Measurements of Strong-Interaction Effects in Kaonic-Helium Isotopes at Sub-eV Precision with X-Ray Microcalorimeters.

We have measured the 3d→2p transition x rays of kaonic ^{3}He and ^{4}He atoms using superconducting transition-edge-sensor microcalorimeters with an energy resolution better than 6 eV (FWHM). We determined the energies to be 6224.5±0.4(stat)±0.2(syst) eV and 6463.7±0.3(stat)±0.1(syst) eV, and widths to be 2.5±1.0(stat)±0.4(syst) eV and 1.0±0.6(stat)±0.3(stat) eV, for kaonic ^{3}He and ^{4}He, respectively. These values are nearly 10 times more precise than in previous measurements. Our results exclude the large strong-interaction shifts and widths that are suggested by a coupled-channel approach and agree with calculations based on optical-potential models.

Search for η

We measured missing mass spectrum of the ^{12}C(γ,p) reaction for the first time in coincidence with potential decay products from η^{'} bound nuclei. We tagged an (η+p) pair associated with the η^{'}N→ηN process in a nucleus. After applying kinematical selections to reduce backgrounds, no signal events were observed in the bound-state region. An upper limit of the signal cross section in the opening angle cosθ_{lab}^{ηp}<-0.9 was obtained to be 2.2 nb/sr at the 90% confidence level. It is compared with theoretical cross sections, whose normalization ambiguity is suppressed by measuring a quasifree η^{'} production rate. Our results indicate a small branching fraction of the η^{'}N→ηN process and/or a shallow η^{'}-nucleus potential.

Two cases of subacute thyroiditis presenting in pregnancy.

Subacute thyroiditis (SAT) is an extremely rare cause of thyrotoxicosis in pregnant women. Untreated, thyrotoxicosis may result in complications, such as prematurity and congenital malformations in the fetus. We report two cases of first trimester subacute thyroiditis, one mild and one severe. The severe case, as demonstrated by laboratory and ultrasound findings, was successfully treated with prednisolone. In this case, it was thought that the benefits of pharmacological therapy outweighed the risk of potential teratogenesis by the medication. In contrast, the milder case was managed conservatively and resolved without treatment. These cases illustrate how laboratory and ultrasound findings can be used to determine whether treatment should be initiated and, once begun, if medication levels need to be adjusted. In both cases, the pregnancies resulted in healthy full-term infants.

Synthesis of RepK of rolling circle plasmid pKYM is regulated by countertranscript and HU protein.

Replication of rolling circle plasmid pKYM was regulated by RepK, a plasmid-encoded initiator protein, with HU protein and antisense RNA (copRNA) that block the expression of RepK. HU protein bound to the repK promoter in the presence of RepK protein and inhibited the transcription of repK mRNA. The copRNA would hybridize to repK mRNA and induce a stem-loop structure in which the repK Shine-Dalgarno sequence is sequestered by base pairing. Sequence substitution experiments demonstrated that this stem-loop not only inhibits translation but induces premature termination.

New diagnostic method for pulmonary allograft rejection by measurement of bronchial mucosal blood flow.

We investigated the relationship between the rejection of lung allografts and the bronchial mucosal blood flow with a laser flowmeter. Nineteen mongrel dogs underwent left lung allotransplantation and were given daily oral immunosuppressive therapy with azathioprine and cyclosporine. The bronchial mucosal blood flow at the carina and the bifurcation of left upper and lower bronchi were measured on days 14, 21, and 28 after left lung transplantation. The bronchial mucosal blood flow of the transplanted lungs was expressed as the ratio of bronchial mucosal blood flow at the bifurcation of left upper and lower bronchi to the bronchial mucosal blood flow at the carina (L/C ratio) instead of the absolute value because bronchial mucosal blood flow was affected by the depth of anesthesia of the dogs. We classified the histologic appearance of the transplanted lung tissue into one of five grades: 0, 1a, 1b, 2, and 3. No rejection was in grade 0, and as the rejection process progressed the higher grades were used in order. The mean L/C ratios for grades 0, 1a, 1b, 2, and 3 were 0.95 +/- 0.03, 0.82 +/- 0.05, 0.68 +/- 0.04, 0.58 +/- 0.07, and 0.30 +/- 0.07, respectively. Thus the L/C ratio decreased as the rejection process progressed. The histologic changes of the donor main bronchus in each rejection grade were investigated. Mononuclear cell infiltration and edema around the small vessels was seen in early rejection. These same histologic changes appeared in muscular arteries as rejection progressed, and the damage to the small vessels and muscular arteries was more severe in late rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of bronchial mucosal blood flow for the monitoring of acute rejection in lung transplantation.

Bronchial mucosal blood flow (BMBF) was measured with a laser-Doppler flowmeter in a canine model (n = 20), and the measurement was evaluated to see if it was a useful method for diagnosing allografted lung rejection. The ratio of the value of BMBF at the level of the donor second carina against that at the level of carina (the L/C ratio, an index of BMBF of donor bronchus) decreased in accordance with the extent of lung rejection, and it increased and entered the normal range with the reversal of lung rejection. Compared with the L/C ratio and the rejection grade by histologic changes in open-lung biopsy, the L/C ratio at grade 0 (latent phase) was 0.91 +/- 0.07; at grade Ia (early vascular phase), 0.86 +/- 0.05; at grade Ib (late vascular phase), 0.68 +/- 0.10; at grade II (early alveolar phase), 0.60 +/- 0.14; and at grade III (late alveolar phase), 0.50 +/- 0.15. A significant difference was noted between grades Ia and Ib (p less than 0.01) and between grades Ib and III (p less than 0.01). The sensitivity and the specificity in the detection of early rejection before grade Ib were 96% and 92%, with only one false-negative and two false-positives resulting from 51 measurements of BMBF. In three cases of serious lung infections, the L/C ratio did not fall, and the rejection could be distinguished from infection. These results suggest that measurement of the BMBF is useful for detecting the early rejection of transplanted lungs.

Histologic changes in donor bronchi may explain the reduced mucosal blood flow seen during acute lung allograft rejection.

We assessed the histologic changes in donor and recipient bronchi from 15 dogs that had received a lung transplant and related these changes to the severity of acute rejection seen in the parenchyma of these same lungs. Minimal rejection was associated with no abnormal change in either the donor or the recipient bronchi. In mild lung rejection, mononuclear cell cuffings were seen around bronchial arteries in donor bronchial adventitia, although few mononuclear cell infiltrates were seen in the submucosa. Moderate lung rejection was associated with more prominent mononuclear cell cuffings in the donor bronchial adventitia and mucosal infiltrates of mononuclear cells in the membranous portion. In cases of severe lung rejection, the mononuclear cell infiltrates were also apparent in the cartilaginous portion of the donor bronchial mucosa. Moreover, submucosal edema and detachment of bronchial epithelium were seen. These histologic changes were not observed in the recipient bronchi during acute rejection, nor were they seen in the donor and the recipient bronchi during lung infection without rejection. They might, therefore, reflect acute rejection in the donor bronchus. These results might provide the histologic support for our previous observation of decreased bronchial mucosal blood flow measured by the laser Doppler flowmeter in relation with the extent of acute lung rejection.

Rupture of a benign mediastinal teratoma into the right pleural cavity.

A 27-year-old woman with a ruptured mediastinal cystic teratoma had high levels of amylase and carcinoembryonic antigen in cystic fluid. The activity of the amylase is thought to be the most likely cause of the rupture. High levels of carcinoembryonic antigen in pleural fluid are not necessarily indicative of a malignant lesion but may suggest the presence of a ruptured teratoma in patients with mediastinal tumors.

Size dependent liposome degradation in blood: in vivo/in vitro correlation by kinetic modeling.

The degradation of liposomes in blood circulation is important in regulating the releasing rate of encapsulated compounds. In this study, the effect of liposome size--one of the principal determining factors in liposome disposition--on their degradation in serum/blood was evaluated quantitatively both in vitro and in vivo. In the in vitro study, the time courses of the degradation of liposomes in fresh rat serum were measured continuously using 5(6)-carboxyfluorescein (CF) as an aqueous phase marker and were described by the kinetic model with the lag time (tau), first order degradation rate constant (k), and the maximum degradation (alpha). Both k and alpha increased with the increase of liposome size, which indicated a higher affinity of larger liposomes for complement activation. In the in vivo study, the degradation of liposomes was evaluated sensitively by a first order degradation rate constant (kd) in blood circulation. The kd was obtained by kinetically modeling the liposome degradation in vivo using 3H-inulin as an aqueous phase marker. The size dependent kd correlated well with the hepatic uptake clearance, which suggests an underlying complement activation mechanism common to both degradation and hepatic uptake of liposomes. There was a good correlation in the degradation rate constant between in vitro and in vivo trials. These kinetic analyses validate the quantitative evaluation of liposome degradation in blood circulation and provide a useful way to predict the degradation of liposomes in vivo from in vitro experiments.

Drug-induced acute pulmonary edema--sequential changes in CT images.

This is a case report of immediate acute pulmonary edema following the intravenous administration of Stronger Neo-Minophagen C (glycyrrhizin) and Chlor-Trimeton (chlorpheniramine maleate). The patient was a 15-year-old Japanese boy who had a previous history of surgery for right testicular tumor and adverse reactions to contrast media. The patient complained of severe headache, nausea, and vomiting just before the end of intravenous administration of these drugs, which were being given to prevent an adverse reaction to contrast enhanced CT. The symptoms disappeared within a few minutes, but chest CT examination performed immediately after the onset of the adverse reaction showed ill-defined consolidations with air bronchogram, especially in the anterior portion of both lungs. One day later, the abnormalities coalesced and poorly marginated patchy opacities developed. A week later, the abnormal densities disappeared. CT findings suggested acute pulmonary edema, especially in the anterior portion of both lungs. Thus CT examination was useful to detect focal pulmonary edema even in a patient with no particular respiratory symptom.

[General pharmacology of T-2588, a new oral cephem antibiotic].

A new oral cephem antibiotic, T-2588, the pivaloyloxymethyl ester of (+)-(6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3- [(5-methyl-2H-tetrazol-2-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2. 0]oct-2-ene-2-carboxylic acid (T-2525), is mainly absorbed from the intestinal tract and biotransformed to T-2525 thereafter. General pharmacological activities of T-2588 were studied and following results were obtained. On the central nervous system, T-2588 did not show any effects at oral doses of 500-2,000 mg/kg and T-2525 produced only a slight elevation of body temperature in rabbits without any other effects at an intravenous dose of 500 mg/kg. On the respiratory and cardiovascular systems, T-2525 caused a slight hypotension and increased both respiratory rate and femoral blood flow, but no changes were observed in heart rate and electrocardiogram in dogs at an intravenous dose of 500 mg/kg. The T-2525 exerted no significant influence on blood pressure response to isoproterenol, acetylcholine or histamine, but showed a slight tendency to decrease pressor response to adrenaline in dogs at intravenous doses of 100-500 mg/kg. For the renal function in rats, T-2588 had no effects on urine volume, electrolytes and PSP excretion at oral doses of 500-2,000 mg/kg. Intravenous administration of T-2525 caused an increase of sodium excretion at 500 mg/kg and dose-dependent increases of PSP excretion at 20-500 mg/kg. Hematological studies revealed that both T-2588 at oral doses of 500-2,000 mg/kg and T-2525 at intravenous doses of 100-500 mg/kg had no effects on bleeding time in mice, blood coagulation and platelet aggregation in rats. The T-2588 exerted no effect on the gastrointestinal system in rats or mice and had no antiinflammatory activity in rats at oral doses of 500-2,000 mg/kg. The T-2525 scarcely affected the motilities of isolated smooth muscle preparations in experimental animals including stomach, ileum, colon, uterus, vas deferens and trachea at a concentration as high as 10(-3) g/ml. The T-2525 increased bile secretion in rats at intravenous doses of 100-500 mg/kg. The T-2525 slightly decreased the twitch tension of musculus gastrocnemius induced by electrical stimulation in rats at an intravenous dose of 500 mg/kg. These results indicate that T-2588 is a pharmacologically inactive antibiotic.

[General pharmacology of T-3262, a new pyridonecarboxylic acid].

General pharmacological activities of (+/-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dih ydro- 4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262), which is a new pyridonecarboxylic acid, were examined with the following results. 1. Central nervous system: T-3262 did not show any significant pharmacological effects at oral doses of 100-1,000 mg/kg but caused slow waves in spontaneous EEG in cats at intravenous doses of 10-30 mg/kg. 2. Respiratory and cardiovascular system: T-3262 produced little effect in normotensive rats and anesthetized rabbits at oral doses of 100-1,000 mg/kg and intravenous doses of 3-30 mg/kg, respectively. But T-3262 caused, dose-dependently, an increase of respiratory rate, hypotension, decrease of heart rate and changes in ECG patterns (elevation of T waves, slow amplitudes of QRS complexes and prolongation of RR interval, etc.) in anesthetized dogs at intravenous doses of 3-10 mg/kg. 3. Renal functions: T-3262 increased electrolyte excretions at oral doses of 300-1,000 mg/kg but did not affect PSP excretion in rats. 4. Autonomic nervous system and smooth muscle organs: T-3262 exerted slight inhibition of gastric output in rats and slight miosis in mice at an oral dose of 1,000 mg/kg. But T-3262 did not affect the contraction of nictitating membrane in anesthetized cats at intravenous doses of 1-30 mg/kg. T-3262 increased spontaneous motilities of isolated stomach, ileum and uterus, but decreased that of isolated colon at concentrations of 10(-5)-10(-4) g/ml. 5. Hematological examinations: T-3262 did not show any significant effects on bleeding time, blood coagulation, platelet aggregation and blood glucose level in rats at oral doses of 100-1,000 mg/kg. 6. Miscellaneous effects: T-3262 exerted slight inhibitions of gastric secretion and of carrageenin-induced hind paw edema in rats at a dose of 1,000 mg/kg administered intraduodenally and orally, respectively. T-3262 did not affect neuromuscular junction and bile secretion in rats at intravenous doses of 3-30 mg/kg and oral doses of 100-1,000 mg/kg, respectively. From these results, it can be assumed that T-3262 has a wide safety margin as an oral antibacterial agent.

[General pharmacology of T-3761, a new oral quinolone antibacterial agent (1). Effect on the central nervous system].

General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the central nervous system were investigated in laboratory animals. The results obtained are summarized as follows. 1. T-3761 exerted no significant effects on spontaneous motor activity, motor coordination, pentobarbital-induced hypnosis, electroshock-, pentetrazole- or strychnine-induced convulsion, acetic acid-induced writhing responses, reserpine-induced hypothermia and ptosis in mice at oral doses of 100, 300 and 1,000 mg/kg. The same oral doses of T-3761 exerted no significant effects on body temperature and passive avoidance response in rats. 2. T-3761 had no effects on EEG in cats and spinal reflex in rats at intravenous doses of 10, 30 and 100 mg/kg. 3. Convulsions were not observed in mice after any oral combinations of T-3761 at a dose of 200 or 1,000 mg/kg with 14 different nonsteroidal anti-inflammatory drugs (NSAIDs) including fenbufen. 4. An oral combination of T-3761 even at a higher doses of 3,000 mg/kg with 4-biphenylacetic acid (BPAA) which is a principally active metabolite of fenbufen also did not induce convulsions in mice. 5. T-3761 did not inhibit GABA receptor binding in rat brain synaptic membranes at 10(-4) M in either the absence or presence of BPAA. These results suggest that T-3761 is an antibacterial agent which would be unlikely to produce any side effects on the central nervous system and to produce convulsion when combined with NSAIDs in clinical use.

[General pharmacology of T-3761, a new oral quinolone antibacterial agent (2). Effect on the respiratory and cardiovascular systems, autonomic nervous system and other functions].

General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the respiratory and cardiovascular systems, autonomic nervous system and other functions were investigated in laboratory animals. The results obtained are summarized as follows. 1. Respiratory and cardiovascular systems: Oral administration of T-3761 at doses of 100-1,000 mg/kg did not affect in conscious rats. But intravenous administration of T-3761 at doses of 10-100 mg/kg caused an increase in respiratory rate, induced hypotension, caused increase or decrease in heart rate and altered ECG patterns (elevation of T waves and reduction of voltage of QRS complexes, etc.) in anesthetized dogs. Intravenous administration of T-3761 at doses of 10-100 mg/kg showed respiratory rate increase or decrease, hypertension, heart rate decrease and ECG patterns changes (T waves elevation and extrasystole) in anesthetized rabbits. 2. Autonomic nervous system and smooth muscle organs: T-3761 increased the epinephrine-induced contraction of the isolated guinea pig vas deferens at concentration of 10(-5)-10(-4) g/ml. T-3761 decreased the acetylcholine-induced contraction of the isolated guinea pig ileum and epinephrine-induced relaxation of the isolated guinea pig trachea-chain at concentration of 10(-4) g/ml. T-3761 increased the norepinephrine-induced contraction of the isolated rabbit thoracic aorta at concentration of 10(-4) g/ml. Oral administration of T-3761 at a dose of 1,000 mg/kg exerted slight mydriasis in mice. 3. Digestive system: T-3761 decreased the spontaneous motilities of isolated ileum and colon at concentration of 10(-4) g/ml. Oral administration of T-3761 at a dose of 1,000 mg/kg inhibited gastric output and intestinal transit time in rats or mice. 4. Renal functions: Oral administration of T-3761 at a dose of 300 mg/kg increased Na+ excretion but did not affect PSP excretion in rats. 5. Hematological examinations: T-3761 showed no effects on resistance to hemolysis, blood coagulation and platelet aggregation in rabbits at concentration of 10(-6)-10(-4) g/ml. Oral administration of T-3761 at dose of 100-1,000 mg/kg did not affect bleeding time or blood glucose level in rats. 6. Miscellaneous effects: Intravenous administration of T-3761 at a dose of 100 mg/kg slightly inhibited the twitch tension of gastrocnemius in anesthetized rats. Oral administration of T-3761 at doses of 300-1,000 mg/kg exerted slight augmentation of carrageenin-induced hind paw edema in rats. From these results, it can be assumed that T-3761 had a wide safety margin as an oral antibacterial agent.

[General pharmacology of cefoperazone, a new cephalosporin antibiotic (author's transl)].

General pharmacological properties of cefoperazone (CPZ) were studied in various experimental animals. CPZ showed the following effects with intravenous injection to experimental animals. On the central nervous system, CPZ caused vomiting in dogs at 500 mg/kg, pyrexia and slow waves in electroencephalogram in rabbits at 1,000 mg/kg. On the motor and sensory nervous systems, CPZ enhanced slightly the twitch tension of musculus gastrocnemius induced by electrical stimulation in rats at 500 mg/kg. On the respiratory, cardiovascular and autonomic nervous systems, CPZ increased transiently the respiratory rate and potentiated the depressor response to Ach at 125 mg/kg, increased femoral blood flow, potentiated the pressor response to Adr in dogs and decreased the contraction of nictitating membrane induced by electrical stimulation in cats at 500 mg/kg, and then raised the systolic blood pressure in rabbits at 1,000 mg/kg. On the blood, CPZ decreased ChE activity in rabbit plasma at 250 mg/kg, prolonged bleeding time in mice at 500 mg/kg and prothrombin time in rabbits at 1,000 mg/kg. On the smooth muscle organs, CPZ enhanced slightly gastric motility in rabbits and ileal motility in guinea pigs at 62.5 and 125 mg/kg respectively, and promoted gastrointestinal propulsion of BaSO4 meal in mice at 1,000 mg/kg. On the urinary organ, CPZ increased urine volume and electrolytes excretion in dogs at 500 mg/kg. Subcutaneous injection of CPZ scarcely showed any significant effect in experimental animals under the dose of 2,000 mg/kg. In the in vitro experiments, CPZ enhanced slightly the motility of isolated rabbit gastrointestinal tract at 10(-3) g/ml. Assuming the single clinical dose of CPZ should be 10 approximately 40 mg/kg, it is concluded that the occurrence of pharmacological effects observed in experimental animals seems to be very rare clinically.

[General pharmacology of T-1982, a new cephamycin antibiotic].

General pharmacological studies on T-1982 produced the following results. On central nervous system, subcutaneous injection of T-1982 at dose of 2,000 mg/kg hastened the onset of pentetrazole-induced tonic extensor in mice. T-1982 had no effect on spontaneous motor activity, pentobarbital hypnosis, body temperature or EEG in mice or rabbits, and also did not show motor incoordinate, anticonvulsive or analgesic activity in mice at intravenous doses of 250--1,000 mg/kg or subcutaneous doses of 500--2,000 mg/kg. On motor and sensory nervous systems, no effect of T-1982 was noted on spinal reflex, neuromuscular junction, conduction anesthesia or surface anesthesia in rats or rabbits. On respiratory, cardiovascular and autonomic nervous systems, T-1982 caused transient increase of respiratory rate, slight hypotension and transient increase of femoral blood flow in dogs at intravenous doses of 250--1,000 mg/kg. However, it caused a slight hypertensive tendency in rabbits. Heart rate and ECG in dogs or rabbits, blood pressure response to epinephrine, isoproterenol, acetylcholine or histamine in dogs, nictitating membrane in cats and pupil size in mice were not affected after intravenous injection of T-1982. No effect was found on isolated guinea pig atrium or rabbit descending aorta following T-1982 application. On renal function in rats, T-1982 caused an increase of PSP excretion but had no effect on urine volume or electrolytes excretion at intravenous doses of 250--1,000 mg/kg. T-1982 prolonged bleeding time in mice at intravenous doses of 500--1,000 mg/kg, but did not show hemolytic property and inhibitory activity on blood coagulation or platelet aggregation in vitro experiments. Spontaneous movement and tone of isolated stomach, ileum, colon, uterus, vas deferens or trachea and acetylcholine-, histamine-, nicotine- or barium chloride-induced contraction of ileum were not affected following T-1982 application. Intestinal propulsion of barium meal in mice, gastric secretion and carrageenin-induced edema in rats were not affected after intravenous injection of T-1982. T-1982 increased bile secretion in rats dose-dependently at intravenous doses of 31.3--125 mg/kg. The local irritative activity of T-1982 in rats was slightly milder than cefoxitin and moderately milder than cefmetazole after intradermal injection. In conclusion, these results suggest that T-1982 would not cause any adverse effects at its estimated clinical doses of 10--20 mg/kg (500--1,000 mg/man).