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Biomedical subjects

T Iwanaga

Publications and source records attributed to T Iwanaga.

At least 289 records · Page 16Linked to original sources

The difference in malignancy between pedunculated and sessile polypoid lesions of the gallbladder.

Surgically resected polypoid lesions of the gallbladder from 97 patients were evaluated to determine both the shape (pedunculated or sessile) and diameter of the polypoid lesions, in association with malignancy. At the time of analysis, the largest polypoid lesion examined was when two or more lesions were detected in one patient because they were histologically the same. Carcinoma was noted in 9 (13%) of the 67 pedunculated lesions and in 10 (33%) of the 30 sessile lesions. The sessile carcinoma was 14 +/- 4 mm (8-20 mm) in maximum diameter, which was not significantly larger than the 8 +/- 4 mm of the benign polyps, but significantly smaller than the 22 +/- 8 mm (14-35 mm) of pedunculated carcinomas (p less than 0.05). Cancer invasion extended beyond the muscular layer in eight cases (80%) of sessile carcinoma, and two of them were 10 mm or less in diameter. On the other hand, cancer invasion was beyond the muscular layer in two cases (22%) of pedunculated carcinoma (p less than 0.05), and these two were 30 mm or more in diameter. Likewise, sessile carcinoma was characterized by both a higher incidence of nodal involvement and poorer prognosis, compared with pedunculated carcinoma. These findings indicate that surgery should be undertaken when sessile polyps are detected by ultrasonography, even though the polyp may be less than 10 mm in diameter. On the other hand, with regard to the pedunculated type, malignancy should be suspected when the polyp is more than 10 mm in diameter.

Adult↗

[Suppressive effect of sex hormones on spreading of stomach cancer].

The frequency of stomach cancer in females is lower than that in males, but the cancers in females are often Borrmann type 4 or poorly differentiated adenocarcinomas. In young patients, the frequency of gastric cancer in females is higher than that in males, and widely spread cancers are often observed just after pregnancy and delivery. The incidence of stomach cancer in female rats is lower than that in males but the incidence increased slightly after pregnancy and delivery. And it decreased when female sex hormones are injected to male rats. It is surmised that female sex hormones or their analogues play a suppressive role on carcinogenesis or progression of stomach cancer, and that pregnancy and delivery may accelerate the growing of stomach cancer. Hormone therapy was performed to get some effects, and to take much more effects, some other new trials on hormone therapy are necessary.

Adult↗

[Surgical treatment and indication for metastatic lung tumor].

Prognostic factors of patients with metastatic lung tumors were evaluated on 72 patients who were treated with pulmonary resection (49 via lateral thoracotomy and 23 via median sternotomy). The 5-year survival rate of these patients was 41.3%. Two factors, i.e., tumor free interval (TFI) and tumor size, significantly affected the survival after surgery. Patients with a longer TFI and smaller tumor(s) were associated with a favorable prognosis. The prognosis, however, was neither affected by the number of metastatic lung tumors nor whether they were unilateral or bilateral. The prognosis of lung metastases from colorectal cancer was the most favorable (61.4% at 5-year). On the other hand, patients with lung metastases from renal cell carcinoma and breast carcinoma showed poor prognosis respectively. As for testicular tumors and bone or soft tissue sarcomas, chemo-sensitivity is the most important prognostic factor. Good responders to prior chemotherapy showed a better prognosis than poor responders. These results urge the reappraisal of the role of surgery in the treatment of metastatic lung tumors and demonstrate that aggressive surgery can be indicated even for multiple or bilateral lung metastases. Nature of metastatic tumors, i.e., their origin and chemo-sensitivity, must be taken into consideration when the indication for surgery is decided.

Bone Neoplasms↗

[Vasoactive intestinal peptide (VIP) protects against acid-induced acute lung injury in isolated perfused rat lungs].

Acute, diffuse lung injury, the principal lesion in ARDS, is often refractory to treatment. Recently, pretreatment with several pulmonary vasodilators that increase cAMP levels: isoproterenol, terbutaline, theophylline, and prostacyclin, was found to reduce the severity of lung injury in animal models. We have investigated the possible modulation of HCl-induced pulmonary edema in rats by VIP, a lung neuropeptide with potent vasodilator and cAMP-producing properties. The lungs of rats were perfused in situ at 10 ml/min with Krebs-4% albumin solution, and ventilated at constant tidal volume (6.5 ml/kg). Peak airway pressure (PAW), mean pulmonary arterial pressure (PPA) were measured throughout the experiment, and wet to dry lung weight ratio (W/D), afterwards. All animals were observed for one hour. In 6 rats receiving HCl only, 0.2 N-HCl was instilled intratracheally at 2 ml/kg. Four rats received 2 ml/kg of physiological saline intratracheally as control. In 6 other animals, VIP was infused into the pulmonary artery at 1 micrograms/kg/min, beginning 10 minutes before HCl and for the rest of the experiment. Another 6 rats were pretreated with atrial natriuretic peptide (ANP, atriopeptin II) just like the VIP group. Lungs of saline control animals showed little or no chage in PAW or PPA. With HCl alone, PAW increased immediately and continued to rise for the rest of the hour, reaching 500% of basal value at 30 minutes. PPA increased by 68% and W/D by 74% compared to saline-instilled lungs. In the VIP + HCl group, all abnormalities were significantly reduced relative to the HCl group. The rise in PAW was attenuated by 79% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[A case-control study of stomach cancer in young females, with special reference to the effects of pregnancy and delivery].

To investigate the effects of pregnancy and delivery on stomach carcinogenesis, we have conducted a case-control study. The cases consisted of females aged 34 or below who had been histologically diagnosed as having a stomach cancer, covering a period from 1967 to 1986 at the Center for Adult Diseases, Osaka. Our birth-year-matched controls were selected from female examinees who had undergone a gastroendoscopy in 1986. In this manner, a total of 79 cases and 158 controls were obtained. For women in the age group from 30 to 34, a history of their pregnancies and deliveries seemed to have protective effects on stomach carcinogenesis (RR = 0.36, P less than 0.05), whereas for those in the age group under 30, it appeared to be a risk factor for stage IV stomach cancer (RR = 4.42, P less than 0.05).

Adult↗

Results of surgical treatment for sternal metastasis of breast cancer.

Nine patients with solitary sternal metastasis of breast carcinoma were treated aggressively, with partial (n = 8) or total (n = 1) resection of the sternum. Parasternal and mediastinal lymph node dissection also was performed concomitantly for every patient. Chest wall defects were reconstructed with acrylic resin plate (n = 3) or rectus abdominus myocutaneous flap (n = 6). All patients received chemoendocrine therapy postoperatively. The median survival of these nine patients was 30 months. The prognosis of the patients (n = 4) with the mediastinal or parasternal lymph node metastasis were poor and all of them died of second relapse within 30 months. The prognosis of those (n = 5) without the lymph node metastasis, however, was quite favorable; three survived more than 6 years. These results suggest that sternectomy should be indicated for the solitary sternal metastasis when no evidence of systemic spread is noted since it can improve the quality of life and occasionally may result in long-term survival.

Adult↗

Augmentation of anticancer effect with angiotensin II in intraarterial infusion chemotherapy for breast carcinoma.

We investigated the effect of angiotensin II (AT II) on blood flow in breast cancer patients using 81mKr and found that it increased tumor blood flow 2.3-fold while decreasing blood flow in adjacent normal tissue 0.7-fold. We, then, used AT II in conjunction with intraarterial infusion chemotherapy (IAC) for locally advanced breast cancer in order to increase drug delivery to the tumor and enhance its anticancer effect. Eleven patients (from 1976-1981) received IAC with doxorubicin through the internal thoracic and subclavian arteries, alternately, for 10 days (AT II- group). Twenty-four patients (from 1981-1985) received IAC with doxorubicin and concomitant infusion of AT II (1.3 micrograms/min through the internal thoracic artery and 2.6 micrograms/min through the subclavian artery) (AT II+ group). The response rate of the primary breast tumor was higher in the AT II+ group (92%) than in the AT II- group (73%) (P = 0.66). Complete tumor necrosis was 46% in the AT II+ group, but only 27% in the AT II- group (P = 0.51). These preliminary results suggest that the anticancer effect of IAC for breast cancer can be enhanced with concomitant infusion of AT II.

Adult↗

A rational technique for surgical operation on Borrmann type 4 gastric carcinoma: left upper abdominal evisceration plus Appleby's method.

Borrmann type 4 gastric carcinoma, including linitis plastica, is difficult to detect at an early stage and the results of surgical treatment remain poor. We have used 'left upper abdominal evisceration plus Appleby's method (LUAE + Apl.)' as a radical surgical procedure for this disease. During the period 1983-86, 30 cases of Borrmann type 4 gastric carcinoma underwent this procedure (Group A). These cases were compared with 30 patients who underwent total gastrectomy with pancreaticosplenectomy (Group B) during the period 1980-82. Although this is not a randomized study and the extent of resection was greater in Group A, the operation time, amount of blood loss, and number of complications were similar for both methods. When the survival rates were compared, the 3-year survival rate in stage II-III cases was higher for Group A (83.3 per cent) than for Group B (42.2 per cent) (P less than 0.05). One patient in Group A and 12 patients in Group B died with peritoneal metastasis within 3 years of operation in stage II-III. The LUAE + Apl. method is a rational and useful technique for the surgical treatment of Borrmann type 4 gastric carcinoma.

Adult↗

An autosomal dominant mutation of facial development in a transgenic mouse.

We have created a transgenic mouse which showed an autosomal dominant mutation of facial development. This facial malformation was characterized by a short snout and a twisted upper jaw. All offspring showing the dysmorphic phenotype carried the injected gene. In order to analyze the primary cause of this mutation, newborn mice and embryos were examined. The outcome was that the malformation of nasal and premaxillary bone was not the primary defect but was a secondary event. The primary cause of this dysmorphism was a developmental defect in the first branchial arch. Genomic DNA fragments flanking the insertion site of this mutant mouse were cloned. Using these fragments, we have assigned the integration site to chromosome 13. The gene responsible for a previously reported mutant mouse, one which also has a short snout, is also reported to be on chromosome 13. In the fragments flanking the insertion site of the transgenic mouse, at least one fragment was highly conserved in mammals. These results indicate that this malformation is due to the insertional disruption of a host gene. However, the possibility that this mutation is caused by an inappropriate expression of the injected gene still remains to be investigated.

Animals↗

Filiform papillae as a sensory apparatus in the tongue: an immunohistochemical study of nervous elements by use of neurofilament protein (NFP) and S-100 protein antibodies.

Nervous elements supplying the filiform papillae of the tongue of cattle and rats were investigated using immunohistochemistry against neurofilament protein (NFP) and glia-specific S-100 protein. The rod-shaped bovine filiform papillae were heavily keratinized along their entire length and lacked the connective tissue core that occurs in other mammals. Instead, the core was located posterior to the filiform papilla. The base of the bovine filiform papillae was invaded vertically by laminar connective tissue papillae. The core contained a large number of NFP-positive nerve fibers, most of them terminating as free endings in its anterior margin. NFP-positive nerves gathered around the anterior ridge of the epithelium at the base of the core and occasionally penetrated into the epithelium. The laminar connective tissue papillae at the base of the filiform papilla also contained NFP-positive nerve fibers. The core contained S-100-immunoreactive lamellated corpuscles, which were identified as "simple corpuscles" in electron micrographs. The structure and innervation of the bovine filiform papilla suggest that they represent a specialized sensory apparatus. The pyramidal filiform papillae of the rat were smaller, each containing a simple connective tissue core. Few NFP-positive nerve fibers from the nerve plexus entered the core. Filiform papillae are thus less specialized in rats than in cattle.

Animals↗

Innervation of periodontal ligament and dental pulp in the rat incisor: an immunohistochemical investigation of neurofilament protein and glia-specific S-100 protein.

Nervous elements in the periodontal ligament and dental pulp of rat incisors were investigated by means of immunohistochemistry for neurofilament protein (NFP) and glia-specific S-100 protein. The periodontal ligament in the incisors was densely innervated by NFP-immunoreactive nerve fibers; the distribution of the nerve fibers and their terminations differed markedly from those in molars. NFP-positive, thick nerve bundles entered the lingual periodontal ligament through slits located in the mid-region of the alveolar socket, and immediately formed numerous Ruffini-like corpuscles. In the labial periodontal ligament, all of the NFP-immunoreactive nerve fibers terminated in free endings. The restricted location of the stretch receptor, Ruffini-like corpuscle, in the lingual periodontal ligament appears to be an essential element, because this region is regularly extended during mastication. The nervous elements were restricted to the alveolar half of the periodontal ligament in every region; they avoided the dental half of the periodontal ligament, which presumably moves continuously with the tooth. Pulpal nerve fibers in incisors also showed a characteristic distribution different from those in molars; individual nerve fibers with beaded structures ran in the center of the pulp toward the incisal edge, and did not form the subodontoblastic nerve plexus of Raschkow. Immunostaining for S-100 protein revealed a distribution pattern of nervous elements similar to that for NFP, suggesting that the nerves supplying the periodontal ligament and dental pulp were mostly covered by a Schwann sheath.

Animals↗

Interaction of surfactants with bilayer of negatively charged lipid: effect on gel-to-liquid-crystalline phase transition of dilauroylphosphatidic acid vesicle membrane.

The interaction of surfactants with the vesicle membrane of the negatively charged lipid, dilauroylphosphatidic acid, was investigated through their effect on the gel-to-liquid-crystalline phase transition of the lipid bilayer. Three types of surfactants (anionic, cationic and non-ionic) with different hydrocarbon chain length were examined. (i) Anionic sodium alkylsulfates affected the phase transition temperature, Tm, only weakly. (ii) Non-ionic alkanoyl-N-methylglucamides decreased Tm monotonously with increasing concentration. The depression of Tm induced by these surfactants was analyzed by applying the van't Hoff model for the freezing-point depression, and the partition coefficients of the surfactants between bulk water and lipid membrane were estimated. (iii) Cationic alkyltrimethylammonium bromides affected Tm in a complex manner depending on the hydrocarbon chain length of the surfactants. Octyl-/tetradecyl-trimethylammonium bromide depressed/elevated Tm monotonously with increasing concentration, whereas the change in Tm induced by decyl- and dodecyltrimethylammonium bromides was not monotonous but biphasic. This complex behavior of the phase transition temperature was well explained, based on the statistical mechanical theory presented by Suezaki et al. (Biochim. Biophys. Acta, 818 (1985) 31-37), which takes into account the interaction between surfactant molecules incorporated in the lipid membrane.

Anions↗

Effect of sodium octanoate and sodium perfluorooctanoate on gel-to-liquid-crystalline phase transition of dipalmitoylphosphatidylcholine vesicle membrane.

The gel-to-liquid-crystalline phase transition of dipalmitoylphosphatidylcholine (DPPC) vesicle membrane was measured in the presence of sodium octanoate (SO) (pH 3 and 10) and sodium perfluorooctanoate (SPFO) (pH uncontrolled) by monitoring the scattered light intensity of the vesicle suspension. The phase transition temperature, Tm, decreased linearly with the concentration of added SO within the measured concentration range; the uncharged form of SO (pH 3) was much more effective for the depression of Tm than the charged form (pH 10). On the other hand, with increasing SPFO concentration, levelling off of Tm was observed after depression at an initial stage. From the depression of Tm, the partition coefficients, K, of these surfactants between bulk solution and DPPC vesicle membrane were estimated and compared with those obtained previously for other surfactant systems. The value of K for charged SO fell on the straight line of log K vs. Nc plot for anionic surfactants, where Nc is the carbon number of the hydrocarbon chain of surfactants, whereas K for uncharged SO showed a large positive deviation from the straight line of the plot for non-ionic surfactants. The latter suggested that some specific interaction, presumably hydrogen bond formation, may act between the protonated carboxyl group of SO and the lipid head group. The K value estimated for SPFO was much larger than that for charged SO. This difference in the affinity for the lipid bilayer between fluorocarbon surfactant and hydrocarbon surfactant may be attributed to the difference in their hydrophobicity.

1,2-Dipalmitoylphosphatidylcholine↗

Electrophysiology of guinea-pig myenteric neurons correlated with immunoreactivity for calcium binding proteins.

Experiments were undertaken to define the electrophysiological characteristics and shapes of neurons in the myenteric plexus of the guinea-pig ileum that are immunoreactive for calcium binding proteins. Recordings were made from the neurons with intracellular microelectrodes containing a mixture of the fluorescent dye Lucifer yellow and KCl solution. The neurons studied were filled with Lucifer yellow so that they could be re-identified after processing the tissue to reveal immunoreactivity for either the calcium binding protein (CaBP), spot 35 protein, or vitamin D-dependent CaBP. Neurons were characterized as being AH-neurons, in which each action potential is followed by a prolonged after-hyperpolarization (greater than 4 s), or S-neurons, in which the prolonged after-hyperpolarizations were not observed and focal stimulation of internodal strands evoked fast excitatory synaptic potentials. S-neurons were never immunoreactive for the CaBPs (108 cells), but most AH-neurons (62 of 74) were immunoreactive. Immunoreactive and non-immunoreactive AH-neurons were indistinguishable on the basis of their electrophysiological properties or their shapes (all the AH-neurons were Dogiel type II in shape, i.e. smooth soma and many long processes). The S-neurons had a variety of shapes, but none could be classified as Dogiel type II. It is concluded that most AH-neurons are immunoreactive for calcium binding proteins, and that these proteins are restricted to AH-neurons.

Animals↗

Comparison of enzyme immunoassay with dextran-coated charcoal method in the determination of progesterone receptor in breast cancer cytosols.

A new enzyme immunoassay (EIA) for progesterone receptor (PR) has been developed by Abbott Laboratories. To study the correlation of the results from this new technique with the currently existing tritiated-ligand binding assay [dextran-coated charcoal (DCC) method], cytosols from 70 human breast cancers were assayed for PR by both the EIA and DCC methods. EIA showed a good reproducibility and was not susceptible to the change in protein concentration of cytosols and types of reducing agents. The correlation between the EIA and DCC methods was excellent with a correlation coefficient of 0.946; regression curve was PR (EIA) = 1.06 X PR(DCC) + 0.19 fmol/mg protein. The concordance of the results obtained from both methods was 91.4% with a cutoff value of 10 fmol/mg protein. These results demonstrate that EIA is a very useful and reliable method in the determination of PR with an excellent correlation with the conventional DCC method.

Breast Neoplasms↗

Expression of tissue-specific genes in transgenic mice.

The ability to introduce cloned genes into mouse germ line has been used for analyzing cis-acting DNA sequences involved in tissue-specific and developmental regulation of the introduced gene. Using this system we have attempted to produce a transgenic mouse model for human dominantly inherited disease, familial amyloidotic polyneuropathy. Recently the mutant transthyretin gene which is considered to be responsible for this disease has been cloned and well characterized at molecular level. We have produced transgenic mice by microinjecting human mutant gene. Amyloid deposition was observed in the mucosa of alimentary tract and renal glomeruli, suggesting that this approach is successful in establishing the mouse model for human genetic disease. In addition, these experiments suggest that the expression of the mutant gene is regulated normally during developmental process and that the cause of adult onset is not due to the dysregulation of this gene expression.

Amyloidosis↗