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Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 649 records · Page 36Linked to original sources

[Pharmacokinetic and clinical studies on sulbactam/ampicillin in the pediatric field].

The new antibiotic, sulbactam/ampicillin (SBT/ABPC) was administered to 25 children. The results obtained are summarized as follows. 1. In 5 cases of children administered with SBT/ABPC (30 mg/kg) by intravenous drip infusion for 30 minutes, the mean values of T 1/2 (beta) were 0.94 hour (SBT) and 0.86 hour (ABPC) and the mean 6.5 hour urinary excretion rates were 64.2% and 42.9%, respectively. 2. The antibiotic was administered to a total of 25 patients with bronchopneumonia, pneumonia, bronchitis, cervical lymphadenitis, tonsillitis, streptococcal infection, urinary tract infection, felon, periappendicular abscess, sepsis or purulent meningitis. Response to the treatment were excellent in 17 cases, good in 7, fair in 1, and poor in none. The efficacy rate was 96%. From our results, this drug appears to be particularly effective against bronchopneumonia, bronchitis and urinary tract infection. 3. Eruption occurred in 1 of 25 patients and elevation of eosinophil, GOT/GPT, platelet in 3 and descent of WBC in 1 were observed, but these were transient. These results showed that SBT/ABPC is a drug which can be safely used in the pediatric field as well as for adults.

Age Factors↗

[Laboratory and clinical investigations of cefodizime in infectious diseases in childhood].

In this study, cefodizime (CDZM, THR-221) was administered to 34 children with infections and the efficacy was evaluated in 30 patients. The efficacy rate was 90.0% and CDZM was proved to be a highly effective antibiotic for infectious diseases in childhood. We also demonstrated that CDZM had strong antibacterial activities against both Gram-positive and Gram-negative bacteria. No severe toxicity related to intravenous injection of CDZM was observed in our 34 cases.

Age Factors↗

[A case report of graft-versus-host reaction after aortocoronary bypass--a clinicopathological study].

An immunologically normal 70-year-old male developed fever and disturbance of consciousness after aortocoronary bypass; this was followed by diarrhea, systemic erythroderma and granulocytopenia. He died as a result of sepsis and acute renal failure. The skin biopsy showed basel vacuolar degeneration, epidermal eosinophilic necrosis and invasion of T-lymphocytes. The autopsy showed necrotic small interlobular bile ducts, severely hypoplastic bone marrow and widespread necrosis of lymphoid tissue. Based on these clinicopathological findings, we made a diagnosis of graft-versus host reaction after transfusion.

Aged↗

[Cataract epidemiological study in west Sumatra].

A cataract epidemiology survey using a photo-documentation system was performed for people over age 40 who live in West Sumatra Island. The percent prevalence of cataracts, including early senile changes, were 28.7% in the 50 year-old population, 64.7% in the 60, 83.8% the 70 and 95.8% for people over 80. Prominent cataractous opacification was recognized in 8.8% the 50-59 year old population, 21.1% for those in their 60s, 38.7% for those in their 70s and 83.3% in people over 80. The most frequently observed cataract types were cortical and nuclear, followed by mixed types which had almost the same ratio. The incidence of nuclear cataracts was 3.5% and 8.5% in the 40-49 and 50-59 year-old population, respectively. The percent of nuclear cataracts seen in the 60 and 70 year-old population were 22.7% and 32.4%, respectively. Cataract incidence in 50-59 year-old diabetic subjects was significantly higher than that in non-diabetic subjects. Cataract incidence in 50-59 year-old subjects with high myopia was significantly higher than in cares of other types of refractive error. The main type of lens opacification seen in the high myopia cases was nuclear. Cataract prevalence in the 50 year-old age group who had received a high level of education was significantly lower than that of others.

Adult↗

Demonstration of intracytoplasmic immunoglobulin in non-T-acute lymphocytic leukemia cases of children with immunoelectron microscopic examination.

Leukemic cells from 25 cases of non-T-acute lymphocytic leukemia (ALL) in children were investigated for intracellular immunoglobulin by the use of immunoelectron microscopic study (immuno-EM). As a result, 12 cases were negative for both heavy and light chains of the immunoglobulin in the neoplastic cells. Of these, one case that was also negative for common ALL antigen (CALLA) was defined as null cell type. The remaining 11 cases were defined as common ALL type. Six cases were defined as pre-B-cell type because they were positive for cytoplasmic mu chain but negative for cytoplasmic light chains. Seven cases were defined as B-cell type, all of which possessed lambda light chains in the neoplastic cells. Immunohistologic studies using monoclonal antibodies showed that most non-T-ALL cases were positive for CALLA and B4, whereas about 50% of them were positive for B1. Our immuno-EM study suggests that it is one of the effective ways of subclassifying non-T-ALL in children.

Antibodies, Monoclonal↗

Limiting dilution comparison of the repertoires of high and low responder MHC-restricted T cells.

To approach the mechanism that determines Ir gene-controlled high or low responsiveness to whole proteins, such as sperm whale myoglobin (SWMb), we compared the repertoires of high and low responder haplotype-restricted T cells for different myoglobin epitopes by limiting dilution frequency analysis. Poisson analysis was performed using long-term limiting dilution cell lines of (B10.BR [low] X B10.D2[high])F1 T cells maintained on high or low responder APCs. The cell lines were tested with SWMb peptides and fragments for T cell repertoire fine specificities and Ia restrictions. The frequency of SWMb-specific F1 T cells responsive on B10.BR (H-2k) APCs was 2.5-3.6-fold lower than on B10.D2 (H-2d) APCs. Strikingly, all of the H-2k-restricted T cells used I-Ek as a restriction element, whereas both I-Ad- and I-Ed-restricted T cells were found among the H-2d-restricted lines. The I-Ad-restricted T cells were dominant, and the majority was specific for the synthetic peptide 102-118. T cells specific for peptide 132-146, dominant in association with I-Ed, were less frequent. However, no detectable H-2k-restricted T cells were specific for either of these peptides, but instead they were specific for fragment 1-55 or peptide 59-80. Fragment 1-55 also stimulated a similar number of H-2d-restricted T cells. Therefore, the low response of F1 T cells on H-2k-presenting cells may be due to the failure to see myoglobin plus I-Ak, in particular the immunodominant site around Glu 109, in contrast to the dominant response of high responder mice (both H-2d and H-2s) focused on the I-A molecule and the site around residue Glu 109. The I-E- low responder B10 strain also failed to respond to peptide 102-118, supporting the idea that the low responder status results from a limited repertoire lacking response to 102-118 plus I-A. In those strains that respond to the immunodominant site 102-118, the frequency of T cells in the repertoire specific for this site was always considerably greater than that for other sites. These results suggest that there is an important difference between immunodominant epitopes and minor epitopes and that Ir gene-controlled low responsiveness to a natural whole protein may be due primarily to the failure to respond to a single immunodominant site, even though a number of other epitopes can be recognized.

Animals↗

Nicorandil shortens action potential duration and antagonises the reduction of Vmax by lidocaine but not by disopyramide in guinea-pig papillary muscles.

Conventional microelectrode techniques were used to examine whether or not nicorandil, which shortens action potential duration (APD), modifies the lidocaine- or disopyramide-induced time-dependent reduction of Vmax in guinea-pig papillary muscles. First, effects of 0.1 and 1 mmol/l nicorandil were examined on the frequency dependence of Vmax and on the recovery process of Vmax. Second, the frequency-dependent reduction of Vmax by 20 mumol/l antiarrhythmic drugs was examined in the presence and absence of 1 mmol/l nicorandil at stimulation frequencies of 1/120 Hz - 5 Hz. Third, the recovery process of Vmax in the presence of 20 mumol/l antiarrhythmic drugs was examined, with and without 1 mmol/l nicorandil, by applying test stimuli at various diastolic intervals after conditioning stimuli. 1 mmol/l nicorandil greatly shortened APD90 to 30-40% of control without changing the frequency dependence of Vmax, the recovery process of Vmax, and the resting potential. The lidocaine-induced, frequency-dependent reduction of Vmax was significantly antagonised by 1 mmol/l nicorandil, but the disopyramide-induced reduction was not. The recovery process of Vmax slowed in the presence of lidocaine was antagonised by 1 mmol/l nicorandil as follows: the time to get the full recovery of Vmax was shortened by nicorandil with a significant decrease in the zero time-intercept (from 0.54 to 0.38) but with an insignificant change in the recovery time constant (from 130 ms to 121 ms). In contrast, the recovery process of Vmax slowed in the presence of disopyramide (a zero time intercept of 0.13 and a recovery time constant of 50 s) was not significantly antagonised by 1 mmol/l nicorandil. In conclusion, nicorandil having an action potential-shortening action antagonises the lidocaine-induced, time-dependent reductions of Vmax, but not the disopyramide-induced reductions. These results suggest that: (1) lidocaine and disopyramide preferentially bind to inactivated and activated sodium channels, respectively, because lidocaine's effects are dependent on and disopyramide's effects are independent of APD (during which sodium channels are in the inactivated state); and (2) nicorandil is a useful drug for estimating whether a sodium channel-blocking action of class I antiarrhythmic drugs is due to an inactivated channel block or an activated channel block. These time-dependent reductions of Vmax by both lidocaine and disopyramide were well simulated by the guarded receptor hypothesis.

Action Potentials↗

Dynamic study of nervous control on prostatic contraction and fluid excretion in the dog.

The effect of the section or stimulation of various nerves on prostatic contraction and fluid excretion was investigated dynamically in the dog using an apparatus devised in our laboratory. Prostatic contraction could be classified into two types from the pattern of the contracting wave. One was a prominent tonic contraction, designated as H-type contraction, observed typically after hypogastric nerve stimulation and followed always by prostatic fluid excretion. The other was a weak clonic contraction, designated as P-type contraction, occurring typically after pelvic nerve stimulation and accompanied by no fluid excretion. The periodical contraction of these two types was noticed even at rest. The H-type contraction was associated with fluid excretion with a mean rate of 0.3 ml./hr. The denervation both of the hypogastric and pelvic nerves showed no distinct influence on contraction and excretion in the resting condition. The pudendal nerve was demonstrated to have no significant effect on prostatic contraction and fluid excretion. From these results, it was considered that dynamic fluid excretion followed by prostatic contraction was regulated chiefly by sympathetic fibers from the hypogastric nerve and the physiological role of parasympathetic fibers from the pelvic nerve was something other than fluid excretion.

Animals↗

Specular microscopy of the anterior lens capsule after endocapsular lens implantation.

Endocapsular phacoemulsification and complete in-the-bag intraocular lens (IOL) fixation was performed on 77 eyes. Specular microscopy of the anterior lens capsule was performed postoperatively, and the process of anterior capsule opacification after endocapsular cataract surgery was classified. Lens epithelial cells on the inner surface of the anterior lens capsule, facing the optical portion of the IOL, underwent a diffuse fibrosis. In more peripheral areas, where the anterior and posterior capsules were tightly adherent, the regularly proliferating lens epithelial cells retained their polygonal shape. These findings suggest the possibility of retaining the transparency of the anterior lens capsule postoperatively by refilling the capsular bag to apply internal pressure.

Aged↗

DRC antigen expression in B-cell lymphomas.

DRC (dendritic reticulum cell) antigen expression was studied in 38 cases of B-cell lymphomas including follicular lymphoma. The results of this study showed DRC-1 to be expressed in 1/3 of small lymphocytic; 3/3 of mantle zone lymphoma (MZL); 10/10 of follicular, small cleaved; 6/7 of follicular, mixed; 1/2 of follicular, large cell lymphomas. However, DRC-1 was not expressed in any of diffuse, small cleaved (0/6) and diffuse, large cell (0/6). Although S-100 protein was positive in the majority of these DRC-1-positive cases on the paraffin embedded specimens, positive nodules were less intense and smaller in number compared with those of DRC-1 on frozen tissue specimens. These results suggest that in case of small lymphocytic lymphoma found to be positive for DRC-1, the networks of the DRCs are expressed in the pseudofollicular proliferation centers. This study also suggests that the networks of the DRCs newly appear accompanying the neoplastic growth rather than originating from residual germinal centers, and that neoplastic small cleaved cells play a major role in inducing the DRCs in the positive cases of follicular lymphoma, MZL, and small lymphocytic lymphoma.

Antigens↗

Immunohistochemical study of mantle zone lymphoma.

Lymph nodes from four cases of mantle zone lymphoma (MZL) were studied immunohistochemically. All the cases had serum M proteins. Immunostaining with paraffin-embedded specimens revealed that proliferating cells of neoplastic nodules possessed the same monoclonal immunoglobulins as those in the serum (IgM, kappa in three and IgM, gamma in one). The plasma cells around neoplastic nodules contained the same monoclonal immunoglobulins as those in the nodules in two cases. In the remainder, most plasma cells around the nodules possessed the same immunoglobulins as those in the nodules. The authors consider these plasma cells to be the cause of paraproteinemia. Immunostaining with paraffin and frozen tissue sections revealed that the neoplastic cells (or neoplastic nodules) were positive for sIgD, sIgM, dendritic reticulum cell antigen (DRC-1), and LN-2 and weakly positive for common acute lymphocytic leukemia antigen (CALLA), and LN-1. These results indicate that the neoplastic cells of MZL have both phenotypes of mantle zone lymphocytes (sIgD, sIgM, and LN-2 positive) and of germinal center cells (sIgM, DRC-1, CALLA, and LN-1 positive). MZL is thus considered to be a neoplasma of B-cells differentiating from mantle zone lymphocytes to germinal center cells.

Cell Division↗

Leu-4 (CD3) antigen expression in the neoplastic cells from T-ALL and T-lymphoblastic lymphoma.

The authors studied Leu-4 (CD3) antigen localization in the neoplastic cells from six cases with T-ALL, eight with T-lymphoblastic lymphoma (T-LL), and eight with peripheral T-cell lymphomas using immunoelectron microscopy (immuno-EM). Other various monoclonal antibody studies were also performed to detect the stages of differentiation of the neoplastic cells light microscopically. The authors' study indicated that cytoplasmic Leu-4 (cLeu-4) antigen expression appeared at the early stage of thymic T-cells, together with Leu-9 (CD7) and T101 (CD5). Their immuno-EM study also disclosed that the neoplastic cells at the early stage of thymocyte differentiation all had positive results for cLeu-4 but negative results for surface Leu-4 (sLeu-4). The Leu-4 antigen expression in the neoplastic cells at the stage of common thymocyte differentiation with OKT6- (CD1) positive phenotype was variable, showing cLeu-4+sLeu-4-, cLeu-4-sLeu-4+, and cLeu-4+sLeu-4+, depending on the cases investigated. From these results, they suggest that cLeu-4 antigen appears at the stage of early thymocyte differentiation, followed by predominant sLeu-4 expression at the stage of common thymocyte differentiation, and finally simultaneous expression of cLeu-4 and sLeu-4 at the stage of peripheral T-cells.

Antibodies, Monoclonal↗

Polyclonal antibodies to DNA modified with 4-nitroquinoline 1-oxide: application for the detection of 4-nitroquinoline 1-oxide-DNA adducts in vivo.

Antibodies against 4-nitroquinoline 1-oxide (4NQO) adducts were elicited in rabbits immunized with 4NQO-modified DNA complexed with methylated bovine serum albumin. In enzyme-linked immunosorbent assay (ELISA), the antibodies could recognize either denatured or native 4NQO-modified DNA, but not unmodified DNA, DNA modified with other carcinogens or free 4NQO derivative. Modification levels as low as 5 mumol of adduct per one mole DNA nucleotide (5 adducts/10(6) nucleotides) can be easily detected by the competitive ELISA. Indirect immunofluorescence staining by anti 4NQO-DNA antibody indicated that the antibodies bound specifically to the nuclei of normal human skin fibroblast cells treated with 4NQO. The intensity of fluorescence was proportional to the dose of 4NQO used to treat the cells, and the fluorescence-positive cells could be detected after treatment with 0.25 microM 4NQO (which resulted in the formation of 10(4) adducts per cell). Applying the competitive ELISA to the quantitation of DNA-adducts in rats treated with 4NQO, it was confirmed that the sensitivity of immunochemical assays was equivalent to that of isotopic assays. These methods should be helpful in studies on the formation of adducts and their removal in cells and tissues.

4-Nitroquinoline-1-oxide↗

Fast inward current properties of voltage-clamped ventricular cells of embryonic chick heart.

To determine ionic properties of the fast inward current of embryonic chick hearts, whole cell voltage-clamp experiments were carried out on single cardiomyocytes. Ventricular myocytes trypsin dispersed (spherical, 10-15 microns in diameter, 10.7 pF in membrane capacitance) from 16- to 18-day-old embryonic chick hearts were used. Cells were bathed in solutions containing 140 mM Na+ at room temperature of 22 degrees C. Action potentials recorded via patch electrodes were approximately 103 mV in amplitude, -73 mV in resting potential, and 400 ms in duration. The maximum amplitude of the fast inward-current peak was -1.34 nA (-0.126 mA/microF) and the voltage at which the current was maximum was -29 mV. The reversal potential (Vrev) for this inward current was +35 mV. The inward current was sensitive to change in extracellular Na+ concentration ([Na+]o) (18-mV change in Vrev for halved [Na+]o) and to tetrodotoxin (TTX; 10(-6)-10(-5) M). The inactivation time constant (tau h) and the time-to-peak current decreased from several milliseconds at -60 mV to 1 ms at positive potentials. The steady-state inactivation (h infinity) characteristics showed an S-shaped dependence on voltages between -110 and -60 mV, giving about -90 mV for the half-inactivation voltage. The steady-state activation characteristics (m infinity) also showed sigmoidal voltage dependence, and the half-activation voltage was -54 mV. Both h infinity and m infinity curves crossed each other in the vicinity of -73 mV, giving a maximum window conductance (m infinity 3.h infinity) of 0.00044 at -50 mV. Compared with inactivation, the reactivation of the fast inward channel proceeded much more slowly. It was concluded that except for the low current density of embryonic chick ventricular cells the voltage- and time-dependent kinetics of the fast inward current channel were quite similar to those reported for the fast Na+ channels in single myocytes of adult hearts of other animal species.

Action Potentials↗

In vivo observation of the crystalline lens capsule.

The crystalline lens capsules of eye bank eyes, intraocular lens (IOL)-inserted eyes and those of monkey and rabbit eyes were observed in vivo and/or in vitro through a specular microscope or Scheimpflug slit images in combination with new image-processing techniques and scanning electron microscopy. Shagreen patterns seen in both human and animal eyes may reflect the lens epithelium and basement-membrane-like layer. As a postoperative examination in IOL-inserted eyes, the distance between the IOL and the posterior lens capsule could be measured with an accuracy of 50 microns.

Animals↗

Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats.

To elucidate the role of the internal elastic lamina in the development of cerebral aneurysm, the bifurcation of the anterior cerebral artery and olfactory artery was histologically studied in control and experimental rats treated with unilateral carotid ligation and renal hypertension. Various stages of aneurysm formation were compared, and it was found that early aneurysmal changes were always present just distal to the apical intimal pad on the anterior cerebral artery side. The internal elastic lamina was thinned and fragmented just distal to the pad even in the very early stage of aneurysm formation when the medial layer was still present. In control rats, the internal elastic lamina had a tendency to thin and fragment at the site where aneurysms would develop in experimental rats. Our study shows that changes of the internal elastic lamina were present just distal to the pad even in control rats, which never develop cerebral aneurysms. Under hemodynamic stress augmented by experimental treatments, further degenerative changes of the internal elastic lamina and involvement of the medial layer are considered to occur and result in aneurysm formation there.

Animals↗