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Biomedical subjects

A Handa

Publications and source records attributed to A Handa.

At least 55 records · Page 3Linked to original sources

Partial thrombosis of canine carotid bifurcation aneurysms with cellulose acetate polymer.

OBJECTIVE: To investigate the usefulness of a cellulose acetate polymer (CAP) solution for partial thrombosis of aneurysms. METHODS: We created 14 canine cervical carotid bifurcation aneurysms, 11 of which were subsequently thrombosed partially with CAP solution. We then conducted angiographic and histological investigations. RESULTS: Nine aneurysms were thrombosed 50 to 70% by volume, although a significant crescent crevice between the aneurysmal sac and the CAP mass was left in four of the aneurysms. In the remaining two aneurysms in which a crescent crevice had been seen in the initial stage of CAP injection, 80% and more than 95% thrombosis were needed to occlude the crevice, respectively. Follow-up angiograms of the seven aneurysms with no crescent crevice revealed no shifts of position of the CAP mass toward the bottom of the aneurysm sac, but slight ballooning of the remnants was observed in two of them. The angiograms of the other four aneurysms with significant crescent crevices demonstrated rupture with a massive hematoma in one and shifts of the CAP mass with marked enlargement of remnants in three. Histologically, the seven aneurysms with no enlarged remnants had newly developed membranes consisting of endothelium, infiltrated spindle-shaped cells, collagen, and elastic fibers. In contrast, in the three markedly enlarged aneurysms, there were only recent clots between the CAP mass and the aneurysm lumen and no development of endothelium. CONCLUSION: Partial thrombosis with CAP solution is useful to keep aneurysms in a stable configuration, unless a crescent crevice has been left.

Aneurysm↗

Transcription-positive cofactor 4 enhances rescue of adeno-associated virus genome from an infectious clone.

While Rep proteins are required for adeno-associated virus (AAV) replication, little is known about cellular proteins that interact with Rep. We demonstrate here that transcription-positive cofactor 4 (PC4, p15) fused to Gal4-activating domain interacted with both AAV-2 and AAV-3 Rep proteins fused to Gal4 DNA-binding domain, leading to reporter activation in the yeast two-hybrid system. In addition to its coactivating function, PC4 recently has been shown to be involved in replication of simian virus 40. To study a functional role for the PC4-Rep protein interaction, 293-31 cells were cotransfected with a PC4 expression plasmid and an infectious clone of AAV-3, followed by super-infection with helper adenovirus. A significantly increased number of AAV-3 genomes were rescued in PC4 transfected cells. Our results support a possible involvement of PC4 in AAV replication and may be used in efficient production of AAV vectors for gene therapy.

Adenoviridae↗

[Cervical myelopathy caused by bilateral vertebral artery compression].

We report a rare case of myelopathy caused by compression of the upper cervical cord by the bilateral anomalous vertebral arteries. A 49-year-old man had dragged his right foot for 4 years. He also complained of a tingling sensation in his right arm and occipitalgia. Neurological examination disclosed right hemiparesis, hypalgesia in the right half of the body and hypertonicity of the lower extremities. MRIs showed a flow void area which compressed and distorted the spinal cord bilaterally at the level of the atlas. A vertebral angiogram showed that the bilateral vertebral arteries had pierced the dura matter under the posterior arch of the atlas, turned upward and laterally in the vertebral canal, making vascular loops at the level of the atlas. 3D CT angiography showed the loops convex medially in the anterior part of the vertebral canal. With these findings, we diagnosed the patient as suffering compression of the cervical cord by the bilateral anomalous vertebral arteries. Suboccipital craniectomy and C1 laminectomy were performed. When the dura mater was opened, the dorsolateral aspect of the spinal cord was found to be compressed and indented markedly by the vertebral arteries. To decompress the spinal cord, the vertebral arteries were retracted dorsolaterally by means of Gore-tex tape and anchored to the spinous process of the axis. Postoperatively, his neurological symptoms improved. Postoperative MRIs showed that the spinal cord was decompressed and had recovered its contour. A review of the literature revealed that only 3 such cases as this one have been reported. The clinical features of these rare cases are nonspecific myelopathy and concomitant occipitalgia or neck pain. The main cause of this rare entity seemed to be the compression of the vertebral artery through its course when it enters the vertebral canal between the atlas and the axis.

Humans↗

[Abnormal hemoglobinopathy (HbE) diagnosed from microcytic hypochromic red blood cells in a 31 year-old Bangladeshian male].

Microcytic hypochromic red blood cells (RBC) were discovered in a 31 year-old Bangladeshi man. Additional laboratory data revealed only slight elevations of LDH and transaminase activities. The patient was clinically asymptomatic and showed no signs of anemia. On this basis, along with biochemical genetic analysis of hemoglobin, a diagnosis of hemoglobinopathy (HbE) was made. HbE is common in southeast Asia with over 30% of the population affected. Most people are asymptomatic. In northern Asia, including Japan, HbE is found in only 0.001% of the population. With ther recent influx of southeast Asians to Japan, care must be taken not to overlook the diagnosis of hemoglobinopathies.

Adult↗

Complications of varicose vein surgery.

A retrospective review was carried out of patients who had undergone surgery for varicose veins over an 8 year period between 1985 and 1993. We wished to determine the incidence of various complications so that the risks of surgery could be openly discussed with patients. A total of 973 limbs were operated upon in 599 patients (413 F, 186 M; mean age 49 years). All patients were under the care of a single consultant vascular surgeon who was present at 92% of operations and all patients were reviewed postoperatively. There was no perioperative mortality. Wound complications (haematoma, cellulitis or abscess) occurred in 2.8% of limbs and minor neurological disturbance (numbness or tingling) in 6.6%. Leakage of lymph from the groin occurred in five patients, all of whom had undergone exploration for groin recurrence. Major complications included three cases of deep venous thrombosis (0.5%), one pulmonary embolus, and one foot-drop. There was one major vascular injury, the common femoral vein being damaged in a patient having a third operation on the groin for persistent recurrence. Vein patch repair was performed and patency was maintained. The overall incidence of major complications was 0.8%. Minor complications occurred in 17% of patients. It is unlikely that major complications can be eliminated. In this retrospective review there will be some under-reporting, but we are confident that this is restricted to minor complications.

Adolescent↗

Granulocyte-colony stimulating factor induced apoptosis in radiation-induced murine leukemia cell line.

Cytokines regulate proliferation and differentiation of hematopoietic progenitor cells. Recently it has been clarified that physiological cell death, apoptosis plays important role of hematopoiesis. So we evaluated the effects of granulocyte-colony stimulating factor (G-CSF) on leukemic cells, especially focused on apoptosis. Intravenous inoculation of radiation-induced murine leukemia cell line, C2M-A5 into the parent C3H mice resulted in the development of myeloid leukemia. However, the leukemic death of the mice was completely suppressed by the daily subcutaneous injection of recombinant human (rh)G-CSF from the next day (Bessho M. et al., Leuk Res 1989:13:1001-1007). In the in vitro study using C2M-A5 cells, we found that apoptosis appears on the cells at 48 hours after addition of G-CSF in culture. The cells in this stage lost the leukemogenicity to C3H mice (Bessho M. et al., Leukemia 8:1185-1190:1994). To clarify the mechanism of the induction of apoptosis by G-CSF we studied cell cycle and molecular changes in C2M-A5 cells cultured in medium with or without rhG-CSF by means of using the flowcytometry and Northern and Western blot analyses. After addition of rh G-CSF to culture, C2M-A5 cells removed to S phase, next arrested at G0/G1 phase on and after 24 hours, and 48 hours later, apoptosis was observed. Overexpression of mRNAs for c-myc (3-24 hours later) and for p53 (6-24 hours later), were observed in the cell cultured in rhG-CSF administered medium with a concomitant down-expression of bcl-2 mRNA (from 6 hours later). Tyrosine-phosphorylated protein (17 kd) appeared at 48 hours after administration of rhG-CSF to cell culture. This protein was suggested for specific apoptosis induction by rhG-CSF. These results are summarized as follows. (1) rhG-CSF induced apoptosis to C2M-A5 and deprived its leukemogenicity to mice. (2) Induction of apoptosis was associated with cell cycle and correlated to the changes of the expression rates of c-myc,p53, and bcl-2. (3) Tyrosine kinase may play an important role in apoptosis induction to C2M-A5 by rhG-CSF.

Animals↗

[Plasma cell leukemia associated with monocytosis].

A 51-year-old man was admitted to our hospital in December 1993, because of fatigue. Peripheral blood tests showed a WBC of 49,400/microliter with 36% plasma cells and 35% monocytes, Hb 14.5 g/dl, and Plt 137,000/microliter. Bone marrow aspirate revealed hypercellularity with 48.7% plasma cells and 22.4% monocytes. Plasma cells in blood were positive for CD38 and PCA-1. Serum calcium, IgA and M-CSF levels were elevated to 14.1 mg/dl, 2,337 mg/dl and 2.7 ng/ml, respectively. Immunoelectrophoresis of serum and urine revealed IgA lambda type M protein and lambda type Bence Jones protein, respectively. Rearrangements of immunoglobulin heavy chain and light chain were demonstrated by Southern blotting analysis. Plasma cell leukemia (IgA lambda type) was diagnosed. He was treated with combination chemotherapy and IFN-alpha and achieved complete remission. However, he suffered a meningeal relapse in February 1995, and died in April 1996. It seems likely that the enhanced production of M-CSF by myeloma cells and/ or activated B cells stimulated monocyte production.

Humans↗

Differential regulation by hematopoietic growth factors of apoptosis and mitosis in acute myeloblastic leukemia cells.

We evaluated the effects of various hematopoietic growth factors (HGFs) on the prevention of apoptosis in blasts from 19 patients with acute myeloblastic leukemia (AML) by assessing DNA ladder formation. After incubation without HGF, apoptosis was noted in all but two patients. HGFs prevented, did not affect, or enhanced apoptosis in 39 (60%), 14 (22%), or 12 (18%) of 65 suspension cultures, respectively. HGFs that prevented apoptosis also stimulated and/or synergized blast colony formation in 35 of 39 corresponding methylcellulose cultures. HGFs that alone stimulated colony formation also prevented apoptosis in all but two of 28 corresponding suspension cultures. In contrast, HGFs that did not prevent apoptosis also failed to stimulate growth in 17 of 26 corresponding methylcellulose cultures. HGFs that enhanced apoptosis alone never stimulated colony formation. After incubation, we noted enhanced c-fos and cjun genes as well as induction of p21 protein. An appropriate dose of HGF elevated c-fos, reduced c-jun and p21, induced G1/S transition, and inhibited apoptosis. In two patients, apoptosis was not induced after incubation. Cells not treated with HGF expressed no c-fos, c-jun, or c-myc, and remained in G0/G1. Taken together, our results support the conclusion that not only c-fos, cjun, and c-myc, but also p53 and p21 are required for blast apoptosis. HGF differentially prevents apoptosis and induces mitosis, and both events seem to be integral to the self-renewal of AML clonogenic cells.

Apoptosis↗

Otomycosis--a clinico-mycological study and efficacy of mercurochrome in its treatment.

A total of 110 patients of symptomatic otomycosis was investigated, prospectively. Aural swabs were collected on 1st, 7th and 14th day and examined by direct microscopy and culture for fungi. Of these, 80 patients found to be having pure fungal infection, were taken up for mycological and therapeutic study. Fungi belonging to genus Aspergillus were isolated in 76 (95.0%) patients of which Aspergillus niger was the commonest isolate in 46 (57.5%), followed by A. flavus in 27 (33.7%), A. fumigatus in 3 (3.7%), Candida species in 3 (3.7%) and Mucor in 1 (1.2%). The patients were of all age groups but majority were between 21 and 30 years and the male-female ratio was equal. Of the total of 40 male patients, twenty-one were Sikhs using turban. Before developing the symptoms, forty five patients used oil, mixture of oil and garlic juice, antibiotics, steroids, antiseptics or wax solvent as ear drops. Only two patients were diabetic. No patient had fungal infection elsewhere in the body. The patients were called for regular follow-up for three weeks. In forty cases mercurochrome was applied as the antifungal agent after cleaning the external auditory canal, in twenty-three clotrimazole and in rest of the seventeen patients miconazole was used. On 7th day, only 11 (13.7%) patients grew different fungi in culture. They became symptom-free on 14th day and no fungal material could be seen on otoscopy, direct microscopy or culture. Mercurochrome was found to be most effective in these patients.

Adult↗

[Detection of angina-related coronary artery in patients with unstable angina pectoris by using 123I-BMIPP myocardial scintigraphy].

To evaluate the diagnostic accuracy of detection of angina-related coronary arteries in patients with unstable angina pectoris. Twenty patients with unstable angina pectoris underwent 123I-BMIPP scintigraphy at rest. A mean duration from last anginal attack to 123I-BMIPP scintigraphy was 408 +/- 3.2 days. Seventeen of 20 angina-related coronary territories were detected by reduced 123I-BMIPP uptake. The sensitivity and specificity for detection of angina-related coronary arteries were 85% and 95%, respectively. The decrease in myocardial uptake of 123I-BMIPP agreed with the decrease in regional wall motion by using ultrasonic echocardiography. 123I-BMIPP scintigraphy may be useful for detection of angina-related coronary artery in a routine clinical examination in patients with unstable angina pectoris.

Aged↗

[Cytokines regulate apoptosis of leukemic cells].

It is clear that cytokines regulate normal hematopoiesis including proliferation, differentiation, and apoptosis (programmed cell death). Leukemia is a disorder of unbalance between excessive proliferation and inappropriate apoptosis. Leukemic cells are also stimulated by cytokines similar to normal hematopoietic cells. It is reported that the oncogenes and tumor suppressor genes are associated with not only leukemogenesis but also cell cycle, for example proliferation, differentiation, and apoptosis (programmed cell death). We found that G-CSF leads to apoptosis of radiation induced murine leukemia cell line (C2M-A5), and its apoptosis is dependent on cell cycle. From these results together with other related reports, cytokines seem to be a key substance of apoptosis of leukemic cells and the apoptosis inducing therapy will be a new strategy for leukemia therapy.

Animals↗

Prophylactic thrombosis to prevent new bleeding and to delay aneurysm surgery.

Six aneurysms in five patients with acute aneurysmal subarachnoid hemorrhages were treated with direct thrombosis using cellulose acetate polymer within 4 hours of rupture. The aneurysms involved the internal carotid and posterior communicating arteries (two patients), the anterior choroidal artery (one patient), the bifurcation of the basilar artery (one patient), and the middle cerebral artery (two patients). Four patients underwent aggressive volume expansion after direct thrombosis with cellulose acetate polymer. The aneurysms remained thrombosed until operations on the necks were performed 2 to 7 weeks after the subarachnoid hemorrhages. Three patients were given intrathecal tissue plasminogen activator. One patient, who remained at neurological Grade V, was not treated surgically and died from cardiac failure. Five aneurysms in the remaining four patients were successfully clipped. These preliminary data suggest that immediate aneurysmal thrombosis, then aggressive preoperative prophylactic volume expansion and/or administration of intrathecal tissue plasminogen activator, can help prevent new bleeding and reduce delayed cerebral ischemia in patients after aneurysmal subarachnoid hemorrhages.

Aged↗

Early treatment of subarachnoid hemorrhage after preventing rerupture of an aneurysm.

Twelve patients with Hunt and Hess neurological Grades III to V underwent thrombosis of aneurysms using cellulose acetate polymer within 23 hours of aneurysm rupture. On computerized tomography (CT), nine of these patients had difuse or localized thick subarachnoid blood clots, two had diffuse thin clots and one had intraventricular clots. Immediately after thrombosis, all patients were administered tissue plasminogen activator (TPA) through spinal or ventricular catheters. The pressure of the lumbar cerebrospinal fluid was maintained at 100 to 150 mm H2O. The TPA was given as multiple injections of 2 mg on Day 0 and 1 to 2 mg on the following 1 to 2 days. In two patients the second injection of TPA was not given because of severe brain damage resulting from the initial subarachnoid hemorrhage. Ten patients showed complete clearance of the cisternal clot on CT within 72 hours after thrombosis. Seven partially thrombosed aneurysms and five multiple aneurysms were clipped during delayed surgery. Only one patient experienced mild vasospasm as shown on the follow-up angiogram. Eight patients improved clinically and had a good recovery, two had severe disability, and two died. Urgent thrombosis of a ruptured aneurysm followed by immediate postthrombotic administration of TPA may be a safe and reasonable means of preventing vasospasm and improving patient outcome.

Aged↗

Detection of neutralizing antibodies against human T-cell leukemia virus type 1 using a cell-free infection system and polymerase chain reaction.

We have developed a cell-free infection system to titrate neutralizing antibodies against human T-cell leukemia virus type 1 (HTLV-1) using the polymerase chain reaction (PCR). S+L-CCC (8C) feline kidney or U-251 MG human glioma cells were infected with a cell-free culture supernatant derived from HTLV-1-infected c77 feline cells. DNA was extracted from 8C or U-251 MG cells after incubation for 24 hr and amplified by PCR. The c77 cell supernatant gave discrete bands, whereas those of HTLV-1-positive T cells did not. When the inocula were treated with HTLV-1 antibody-positive human sera or the monoclonal or polyclonal antibody against the peptide 190-199 of HTLV-1 envelope protein gp46, the subsequent formation of HTLV-1 proviral DNA was inhibited. We determined the titers of neutralizing antibodies by densitometrically scanning the intensity of the PCR bands. These titers correlated well with those determined by the plaque assay using a pseudotype of vesicular stomatitis virus bearing the envelope antigens of HTLV-1. At high serum concentrations, many seronegative samples markedly inhibited the plating of the HTLV-1 pseudotype whereas they barely affected results obtained by PCR. Thus, the c77-PCR system can detect neutralizing antibodies against HTLV-1 even at low titers.

Animals↗

Inhibition of adsorption of human T-cell-leukemia virus type 1 by a plant lectin, wheat-germ agglutinin.

Thirty-six lectins that recognize various sugar chains were examined for inhibitory activities against infection with human T-cell leukemia virus type I (HTLV-I). Wheat-germ agglutinin (WGA) was the most inhibitory among them: plating of the pseudotype of vesicular-stomatitis virus (VSV) bearing envelope antigens of HTLV-I was markedly inhibited by treatment of indicator cells with WGA just before adsorption, but not by treatment after virus adsorption. Treatment with WGA before adsorption, however, could not inhibit the plating of VSV, VSV pseudotypes of bovine leukemia virus, Moloney murine leukemia virus and human immunodeficiency virus type I. Syncytium formation induced by HTLV-I was also inhibited by WGA upon co-cultivation of U-251 MG human glioma cells or MOLT-4 human T-cells with HTLV-I-producing C91/PL cells. Formation of proviral DNA detected one day after infection was also inhibited when indicator cells had been treated with WGA before adsorption of HTLV-I, but not after its adsorption. These findings indicated that WGA specifically inhibits plating of HTLV-I when added to culture just before adsorption and suggested that a substance(s) containing sugar chains recognized by WGA might be involved in an adsorption step of HTLV-I.

Adsorption↗