Stresgenin B, an inhibitor of heat-induced heat shock protein gene expression, produced by Streptomyces sp. AS-9

Stresgenin B was isolated as an inhibitor of heat-induced heat shock protein (HSP) gene expression from a culture broth of Streptomyces sp. AS-9 by silica gel chromatography and HPLC. The molecular formula of the novel compound was determined as C11H13NO5 by high resolution FAB-MS analysis, and the structure was determined by UV, 1H NMR, 13C NMR, HMQC, HMBC, and NOESY spectra. Stresgenin B inhibited heat-induced luciferase reporter-gene expression directed by the human hsp70B promoter in Chinese hamster ovary (CHO) cells at concentrations lower than the concentrations for inhibition of dexamethasone-induced luciferase reporter-gene expression directed by the mouse mammary tumor virus (MMTV)-LTR promoter. The inhibition of heat-induced reporter gene expression was evident even when cells were exposed to stresgenin B only during heat stress treatment. Moreover, the compound inhibited heat-induced syntheses of hsp72/73, hsp90, and hsp110 and thereby suppressed the induction of thermotolerance. Stresgenin B showed moderate cytotoxic activities against several neoplastic cell lines and also showed antibacterial activities against Micrococcus luteus, Bacillus subtilis and Staphylococcus aureus strains.     

Endogenous ATP released by electrical field stimulation causes contraction via P2x- and P2y-purinoceptors in the isolated tail artery of rats

Electrical field stimulation (EFS) caused contraction of isolated tail arteries of rats. The EFS-induced contraction showed frequency-dependence and was entirely abolished by the sodium channel blocker tetrodotoxin (1 x 10(-7) M). The EFS-induced (at 20 Hz) contraction was reduced by about 60% in the presence of phentolamine (1 x 10(-6) M). Therefore, later experiments were carried out in the presence of phentolamine. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (1 x 10(-8)-1 x 10(-6) M) and basilen blue E-3G (3 x 10(-5)-5 x 10(-5) M), P2-receptor antagonists, significantly inhibited the contraction evoked by EFS. In addition, PPADS significantly inhibited the contractions induced by ATP (1 x 10(-4) M) and a selective P2x-receptor agonist, alpha,beta-methylene ATP (1 x 10(-6) M). In contrast, basilen blue E-3G did not inhibit alpha,beta-methylene ATP-induced contraction. The ecto-ATPase activator apyrase (5 and 10 U/ml) significantly reduced the EFS-induced contractions. These findings suggest that endogenous ATP released by EFS causes contractions of rat tail artery via both the P2x-receptors and P2y-receptors.     

Flavonoids from Cleome droserifolia suppress NO production in activated macrophages in vitro.

The effect of an Egyptian medicinal plant, Cleome droserifolia (Forssk.) Del. on nitric oxide (NO) production in bacillus Calmette-Guérin-induced mouse peritoneal macrophages activated by lipopolysaccharide was investigated in vitro. The methanol extract of C. droserifolia reduced the NO production, and two flavonoids were isolated as the active components. The new one was determined to be 5,4'-dihydroxy-6,7,8,3',5'-pentamethoxyflavone (1) and the other was identified as 5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone (8-methoxycirsilineol; 2). Compound 1 concentration-dependently suppressed the NO production and was effective at a non-toxic concentration (12.5 micrograms/ml). The suppressive activity of 2 was weaker than that of 1.     

Intravaginal contraceptive sponge impregnated with nonoxynol-9. The development of sponge for clinical efficacy trials.

Newly designed intravaginal polyurethane sponges containing the spermicide nonoxynol-9 were developed for contraceptive purposes. The sponges were made by the polymerization of urethane monomers in a solution of nonoxynol-9. This new biomaterial is analogous to a large, thick cervical cup with a dimple in the center for ease of insertion and positioning to the cervix (and external os). There is no need for precoital planning or preparation for usage of this sponge. The release of the spermicidal agent from the sponges was 1st determined by soaking the sponges in saline and squeezing the nonoxynol-9 solution from them. In order to determine the actual amount of nonoxynol-9 released from the sponge, 2 analytic techniques were used. 1 method was ultraviolet spectoscopy and its accuracy ranged from 85-97%. The other was bioassay for the spermicidal activity and its accuracy ranged from 100-124%. To simulate the actual wearing of the sponge by a patient, the sponges were soaked in a large volume of saline and almost 50% of the spermicidal agent was released during the first 24 hours. In conjunction with the laboratory studies, a limited study to determine acceptability of the devices was investigated in normal women. The women were asked to wear the sponges for 1, 2, 3, 4, 5, 6, and 7 consecutive days. It was found that all women in the population could not tolerate the sponge longer than 5 days due to the odor. Thus, with the good release rates for 2-4 days and patient acceptability for 2 days of wear, a protocol for the use of the intravaginal sponge as a 2-day device was established. (author's)     

A case of Morgagni's hernia: availability of CT scan, ultrasonography, and trans-abdominal surgical approach

A 60-year-old obese woman was admitted to our hospital to receive surgical treatment for "slow-growing mediastinal lipoma". With the non-invasive examination such as CT scan and ultrasonography, she was revealed as Morgagni's hernia containing a greater omentum. With a trans-abdominal approach, we could take a good surgical field for the bilateral foramina of Morgagni. Several discussions were described for availability of CT scan, ultrasonography and a trans-abdominal approach.     

Development of rotary blood pump technology: past, present, and future

Even though clinical acceptance of a nonpulsatile blood flow was demonstrated almost 45 years ago, the development of a nonpulsatile blood pump was completely ignored until 20 years ago. In 1979, the first author's group demonstrated that completely pulseless animals did not exhibit any abnormal physiology if 20% higher blood flows were provided to them. However, during the next 10 years (1979-1988), minimum efforts were provided for the development of a nonpulsatile, permanently implantable cardiac prosthesis. In 1989, the first author and his team at Baylor College of Medicine initiated a developmental strategy of various types of nonpulsatile rotary blood pumps, including a 2-day rotary blood pump for cardiopulmonary bypass application, a 2 week pump for ECMO and short-term circulatory assistance, a 2 year pump as a bridge to transplantation, and a permanently implantable cardiac prosthesis. Following the design and developmental strategy established in 1989, successful development of a 2-day pump (the Nikkiso-Fairway cardiopulmonary bypass pump) in 4 years (1989-1993), a 2 week pump (Kyocera gyro G1E3 pump) in 6 years (1992-1998), and a bridge to transplant pump (DeBakey LVAD-an axial flow blood pump) in 10 years (1988-1998) was made. Currently, a permanently implantable centrifugal blood pump development program is successfully completing its initial Phase 1 program of 5 years (1995-2000). Implantation exceeded 9 months without any negative findings. An additional 5 year Phase II program (2000-2005) is expected to complete such a device that will be clinically available.     

Effects of local injection of ex vivo expanded autologous tumor-specific T lymphocytes in cases with recurrent malignant gliomas.

PURPOSE: The aim of this report was to indicate both the advantages and disadvantages of local cell transfer therapy using ex vivo expanded autologous tumor-specific T lymphocytes (ATTLs) for recurrent cases of malignant gliomas. EXPERIMENTAL DESIGN: Subjects are 10 cases of malignant gliomas consisting of 7 cases of glioblastoma multiforme, 2 cases of anaplastic astrocytoma, and 1 case of anaplastic oligoastrocytoma. All cases were recurrences. ATTLs were induced by coculturing peripheral blood mononuclear cells with autologous tumor cells in medium containing interleukin-1, -2, -4, and -6 and administered into the local tumor site in total numbers of 3-247 x 10(7) cells. As end points, tumor response and survival time were analyzed observing clinical state. RESULTS: Five cases responded to this therapy (namely, one case showed complete remission, and four cases had a partial response). There were three cases of no change, and two cases of progressive disease. The overall tumor response rate was 50%. No complications were noticed, except for two cases of minor local hemorrhage and eight cases of temporary fever. Nine cases died of further tumor progression, and one case died of aspiration pneumonia, and the cause-specific survival analysis indicates that the median survival time was 5 months from the initial ATTL injection. CONCLUSIONS: The results suggest that local administration of ATTLs is effective in recurrent malignant gliomas in that it demonstrated a high benefit:risk ratio with minor side effects. Although its antitumor effect may be temporary in some advanced cases, it is highly possible that the tumor could be stabilized when conditions are optimal.     

A Question and Answer E-Mail System for Responding to Query from the General Public with Which the System Manager Can Identify Delayed Replies

We constructed a question and answer system for direct delivery of E-mail queries from the general public to the proper hospital representative and with which the system administrator can monitor E-mail replies. The system consists of two sub-systems; one is an E-mail questionnaire sub-system that automatically delivers E-mail queries to the proper person and an E-mail reply monitor sub-system with which the system administrator can monitor the E-mail replies. The monitor system compares the origin address of the E-mail reply and the destination address on a questionnaire filled out at the time the query is made. In a test of the system, 56 queries were received in 31 days, with 37 replied to. The interval from receipt of an E-mail query to reply was calculated. Nineteen replies were submitted within 2 days.     

Involvement of M3 muscarinic receptors of the spinal cord in formalin-induced nociception in mice

Subcutaneous injection of formalin into a paw of mice caused two distinct phases of licking and biting, first phase (1-5 min) and the second phase (7-30 min) after the injection. The muscarinic antagonist atropine (0.1-10 ng, i.t.) and the M(3) receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (0.1-20 ng, i.t.) inhibited the second phase of this response, whereas higher doses of atropine (20-100 ng, i.t.) did not cause inhibition. The M(1) muscarinic receptor antagonist pirenzepine (10-100 ng, i.t.) did not inhibit either the first or the second phase response, but a high dose of pirenzepine (1000 ng, i.t.) tended to inhibit the second phase response. On the other hand, the M(2) muscarinic receptor antagonist 11-?(2-[(diethylamino)methyl]-1-piperidinyl?acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one (AF-DX116; 10-1000 ng, i.t.) had no effect on either the first or the second phase of response. The opioid receptor antagonist naloxone did not affect the 4-DAMP-induced anti-nociceptive response. The i.t. injection of the acetylcholinesterase inhibitor neostigmine (25 ng) significantly inhibited only the second phase. The acetylcholine (ACh) depletor hemicholinium-3 (HC-3) (1 microg, i.t.) completely abolished the 4-DAMP-induced anti-nociceptive response. The ACh content of the spinal cord was significantly increased 14 min after formalin injection. This significant increase in the ACh content was inhibited by pretreatment with 4-DAMP (10 ng, i.t.). These results suggest that endogenous ACh in the spinal cord acts as a transmitter anti-nociception, and that ACh release regulated by presynaptic M(3) muscarinic receptors in the spinal cord is involved in the second phase of nociception induced by formalin.