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Biomedical subjects

K Kawamoto

Publications and source records attributed to K Kawamoto.

At least 253 records · Page 14Linked to original sources

[A phase I study of VP-16-213 (VP, etoposide) by single and 5-day intravenous administration].

A phase I study of VP was undertaken using the methods of a single (40 cases; range of dose levels 30-540 mg/m2) and 5-day (41 cases; range of dose levels 40-140 mg/m2/day) intravenous administration. The dose-limiting toxicity of VP was moderate to severe leukopenia. MTD was estimated to be 540 mg/m2 for a single and 140 mg/m2/day for 5-day administration. The median days to WBC nadir from the start of therapy and to recovery from reaching the nadir were 10 and 10.5 for single, and 15 and 7 for 5-day administration, respectively. Thrombocytopenia was less frequent and less pronounced than leukopenia. Mild gastrointestinal disturbances and alopecia were frequently observed. Transient hepatic dysfunction, fever, headache, fatigue, dyspnea, hypotension, and pain along the vein were also encountered in a small number of patients. There were no cases with renal, neurologic or cardiac toxicity. Objective tumor regression was seen in one case each of IBL(CR), bladder cancer, non-Hodgkin's lymphoma and ATL (PR). The post-infusion plasma decay of VP in 4 cases given 80-120 mg/m2 by a single administration was biphasic with t1/2 alpha ranging from 0.13 to 0.39 h and t1/2 beta ranging from 3.33 to 4.85 h. No accumulation of VP was found in plasma after five repeated daily doses. Doses of 360-480 mg/m2 by single and 80-100 mg/m2/day by 5-day administration repeated every 3 to 4 weeks can therefore be recommended for phase II studies in good-risk patients.

Adult↗

Plasticity of vasopressin- and oxytocin-containing fibers in the median eminence in hypophysectomized young and old mice.

Rearrangements of vasopressin- and oxytocin-containing fibers in the external layer of the median eminence after hypophysectomy were compared between young and old mice. In 3-month-old hypophysectomized mice, the increase in the number of fibers containing vasopressin was greater than that observed in 19-month-old hypophysectomized ones, suggesting a decrease in axonal plasticity in old mice. No difference with age was detected for the plasticity of fibers containing oxytocin.

Age Factors↗

Ultrastructural study of a cerebral gangliocytoma.

A pure cerebral gangliocytoma leaving no sign or symptom of recurrence after surgical removal is reported, with special reference to its CT scan and the ultrastructural findings. Unusual, large, dense bodies having the size of 800-1200 m mu and radiating from a central core were identified on the ultrastructural study. Microcystic formations might have been produced by active secretory granules containing dense core vesicles. The literature concerning the dense core vesicle of ganglion cell tumors is reviewed.

Adult↗

Ultrasonic electrocochleography in guinea pig.

In order to obtain information about how ultrasonic stimuli are perceived (USP) in man, guinea pig cochleae were stimulated by bone conduction with frequencies (98.8 and 143.5 kHz) above the normal auditory field of this animal. The cochlear potentials recorded consisted of CM, SP and AP originating from the basal turn of the cochlea, and were found to be influenced by asphyxia, administration of ethacrynic acid, hypothermia and change of interstimulus interval. In addition, in kanamycin-treated animals the mean AP amplitude decreased to about one fourth of the normal value, and the mean AP latency increased significantly. These findings suggest that there is no special sense organ for the detection of USP but that such sounds activate hair cells in the basal turn of the cochlea.

Animals↗

Changes of vasopressin- and oxytocin-immunoreactive neurons after hypophysectomy in young and old mice.

Changes of magnocellular neurons after hypophysectomy were immunohistochemically studied using antisera to arginine vasopressin (AVP) and oxytocin (OXT) in young and old female mice of the C57BL/Tw strain. AVP-immunoreactive neurons in the supraoptic and paraventricular nuclei of intact 19-month-old mice showed a marked reduction in number and immunoreactivity as compared with those of intact 3-month-old mice. Age difference of OXT-immunoreactive neurons was less pronounced than that of AVP-immunoreactive neurons. After hypophysectomy, both AVP- and OXT-immunoreactive neurons showed an intense stainability 10 days after the operation regardless of ages. However, the rate of reduction in number of immunoreactive neurons after hypophysectomy was less marked in 19-month-old than 3-month-old mice.

Aging↗

Clinical and experimental studies on the pathogenesis of otitis media with effusion.

Otitis media is the most common pediatric disease as a complication of the upper respiratory infection and at least 10% of the otitis prone children will suffer from prolonged episodes of minor conductive hearing loss and communication disorder due to the presence of middle ear effusion (MEE). In spite of exhaustive studies presented in the past three international symposia on otitis media with effusion (OME), there still remain wide gaps in our knowledge regarding the etio-pathogenesis and appropriate treatments of the disease. A couple of years ago, a new project of clinical and laboratory researches on OME were initiated in the Department of Otolaryngology, Tohoku University School of Medicine and some results of the studies have been reported in recent Japanese academy meetings as well as in the 2nd and 3rd International Symposium of Recent Advances in OME. The purpose of this paper is to summarize the results of our recent studies performed by several investigators in our department and related hospitals.

Animals↗

Endotoxin in middle ear effusions: in cases with persistent effusion after acute otitis media.

Endotoxin in persistent middle ear effusions (MEEs) from children with acute otitis media (AOM) whose acute inflammation had cleared was assayed by Limulus test, parallel with the detection of bacteria. Seventy-five percents of MEEs were endotoxin positive, and the concentration of endotoxin in MEE was not related to the interval between the onset of AOM and the date of sample collection. However, the cases with MEE that had high concentration of endotoxin tended to have persistent MEE for more than one month after sample collection. Therefore, the presence of endotoxin may be one of the causal factors of a delayed recovery of AOM and of the development of otitis media with effusion.

Acute Disease↗

Gas analysis of the middle ear cavity in normal and pathological conditions.

The gas of the tympanic bulla was measured using 18 normal and 14 tube-obstructed guinea pigs. The concentrations of CO2 and O2 were 4.8 +/- 1.0% and 7.2 +/- 1.8% in normal animals, and 4.3 +/- 1.6% and 8.1 +/- 2.0% in tube-obstructed animals, respectively. The bulla was opened to room air and then closed again. The recovery process of each gas was examined. In normal animals, CO2 and O2 were exponentially changed toward the pre-open value with time. The time constants of this recovery process were 15 min and 97 min in CO2 and O2, respectively. In tube-obstructed animals, however, this quick recovery of CO2 was significantly delayed (time constant, 50 to 80 min), although there was no effect upon the recovery of O2. This delayed recovery of CO2 is likely to be due to the edema of the mucous membrane.

Animals↗

Experimental model for the otitis media with effusion induced by Arthus' reaction.

The Arthus' reaction in the middle ear cavity was studied using histochemical technique. The deposition of immune complex on the basement membrane and the immune complex in the middle ear effusion were the initial features of these animal models. But, these immune complexes were clearly removed from the tympanic cavity during the early phase of reaction. Immune complexes were supposed to be just a initiation of otitis media with effusion. The tubal dysfunction and local immunity of middle ear mucosa caused by the Arthus' reaction seemed to be responsible for the chronicity and relapsing of otitis media with effusion respectively.

Animals↗

Forward-backward tracing tympanometry in the diagnosis of middle ear pressure.

Two tympanograms (TG) were routinely recorded on each ear by changing the pressure in the external auditory meatus (EAM), one in the decreasing (forward tracing: TG-F) followed by the other in the increasing direction (backward tracing: TG-B). Both TG were drawn on the same chart and the peak locations were compared. In a normal ear the TG-F peak tended to be formed in the negative pressure area and that of TG-B in the positive area. In a model whose middle ear pressure (MEP) was adjusted to the atmospheric pressure, the TG-F peak always indicated a negative pressure and that of TG-B a positive pressure value. As long as the same model was used, the magnitude of peak shift was identical irrespective of the middle ear pressure. The magnitude of the peak shift was influenced by the speed of EAM pressure change and a linear increase was observed up to the speed of 70 mmH2O/sec, both in a normal ear and a model. These findings seem to suggest that the peak location of a unidirectionally drawn TG can not be regarded as indicating the precise MEP. A valid MEP can better be estimated by averaging the peak pressure of TG-F and TG-B of forward-backward tracing tympanogram. In ears with pathology considerable variation was noted in the magnitude of the peak shift, so that relying solely on unidirectionally drawn TG could have lead to misdiagnosis in some cases. This was especially true with ears having small perforations covered with granulation or fluid.

Acoustic Impedance Tests↗

Tympanograms of otitis media with effusion: an experimental study.

A sufficient explanation concerning tympanogram (TG) of otitis media with effusion (OME) has not been reported. The purpose of the present study was to investigate the relationship between the types of TG and actual pathological status of the middle ear system by means of experimentally modified middle ear clefts. In the present experiments, human temporal bones, guinea pigs' bullae and plastic models were used. The results were as follows: (1) Water was gradually poured into the middle ear cleft through the Eustachian tube. When the water level rose above the umbo, the height of TG slightly exceeded that of the original TG. Further addition of water produced M-shaped TG, however, flat TG (type B) was not detected until the water-line nearly reached the aditus. A similar phenomenon was observed in the plastic models when the water level reached the aditus-equivalent-site. (2) Tympanometrically measured middle ear pressure (MEP) was almost equivalent to the actual MEP recorded by a manometer when the tympanic membrane was normal. However, this result could not be duplicated in flaccid or adhesive tympanic membrane cases. (3) A clear reduction in the height of TG in guinea pigs' bullae was observed with decreased air volume. In addition, shallow TG was produced by an occlusion of the aditus of the human temporal bones and of the aditus-equivalent-site of the plastic models. It was demonstrated that the TG pattern depends on the fluid volume and location, air volume of mastoid cavity, intratympanic pressure and eardrum condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Impedance Tests↗

Primary pancreatic carcinoma in childhood. Pancreatoblastoma.

A case of primary pancreatic carcinoma confirmed by postmortem examination in a 15-year-old girl is presented. The tumor was studied by light and electron microscopy and an indirect immunoperoxidase technique. Some of the tumor cells contained eosinophilic, PAS-positive, diastase-resistant granules. Electron microscopy revealed large electron-dense granules resembling zymogen granules. The granules seen in the islet cell tumors were not demonstrated by electron microscopy and immunoperoxidase technique. These findings suggest that the tumor is of duct cell origin with some differentiation toward the acinar cells. The tumor appears to belong to the so-called "pancreatoblastoma".

Adolescent↗

Developmental changes in the binding of follicle-stimulating hormone (FSH) to testicular preparations of mice and the effects of hypophysectomy and administration of FSH on the binding.

Changes with age in testicular FSH binding and the effects of hypophysectomy and administration of FSH on FSH binding were studied in mice. The binding per unit testicular weight reached a peak at 10-20 days of age and it rapidly decreased during 20-37 days. The total binding per two testes increased from 4 days of age, reaching a peak at 31 days, and decreased thereafter when the testis still continued growing. Scatchard plot analyses of the binding showed that the equilibrium constant of dissociation (Kd) was about 3 X 10(-10) M regardless of age, and the changes in FSH binding were due to changes in the number of binding sites. Hypophysectomy at 90 days of age induced a significant decrease in the testicular weight, but the concentration of FSH binding sites markedly increased 16 days after the operation. In hypophysectomized mice the total number of FSH binding sites was increased 1.8-fold as compared with intact mice. In contrast, hypophysectomy induced a decrease in the total number of LH-binding sites. Injections of 100 micrograms NIH-FSH-P-2 for 10 days to hypophysectomized mice significantly decreased the concentration and the total number of FSH binding sites as compared with those in saline-injected hypophysectomized mice. These results suggest that FSH reduces its own receptors in the testis of mice.

Animals↗

[Clinico-immunological evaluation of T cells bearing IgG Fc receptors in brain tumor patients].

T cells bearing IgG Fc receptors (Tr cells) were determined in 40 cases of brain tumor using the double rosette method, and compared with the changes of PHA reaction, immunoglobulin (IgG A M), performance status, and mass effect on CT in 20 pre-and post-operative and/or radio-clinico-immunotherapeutic patients. The proportion of control Tr cells was 8-19% in 20 healthy adults. Values of Tr cells over 20% were correlated with a poor grade of performance status, and large mass effects on CT. Post-therapeutic change in the value was well correlated with change in performance status, mass effects, and IgG. Our results suggest a correlation between the value of Tr cells and clinico-radiological findings. Immunological analysis of Tr cells serves as a parameter of tumor expansion or prognosis, and could be of significant importance clinically.

Antineoplastic Combined Chemotherapy Protocols↗

[Recombinant interferon alpha-2 (Sch 30500) in patients with head and neck cancer].

Fifteen patients with advanced recurrent or metastatic carcinoma of the head and neck were treated with recombinant interferon alpha-2. Cumulative doses for evaluation of at least 1.2 X 10(8) IU were given over a period of 4 weeks. No significant regression was shown in 14 evaluable patients, 6 of which showed no change and 8 progression. Toxicities were minimum and acceptable. All patients had an episode of elevated body temperature. One patient showed transient effects on the central nervous system, which may be a dose-limiting factor. Recombinant interferon alpha-2 was therefore not recommended as a modality for the treatment of recurrent head and neck cancer.

Adult↗