Prevention of hepatitis C virus infection in a chimpanzee by vaccination and epitope mapping of antiserum directed against hypervariable region 1.

We previously reported on a chimpanzee immunized with both putative envelope glycoproteins (E1 and E2) of hepatitis C virus (HCV), strain HCV-N2, and synthetic peptides of hypervariable region 1 (HVR1) of a different isolate, HCV-#6. The chimpanzee showed complete protection against HCV-#6 infection only when the titer of anti-HVR1 increased, suggesting that an immune response to the HVR1 is more essential in protecting a chimpanzee from HCV infection than an immune response to E1 and E2. In this study, we immunized this chimpanzee with only synthetic HVR1 peptides after anti-E1 and anti-E2 antibody levels dropped and then rechallenged with 10 infectious chimpanzee doses of HCV. The immunized animal was protected, and neutralization of HCV with the antiserum from the protected animal was achieved by inoculating another chimpanzee with HCV preneutralized by this antiserum mixture. Epitope analysis of HVR1 by Pin-ELISA using this antiserum seemed to demonstrate that the antibody response was directed mainly against the C terminus of HVR1. Moreover, our results showed that, if a part of the sequences was conserved, a broad cross-reactivity of the antiserum could be observed, even if amino-acid sequences in this epitope were substituted for those of other HCV strains.

In SCID-hu mice, passive transfer of a humanized antibody prevents infection and atrophic change of medulla in human thymic implant due to intravenous inoculation of primary HIV-1 isolate.

Using SCID-hu mice, it was tested whether humanized mAb Rmu5.5 could prevent infection by HIV-1 i.v. inoculation. The Ab that recognizes the IHIGPGRAFYT motif in the principal neutralizing determinant (PND) of HIV(MN), as well as the original mouse mAb mu5.5, neutralized HIV(MN) with high activity. Seven primary field isolates from Japanese hemophiliacs seropositive for HIV-1 clade B were compared for their reactivities to Rmu5.5. Rmu5.5 was effective, particularly against the viruses that matched amino acid sequences of the PND region of HIV-1, and it completely neutralized primary isolates. Moreover, the passive transfer of the Ab elicited protection against challenge by the primary isolates in SCID-hu or hu-PBL-SCID mice after i.v. inoculation with the virus by both quantitative PCR and PBMC-based virus isolation in vitro. Further, inoculation with the Ab also prevented the atrophic change in the medulla of the thymic transplant that was induced by i.v. inoculation of the virus. Thus, the humanized neutralizing Ab Rmu5.5 appears to protect SCID-hu mice from infection by primary field isolates.

Uterine lipoleiomyoma: MRI appearances.

A case of uterine lipoleiomyoma demonstrated on computed tomography (CT) and magnetic resonance imaging (MRI) is described and usefulness of MRI is discussed in diagnosing this entity.

[Experimental studies on urinary tract infection--bladder and kidney lodgement in mice by strains of Staphylococcus epidermidis].

Eight strains of Staphylococcus epidermidis were isolated from clinical specimens and were subjected to the tests for encapsulation, slime-production, mouse-virulence, capsular-typing and adherence to the plastic surface, the renal cells and the bladder epithelial cells. With the intraperitoneal injection of these strains into mice, three encapsulated strains were observed in mouse-virulent, while two slime-producing and three unencapsulated strains were mouse-avirulent. In ultra-thin sections of mouse-virulent strains, capsules were demonstrated by electron microscopy, however no capsule was seen around the walls of mouse-avirulent strains. On the other hand, slime-producing strains were shown to have higher adherence rate to plastic surface, compared to encapsulated strains. The direct adherence rate to the bladder epithelial cells was greater in the encapsulated strains than the slime-producing strains, although there was no difference to the renal cells. Also, cell suspension containing 10(7) colony forming units of these strains were injected intravenously or intravesically into mice. Of these encapsulated strains showed kidney and bladder lodgement with in 28 and 21 days after intravesical injection, respectively, although slime-producing and unencapsulated strains could only be obtained for 7 days in the kidney and 3 days in the bladder. However, there was no difference in the internal organs lodgement of the strains after intravenous injection into mice. These experimental results suggested that the encapsulation of the strains would be an important factor for bladder lodgement, however, significant effects were not observed with the slime-producing and unencapsulated strains.

A patient with congenital plasminogen deficiency manifesting primary pulmonary hypertension.

A 25-year-old Japanese man was diagnosed as having primary pulmonary hypertension, on the basis of the findings of cardiac catheterization and ventilation-perfusion scintiscans. The plasma level of plasminogen in this patient was found to be reduced to 43% by a functional assay and 61 mg/l by an antigenic assay. Based on the family study, the patient was considered to have a heterozygous congenital plasminogen deficiency. Accordingly, it is suggested that the defective fibrinolysis in this patient may have played an important role in the development of primary pulmonary hypertension through microthrombosis.

Hereditary spherocytosis with congestive heart failure: report of a case.

We report herein a case of 62-year-old woman with hereditary spherocytosis (HS) and congestive heart failure (CHF). Although her history revealed jaundice in the early neonatal period, she had never undergone a physical examination and thus, the diagnosis of HS and CHF was not made until the age of 61 when she complained of dyspnea and palpitations on exertion. The CHF was subsequently found to be related to severe anemia in the presence of underlying heart disease. Splenectomy was performed in an attempt to relieve the severe hemolytic process. Following this, all the symptoms improved without the need for any cardiovascular drugs and she has been well throughout the 34 months follow up.

Successful treatment of acute right cardiac failure due to pulmonary thromboembolism in mixed connective tissue disease.

Mixed connective tissue disease (MCTD) is characterized as a benign rheumatic disease with a favorable response to therapy. When pulmonary hypertension is a complication, however, it is often reported to be fatal. A 32-year-old female patient with MCTD who had developed rapidly progressive pulmonary hypertension and disseminated intravascular coagulopathy was admitted to our hospital and was successfully treated with corticosteroids and anticoagulants. The failure of microcirculation due to coagulopathy is considered to be one of the possible entities of pulmonary hypertension.

Expression of herpes simplex virus glycoprotein B gene in yeast.

The DNA sequence coding for herpes simplex virus type 1 glycoprotein B was placed under control of the acid phosphatase promoter of the yeast Saccharomyces cerevisiae in a plasmid capable of replicating in both yeast and Escherichia coli. Yeast transformed by the plasmid synthesized immunologically active glycoprotein B polypeptide.