The beta thalassaemia trait in Jamaica.

The objective of this study was to review the prevalence and features of the beta thalassaemia trait in Jamaican populations. Screening of 221,306 newborns over the last 46 years has given an indication of the distribution and prevalence of beta thalassaemia genes, and screening of 16,612 senior school students in Manchester parish, central Jamaica, has provided their haematological features. The prevalence of the beta thalassaemia trait predicted from double heterozygotes was 0.8% of 100,000 babies in Kingston, 0.9% of 121,306 newborns in southwest Jamaica, and 0.9% of school students in Manchester. Mild beta+ thalassaemia variants (-88 C>T, -29 A>G, -90 C>T, polyA T>C) accounted for 75% of Kingston newborns, 76% of newborns in southwest Jamaica, and 89% of Manchester students. Severe beta+ thalassaemia variants were uncommon. Betao thalassaemia variants occurred in 43 patients and resulted from 11 different variants of which the IVSII-849 A>G accounted for 25 (58%) subjects. Red cell indices in IVSII-781 C>G did not differ significantly from HbAA, and this is probably a harmless polymorphism rather than a form of beta+ thalassaemia; the removal of 6 cases in school screening had a minimal effect on the frequency of the beta thalassaemia trait. Red cell indices in the beta+ and betao thalassaemia traits followed established patterns, although both were associated with increased HbF levels. The benign nature of beta+ thalassaemia genes in Jamaica means that cases of sickle cell-beta+ thalassaemia are likely to be overlooked, and important clinical questions such as the role of pneumococcal prophylaxis remain to be answered.

Success of sentinel lymph node mapping after breast cancer ablation with focused microwave phased array thermotherapy.

BACKGROUND: Breast cancer tumor ablation as part of a multimodality approach in the treatment of breast cancer is the subject of recent interest. This study was conducted to determine if the ability to perform sentinel node biopsy was impaired after thermal-induced ablation of breast cancer. METHODS: We studied patients who had sentinel node biopsy after preoperative focused microwave phased array for breast cancer ablation. RESULTS: Twenty-one patients with T1-T2 breast cancer and clinically negative axilla underwent wide local excision and sentinel node biopsy guided by blue dye and sulfur colloid. Surgery was done an average of 17 days after microwave ablation. Fifteen of 22 patients (68%) had histologic evidence of tumor necrosis. Sentinel lymph node mapping was successful in 19 of 21 patients (91%). Axillary metastases were detected in 42% of cases. CONCLUSIONS: This study documents successful sentinel lymph node mapping for patients treated with antecedent local tumor ablation using focused microwave phased array ablation.

Targeting of PKA in mammary epithelial cells. Mechanisms and functional consequences.

Targeting of protein kinases, promoting association with specific partner-molecules and localisation to particular sites within the cell, has come to be recognised as a key mechanism for attributing specificity to these enzymes. In mammary epithelial cells, the repertoire of acute regulatory roles played by cyclic AMP-dependent protein kinase (PKA) differs from that in other lipogenic cell-types. Furthermore, PKA is implicated in the regulation of mammary-specific function, mediating a tonic stimulation of the flux of newly-synthesised casein through its basal secretory pathway. Both these observations imply mammary-specific properties of either PKA targeting systems or of PKA itself. Evidence for the latter is currently lacking. Pulse-chase labelling experiments in the presence and absence of selective effectors of PKA have enabled the site(s) of action of this protein kinase on casein secretion to be localised to the early stages of the secretory pathway. Possible mechanisms are considered for the physical targeting of PKA to the membrane-enclosed components of the secretory pathway and evidence for their occurrence in mammary epithelial cells is presented.

Nonsustained ventricular tachycardia in 193 U.S. military aviators: long-term follow-up.

BACKGROUND: Despite its importance to the aeromedical community, the occupational implications of asymptomatic, nonsustained ventricular tachycardia (VT) are not well described. We sought to clarify this issue via a review of military aviators evaluated for nonsustained VT by defining event rates for sudden cardiac death, syncope, presyncope and sustained VT, and by determining whether any cofactors predicted a subgroup at increased risk for such outcomes. METHODS: We reviewed the records of 193 military aviators evaluated at the U.S. Air Force Aeromedical Consultation Service for nonsustained VT from September 1960 to December 1992. Follow-up information was available on 192 of the 193 aviators over a mean of 10.6 yr. Cofactor analysis focused on idiopathic VT (no associated underlying cardiac disease) and VT associated with mitral valve prolapse (MVP). RESULTS: There was no documented sustained VT; 9 (4.6%) had events including syncope (1), presyncope (5) and sudden death (3). Of these 9, 4 had idiopathic VT. The 3 deaths were associated with coronary artery disease, MVP and cardiomyopathy. No cofactors predicted events in aviators initially presenting with asymptomatic nonsustained VT. For asymptomatic nonsustained VT, the maximum predicted annual event rate was 0.33% for idiopathic VT and 2.3% for VT with MVP (95% confidence limit). CONCLUSIONS: Nonsustained VT did not predict future documented sustained VT. Cofactors failed to predict a subgroup at increased risk for events. Idiopathic nonsustained VT appeared to be a low risk population for whom expanded waiver criteria are proposed with suggested limits on duration and number of episodes of VT.

Interactive use of sign language by cross-fostered chimpanzees (Pan troglodytes).

Cross-fostered as infants in Reno, Nevada, chimpanzees (Pan troglodytes) Washoe, Moja, Tatu, and Dar freely converse in signs of American Sign Language with each other as well as with humans in Ellensburg, Washington. In this experiment, a human interlocutor waited for a chimpanzee to initiate conversations with her and then responded with 1 of 4 types of probes: general requests for more information, on-topic questions, off-topic questions, or negative statements. The responses of the chimpanzees to the probes depended on the type of probe and the particular signs in the probes. They reiterated, adjusted, and shifted the signs in their utterances in conversationally appropriate rejoinders. Their reactions to and interactions with a conversational partner resembled patterns of conversation found in similar studies of human children.

Postorthodontic dental changes: a longitudinal study.

The conventional adolescent orthodontic patient is treated during a phase of active growth, but growth of the skeletodental complex continues after treatment and into adulthood at a much slower pace. Selection of orthodontic diagnostic and treatment regimens that produce stable and esthetic dental relationships is a continual endeavor for the orthodontic specialist. Patients should be recalled for long periods of time and the results evaluated. The present longitudinal study was completed on 36 individuals, all of whom had received comprehensive orthodontic treatment. Dental changes were assessed from cephalograms for the in-treatment period (ca. 12 to 15 years of age), posttreatment to first recall (0 = 22 years of age), and first to second recall period (0 = 30 years of age). There was considerable change in the absolute locations of the teeth, but, in reality, these changes are almost wholly attributable to growth of the bony reference structures, not dental changes per se. Growth proceeded at a very slow pace after the first recall (ca. 22 to 30 years of age ). Dental relationships, eg., FMIA, IMPA, 6L angulation, exhibited no systematic change after treatment.

The Burgess decision and the Wallerstein brief.

Divorcing couples traditionally incorporate into their settlement contracts a stipulation regarding relative degree of freedom to relocate, especially if the relocating parent has primary custody of the children. Typically, the primary custodial parent might be restricted from moving outside of the state in which the divorcing couple has resided, or there may be a specific mile radius or travel time radius beyond which the primary custodial parent cannot relocate. In recent years, courts have become increasingly permissive with regard to allowing relocation by primary custodial parents, and the once stringent requirements that needed to be satisfied to justify relocation are being progressively relaxed. In 1996, the Supreme Court of California in In Re the Marriage of Burgess, 913 P.2d 473 (Cal. 1996), has set a precedent for even further relaxation of these once rigid restrictions. The Burgess decision has been frequently quoted in the State of California and is receiving widespread attention elsewhere. It is the author's opinion that this precedent is ill conceived and will most likely result in significant grief and suffering for the nonrelocating parent as well as the relocating children.

Casein secretion in mammary tissue: tonic regulation of basal secretion by protein kinase A.

Despite its quantitative importance in the secretion of lactoproteins, little is known about the triggering and control mechanisms that initiate, regulate and terminate the operation of the basal pathway of lactoprotein secretion throughout the lactation cycle. This study investigated the possible modulation by cAMP-mediated mechanisms, of cellular transit of newly-synthesised caseins and their basal secretion in explants of mammary tissue from lactating rats and rabbits. Enhancement of the rate of secretion of newly-synthesised caseins occurs when mammary explants are challenged in vitro with agents that activate protein kinase A (PKA). Inhibition of PKA slows casein secretion. The PKA-sensitive step(s) in casein secretion is early in the exocytosis pathway but inhibition of PKA does not impair casein maturation. Ultrastructural, immunochemical and biochemical methods locate PKA on membranes of vesicles situated in the Golgi region. Exposure of tissue to a cell-permeant PKA inhibitor results in morphological modification of these vesicular structures. We conclude that PKA mediates tonic positive regulation of the basal secretory pathway for lactoproteins in the mammary epithelial cell.

Cyclic AMP-dependent protein kinase in rat mammary tissue: expression of catalytic and regulatory subunits throughout pregnancy and lactation.

'Expressed' and 'total' activities of cyclic AMP-dependent protein kinase (PK-A) were measured in extracts of rat mammary tissue sampled throughout pregnancy and lactation. Expression of the genes encoding the catalytic subunit (C-subunit) isoforms C alpha and C beta was examined by Northern blotting, as a function of mammary development, to determine relative levels of their respective mRNAs. The content of C-subunit protein (all isoforms) was estimated immunochemically and related to levels of C-subunit catalytic activity and of mRNAs. It was found that C-subunit isoform mRNAs are expressed co-ordinately during mammary development and that a marked decline in expression, per cell, at around parturition is paralleled by a fall in 'total' PK-A activity. The 'expressed' activity of PK-A activity underwent characteristic changes throughout pregnancy and lactation, reaching a peak late in pregnancy. The PK-A activity ratio reached a peak in early lactation. C-subunit protein mass closely parallel 'total' PK-A activity throughout pregnancy and lactation, thereby demonstrating the constancy of C-subunit specific catalytic activity during these developmental events. Regulatory subunits (R-subunits) were probed with the photoaffinity label 8-azido-[32P]cAMP. The abundance of R-II as a proportion of total R-subunit increased throughout pregnancy and lactation, and quantitative analysis of the photoaffinity labelling suggested inconstancy in the ratio of R:C subunits, with highest values occurring in late pregnancy/early lactation.

Categorical replies to categorical questions by cross-fostered chimpanzees.

The chimpanzees Washoe, Moja, Tatu, and Dar were reared under human cross-fostering conditions that included the use of American Sign Language (ASL) as the medium of two-way communication. In the course of everyday conversation they were asked, in signs, the Wh-questions that are typically asked of young children. In earlier studies, extensive samples showed a pattern of replies, most significantly a developmental sequence, that closely matched the pattern found in the replies of young children. Part 1 of this report is based on a special sample taken when Tatu was 63 months old and Dar was 56 months old, in which experimenters used a large pool of nameable objects, and asked a naming question and at least one descriptive question about the same object in the same context. Tatu and Dar replied to naming questions (WHAT THAT? or WHAT NAME THAT?) with signs that were nouns and to descriptive questions with signs that were modifiers: possessive pronouns for WHOSE THAT?, colors for WHAT COLOR THAT?, and materials for WHAT THAT MAKE FROM? Part 2 is a reanalysis of the Part 1 sample and several other samples of replies, demonstrating that even when their reply was incorrect, these chimpanzees usually replied with a sign from the category specified by the question. The continuities that biologists seek are continuities of laws, patterns of resemblance rather than overlapping data points. Results reported here add depth to the patterns demonstrated in earlier studies.

Schizotrypanum in British bats.

Two species of Schizotrypanum, T. (S.) dionisii and T. (S.) vespertilionis, were identified from British bats. Laboratory studies on stocks of isolated trypanosomes from 5 species of bat (Pipistrellus pipistrellus, Nyctalus leisleri, N. noctula, Eptesicus serotinus and Myotis brandti) indicated that the predominant species was T. d. dionisii. Collections and dissection of the bat bug Cimex pipistrelli from bat roosts revealed flagellate infection in a total of 12 out of 20 bugs; 7 of these bugs had metacyclic trypanosomes present. C. pipistrelli and the human bed bug, C. lectularius were reared in the laboratory and allowed to feed on wild-caught bats known to be infected with T. d. dionisii. Development occurred in both species of Cimex. Cimex spp. could be used to detect subpatent Schizotrypanum infections by xenodiagnosis. This technique was used to test the parasitological status of bats collected in the wild or reared in captivity. On a single occasion an apparent transmission of T. d. dionisii to an uninfected (by xenodiagnosis) laboratory reared bat was achieved. A stock of Schizotrypanum isolated from a wild-caught C. pipistrelli collected in a N. leisteri roost was identified by DNA buoyant density centrifugation as T. (S.) vespertilionis. A P. pipistrellus known to be infected with T. d. dionisii was found to have cyst-like structures in thoracic skeletal muscle containing amastigotes. The study provided the strongest evidence yet that C. pipistrelli is the vector of Schizotrypanum in British bats.

Trypanosoma (Megatrypanum) incertum from Pipistrellus pipistrellus: development and transmission by cimicid bugs.

Trypanosoma (Megatrypanum) incertum Pittaluga 1905 was found in 33 out of 206 Pipistrellus pipistrellus caught at various sites in Britain. The trypanosome is described from blood smears. Development took place in laboratory-reared Cimex pipistrelli and Cimex lectularius. Epimastigote forms initially multiplied rapidly in the ventriculus and midgut of Cimex. Metacyclic trypanosomes were found in the rectum of both species of Cimex after 8 days when bugs were maintained at 20 degrees C and as early as 3 days at 30 degrees C. Electron microscopy of infected bugs revealed that there was no attachment to epithelial cells of the ventriculus or midgut, but within the rectum epimastigotes were attached by their flagella to the cuticle of the rectum by hemidesmosomes. Transmission was achieved by feeding experimentally infected bugs to bats kept in the laboratory. These bats were negative as judged by xenodiagnosis using laboratory-reared Cimex. Bats which had been caught in the wild demonstrated low-grade or sub-patent parasitaemias (positive in xenodiagnosis) for up to 400 days after the day of capture. Despite an extensive search of impression smears of tissues immediately after trypanosomes first appeared in the blood of experimentally infected bats no multiplicative stages were found.

Polychromophilus murinus: a malarial parasite of bats: life-history and ultrastructural studies.

Polychromophilus murinus, a malaria parasite of Chiroptera is reported from Myotis daubentoni in England. The vector was suspected to be the ectoparasitic Nycteribiid fly, Nycteribia kolenatii. N. kolenatii collected from wild-caught M. daubentoni were found to have oocysts on the midgut and sporozoites in the salivary glands. Wild-caught N. kolenatii were maintained on two wild-caught M. daubentoni harbouring heavy (patent) infections of P. murinus; both oocysts and sporozoites were found in these flies. The mature oocysts measured 52-71 micron in diameter. Sporozoites were straight or slightly crescentic and had a mean length of 7.4 micron. Electron microscopy of immature and mature oocysts revealed a morphology similar to that of malaria parasites. Sporozoites were also similar in structure to Plasmodium sporozoites and were found in the epithelial cells of the salivary gland and within the lumen; a cytostome was present and transverse sections revealed 21 microtubules arranged evenly around the periphery. Sporozoites were observed within the basement membrane of the salivary gland of N. kolenatii; such sporozoites appeared to be penetrating the gland, a process hitherto not described in malaria parasites. Rickettsia-like bodies were found within the cytoplasm of the epithelial cells of the salivary gland. Exflagellation of microgametocytes was achieved. An ultrastructural study of the gametocytes revealed a structure similar to that described in other Haemoproteidae. A common feature of infected erythrocytes was a projecting erythrocyte membrane. Attempts to find schizogony in impression smears and sections of tissues of two infected M. daubentoni were not successful.