The effect of testosterone on plasma GH secretory profiles was examined in unrestrained adult female Wistar rats. Some of the rats were ovariectomized. One or 2mg testosterone propionate was injected sc daily for 21 days starting 3 weeks after the ovariectomy. The control rats received Sesame oil. Four to 5 days prior to use, all of the rats were provided with two indwelling cannulae, one in the right atrium for undisturbed blood collection and the other in the inferior vena cava for vehicle or synthetic human GH-releasing factor [1-44] NH₂, (GRF) infusion. Vehicle or GRF was administered by infusion pump (0.6ml/h) at a dose of 50ng/kg BW/min for 6h. Serial blood specimens were obtained every 20 min.
In intact female rats, pulsatile GH secretion occurred irregularly at 1-2h intervals and GH values at the trough period fluctuated during a 6-h vehicle infusion. During a 6-h GRF infusion, a striking elevation of basal GH levels was observed and the number of pulsatile GH secretion increased. GH secretory profiles during a 6-h vehicle and GRF infusion in the ovariectomized rats did not differ from those observed in the intact female rats. A dramatic change in plasma GH secretory profile was observed in the ovariectomized rats that had received testosterone. In these rats, pulsatile GH secretion occurred regularly every 3-3.2h during a 6-h vehicle infusion and trough GH values were maintained at a low level with little fluctuations. Among ovariectomized rats that had received testosterone, the amplitude of pulsatile GH secretion was augmented significantly while GH secretion during the trough period was markedly inhibited. These effects of testosterone on GH secretory profiles were dose dependent.
The results suggest that testosterone increases the release of somatostatin, which mediates intermittent tonic inhibition on GH secretion, and thereby alters plasma GH secretory profiles in female rats.

View full abstract

Nicardipine hydrochloride, which is one of the Ca²⁺ antagonists, was administered to two SHRSR (stroke-resistant spontaneously hypertensive rats) groups. In one group it was administered for 3 weeks (short-term T-SHR) and in the other for 8-10 weeks (long-term T-SHR). The degree of cerebral ischemia induced by BLCL (bilateral common carotid artery ligation) was investigated in the two groups as well as in two corresponding controls (U-SHR). The brain metabolites. (ATP, lactate, c-AMP) and brain water content were analysed 4h after BLCL, and histopathological changes were observed by scanning electron microscopy (SEM) 3h after BLCL. The influence. of duration of antihypertensive treatment and the ameliorating effect of the long-term treatment on experimental cerebral ischemia were discussed in this report.
ATP level in the short-term T-SHR group was higher than that in the U-SHR group after BLCL. However, there was no significant difference in lactate and c-AMP levels between these two groups. The brain water.content in the occipital region after BLCL in the. short-term T-SHR group was significantly lower than that in the U-SHR group, but there was no difference in the frontal region between the two groups. In the long-term T-SHR group, ATP and c-AMP levels were significantly higher than in the U-SHR group, and the lactate level was significantly lower. Furthermore the brain water content after BLCL in the long-term T-SHR group was significantly lower than in the USHR group in both the frontal and occipital portions. There was a more significant amelioration of the brain metabolism and brain edema after BLCL in the long-term T-SHR group than in the shortterm T-SHR group.
From the observation of SEM in the brain vessels after BLCL, the short-term and long-term TSHR groups showed less propagation of microvilli on the endothelial surface than either U-SHR group. Vasoconstriction was observed in these U-SHR groups. The marginal folds were shown to remain in both the short-term and long-term T-SHR groups after BLCL. However, in this histopathological study, the vascular endothelial ischemic changes of the brain vessels were much less in the long-term T-SHR group than in the short-term T-SHR group.
These results indicate that long-term antihypertensive treatment significantly contributed to the amelioration of ischemia.

View full abstract

A new type of amphipathic antigen was purified from phenol-water extracts of whole cells and culture supernatant of Streptococcus sanguis ATCC 10557 (biotype B, serotype II) and characterized as a fatty acid-substituted heteropolysaccharide.
The phenol-water extract was applied to columns of Sepharose 6B and octyl-Sepharose CL-4B. Immunologic activity of each fraction was checked by passive heamagglutination (PHA) and immunodiffusion tests against anti-10557 serum obtained by immunizing rabbits with whole cells of strain ATCC 10557. Gel filtration of the extract on a column of Sepharose 6B showed that strong PHA activity was present in the first hexose-containing fraction eluted near the void volume, indicating that this fraction contained an amphipathic antigen. Chromatography of this fraction on a column of octyl-Sepharose CL-4B showed that strong PHA activity existed in the hexose-containing peak which was eluted with 33% (v/v) n-propanol. This peak contained only 1% of phosphorus, indicating that the cells of strain ATCC 10557 posess an amphipathic antigen which differs from lipoteichoic acids that are common in many Gram-positive bacterial strains. This amphipathic antigen was a fatty acid-substituted heteropolysaccharide composed of mannose, glucose, galactose, rhamnose, galactosamine, glycerol and fatty acids in a molar ratio of approximately 4.3 : 1.0 : 1.5 : 0.6: 0.5: 0.1: 0.9. The PHA reaction was inhibited in the presence of polymelized mannose.
The second hexose-containing peak in the chromatography of Sepharose 6B produced a heavy band against anti-10557 serum in immunodiffusion test but had no PHA activity. The isolated material of this peak contained glucose, galactose, rhamnose and N-acetylgalactosamine in a molar ratio of approximately 1.0 : 1.4 : 0.8: 0.8, which was essentially identical to serotype II carbohydrate antigen reported previously.

View full abstract

The positive rate of patch test reactions to neomycin was studied for a period of 19 years. A patch test for 20% neomycin in white petrolatum was performed in 1867 cases of contact dermatitis or drug eruption. The comparison of this positive rate was made by dividing the 19 years into four periods. In the first period (1966-1970), the positive rate of patch test reactions to neomycin was comparatively higher than in the other three periods (p<0.01, x²-test). All of the positive patients tested had a history of neomycin use. After 1971, the frequency of positive reactions was stabilized at the rate of 3-5% in all of the patients tested : and also 1-3% in the patients with an obvious history of neomycin use. The difference in the frequency was considered to be caused by crosssensitization due to other aminoglycosides.
The positive rate of patch test reactions to the other aminoglycosides was also studied for 10 years (1975-1984). This patch test was performed in 473 cases of contact dermatitis or drug eruption caused by the use of antibiotics. The positive rate of patch test reactions to either one or more of the aminoglycosides was 11% (52 among 473 cases). As the positive rate of patch test reactions is not stabilized each year, there has been no obvious tendency of a gradual increase in the positive rate in recent years. However, close attention to the usage of the term, "cross-sensitization", seems to be necessary because of the increase in the indeterminate variety of allergens and their proceedings.
The suitable concentration of each allergen used for a patch test was also examined on the basis of the relationship between the concentration of allergens and the results of patch test reactions. From the results of our study, the suitable concentration of allergen used for a patch test is considered to be as follows : 10% in neomycin, bekanamycin, kanamycin, gentamicin and amikacin, and 20% in toburamycin and aminosidine.

View full abstract

It is generally accepted that herpes zoster, localized or disseminated, is one of the dermadrome (viscerocutaneous syndrome), which often combine with malignant complications such as visceral malignant tumor, leukemia, malignant lymphoma and so forth. However, as far as concerning to the general outpatients, the rate of the occurence of malignant complications in the patients with herpes zoster is not very high.
A rapid and reliable method for screening the malignancy in these patients with herpes zoster is required, therefore, instead of that all the patients should be received cumbersome examinations.
In the present paper, the author tried to examine two kinds of skin tests, a tuberculin test and a 2, 4 dinitro-l-chlorobenzene (DNCB) induced cutaneous hypersensitivity reaction, if these tests are effective in this respect. The results showed that the risk of complicated malignancy was distinctly high when both skin tests were negative, whereas the risk of malignancy was low when either one of the tests was negative.
It may be conculuded that it is better to do both the tuberculin and the DNCB skin tests to all of the patients with herpes zoster, and only when both tests are negative, the detailed examinations for malignancy and their follow-up should be done.

View full abstract

The effect of water-soluble iodinated contrast media on erythrocyte membrane was investigated systematically by the measurement of shape change and viscosity of red cell suspension the osmolality, viscosity and iodine content of all agents were arranged in proper. There was little difference in blood viscosity under the isoosmolality condition (300mOsm/kgH₂O) between ioxaglate solution (1.46cp), diatrizoate solution (0.96cp) and NaCl solution (0.8cp), while a little shape change was induced by ioxaglate and by diatrizoate under this condition. It was, therefore, evident that the difference in blood viscosity was due mainly to the difference in viscosity of contrast solution. Metrizamide caused a striking shape change and an increase in blood viscosity under this condition. An increase in blood viscosity was induced by hypertonic diatrizoate solution under the condition of equal viscosity (1.29cp, 618mOsm/kgH₂O) and of equal iodine content (115mgI/ml, 623mOsm/kgH₂O). These hypertonic diatrizoate solutions also caused remarkable shape changes, which were almostly equivalent to those induced by hypertonic NaCl solution (628mOsm/kgH₂O). Ioxaglate solution, the osmolatity of which was almost isotonic under these conditions, had less rheological and morphological effects on erythrocytes than diatrizoate solution. It was, consequently, clear that the rheological effect of the contrast solution was attributable only to the viscosity of contrast solution but also to the osmolality of it. There was little difference in blood viscosity and in red cell shape between ioxaglate, diatrizoate and NaCl solution under the physiological condition (300mOsm/kgH₂O, 15.0mgI/ml, 0.8cp). Metrizamide, however, caused obvious shape change and increase in blood viscosity even under this condition. It appeared that the effect of metrizamide solution on erythrocyte membrane was not attributable to viscosity or osmolality but to loss of membrane stability induced by certain direct effect of metrizamide on cell membrane. This experiment showed also that the iodine conjugated in contrast compounds were less toxic than free iodine ion.
In conclusion, it, was revealed that the membrane stability of erythrocytes ought not to be changed by contrast media. Furthermore, the osmolality of a contrast solution was elucidated as animportant factor more than the viscosity or iodine content in reference to the physiological behavior of erythrocytes.

View full abstract

The effects of propranolol on portal venous pressure were evaluated in 17 patients with hepatic cirrhosis, three with precirrhosis, one with PBC and one with chronic aggressive hepatitis.
After intravenous infusion of 5mg of propranolol for 10 minutes, wedged (WHVP) and free hepatic venous pressure (FHVP), estimated hepatic blood flow (EHBF), cardiac index (CI) and total systemic vascular resistance (TSR) were measured.
Thirty minutes after the initiation of the infusion, portal venous pressure (PP: WHVP-FHVP) decreased significantly by 26% and this effect persisted for 60 minutes. The heart rate, CI and EHBF were reduced significantly by 12%, 21% and 14%, respectively, whereas TSR increased by 28%. In 6 patients with cirrhosis, the serum propranolol level measured by high liquid chromatography registered 16.2±5.3ng/ml 30 minutes after the infusion.
After the infusion of vasopressin (0.2U/min), given for a comparative study with propranolol, PP decreased by 36% at 5 minutes. However, the difference of reduction in PP between the two agents was insignificant.
Following the oral administration of 30mg of propranolol per day over a period of one month to 8 patients with cirrhosis, the serum propranolol level measured in fasting state in the morning was 37.8±20.Ong/ml.
The present investigation demonstrates that the intravenous administration of 5mg of propranolol results in a sufficient serum concentration of propranolol and a significant reduction in PP. It was also found that the serum concentration of propranolol can be maintained if a dosage of 30mg of propranolol per day is administered to patients with cirrhosis. Consequently, it is well documented that this dosage would serve as a suitable treatment of portal hypertension in cirrhotic patients.

View full abstract

The author carried out an ultrastructural investigation into the causative mechanism of pulmo nary fibrosing alveolitis induced by Paraquat administration to the rats on a chronological basis. An attempt was made to correlate the morphological changes with the surfactant activity which was measured by the modified Wilhelmy Balance (Nozaki).
The results obtained are as follows :
1) After Paraquat administration, swelling and degeneration of the type I epithelial cells were observed. The aggregate of fibrin and polymorphonuclear cells was also noted. Then the changes of the osmiophilic bodies of type II epithelial cells were discernible, followed by interstitial edema.
2) In a rather prolonged stage, activated fibroblasts and myofibroblasts increased in number while fibro-collagenous tissue proliferated in alveolar space. Activation of type II epithelial cells and alveolar macrophages was also striking. Intra-luminal narrowing of vasculature, microthrombus formation as well as perivascular fibrosis were also remarkable.
3) The tannic acid stain disclosed the elastic fiber component. The elastic fibers which were basically composed of elastin and elastic microfilaments were undergoing extensive degeneration which was clearly associated with the proliferation of the fibro-collagenous fibers. In this context, the alteration of the elastic component was closely associated with the causative mechanism of pulmonary fibrosis in this particular condition.
4) The alteration of the pulmonary surfactant which was measured by the modified Wilhelmy Balance (Nozaki) disclosed an intimate interrelation between disruption of the alveolar lining layer as well as degeneration and loss of the type II epithelial cells.
5) Thus it is concluded that the pulmonary fibrosing pathology induced by the Paraquat injection may offer a very versatile experimental model to clarify the initial and progressive stages of fibrosis of the lung.

View full abstract