Jaroslav Cervenka

Successful bone-marrow transplantation for infantile malignant osteopetrosis

A five-month-old girl with autosomal-recessive osteopetrosis received a bone-marrow transplant from her five-year-old HLA-MLC-identical brother after preparation with cyclophosphamide and modified total-body irradiation. Engraftment was documented by chromosomal analysis. Anemia, thrombocytopenia, and leukoerythroblastosis corrected within 12 weeks of transplantation. Low serum calcium and elevated serum alkaline and acid phosphatase levels became normal. Serial x-ray studies revealed bony remodeling and new nonsclerotic bone formation. A pretransplantation bone biopsy revealed small marrow spaces, rare marrow elements, increased osteoclasts, and no bony resorption. After transplantation, osteoclasts were actively resorbing bone, and medullary cavities contained normal bone marrow. Fluorescent Y-body analysis after transplantation revealed donor (male) osteoclasts and recipient (female) osteoblasts. Monocyte bactericidal activity, markedly decreased before transplantation, became normal. Vision, hearing, growth, and development were progressively improving 16 months after transplantation. Allogeneic bone-marrow transplantation appears to be the treatment of choice in this fatal disorder.

Multiple mucosal neuromas, pheochromocytoma and medullary carcinoma of the thyroid—a syndrome

An analysis of 17 cases of the syndrome of multiple mucosal neuromas, pheochromocytoma and medullary carcinoma of the thyroid is presented and its relationship to similar syndromes discussed. The mucosal neuromas primarily involve the lips, anterior tongue, conjunctiva and nasal and laryngeal mucosa. Medullated corneal nerve fibers traverse the cornea and anastomose in the pupillary area. A Marfanoid build and diverticulosis may be associated findings.

Elevated sister chromatid exchange rate in lymphocytes of subjects treated with arsenic.

SummaryAn elevated sister chromatid exchange (SCE) rate was found in the lymphocytes of six patients treated with arsenic. All had stigmata of arsenic use as well as biopsy-proven skin cancers. The arsenic exposed patients had a mean of 14.00 SCE/mitosis while 44 normal controls had a mean of 5.8 SCE/mitosis. Chromosome breakage analysis revealed no difference between the two groups.SCE rate has been shown to be elevated in a variety of systems where cell cultures or experimental animals were exposed to known mutagens and carcinogens. We suggest that the relationship carcinogen exposure-elevated SCE rate-cancer may also be valid in humans treated with arsenic.

Sister chromatid exchange in lymphocytes from patients with malignant lymphoma

SummarySister chromatid exchange (SCE) frequencies were studied in differentially stained lymphocytes from 47 patients with malignant lymphoma. Thirteen patients were untreated when studied. The mean SCE frequency [±standard error (SE)] for these patients was 12.7±0.9 per mitosis. The mean score for 40 controls was 6.1±0.3. SCE mean scores were significantly higher in the untreated patients than in the controls (P<0.001). Seven patients were treated with radiotherapy alone. They demonstrated a mean SCE frequency (8.8±0.8) significantly lower (P<0.01) than that found in untreated patients. Eleven patients received cyclophosphamide within 4 weeks prior to study. They demonstrated a mean SCE frequency (14.3±1.3) significantly higher (P<0.05) than that found in patients who had received regimens that did not contain cyclophosphamide in the prior 4 weeks (11.1±1.3) or who had been off drugs for at least 8 weeks (10.1±0.8). Our data suggest that untreated patients with malignant lymphoma have elevated SCE frequencies, which may be further increased by certain chemotherapeutic agents.

Partial trisomy 4q syndrome: Case report and review

SummaryThis communication contributes an additional case of partial trisomy for the long arm of chromosome 4[46,XX,t(X;4)(q27;q25)]. Three generations of the patientss family were karyotyped and her mother and brother were found to be balanced translocation carriers. From the patients clinical examination and from review of 13 similar cases reported in the literature, the following phenotype emerged: constant features were psychomotor retardation, muscle hypotonia at birth, undescended testes in all males and abnormal auricles, typically with a prominent antitragus. Anomalies of kidneys and other structures of the urinary system were present consistently as probably the most characteristic feature of the syndrome.Over 200 structural anomalies of other systems were reported, many of them common to other autosomal chromosomal syndromes.

Mutagenic activity of anticancer agent cis-dichlorodiammine platinum-II.

cis-Dichlorodiamminoplatinum-II (cis-DDP) has been widely used as an anticancer chemotherapeutic agent. The mutagenicity of cis-DDP was investigated in vitro and in vivo using sister-chromatid exchange analysis and the analysis of chromosomal aberrations. Parallel human lymphocyte cultures were incubated with and without the addition of BrdU at 4 concentrations of cis-DDP. Significant increases in SCE rate were observed at 0.25 micrograms/ml and higher, showing a clear dose-response relation between SCE rate and cis-DDP concentration. A significant increase in chromosome breakage and tetraradial figures was observed in BrdU free cultures treated with cis-DDP again showing a dose dependency. Analysis of the distribution of cells in the first, second and third division in cis-DDP treated cultures demonstrated the depressing effect of the drug on mitotic activity. In vivo analysis of SCE and chromosome aberrations in mouse showed that 13.85 mg/kg i.p. of cis-DDP produces significant increases in the rate of SCE and chromosome aberrations in bone-marrow cells.

Sister chromatid exchange in patients with viral disease

Sister chromatid exchange (SCE) frequencies were studied in differentially stained chromosomes from lymphocytes of 17 patients with viral disease. The mean SCE score for the patients was 8.7 +/- 2.9 standard deviations. SCE scores were significantly elevated in the patients compared with the controls (p less than 0.01); however, variability in SCE means was observed in the patients. SCE elevations were also present in long term cultured Epstein Barr virus positive human B lymphocytes.

A severe autosomal recessive acromesomelic dysplasia, the Hunter-Thompson type, and comparison with the Grebe type

SummaryTwo siblings with a short-limb dwarfing condition which we call acromesomelic dysplasia, Hunter-Thompson type are reported. Abnormalities are limited to the limbs and limb joints in this severe form of dwarfism. The middle and distal segments of the limbs are most affected. The lower limbs are more affected than the upper. We are aware of one previously published case of this entity reported by A. G. W. Hunter and M. W. Thompson in 1976. Dislocations of the elbows and ankles were present in all three patients and dislocations of the hips and knees in two. One of the siblings who did not have hip and knee dislocations clinically resembled Grebe chondrodysplasia, another severe acromesomelic dwarfing condition. However, radiological analysis suggests that while acromesomelic dysplasia, Hunter-Thompson type and Grebe chondrodysplasia are related, they are not identical. Grebe chondrodysplasia has been established as an autosomal recessive trait. It appears probable that the entity we describe has the same mode of genetic transmission.

Prevalence of Malocclusion in Chippewa Indian Children

Prevalence and types of malocclusion were assessed for 651 children enrolled in public school at the Red Lake Indian Reservation in Minnesota. The influence of the percentage of Indian ancestry on the prevalence and type of malocclusion was also determined.

DNA replication and inactivation patterns in structural abnormality of sex chromosomes

SummaryHigh resolution chromosome analysis and bromodeoxyuridine (BrdUrd) incorporation have been applied to study patterns of chromosomal replication (inactivation) in two cases of unbalanced X-autosome translocations, seven cases of X and Y chromosome rings or fragments, and five cases of dicentric isochromosomes (Xq). Our results indicate the following: (1) In (X-A) translocations, detailed replicational analysis of the translocated autosomal segment is informative. Absence of “spreading effect” and partial-incomplete spreading effect are the most common observations. (2) Sex chromosome derived fragments and rings can be differentiated based on their replicational features. (3) Dicentric isochromosomes (Xq) can be classified based on intercentromeric distances, replicational asynchrony, and centromere inactivation. (4) A correlation between intercentromeric distance and degree of 45,X mosaicism was observed in dicentric “i(Xq)” chromosomes.Evidence for spreading effect based on our results and on the review of the literature has been critically analyzed and general rules in evaluating spreading effects (SE) proposed. The cytologic detection of active regions on the late replicating X chromosome and the inactivation capacity of the juxtacentromeric region of Xp is evaluated. It is proposed that centromere suppression and underreplication are related phenomena. Finally, the analysis of informative replicational stages is emphasized and the application of their analysis in basic and clinical cytogenetics demonstrated.