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Biomedical subjects

W Nakamura

Publications and source records attributed to W Nakamura.

At least 19 recordsLinked to original sources

Contribution of chemical and non-chemical drives to breath-holding determined by visual analog scale (VAS).

Chemical and non-chemical contributions to breath-holding time (BHT) were directly determined by using a visual analog scale (VAS). These values were compared with those indirectly calculated from the method proposed by Godfrey and Campbell (1968). The magnitude of non-chemical factor at low PCO2 in our study was substantially less than the one obtained by the above investigators. We conclude that Godfrey and Campbell's model postulating linear augmentation of non-chemical sensation is inappropriate to explain dyspnea profile during breath-holding.

Biometry

Facial cold receptors and the survival reflex "diving bradycardia" in man.

We measured heart rate (HR), stroke volume (SV), systemic arterial blood pressure (BP), and mean arterial pressure (MAP) in 7 healthy volunteers in response to face immersion in water with concomitant breath-holding at different lung volumes. The subjects were at rest in the prone position. During breath-holding at total lung capacity (TLC), baseline HR (70 to 75 beats/min) fell by 10% within fractions of a second, both in the control preimmersion state when the head was surrounded by room air, and when it was immersed in water of 33 degrees C. This response was associated with rises in MAP and in SV. Immersion of the face in 10 degrees C water while breath-holding, was associated with a strong, negative chronotropic effect (22% fall in HR), which developed within 10 s. Breath-holding at functional residual capacity (FRC) reduced HR substantially only in 10 degrees C water, and in contrast to that at TLC, the response was slowly developing with a latency of 10-15 s. All these reductions in HR were significant and accompanied by increases in BP and MAP. The strong, negative chronotropic effect of cold water was typically linked to a rise in SV. The study identified two temporal components of HR reduction to face immersion: a fast parasympathetic response dependent on the input from the high pressure baroreceptors, and a late response mediated, in all likelihood, by sympathetic efferent activity. Facial receptors sensitive to cold seem to be vital in the largest responses observed. The fast response to breath-holding with the face in water of neutral temperature was equal to that in air. Thus "diving bradycardia" is in fact a basic survival response independent of water.

Adult

[Combined effect of cis-DDP (II), OK-432 and systemic hyperthermia in ascites tumor in mice].

Combined effect of cis-DDP (II) (CDDP), a streptococcal preparation (OK-432) and systemic hyperthermia on ascites tumor in mice was studied. Tumor cells were of a syngeneic cloned cell line FMA3 which was derived from Furth's mastocytoma. When number of cells transplanted into the abdominal cavity was at 10(5), a single i.p. injection of CDDP at a dose of 4 mg/kg was effective to increase the mean survival time by a factor of 1.6. OK-432 given i.p. at a dose of 5 KE/kg on every two days between day 2 and day 10 after transplantation decreased the mean survival times. Even when it was used in combination with CDDP, enhancement of the effect of CDDP was not statistically significant. However, by the factorial analysis of the all data obtained in the experiments carried out with tumor cells of the number of 10(2), 10(3), 10(4) and 10(5), enhancement of the effect of CDDP by OK-432 was significant. Systemic hyperthermia of the core-body temperature of 40 degrees C was not effective when used alone, and did not enhance the effect of CDDP. However, combined use of it and OK-432 significantly enhanced the effect of CDDP.

Animals

Adenocarcinoma and carcinoid developing spontaneously in the stomach of mutant strains of Mastomys natalensis.

Neoplastic and nonneoplastic lesions developing spontaneously in antral and fundic mucosae of stomachs of mutant chamois-coloured Z (130 animals) and Y (67 animals) strains of Mastomys aged 18 to 24 months were examined histologically and histochemically. The Z strain developed both antral lesions (hyperplasia 29.2%; dysplasia 23.8%; adenocarcinoma 17.7%) and fundic carcinoid(s) (72.3%). The antral lesions were limited to the lesser curvature near the pyloric ring. Macroscopically, adenocarcinomas resembled human gastric carcinomas of either Borrmann's type I or II. Histochemically, adenocarcinoma cells were characterised by marked reduction of total mucins produced and predominance of mucins with both periodic acid-Schiff and Alcian blue reactivities (neutral and sialated class II mucins). An infiltrating adenocarcinoma was successfully transplanted into nude mice, reaching the 7th generation of transplantations over 4 years, and retained histological features of the primary tumour. The ultrastructural appearance of growing transplanted tumours supported the reduced production of mucins by adenocarcinoma cells with scarcity of mucin granules and intracellular cysts. However, the Y strain never developed antral lesions like the wild strain, developing fundic carcinoid(s) only. Microscopically, these carcinoids contained argyrophilic nonargentaffin granules, and biochemically produced histamine consistently but no 5-hydroxytryptamine (5-HT, serotonin) like those of the wild strain. Since we found unexpectedly that a line of F2 but not F1 hybrids between wild and Z strains developed the same antral lesions as Z strain, a preliminary experiment was performed to confirm the development of antral lesions in F2 hybrids newly produced by brother-sister mating. Among 41 surviving F2 offspring, 4 (9.8%) developed hyperplasia, 2 (4.9%) dysplasia and none adenocarcinoma. The numbers (6) of animals observed with these lesions approximated to their expected numbers (7.3).

Adenocarcinoma

Whole-body hyperthermia-induced renal atrophy of mice as evinced by obstruction and degeneration of renal tubules caused by acute ischemia.

Effects of microwave-induced whole-body hyperthermia (WBH) on the mouse kidney were examined histologically for acute and late effects up to 150 days after WBH treatment at 43.5 degrees C (rectal temperature) for 20 min or 42 degrees C for 40 min. As a whole the damage could be divided into two types. One was the damage to distorted epithelial cells in the subcapsular region. This lesion was common in most animals, possibly caused by direct hyperthermic effect of microwave. The other was general renal atrophy accompanied with aqueous or protein-rich cysts due to a chain of physiological reactions of the whole body to WBH. The first reaction was characterized by general stasis of the blood stream in all parts of the kidney, which resulted in acute ischemia of some tissues. This was seen immediately by dilatation of the renal and interlobular veins as well as the bundles of capillaries in the medulla region. The subsequent event was rather specific cell necrosis of distal and collecting tubular epithelium as compared to proximal tubules. The cell destruction induced cell proliferation of the proximal tubular epithelia after two days. Later on, in accord with the recovery of the blood circulation, the proliferated cells were carried away into the lumen, these processes then resulting in obstruction of tubules through formation of protein casts in the lumen. The block incidentally led to the destruction of nephrons. The degenerated area sometimes consisted of aqueous or protein-rich cysts of various sizes after 7 to 30 days. Thereafter these cysts degenerated, decreasing in both number and size. Thus irreversible atrophy of the kidney developed after WBH.

Acute Disease

Circulatory and respiratory responses to lower body negative pressure in man.

Circulatory and ventilatory responses to lower body negative pressure (LBNP) were simultaneously investigated in 8 healthy men before, during, and after the application of -20, -40, and -60 mmHg pressure. Minute ventilation (VE) decreased during LBNP due to a fall in respiratory frequency with sustained tidal volume. The cardiac output (Q) was reduced in proportion to the applied LBNP exposure, while VE decreased to almost the same level at all LBNP applications. In spite of decreased VE, end-tidal PO2 and PCO2 were increased and decreased, respectively, indicating a relative alveolar hyperventilation. The ventilation equivalent for O2 (VE/VO2) increased, while the cardiac output equivalent for O2 (Q/VO2) decreased. The relation between VE/VO2 and Q/VO2 showed a significant negative correlation (r = -0.93, p less than 0.01). The veno-arterial CO2 concentration difference (CvCO2--CaCO2) increased with LBNP, due to a fall in CaCO2 with constant CvCO2. The constant CvCO2 indicated a constant tissue acid-base balance. These observations suggest the existence of a ventilatory mechanism improving the efficiency of respiration in order to compensate for the sustained LBNP depression of Q at a given gas exchange.

Adult

[Accumulation of liquids in the small intestine in mice after hyperthermia].

Female adult mice were subjected to 1) sublethal, 2) midlethal and 3) supralethal doses of systemic hyperthermia. In these mice, death occurred soon or several hours after the heat treatment depending on the severity of heating. In every cases, however, progression of the disseminated intravascular coagulation (DIC) syndrome such as decrease in thrombocyte count, condensation of circulating blood and liquid accumulation in the lumen of small intestines was with nearly the same speed indicating that the DIC was not the main cause of the death.

Animals

Respiratory and cardiac responses to dynamic exercise in man.

Ventilation (VE), cardiac output (Q), oxygen consumption (VO2), carbon dioxide production (VCO2), and end tidal gas tensions (PETO2 and PETCO2) were measured in four healthy men during stepwise, steady state increases in work rate on a bicycle ergometer (25, 50, 75, 100, 125, and 150 W). Both the ventilation equivalent (VE/VCO2) and the cardiac equivalent (Q/VCO2) for carbon dioxide, fell during a steady state exercise at 150 W to 2/3 and to 1/3 of the initial levels, respectively. This stepwise reduction in the carbon dioxide production with increasing work rate was compatible with a non-chemical stimulus increasing in proportion to work rate, and governing both ventilation and circulation. These observations do not support the cardio-dynamic hypothesis.

Adult

Brady- and tachycardia in light of the Valsalva and the Mueller maneuver (apnea).

With a computerized impedance cardiograph we measured stroke volume (sv), cardiac output and heart rate (HR) in four men, during apnea with positive or negative intrapulmonic pressure (i.e., Valsalva and Mueller maneuver) in air. During Valsalva maneuvers the sv was reduced, and the compensatory rise in HR failed to keep the cardiac output at the control level before apnea. During both types of apnea, the diastolic pressure was increased as was the total peripheral resistance (TPR). The vasoconstriction and tachycardia during Valsalva maneuvers can be explained as a sino-aortic baroreceptor phenomenon in man. The smaller changes occurring during Mueller maneuvers result in no change in the transmural arterial pressure in the thorax, compared to the control level. Thus, without a stimulus there is no change in heart rate. The alveolar oxygen uptake and carbon dioxide elimination during apnea at total lung capacity was much larger than in the control phase before both types of apnea. The arteriolar vasoconstriction with increased TPR during the Valsalva apnea, was accompanied by a reduction in the stroke work of the left ventricle to approximately 50% of the work in the control phase.

Adult

[On a factor present in tumor cells, capable of decreasing thermotolerance in mice].

Comparison was made of the capacity of tumor cells of three different cell lines to decrease the thermotolerance in mice. Tumor cells used were that of three cell lines of mastocytoma, FMA1 and FMA3, and of Ehrlich's ascites tumor, EAT. Temperature for the assay of thermotolerance of the animal was 42.0 +/- 0.2 degrees C in the core body. Thermotolerance of animal was expressed with LD50, 42 degrees C. Tumor cells were transplanted at a dose of 10(5) cells per mouse. In the animals transplanted with tumor cells of every three cell lines, the minimal value of the LD50, 42 degrees C was obtained one or two days after the transplantation. Thermotolerance ratios (TTRs) calculated with the minimal values of LD50, 42 degrees C were 0.54, 0.19 and 0.62 for the FMA1, FMA3 and EAT cells, respectively. The thermotolerance decreasing effect of the FMA3 cells was kept unchanged even after destruction of the cells by suspending in distilled water and repeated freezing and thawing. But it disappeared partially after heating the cells for 10 min at 90 degrees C, and completely after the heating the cells for 60 min at the same temperature.

5-Hydroxytryptophan

[Sensitivity of mice to systemic hyperthermia: effect of the transplantation of ascites tumor cells modified by preheating, and by an injection of CDDP or interferon].

Effects of preheating and injection of cis-DDP (CDDP) or interferon on tumor-induced sensitization to systemic hyperthermia (SH) was investigated in mice. LD50 of SH at 42.0 +/- 0.2 degrees C (core body temperature) was 43 min in normal mice and 8 min in mice which were i.p. transplanted with FMA3 cells at a dose of 10(5) one day before. In mice which had received the SH for 10 min one hour before, one hour after or one day before the transplantation, LD50 of the SH one day after the transplantation was 41, 35 and 22 min, respectively. An injection of CDDP given i.p. at a dose of 4 mg/kg one day after the transplantation, which was effective to kill about 99% of the tumor cells, did not change the course of thermosensitization after the transplantation. An i.p. injection of mouse interferon did not change the thermosensitivity of normal mice, but greatly suppressed the thermosensitizing effect of tumor cells when it was given one day before the transplantation.

Animals

[Combined effects of cis-DDP and OK-432 on ascitic mastocytoma in mice: optimal period for the administration of OK-432].

Combined effects of cis-DDP and OK-432 on the ascites mastocytoma was studied in mice laying emphasis on the best timing for the administration of the OK-432. Mice were transplanted with FMA3 mastocytoma cells into the abdominal cavity at a dose of 10(5) cells per mouse. They were injected with cis-DDP next day at a single shot of 8 mg/kg in the abdominal cavity. A streptococcal preparation, OK-432, was i.p. injected two times at intervals of one week at a dose of 50 KE/kg per injection. The pair of injections started 1, 2, 3, 4 or 5 weeks after the transplantation. Mean survival time (M. S. T.) of mice was 16.8, 16.2 and 52.3 in the groups of mice nontreated, given OK-432 alone, and given cis-DDP alone, respectively. In comparison of M. S. T. within the groups of mice treated with the combination of cis-DDP and OK-432, the highest value was observed in the group which was given OK-432 between 3 and 4 weeks after the transplantation.

Animals

[Sensitivity of mice to systemic hyperthermia: effect of ascites tumor cell transplants].

The effect of a transplantation of mastocytoma cells in the abdominal cavity on the sensitivity of mice to a systemic hyperthermia was studied. The systemic hyperthermia was induced by exposing whole-body of animals to 2,450 MHz waves under anesthesia. Core body temperature was raised up to 42.0 +/- 0.2 degrees C in 15 min and maintained constant at the temperature for variable length of time. Thermosensitivity of animal was expressed with LD50, 42 degrees which was the length of heating time at the temperature of 42 degrees C lethal for 50% of the animals examined. The transplants were mastocytoma FMA3 cells. They were transplanted at a dose of 10(5) cells per mouse. The LD50, 42 degrees observed 3, 12 hrs, 1, 2, 3 and 6 days after the transplantation was 33, 23, 17, 24 and 35 min, respectively. In mice without tumor it was 43 min.

Animals

[Tolerance to induced systemic hyperthermia in the mouse].

The effect of exposure of organisms to systemic hyperthermia on induction of tolerance to the lethal effect of subsequently assigned systemic hyperthermia was studied in mice. The length of time of the pretreatment at 42.0 +/- 0.2 degrees C (core body temperature) was 5, 10 or 15 mn. The temperature of the second systemic hyperthermia was 42.0 +/- 0.2 degrees C and 43.5 +/- 0.2 degrees C. In mice which had no experience of systemic hyperthermia, lethal dose required to kill 50% of animals at 42.0 degrees C and 43.5 degrees C, namely LD50, 42 degrees and LD50, 43 degrees 5 was 43 and 8.5 mn, respectively. While, in mice which had received the pretreatment at 42 degrees C for 10 mn, the LD50, 42 degrees was 97 mn one day after and 48 mn two days after the pretreatment. In mice which had received the pretreatment at 42 degrees C for 5, 10 or 15 mn, the LD50, 43 degrees 5 was 17, 20 and 19 mn one day after the pretreatment, and 10, 10 and 6 mn two days after the pretreatment, respectively. With the data obtained, thermotolerance ratio (TTR) was calculated. The maximum TTR of 2.35 was obtained in mice examined one day after the pretreatment at 42.0 degrees C for 10 mn.

Animals

[Does weak local gamma irradiation modify the effect of CDDP on mouse mastocytoma?].

The possibility that an irradiation with small doses of gamma rays given shortly before might enhance the cure effect of cis-diammine-dichloroplatinum (II) (CDDP) was tested in tumor bearing mice. Tumor cells of FMA3, a cloned cell line of murine mastocytoma, were transplanted in the muscle of a hind leg in one experiment and in the abdominal cavity in another experiment. In both cases, a single injection of CDDP at 4 mg/kg was effective to lengthen the mean survival time of mice. gamma rays at the dose of 1, 2 and 4 Gy given 3 hours before did not modify the effect of CDDP.

Animals

[Combined effects of gamma rays, cis-diamminedichloroplatinum (CDDP) and systemic hyperthermia mastocytoma transplanted into muscle in the mouse].

Comparison was made between the effects of local irradiation of gamma rays, s. c. injection of cis-diamminedichloroplatinum (II) (CDDP), systemic hyperthermia and their combinations on the i. m. transplanted murine mastocytoma. Increase of the mean survival time (M. S. T.) by a factor of 1.72 and of 1.68 was achieved by a single irradiation at 20 Gy, given on day 5 after transplantation, and by injections of CDDP at 2 mg/kg, given s. c. on days 5 and 12 after transplantation, respectively. Increase of M. S. T. by a factor of 1.10 which was achieved with systemic hyperthermia of 41.8 degrees C of the core body temperature for 5 min, given twice, on days 5 and 12 after transplantation, was not statistically significant. The most effective one among all possible combinations within the 3 modalities was that of radiation and CDDP. Increase of M. S. T. was by a factor of 4.01.

Animals