Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 775 records · Page 43Linked to original sources

PubMed1991

Comparative pharmacokinetic properties of murine monoclonal antibody A7 modified with neocarzinostatin, dextran and polyethylene glycol.

The murine monoclonal antibody A7 (Mab A7) was chemically modified with several macromolecules: dextran, polyethylene glycol and the anti-cancer polypeptide neocarzinostatin. The pharmacokinetic properties of the combinations were subsequently examined. Radioimmunoassay revealed that all preparations retained their antigen-binding activities. The Mab A7-neocarzinostatin conjugate was cleared from the blood circulation with a kinetic pattern almost identical to that of the parent Mab A7. Of the three preparations, Mab A7-dextran (A7-Dx) was removed the most rapidly from the circulation. Mab A7-polyethylene glycol (A7-PEG) exhibited the slowest blood clearance curve, with twice the half life of the parent Mab A7 in the circulation. In normal organ distributions, A7-Dx exhibited the highest liver, spleen and kidney uptake, and A7-PEG showed the lowest uptake, when expressed as tissue:blood ratio. Although A7-Dx exhibited lower tumor uptake, there was no significant difference among the three conjugates in tumor-bearing nude mice. A7-PEG seems to be a good candidate for targeted cancer therapy using antibody due to its high blood retention but low normal organ uptake.

Animals↗

PubMed1991

Tumor localization and in vivo antitumor activity of the immunoconjugate composed of anti-human colon cancer monoclonal antibody and mitomycin C-dextran conjugate.

The tissue distribution and in vivo antitumor activity of a novel monoclonal antibody-mitomycin C conjugate (A7-MMCD) composed of anti-human MAb A7 and MMC-dextran conjugate were investigated using tumor-bearing mice. A7-MMCD was prepared via an anionic dextran intermediate for the purpose of keeping the non-specific uptake by the reticuloendothelial system to a minimum. 111In-labeled A7-MMCD showed about a 5-times-greater accumulation in SW1116 (targeted tumor) than in S180 (non-targeted tumor) 48 h after injection, and produced a tumor-to-blood ratio which was 3 times higher in SW1116-bearing mice than in S180-bearing mice 96 h after injection. Accumulations in the liver, spleen, and kidney were also observed to some extent. Pharmacokinetic analysis revealed that A7-MMCD had nearly the same properties in the body as MMCDan (MMCD with an anionic charge), i.e., those of a negatively charged macromolecule. Both A7-MMCD and MMCDan had relatively similar tissue uptake rate indices for the liver and spleen. The tumor uptake rate index for SW1116 was about 2.5 times greater than that for S180, and the total amount of 111In-A7-MMCD accumulated in SW1116 was calculated to be approximately 5 times greater than the amount in S180. These results indicated that A7-MMCD could achieve site-specific targeting in the body. Furthermore, in the therapeutic experiment using SW1116 implanted subcutaneously, A7-MMCD suppressed tumor growth significantly, compared to free MMC and MMCDan. These results suggest that in designing an monoclonal antibody-drug conjugate via an intermediary, the physicochemical properties of intermediate macromolecules must also be taken into consideration to obtain a high degree of efficacy in vivo.

Animals↗

PubMed1991

Pinacidil inhibits the ryanodine-sensitive outward current and glibenclamide antagonizes its action in cells from the rabbit portal vein.

Pinacidil, a potassium-channel opener, inhibited the ryanodine-sensitive oscillatory outward potassium current induced by Ca released from an intracellular store. Glibenclamide, a blocker of the ATP-sensitive K-channel, prevented the action of pinacidil, suggesting the presence of an additional site (to K channels) for the vasodilator actions of pinacidil at which glibenclamide can act as an antagonist.

Adenosine Triphosphate↗

PubMed1991

A probable role for vaccines containing thimerosal in thimerosal hypersensitivity.

We patch tested 141 patients with 0.05% aq. thimerosal and 222 patients with 0.05% aq. mercuric chloride, including 63 children. The frequency of positive patch test reactions to thimerosal was 16.3%. There was a marked preponderance in the young age groups after vaccination, while none of 36 infants (aged 3-48 months) reacted to thimerosal. Positive reactions to mercuric chloride were found in 23 (10.4%) of 222 patients. We also sensitized guinea pigs with diphtheria-pertussis-tetanus (DPT) vaccine containing 0.01% thimerosal and succeeded in inducing hypersensitivity to thimerosal. From patch testing in humans and animal experiments, it is suggested that 0.01% thimerosal in vaccines can sensitize children, and that hypersensitivity to thimerosal is due to the thiosalicylic part of the molecule and correlates with photosensitivity to piroxicam.

Adolescent↗

PubMed1991

Cross-reactivity between sensitivity to thimerosal and photosensitivity to piroxicam in guinea pigs.

Piroxicam (PXM) is a nonsteroidal anti-inflammatory drug which may induce a photosensitive eruption shortly after administration. We examined whether animals sensitized to thimerosal developed a photosensitivity to PXM. Male Hartley strain guinea pigs were sensitized to thimerosal, thiosalicylate and PXM separately. The open patch test was used to evaluate sensitization to each drug and cross-reactions between the drugs. Animals sensitized to thimerosal exhibited positive patch test reactions to thiosalicylate and positive photopatch test reactions to PXM. Both those sensitized to thiosalicylate and to PXM showed positive patch test reactions to PXM. This study demonstrated that thimerosal induces cross-sensitivity to PXM in vivo and that the common active component among these compounds may be thiosalicylate.

Animals↗

PubMed1991

ATP activates cationic currents and modulates the calcium current through GTP-binding protein in rabbit portal vein.

1. Effects of adenosine 5'-triphosphate (ATP) on ionic currents of dispersed smooth muscle cells of the rabbit portal vein were investigated using the voltage-clamp procedure. 2. ATP (greater than or equal to 300 microM) produced transient and maintained inward currents. The former was inactivated within a few seconds, but the latter lasted more than several minutes. The transient but not the maintained current was blocked by pre-treatment with alpha,beta-methylene adenosine 5'-triphosphate (AMP-CPP). The amplitude of the latter was increased by ATP in a concentration-dependent manner. The following investigations were made on the ionic mechanism of the ATP-induced maintained inward current. 3. In 2.5 mM-Ca(2+)-containing tetraethylammonium chloride (TEA-Cl) solution (2.5 mM-Ca(2+)-TEA+ solution), the reversal potential for the ATP-induced inward current was close to the Cl- equilibrium potential, and in 140 mM-Na+ (nominally Ca(2+)-free or 0.3 mM-EGTA-containing) solution, the reversal potential was coincident with the Na+ equilibrium potential. 4. In 2.5 mM-Ca(2+)-TEA+ solution but not in 140 mM-Na+ solution and in physiological salt solution (PSS), niflumic acid (10 microM), a Cl- channel blocker, and Cl(-)-deficient perfusate in the pipette markedly inhibited the ATP-induced inward current. These results imply that in 2.5 mM-Ca(2+)-TEA+ solution the ATP-activated ion channel may admit Ca2+ which then accelerates the Ca(2+)-dependent Cl- current, but in 140 mM-Na+ solution and in PSS this channel may admit only Na+. 5. Intracellular perfusion of guanosine 5'-O-(3-thio triphosphate (GTP gamma S) did not provoke the current, but significantly increased the amplitude of the ATP-induced inward current in 2.5 mM-Ca(2+)-TEA+, 140 mM-Na+ and 2.5 mM-Ba(2+)-containing TEA+ (2.5 mM-Ba(2+)-TEA+) solutions. On the other hand, intracellular perfusion of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) reduced the amplitude of the ATP-induced inward current in the above solutions. 6. A low concentration of ATP (30 microM) transiently augmented the amplitude of the voltage-dependent Ca2+ current recorded in both 2.5 mM-Ca(2+)-TEA+ solution and PSS, but a high concentration of ATP (3 mM) consistently inhibited the voltage-dependent Ca2+ current in both solutions (4 mM-EGTA in the pipette). Such inhibition was partly prevented by application of 20 mM-EGTA in the pipette.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMed1991

Guanosine diphosphate activates an adenosine 5'-triphosphate-sensitive K+ channel in the rabbit portal vein.

1. Properties of the pinacidil-sensitive K+ channel in the smooth muscle of the rabbit portal vein were investigated using cell-attached and inside- and outside-out patch clamp techniques. 2. In the cell-attached patch configuration, a K+ channel with a unitary conductance of 150 pS could be recorded when physiological salt solution (PSS) was in the pipette and high-K+ solution was in the bath. Tetraethylammonium (TEA; less than 1 mM) and charybdotoxin (CTX; greater than 50 nM) inhibited the 150 pS K+ channel from the outside of the membrane. This channel was activated by an increase in the concentrations of intracellular Ca2+ but not by pinacidil (less than or equal to 500 microM). 3. In the cell-attached patch configuration, bath application of pinacidil (greater than 3 microM) activated a K+ channel (ATP-sensitive K+ channel) with a unitary conductance of 15 pS and the enhancing action of pinacidil was blocked by glibenclamide. However, in the cell-free patch configuration, pinacidil (100 microM) failed to open the 15 pS K+ channel. With pinacidil in the pipette, the 15 pS K+ channel was completely inactivated within 5 s of the excision of the membrane. Opening of the 15 pS K+ channel also disappeared after saponin treatment (50 micrograms/ml). 4. In the cell-free patch configuration, application of guanosine 5'-diphosphate (GDP; greater than 100 microM) re-activated the inactivated 15 pS K+ channel only when pinacidil was present either in the pipette or bath. GDP increased the mean open time and open probability of the 15 pS K+ channel in a concentration-dependent manner. Simultaneous application of MgCl2 (less than or equal to 1 mM) with GDP did not modify the GDP-induced activation. Neither GDP nor GTP (1 mM) had any effect on the 150 pS K+ channel. 5. Guanosine 5'-triphosphate (GTP; 1 mM) activated the 15 pS K+ channel to a lesser extent that did GDP. Other guanine nucleotides (guanosine 5'-monophosphate, GMP, 1 mM; guanosine 5'-O-(3-thiotriphosphate), GTP gamma S, 100 microM; and guanosine 5'-O-(2-thiodiphosphate), GDP beta S, 1 mM) failed to activate the 15 pS K+ channel. However, GDP beta S, but not GMP or GTP gamma S, inhibited this channel when it was activated by 1 mM-GDP. 6. In the presence of pinacidil, adenosine 5'-triphosphate (ATP; greater than or equal to 10 microM) inhibited the ATP-sensitive K+ channel when it was activated by 1 mM-GDP.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMed1991

Characterization of immunodominant epitopes of gag and pol gene-encoded proteins of human T-cell lymphotropic virus type I.

A series of synthetic peptides derived from the corresponding regions of the gag, pol, and env proteins of human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II) were used in an enzyme immunoassay to map the immunodominant epitopes of HTLV. Serum specimens from 79 of 87 (91%) HTLV-I-infected patients reacted with the synthetic peptide Gag-1a (amino acids [a.a.] 102 to 117) derived from the C terminus of the p19gag protein of HTLV-I. Minimal cross-reactivity (11%) was observed with serum specimens from HTLV-II-infected patients. Peptide Pol-3, encoded by the pol region of HTLV-I (a.a. 487 to 502), reacted with serum specimens from both HTLV-I- and HTLV-II-infected patients (94 and 86%, respectively). The antibody levels to Pol-3 were significantly higher (P less than 0.01) in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis than in either adult T-cell leukemia patients or HTLV-I-positive asymptomatic carriers. None of the other peptides studied demonstrated significant binding to serum specimens obtained from HTLV-I- or HTLV-II-infected individuals. While Gag-1a did not react with serum specimens from normal controls, Pol-3 demonstrated some reaction with specimens from seronegative individuals (11.4%). The antibodies to Gag-1a and Pol-3 in serum specimens from HTLV-I-infected patients could be specifically inhibited by the corresponding synthetic peptides and by a crude HTLV-I antigen preparation, indicating that these peptides mimic native epitopes present in HTLV-I proteins that are recognized by serum antibodies from HTLV-I- and -II-infected individuals.

Amino Acid Sequence↗

PubMed1991

Identification of pre- and postcentral gyri on CT and MR images on the basis of the medullary pattern of cerebral white matter.

The authors illustrate a new method to identify the pre- and postcentral gyri on computed tomographic (CT) and magnetic resonance (MR) images of the brain on the basis of the pattern of the medullary branches of the cerebral white matter. The most commonly used method to identify the gyri depends on recognition of the central sulcus by surface arrangement of the sulci. The two methods were compared by analysis of CT images of 104 subjects who had normal findings (age range, newborn to 60 years; 57 males and 47 females). The usefulness of the new method was also determined in angiographic studies of nine patients with space-occupying lesions. The method is especially helpful for identification of gyri on the lower level of the centrum semiovale and if space-occupying lesions are present that may result in a blurred depiction of sulci. Since MR imaging depicts the medullary branches more clearly than does CT, this new method should facilitate identification of the gyri with either modality.

Adolescent↗

PubMed1991

Preferential increase in the free form of atrial natriuretic peptide in adriamycin-induced nephrotic rats.

In order to evaluate the pathophysiologic role of a free form of atrial natriuretic peptide (ANP) in the nephrotic syndrome, the plasma concentration of immunoreactive ANP was measured by radioimmunoassay using direct (unextracted) and extraction methods in adriamycin-induced nephrotic and normal control rats. The ir-ANP levels measured using unextracted or extracted plasma were representative of total and the free form of ANP, respectively. The plasma levels of total and the free form of ANP were significantly higher in nephrotic rats than in controls (p less than 0.01, p less than 0.001). However, plasma levels of the bound form of ANP, calculated by subtracting the free form of ANP from total ANP, were comparable between the two groups. The free form of ANP was inversely correlated with the daily urinary sodium excretion (r = -0.71, p less than 0.001) and plasma albumin (r = -0.83, p less than 0.001), and positively correlated with the daily urinary protein excretion (r = -0.85, p less than 0.001) in both control and nephrotic groups. Based on these results, the preferential increase in the free form of ANP in nephrotic rats is considered to be a compensatory phenomenon induced by the decreased renal ability to eliminate sodium and water. An increase in the free form of ANP may have some role in urinary protein excretion in the nephrotic syndrome.

Animals↗

PubMed1991

Adenocarcinoma and squamous cell carcinoma in the same lobe of the lung. A case report.

Multiple primary lung cancers, either synchronous or metachronous, are unusual. We treated a 70-year-old man with double synchronous lung cancers in the right upper lobe, an adenocarcinoma and a squamous cell carcinoma. As multiple malignant lesions in an early stage may be curable, those patients in whom a lung cancer has already been detected, and who have an increased risk, such as long history of heavy smoking or of exposure to some carcinogens, an aggressive check-up should be performed and should be closely watched.

Adenocarcinoma↗

PubMed1991

Primary localized cutaneous nodular amyloidosis: case report and biochemical analysis of amyloid.

We report a patient with scalp lesions of primary localized cutaneous nodular amyloidosis. The extensive examination revealed no systemic involvement. Analysis of glycosaminoglycans (GAGs) in amyloid deposits showed a twofold increase as compared with normal skin, which was due to the increase in dermatan sulfate. Local disorders of GAG metabolism may be related to the amyloid fibril formation. Amyloid fibrils were purified and identified electron-microscopically, which consisted of two major 12,000- and 13,000-dalton and minor 29,000- and 48,000-dalton peptides. Western blotting analysis showed a minor 29,000-dalton peptide reactive with antibodies against both kappa and lambda light chains of immunoglobulin. There is a possibility that some components of amyloid in some cases of primary localized cutaneous nodular amyloidosis may consist of both kappa and lambda immunoglobulin light chains.

Amyloidosis↗

PubMed1991

Immunoreactive endothelin in human kidney.

Using a sensitive and specific radioimmunoassay for endothelin, we examined immunoreactive endothelin in human kidney tissue obtained from three necropsy and three nephrectomy cases. Immunoreactive endothelin was present in high concentrations in human kidney inner medulla (necropsy cases: 1.08 +/- 0.47 pg/mg wet weight:mean +/- SE)(nephrectomy cases: 2.77 +/- 0.46). Characterization by reverse phase high performance liquid chromatography indicated that the only immunoreactive endothelin in human kidney inner medulla is endothelin-1, although immunoreactive endothelin in rat and pig kidney inner medulla comprises both isopeptides endothelin-1 and -3, suggesting that the genetic expression of endothelin differs according to species.

Aged↗

PubMed1991

Anomalous origin of the left main coronary artery from the right aortic sinus of Valsalva with vasospastic angina.

A case of anomalous origin of the left main trunk of the coronary artery from the right aortic sinus of Valsalva with vasospastic angina is described. Vasospasm was induced in the left main coronary artery by intracoronary administration of ergonovine. To our knowledge, this is the first reported case of vasospastic angina occurring in the presence of the anomalous origin of the left main coronary artery from the right aortic sinus.

Aged↗

PubMed1991

Anti-thyroid antibodies in patients with hyperprolactinemia.

To clarify the possible role of prolactin in the regulation of immune responses in man, we measured circulating anti-thyroid antibodies in 172 normal subjects, 84 patients with prolactinoma and 63 patients with acromegaly with normal thyroid and adrenocortical functions. Frequencies of positive thyroidal microsome and thyroglobulin antibodies were significantly (p < 0.05 and p < 0.01, respectively) higher in women with prolactinoma (20.6% and 20.6%) than in normal women (7.5% and 4.7%). Men with prolactinoma had a significantly (p < 0.05) higher frequency of positive thyroglobulin antibody (18.8%) than normal men (1.5%). When the subjects were divided by decade, women with prolactinoma in the 4th decade had significantly (p < 0.05) higher frequencies of positive thyroidal microsome and thyroglobulin antibodies (30.8% and 30.8%) than normal women of corresponding age (3.7% and 3.7%). In contrast, there was no significant difference in the frequencies of positive anti-thyroid antibodies in patients with acromegaly and in normal subjects. Analysis of the peripheral lymphocyte population revealed that patients with prolactinoma had a higher percentage of B cells than normal subjects, while there was no significant difference in the percentages of total T lymphocytes or in the helper and suppressor T cell ratios in the two groups of subjects. These results suggest that prolactin regulates humoral immune responses in man directly by stimulating B lymphocytes or indirectly by inhibiting suppressor T lymphocyte activity.

Acromegaly↗

PubMed1991

Pharmacokinetic analysis of the monoclonal antibody A7-neocarzinostatin conjugate administered to nude mice.

The pharmacokinetics of a disulfide linked conjugate of a murine monoclonal antibody A7 with neocarzinostatin (A7-NCS) was studied following its intravenous administration to nude mice. Disappearance of the conjugate from the circulation was biphasic: an early rapid phase was followed by a much slower phase. The conjugate was removed from the blood circulation with a half-life of 12 hr, showing nearly the same kinetics as the free antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the disulfide linkage in A7-NCS was stable at least for 48 hr after administration of the conjugate to nude mice. The conjugate concentration in a human colon cancer SW1116 derived tumor reached maximum at 24 hr after injection and remained high for an additional 24 hr. The passive hemagglutination inhibition assay revealed that NCS in the conjugated form can be efficiently delivered to the target tissue. The present report indicates that A7-NCS was sufficiently stable in circulation to reach the target tumor without releasing NCS.

Animals↗

PubMed1991

An ultrastructural study on vestibular sensory cells in a new-mutant mouse.

The ultrastructural characteristics of the vestibular epithelium and light microscopical study of the central nervous system of a strain of new-mutant mice were analyzed. For the vestibular study, we used 72 homozygotes with ages ranging from 10 days to 18 months. The most striking findings observed in these mice were the disarray of the stereocilia of the utricular and saccular maculae and disintegration of the saccular otoconia. Many hair cells displayed abnormality of the stereocilia such as reduced number, disorganized distribution, and giant cilia, although the hair cell cytoplasm, including the nerve terminals, became fully developed. Demineralization of the saccular otoconia was age dependent, and a complete loss of the saccular hair cells was demonstrated. In conjunction with the disarray of the outer hair cells of the cochlea, morphological manifestation of the gene abnormality of these mice was related to immaturation of the stereociliary tufts. Because no morphological abnormality was observed in the central nervous system, the abnormal behavior in these mice was primarily correlated with morphological abnormalities of the vestibule.

Animals↗

PubMed1991

Anionic sites of the basement membrane of the labyrinth.

The presence of anionic sites in the labyrinth is demonstrated in this study, using polyethyleneimine as a cationic probe. Hartley-strain guinea pigs (200-300 g) with a normal Preyer's reflex were used. A 0.5% polyethyleneimine (PEI, MW 1,800) solution adjusted to pH 7.3 with HCl following Schurer's method was systemically administered through an axillary vein. In the cochlea, the presence of anionic sites was demonstrated on the basement membrane of the capillary wall in the stria vascularis. The presence of anionic sites was also confirmed on the basement membrane in Reissner's membrane but its density was much lower than that in the stria vascularis. In the ampulla and macula, the anionic sites were present on the basement membrane of the capillary wall and sensory epithelium.

Animals↗