Protective role of protein C inhibitor in monocrotaline-induced pulmonary hypertension.

BACKGROUND: Protein C inhibitor (PCI) plays a role in multiple biological processes including fertilization, coagulation, fibrinolysis and kinin systems. OBJECTIVES: We hypothesized that PCI participates in the pathogenesis of pulmonary hypertension. To demonstrate this, we compared the development of pulmonary hypertension in mice overexpressing PCI in the lung with wild-type (WT) mice. Pulmonary hypertension was induced by s.c. injection of 600 mg kg-1 of monocrotaline weekly for 8 weeks. RESULTS: Right ventricular arterial pressure was significantly increased in monocrotaline-treated WT mice compared with that in monocrotaline-treated transgenic mice. Bronchoalveolar lavage fluid (BALF) levels of thrombin-antithrombin complex, monocyte chemoattractant protein-1 and platelet-derived growth factor, and the plasma level of tumor necrosis factor-alpha were significantly increased in monocrotaline-treated WT mice as compared with monocrotaline-treated PCI transgenic mice. Increased level of PCI-thrombin complex was detected in BALF from monocrotaline-treated PCI transgenic mice as compared with saline-treated PCI transgenic mice. CONCLUSIONS: This study showed that increased expression of PCI in the lung is protective against monocrotaline-induced pulmonary hypertension, suggesting a potential beneficial effect of PCI for the therapy of this disease.

Release of tetrodotoxin and paralytic shellfish poison from puffer liver by RNase.

A nontoxic high-molecular fraction was separated from the extracts of toxic liver of a puffer, Takifugu poecilonotus, by Sephadex G-50 gel filtration. This fraction became toxic when digested with RNase T2. The toxins were partially purified by activated charcoal treatment, followed by chromatography on Bio-Gel P-2 and Bio-Rex 70, and were analyzed by TLC and electrophoresis. The results showed that most of the toxicity is accounted for by tetrodotoxin, and the remainder by saxitoxin and other unidentified toxins. The corresponding high-molecular fraction separated from nontoxic liver of another puffer, T. rubripes, did not release any toxin on RNase digestion.

Intrathecal injection of high-dose meglumine amidotrizoate with complete recovery.

Rarely we are faced with accidental spinal injection of potentially toxic substances. We present 2 cases in which amidetrizoate, water-soluble ionic contrast medium, was accidentally injected intrathecally. Our treatment consisted of vigorous hydration and barbiturate coma. This report suggests that for water-soluble ionic contrast media increasing cerebrospinal fluid circulation by vigorous hydration may be as effective as spinal lavage in diminishing toxicity.

Acetylcholine-induced endothelium-derived contracting factor in hypoxic pulmonary hypertensive rats.

We determined the role of an endothelium-derived contracting factor in the impaired relaxation response to ACh of conduit pulmonary arteries (PAs) isolated from rats with hypoxic pulmonary hypertension (PH). A PGH2/thromboxane A2 (TxA2)-receptor antagonist (ONO-3708) partially restored the impairment of ACh-induced relaxation, whereas TxA2 synthase inhibitors (OKY-046 and CV-4151) did not affect the impaired relaxation in phenylephrine-precontracted hypertensive PAs. Endothelium-denuded hypertensive PA rings showed no difference in the response to ACh between preparations with and without ONO-3708. In both endothelium-denuded control and hypertensive PAs, exogenous PGH2 induced contractions, and the magnitude of the contractions was greater in the control than in hypoxic PH preparations. An endothelin A-receptor antagonist (BQ-485), an endothelin B-receptor antagonist (BQ-788), and a superoxide anion scavenger (superoxide dismutase) did not restore the impaired response to ACh in hypertensive PAs. These findings suggest that PGH2 produced from the conduit PAs of rats with chronic hypoxic PH may be the endothelium-derived contracting factor responsible for the impairment of ACh-mediated vasorelaxation.

Effects of lisinopril and nitrendipine on urinary albumin excretion and renal function in patients with mild to moderate essential hypertension.

The present study was designed to evaluate the effects of an ACE inhibitor, lisinopril, and a calcium antagonist, nitrendipine, on urinary albumin excretion (UAE) and renal function in mild to moderate essential hypertensive patients with microalbuminuria. After the 4-week drug-free period, 17 patients were randomly divided into two groups. The first group (group 1: n=8) received lisinopril 10-20 mg daily for 8 weeks followed by nitrendipine 5-10 mg daily for another 8 weeks. The second group (group 2: n=9) received nitrendipine 5-10 mg daily for 8 weeks followed by lisinopril 10-20 mg daily for another 8 weeks. The mean blood pressure (MBP) significantly decreased in a similar manner in both groups. UAE significantly decreased after 8 weeks of treatment with lisinopril in group 1 and after 8 weeks of subsequent treatment with lisinopril in group 2. On the other hand, UAE was not altered by treatment with nitrendipine. The changes in UAE were significantly correlated with changes in MBP after 8 weeks of treatment with nitrendipine, but not after 8 weeks of treatment with lisinopril. No significant changes in creatinine clearance, urinary excretion of sodium or urinary N-acetyl-beta-D-glucosaminide were observed by any treatment in either group. These results suggest that lisinopril, not nitrendipine, reduces UAE in essential hypertensive patients with microalbuminuria independently of its effective antihypertensive properties.

Occurrence of tetrodotoxin in the gastropod mollusk Tutufa lissostoma (frog shell).

Paralytic toxicity was detected in gastropod mollusk Tutufa lissostoma (frog shell) specimens collected from Suruga Bay, Shizuoka Prefecture, Japan. Seventeen of the 22 digestive glands removed were toxic; the highest toxicity, expressed as tetrodotoxin (TTX), being as high as 700 mouse units (MU) per gram. Attempts were made to isolate the toxin from pooled digestive glands by activated charcoal treatment and column chromatography on Amberlite IRC-50, CM-Sephadex C-25 and Bio-Rex 70. The toxin showed a specific toxicity (as TTX) of 4200 MU/mg. It exhibited the same thin-layer chromatographic and electrophoretic behaviors and 1H-NMR spectrum as TTX. The toxin gave the same pattern as the TTX standard when alkali-hydrolyzed and analyzed by GC--MS, indicating that it contains the quinazoline skeleton specific to TTX. From these results the frog shell toxin was identified as TTX.

Occurrence of saxitoxin and other toxins in the liver of the pufferfish Takifugu pardalis.

Highly toxic livers of the pufferfish Takifugu pardalis were extracted with acidic ethanol. The toxins extracted were partially purified by chromatography on Bio-Gel P-2 and then Bio-Rex 70, resulting in separation into three fractions I, II and III. ratios of total mouse units per fraction were approximately 0.1:100:0.01, respectively, with tetrodotoxin (TTX) as standard. By TLC, electrophoresis and a TTX analyzer, Fr. II was identified as TTX and, unexpectedly, Fr. III as saxitoxin, while Fr. I remains unidentified.

Occurrence of tetrodotoxin in the flatworm Planocera multitentaculata.

The paralytic toxin which occurs in a flatworm Planocera multitentaculata was partially purified by column chromatography using Bio-Gel P-2 and Bio-Rex 70 (H+ form). Thin-layer chromatographic, electrophoretic and gas chromatography-mass spectrometric analyses demonstrated that the flatworm toxin is tetrodotoxin.

Mathematical modelling for intra-specific brood-parasitism: coexistence between parasite and non-parasite.

In this paper, we consider an aspect of the intra-specific brood-parasitism with a mathematical modelling. As in case of moorhen Gallinula chloropus, the case dealt with in this paper in such that just a part of the whole population has the parasitising behaviour against the individuals belonging to another part of non-parasite subpopulation that does not have such behaviour. Analysing the expected fitness gain from the brood-parasitism, we consider the condition in order that parasite individuals coexist with non-parasite ones within a population. From the mathematical modelling analysis, it is shown that the stable equilibrium frequency of parasite individuals within a population, if exists, depends on the difference among individuals in terms of the individual quality reflected to the survival probability of bred offsprings.

The optimal strategy for brood-parasitism: how many eggs should be laid in the host's nest?

We consider the optimal strategy for intra-specific brood-parasitism, especially with respect to the number of eggs laid by the parasitic individual in the nest of non-parasitic individual, in particular, a host that does not reject the parasite's eggs. With a fundamental mathematical model, assuming that the survival probability of the parasite's offspring in the nest of the host is significantly smaller than that in parasite's own nest, we determine the optimal number of eggs laid in the nest of host that maximizes the expected reproductive fitness of the parasite. We show that the invasion success of brood-parasitism could significantly depend on the total number of eggs laid by the parasite in a breeding season, and that the successfully invading brood-parasitism could realize maximum fitness with a specific number of parasite's eggs laid in the nest of the host.

Production and product quality assessment of human hepatitis B virus pre-S2 antigen in submerged and solid-state cultures of Aspergillus oryzae.

Pre-S2 is a diagnostically important antigen of human hepatitis B virus (HBV). In order to produce pre-S2 antigen in Aspergillus oryzae, the gene [pre-S2]3, which encodes a tandemly triplicated repeat of pre-S2 polypeptides was fused with the partial glaA gene encoding glucoamylase lacking the starch-binding domain. In submerged culture, A. oryzae transformants carrying glaA-[pre-S2]3 secreted a heterogeneously glycosylated form of the fusion protein that was partially degraded. Contrarily, utilization of a wheat brain solid-state culture system resulted in the secretion of a homogeneous glycosylated form of the whole fusion protein. This is the first report of a dissimilarity in glycosylated modification between submerged and solid-state culture conditions in heterologous protein production in A. oryzae.

Characteristics of bath-related burns in Japan.

A retrospective study of bath-related burn injuries was carried out at our institution. A total of 216 patients with burns were admitted between 1982 and 1996. Bath-related burns were identified in 58 patients (26.9%). The number of patients with bath-related burns increased throughout the study period. The percentage body surface area burned was 43.8 +/- 25.7% in the bath-related burn group and 27.3 +/- 28.3% in the bath-unrelated burn group. This difference was significant. There was no significant difference between the two groups with respect to mortality rate. The mechanism by which the patients sustained a bath-related burn clearly differed according to age. The percentage of burns which are bath-related and the severity of bath-related burns are higher in Japan than in any other country. This can be attributed to lifestyle, bathing systems, bathroom architecture, housing conditions and an increase in the elderly population. These burns can be prevented. Education based on this study will play a critical role in the prevention of the bath-related burn injuries.

Burns in a suicide attempt related to psychiatric side effects of interferon.

A 50-year-old woman was admitted to our critical care center after pouring lamp oil on herself and setting herself on fire. Diagnosed with chronic hepatitis, she had received interferon-alpha at another hospital. During interferon therapy she developed anxiety, irritability, sleeplessness, and depression. At our hospital she underwent fluid resuscitation according to the method of Baxter. After treatment with topical cream and ointment, she underwent skin grafting. Interferon was not given. After discharge, wound healing proved satisfactory. She was intelligent and insightful, and her mental condition remained stable with no apparent emotional problems. As she had no significant past medical or psychiatric history and no history of substance abuse, we believe that her depression was a side effect of interferon therapy. A number of reports have described depression and other psychiatric disorders associated with interferon, but none of these accounts have concerned burns sustained in suicide attempts. This case underscores the potential seriousness of adverse reactions to interferon characterized by emotional disturbance and also illustrates that physicians who treat burn patients need to have an understanding of affective disorders and unusual side effects of medication.

Transient pulsus alternans induced by isosorbide dinitrate: echocardiographic and hemodynamic evidence of reduced venous return--a case report.

Transient pulsus alternans was induced by isosorbide dinitrate (ISDN) in a patient with postmyocarditis congestive heart failure under diuretic therapy. The severity and duration of pulsus alternans depended on the dose of ISDN. According to the echocardiographic and hemodynamic examinations, the superimposed preload reduction caused by ISDN combined with decreased blood volume owing to diuretic therapy most likely contributed to the development of pulsus alternans.

Effects of lidocaine on basilar membrane vibration in the guinea pig.

The effects of lidocaine on basilar membrane (BM) vibration and compound action potential (CAP) were studied in guinea pigs in order to elucidate the site of lidocaine action in the cochlea. BM vibration was measured with a laser Doppler vibrometer through an opening made in the lateral bony wall of the scala tympani at the basal turn. Ten min after local administration of lidocaine (250 microg) into the scala tympani, the velocity of BM vibration and the CAP amplitude decreased significantly at around the characteristic frequency of the stimulus sound (p < 0.05). The maximum decreases were 4 dB in the velocity of the BM vibration and 40 dB in the CAP amplitude. In contrast, such changes were not observed after i.v. injection of lidocaine (1.5 mg/kg). These results suggest that when lidocaine is administered locally in the cochlea it acts not only on the cochlear nerve but also on the outer hair cells.

[Clinical study of imipenem/cilastatin sodium in serious infections in critical care medical center].

Patients with severe trauma and illness were treated at our critical care medical center. Many of these patients have diabetes, anemia and other underlying conditions which sometimes lead to serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. A clinical study imipenem/cilastatin sodium (IPM/CS) was performed at our Medical Center. IPM/CS was administered to 30 patients with serious infections. Clinical results were excellent in 11, good in 5, fair in 9 and poor in 5 patients, thus an overall efficacy rate of 53.3% was obtained. Bacteriological efficacy rate was 50% with eradications in 11 cases and decreases in 3 cases out of 28 cases examined. No side effects were observed in any patients.

[Rectal cancer therapy compatible with preservation of function].

Rectal cancer surgery causes often postoperative morbidities such as defecation disturbance, dysuria and male sexual impotence. Compatibility of cancer eradication and function preservation are the problem should be resolved in the rectal cancer surgery. Defecation function were preserved in the patients with middle and upper rectal cancer by anterior resection transsacral resection, invagination or pull-through operation. Since 1984, usage of suture instruments made it practicable to increase sphincter preserving operation up to more than 65% of rectal cancer. Postoperative 5-years survivals were 81% of anterior resection, 71% of invagination operation and 57% of pull-through. Autonomic nerves preserving operation (ANP), aimed to prevent the urinary and sexual disfunction were studied both sides of the cancer spreads and extend of nerve plexuses. And ANP were adopted to the 185 cancers, limited to the submucosa or the proper muscle coat, by Study Group of Welfare Ministry. Their postoperative disfunction decreased to 15% of urination and 21% of male potency, while 33% and 81% respectively following conventional operation. Local excision for early cancer, which are defined as mucosal or submucosal cancer are discussed.

[Study of long-survival cases with liver metastasis of colorectal cancer by hepatic arterial infusion chemotherapy].

We performed arterial infusion chemotherapy through hepatic artery in 33 patients with liver metastasis of colorectal cancer. Regarding the survival rate, the 1-year survival rate was 55.6% and the 5-year rate was 27.8% in cases of H2, and 1-year as 28.9% in H3. According to criteria of Saito-Koyama, the response rate was 24.2%, including 2 CR and 6 PR cases. There were more patients with H2 factor and without peritoneal dissemination who survived for one year and more. The dose of 5-FU was 9.6 +/- 3.6 g in case of longer survivals and 5.1 +/- 3.0 g in non-responders. There were significant differences between them. The pretreatment value of CEA was lower than 100 ng/ml in 8 of 11 longer survivals, and the CEA values were decreased after this treatment in 9 of 11 responders. On the other hand, it was noted that the non-responders had a higher level of CEA such as more than 100 ng/ml, and in these cases CEA was not decreased after treatment. There are two favourable responders who are still living 9 and 5 years after successful treatment. Their pretreatment value of CEA was lower at 13.6 and 23.8 ng/ml, respectively, and these levels were decreased to 1.0 ng/ml with administration of 5-FU with ADM and 5-FU with MMC. It was concluded that arterial infusion chemotherapy was good for treatment of metastatic liver tumors from colorectal cancers.

[Diagnostic value of magnetic resonance imaging in postoperative maxillary cyst].

Magnetic resonance imaging (MRI) is superior to conventional X-ray tomography and CT scanning in detecting postoperative maxillary cysts (POMCs). We analyzed the MRI features of 51 cases (72 sides) and compared them with the operative findings of 42 cases (52 sides) of POMC. The total number of cysts diagnosed was 121. Multiple cysts were found in 37 sides (51%) and bilateral cysts were found in 21 cases (45%). According to classification of POMC based on location in the maxilla the central cysts were found in only 38% of all cysts (peripheral ones in 62%). In the 42 patients operated on, 69 of 83 cysts which had been detected by MRI were confirmed, whereas there were two additional cysts which could not be diagnosed preoperatively. Sixty four of 71 cysts were opened to the nasal cavity under endonasal endoscopic control. The other seven cysts (five sides) were operated on via a buccogingival incision. Detailed and accurate diagnosis by MRI and development of endoscopic instruments enabled endonasal surgery in most (91%) sides of the POMC. In five cysts of the superior type which are small isolated and distant from the lateral wall of the nasal cavity, endoscopic endonasal surgery was not indicated. In conclusion, MRI for POMC was extremely helpful in selecting a surgical approach.