immunoreactivity appeared weakly in clusters of chromaffin cells and strongly in relatively numerous varicose nerve fibers. The immunoreactive nerve fibers were densely distributed in the small immunonegative chromaffin cells and large ganglion cells, but only sparsely so in the weak immunoreactive chromaffin cells. At postnatal week 3, the number of the immunoreactive chromaffin cells and nerve fibers further increased compared to that at postnatal week 2. The staining pattern of GABA-immunoreactive nerve fibers in the medullas was similar to that at postnatal week 2. From postnatal week 4 until postnatal week 8, the distribution and frequency of the immunoreactive chromaffin cells and nerve fibers were also similar to those at postnatal week 3. These results suggest that the expression of GABA in the chromaffin cells and in the nerve fibers of the mouse adrenal gland may be completed by postnatal week 3.

Adrenal Glands↗

FK506 prevents induction of rat experimental autoimmune myasthenia gravis.

Myasthenia gravis (MG) is an organ-specific autoimmune disease attacking nicotinic acetylcholine receptors (AChR) of the neuromuscular junction. Autoantibody production is regulated by autoimmune helper T cells that are specific to AChR. Therefore the suppression of autoimmune T cell activity could reduce myasthenic symptoms. Amongst immunomodulatory therapies aimed at T cells, we studied the therapeutic effect of FK506 as a T cell-specific immunosuppressive agent. Rats in which experimental autoimmune myasthenia gravis (EAMG) was induced by immunization with synthetic peptide of human AChR alpha-subunit residues 125-147 (H alpha 125-147) were treated daily with FK506 (1 mg/kg). FK506 prevented the reduction in amplitude of miniature endplate potential (MEPP) which was induced by H alpha 125-147 immunization. FK506 also suppressed anti-H alpha 125-147 and anti-rat AChR antibody production accompanied by a decrease in the antigen-specific T cell response against H alpha 125-147. These findings indicate that FK506 prevents induction of rat EAMG evoked by immunizing T cells against H alpha 125-147.

Amino Acid Sequence↗

Leiomyosarcoma of the colon presenting as acute suppurative peritonitis.

A surgical case of leiomyosarcoma arising from the ascending colon, presenting as acute suppurative peritonitis, is herein described. A 70-year-old woman complaining of lower abdominal pain presented to our clinic on October 12, 1994. She was admitted with a tentative diagnosis of peritonitis. At emergency laparatomy, purulent intraabdominal fluid was present, and a fist-sized mass was seen in the ascending colon just proximal to the hepatic flexure. A right hemicolectomy was thus performed based on a diagnosis of perforating colon cancer. The histologic findings were consistent with leiomyosarcoma with abscess formation in and around the tumor. Five mitotic figures per field were observed at 10x magnification. Immunohistochemical studies revealed immunoreactivity for alpha-smooth muscle antigen (alpha-SMA), vimentin, and desmin. After reviewing the clinicopathologic characteristics of colon leiomyosarcoma as described in 78 Japanese cases and 70 cases from the foreign literature, we thus propose that colon leiomyosarcoma frequently arises from the transverse colon. In addition, our case also represents the only reported case in Japan in which an adult patient underwent a successful operation for perforated leiomyosarcoma of the colon.

Acute Disease↗

Antimicrobial activity of some 13-alkyl substituted protoberberinium salts.

Several 13-alkyl substituted analogs of berberine and palmatine were found to be highly active against two types of Staphylococcus aureus (S1 and S2) of different origin. The most active 13-hexylberberine was 8 times more active (against S1) and the same order active (against S2) as kanamycin sulfate. 13-Hexylpalmatine displayed an activity against S. aureus (S1) 4 times greater than that of kanamycin sulfate. The activities of 13-hexylberberine against two types of S. aureus were 64 and 128 times greater than those of the clinically used alkaloid berberine. Additionally two hexyl derivatives possessed antifungal activity.

Berberine↗

Morphological study of bovine pregnant corpus luteum cells.

The bovine pregnant corpus luteum was examined morphologically, to clarify the appearance and properties of the intramitochondrial bodies (IMB) in mitochondria of the large luteum cell (LLC). The incidence and diameter of the IMB (200-900 nm) showed a tendency to increase with the advance of pregnancy. Histochemically, the IMB reacted positively with protein, and immunohistochemically, they reacted IMB with 11 alpha-hydroxyprogesterone-1-11 succinyl-bovine serum albumin (P-BSA). The IMB seemed to combine with protein, and these granules did not undergo exocytosis. The cytoplasm of LLC contained another type of small electron-dense granules that were 150-200 nm in diameter, had an orifice for secretion, and reacted with relaxin. Small luteum cells (SLC) revealed crystalline-like inclusions. It is suggested that these inclusion cells participate in the synthesis of steroids.

Animals↗

Antibodies to synthetic peptides of the alpha1A subunit of the voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome.

To search for antigenic sites in the molecular structure of alpha1A subunit of the voltage-gated calcium channel (VGCC) (P/Q-type) in the Lambert-Eaton myasthenic syndrome (LEMS), we studied by immunoprecipitation assay serum samples from 30 LEMS patients (16 with small cell lung carcinoma (SCLC), 20 disease controls (10 with SCLC without LEMS and 10 with myasthenia gravis), and 15 healthy controls. Synthetic peptide antigens corresponded to the extracellular region (S5-S6 linker region) of each of the four domains forming the alpha1 subunit of P/Q-type VGCC. In addition, we studied serum samples for anti-P/Q-type VGCC antibodies by using omega-conotoxin MVIIC-labeled extract of human cerebellum as an antigen. Among sera of 30 LEMS patients, nine samples (30%) (six with SCLC) were positive for antibodies to the domain IV S5-S6 linker peptide, and six samples (20%) (five with SCLC) were positive for antibodies to the domain II S5-S6 linker peptide. Only two of 15 antipeptide-positive sera were positive for both antibodies. Titers for antibodies to domain IV, as well as those for antibodies to domain II, correlated with those of anti-P/Q-type VGCC (human cerebellum extract) antibodies. The antipeptide antibody was present in only one of 20 disease controls, a patient with SCLC without LEMS. Our observations suggest two potential epitopes of LEMS antibodies.

Antibodies↗

[Molecular biology and immunology of acetylcholine receptor in relation to myasthenia gravis].

In search for the myasthenogenic sites in the molecular structure of acetylcholine receptor (AChR) alpha-subunit, the conformation-dependent B-cell epitopes, and the MHC class II-restricted, immune cofactors-modified T-cell epitopes were studied. Using the peptides synthesized corresponding to AChR amino acid sequence, the alpha 183-200 (as an antigen to raise "blocking antibody") and the alpha 70-90, alpha 125-147 and alpha 67-76 with alpha 107-116 (as antigens to raise "binding antibody") were found immunogenic in the induction of the disease in animals. Phenotypic changes in the T-cell lineages in the thymus were discussed. An impairment of excitation-contraction coupling in some of myasthenic muscles was attributed to a defect caused by antibodies raised against ryanodine receptor protein. Myasthenia gravis patients' sera containing anti-ryanodine receptor antibodies inhibited the calcium-induced release of calcium in response to caffeine in human rhabdomyosarcoma cell line. Buffalo/Mna rats with spontaneous benign thymoma showed (1) ryanodine receptor expressed in the thymic epithelial cells, (2) anti-ryanodine receptor antibodies in serum, and (3) reduced twitch and tetanic force without abnormality in synaptic transmission and muscle membrane properties. It is suggested that thymic epithelial cell and skeletal muscle share common ryanodine receptor antigen. The finding seen in this rat strain can be a counterpart of the feature reflecting an immune attack directed against a compartment of skeletal muscle in myasthenia gravis.

Animals↗

[Molecular immunology of voltage-gated calcium channel and Lambert-Eaton myasthenic syndrome].

Lambert-Eaton myasthenic syndrome(LEMS), an autoimmune disease that is often associated with small cell lung carcinoma(SCLC), impairs the quantal release of acetylcholine by directing antibodies against voltage-gated calcium channels (VGCC) in the motor nerve terminal. We focused attention on the P/Q type VGCC, to which there are antibodies in LEMS patients in higher frequency than antibodies to other types of VGCC. To search for antigenic sites in the molecular structure of alpha 1A subuuit of P/Q type VGCC in LEMS, we synthesized 4 peptides corresponding to the extracellular region (S5-S6 linker) of each of 4 domains that form alpha 1A subunit of VGCC. Also, LEMS patients' sera were studied by immunoprecipitation assay using these antigens. Peptides corresponding to the extracellular region (S5-S6 linker) of domains II and IV were specifically reactive with LEMS antibodies; their titiers respectively correlated with those of anti-P/Q type calcium channel (omega-conotoxin MVIIC-sensitive human cerebellum extret). Lewis rats were immunized with the domain II S5-S6 linker peptides conjugated with KLH. The immunized rats showed LEMS features characterized by reduced acetylcholine quantum content of endplate potentials and antibodies reactive with P/Q type VGCC. Our observations suggest 2 potential epitopes of LEMS antibodies. Synaptotagmin is a Ca2+ and phospholipid binding protein integrated in synaptic vesicle membranes. It plays a crucial role in neurotransmitter release, probably as a Ca2+ sensor for exocytosis of synaptic vesicles. The extracellular region of synaptotagmin was found antigenic for the induction of a rat model of LEMS. A proportion of human LEMS antibodies reacted with the recombinant synaptotagmin in immunoblot.

Acetylcholine↗

Modulation of sensitivity to mitomycin C and a dithiol analogue by tempol in non-small-cell lung cancer cell lines under hypoxia.

We examined the mechanisms involved in the bioactivation of mitomycin C (MMC) and a newly developed MMC analogue: 7-N-(2-([2-(gamma-L-glutamylamino)ethyl]dithio)ethyl)mitomycin C, KW-2149, in non-small-cell lung cancer (NSCLC) cell lines under aerobic and hypoxic conditions. To investigate these mechanisms, we used MMC-resistant non-small-cell lung cancer cell lines (PC-9/MC4) that had been established in our laboratory from the parent PC-9 cell line by continuous exposure to MMC. We previously reported that the MMC-resistant cell line (PC-9/MC4) was poor in NAD(P)H dehydrogenase (quinone) activity and approximately 6-fold more resistant than the parent cells (PC-9) to MMC on 2-h exposure under aerobic conditions. In this study, the subline PC-9/MC4 was 6.7-fold more resistant to MMC than PC-9, the parent cell line, under aerobic conditions, and 5.2-fold more resistant under hypoxic conditions after 2-h exposure to MMC. However, on co-incubation with tempol, an inhibitor of the one-electron reduction pathway, the sensitivity of PC-9/MC4 to MMC was impaired under hypoxic conditions, but the impairment was not evident under aerobic conditions. KW-2149, the newly developed MMC analogue, was cytotoxic for both PC-9/MC4 and PC-9 cells, and the sensitivity of both cell lines to KW-2149 was not changed by exposure to hypoxic conditions or by coincubation with tempol. There were no significant differences in the intracellular uptake of MMC and the activities of cytosolic detoxification enzymes between the PC-9 and PC-9/MC4 cell lines. These results support the hypothesis that the one-electron reduction pathway plays a partial role in the bioactivation of MMC, but not of KW-2149, and that KW-2149 is excellent at circumventing resistance to MMC in NSCLC.

Antineoplastic Agents↗

Effect of estrogen replacement therapy on hepatic triglyceride lipase, lipoprotein lipase and lipids including apolipoprotein E in climacteric and elderly women.

Estrogen provides beneficial effects on hyperlipidemia in climacteric and elderly women. In this study of 68 women (37 to 67 years old), hepatic triglyceride lipase (HTGL), lipoprotein lipase (LpL) serum lipids and apolipoproteins were analyzed to investigate the effects of estrogen replacement therapy (ERT). After menopause, LpL, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B increased. But ERT suppressed total cholesterol, LDL-cholesterol, apolipoprotein B, and especially apolipoprotein E in menopausal women. The mechanism was thought that ERT significantly suppressed HTGL, but LpL was not affected. Estrogen also increases hepatic LDL receptors and accelerates transfer of serum LDL-C (and TC). It was said that HTGL accelerates conversion of intermediate-density lipoprotein (IDL) to LDL. The suppression of HTGL by the ERT may decrease conversion of IDL to LDL and lower LDL-C (and TC). These estrogen's beneficial effects on lipids, may prevent the atherosclerosis. In addition, apolipoprotein E increases senile plaques in senile dementia-Alzheimer's type. The decrease in apolipoprotein E with ERT may be related to cognitive functions of elderly women.

Adult↗

Immunohistochemical analysis of the endocrine cells in the pancreatic islets of cattle.

The distribution of endocrine cells and the areas of islets in the bovine pancreas were investigated by immunohistochemical methods. The islets in the A-region, which consisted of the left lobe, the ventral portion of the body, and the ventral and distal portions of the right lobe, contained a central core of insulin-containing (B-) cells surrounded by glucagon containing (A-) cells, a few somatostatin-containing (D-) cells and sporadic pancreatic polypeptide-containing (PP-) cells. The islets in the B-region, which consisted of the uncinate process, and the dorsal and proximal portions of the body and the right lobe, contained a central mass of B-cells, and peripheral cells which were predominantly PP-cells with a few D-cells but no A-cells. The areas of islets in the B-region were small as compared with those in the A-region. From these findings it is suggested that A- and PP-cells have a complementary relationship to one another. In view of this hypothesis, two types of islet, A-cell-rich and PP-cell-rich islets, were identified. The A-region contained A-cell-rich islets derived from the dorsal pancreatic primordium, while the B-region contained PP-cell-rich islets that originated from the ventral primordium. In the bovine pancreas, the areas containing PP-cell-rich islets are greater than those in previously examined species.

Animals↗

Anaplastic thyroid carcinoma producing the granulocyte colony stimulating factor (G-CSF): report of a case.

We report herein the unusual case of a 60-year-old woman with an anaplastic thyroid carcinoma which produced granulocyte colony stimulating factor (G-CSF). She presented with large neck masses, respiratory difficulty, and a high fever. Laboratory examinations revealed marked leukocytosis of 43,200/mm3 with 85% granulocytes and an elevated G-CSF level of 67 pg/dl. Total thyroidectomy with bilateral node dissection and tracheostomy was performed, and a histological diagnosis of large-cell anaplastic thyroid carcinoma was confirmed. Immunohistochemical examination with a polyclonal antibody against G-CSF stained the tumor cells. Although the respiratory difficulty, fever, and marked granulocytosis subsequently improved, she died 1 month after undergoing surgery due to metastatic mediastinal disease.

Carcinoma↗

Antibodies to recombinant synaptotagmin and calcium channel subtypes in Lambert-Eaton myasthenic syndrome.

Several proteins have been postulated as possible targets of immune attack in Lambert-Eaton myasthenic syndrome (LEMS). Heterogeneity of autoantibodies in sera from 20 LEMS patients was studied by comparing their reactivity to synaptotagmin, a synaptic vesicle protein, and voltage-gated calcium channels (VGCCs). Six patients' sera (1 with small cell lung carcinoma (SCLC)) contained antibodies specifically recognizing the recombinant synaptotagmin on immunoblots. Thirteen (11 with SCLC) and 16 (11 with SCLC and 1 with poorly differentiated cell carcinoma in the lung) patients' sera immunoprecipitated omega-conotoxin GVIA-labeled N-type and omega-conotoxin MVIIC-labeled Q-type VGCCs, respectively. Three of 6 synaptotagmin-positive sera had cross-reactivity with N and/or Q subtypes of VGCC; the remaining 3 showed no cross-reactivity with VGCCs. Results indicate that LEMS sera are heterogeneous in the spectrum of containing antibodies, and suggest that this heterogeneity reflects the immune response to various synaptic proteins including not only multiple VGCCs but also synaptosecretory complex proteins.

Adult↗

Fine structure of podocytes in the bovine renal corpuscle.

Thick primary processes issued from the hemispherical or plate-like cell bodies of podocytes in bovine renal corpuscles. These processes branched into secondary and tertiary ones, but no fine pedicels were observed on the outer surface of the podocytes by scanning electron microscopy, because each primary process closely interdigitated with those of adjacent cells. Many pedicels, however, were observed under the processes by using the freeze-fractograph and a transmission electron microscope.

Aging↗

Microvascular changes in the bovine corpus luteum during pregnancy.

The microvasculature of bovine corpora lutea during pregnancy was studied by scanning electron microscopy using corrosion casts. Only one spiral arteriole branched directly from the ovarian artery entered the blood vascular bed of the pregnant corpora lutea. The bed consisted of numerous lobular sinusoidal capillary plexuses during pregnancy, and were characteristic to the microvasculature of a large corpus luteum. At the late stage of pregnancy, arteriovenous anastomoses were situated within the lobular sinusoidal capillary plexus composed of thin sinusoidal capillaries. These anastomoses may induce a decrease in blood flow to the lobular sinusoidal capillary plexus, suggesting that they may have an important role to induce the initial degeneration of the bovine pregnant corpora lutea.

Animals↗

Microvascular changes during the development of follicles in bovine ovaries: a study of corrosion casts by scanning electron microscopy.

Microvascular changes during the development of follicles in bovine ovaries were studied by scanning electron microscopy of corrosion casts. A clear vascular plexus of ovarian follicles appeared at the stage when secondary follicles were 200-400 microns in diameter. The plexus consisted initially of a thin, roughly structured and single-layered capillary network. During follicular development, the microvascular architecture of antral follicles was arranged as two independent vascular plexuses. The inner plexus, which received a spiral arteriole, consisted of a dense sinusoidal capillary network with an arterial and a venous layer; it functioned as an independent microcirculatory unit. The inner plexus developed from the capillary plexus of the theca interna of the secondary follicles. The outer plexus, which anastomosed with several stromal capillaries, consisted of a thin, coarse and basket-like capillary plexus. The outer plexus was formed from the stromal capillary plexus as a consequence of the rapid enlargement of developing antral follicles.

Animals↗