Tuberculosis control policy in Nepal.
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Antitubercular Agents↗
Biomedical subjects
M Aoki
Publications and source records attributed to M Aoki.
Expression of local hepatocyte growth factor system in vascular tissues.
Since endothelial cells (EC) are known to secrete various anti-proliferative and vasodilating factors, an agent that promotes seeding or regeneration of EC may have potential therapeutic value against vascular smooth muscle cell (VSMC) proliferation. For the above purpose, we have found that hepatocyte growth factor (HGF) fulfills such conditions. However, the local HGF system has not yet clarified. Therefore, we investigated endogenous HGF production and its specific receptor (c-met) in vascular tissues. Our results revealed the expressions of HGF and its receptor (c-met) mRNA in endothelial cells, VSMC and neointimal VSMC of rat assessed by RT-PCR. HGF and c-met mRNA were also detected in human aortic endothelial cells and VSMC. Endothelial cells and VSMC of both rat and human produce and secrete immunoreactive HGF as assessed by ELISA. Of importance, the existence of local HGF system (HGF and c-met) was also observed in vivo in intact abdominal aorta of SD and Wistar rats. Overall, this study demonstrated that HGF is expressed and secreted from endothelial cells and VSMC of both rat and human in vitro as well as in vivo. Since HGF has characteristics of an endothelium-specific growth factor, locally synthesized HGF in endothelial cells and VSMC may have a role in vascular functions in autocrine-paracrine manner.
Animals↗
Images in cardiovascular medicine. Primary cardiac neurilemoma.
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Female↗
Early immunohistochemical changes of microtubule based motor proteins in gerbil hippocampus after transient ischemia.
Changes of immunoreactivities for microtubule based motor proteins, kinesin and cytoplasmic dynein, and non-motor protein, microtubule associated protein (MAP) 2 were investigated in gerbil hippocampus after transient ischemia. The immunoreactivities for kinesin showed a progressive decrease in hippocampal CA1 cells from 8 h after transient 5 or 15 min of ischemia that is lethal to the CA1 cells, while it showed no change after 2 min of ischemia that is non-lethal to the cells. The immunoreactivities for cytoplasmic dynein showed a decrease from 3 or 1 h of reperfusion in the CA1 cells after 5 or 15 min of ischemia, respectively. In contrast, the immunoreactivity for MAP2 remained normal until 2 days in the CA1 cells after 5 min of ischemia. These results showed an early changes of microtubule based motor proteins, such as kinesin and cytoplasmic dynein in vulnerable CA1 neurons. These changes may affect the mitochondrial shuttle system between neuronal cell body and the peripheries such as axon terminal and dendrites. This early disturbance may cause a failure to obtain newly synthesized nuclear encoded mitochondrial protein, and result in mitochondrial dysfunctions and the subsequent cell death.
Animals↗
Variance of age at onset in a Japanese family with amyotrophic lateral sclerosis associated with a novel Cu/Zn superoxide dismutase mutation.
Although about 5 to 10% of amyotrophic lateral sclerosis (ALS) cases are familial, the pathophysiology of ALS remains unknown. A new point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene, resulting in an amino acid substitution of leucine84 by valine (L84V), in a Japanese patient with familial ALS (FALS) was identified. This L84V substitution was not observed in 57 normal Japanese control subjects. The enzymatic activities of Cu/Zn SOD of skin fibroblasts were significantly reduced to 75% of the control level in the affected patient. The progression of the disease with this mutation is very rapid, but the age at onset varies with sex or generation within a family.
Adult↗
Monosynaptic rubrospinal projections to distal forelimb motoneurons in the cat.
In the present electrophysiological experiments, we examined whether or not there are short-latency excitatory postsynaptic potentials (EPSPs) suggesting monosynaptic rubro- and corticomotoneuronal connections in the cervical spinal segments in cats. Under pentobarbital anesthesia and immobilization with gallamine triethiodide, intracellular recordings were made from forelimb motoneurons (Mns) following stimulation of the red nucleus (RN) and the cerebral peduncle (CP). Mns comprising the musculocutaneous nerve (Musc. Mns), the radial nerve (Rad. Mns), the ulnar nerve (Uln. Mns), and the median nerve (Med. Mns) were identified by their antidromic activation. Single-pulse stimulation of RN produced EPSPs with a mean amplitude of 0.35 mV in the majority of forelimb Mns (88 of 122, 72%). Half of the forelimb Mns (23 of 46) of the C8-T1 segments in which RN-EPSPs were detected by single shocks exhibited segmental latencies of RN-EPSPs shorter than 1.0 ms, while only 3 of 43 (7%) forelimb Mns in the C6-7 segments showed such latencies. These results suggest that rubromotoneuronal connections are, at least in part, monosynaptic for forelimb Mns that innervate in particular the hand and digit muscles. When paired-pulse stimuli (interpulse interval of 3 ms) were applied to RN, the second EPSPs were potentiated moderately (mean amount of temporal facilitation 24%) for EPSPs with short segmental latencies (< 1.0 ms). By contrast, single shocks to CP rarely produced EPSPs in forelimb Mns (9 of 106, 8%). There was no obvious evidence to suggest monosynaptic connections between corticospinal fibers and the forelimb Mns. The present results suggest the presence of preferential direct rubrospinal projection to Mns innervating distal forelimb muscles in the cat.
Animals↗
Phylogenetic relationships of some Microsporum and Arthroderma species inferred from mitochondrial DNA analysis.
Thirty-eight strains of 12 Microsporum and 10 Arthroderma (Nannizzia) species were investigated by analysis of mitochondrial DNA with 6 restriction enzymes, and classified into 13 genetic groups. The phylogenetic tree of the 13 groups thus established was constructed. On the tree, M. audouinii, M. langeronii, M. rivalieri, M. distortum, M. equinum, M. ferrugineum and A. otae comprise one genetic group and are suggested to be the same species. A. gypseum, A. fulvum, M. duboisii, M. ripariae, A. incurvatum, A. persicolor and A. obtusum are clustered on one of five boughs of the tree indicating their close relation. A. racemosum and A. cajetani are also closely related.
Ascomycota↗
pH strategies and cerebral energetics before and after circulatory arrest.
The pH-stat strategy compared with the alpha-stat strategy provides more rapid recovery of brain high-energy phosphate stores and intracellular pH after 1 hour of hypothermic circulatory arrest in pigs. Possible mechanisms for this difference are (1) improved oxygen delivery and homogeneity of brain cooling before deep hypothermic circulatory arrest and (2) greater cerebral blood flow and reduced reperfusion injury owing to extracellular acidosis during the rewarming phase. To identify which of these mechanisms is predominant, we studied 49 4-week-old piglets undergoing 1 hour of deep hypothermic circulatory arrest. Four groups were defined according to cooling/rewarming strategy: alpha/alpha, alpha/pH, pH/alpha, and pH/pH. In 24 animals cerebral high-energy phosphate levels and intracellular pH were measured by magnetic resonance spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 5). In 25 animals cerebral blood flow was measured by labeled microspheres, cerebral metabolic rate by oxygen and glucose extraction, and the redox state of cytochrome aa3 and hemoglobin oxygenation by near infrared spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 6). Cerebral blood flow was greater with pH-stat than alpha-stat during cooling (56.3% +/- 3.7% versus 32.9% +/- 2.1% of normothermic baseline values, p < 0.001). Cytochrome aa3 values became more reduced during cooling with alpha-stat than with pH-stat (p = 0.049). Recovery of adenosine triphosphate levels in the initial 45 minutes of reperfusion was more rapid in group pH/pH compared with that in the other groups (p = 0.029). Recovery of cerebral intracellular pH in the initial 30 minutes was faster in group pH/pH compared with that in group alpha/alpha (p = 0.026). Intracellular pH became more acidic during early reperfusion only in group alpha/alpha, whereas it showed continuous recovery in the other groups. This study suggests that there are mechanisms in effect during both the cooling and rewarming phases before and after deep hypothermic circulatory arrest that could contribute to an improved cerebral outcome with pH-stat relative to more alkaline strategies.
Adenosine Triphosphate↗
Effect of suture knots on tensile strength of repaired canine flexor tendons.
59 dog cadaver flexor digitorum profundus tendons were repaired with one or two knots inside or outside the tendon, using two, four and six suture strands. The ultimate tensile strength and gap strengths were compared. Locating the knots outside rather than within the tendon repair site showed significantly higher ultimate tensile strength for two, four, and six strand sutures. The strength was greater in one knot than in two knot sutures; the value of the six-strand suture using the one knot outside technique was the greatest. Similarly, increased gap strength was also obtained from the one-knot-outside technique. We concluded that the knots should be located away from the tendon repair site and there should be as few as possible.
Animals↗
Work of flexion after tendon repair with various suture methods. A human cadaveric study.
After flexor tendon repair there is often increased resistance to tendon gliding at the repair site, which is greater for techniques using increased suture strands or suture material. This increased "friction" may be measured as the "work of flexion" in the laboratory setting. Tendon repairs performed in zone 2 in human cadaver hands using the two strand Kessler, the lateral Becker, the six strand Savage, internal and dorsal tendon splint, or the external mesh sleeve techniques, had "work of flexion" measurements made both before and after the laceration and repair. The average increase in work of flexion was 4.8% for Kessler; 6.5% for Becker; 10.9% for Savage; 19.3% for the internal tendon splint, 16.2% for the dorsal tendon splint and 44.3% for the external mesh sleeve. The work of flexion was found to increase in direct proportion to the amount of suture material at the repair site.
Biomechanical Phenomena↗
Anti-CD18 attenuates deleterious effects of cardiopulmonary bypass and hypothermic circulatory arrest in piglets.
Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest induce leukocyte and platelet activation and cytokine production as part of the inflammatory response to bypass. These events are thought to be responsible for producing at least some of the morbidity of bypass. We studied the effects of a monoclonal antibody to a specific leukocyte adhesion integrin, CD18, on the deleterious effects of CPB and circulatory arrest in piglets using techniques from infant heart surgery. Seventeen immature piglets were subjected to CPB, cooling, 1 hour of circulatory arrest at 15 degrees C, and subsequent reperfusion and rewarming. Nine piglets received anti-CD18 monoclonal antibody (group MAb), and eight randomly selected control piglets received none (group C). Monoclonal antibody to leukocyte integrin CD18 significantly decreased deleterious effects of CPB and hypothermic circulatory arrest in our immature animal model. This study suggests that antiadhesion therapy that alters fundamental leukocyte/endothelial interactions during open heart surgery may be protective against some deleterious effects of bypass and circulatory arrest in infants.
Animals↗
Glutathione S-transferases as a cefpiramide binding protein in rat liver.
To clarify the intrahepatical transport mechanism of cefpiramide, we investigated effects of various agents mainly excreted into the bile by several different mechanisms on the biliary excretion of cefpiramide in rats. Sulfobromophthalein, indocyanine green, bilirubin and probenecid, known to be bound to glutathione S-transferases (GST) (EC 2.5.1.18) in liver cytosol, reduced the biliary excretion of cefpiramide, while neither secretory IgA, which is transported via vesicles in the liver, nor colchicine, which inhibits movements of vesicles, had any effect on the excretion of cefpiramide. Propranolol and metoprolol, metabolized by mixed function oxidases, had no effect on the biliary excretion of cefpiramide. In the chromatography of liver cytosol, the amount of sulfobromophthalein or benzylpenicillin bound to the GST fraction decreased in the presence of cefpiramide or probenecid. The study showed that cefpiramide was transported in the liver without relation to mixed function oxidases or vesichle-mediated transporting system, but in relation to GST which binds cefpiramide, sulfobromophthalein, benzylpenicillin and probenecid, indicating an important role of GST in the cefpiramide excretion into the bile.
Animals↗
[Useful abdominal ultrasonography for diagnosis of Fitz-Hugh-Curtis syndrome: two case reports].
Recently, Chlamydia trachomatis infection in sexually active women has increased. C. trachomatis cause pelvic inflammation. A few of these patients develop Fitz-Hugh-Curtis syndrome (FHCS). Clinical symptoms of FHCS include pain of sudden onset in the right upper quadrant mimicking acute biliary disease. Diagnosis of FHCS has been weighed upon laparoscopic findings. Since FHCS is a benign disorder which responds to appropriate antibiotics, non-invasive diagnostic method would be expected. We report here two cases of FHCS, diagnosed by a high serum antibody titer against C. trachomatis and clinical manifestations. Both cases showed small effusion in the pelvic cavity detected by ultrasonography, one of them was associated with small effusion in the right perirenal space suggesting perinephritis. Detection of small effusion intra abdominal cavity or pelvic space could be useful for non-invasive diagnosis of FHCS.
Adult↗
[Clinical efficacy of lomefloxacin (100 mg or 300 mg) single-dose therapy in female acute uncomplicated cystitis].
Female acute uncomplicated cystitis responds relatively well to antimicrobial chemotherapy. In particular, new quinolones are suited for use as antimicrobial agents in single-dose therapy of female acute uncomplicated cystitis since they have a long serum half-life and express potent antimicrobial activity against the causative microbes of this infection. Lomefloxacin (LFLX) is one such new quinolone which shows a long serum half-life, expresses potent antimicrobial activity against Escherichia coli (E. coli) and maintains an effective urinary drug concentration for approximately three days after a single administration. The authors carried out a comparative investigation of the clinical efficacy of single doses of 100 mg and 300 mg of LFLX in the treatment of female acute uncomplicated cystitis. The clinical efficacy rates with these doses, evaluated on the 3rd day after administration, were 98.2% (56/57 cases) for the 100mg-LFLX dose and 100% (62/62 cases) for the 300-mg LFLX dose. When the evaluation was performed on the 7th day after administration, the clinical efficacy rates were 91.3% (42/46 cases) for the 100-mg LFLX dose and 95.8% (46/48 cases) for the 300-mg LFLX dose. In addition, the microbial eradication rates were 73.7% (42/57 cases) for the 100-mg LFLX group and 75.8% (47/62 cases) for the 300-mg LFLX group on the 3rd day after administration, and 71.7% (33/46 cases) for the 100-mg LFLX group and 83.3% (40/48 cases) for the 300-mg LFLX group on the 7th day after administration. Although there were no statistically significant differences between the two LFLX dosage groups for these parameters at either of the evaluation times, the rates for the 300-mg LFLX dose were slightly superior. The investigators judged the efficacy of the LFLX treatment as having been insufficient in 12 patients, and urological examinations performed on six of those cases determined that there were mild underlying diseases in four cases, such as stenosis of the urethral meatus. On the basis of the findings described above, it is clear that a single 100-mg dose of LFLX provided sufficient clinical efficacy in the treatment of female acute uncomplicated cystitis, but the efficacy of the 300-mg dose of LFLX was even better. In addition, it was surmised that performance of detailed urological examinations provides an opportunity to detect mild underlying diseases that may be the cause of the intractability in female acute uncomplicated cystitis cases showing an insufficient response to treatment with antimicrobial agents such as LFLX.
Acute Disease↗
[An autopsy case of fungal (Mucor) cerebral aneurysm].
An autopsy of rupture of Mucor cerebral aneurysm, not diagnosed during the patient's life, was experienced. A 63-year-old female was admitted to our hospital with the chief complaint of disturbance of consciousness and high fever. Her past histories were diabetes mellitus, liver cirrhosis and nasal sinusitis. The remarkable findings on admission were moderate inflammatory data, high blood sugar level in serum and ascites. Brain CT film revealed a non-enhanced low-density area in the frontal region. The cerebrospinal fluid showed bloody color and white blood cell counts were 3300/microliter (mostly neutrophils). Under our suspected of bacterial encephalomeningitis, intravenous cefotaxime and ampicillin therapy was started immediately. Cultures of cerebrospinal fluid for bacteria were negative. The disturbance of her consciousness gradually improved under general treatment. However, her conscious level suddenly became a coma on the 6th hospital day and she died on the 9th hospital day. An autopsy revealed Mucor at the site of the rupture of the cerebral aneurysm.
Aneurysm, Infected↗
[Long-term monitoring of female acute uncomplicated cystitis cases after lomefloxacin single-dose therapy].
Female acute uncomplicated cystitis responds relatively well to antimicrobial chemotherapy, but this is also a disease which shows a high frequency of recurrence. However, there have been no published reports regarding long-term monitoring of the course of this disease after therapy has been administered. Accordingly, using primarily a questionnaire, the authors carried out long-term monitoring (for a mean of 242 days) of the natural course of cases of female acute uncomplicated cystitis after single-dose therapy with lomefloxacin (LFLX), a new quinolone antimicrobial agent. The subjects of this study were female patients diagnosed as having acute uncomplicated cystitis with pain upon urination, pyuria (> or = 10 WBCs/hpf) and bacteriuria (> or = 10(4) cfu/ml). LFLX was orally administered as a single dose of 100 mg or 300 mg, and the therapeutic efficacy was evaluated on the 3rd and 7th days thereafter. In principle, the evaluation of cure was performed on the 7th day after LFLX administration, and monitoring was conducted to detect early recurrence during the next 7 days (i.e., through the 14th day after treatment). Then the subjects were monitored for late recurrence during a mean follow-up period of 242 days by means of a questionnaire. Confirmation of recurrence was carried out to the greatest extent possible. It was possible to carry out long-term monitoring of the natural course of 101 cases of female acute uncomplicated cystitis in which the clinical efficacy on the 3rd day after LFLX treatment had been evaluated as good or excellent.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Transient decrease in high blood pressure by in vivo transfer of antisense oligodeoxynucleotides against rat angiotensinogen.
The renin-angiotensin system plays an important role in blood pressure regulation. Angiotensinogen, which is mainly produced in the liver, is a unique component of the renin-angiotensin system, because angiotensinogen is only known as a substrate for angiotensin I generation. It is unclear whether circulating angiotensinogen is a rate-limiting step in blood pressure regulation. Recent findings of genetic studies and analyses suggest that the angiotensinogen gene may be a candidate as a determinant of hypertension. To test the hypothesis that angiotensinogen may modulate blood pressure, we transfected antisense oligonucleotides against rat angiotensinogen into the rat liver via the portal vein using liposomes that contain viral agglutinins to promote fusion with target cells, a technique that has been reported to be highly efficient. Transfection of antisense oligonucleotides resulted in a transient decrease in plasma angiotensinogen levels in spontaneously hypertensive rats from day 1 to day 7 after the injection, consistent with the reduction of hepatic angiotensinogen mRNA. Plasma angiotensin II concentration was also decreased in rats transfected with antisense oligonucleotides. Moreover, a transient decrease in blood pressure from day 1 to day 4 was observed, whereas transfection of sense and scrambled oligonucleotides did not result in any changes in plasma angiotensinogen level, blood pressure, or angiotensinogen mRNA level. Overall, our results demonstrate that transfection of antisense oligonucleotides against rat angiotensinogen resulted in a transient decrease in the high blood pressure of spontaneously hypertensive rats, accompanied by a decrease in angiotensinogen and angiotensin II levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Ischemic delayed neuronal death. A mitochondrial hypothesis.
BACKGROUND: A brief period of global brain ischemia causes cell death in hippocampal CA1 pyramidal neurons days after reperfusion in rodents and humans. Other neurons are much less vulnerable. This phenomenon is commonly referred to as delayed neuronal death, but the cause has not been fully understood although many mechanisms have been proposed. SUMMARY OF REVIEW: Hippocampal CA1 neuronal death usually occurs 3 to 4 days after an initial ischemic insult. Such a delay is essential for the mechanism of this type of cell death. Previous hypotheses have not well explained the reason for the delay and the exact mechanism of the cell death, but a disturbance of mitochondrial gene expression could be a possibility. Reductions of mitochondrial RNA level and the activity of a mitochondrial protein, encoded partly by mitochondrial DNA, occurred exclusively in CA1 neurons at the early stage of reperfusion and were aggravated over time. In contrast, the activity of a nuclear DNA-encoded mitochondrial enzyme and the level of mitochondrial DNA remained intact in CA1 cells until death. Immunohistochemical staining for cytoplasmic dynein and kinesin, which are involved in the shuttle movement of mitochondria between cell body and the periphery, also showed early and progressive decreases after ischemia, and the decreases were found exclusively in the vulnerable CA1 subfield. CONCLUSIONS: A disturbance of mitochondrial DNA expression may be caused by dysfunction of the mitochondrial shuttle system and could cause progressive failure of energy production of CA1 neurons that eventually results in cell death. Thus, the mitochondrial hypothesis could provide a new and exciting potential for elucidating the mechanism of the delayed neuronal death of hippocampal CA1 neurons.
Animals↗