Electric birefringence of myosin subfragments.

Electric birefringence measurements have been made on aqueous solutions of myosin subfragments, heavy meromyosin, subfragments 1 and 2 (S-1 and S-2). All of these showed positive electric birefringence. Heavy meromyosin and S-2 showed a large intrinsic Kerr constant. From the analysis of the build up and decay process of the birefringence, the contribution of the slow induced dipole moment was concluded in heavy meromyosin and S-2, although the existence of the permanent dipole moment was not completely excluded. The decay process of the birefringence of heavy meromyosin was found to consist of two components; the fast one of which had a relaxation time of the same order as that of S-1. This is probably due to the presence of a flexible hinge in heavy meromyosin.

Gastric and small intestinal lesions after partial stomach resection with Billroth II or Roux-en-Y reconstruction in the rat.

The evolution and phenotypic expression of mucosal lesions of the gastric stump were investigated in male rats submitted to gastric resection with reconstruction by the Billroth II technique (BII with biliopancreatic reflux, BPR) or by the Roux-en-Y procedure (without BPR). Animals were studied at 24, 36, 54 and 64 weeks after surgery and the phenotypic expression of lesions analysed using routine hematoxylin and eosin staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical concanavalin A, galactose oxidase Schiff (GOS) and sialidase GOS reactions). BPR was found to be responsible for the formation of adenomatous hyperplasia (AH), increasing in incidence and size with time, since the Roux-en-Y procedure failed to induce the gastric stump lesions observed after BII reconstruction. AHs always occurred in the transition of the gastrojejunal junction, a site offering special conditions for BPR influence, and were classified as gastric (G), intestinal (I) and G+I types according to their phenotypic expression. No pure I type AH was diagnosed at any time point. The G and G+I types developed at approximately equal incidences (i.e., G type 7/17, G+I type 10/17 at the 64th week). It was suggested that both gastric and intestinal mucosal elements were stimulated to proliferate by BPR, with the gastric mucosa tending to demonstrate AH. Intestinal type components of AH were found adjacent to the jejunum and not at the stomach margin, indicating an origin from intestinal mucosa. No metaplasia of the gastric mucosa was observed in any animal after partial gastric resection. In 101 rats submitted to the BII procedure, 5 mucinous adenocarcinomas were eventually diagnosed, mostly located in the subserosa of the gastrojejunal junction. All carcinomas expressed the phenotype of cells of the small intestine. Evidence of malignant transformation within the gastric components of AH was not observed even at the 64th week. In conclusion, all lesions induced by BPR in the rat remnant stomach are benign, and the few true cancers that arise in association are derived from the small intestine.

Biological differences between reflux stimulated proliferative stomal lesions and N-methyl-N'-nitro-N-nitrosoguanidine induced carcinomas in Wistar rats.

The morphology and evolution of epithelial lesions that developed at a gastrojejunal stoma due to reflux of duodenal contents were compared with MNNG-induced carcinomas in the pyloric mucosa of rats in a long term experiment. Random bred male Wistar rats were given MNNG in drinking water (100 mg/l) for 12 weeks and then one group was submitted to a gastrojejunal anastomosis at the greater curvature in the oxyntic mucosa. Untreated rats underwent either gastrojejunostomy or gastrotomy. The animals were killed at the 24th and 66th weeks of the experiment. The lesions obtained in the pyloric mucosa and in the mucosa of the gastrojejunal stoma were analyzed histologically using hematoxylin and eosin staining and immunohistochemistry for pepsinogen isoenzyme 1. Duodenal reflux induced proliferative lesions at the gastrojejunal junction that increased in incidence and size with time. Histologically they consisted of benign epithelial proliferation of gastric type. No evidence of malignant transformation within the gastric components of the proliferative lesions at the gastrojejunal stoma was observed even at the 66th week. Adenocarcinomas induced by MNNG in the pyloric mucosa increased in size during the experiment and were morphologically and histochemically distinct from the proliferative lesions at the gastrojejunal junction. In conclusion, proliferative lesions at the gastrojejunal stoma stimulated by duodenal reflux are biologically distinct from adenocarcinomas induced by MNNG in the pyloric mucosa. They do not seem to be precursor lesions of gastric carcinogenesis, as they do not undergo malignant transformation even after long-term, up to 66 weeks, follow-up.

Responses of paraventricular and supraoptic units to angiotensin II, sar1-ile8-angiotensin II and hypertonic NaCl administered into the cerebral ventricle.

Extracellular recordings of action potentials were made from neurones antidromically identified as neurosecretory cells in the paraventricular and supraoptic nuclei of urethane-anesthetized female rats. Eighty-six neurones were examined for their responsiveness to 10 ng of angiotensin II (AII) injected into the third cerebral ventricle and 78 (91%) of them increased their firing rate following the AII injection. None of the neurosecretory cells tested showed a response to the intraventricular (IVT) injection of isotonic NaCl. Thalamic neurones and non-neurosecretory hypothalamic neurones did not respond to the AII given IVT. Firing activity of 13 neurosecretory neurones was recorded during reflex milk ejection induced by suckling pups in the lactating rats. Seven of them were classified as oxytocinergic cells because they showed a burst of activity before reflex milk ejections and the remaining 6 neurones which gave no burst of firing before milk ejections were classified as nonoxytocinergic neurones. The IVT application of AII resulted in activation of all the oxytocinergic neurones and 5 of the 6 non-oxytocinergic neurones. The effect of AII on the firing of the neurosecretory cell was inhibited by the simultaneous application of Sar1-Ile8-AII (1 microgram), a competitive AII antagonist. The IVT injection of the antagonist alone inhibited the spontaneous firing of the neurosecretory cells, but it did not affect the firing of thalamic or non-neurosecretory hypothalamic neurones. Hypertonic NaCl (0.85 M NaCl, 1 mu1 IVT) also activated 13 of 20 neurosecretory cells tested. Combined application of AII and hypertonic NaCl elicited a marked potentiation of the response of neurosecretory cells to each of the stimuli. These findings indicate that AII activates neurosecretory cells stimulating specific AII receptors in the brain and that AII has a synergistic action with hypertonic NaCl. Inhibition of spontaneous activity of neurosecretory cells by a competitive AII antagonist suggests that endogenous AII may participate in the maintenance of basal activity of neurosecretory cells.

Electrophysiological evidence for multiple sites of actions of angiotensin II for stimulating paraventricular neurosecretory cells in the rat.

Microelectrophoretically (MEPh) applied angiotensin II (AII) excited about half of the PV neurosecretory cells recorded. The excitation was blocked by MEPh applied Sar1-Ala8-AII. Intraventricular (IVT) injection of AII excited both the sensitive cells and insensitive cells to the MEPh applied AII. MEPh-applied Sar1-Ala8-AII, however, blocked the IVT AII induced excitation only in the former type of the cells.

Early and late effects of wound healing on development of colon tumours in a model of colon carcinogenesis by 1,2-dimethylhydrazine in the rat.

The early and late effects of wound healing on tumour development at a distant site were evaluated morphologically in an experimental model of colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Random bred male Wistar rats were given subcutaneous injections of DMH (20 mg/kg) or saline, once a week, for eight weeks. One week after the last DMH injection the animals received a full thickness skin wound in their dorsal skin and the wound was left open to heal by second intention. Control and DMH treated rats, with or without skin wounds were sacrificed at the twelfth and twentieth weeks. The colons were removed and the incidence, distribution and morphology of any tumours were recorded. Tumours induced by DMH in the colonic mucosa increased in size during the experiment. At the twelfth week, just after healing of the skin wound was complete, the total number of tumours in the colonic mucosa and the number of tumours per rat was significantly higher in the skin-wounding DMH-treated group than in the unwounded group. No differences on tumour incidence and multiplicity were observed among the groups at the twentieth week. Histologically the number of poorly differentiated mucin-secreting carcinomas was increased in the skin-wounding DMH-treated group than in the unwounded group at the twelfth week. This effect was not observed at the twentieth week. The present results suggest that wound healing enhances tumour development at a distant site. This effect coincides with the period of repair and does not have a marked impact on later stages of tumour progression.

Altered foci of hepatocytes in rats initiated with diethylnitrosamine after prolonged fasting.

The influence of fasting on the potential of diethylnitrosamine (DEN) to initiate liver carcinogenesis was tested in a medium-term assay using the development of putative preneoplastic altered foci of hepatocytes (AFH) as the endpoint. Male Wistar rats fasted for 48 hr were given a single ip injection of DEN (200 mg/kg body weight). Partial hepatectomies were carried out at wk 3 and the rats were killed at wk 8. Fasted rats exhibited a small increase in the numbers of AFH with glutathione S-transferase in the placental form and eosinophilic AFH when compared with non-fasted animals. However, after a 6-wk exposure to 0.05% sodium phenobarbital in the diet, there were no differences in the numbers of AFH between fasted and non-fasted animals. Fasting also increased DEN-dependent centrilobular cell necrosis and specifically drug metabolism as indicated in vivo by a decreased time of paralysis of the lower limbs induced by zoxazolamine (40 mg/kg body weight, ip) and by an unaltered sleeping time induced by sodium pentobarbital (40 mg/kg body weight, ip). The results indicate that although fasting during the initiation stage of carcinogenesis increases DEN hepatoxicity, it does not interfere quantitatively with the development of liver preneoplastic lesions.

Effect of body temperature on respiratory frequency in vagotomized rabbits.

The temperature coefficients of the fundamental central respiratory frequency (fo), cycle duration (Tco), and inspiratory duration (TIo) were estimated, and their values were 5.3, -5.3 and -2.7, respectively. These results suggest that the fundamental respiratory pacemaker is under the influence of some thermosensitive mechanisms or is thermosensitive by itself, while the mechanism controlling the inspiratory duration is unaffected by thermosensitive mechanisms.

[Anatomo-radiological study of venous drainage of the pancreas in the dog]. / Estudo anátomo-radiológico da drenagem venosa do pâncreas no cão.

The anatomic radiological patterns of the venous drainage of the pancreas were studied in 20 dogs, utilizing injection of Schlesinger mass by means of catheter placed on the cranial mesenteric, portal and splenic veins. The drainage of the cranial 2/3 of the right lobe of the pancreas is made by the cranial pancreaticoduodenal vein, while the caudal third is made by the caudal pancreaticoduodenal vein. There are communications between these two veins. The drainage of the angular pancreatic portion in made by venous branches which drain in the gastroduodenal vein. Conversely the drainage of the cranial portion of the left lobe is made by venous branches which drain in the gastroduodenal vein or in the portal vein. The caudal portion is drained by a variable number of veins which are tributary of the splenic vein and a communication between the venous branches from the caudal and cranial portion of this lobe are present in 8 of the 20 dogs studied. The authors emphasize the importance of the careful knowledge of the pancreatic venous anatomy in order to present misinterpretation of the physiological and physiopathological events observed in research which utilizes the dog as the experimental animal.

[Clinical study of grade 3, superficial transitional cell carcinoma of the urinary bladder].

PURPOSE: To evaluate the treatment of grade 3 superficial (stage pTa and pT 1) transitional cell carcinoma (T.C.C.) of the urinary bladder, retrospective analysis was performed with special reference to tumor prognostic factors. MATERIALS AND METHODS: From July 1971 to september 1995, 51 cases with grade 3 superficial T.C.C. of the urinary bladder were treated. The survival rates and prognostic factors of these patient were analyzed. RESULTS: Five year survival rate of grade 3, superficial tumors was 92.3% and showed significantly better prognosis compared to patients with pT 2 and pT 3 tumors of grade 3 (p < 0.001). As a initial treatments, transurethral resection (TUR) was conducted in 45 patients (88%). Intravesical recurrence was observed in 20 of 45 patients (44%) and 12 of 20 patients (60%) were recurred within 1 year. Non-recurrent rates of the patients treated with TUR were 69.6% at 1 year, 58.8% at 3 year, 49.7% at 5 year, respectively. No significant differences were noted regarding factors of tumor size, figures and a number of tumor. Of the 51 patients, 10 (19.6%) progressed beyond stage T 2 and 6 died with the disease. Survival rates at 10 years follow up in patients with non-papillary and papillary tumor were 57.1% and 97.8%, respectively. CONCLUSION: These results suggested that TUR should be performed as a initial treatment for the patients with grade 3 superficial T.C.C. of the urinary bladder. However, non-papillary tumors should be considered of more intensive treatment like as radical cystectomy, adjuvant chemotherapy or irradiation.

[Clinical effects of Juzendaiho-to on immunologic and fatty metabolic states in postoperative patients with gastrointestinal cancer].

Juzen-daiho-to is one of the Chinese traditional medicines which is usually applied with patients suffering from anemia or chronic exhaustive disease. Twenty-three patients after gastrectomy and 16 patients after colectomy were studied for NK cell activity, blastogenesis by PHA, several T-lymphocyte subsets, serum triglyceride and serum lipo-protein before drug administration at one, three, six, nine months and one year after the start of drug administration respectively. A remarkable elevation in NK cell activity was noted 3 and 6 months after the drug administration. Statistical analysis shows a significant converse correlation between NK cell activity and lipo-protein value in the group given Juzendaiho-to.

[Efficacy of etoposide in bone metastasis of breast cancer].

We have used ADM, MMC, CDDP and other drugs for a case of bone metastasis of breast cancer, but the bone destruction was advanced and she could not walk. We have also used etoposide, a new chemotherapeutic drug, for the same case. Two months later bone sclerosis was seen by X-ray film and pain disappeared. Bone sclerosis then advanced after 6 months, she has begun to stand, and after 8 months she has been able to walk with a cane. There was no severe side effect. Etoposide was very effective for bone metastasis of the breast cancer.