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Biomedical subjects

F Kobayashi

Publications and source records attributed to F Kobayashi.

At least 163 records · Page 9Linked to original sources

[Clinical and experimental study of the host defense mechanism from the aspect of tumor immunology].

The host defense mechanism was fundamentally and clinically investigated from the aspect of tumor immunology. The behavior of macrophages in the immune systems of experimental animals demonstrated different patterns of response in the bone marrow, peritoneal cavity and spleen, respectively. It was doubtless that the spleen occasionally exerted an immunosuppressive action. Ectopic immunization of syngeneic rats with normal liver cells resulted in specific inhibition of the growth of the tumor cells (AH-I30) derived from liver. This seemed to strongly suggest a local immune response. In clinical cases, the host defense mechanism was found to collapse due to surgical intervention, malnutrition and immunosuppressive substances. The relation between complements and host defense mechanism has been controversial. Our studies indicated the serum complement level to be the most reliable parameter for understanding the host defense mechanism. Since the combination of immunostimulants and anticancer drugs is likely to induce anticancer drugs to exert an adverse effect depending on the time of such combination, timing of combined administration of drugs should be chosen with great care.

Animals↗

[The effects of the intracerebroventricular administration of 5-hydroxytryptamine on hemodynamics in conscious rats. Participation of the serotonin receptor and the sympathetic nervous system].

We have previously reported that the intracerebroventricular (i.c.v.) administration of 5-hydroxytryptamine (5-HT) in conscious rats elicited significant pressor response, which was accompanied with an increase in plasma norepinephrine and the pressor response, was abolished by peripheral phenoxybenzamine pretreatment. For further investigation of the relationship between the serotonergic nervous system and the sympathetic nervous system, the effect of either i.c.v. or intravenous (i.v.) serotonin receptor antagonist, methysergide pretreatment on hemodynamic response to centrally administrated 5-HT was studied. Male Wistar rats weighing approximately 250g were used. On the day before the study, the unilateral carotid artery was cannulated (PE-50) to facilitate mean arterial pressure (MAP) and pressure triggered heart rate (HR) observation. Also, a cannula (PE-10) was inserted stereotaxically into the anterior horn of the lateral cerebral ventricle. The experiment was performed under a conscious and minimumly restrained state. After the observation of resting MAP and HR for at least 20 minutes, 5 microgram of 5-HT was given i.c.v. and MAP and HR were recorded for 50 minutes. Then, the rats were divided into two groups, one group (n = 9) received 1 microgram of i.c.v. methysergide and the other group (n = 10) received 1 mg/kg of i.v. methysergide. Ten minutes after either methysergide i.c.v. or i.v. treatment, 5 microgram of 5-HT was administrated i.c.v. again, and MAP and HR were observed for 30 minutes. Resting MAP and HR were 101.6 +/- 3.0mmHg and 413.8 +/- 20.0/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High incidence of Langerhans cells in lymph nodes of athymic nude mice: an ultrastructural and morphometric study.

Cervical and axillary lymph nodes of athymic nude mice were compared morphometrically and ultrastructurally with those of normal littermates. The lymph nodes of the nude mice were larger and the volumes of the follicle, paracortex, and medulla of the lymph nodes were all larger. The paracortex of nude mice had few lymphocytes and a large number of interdigitating cells (IDC) and Langerhans cells (Lc). The results suggest that the high incidence of Lc and IDC in the lymph nodes of nude mice is due to cell accumulation and not lymphocyte depletion.

Animals↗

Role of prolactin in controlling prolactin surges in pseudopregnant rats.

The present study investigated whether prolactin (Prl) itself acts as a physiological factor in the control of nocturnal Prl surges in pseudopregnant (PSP) rats. Intracerebroventricular (ICV) injection of ovine Prl at doses of 0.1, 1 and 10 micrograms/rat given 1 h before the start of the nocturnal Prl surge inhibited its occurrence completely and dose-dependently. The same inhibition of nocturnal Prl surge was observed 4 and 1 h before, and even 1.5 h after, the start of the nocturnal Prl surge. Prl concentrations in the cerebrospinal fluid (CSF) increased twice a day, the timings of which were similar to those of diurnal and nocturnal surges of Prl in PSP rats. Changes of Prl concentrations in the CSF correlated closely with those of plasma Prl concentrations. ICV injection of antiserum to rat Prl in the first half period of nocturnal Prl surges did not modify the elevation pattern of plasma Prl concentrations. Inhibition of nocturnal Prl surge produced by ICV injection of ovine Prl was overcome by subcutaneous administration of pimozide (1 mg/kg). These results suggest that Prl itself may act as an important physiological modulatory factor in the control mechanism(s) of nocturnal Prl surge in PSP rats. Prl may inhibit further discharge of Prl by a feedback mechanism through the hypothalamic dopaminergic system within a very short time period.

Animals↗

In vitro and in vivo antibacterial activities of K-4619, a new semisynthetic aminoglycoside.

The antibacterial activities of K-4619 (3-de-O-methylsporaricin A sulfate) were compared with those of sporaricin A, amikacin, dibekacin, and gentamicin. K-4619 exhibited a high order of activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its activity against Providencia species and Serratia marcescens was the highest of all drugs tested. K-4619 was highly effective against bacteria that produce various aminoglycoside-inactivating enzymes, except for 3-acetyltransferase I. The bactericidal activity of K-4619 was somewhat greater than that of amikacin. The activity of K-4619 against gram-negative bacteria increased at alkaline pH and was hardly affected by inoculum size, addition of horse serum, and composition of the medium. The in vivo protective effect of K-4619 against infections with Klebsiella pneumoniae, S. marcescens, and P. aeruginosa in mice was greater than that of sporaricin A. K-4619 was also active in mice infected with gentamicin- or amikacin-resistant strains bearing some of the aminoglycoside-inactivating enzymes.

Amikacin↗

[Pharmacological studies on new cephamycin, MT-141. (1) Its effect on central nervous system, respiration and cardiovascular system].

The results on pharmacological effects of MT-141 were as follows. MT-141 did not exert effect on central nervous system in mice and rabbits but potentiated the anesthetic effect of thiopental at doses above 800 mg/kg i.v. MT-141 slightly raised a level of blood pressure in dogs and also caused a slight increase in the blood flow and heart rate when intravenously given more than 400 mg/kg. This compound did not affect the spontaneous contraction of isolated guinea pig atria and the blood vessels in perfused rabbit ears. MT-141 did not significantly affect the spontaneous contraction and coronary flow in isolated hearts of guinea pig. The body temperature was raised slightly by an injection of more than 400 mg/kg of MT-141. These results suggest that MT-141 does not possess specific effect on central nervous system but at a high dose slightly affects the autonomic nervous system such as blood pressure, body temperature, heart rate and blood flow in experimental animals.

Animals↗

[Pharmacological studies on a new cephamycin, MT-141. (2) Its effect on preparations of neuromuscular junction, smooth muscle organs and gastro-intestinal system].

The results for pharmacological experiments of MT-141 were as follows; Twitch tension of gastrocnemius muscle evoked by the stimulation of sciatic nerve was slightly reduced with 400 mg/kg MT-141 i.v. and upper doses. As the change was very small, however, it seems that MT-141 has no neuromuscular junction blocking action. Although MT-141 did not show any effects on most of isolated smooth muscle organs, only isolated tracheal muscle was somewhat relaxed with 10(-3) g/ml MT-141. The spontaneous motility of smooth muscle in situ was temporarily increased with 800 mg/kg MT-141 i.v. and upper doses. Two hundred mg/kg MT-141 showed no effect on the value of blood sugar and functions of kidney and liver. Any hemolysis did not appear even in the highest dose of 200 mg/kg MT-141 used in this experiment. From the present results and previous report (Krebe, M. et al., Jap. J. Antibiotics, in press), it seems that MT-141 is promised to be a highly safe and useful antibiotic agent in clinical use.

Anesthetics, Local↗

[Vibration hazards in quarry workers].

Vibration hazards were surveyed in a population of quarry workers using chipping hammers and to a lesser extent, rock drills. Sixty-nine male quarry workers, aged 49.1 +/- 8.7 and exposed to vibration for 16.4 +/- 5.1 years, were surveyed in 1981-82. They were exposed to vibration for about 2-4 hours per days, mainly under a piece-work pay system. They had a high prevalence of Raynaud's phenomenon (36.2%) and numbness in upper extremities (53.6%). It is considered that the high prevalence was mainly due to large vibration levels in chipping hammers and rock drills and long daily exposure time. The attacks of Raynaud's phenomenon were found predominantly in the left hand, which held chisels, whereas the restriction of motion in the elbow was predominantly in the right arm which pushed chipping hammers. The same 49 male quarry workers in this population were also surveyed in 1976-77 and the prevalence of their complaints between 1976-77 and 1981-82 was compared. The prevalence of Raynaud's phenomenon was the same, but the frequency of the attacks increased between the two periods. The prevalence of other complaints such as numbness, pain and chills in the upper extremities also increased. Between 1976-77 and 1981-82, the prevalence of Raynaud's phenomenon, numbness, and pain in the upper extremities increased in the population of quarriers exposed to vibration for above 2.6 hours per day and 200 days per year, or 600 hours per year. On the other hand, the prevalence of these complaints mostly decreased in the population of quarriers with less exposure.

Adult↗

[The role of the cholinergic system in controlling the nocturnal prolactin surge in pseudopregnant rats].

To elucidate the role of the cholinergic system in controlling the nocturnal prolactin (PRL) surge in the early stage of rat pseudopregnancy, the effects of subcutaneous or intracerebroventricular (ICV) injections of various cholinergic agonists and antagonists on the pattern of the nocturnal PRL surge were investigated. Pseudopregnancy was induced by stimulating the uterine cervix with a vibrator between 0630 h and 0700 h on the morning of estrus (Day 0). Blood samples for PRL analysis by RIA were obtained every two hours from 2300 h on Day 2 to 0900 h on Day 3 through an indwelling venous cannula, which was implanted on Day 1 under pentobarbital-Na anesthesia, or by decapitation at 0300 h on Day 3. For ICV injection of the drug, rats were implanted with a stainless steel guide cannula 1.0 mm above the right lateral ventricle on diestrus 1 of the estrous cycle. They were given cervical stimulation on the initial estrous morning after the above operation. Control rats given saline solution showed a nocturnal PRL surge between 0100 h and 0700 h on Day 3 in the present study. Atropine sulfate (70 and 700 mg/kg) injected subcutaneously resulted in the complete inhibition of the nocturnal PRL surge whenever given at 2100 h on Day 2, 0000 h on Day 3 and 0300 h on Day 3, which corresponded to 4 hours and 1 hour before and 2 hours after the starting of the nocturnal PRL surge, respectively. ICV injection of atropine sulfate (250 micrograms/rat) also inhibited the occurrence of the nocturnal PRL surge when given at 0000 h on Day 3, though a slight and transient elevation of plasma PRL levels were seen. Subcutaneous injection of pilocarpine hydrochloride (5 and 50 mg/kg), a cholinergic agonist, did not affect the elevation of plasma PRL concentration observed at 0300 h on Day 3 when administered 3 hours before. The other agonist, arecoline hydrochloride, also did not affect the pattern of the nocturnal PRL surge when administered intravenously between 2315 h on Day 2 and 0515 h on Day 3. Subcutaneous injection of pimozide (1 mg/kg), a dopaminergic antagonist, just after the administration of atropine sulfate (700 mg/kg) given at 0000 h on Day 3 overcame the inhibitory effect of the later compound on the nocturnal PRL surge. However, the high levels of plasma PRL concentration still remained at 0700 h and 0900 h on Day 3 without any decrease as observed in the controls. These results suggest that the cholinergic system may be involved as a modulator in controlling physiological mechanism(s) of the nocturnal PRL surge in pseudopregnant rats.

Animals↗

Extrahypothalamic control of daily surges of prolactin secretion in pseudopregnant rat.

The role of the limbic forebrain structures in controlling twice daily surges of prolactin (PRL) induced by cervical stimulation was investigated after acute or chronic deafferentation of the limbic forebrain afferents to the hypothalamus in rats. The preoptic area-roof section (POA-RS), which interrupted the rostral limbic afferents at the dorsal level of the anterior commissure, induced pseudopregnancy (PSP) and initiated the same nocturnal PRL surges as those initiated by the cervical stimulation. Diurnal PRL surges, however, did not occur following this procedure. The nocturnal PRL surge by POA-RS also occurred in ovariectomized rats. Deafferentation between the diagonal band of Broca and the medial preoptic area (F2-cut) initiated PSP in 37 % of the rats and induced an apparent but small nocturnal PRL surge. The rats with POA-RS or F2-cut showed restoration of their regular estrous cyclicities. Cervical stimulation after POA-RS did not affect the initiation of nocturnal PRL surge induced by POA-RS alone. POA-RS after cervical stimulation also did not affect the initiation of nocturnal PRL surge induced by cervical stimulation, though a diurnal PRL surge was initiated in these rats. The cut made just before the diagonal band of Broca after cervical stimulation did not inhibit the occurrence of either surge. Nocturnal and diurnal PRL surges were manifested after cervical stimulation in the rats with chronic POA-RS or F2-cut and their vaginal cyclicities were resumed. These results suggest that the limbic forebrain structures are not indispensable for the initiation of nocturnal PRL surges induced by cervical stimulation but may modify the hypothalamic mechanism(s) initiating a nocturnal PRL surge through the rostral part of the hypothalamus.

Animals↗

Morphological changes of isolated rat hepatocytes induced by imipramine.

Effect of imipramine on freshly isolated rat hepatocytes was investigated by scanning and transmission electron microscopy. Soon after the treatment of the cell with imipramine, marked changes in plasma membrane and mitochondria were found. Amitriptyrine, a structurally related drug, produced similar changes in the hepatocytes. On the other hand, Triton X-100, a nonionic surfactant, damaged the cell surface but little influence the features of the organelles.

Animals↗

Antimicrobial and beta-lactamase inhibitory activities of carpetimycins A and B, new carbapenem antibiotics.

Carpetimycins A and B showed widely broad spectra and potent activity against gram-positive and gram-negative bacteria, including various species of anaerobic bacteria. The antimicrobial activity of carpetimycin A was 8 to 64 times greater than that of carpetimycin B and 4 to 128 times greater than that of cefoxitin. The inhibitory concentration of carpetimycin A required to inhibit more than 90% of clinical isolates was 0.39 micrograms/ml for Escherichia coli and klebsiella and 1.56 microgram/ml for Proteus and Staphylococcus aureus. At a concentration of 3.13 micrograms/ml, carpetimycin A inhibited almost all clinical isolates of Enterobacter and Citrobacter, which showed resistance to many clinically used beta-lactam antibiotics. Carpetimycins A and B furthermore were shown to have potent inhibitory activities against several kinds of beta-lactamases produced by beta-lactam-resistant strains; they inhibited not only penicillinase-type beta-lactamases but also cephalosporinase-type beta-lactamases, which were insensitive to clavulanic acid. In combination with beta-lactam antibiotics such as ampicillin, carbenicillin, and cefazolin, carpetimycins A and B showed synergistic activities against beta-lactam-resistant bacteria.

Animals↗

Purification and properties of inducible penicillin beta-lactamase isolated from Pseudomonas maltophilia.

Two types of beta-lactamase were found in the cell-free extract from Pseudomonas maltophilia GN12873. One was an inducible penicillin beta-lactamase, and the other was an inducible cephalosporin beta-lactamase. The purified penicillin beta-lactamase gave a single protein band on polyacrylamide gel electrophoresis. The isoelectric point was 6.9, and the approximate molecular weight was 118,000 by gel filtration and 26,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that this enzyme consisted of four subunits. For the hydrolysis of penicillin G, the optimal pH was 8.0 and the optimal temperature was 35 degrees C. The enzyme activity was inhibited by cephamycin derivatives, carpetimycins A and B, iodine, and HgCl2, but not by clavulanic acid. Furthermore, beta-lactamase activity was almost completely inhibited by EDTA but was recovered by the addition of zinc ion. The enzyme showed a unique substrate profile, hydrolyzing N-formimidoyl thienamycin at a significant rate.

Bacteria↗

[Cold water immersion test for diagnosis of vibration diseases. Comparison between water at 5 degrees C and 10 degrees C].

5 degrees C-water 10-minute immersion test, generally used in Japan, is useful to diagnose vibration diseases. But severe pains during the immersion is troublesome. We studied the availability of 10 degrees C-water 10-minute immersion test to reduce the pain during the test. Subjects were forty-nine chainsaw operators, nineteen patients with vibration disease, and twelve controls. The same subject underwent both 5 degrees C and 10 degrees C immersion tests. The following results were obtained. 1) Skin temperatures in the highest score group after the immersion tests both at 5 degrees C and 10 degrees C was lower than that in the control group. Mean skin temperatures for the last five minutes during the immersion and the recovery activity in both the immersion tests showed a similar trend among subjects groups. Skin temperatures in patients under medical treatment (R'group) did not differ from those in the control group. 2) Hyperemia time by nail press test in the R'group and in the high score group after both immersion tests was longer than that in the control group. But this difference between chainsaw operators and the control group after 5 degrees C immersion test was more marked than that after 10 degrees C immersion test. 3) Vibratory sense as well as pain sense in the R'group and in the high score group after both immersion tests were less sharp than those in the control group. 4) Skin temperatures, nail press test, vibratory sense, and pain sense after 5 degrees C immersion test and those after 10 degrees C immersion test showed statistically significant positive correlation. 5) 10 degrees C immersion test is as effective as 5 degrees C immersion test in finding nervous disorders, but 5 degrees C immersion test is more effective than 10 degrees C immersion test in finding circulatory disorders. However patients with Raynaud's phenomena or moderate circulatory disorders can also be found even by 10 degrees C immersion test. 6) Cold water immersion test revealed disorders not only in skin temperature and by nail press test but revealed also disorders in vibratory sense and pain sense, therefore it is desirable that cold water immersion test should be done in the examination of vibration diseases.

Blood Circulation↗

[On vibration hazards of chipping-hammer operators in an iron foundry. Part 2. Results of the hygienic control].

We previously reported that the working and health conditions of vibrating tool operators in an iron foundry were investigated in 1975 and vibration hazards were observed to occur frequently in workers operating chipping-hammers powered by compressed air. After that, we instituted medical treatment for the afflicted workers and improvement of working conditions in the foundry, and have performed annual medical examinations for four years. In this paper, the course of hygienic control and the change in the medical findings of twenty-four chipping-hammer operators are reported. 1. The following measures were taken to improve the working conditions of chipping-hammer operators and therapy for patients (Table 1): (1) The operating time of vibrating tools, including chipping-hammer, was limited to two hours per day. The casting process was improved to diminish the flashes that are the objects of chipping-hammer operation. For the purpose of reducing the vibration transmitted to the operator, a servo-arm that has a servomechanism for the chipping-hammer was developed and introduced. (2) Infrared lamps in the foundry and air curtains at the doorway were installed for keeping the chipping-hammer operating area warm. A warm room was set up in the foundry for providing warmth during rest periods and protective clothing against the cold was provided. (3) Workers who displayed health disturbances by medical examinations were treated during the cold season from November to April by periodic visits to the clinic or extended hospitalization, or transferred to job without vibration exposure, according to their stage of disease. Preventive treatment with vasodilator and bubble bath was performed in winter for the chipping-hammer operators. 2. In order to estimate the effect of these countermeasures, annual medical examinations were conducted in March 1975, March 1976, April 1977 and March 1978. Such subjective symptoms as Raynaud's phenomenon, finger numbness, finger listlessness, heavy-headedness, forgetfulness, irritability and hearing disorder showed a tendency for improvement, but other complaints did not (Tables 2-4). The improvement of Raynaud's phenomenon is considered to be due not merely to the countermeasures but also to reducing the chance of provocation and therefore the countermeasures should not be overestimated as a factor of recovery of vibration hazards. Of the functional tests, a tendency for improvement was recognized in sensory functions and peripheral circulatory functions, but not in motor functions (Tables 5, 6). However, the course of recovery was not fast and some advanced cases, especially those using chipping-hammers for more than ten years, showed less improvement after hospital treatment (Table 7, Fig. 1). This indicates the importance of hygienic control which enables vibration hazards patients to have early diagnosis and treatment. Furthermore, in order to eradicate the vibration hazards in the cast metal industry, a drastic reform of the finishing process is considered to be necessary.

Adult↗