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Biomedical subjects

S Kawamura

Publications and source records attributed to S Kawamura.

At least 19 recordsLinked to original sources

Differential projections to the superior collicular layers from the perihypoglossal nuclei in the cat.

The primary objective of the present study is to demonstrate the presence of a projection to the superficial layers of the superior colliculus (SC) from the perihypoglossal nuclei, specifically from the nucleus intercalatus (INT) in the cat. Iontophoretic application of WGA-HRP into the perihypoglossal complex produced orthogradely labeled terminals in the SC contralaterally forming two bands: one is in the superficial gray layer, and the other in the intermediate gray layer. The superficial band was evenly distributed in the upper portion of the superficial gray layers (layers II1-2) and the deeper band existed in the intermediate gray layer (layer IV) being arranged in a discontinuous manner. Injections of the tracer into the superficial layers of the SC yielded retrogradely labeled cells only in the rostral part of the contralateral INT; by contrast, the injection confined to the deep layers produced labeling of cells exclusively in the nucleus prepositus hypoglossi (PH). Thus, the INT and the PH each project separately to the functionally different superficial and intermediate layers of the SC, respectively. On the basis of the present anatomical findings, it is suggested that the perihypoglossal nuclei as a whole contribute not only to the oculomotor but also to the visuosensory regulatory function in the SC.

Afferent Pathways

Purification and characterization of S-modulin, a calcium-dependent regulator on cGMP phosphodiesterase in frog rod photoreceptors.

S-modulin is a 26 kDa protein that regulates light sensitivity of cGMP phosphodiesterase in a Ca(2+)-dependent manner in frog rod outer segments (ROSs). In the present study, we purified S-modulin by taking advantage of a hydrophobic interaction between Phenyl Sepharose and S-modulin at high Ca2+ concentrations. The yield was greater than 90%. 45Ca(2+)-binding experiment showed that S-modulin is a Ca(2+)-binding protein. At high Ca2+ concentrations, S-modulin binds to ROS membranes. The binding target of the Ca2+/S-modulin complex is possibly a ROS membrane lipid(s), but it was difficult to identify. The binding was observed mainly at greater than 1 microM Ca2+. The amino acid sequence deduced from proteolytic fragments of S-modulin was approximately 80% and 60% identical to those of recovering and visinin, respectively.

3',5'-Cyclic-GMP Phosphodiesterases

Concerted evolution of the primate immunoglobulin alpha-gene through gene conversion.

We determined four nucleotide sequences of the hominoid immunoglobulin alpha (C alpha) genes (chimpanzee C alpha 2, gorilla C alpha 2, and gibbon C alpha 1 and C alpha 2 genes), which made possible the examination of gene conversions in all hominoid C alpha genes. The following three methods were used to detect gene conversions: 1) phenetic tree construction; 2) detection of a DNA segment with extremely low variability between duplicated C alpha genes; and 3) a site by site search of shared nucleotide changes between duplicated C alpha genes. Results obtained from method 1 indicated a concerted evolution of the duplicated C alpha genes in the human, chimpanzee, gorilla, and gibbon lineages, while results obtained from method 2 suggested gene conversions in the human, gorilla, and gibbon C alpha genes. With method 3 we identified clusters of shared nucleotide changes between duplicated C alpha genes in human, chimpanzee, gorilla, and gibbon lineages, and in their hypothetical ancestors. In the present study converted regions were identified over the entire C alpha gene region excluding a few sites in the coding region which have escaped from gene conversion. This indicates that gene conversion is a general phenomenon in evolution, that can be clearly observed in non-functional regions.

Animals

Sequential changes in cerebral blood flow and metabolism in patients with subarachnoid haemorrhage.

Haemodynamic and metabolic sequences were investigated in nine patients having subarachnoid haemorrhage (SAH) up to 3 months following aneurysmal rupture, using positron emission tomography (PET). In the pre-spasm stage (2-4 days after SAH) cerebral blood flow (CBF, ml/100 ml/min) was 45 +/- 11, the cerebral metabolic rate of oxygen (CMRO2, ml/100 ml/min) was 2.68 +/- 0.50, and cerebral blood volume (CBV, ml/100 ml) was 5.5 +/- 1.2. CBF within the normal range and a relatively low CMRO2, indicated relative hyperaemia. This was possibly due to the direct toxic effect of SAH on the brain metabolism. CBV was considerably elevated. The spasm stage (6-15 days after SAH) showed CBF values of 39 +/- 7, CMRO2 values of 2.42 +/- 0.50, and CBV values of 5.4 +/- 1.7. CBF decreased significantly (p less than 0.05 vs pre-spasm stage), and CMRO2 also tended to decrease, while they were coupling. It is likely that this may have been induced by vasospasm. Thereafter, the PET parameters normalized gradually. During all the stages studied, significant laterality of the PET parameters was not observed. This may be because SAH and vasospasm provide diffuse pathophysiological conditions for the entire brain and cerebral arteries.

Adult

Observation of the blood-brain barrier function and vasomotor response in rat microcirculation using intravital fluorescence microscopy.

The blood-brain barrier function and the vasomotor response in rat microcirculation was studied using a closed cranial window technique and an intravital fluorescence microscope with an attempt to reduce both the light intensity and the amount of 2% Na(+)-fluorescein to as little as possible. The light intensities in the focus were less than or equal to 2.5 mW/cm2, and with the low-light TV camera we were able to reduce the total amount of the dye to less than or equal to 0.7 ml during 6-h experiments. Observing the brain surface every 30 min showed that the barrier function remained intact for up to 6.0 h following the first iv administration of the dye. This study has reconfirmed that the pial vessels have physiological vasomotor responses (e.g., CO2 reactivity). The osmotic barrier disruption started at a small venule 10 min after the start of superfusion with mannitol (1000 mOsm/liter). In conclusion, the microscope system and the small animal model used in this study were useful in studying the blood-brain barrier function and the vasomotor response simultaneously under various experimental conditions.

Animals

Chronic clonidine treatment and its termination: effects on penile erection and ejaculation in the dog.

The effects of chronic administration (4 weeks) of the alpha-2 adrenoceptor agonist clonidine (CL) and its termination on penile erection and ejaculation were investigated in male dogs. Penile erection and ejaculation were elicited by manual penile stimulation (for 5 min). CL (10 micrograms/kg/hr, s.c.) was delivered via osmotic minipump (Alza, 2ML-4). 3 or 7 days after the minipump implantation, CL caused a significant decrease in the amount of ejaculate produced by the genital stimulation without affecting the erectile potency. Ejaculatory ability returned to pretreatment levels despite continued CL administration, becoming evident in tests 14 days after initiation of treatment. Further, chronic CL (23 days) antagonized the inhibitory effects of acute administration of CL (0.05 mg/kg, i.p.). These data indicate tolerance to continued delivery of low doses as well as to acute administration of a higher dose. In the acute drug experiments, the ejaculatory inhibition elicited by CL (0.05 mg/kg, i.p.) was completely antagonized by pretreatment with yohimbine (0.05 and 0.10 mg/kg, i.p.), an alpha-2 adrenoceptor antagonist, but not with naloxone (1.0 mg/kg, i.p.), an opioid receptor antagonist. Furthermore, DG-5128 (1.0 and 2.0 mg/kg, i.p.), a selective alpha-2 adrenoceptor antagonist that poorly penetrates the blood-brain barrier, failed to antagonize the CL-induced ejaculatory inhibition. This study suggests that functional alterations in the central alpha-2 adrenoceptor mechanism may be related to the changes in the ejaculatory capacity during chronic treatment with CL.

Adrenergic alpha-Antagonists

Effects of mucosal metallothionein in small intestine on tissue distribution of cadmium after oral administration of cadmium compounds.

The effect of mucosal metallothionein (MT) preinduced by zinc (Zn) on tissue distribution of cadmium (Cd) after administration of Cd with several chelating agents was studied in rats. After Cd-cysteine (Cd-Cys) was incubated with intestinal Zn-MT in vitro, all the Cd dissociated from Cys and exchanged the Zn bound to MT. However, dissociation of Cd bound to EDTA (Cd-EDTA) was not observed in the incubation mixture containing intestinal Zn-MT. The concentration of Cd in intestinal mucosa reached a maximum 16 hr after oral administration of Cd-Cys. The Cd level in the intestine was higher than that in the liver and kidney and was similar to that occurring after oral administration of CdCl2. The amount of Cd distributed to the liver and kidney after Cd-EDTA administration was about 30% of the level after CdCl2 administration. Even at 15 mg Cd/kg Cd-EDTA, the Cd level in the intestinal mucosa reached a plateau after 2-4 hr, as it did in the liver and kidney. When Cd-Cys was administered po to control or to Zn-pretreated rats, it was found that Zn pretreatment increased the concentration of Cd in the kidney, as was the case after oral administration of CdCl2. This effect of Zn pretreatment was not observed after oral administration of Cd-EDTA. When Cd-MT was injected into the duodenum, the intestinal absorption of Cd was 60% of that after CdCl2 administration. After the duodenal administration of Cd-MT, at all doses, the concentration of Cd in the kidney was higher than that in the liver. These results suggest that mucosal MT in the small intestine might trap Cd absorbed from the intestinal lumen and transport it to the kidney.

Administration, Oral

Immunoglobulin CH gene family in hominoids and its evolutionary history.

The organization of the human immunoglobulin CH gene suggests that a gene duplication involving the C gamma-C gamma-C epsilon-C alpha region has occurred during evolution. We previously showed that both chimpanzee and gorilla have two 5'-C epsilon-C alpha-3', as in human, and that orangutan, gibbon, and Old World monkeys have one C epsilon gene and one, two, and one C alpha gene(s), respectively. In addition to these clustered CH genes, there is one processed C epsilon pseudogene in each species. The present study revealed that orangutan and crab-eating macaque (an Old World monkey) both have one 5'-C epsilon-C alpha-3' and that gibbon has two 5'-C epsilon-C alpha-3', one C epsilon gene of which is completely deleted. By Southern analysis, the number of C gamma genes in all the nonhuman hominoids was estimated to be four to five, as in human, in comparison with two for crab-eating macaque. The C mu and C delta genes were estimated to be present as single copies in both hominoids and crab-eating macaque. Furthermore, it was proved that there are two copies of the C epsilon 5'-flanking region in both the orangutan and the gibbon genomes. These results show that gene duplication including the C gamma-C gamma-C epsilon-C alpha genes occurred in the common ancestor of hominoids and that subsequent deletion of the C epsilon gene (in orangutan, including one of the C alpha genes) occurred independently in each hominoid species.

Animals

Light-sensitivity modulating protein in frog rods.

Cyclic GMP is the second messenger in the phototransduction mechanism in rod photoreceptors. Light-induced activation of cGMP phosphodiesterase (PDE), the hydrolyzing enzyme of cGMP, reduces cytoplasmic cGMP concentration to close the cGMP-activated channel and thereby causes a hyperpolarizing light response. Ca2+ concentration decreases during light-adaptation and this decrease is thought to be at least one of the underlying mechanisms of light-adaptation. Our previous electrophysiological work suggested that PDE in frog rod photoreceptors is regulated by this Ca2+ concentration decrease. In the present work, we isolated a protein that binds to disk membranes at high Ca2+ concentrations. In the presence of this protein (a 26 kDa protein), PDE light sensitivity becomes high at high Ca2+ concentrations. The effect was observed at physiological ranges of Ca2+ concentrations. Thus we could explain high light-sensitivity of photoreceptors under the dark-adapted condition. According to its function, we termed the 26 kDa protein 'sensitivity-modulating protein' or 'S-modulin'. During the purification we noticed that there are additional mechanisms present that may contribute to light-adaptation in frog rod photoreceptors.

3',5'-Cyclic-GMP Phosphodiesterases

Uncoupling between CBF and oxygen metabolism in a patient with chronic subdural haematoma: case report.

The regional cerebral blood flow (rCBF) and oxygen metabolism of a patient with a chronic subdural haematoma were examined quantitatively, using positron emission tomography (PET). Before operation, the rCBF was decreased slightly throughout the brain, whereas the regional oxygen extraction fraction (rOEF) was increased throughout the brain, with values ranging from 0.36 to 0.60. One month after operation, the rCBF had recovered remarkably in almost all regions and rOEF had decreased to within the normal range.

Blood Volume

Glycolipid expression in prostatic tissue and analysis of the antigen recognized by antiprostatic monoclonal antibody APG1.

The expression patterns of glycolipid from prostatic hyperplasia, prostatic cancer and normal prostate tissue were observed. A further analysis of antigen recognized by mouse monoclonal antibody APG1, which was gained by immunizing glycolipids extracted from human prostate cancer, was also performed. In cancer tissue, both of the lactosyl and globoside series glycolipids were found to be generally reduced, although in the ganglioside series, GM3 and GD3 were not reduced and only the glycolipids with longer chains than GD2 were found to be reduced. These results indicated that the inhibition of sugar chain elongation, but not sialylation, was the main synthetic change occurring with carcinogenesis of the human prostate. APG1 reacted with only two bands near GM2 and GD2 of the ganglioside fraction on a thin-layer chromatography plate, but it did not react with any of the known gangliosides of the ganglioside series including GM2 and GD2. Histochemically, APG1 showed intense reaction only in frozen tissue sections of human prostate, and the reactivity decreased with the increasing grade of cancer. Therefore, this antigen was considered to be a prostate-specific and differentiated antigen reacting with nonganglioseries gangliosides.

Antibodies, Monoclonal

Postremission therapy without prednisolone improves survival in adults with acute leukemia.

This prospective randomized clinical trial was to clarify whether postremission therapy without prednisolone (PSL) was more effective than therapy with PSL in improving the 5-year survival of adults with acute leukemia. Thirty consecutive adult patients with newly achieved complete remission were randomized to receive postremission therapy either with or without PSL between September 1985 and September 1988. The patients ranged from 16 to 57 years in age. Patients treated without PSL had a significantly better 5-year survival rate than those receiving PSL according to Kaplan-Meier analysis (53.5% vs 15.3%, p < 0.05). In the group treated without PSL, eight out of 15 patients were alive at 72 months, and seven patients maintained their first complete remission at 72 months. Among patients with acute lymphoblastic leukemia (ALL) who were treated without PSL the median duration of remission was 24 months, and the survival rate at 72 months was 50.0%. On the other hand, the median survival was only 13 months for the 5 patients with ALL treated with PSL. Thus, it is desirable that adults with acute leukemia are treated by postremission therapy without PSL.

Acute Disease

Lung cancer with eosinophilia in the peripheral blood and the pleural fluid.

A case of lung cancer associated with eosinophilia in the peripheral blood and pleural fluid is reported. A 55-year-old man with a tumor in the right lower lung lobe and right pleural effusion was admitted to Ehime University Hospital. Histology of specimens biopsied under a bronchoscope revealed that he had poorly differentiated squamous cell carcinoma. On admission, his peripheral blood leukocyte count was 11,500/microliters with 7.8% eosinophils and the pleural fluid showed a high eosinophil count (60.5%). After chemotherapy, blood eosinophilia disappeared and the pleural effusion was decreased with the reduction of the tumor. The patient's serum had the activity to stimulate eosinophil proliferation in human bone marrow cell culture, suggesting that the tumor may have produced an eosinophil proliferating factor.

Carcinoma, Squamous Cell

[A case of scrotal bladder hernia containing bladder cancer].

A 70-year-old man had a history of total laryngectomy for laryngeal cancer and bilateral inguinal hernia repair 5 years previously. The patient had suffered from difficulty with urination since then and had been treated for prostatic hypertrophy at our department. He developed microscopic hematuria from June 1991, and was admitted because a bladder tumor was detected by cystoscopy. Cystography showed a scrotal bladder hernia with filling defects in the bladder per se and the bladder hernia as well. Cystoscopy revealed tumors in the hernia and in the vicinity of the ureteral orifice. Biopsy indicated transitional cell carcinoma. Voiding cystourethrography showed normal urination and no residual urine. Excision of the tumor-containing hernia, partial cystectomy with right ureteral orifice, and reconstruction of the right inguinal canal were performed on October 25, 1991. The postoperative course was favorable and he was discharged on the 40th postoperative day. The tumors were respectively stage as TCC, G1, and pT1a, and TCC, G1 greater than G2, and pT1b. Thirty five cases of bladder hernia that have been reported in Japan. Eight cases of accompanied by cancer have been reported in Japanese (3 cases) and foreign (5 cases) literatures. These are reviewed and discussed.

Aged

[Anatomy and function of the upper urinary tract].

This report deals with the histologic and gross anatomy of the upper urinary tract (calyces, pelvis, and ureter) as well as the nerve supply to this region. It also covers the physiological transport of urine from the kidneys to the bladder, which is reviewed on the basis of experimental and clinical studies. A pacemaker system present in the proximal calyces has been found to have an important physiological role in urine transport. However, clinical experience has shown that urine transport is not affected by surgery such as pyeloplasty and pyelolithotomy which impairs the activity of this pacemaker. Electron microscopic and histochemical studies as well as the maintenance of urine transport after renal grafting suggest that the nerve supply to the upper urinary tract is not dominant in regard to this function. This study also investigated urinary transportation in the presence of urinary tract obstruction due to various diseases, and demonstrated that urine is also conveyed by gravity and not solely by ureteric peristalsis. The use of internal stenting and percutaneous urinary diversion thus appears to be reasonable. Although the detailed etiology congenital hydronephrosis is still unknown, there is no doubt that it involves dysfunction of the ureteropelvic junction, since urine transport is improved by the endoscopic or surgical formation of a physiological tunnel at this junction which can regulate the volume of urine transported according to urine output. It is important for studies of upper urinary tract function to be conducted in close relation to clinical practice and not to simply be confined to esoteric experimental situations.

Animals

[Small cell carcinoma of the bladder. Small cell lung cancer-associated ganglioside (Fuc GM1) expression].

A 61-year-old male visited us with chief complaints of macroscopic hematuria and bladder irritation symptoms. Cystoscope, U/S, MRI, and CT showed an extensive non-papillary, wide-based tumor centering around the anterior wall of the bladder. Transabdominal U/S-guided full-thickness biopsy indicated a pT3a (Biopsy) primary small cell carcinoma of the bladder containing neuroendocrine granules. Immunohistochemical studies revealed Fuc GM1, an antigen related to small cell carcinoma of the lung. Neoadjuvant therapy consisted of preoperative irradiation at 50 Gy and intra-arterial infusion chemotherapy with CDDP and THP. Since a follow-up full thickness biopsy indicated pT0 (Biopsy), total cystectomy was performed. Examination of the resected specimen also indicated pathological CR.

Carcinoma, Small Cell