Autoradiographic analysis of second messenger and neurotransmitter system receptors in the gerbil hippocampus following transient forebrain ischemia.

Changes in second messenger and neurotransmitter system receptor ligand binding induced by transient forebrain ischemia were studied in the gerbil hippocampus. The animals were allowed variable periods of recovery ranging from 2 h to 7 days after 5-min bilateral carotid artery occlusion. The binding of second messenger systems ([3H]inositol 1,4,5-trisphosphate ([3H]IP3)to inositol 1,4,5-triphosphate, [3H]forskolin to adenylate cyclase and [3H]phorbol 12,13-dibutylate to protein kinase C) and neurotransmitter receptor systems ([3H]PN200-110 to L-type calcium channels. [3H]N6-cyclohexyl-adenosine to adenosine A1 and [3H]quinuclidinyl benzilate to muscarinic cholinergic receptor) were assayed using quantitative autoradiography. In the CA1 subfield, 2 h after ischemia, [3H]IP3, [3H]forskolin, and [3H]quinuclidinyl benzilate binding activities significantly decreased by 25, 17 and 13%, respectively, though no morphological abnormalities were obvious. Six hours after ischemia, the [3H]phorbol 12,13-dibutylate binding activity in the stratum oriens of the CA1 subfield increased by 15%. One day after ischemia, [3H]PN200-110 binding activity in this subfield decreased by 26%, and 7 days after ischemia, [3H]phorbol 12,13-dibutylate and [3H]N6-cyclohexyl-adenosine receptor binding activities decreased in this subfield. In particular, at 7 days after ischemia, [3H]IP3 binding activity in the CA1 subfield showed a complete decline. In the CA3 subfield, [3H]PN200-110 binding activity decreased 2 days after ischemia, and [3H]IP3 and [3H]N6-cyclohexyl-adenosine binding activities decreased 7 days after ischemia. In the dentate gyrus, the structure of which remained histologically intact after ischemic insult, [3H]IP3 and [3H]forskolin binding activities decreased 7 days after ischemia. In contrast, the [3H]phorbol 12,13-dibutylate binding activity increased in the molecular layer of the dentate gyrus 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield and that the histologically intact CA3 and dentate gyrus also shows modulated neuronal transmission after ischemia.     

Improved high performance liquid chromatography determination of hippuric acid and methylhippuric acid isomers in urine

A study was made on the effect of detection wavelength and separation mode of HPLC on determination of urinary hippuric acid (HA) and three isomers of methylhippuric acid (MHA). The interference of other constituents of urine in the determination was effectively decreased by detection at a short wavelength of 227.6 nm. Meta and para MHAs were separated by the addition of beta-cyclodextrine to the mobile phase. Four metabolites were successfully separated from other components of urine by the combination of ODS-silica packed-column and mobile phase (method F). The detection limits were found to be 50 and 5 mg/l for HA and MHAs, respectively. MHAs could not be detected in the non-exposed subjects. Average levels (+/- SD) of HA in non-exposed males and females were 272.2 (+/- 210.8) and 393.0 (+/- 269.8) mg/l, respectively. The urinary levels of HA in females were significantly higher than those in males.     

T Cell Receptor Vβ Repertoires of Angioimmunoblastic Lymphadenopathy-like T Cell Lymphoma

To elucidate the pathogenesis of angioimmunoblastic lymphadenopathy-like T cell lymphoma (AILD-T) we investigated the T cell receptor Vβ gene repertoires of four AILD-Ts and compared them with those of other histological types of lymphomas and three cases with reactive disorders. All lymphoma patients had rearrangement bands detected by Southern blot analysis. Only 1 of the 4 cases of AILD-T showed a single predominant usage of Vβ 20 gene by PCR with 20 different Vβ specific primers and the others had repertoires somewhat restricted but similar to reactive lesions. Subsequent sequencing of this PCR product revealed that only 2 of 7 clones were identical. These results suggest the monoclonal malignant cells in AILD-T are scant and that the infiltrating T cells show a reactive pattern. In the only AILD-T case with a single dominant Vβ usage, the relationships of this repertoire and lymphoma cells seems to be of some consequence.     

Myasthenia gravis and steroid therapy]

In the past 20 years, we experienced 242 myasthenic patients in our hospital. Fifty five cases were administered high doses of adrenocorticosteroid hormone for a long time. Among them, we analysed 39 cases with complete clinical records from admission to the present. We analysed 5 additional cases in whom responses to the therapy somewhat unique in that four cases have not shown any improvement until the drug was reduced to certain dosages, and in the 5th case change of method from alternate-day to every day brought good recovery of the symptoms. As a result, adrenocorticosteroid hormone was effective for 100% of the patients in this series. However, complete remission appeared in the above mentioned 10 patients (26%), after 2-3 years' continuous administration. Prognosis was far better in those who showed shorter durations between the onset of the disease and thymectomy or thymectomy than in those of longer one. In these cases, the maximum daily doses were 60-100 mg in alternate-day administration, and the total amount of prednisolone was 9-15 g in individual cases. Through data of these cases, it is recommended that the maximum dosage is to be continued for as long as 2 to 19 weeks with average 7 weeks.     

Effects of naftidrofuryl oxalate, a 5HT2 antagonist, on neurotransmission and transduction systems in the gerbil hippocampus

We investigated the effects of age and naftidrofuryl oxalate (Naftidrofuryl), a 5-HT₂ antagonist, on neurotransmission and transduction systems in the gerbil hippocampus using quantitative autoradiography. [³H]Quinuclidinyl benzilate (QNB), [³H]cyclohexyl-adenosine (CHA), [³H]MK-801, and [³H]muscimol were used to label muscarinic acetylcholine, adenosine A1, N-methyl-d-aspartate (NMDA), and γ-aminobutyric acid-A (GABA_A) receptors, respectively. [³H]PN200-110 labeled L-type Ca²⁺ channels. [³H]Forskolin, [³H]cyclic adenosine monophosphate (cAMP), [³H]phorbol 12,13-dibutyrate (PDBu), and [³H]inositol 1,4,5-triphosphate (IP₃) were used to label adenylate cyclase, cAMP-dependent protein kinase, protein kinase C (PKC), and IP₃ receptors, respectively. Approximately 20% reductions in [³H]QNB, [³H]forskolin, and [³H]PDBu binding were observed in the hippocampus of 9-month-old gerbils in comparison with 5-week-old gerbils. Treatment with Naftidrofuryl (10 mg/kg, i.p., once a day for 7 days) ameliorated these reductions. No changes were found in [³H]CHA, [³H]MK-801, [³H]muscimol, [³H]PN200-110, [³H]cAMP, and [³H]IP₃ binding. The results suggest that Naftidrofuryl may have beneficial effects on the age-related alterations in signal transmission and transduction systems in the brain. Because the acetylcholine system, adenylate cyclase, and PKC are considered to be involved in learning and memory processes, the result may have clinical implications.     

Inhibitory effect of activated protein C and heparin on arterial thrombosis]

Activated protein C (APC) exerts an anticoagulant effect by inactivating coagulation factors Va and VIIIa, preferentially on the surface of the cell membrane, and may enhance fibrinolysis by inhibiting PAI-1. APC inhibits venous and microvascular thrombosis, as well as, platelet-rich thrombus formation on the Dacron graft inserted in the arteriovenous shunt. We examined the effect of APC and heparin on arterial thrombosis using small mesenteric arteries of the rat, in which platelet-rich thrombus formation was induced by segmental deep vessel injury and the changes were monitored using a video-microscope system. Both APC (0.9 and 3.0 mg/kg, iv) and heparin (300 and 1000 U/kg) inhibited thrombus formation similarly. APC did not prolong APTT compared with heparin. APC may inhibit arterial thrombosis after vascular damage without serious bleeding side effects.     

Effects of minaprine and sulpiride injected into the amygdaloid nucleus on the duration of immobility in rats forced to swim

We examined the effects of minaprine and sulpiride injected into the medial amygdaloid nucleus on the duration of immobility in rats forced to swim. Minaprine (50 micrograms/microliter) significantly reduced the duration of immobility, while sulpiride (50 micrograms/microliters) remarkedly enhanced it. These results suggest that the medial amygdaloid nucleus might be involved in the suppressive effect of minaprine on the duration of immobility, as was seen with the tricyclic antidepressants. The pattern of behavior seen with sulpiride administrations differs considerably from that seen with the tricyclic antidepressants.     

Uveitis associated with human T-cell lymphotropic virus type I.

Seroepidemiologic, clinical, and virologic studies were performed to determine whether human T-cell lymphotropic virus type I was closely associated with uveitis in two hospitals. One hospital was in an endemic area of the virus (Miyakonojo, Miyazaki) and the other hospital was in a less endemic area (Kurume). In the endemic area, the seroprevalence of the virus in patients with uveitis without defined causes (35.4%, 62 of 175 patients) was significantly higher than that in patients with nonuveitic ocular diseases (16.1%, 42 of 261 patients), or in patients with uveitis with defined causes (10.3%, eight of 78 patients). The seroprevalence in younger patients (20 to 49 years of age) with uveitis without defined causes in the area was 44.8% (30 of 67 patients), whereas it was only 9.3% (ten of 107 patients) in the other two groups. A similar observation was recorded even in the less endemic area (Kurume). Because the seroprevalence of the virus in the general population is known to be low in younger patients and to increase with age, these findings were interpreted to indicate that the association of human T-cell lymphotropic virus type I with uveitis was significant. Most patients, particularly those aged 20 through 49 years, had an intermediate uveitis characterized by a moderate inflammation in the vitreous body accompanied by an iritis and retinal vasculitis. The ocular symptoms in the patients differed from those of other types of uveitis common in Japan (Beh?et's disease, Vogt-Koyanagi-Harada's disease, and toxoplasmosis, for example).(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of Machado-Joseph disease--cerebral blood flow and cerebral metabolic rate of oxygen]

A 51-year-old woman, with progressive gait disturbance and dysarthria, had been diagnosed as Menzel-type spinocerebellar degeneration. Later, she developed dystonic posture of upper limbs and bulging eyes. She was diagnosed as Machado-Joseph disease from neurological findings, which consisted of cerebellar signs, pyramidal tract signs and extrapyramidal tract signs and peripheral neuropathy. She died suddenly of unknown origin. Her illness lasted about 13 years. Neuropathological findings showed moderate neuronal loss with gliosis in the subthalamic nucleus, globus pallidus, substantia nigra, dentate nucleus, oculomotor and hypoglossal nucleus and anterior horn. Positron emission tomography (PET) using 15O steady state inhalation technique revealed reduction of cerebral blood flow and cerebral metabolic rate of oxygen in not only cerebellum but also cerebral cortex. These findings are different from typical PET findings of spinocerebellar degeneration.     

Repair of skin defect after extensive resection for penile cancer: report of two cases, and clinical observation of patients with penile cancer at Mie University hospital]

Case 1: A 48-year-old male with stage 4 penile cancer is reported. We used peplomycin (PEP) and cisplatinum (CDDP) for preoperative chemotherapy. Chemotherapy was effective. Radical surgery with bilateral inguinal lymphadenectomy was done and skin defect was covered with a skin flap. Case 2: A 61-year-old male with stage 4 penile cancer underwent radical surgery after modified MBD therapy with methotrexate (MTX), PEP and CDDP. Emasculation with skin resection and inguinal and pelvic lymphadenectomy were performed. The skin defect was deep and wide. It was covered with a glacilis myocutaneous skin flap. Distal end of the flap became necrotic. It was covered with tensor fascia lata myocutaneous flap. Seventeen patients with penile cancer were treated between 1972 and 1990 at Mie University Hospital. Nine patients were in stage 1, 4 stage 2, 1 stage 3, 3 stage 4. Treatment consisted of surgery (3), surgery+chemotherapy (10), surgery+chemotherapy+irradiation (2), chemotherapy+irradiation (1), and surgery+irradiation(1). Cancer death was observed in 2 cases (stage 2), 2 patients died of other diseases, 10 are alive, and 3 patients were lost to follow up.