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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 19 recordsLinked to original sources

Familial omphalocele: considerations in genetic counseling.

Nonsyndromal omphalocele is generally regarded as a sporadic malformation. Recurrence risk is considered negligible. We report on a patient in whom 5 consecutive pregnancies (by 2 separate nonconsanguineous partners) were complicated by omphalocele as an isolated defect. Neither the patient nor her partners had history of relatives with omphalocele, although the patient's brother and his son had large umbilical hernias requiring repair in infancy. Some familial cases of nonsyndromal omphalocele have been previously reported; most such pedigrees suggest vertical transmission, although there are a few cases with only a single generation involved. In our case, the multigenerational finding of ventral wall hernias makes an autosomal dominant mechanism with variable expressivity a tenable explanation. The collected instances of familial nonsyndromal omphalocele emphasize omphalocele heterogeneity and caution in counseling recurrence risks.

Female

Polyarthritis associated with hydatid disease (echinococcosis) of the liver.

A 36-year-old male developed asymmetric polyarthritis during the course of hydatid disease of the liver. Excision of the hydatid cyst was accompanied by full remission of the arthritis without recurrence during the 7-year follow-up period. This sequence of clinical events suggests an eventual cause and effect relationship. A "reactive" immune mechanism, triggered by a parasite located at a distant site, appears to be responsible for this type of arthritis.

Adult

Treatment of lymphangioleiomyomatosis by ovariectomy, interferon alpha 2b and tamoxifen--a case report.

The gender-specific prevalence of lymphangioleiomyomatosis (LAM) in premenopausal women suggests a hormonal etiology. Despite the antiestrogenic treatment (ovariectomy, tamoxifen) this disease is often refractory to therapy and almost inevitably leads to the patient's death. We describe a case where the antiproliferative effect of systemically applied interferon alpha 2b was successfully employed in addition to ovariectomy and the patient reached complete remission.

Adult

Non-ovarian peritoneal papillary serous carcinoma with high CA125 levels.

A patient with peritoneal papillary serous carcinoma involving the colon and omentum is presented. Following palliative right-sided hemicolectomy and partial omentectomy, chemotherapy was given. The patient had a second look operation after 6 months when a pelvic clearance was done and histology revealed some residual tumor in one mesosalpinx. She was well and clinically free of recurrence after a further 6 months. Serum CA125 and CEA levels were measured and CA125 levels remained high throughout.

Adenocarcinoma, Papillary

Comparative analysis of the immunostimulatory properties of different adjuvants on the immunogenicity of a prototype parainfluenza virus type 3 subunit vaccine.

The immunogenicity of a parainfluenza virus type 3 (PIV-3) subunit vaccine consisting of affinity-purified haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins was tested in guinea-pigs and hamsters. The ability of several different immunopotentiating agents to enhance the antibody response of animals to the PIV-3 surface glycoproteins was evaluated. The immunity induced by HN and F alone was compared with the response elicited by purified proteins combined with Freund's complete adjuvant, aluminium phosphate, Syntex's threonyl-muramyl dipeptide (MDP) SAF-MF formulation, or Ribi's adjuvant formulation containing BCG cell wall skeleton (CWS), trehalose dimycolate (TDM) and monophosphoryl lipid A (MPL) in a 2% squalene-in-water emulsion. Purified proteins were also incorporated into three different liposome formulations prepared by the detergent dialysis procedure. Immunization of guinea-pigs and hamsters with two 15 micrograms doses of the PIV-3 surface glycoproteins administered in the absence of adjuvant elicited high haemagglutination inhibition, neutralization and anti-fusion titres. The liposome preparations failed to enhance the antibody titres. Ribi's adjuvant formulation was effective at inducing a good secondary response to the purified proteins while the immunostimulatory effects of aluminium phosphate, Syntex and Freund's adjuvants were clearly demonstrated in both primary and secondary responses. When administered without adjuvant, a 15 microgram dose of the HN and F mixture was capable of protecting hamsters against live virus challenge. The immunoprotective dose of the purified proteins could be reduced to at least 0.1 microgram by the addition of aluminium phosphate, Syntex or Freund's adjuvants.

Adjuvants, Immunologic

Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis

Subsequently occurring leiomyosarcoma and desmoid tumor of the right thigh.

We present the case of a 44-year-old patient with a primary leiomyosarcoma of the right upper thigh, who developed a second mesenchymal lesion at the same thigh, diagnosed as an extra-abdominal desmoid tumor, some months after surgical treatment of his leiomyosarcoma. Clinically, histomorphologically, DNA cytometrically, immunohistochemically and radiologically the different histogenetic origin of the two lesions could be proven. The patient died 17 months after his first tumor diagnosis of lung metastases of his leiomyosarcoma.

Adult

'Sports anemia'--a real or apparent phenomenon in endurance-trained athletes?

In order to critically define the apparently widespread condition 'sports anemia', the red cell indices and iron status of male distance runners and triathletes, and female distance runners and ballet dancers were compared to non-exercising controls of both sexes. The mean hemoglobin (Hb) levels of all groups were within the normal ranges and there was no difference between the athletic and control groups of each sex. The mean serum ferritin (SF) concentration of the male distance runners (79.8 micrograms/l) was significantly lower than that of the triathletes (123.5 micrograms/l) and controls (138.3 micrograms/l). Iron deficiency (SF less than 12 micrograms/l, % saturation less than 18%) was evident in 3.3% and 5% of the male and female runners respectively, and 3.3% of the ballet dancers. Iron deficiency anemia (abnormal red cell indices and iron status) occurred in only 1.7% and 3.3% of the male and female distance runners respectively, and 3.3% of the dancers. However, 7 (11.7%) each of the male and female distance runners and 6 (20.0%) of the ballet dancers recorded hemoglobin values lower than the normal range of 140 g/l and 120 g/l for males and females respectively. This anomaly can be explained by a significantly expanded plasma volume in endurance-trained individuals, causing a 'pseudoanemia'. We conclude therefore that athletes are at no greater risk for developing a frank anemia than the non-exercising population, and that the term 'sports anemia' is misleading, as it does not describe a specific clinical entity.

Adolescent

[Obstetrical management of dysfibrinogenemia with increased thrombophilia].

Dysfibrinogenaemias are characterised by qualitatively abnormal fibrinogen, causing functional defects. In pregnant women, the incidence of recurrent abortions and placental abruption as well as haemostatic complications is high. In this case report, we report on a 22 year old woman with dysfibrinogenaemia complicated by thrombotic episodes. After two stillbirths under dramatic circumstances (placental abruption, eclampsia) and after an early abortion (7th gestational week), the patient was treated by subcutaneously administered heparin. Pregnancy ended successfully by delivery in the 39th gestational week.

Adult

Overexpression and structure--function analysis of a bioengineered IL-2/IL-6 chimeric lymphokine.

A synthetic chimeric IL-2/IL-6 gene was synthesized to engineer a bifunctional lymphokine which was overproduced in Escherichia coli. Following denaturation of the inclusion bodies in 6 M guanidine and refolding and reoxidation in the presence of a redox system, the fusion protein (rIL-2/IL-6) was purified to homogeneity and shown to react with both monospecific anti-IL-2 and anti-IL-6 antisera. A collagen-like spacer was introduced between the two cytokine moieties to generate IL-2 and IL-6 molecules upon collagenase digestion. After cleavage, the two subunits, purified in a single-step procedure, were found to be correctly reoxidized and functionally as active as their native counterparts. Circular dichroism studies of rIL-2/IL-6 revealed that both cytokine subunits refolded independently and exhibited the alpha-helical structures characteristic of the corresponding wild-type lymphokines. The chimera displayed full IL-2 activity in the CTLL-2 cell proliferation assay. It also retained the IL-6 property to enhance IgM synthesis in SKW6.4 cells, induce the proliferation of B-cell hybridomas and stimulate the production of fibrinogen in hepatocytes. Because IL-2 amplifies the cellular immune response and IL-6 up-regulates the humoral response, this bifunctional lymphokine represents a potentially useful therapeutic adduct and may serve as an immunomodulator to enhance the host's response to vaccination.

Amino Acid Sequence

Identification of T- and B-cell epitopes of the S2 and S3 subunits of pertussis toxin by use of synthetic peptides.

To design an optimized synthetic vaccine against whooping cough, we have studied the biological and immunological properties of three peptides of the S2 subunit and nine overlapping synthetic peptides covering the entire sequence of the S3 subunit of pertussis toxin (PT). Synthetic peptides corresponding to sequences 18 to 41, 78 to 108, 134 to 154, and 149 to 176 of S3 were found to be consistently capable of stimulating the proliferation of PT-specific T-cell lines primed with pertussis toxoid in both BALB/c and A/J strains of mice. All synthetic peptides were recognized by rabbit antisera raised against PT or pertussis toxoid. Both S2 and S3 peptide-keyhole limpet hemocyanin (KLH) conjugates in the presence of complete Freund's adjuvant induced peptide-specific antibody responses in rabbits, and the antisera raised against S2(1-23), S3(18-41), S3(37-64), and S3(149-176) peptide-KLH conjugates cross-reacted with both subunits in the immunoblots. All antisera except those against S2(123-154) and S3(103-127) reacted with native PT in an enzyme-linked immunosorbent assay (ELISA) with PT directly coated onto microtiter wells. In contrast, antisera raised against S2(123-154), S3(1-23), S3(18-41), S3(37-64), S3(60-87), and S3(103-127) peptide-KLH conjugates recognized native PT in a fetuin-PT capture ELISA. S2(78-98), S3(1-23), and S3(149-176) peptide-KLH conjugates elicited good PT-neutralizing antibody responses as judged by the antitoxin CHO cell assay. Identification of these B-cell neutralization epitopes and T-cell immunodominant determinants represents a first step towards the rational design of a synthetic vaccine against whooping cough.

Amino Acid Sequence