Immunohistochemical study of adenohypophysial gonadotropes in the musk shrew, Suncus murinus L. (Insectivora)

Most gonadotropes in the pituitary of male Suncus murinus L. are immunostained with both LH beta and FSH antisera, whereas only a few gonadotropes are positive only for LH beta. The former gonadotropes consist of polygonal or polyhedral cells of medium size, and can be identified by the presence of two types of secretory granules of low density: smaller ones (about 150-250 nm in diameter) which are spherical in shape, and larger ones of irregular form with a maximum diameter of about 1,500 nm. The endoplasmic reticulum is not prominent, while the Golgi apparatus is distinct. Mitochondria are found throughout the cytoplasm but are often concentrated in and around the region of the Golgi apparatus. These fine structural features are somewhat similar to those of the classical Barnes "FSH cells" and Kurosumi-Oota "FSH cells".     

Calcium uptake in the skin of a freshwater teleost.

The skin, particularly the opercular membrane of some teleosts, contains mitochondrion-rich "chloride" cells and has been widely used as a model to study branchial salt-extrusion mechanisms in seawater fish. Skin isolated from the operculum of the freshwater Nile tilapia (Oreochromis niloticus) can transport Ca2+ against an ionic and electrical gradient. Adaptation of Nile tilapia to a low-Ca2+ environment increased the capacity of the opercular membrane to transport Ca2+. The density of mitochondrion-rich cells increased in parallel with Ca2+ transport capacity. The results demonstrate net Ca2+ uptake by vertebrate skin and strongly implicate mitochondrion-rich cells as the site of Ca2+ uptake in fresh water.     

Spinal cord lesions block seizures or delay their onset in myelin-deficient rats: evidence that generalized tonic seizures can be triggered by abnormal spinal cord activity

The myelin-deficient mutant rat develops generalized tonic seizures and dies during the fourth postnatal week. Surgical constriction of the lower thoracic spinal cord, performed either after the seizures have appeared or before, eliminates the seizures, or delays their onset, and prolongs the life of the animals. These observations support the view that the seizures in these animals can be triggered by abnormal activity originating in the myelin-deficient spinal cord and can be blocked by preventing that activity from ascending to higher levels. Similar seizures and "paroxysmal" phenomena occur in other myelin-deficient conditions including multiple sclerosis.     

Change of blood pressure and pulse rate in intravenous urography

We monitored the blood pressure and pulse rate during routine excretory urography in 3002 patients (4832 examinations) using high osmolality contrast medium. After injection of contrast medium, the blood pressure was changed more than 20% of the pre-injection blood pressure lasting for more than 1 minute in 27 patients (27 examinations, 0.56%), including 8 patients with a hypertensive reaction (0.17%) and 19 patients with a hypotensive reaction (0.39%). In all 27 patients, transient tachycardia was seen along with the progress of blood pressure change. Bradycardia was associated with a severe hypotensive reaction in 2 patients. In 19 patients with a hypotensive reaction, the blood pressure was progressively decreased beyond 60 mmHg in 9 patients (0.18%) while the blood pressure was remained above 60 mmHg in 10 patients (0.21%). Treatment was not necessary in 8 patients with a hypertensive reaction as well as in 10 patients with a mild hypotensive reaction (above 80 mmHg). In these 18 patients, the examination would have been finished without a suspicion of the blood pressure change unless the blood pressure was monitored. In 9 patients with a severe hypotensive reaction (below 60 mmHg), the subjective or objective symptoms were present during the examination in 7 patients. They should be considered to have had "severe adverse reaction". In remaining 2 patients, there was no subjective or objective symptoms. We discussed possible mechanisms regarding the change of blood pressure and pulse rate after injection of contrast medium.     

Clinical experiences with a new membrane oxygenator with low priming volume (D702 MASTER FLO 51), studies during pulsatile and constant flow perfusion

The newly developed oxygenator "D702" is a compact hollow fiber membrane oxygenator with a priming volume of 170 ml. The maximum flow allowance is 4 liters per/minute. We used this oxygenator in 16 patients (11 infants and children, and 5 adults) undergoing various open heart surgery, and function of this oxygenator was studied. Pulsatile cardiopulmonary bypass was performed in 8 patients and nonpulsatile constant flow perfusion was employed in the remaining 8 patients. Our clinical experience showed excellent maintenance of PaO2 and PaCO2 during both pulsatile and constant flow bypasses. A low pressure drop was encountered across the membrane oxygenator, and therefore, this oxygenator is applicable for pulsatile cardiopulmonary bypass. The D702 is a very useful and applicable for a wide range of patients from infants to adults with a small body structure.     

Clinical application of indocyanine green angiography to choroidal neovascularization

In order to evaluate the clinical usefulness of indocyanine green video-angiography (IA), the angiographic features of choroidal neovascular membranes (CNM) were investigated in 27 eyes with choroidal neovascular diseases by means of standard fluorescein angiography (FA) and IA. FA showed the existence of CNM in 21 eyes and IA demonstrated evidence of CNM in 19 eyes, as "fan, comb or spotty hyperfluorescence" in the early stage and "leakage" in the late stage. In 6 out of 19 eyes the existence of CNM was shown by IA, while FA failed to identify the precise location and size of CNM due to the masking effect of overlying turbid fluid, massive hemorrhage or a large amount of serous fluid. The results imply that IA has an advantage over FA in cases where FA shows only the sign of occult choroidal neovascularization, and that IA can be applied to neovascular maculopathy as a routine examination.     

A new HPLC fluorimetric method to monitor urinary delta-aminolevulinic acid (ALA-U) levels in workers exposed to lead

Summary A new sensitive HPLC method for the determination of urinary delta-aminolevulinic acid (ALA-U) was used to evaluate the relationship between blood-lead (Pb-B) and ALA-U levels in male workers exposed to lead. The differences between the ALA-U levels determined by this method (ALAU-HP) and by a colorimetric method (ALA-U-CL) are discussed. The HPLC method gave values similar to the ALA-U-CL values at high ALA-U level. However, at low blood-lead levels (58 ± 22 g/l, n = 23), the mean ALA-U-HP level corrected by urinary creatinine level was one-third of the corrected ALA-UCL level (0.83 ± 0.14 and 2.4 ± 0.5 mg/g creatinine, respectively). A significant increase of the mean corrected ALA-U-HP level was observed at 162 ± 22 g/l Pb-B (P < 0.05, n = 26), while that of ALA-UCL was observed at 245 ± 30 g/l Pb-B (P < 0.01, n = 37). The regression equation based on the logistic model fitted well to the relationship data between the Pb-B level and the percentage of the subjects with corrected ALA-U-HP above the cut-off point (1.12 mg/g creatinine) and the expected Pb-B level for 50% response was 270 g/l Pb-B, while it did not fit well to the relationship data between Pb-B level and the percentage of the subjects with corrected ALAU-CL above the cut-off point (3.5 mg/g creatinine). The maximum responses for the two sets of corrected ALA-U levels were both observed at 625 ± 25 g/l. The corrected ALA-U level by HPLC method seems to be a useful indicator for biological monitoring of exposure to lead at low levels (< 400 g/l Pb-B = health-based biological limit, WHO) as well as high ones.     

In vivo activity on murine tumors of a novel antitumor compound,N-β-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]phenazine-6-carboxamide sodium salt (NC-190)

Summary A novel antitumor compound, N--dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of >200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1–5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a >280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1–5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1–5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a >300% ILS with a 60-day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3–10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1–5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3–10), and a >161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3–10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1–5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis.Abbreviations ILS increase in life span - MST median survival time - MMC mitomycin C - ADM adriamycin - CPA cyclophosphamide - 5-FU 5-fluorouracil     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.